A Selected Chronological Bibliography of Biology and Medicine — Part IV

1964 — ca. 2008

Compiled by James Southworth Steen, Ph.D.
Delta State University

Dedicated to my loving family

This document celebrates those secondary authors and laboratory technicians
without whom most of this great labor of discovery would have proved impossible.

Please forward any editorial comments to:

John D. Tiftickjian, Jr., Ph.D., Professor of Biology
Delta State University
Box 3262, Cleveland, MS 38733
e-mail: jtift@deltastate.edu


“We can and should devote ourselves with truly religious devotion to the cause of ensuring greater fulfillment for the human race in its future destiny. And this involves a furious and concerted attack on the problem of population; for the control of population is…a prerequisite for any radical improvement in the human lot.” Julian Sorell Huxley(1).

“I wish I had the voice of Homer

To sing of rectal carcinoma,

Which kills a lot more chaps, in fact,

Than were bumped off when Troy was sacked.” John Burdon Sanderson Haldane(2).

Dorothy Mary Crowfoot-Hodgkin (GB) was awarded the 1964 Nobel Prize in Chemistry for her determinations by x-ray techniques of the structures of important biochemical substances.

Konrad Emil Bloch (US) and Feodor Felix Konrad Lynen  (DE) were awarded the Nobel Prize in Physiology or Medicine for their discoveries concerning the mechanism and regulation of the cholesterol and fatty acid metabolism.

David A. Yphantis (US) introduced the ‘meniscus depletion’ (a.k.a. ‘high speed’ and ‘Yphantis’) technique to equilibrium ultracentrifugation of dilute solutions. This method required spinning the sample at a rotor speed high enough to deplete the meniscus of macromolecules(3).

Patrick Andrews (GB) developed a way to determine the molecular weights of proteins using Sephadex gel-filtration(4).

Leonard Ornstein (US) and Baruch J. Davis (US) introduced the use of synthetic polyacrylamide gels in disc (discontinuous) electrophoresis(5, 6).

Alfred Zettner (US) and David Seligson (US) were the first to use atomic absorption spectrophotometry to measure serum calcium(7).

David L. Trudeau (US) and Esther F. Freier (US) first described the use of lanthanum in the measurement of calcium in biological fluids(8).

Gerald Kessler (US) and Morris Wolfman (US) provided the first auto analyzer method for the simultaneous measurement of calcium and phosphorus without preliminary sample treatment(9).

Luis Federico Leloir (AR), Carlos Eugenio Cardini (AR), Jose M. Olavarría (AR), Sara H. Goldemberg (AR), and Hector Carminatti (AR) discovered that glycogen can be synthesized by a process in which the reactive intermediate uridine diphosphate glucose (UDP-glucose) transfers glucose to the growing glycogen chain. They found that galactose is broken down to yield glucose in a similar pathway. They identified the enzyme glucose1-phosphate kinase acting in a separate glycogen synthesis. The product of this reaction, glucose 1,6-diphosphate, is a coenzyme of the glycolysis pathway enzyme, phosphoglucomutase. They went on to identify galactokinase and discovered that the product, galactose 1-phosphate, is converted into glucose 1-phosphate(10-13). 

Herman Moritz Kalckar (DK-US), Beatriz Braganea (DK), and Agnete Munch-Petersen (DK) had presented direct evidence that the synthesis of UDP galactose does occur in extracts of the yeast Saccharomyces fragilis, catalyzed by galactose-1-P uridyl transferase(14). 

CIBA Chemical Company introduced the herbicide fluometuron, a substituted urea, useful in cotton (Gossypium spp.) and sugar cane (Saccharum officinarum). Ref

Clinton E. Ballou (US) and Yuan Chuan Lee (TW-US-TW) determined the structures of the family of mannosyl phosphoinositides in the mycobacteria(15, 16).

Karl Sune Detlof Bergström (SE), Henry Danielsson (SE), and Bengt Samuelson (SE) demonstrated the enzymatic conversion of arachidonic acid to prostaglandin E2(17). Because arachidonic acid is synthesized from linoleic acid in humans, this discovery helped establish prostaglandins as products of the metabolism of essential fatty acids.

Choh Hao Li (CN-US) and Yehudith Burk (US) isolated and purified beta-lipotropin (beta-LPH)(18).

Choh Hao Li (CN-US), Livio Barnafi (CL), Michel Chretien (US) and David Chung (US) determined the amino-acid sequence of beta-LPH. They found contained within the 91 residues of beta-LPH the 18-residue sequence of melanocyte-stimulating hormone (MSH). Beta-LPH may be viewed as a prohormone from which MSH is derived(19).

Michel Chretien (US) and Choh Hao Li (CN-US) isolated, purified, and characterized gamma-lipotropin hormone from sheep pituitary glands. It consists of the first 58 residues of beta-lipotropin and contains the MSH sequence(20).

J. Michael Poston (US), Kazuoki Kuratomi (US), and Earl Reece Stadtman (US) determined that methyl-B12 is involved in acetate synthesis and is the first step in the acetyl-CoA pathway(21). This was a major clue to unraveling the acetyl-CoA pathway.

Merton Franklin Utter (US), D. Bruce Keech (US), and Michael C. Scrutton (US) demonstrated that acetyl-CoA regulates the activity of pyruvate carboxylase (adds CO2 to pyruvate in glucogenesis), thus providing one of the first examples of allosteric control of enzymes(22, 23).

Myron Lee Bender (US), Ferenc J. Kézdy (US), and Claude R. Gunter (US) concluded that the enzymatic reactivity of alpha-chymotrypsin could be accounted for by (1) the intramolecular character of the enzymatic process and the concomitant increase in effective concentration of the catalytic group(s); (2) general basic catalysis by imidazole; (3) the change in rate-determining step of the amide hydrolysis to an alcoholysis; (4) the freezing of the substrate in a conformation resembling the transition state, and (5) the general acidic catalysis by imidazole(24).

Waclaw Szybalski (US) and Zofia Opara-Zubinska (US) concluded that DNA in which thymidine is replaced by 5-bromodeoxyuridine (BUdR) in either or both strands is many times more sensitive to damage by x-rays, short and medium wavelength ultraviolet light, subcritical heat, and hydrodynamic shear(25). 

Kendrick W. Dungan (US) and Paul M. Lish (US) were the first to describe sotalol(26). Initially it was used as a beta-blocker but was later demonstrated to have effects on the action potential (repolarization delay), which led to its use as a class III antiarrhythmic drug(27).

Sipra Guha (IN) and Satish C. Maheshwari (IN) obtained haploid plants of Datura innoxia Mill (Angel's trumpet) from anther cultures(28, 29).

William R. Sharp (US), Donald K. Dougall (US), and Elton F. Paddock (US) obtained haploid plantlets and callus from immature pollen grains of tobacco (Nicotiana) and tomato (Lycopersicon)(30).

Yechiel Becker (IL) and Wolfgang Karl Joklik (AT-AU-US) investigated  the genesis of vaccinia virus specific polyribosomes. Messenger RNAs were found to combine first with 40 S subribosomal particles (the free half-life of mRNA being about 30 s)and then with 60 S subribosomal particles to form polyribosomes. 40 S and 60 S subribosomal particles are always present in strictly equivalent numbers; they are made in the nucleus and enter the cytoplasm as individual entities(31).

Wolfgang Karl Joklik (AT-AU-US) found that uncoating of poxvirus DNA is a two-step process. Enzymes present in uninfected cells release the viral cores and the viral inducer protein. The second, namely the breakdown of cores to liberate the viral genome, requires de novo synthesis of the uncoating protein elicited by the inducer protein(32).

David Pettijohn (US) and Philip C. Hanawalt (US), using Escherichia coli strain TAU-bar, found that in ultraviolet-resistant organisms a mechanism for repair replication exists in which damaged single-strand regions of the chromosome can be excised and replaced, using the undamaged DNA strand as template(33).

Anadi N. Chatterjee (US), James Theodore Park (US), Pauline M. Meadow (GB), John S. Anderson (US), and Jack Leonard Strominger (US) determined that the second phase of the synthesis of bacterial cell wall material occurs in the membrane of the cell. Here UDP-acetylmuramyl-pentapeptide and UDP-acetylglucosamine are joined to form a linear peptidoglycan(34-36). The antibiotics ristocetin, vancomycin, and bacitracin inhibit this second phase of cell wall synthesis.

Maria C. Michaelides (US), Roger Sherman (US), Ernst Helmreich (US), Carl Ferdinand Cori (US), Agnes Ullmann (FR), Pindaros Roy Vagelos (FR-US), Jacques Lucien Monod (FR), Donald L. DeVincenzi (US), and Jerry L. Hedrick (US) presented evidence that muscle glycogen phosphorylase b is an allosteric enzyme influenced by 5’AMP at the allosteric site(37-40). 

Merrill Burr (US) and Daniel Edward Koshland, Jr. (US) developed a technique called reporter groups to correlate function with structure in protein molecules. A chemical group sensitive to environmental changes and which will transmit a signal to an appropriate detector is introduced into a specific position in the protein(41). 

Donald G. Comb (US) and Solomon Katz (US) presented evidence that tRNA precursor molecules are synthesized in the nucleolus, move to the cytoplasm where base methylation occurs and perhaps other alterations, then moves back to the nucleolus(42).

Luigi Gorini (IT-US) and Eva Kataja (US) presented evidence that streptomycin was altering the specificity of translation via an interaction with the ribosome. They suggested that, "the ribosomal structure could include the accuracy of the reading of the code during translation"(43).

Julian E. Davies (US), Luigi Gorini (US), Eva Kataja (US), Walter Gilbert (US), Bernard David Davis (US), Theophil Staehelin (US) and Matthew Stanley Meselson (US) determined that streptomycin and related antibiotics interfere with the protein translation process(44-49).

Jonathan R. Warner (US) and Alexander Rich (US) found that each ribosome possesses two tRNA binding sites. They postulated that the two binding sites are adjacent. One of them they called the A site, which binds aminoacyl tRNA, and the other the P site, which binds peptidyl tRNA(50).

Ute Geigenmuller (DE) and Knud H. Nierhaus (DE) postulated the existence of a third tRNA binding site on the surface of the ribosome, the E site (Exit). When the tRNA from the P site has had its peptide chain transferred to the adjacent tRNA, it does not leave the ribosome promptly. Rather, it delays slightly at the E site(51). 

Ralph B. Arlinghaus (US), Joseph Schaeffer (US), Richard S. Schweet (US), Joanne M. Ravel (US), Jean Lucas-Lenard (US), Anne-Lise Haenni (US), Richard W. Erbe (US), and Philip Leder (US) found that the so called T factor, together with GTP, participates in the attachment of aminoacyl tRNAs to ribosomes(52-55).

Te-Wen Chang (US) and Louis Weinstein (US) report that the antibiotic cephalothin inhibits cell wall peptidoglycan synthesis(56).

Max Bernard Lurie (LT-US) discovered that macrophages must be activated to digest cells of Mycobacterium tuberculosis(57).

Irwin A. Rose (US), Jessie V.B. Warms (US), and Edward L. O’Connell (US) observed that during glycolysis inorganic phosphate counteracts the glucose-6-phosphate inhibition of hexokinase(58).

Cyril Moore (US) and Berton Charles Pressman (US) presented evidence that the antibiotic valinomycin acts as an ionophore which transports potassium ions down its electrochemical gradient and across the cell membrane. It is an energy dependent accumulation of potassium ions in mitochondria(59).

Daniel Nathans (US) demonstrated that puromycin inhibits protein synthesis by being incorporated into the growing polypeptide chain, resulting in premature termination of translation(60).

Alwin Max Pappenheimer, Jr. (US), R. John Collier (US), Ronald S. Goor (US), Elizabeth Ames (US), D. Michael Gill (US), Robin Brown (US), James T. Kurnick (US), Tasuku Honjo (JP), Yasutomi Nishizuka (JP), Osamu Hayaishi (JP), Iwao Kato (JP), Tsuyoshi Uchida (JP), and Annabel A. Harper (US) demonstrated that diphtheria toxin acts by inhibiting protein synthesis. It specifically inactivates elongation factor 2 (EF-2) by an ADP-ribosylation reaction in the presence of nicotinamide adenine dinucleotide (NAD)(61-68).

Humberto Fernández-Morán (VE), Takuzo Oda (JP), Paul V. Blair (US), and David Ezra Green (US) demonstrated the presence of thousands of elementary particles (EP) embedded within the inner membrane of mitochondria from various sources. Each EP was composed of: (1) a head (80-100 angstroms), (2) a cylindrical stalk (about 50 angstroms long and 30-40 angstroms wide), and (3) a base piece (40 X 110 angstroms)(69).

Lucien G. Caro (US) and George Emil Palade (RO-US) examined the synthesis, intracellular transport, storage, and discharge of secretory proteins in and from the pancreatic exocrine cell of the guinea pig using light- and electron microscopical autoradiography with DL-leucine-4,5-H(3) as label. The autoradiographic observations show that, at approximately 5 minutes after injection, the label is localized mostly in cell regions occupied by rough surfaced elements of the endoplasmic reticulum; at approximately 20 minutes, it appears in elements of the Golgi complex; and after 1 hour, in zymogen granules. The evidence conclusively shows that the zymogen granules are formed in the Golgi region by a progressive concentration of secretory products within large condensing vacuoles.

James D. Jamison (US) and George Emil Palade (RO-US) provided direct evidence that secretory proteins are transported from the cisternae of the rough ER to condensing vacuoles via the small vesicles of the Golgi complex(70, 71).

Joseph E. Varner (US), G. Ram Chandra (US), and Maarten J. Chrispeels (US) discovered that the plant hormone gibberellin regulates the expression of alpha-amylase in barley aleurone cells at the level of the gene(72, 73).

George Joseph Todaro (US), Howard Green (US), and Burton D. Goldberg (US) noted that contact inhibition is abolished or greatly diminished when cells are transformed by polyoma virus or simian virus 40(74).

Sir James L. Gowans (GB), E. Julie Knight (GB), and Vincent T. Marchesi (US) showed that lymphocytes recognize post-capillary high-walled endothelial venule (HEV) cells that are present under normal circumstances only in lymphoid tissues. These lymphocytes when taken from a particular lymphoid site tend to return, or home back to the same site when reinjected, suggesting that they possess homing receptors(75, 76).

Sir Michael Francis Addison Woodruff (GB) and James L. Boak (GB) demonstrated that animals experience a stimulation of their immune system and an inhibition of transplantable tumors when injected with species of Corynebacterium parvum(77).

Robert S. Edgar (US) and Ilga Lielausis (US) isolated temperature sensitive mutants of T4 bacteriophage and showed that its linkage map had no ends, and so could be drawn as a circle(78).

Marshall Warren Nirenberg (US), and Philip Leder (US) announced their technique by which artificially synthesized RNA trinucleotides cause specific tRNAs to bind to the surface of ribosomes. These tRNAs each carry a specific amino-acid called for by the one-word codon in the synthetic trinucleotide. Using this methodology they rapidly determined many of the codons used by the cell to specify amino acids. These became part of what is now called the RNA dictionary(79-84).

James Dewey Watson (US), Yasutomi Nishizuka (JP), Fritz Albert Lipmann (US), Julian Gordon (CH), Jean Lucas-Lenard (US), and Maxwell E. Gottesman (US), proposed that GTP and the G (ribosome-linked GTPase) factor are involved in messenger RNA movement and, simultaneously, in translocation of the newly synthesized peptidyl-tRNA from the aminoacyl to the peptidyl site(85-87).

Francois Jacob (FR), Agnes Ullmann (FR), and Jacques Lucien Monod (FR) discovered the element in the genetic mechanism of control in microorganisms at which molecules of the enzymes that make messenger RNA must attach in order to start transcribing from DNA into RNA. They named this element the promoter(88).

Patricia Farnes (US), Barbara E. Barker (US), L.E. Brownhill (US), and H. Fanger (US) discovered that the extract of pokeweed is mitogenic to lymphocytes of peripheral blood(89).

Tsvi Sachs (IL) and Kenneth Vivian Thimann (GB-US) showed that the growth of axillary buds, which remain dormant in the presence of terminal buds, can be initiated by the exogenous application of cytokinins. Thus one could induce the release of lateral buds on a growing shoot with an intact terminal bud by growing the shoot in a medium containing cytokinin. This would release buds from apical dominance(90).

Arnold E. Reif (US) and Joan M.V. Allen (US) discovered the theta—later changed to thy—antigenic marker for thymus-derived (T) lymphocytes and found it to be specific for lymphocytes of thymic origin(91).

Herman N. Eisen (US), Gregory W. Siskind (US), and Baruj Benaceraff (US) discovered that a feature of the immune response to T cell-dependent antigens is an increase in the average affinity of antigen-specific antibody during the course of the response(92, 93). 

Stanley D. Beck (US), Nancy J. Alexander (US), John L. Shane (US), and Irene B. Colvin (US) investigated whether the hormone proctodone, which they discovered and named, plays a role during diapause development in insects. They proposed a two-oscillator model to explain the interaction between the secretion of proctodone and the secretion of prothoracicotropic hormone from the cerebral neurosecretory system. This model suggested that an eight hour subcircadian proctodone rhythm is phase set by the onset of darkness, and that an eight hour cerebral neurosecretory rhythm is phase set by the onset of illumination. They concluded that proctodone activates the neurosecretory system under long days, when the two rhythms are in phase, but this does not occur under short days, when the two rhythms are out of phase(94-97).

Philip J. Hoedemaeker (NL), J.J. Abels (NL), J.J. Wachters (NL), A. Arends (NL), and H.O. Nieweg (NL) determined the site of intrinsic factor production to be parietal cells of the stomach in man, monkey, rabbit, guinea pig, cat, and ox; peptic cells in the rat and mouse, and pyloric duodenal cells in the hog(98, 99).

Ralph Gräsbeck (FI), Kai Lennart Simons (DE), and Irma Sinkkonen (FI) isolated intrinsic factors from human gastric juice and determined it to be a 60K Da glycoprotein(100, 101). 

Patrick B. Jones (US), Sidney P. Kent (US) and Charles E. Butterworth, Jr. (US) determined the chemical and biological properties of fractions derived from hog intrinsic factor concentrate by disc electrophoresis(102).

Theodore Thomas Puck (US) carried out experiments in which he demonstrated that the large variation in the apparent radiosensitivity of different organs is due essentially to regional differences in the rate of cell turnover(103).

Liliana Lubínska (PL) showed that axonal transport is not a simple flow of axoplasm. She described in nerve fibers the retrograde and anterograde movements of radioactive acetylcholinesterase(104).

Susumu Hagiwara (JP-US), Ken-ichi Naka (JP), Shiko Chichibu (JP), and Charles Edwards (US) described ionic mechanisms in active membranes and especially calcium channels. They discovered blocking ions, flux saturation, and that intracellular calcium blocks calcium channels. All of this work was done in muscle fibers of the giant barnacle(105-108).

Graham Hoyle (US) and Thomas Smyth, Jr. (US) had discovered the giant muscle fibers in the North Pacific barnacle(109).

Ian MacPherson (GB) and Luc Montagnier (FR) demonstrated that with polyoma virus there is a systematic relationship between dose of virus and number of transformed colonies of cells(110).

John W. Littlefield (US) introduced HAT medium (hypoxanthine, aminopterin, and thymidine) for the selective growth of somatic cell hybrids(111). Together with the technique of cell fusion, this made somatic-cell genetics possible.

Kjeld Adrian Marcker (DK) and Frederick Sanger (GB) discovered that when protein synthesis occurs in Escherichia coli the first amino acid in every new polypeptide is N-formylmethionine brought to the ribosome by N-formyl-tRNAf(112).

David Guthrie Catcheside (GB-AU), Adrienne P. Jessop (GB), and Brian R. Smith (GB) discovered rec genes in Neurospora. These are unlinked or nonadjacent genes which influence local recombination frequencies(113).

Edmund Brisco Ford (GB) coined ecological genetics to refer to the study of evolution in action by a mixture of laboratory and field work(114).

Edwin T. Mertz (US), Oliver Evans Nelson, Jr. (US), Lynn S. Bates (US), and Olivia A. Vernon (US) demonstrated that the opaque 2 and floury 2 mutants of maize (Zea mays L.) produce seed containing elevated concentrations of two essential amino acids, lysine and tryptophan, that are deficient in normal corn seed(115, 116).

Marcia L. Craig (US) and Elizabeth Buckley Shull Russell (US) demonstrated that in mice embryonic hemoglobins are expressed only in the large nucleated erythrocytes from the yolk sac while adult hemoglobins are produced in the fetal liver(117). This finding supported arguments that differential gene expression is dependent on factors intrinsic to ontogenic stages.

Eugene H. Labrec (US), Herman Schneider (US), Thomas J. Magnani (US), and Samuel B. Formal (US) found that the essential step in the pathogenesis of bacillary dysentery (Shigella flexneri) is the invasion of the colonic mucosa(118).

M.V. Voino-Yasenetsky (HU), Th. N. Khavkin (HU-RU), Akio Takeuchi (US), Samuel B. Formal (US), Eugene H. Labrec (US), and Helmuth Sprinz (US) determined that the process of invasion by Shigella includes penetration into epithelial cells, intracellular replication leading to host cell death, and spreading to adjacent cells and conjunctive tissue of intestinal villi(119, 120).

Philippe J. Sansonetti (FR), Dennis J. Kopecko (US), and Samuel B. Formal (US) discovered that a plasmid within Shigella is encoded with the information necessary to invade host cells(121, 122).

Anand S. Sarabhai (IN), Anthony O.W. Stretton (US), Sydney Brenner (ZA-GB), and Antoinette Bolle (CH), working with the T4 virus of Escherichia coli, demonstrated that nonsense codons determine the length of polypeptides destined to be incorporated into the head protein of the virus. This strongly suggested that nonsense codons act as termination signals during polypeptide synthesis(123).

Robin Holliday (GB) proposed that genetic recombination in yeast proceeds through two single stranded breaks made simultaneously at the same sites on the two DNA molecules to be recombined (the Holliday Junction). During recombination, the nicked strands unwind then invade the DNA of the opposite homolog by rewinding with one of its DNA chains. At this point the rewinding structure rotates to take on a crossed configuration. In his honor this crossed configuration is called a Holliday intermediate(124).

Donald D. Hurst (US), Seymour Fogel (US), and Robert K. Mortimer (US) investigated the relationship between gene conversion and crossing-over at several different loci in Saccharomyces cerevisiae. They demonstrated that for a given marker about 50% of conversion events are associated with crossing-over, whereas the other 50% do not show an associated crossing-over(125). Gene conversion represents the nonreciprocal transfer of information between two homologous sequences where one allele is duplicated while another is lost.

Jack William Szostak (GB-US), Terry L. Orr-Weaver (US), Rodney J. Rothstein (US), and Franklin W. Stahl (US) proposed the double-strand-break repair (DSBR) model to explain tetrad data generated by Saccharomyces cerevisiae matings(126).

Alain Nicolas (FR), Douglas Treco (US), Neil P. Schultes (US),  Liang Cao (US), Eric  Alani (US), Nancy Kleckner (US), and Jack William Szostak (GB-US) went on to provide strong support for this conjecture, showing that double-strand breaks do occur at the time and place of initiation of meiotic recombination and that genetic defects that block the appearance of double-strand breaks also block the initiation of recombination(127, 128). 

Hunt Potter (US) and David Dressler (US-GB) demonstrated the validity of the Holliday model of recombination(129).

Paul Ichiro Terasaki (US) and John D. McClelland (US) developed the microcytotoxicity test, critical for further development and practical use of HLA typing(130).

Fritz H. Bach (US) and Kurt Hirschhorn (US) along with Barbara Bain (CA), Magdalene R. Vas (CA), and Louis Lowenstein (CA) independently developed the mixed lymphocyte culture (MLC) test of histocompatibility(131, 132).

Richard J. Haslam (GB) observed that platelets themselves under the influence of a suitable agent such as thrombin, release enough adenosine diphosphate (ADP) to induce their own aggregation(133).

Robert Gwyn MacFarlane (GB) set out for the first time the concept of blood coagulation as a cascade of eight enzymatic reactions which culminate in the formation of fibrin, and which involve activation of factors, as well as biochemical amplification and negative feedback to control the process(134).

Roger L. Lundblad (US) and Earl W. Davie (US) suggested that activated Christmas factor converted anti-hemophilic factor to an active form, and it in turn converted Stuart factor to an active form in the presence of phospholipid and calcium(135).

Earl W. Davie (US) and Oscar D. Ratnoff (US) presented a blood coagulation scheme they called a "waterfall sequence for intrinsic blood clotting"(136).

Rose Payne (US) Millie Tripp (US), Joan Weigle (CH-US), Sir Walter Fred Bodmer (GB), and Julia Bodmer (GB) defined the allelic system now known as HLA-A 1, 2, and 3(137).

Jack S. Remington (US), Kenneth L. Vosti (US), Arthur Lietze (US), A. Leonard Zimmerman (US), Malcolm S. Artenstein (US), Joseph A. Bellanti (US), and Edward L. Buescher (US) simultaneously reported that immunoglobulin alpha (IgA) is the predominant immunoglobulin in normal human nasal secretions collected by lavage of the nasal cavities with isotonic salt solution(138, 139).

Robert L. Hirsch (US), Donald G. McKay (US), Rosemary I. Travers (US), and Ruth K. Skraly (US) found that hypertriglyceridemia is common during a state of infection(140).

Carol A. Rouzer (US), Anthony Cerami (US) found that defective triacylglycerol clearance during infection is caused by systemic suppression of the enzyme lipoprotein lipase (LPL)(141).

Masanobu Karakami (JP), Anthony Cerami (US), Phillip H. Pekala (US), and M. Daniel Lane (US) found that macrophages secrete cachectin which suppresses lipoprotein lipase activity(142, 143).

Edward Claus Franklin (DE-US), Jerome Lowenstein (US), B. Bigelow (US) and Martin Meltzer (US) reported the first gamma heavy chain disease. The patient presented with an unexplained lymphadenopathy, fever, and a spike in the gamma fraction of serum(144).

Elliott F. Osserman (US) and Kiyoshi Takatsuki (JP) coined the phrase gamma heavy chain disease(145).

Wolfgang Rapp (FR), Samuel B. Aronson (US), Pierre Burtin (FR), Pierre Grabar (RU-DE-FR), Paul A. Crabbé (BE), Joseph Felix Heremans (BE), R. Havez (FR), F. Guerrin (FR), Jean-Pierre Muh (FR), Gérard Biserte (FR), Lars A. Hanson (SE), and Bengt G. Johansson (SE) reported that in addition to contribution from the plasma, the gastric mucosa actively secretes four classes of immunoblobulins—IgA, IgG, IgM, and IgD—into the gastric fluid(146-150).

Jerome W. Conn (US), Edward L. Cohen (US), and David R. Rovner (US) noted that hypertension associated with overproduction of aldosterone, the salt-active adrenal hormone, results from either an abnormality of the adrenal gland itself or a circulatory deficiency of the kidney. This paper demonstrates that these two causes of hypertension can be distinguished functionally by measuring the level of plasma renin activity, subnormal in adrenal cases and supernormal in renovascular cases(151).

John B. West (US), Colin T. Dollery (US), and Arnold Naimark (US) determined the distribution of blood flow in isolated lung and its relation to vascular and alveolar pressures. This is the paper that originally described the "zones of the lung." The paper and its final figure can be used to teach or review a number of physiological concepts. These include the effects of gravity on pulmonary blood flow and pulmonary vascular resistance; recruitment and distention of pulmonary vessels; the importance of the transmural pressure on the diameter of collapsible distensible vessels; the Starling resistor; the interplay of the pulmonary artery, pulmonary vein, and alveolar pressures; and the vascular waterfall. In addition, the figure can be used to generate discovery learning and discussion of several physiological or pathophysiological effects on pulmonary vascular resistance and the distribution of pulmonary blood flow(152).

Allan Kliman (US) and Mark E. Lesses (US) introduced plasmapheresis as a means of collecting plasma for fractionation(153).

William Grey Walter (GB-US) discovered a very slow change in electrical potential at and around the vertex of the head, measured with respect to indifferent reference points such as the ear lobes. Walter named this event the contingent negative variation (CNV), because it was seen only after a warning signal had been given to a human subject, who would then plan a possible movement in anticipation of a second signal. German researchers discovered a comparable slow potential in a similar behavioral context, calling it the bereitsschaftpotential (readiness potential). These electrical potentials permit the observer to predict that a subject will make a response within the next half to one second, before the subject is aware of an intention to act. Some psychologists regard this cerebral phenomenon as evidence that intentional actions are initiated before awareness of such actions emerges, and that consciousness is involved in judging the values of actions rather than in the execution of them(154).

John Holmes Dingle (US), George F. Badger (US), and William S. Jordan, Jr. (US) wrote, Illness in the Home: A Study of 25,000 Illnesses in a Group of Cleveland Families. Among its findings were: 1) three uncultivatable filterable agents are responsible for atypical pneumonia (now know to caused by Mycoplasma pneumoniae), influenza-like illness (now known to be caused by several different adenoviruses), and the common cold (now known to be caused by a number of rhinoviruses), 2) many children are infected by certain types of adenovirus early in life, often without symptoms, 3) adenovirus types responsible for acute respiratory disease in military recruits are not important causes of illness in civilians, 4) antihistamine is ineffective for the treatment of colds, 5) and there are two kinds of non-bacterial gastroenteritis(155).

Irving J. Selikoff (US), Jacob Churg (US), and E. Cuyler Hammond (US) reported on the mortality experience of a cohort of 632 asbestos insulation workers in the New York area, during their working years of 1943-1962. They found significant increases in deaths from lung cancer, mesothelioma, gastrointestinal cancer, and asbestosis(156).

Michael Lesch (US), William Leo Nyhan (US), and William J. Oliver (US) described two young male patients (brothers) presenting with excessive uric acid and blood in the urine, spasticity, choreoathetosis, mental retardation, and compulsive aggressive behavior that led them to bite away their lips and tongue and to bite away the ends of their fingers(157, 158). This metabolic disease was later named The Lesch-Nyhan Syndrome.

Werner Catel (DE) and J. Schmidt (DE) were probably the first to describe this syndrome(159). 

Jarvis Edwin Seegmiller (US), Frederick M. Rosenbloom (US), and William N. Kelley (US) found that Lesch-Nyhan Syndrome is a rare condition caused by a defective gene on the X chromosome leading to a nearly complete absence of the enzyme hypoxanthine guanine phosphoribosyltransferase (HGPRTase). Absence of this enzyme leads to an excessive production of uric acid(160).

William N. Kelley (US), Frederick M. Rosenbloom (US), and Jarvis Edwin Seegmiller (US) found that a partial loss of hypoxanthine guanine phosphoribosyltransferase (HGPRTase) activity is associated with excessive purine synthesis in some patients with gout(161).

Roland Kuhn (CH) observed that imipramine, a tricyclic compound, can relieve depression in patients(162).

Jacques Glowinski (FR) and Julius Axelrod (US) found that tricyclic antidepressant drugs block the uptake of 3H labelled-norepinephrine in brain neurons(163).

Susan G. Amara (US) and Michael J. Kuhar (US) reported that cocaine, amphetamines, and antidepressants also block the uptake of dopamine and serotonin(164). Prozac (fluoxetine), a specific serotonin uptake inhibitor is the best known antidepressant which works in this manner.

Lionel Gordon Whitby (GB), Georg Hertting (AT), and Julius Axelrod (US) found that cocaine blocks the uptake of norepinephrine in sympathetic nerves. This allows greater amounts of the neurotransmitter to remain in the synaptic cleft after cocaine and act on the post-synaptic receptors more intensely and for longer periods of time(165).

Julius Axelrod (US) found that amphetamine blocks the uptake as well as the release of 3H-labelled-norepinephrine in the brain(166).

Thomas Earl Starzl (US), David T. Rowlands, Jr. (US), Charlie H. Kirkpatrick (US), W.E.C. Wilson (US), David Rifkind (US), and William R. Waddell (US) discovered that splanchnic venous blood of dogs contains hepatotrophic factor(s), the most important of which was later proved to be insulin; the finding dictated methods of liver allograft revascularization(167).

Thomas Earl Starzl (US) established rules to prevent ABO-incompatibility in renal transplantation surgery(168). 

Alfred J. Luessenhop (US) and Alfredo C. Velasquez (US) introduced endovascular surgery for arteriovenous malformations (AVMs) and aneurysms(169).

Emil Frei III (US), Emil J. Freireich (US), James F. Holland (US), and Donald Pinkel (US) were pioneers in the use of combination chemotherapy, and supportive care of patients receiving combination chemotherapy for lymphoma and acute leukaemia(170-174).

Roy Hertz (US), Griff T. Ross (US), Mortimer B. Lipsett (US), Charles B. Hammond (US), William D. Odell (US), Delbert M. Bergenstal (US), Edward B. Price (US), Theodore F. Hilbish (US) and Min Chiu Li (US) made outstanding contributions to the successful chemotherapeutic treatment of human gestational choriocarcinoma, a solid tumor(175-180).

Jerold F. Lucey (US), Emerson Hibbard (US), Richard E. Behrman (US), F. Ofelia Esquivel de Gallardo (US), William Frederick Windle (US), and Maria D. Faro (US) discovered a consistent and precise pattern of brain damage following asphyxiation and resuscitation of the infant at birth. They found that this suffocation is a frequent cause of mental retardation, and cerebral palsy. They were also the first to correlate this pathology with the clinical symptoms of cerebral palsy, and the first to associate it with the condition known as kernicterus, in which specific centers of brain are colored yellow(181-183).

Charles Theodore Dotter (US) and Melvin P. Judkins (US) were the first to use the catheter for intentional percutaneous transluminal angioplasty. It was used to benefit a patient with a painful left foot. The foot had a nonhealing ulcer and gangrenous toes(184). Charles Theodore Dotter (US) is generally credited with developing a new medical specialty, interventional radiology.

Andreas Grüntzig (CH) and Heinrich Hopff (CH) developed a balloon catheter capable of dilating peripheral arteries(185).

H. Vernon Ingram (DE-GB-US) introduced the use of the laser for eye surgery(186).

Charles R. Hamilton (US) and Michael S. Gazzaniga (US) reported evidence of laterality (hemispheric preference) in discrimination of visual tasks (color and brightness) in non-human primates(187).

Victor H. Denenberg (US) following his work with hemispheric laterality in rats presented his theory that the brain possesses innate functional asymmetry(188). 

William Donald Hamilton (GB) proposed a theoretically robust genetical basis for altruism, kin selection, and inclusive fitness. If the success of genes shared with relatives is included in total fitness, then even sterile individuals can have fitness if their relatives are very successful. Helping behavior of sterile social insects could assure their fitness in this way. Hamilton offered the simple inequality that the ratio of cost and benefit incurred by helping must be less than the degree of relatedness (C/B<r)(189). These ideas have since been extended to social behaviors of many species—vertebrate as well as invertebrate.

Henry de Lumley (FR) and Marie-Antoinette de Lumley (FR), in 1964, discovered the fossil remains of a Homo erectus/Homo sapiens transitional form in the Verdouble Valley in Southeastern France. The age of this fossil man (Arago man) is uncertain (ca. 130,000)(190).

Paul Ralph Ehrlich (US) and Peter Hamilton Raven (US) defined the process of coevolution as a reciprocal interaction in which evolution of new chemical defenses in a plant taxon is followed by evolution of new means of circumventing those defenses in specialist butterfly herbivores. They concluded that repeated coevolutionary interactions of this sort have been critical to the diversification of both butterflies and flowering plants(191).


What Goes in Must Come Out

The great Dr. Starling, in his Law of the Heart

Said the output was greater, if, right at the start,

The cardiac fibers were stretched a bit more,

So their force of contraction would be more than before.

Thus, the larger the volume in diastole,

The greater the output was likely to be.

But when the heart reaches a much larger size,

This leads to Heart Failure, and often, Demise.

The relevant law is not Starling's, alas,

But the classical law of Lecompte de Laplace.

Your patient is dying in Decompensation,

So reduce his Blood Volume, or call his Relation.

If the right heart keeps pumping more blood than the left,

The lung circuit's congested; the systemic -- bereft.

Since no one is healthy with pulmo-congestion,

The law of Doc. Starling's a splendid suggestion.

The balance of outputs is made automatic

And blood-volume partition becomes steady-static.” Alan Chadburn Burton (CA)(192).

Robert Burns Woodward (US) was awarded the Nobel Prize in Chemistry for his achievements in organic synthesis.

Francois Jacob (FR), Jacques Lucien Monod (FR), and André Michael Lwoff (FR) shared the Nobel Prize in Physiology or Medicine for their discoveries concerning genetic control of enzyme and virus synthesis.

Cambridge Instruments produced the first commercial scanning electron microscope. ref

Robert Burns Woodward (US) accomplished the total synthesis of colchicine(193).

ICI Chemical Company introduced the herbicide paraquat, a bipyridyl quaternary ammonium salt, useful in sugar cane (Saccharum officinarum) and fruit trees. ref 

John Holmes Dingle (US) developed a rapid method for separating and determining DDT in fat(194).

Seiichiro Tauri (JP), Giichi Okuno (JP), Yuji Ikura (JP), Takehiko Tanaka (JP), Masami Suda (JP), and Mitsuo Nishikawa (JP) reported phosphofructokinase deficiency, also known as glycogen storage disease type VII or Tarui's disease. They found phosphofructokinase activity was decreased in erythrocytes with patients inheriting the disorder in an autosomal recessive pattern(195). 

Walton H. Marsh (US), Benjamin Fingerhut (US), and Henry Miller (US) published modifications of the direct assay of urea with diacetyl monoxime, applicable to both manual and automated procedures(196).

Giuliana Mancini (IT), Angelo O. Carbonara (IT), and Joseph Felix Heremans (FR) developed a method for the immunochemical quantification of antigens by single radial immunodiffusion(197).

Vida K. Vambutas (US) and Efraim Racker (PL-AT-US) purified chloroplast F1 (termed CF1) which restored light-driven ATP synthesis to EDTA-treated chloroplast fragments, but did not cleave ATP unless it was gently shaken with trypsin. This result confirmed the general expectation that photophosphorylation and oxidative phosphorylation function by a similar mechanism(198).

George Alan Robison (US), Reginald William Butcher (US), Ivar Øye (NO), Howard E. Morgan (US) and Earl Wilbur Sutherland , Jr. (US) found that epinephrine (adrenaline) causes a rapid raise in the level of cellular adenosine 3’,5’-phosphate (cyclic AMP) in perfused rat heart(199).

Reginald William Butcher (US), Ren-Jye Ho (US), H.C. Meng (US), and Earl Wilbur Sutherland, Jr. (US) showed that elevated cellular cyclic AMP stimulates lipolysis(200).

Jerome R. Vinograd (US), Jacob Lebowitz (US), Roger J. Radloff (US), Robert Watson (US), and Philip J. Laipis (US) showed that covalently closed circular DNAs can assume a superhelical configuration(201).

Ronald A. Cooper (GB) and Hans Leo Kornberg (GB-US) discovered that E. coli can grow on C3 compounds such as alanine, lactate, or pyruvate because it contains the, heretofore, unknown enzyme, phosphoenolpyruvate synthase. This enzyme catalyzes the interaction of ATP with pyruvate yielding phosphoenolpyruvate, phosphate-inorganic, and adenosine monophosphate; the energy barrier is surmounted by using two of the "energy-rich" bonds of adenosine triphosphate. This essentially allows the reversal of glycolysis(202-205).

John Leslie Fahey (US) and Eugene M. McKelvey (US) performed a quantitative determination of serum immunoglobulins in antibody-agar plates(206).

E. Frederick Wheelock (US) found that phytohemagglutinin (PHA) from the kidney bean induces in human leucocyte cultures an inhibitor of the cytopathic effects of Sindbis virus. The physicochemical and biological properties of this virus-inhibitor are similar to those of interferon induced by Newcastle disease virus(207).

Philip Leder (US), Maxine Frank Singer (US), Richard L.C. Brimacombe (DE), Robert E. Thach (US), and Paul Mead Doty (US) announced methods for the in vitro enzymatic synthesis of oligonucleotides of known base sequence using nucleotide phosphorylase(208, 209).

Bruce Woodson (US) and Wolfgang Karl Joklik (AT-AU-US) found that isatin-beta-thiosemicarbazone (IBT) affects the ability of late vaccinia virus mRNA to express itself normally. This inhibits replication of the virus(210). 

Fumio Imamoto (JP), Nobuko Morikawa (JP), Koki Sato (JP), S. Mishima (JP), Tetsuji Nishimura (JP), and Aizo Matsushiro (JP) isolated messenger RNA produced by the tryptophan operon in Escherichia coli. Because the production of this messenger is reduced by the addition of tryptophan, they concluded that regulation in the tryptophan system operates at the gene level(211).

Igor Bert Dawid (US) found that an egg of the frog Xenopus laevis contains orders of magnitude more high molecular DNA than the amount expected of a single cell(212).

Igor Bert Dawid (US) showed that the egg DNA of Xenopus laevis is a select group of sequences rather than representative of the entire frog genome. He demonstrated that the extra egg DNA is mitochondrial DNA(213). These discoveries led to the realization that an individual's mitochondria are maternally inherited.

Satoshi Suzuki (JP), Kiyoshi Isono (JP), Junsaku Nagatsu (JP), T. Mizutani (JP), Y. Kawashima (JP), and T. Mizuno (JP) were the first to isolate the antifungal antibiotic polyoxin. It is produced bt Streptomyces cacaoi(214).

Susumu Nishimura (JP), David S. Jones (GB), and Har Gobind Khorana (IN-US) developed a non-enzymatic in vitro technique for synthesizing long strands of RNA with known, simple repeating units. Using these he and his colleagues determined the base sequence for many codons(215-217).

C. Fred Fox (US) and Eugene Patrick Kennedy (US) partially purified a surface protein (permease) of Escherichia coli which specifically recognizes beta-galactosides(218). Rickenberg, Cohen, and Monod had predicted its existence in 1956.

Donald J. Tipper (US), Jack Leonard Strominger (US), Edmund M. Wise, Jr. (US), and James Theodore Park (US) found that the final step in bacterial cell wall synthesis is the peptide cross-linking of the linear peptidoglycan strands. This reaction occurs at the outside of the cell membrane. It is this final step which is inhibited by penicillins and cephalosporins(219-221).

Robert William Holley (US), Jean Apgar (US), Susan H. Merrill (US), James T. Madison (US), John Robert Penswick (US), George A. Everett (US), Mark Marquisee (US), and Ada Zamir (US) worked out the complete primary nucleotide sequence of an alanine transfer RNA isolated from yeast. This was the first nucleic acid for which the structure was known. They also proposed that it had a clover-leaf like secondary structure(222).

Hans Bremer (US), Michael W. Konrad (US), Kathleen Gaines (US), Gunther Siegmund Stent (US), Umadas Maitra (US), and Jerard Hurwitz (US) determined that polynucleotide chain growth during RNA synthesis proceeds from the 5 prime to the 3 prime end of the molecule(223, 224). 

Beatrice Mintz (US) created allophenic mice to generate alternative phenotypes that would function as contrasting cell labels, permitting cell lineages, fusions, and deployments to be revealed, and allowing the underlying developmental organization of tissues to be analyzed.

Allophenic mice were created by taking two cleavage stage embryos of dissimilar genotypes, removing them from the uteri of pregnant females, lysing the acellular zone pellucida in pronase, then culturing them in contact at 37°C for a day. During this time the cells aggregate into a normal, but double-size blastocyst. This blastocyst is surgically transferred to the uterus of a pseudopregnant incubator mother. Usually normal viable mosaic mice result from this procedure(225).

Erich Pfaff (DE), Martin Ernst Klingenberg (DE), and Hans W. Heldt (DE) demonstrated that for mitochondria : (1) ATP, ADP, and AMP penetrate them very rapidly, (2) a rapid, but considerably slower exchange of exogenous and endogenous adenine nucleotides occurs, (3) the exchange is specific for adenine nucleotides suggesting that it is catalyzed(226).

Solomon Spiegelman (US), Ichiro Haruna (JP), I. Barry Holland (FR), George S. Beaudreau (US), Donald R. Mills (US), and Norman Richard Pace, Jr. (US) devised an in vitro system for the replication of RNA. They found that a virally encoded replicase from phage Q beta can synthesize infectious viral RNA from precursor nucleotides(227, 228). This established the concept of viral RNA acting as a genome.

Ina E. Mattern (NL), Maria P. van Winden (NL), and Arthur Rörsch (NL), using Escherichia coli, determined that a number of genes (including hcr, dar1, dar2, dar3, dar4, dar5, and dar6) must be involved in the repair of otherwise lethal UV damage to DNA(229).

Pierre Baudhuin (FR), Miklós Müller (HU-US), Brian Poole (US), Christian Rene de Duve (GB-BE-US), and James F. Hogg (GB) showed the existence in some non-plant organisms of peroxisomes which, like plant glyoxysomes, contain enzymes of the glyoxylate cycle(230, 231).

Robert Hill (GB) discovered that illuminated chloroplasts can effect chemical reductions(232).

Margarita Salas (ES), Marvin A. Smith (US), Wendell M. Stanley, Jr. (US), Albert J. Wahba (US), and Severo Ochoa (ES-US) discovered that the polynucleotide message (mRNA) must be translated in the direction from the 5 prime to the 3 prime end(233).

Efraim Racker (PL-AT-US), Howard Zalkin (US), Maynard E. Pullman (US), Gottfried Schatz (AT-CH), Yasuo Kagawa (US), June M. Fessenden (US), June M. Fessenden-Raden (US), M. Anne Dannenberg (US), Harvey S. Penefsky (US), Lawrence L. Horstman (US), Peter C. Hinkle (US), Ronald A. Butow (US), Britton Chance (US), Bernard Bulos (US), Alex J. Lange (US), Donna Kling (US), William J. Arion (US), Aileen F. Knowles (US), Richard J. Guillory (US), M. Anne Kandrach (US), and C. Ian Ragan (US) found through studies of submitochondrial vesicles that the enzymes for electron transport are bound tightly to the mitochondrial membrane and that the enzyme catalysis of ATP is carried out by an enzyme—the F1/Fo complex—loosely bound to the mitochondrial membrane. Electron flow and simultaneous ATP formation require that these two fractions be together. This work showed that the characteristic knobs which line the inner face of the mitochondrial inner membrane in electron micrographs are, in fact, F1 units (F1 is Factor 1, the o in Fo is for oligomycin sensitive Factor)(234-252).

Britton Chance (US) did work critical in assigning carriers to a sequence in mitochondrial electron transport(253).

Peter Banks (GB) and Karen Blaauw Helle (NO) produced antibodies against the soluble protein of chromaffin vesicles and used them for the first demonstration of exocytosis(254).

Wilmar Dias Da Silva (BR), Irwin H. Lepow (US), Charles G. Cochrane (US), and Hans J. Müller-Eberhard (US) determined that C3a and C3b, the cleavage products of C3 during the complement cascade, are anaphylotoxins which possess biological properties that play an important role in immune and allergic processes by releasing histamine and increasing capillary permeability, i.e., they promote inflammation(255-257).

Jeorg Jensen (US), Charles G. Cochrane (US), Hans J. Müller-Eberhard (US), Hyun S. Shin (US), Ralph Snyderman (US), Eileen Friedman (US), Alice Mellors (US), Manfred Martin Mayer (DE-US), Peter A. Ward (US), and Larry J. Newman (US) found that C5a, a cleavage product of C5 in the complement cascade, is also an anaphylatoxin which can cause the release of histamine and is a potent chemotactic agent thus promoting the inflammatory response(255, 258-260).

Max D. Cooper (US), Raymond D.A. Peterson (US), and Robert A. Good (US) presented evidence suggesting that the lymphoid system is composed of two distinct cell populations each with a separate embryonic origin and different morphologic and functional characteristics. One population is thymus dependent and represented by small lymphocytes in the blood and spleen. They appear to be especially important in cellular immunity and facilitating the immunoglobulin response of the other population. The immunoglobulin producing population is represented by cells in the germinal centers and plasma cells. A normal immune response is usually the result of an interaction between these two populations(261).

Shinpei Kasakura (CA), Louis Lowenstein (CA), Julius Gordon (CA), and Lloyd D. MacLean (CA) found that the medium from human leucocytes cultured in vitro with homologous leucocytes or heterologous leucocytes contains a mitogenic substance produced by the leucocytes(262, 263).

Alvin John Clark (US) and Ann Dee Margulies (US) discovered recombinationless, or Rec-, mutants of Escherichia coli. These mutants are unable to produce genetic recombinants in conjugational crosses. This defect can be traced back to mutations in several bacterial genes, to which the designation rec has been assigned. The first one of these genes they called recA(264).

Robert W. Atchison (US), Bruce C. Casto (US), and William MacDowell Hammon (US) discovered adeno-associated virus (AAV) as a contaminant in purified adenovirus stocks(265). AAV does not productively infect cells in culture unless there is a coinfection by an unrelated helper virus, which in most cases is adenovirus.

M. David Hoggan (US), Gunter F. Thomas (US), and F. Brent Johnson (US) found that AAV is not a defective virus but preferentially establishes a latent infection and is only induced to replicate vegetatively when the host cell is stressed(266).

Robin C. Valentine (GB) and Helio Gelli Pereira (BR-GB-BR) reported the first analysis of the structure of adenovirus(267).

Yoshihisa Suyama (JP) and John R. Preer, Jr. (US) discovered that the mitochondrial DNA of Tetrahymena is linear(most known mtDNA is circular)(268).

C.C. Bowen (US) and Thomas E. Jensen (US) published an account of the fine structure of vacuoles in cyanobacteria. They proved that structures, which they called gas vesicles, were the building blocks of gas vacuoles(269).

Suzanne Bourgeois (FR), Melvin Cohn (US), and Leslie Eleazer Orgel (GB) showed that some of the constituitive mutations of the regulator gene i in the Escherichia coli lactose operon are nonsense mutants and that, consequently, the active product of this gene is a protein(270). This result indicated that recognition of the operator and inducer is linked to the structure of the protein produced by the i gene(270).

Paul F. Kruse, Jr. (US) and Ed Miedema (US) established that for all cell types grown in vitro the limit of growth (the saturation density of cells) is governed by the nutrient supply(271).

Paul H. Black (US) and George Joseph Todaro (US) found that a virus which is a hydrid between the Simian virus 40 and Adenovirus 7 can induce transformation in both human and hamster tissue in vitro(272).

Paul H. Black (US) and Wallace Prescott Rowe (US) performed experiments demonstrating that there is not an association between morphological transformation and tumorigenicity(273).

Sir Henry Harris (AU-GB), John F. Wilkins (GB), Charles Edmund Ford (GB), and Gutta I. Schoefl (AU) used irradiated Sendai virus to fuse mouse Ehrlich ascites cells with human HeLa cells. The procedure provided a general method for fusing together cells from almost any tissue and any species(274).

Camillus L. Witzleben (US) and Shirley G. Driscoll (US) presented evidence in humans  for the possible vertical transmission of herpes simplex from mother to neonate(275). 

Sir Henry Harris (AU-GB) studied RNA and DNA synthesis in various animal heterokaryons and discovered that the regulation of nucleic acid synthesis in heterokaryons is controlled by positive signals: whenever a cell that did not make a particular class of nucleic acid, either RNA or DNA, is fused with one that did, synthesis is initiated in the nucleus of the inactive partner(276).

Earl Wilbur Sutherland, Jr. (US), Ivar Øye (NO), Reginald William Butcher (US), and George Alan Robison (US) deduced that cyclic AMP behaves as a second messenger in hormone action, with the hormones themselves acting as first messengers(277, 278).

Michel Ramuz (FR), Janine Doly (FR), Paul Mandel (FR), and Pierre M. Chambon (FR) demonstrated that there exists different species of DNA dependent-RNA polymerase(279-283).

Robert Gayle Roeder (US) and William J. Rutter (US) demonstrated that eukaryotes possess multiple types of DNA dependent-RNA polymerase (designated poly I, II, and III by Roeder)(284). Each type of polymerase is devoted to the transcription of a different category of genes (ribosomal genes, protein-encoding genes, and genes for small RNAs, respectively).

Claude Kedinger (FR), Marek Gniazdowski (FR), Jean-Louis Mandel, Jr. (FR), Francis Gissinger (FR), and Pierre M. Chambon (FR) supported previous studies indicating that the bacterial RNA polymerase differed from eukaryotic RNA polymerases, and allowed speculation that there were structural differences between polymerases A (I) and B (II)(285).

Robert Gayle Roeder (US), Virgil E.F. Sklar (US), and Lawrence B. Schwartz (US) isolated and analyzed the three DNA dependent-RNA polymerases then developed assays for their activities(286-288).

Merton R. Bernfield (US) and Marshall Warren Nirenberg (US) provided evidence that one molecule of AA-tRNA can respond to two kinds of codons, e.g. most molecules of Phe-tRNA respond to both UUU and UUC(289).

Brian F.C. Clark (GB-DK), Kjeld Adrian Marcker (DK), Donald A. Kellogg (US), Bhupendra P. Doctor (US), Judith E. Loebel (US), Marshall Warren Nirenberg (US), Dieter Söll (US), Diane S. Jones (US), Eiko Ohtsuka (US), Robert D. Faulkner (US), Rolf Lohrmann (US), Hikoya Hayatsu (JP), Har Gobind Khorana (IN-US), Joseph D. Cherayil (US), Arnold E. Hampel (US), Robert M. Bock (US), Susumu Nishimura (JP), Uttam L. RajBhandary (US), Charles Thomas Caskey (US), Arthur L. Beaudet (US), Richard E. Marshall (US), Richard L.C. Brimacombe (DE), Dolph L. Hatfield (US), Judith G. Levin (US), Fritz M. Rottman (US), Sidney Pestka (US), Michael Wilcox (US), and W. French Anderson (US) would show that a purified species of tRNA responds to either 1, 2, or 3 codons(79, 80, 83, 84, 290-296).

Francis Harry Compton Crick (GB) proposed that although the first two bases in a codon always pair with tRNA in a rather strict DNA-like fashion, the pairing in the third position is less restrictive, due to wobble. He theorized that such wobble could explain the general nature of the degeneracy of the genetic code(297).

Michael H. Malamy (US), Peter Starlinger (DE), Elke Jordan (DE), Heinz Saedler (DE), James A. Shapiro (US), Philippe Brachet (FR), Harvey A. Eisen (US), and Alain Rambach (FR) discovered insertion sequences (ISs) in bacteria. They were defined as bacterial mobile DNA elements which cause various kinds of genome rearrangements, such as deletions, inversions, duplications, and replicon fusions, by their ability to transpose. These were discovered during investigation of mutations that are highly polar in the galactose and lactose operons of Escherichia coli K-12 and in the early genes of bacteriophage lambda(298-302). Insertion sequences (ISs) have subsequently been discovered in many eukaryotes (Eucarya) and other prokaryotes (Archaea) and viruses.

Peter Starlinger (DE) and Heinz Saedler (DE) discovered that Escherichia coli DNA includes at least two different classes of insertion sequences, or IS’s. One IS class, 0.8 kb in length, was designated as IS-1, and the other IS class, 1.5 kb in length, as IS-2. A third IS class, designated IS-3 and of the same length as IS-2, was identified later. The elements have the capacity for insertion into the bacterial chromosome at a diversity of genetic sites, in either a clockwise or counterclockwise orientation. Quantitative hybridization tests show that the normal Escherichia coli chromosome contains eight copies of IS-1 and five copies of IS-2 distributed over its length. In Hfr strains the integrated F-plasmid DNA is flanked by one IS at each end. The two flanking IS’s always belong to the same class and both of them lie in the same orientation with respect to the chromosomal map. Non-integrated F plasmids were found to contain several IS copies. IS’s are also present in the DNA of R plasmids which transport blocks of drug-resistance genes between bacterial cells. Unlike F plasmids, R plasmids are not themselves inserted into the bacterial chromosome, but the resistance genes they carry are readily transferred as a block to the host-cell chromosome, or to other plasmids that may be present in the same cell. For instance, if a bacterium happens to contain the DNA of both an R plasmid and a phage, that host cell can liberate phage particles that carry the drug-resistance genes as insertions in their DNA.

It appears that genetic recombination can readily transpose a block of genes flanked by an oppositely orientated IS pair from one chromosome to another. For that reason, such genes with their flanking IS pair have been designated as a transposon (303).

Andrew Wright (US), Marcelo A. Dankert (AR), and Phillips W. Robbins (US) discovered and elucidated the role of carrier lipids in polysaccharide synthesis(304).

Max Ferdinand Perutz (AT-GB), John Cowdery Kendrew (GB), and Herman C. Watson (GB) reached the conclusion that the capacity of a protein to refold after denaturation and retain its functionality depends principally on internal residues, and not those exposed to the solvent. Internal residues in the hydrophobic core of the protein must be carefully conserved(305).

A. Burgerjon (FR), and P.F. Galichet (FR) discovered that Bacillus thuringiensis endospores contain a protein crystal (Bt toxin) which kills certain insect larvae(306). In more recent times the Bt gene has been transferred to plants such as tomatoes making them resistant to certain insects(307).

Miklós Müller (HU-US), Pierre Baudhuin (FR), and Christian Rene de Duve (GB-BE-US), in their studies of the protozoan Tetrahymena pyriformis, identified two types of lysosomes which discharge their enzymes, one in phagocytic vacuoles and the other in the outside medium(308).

Brian S. Cox (US) discovered a non-Mendelian determinant, [PSI+], that affects the level of expression of nonsense suppressors(309).

Francois Lacroute (FR) discovered another non-Mendelian element, [URE3], that affects the level of expression of nonsense suppressors(310).

Reed B. Wickner (US) proposed that these cytoplasmically inherited elements are prions(311).

Emanuel Margoliash (IL), Jay R. Schenck (US), Martha P. Hargie (US), S. Burokas (US), W.R. Richter (US), G.H. Barlow (US), Jack E. Lilien (US), and Aron Arthur Moscona (IL-US) demonstrated that animal cells, if placed in a multicellular and multi-tissue-type suspension, will seek out other cells with which they share a common species and tissue origin(312, 313). 

Ronald Melzack (CA) and Patrick Wall (GB), proposed the gate control theory of pain. They suggested a gating mechanism within the spinal cord that closed in response to normal stimulation of the fast conducting touch nerve fibers; but opened when the slow conducting pain fibers transmitted a high volume and intensity of sensory signals. The gate could be closed again if these signals were countered by renewed stimulation of the large fibers(314).

Wolfgang Karl Joklik (AT-AU-US) and Thomas C. Merigan, Jr. (US) found that in interferon-treated cells viral mRNA and ribosomes do not combine to form polyribosomes(315).

Walden K. Roberts (GB), Ara G. Hovanessian (FR), Ronald E. Brown (GB), Michael J. Clemens (GB), and Ian M. Kerr (GB) discovered the interferon-induced nuclease activating oligonucleotide which is compatible with a two-step model for the inhibition of viral replication in which a pre-inhibitor is activated by dsRNA, the activated inhibitor then interacting with the protein synthesis system to inhibit translation(316, 317).

J. Thomas Grayston (US), E. Russell Alexander (US), George E. Kenny (US), Edmund R. Clarke (US), John C. Fremont (US), William A. MacColl (US) and George E. Enny (US) isolated Chlamydia pneumoniae(318, 319). See, Pekka Saikku, 1985.

Geoffrey Clough Ainsworth (GB), Frederick Kroeber Sparrow (US), and Alfred S. Sussman (US) edited, The Fungi; An Advanced Treatise, one of the most important publications in the history of mycology(320).

Ola Nilsson (SE), Luciano Barajas (US), Jacqueline Müller (US), Svatopluk Dolezel (SE), Lars Edvinsson (SE), Christer Owman (SE), and T. Owman (SE) established the intimate relationship between the renin producing cells of the juxtaglomerular apparatus in the kidney and sympathetic nerve terminals(321-323).

Thomas B. Tomasi, Jr. (US), Eng M. Tan (US), Alan Solomon (US), and Robert A. Prendergast (US) identified the three antibody forms of immunoglobulin alpha (IgA) and ruled out serum as a source of secretory IgA(324). Joseph Felix Heremans (BE) first described IgA in serum in 1959.

Stewart Sell (US) and Philip George Houthem Gell (GB) discovered the ability of antibodies to rabbit immunoglobulin allotypes to stimulate small resting peripheral blood lymphocytes to undergo 'blast' transformation, synthesize DNA, and divide. This is the first demonstration that some lymphocytes possess a surface immunoglobulin (sIg) receptor that can activate the cell(325).

Richard Jay Wurtman (US) and Julius Axelrod (US) found that the adrenal cortical hormones influence the activity of the enzyme that converts norepinephrine (noradrenaline) to epinephrine (adrenaline) (phenylethanolamine N-methyltransferase), creating the situation whereby the medulla secretes the generally more active catecholamine epinephrine (adrenaline) into the bloodstream(326).

Edmund F. LaGamma (US), Joshua E. Adler (US), Byron C. Yoburn (US), Steve O. Franklin (US), Steve E. Calvano (US), Charles E. Inturrisi (US), Martina Sietzen (AT), Maria Schober (AT), Reiner Fischer-Colbrie (AT), Daniel Scherman (FR), Günther Sperk (AT), and Hans Winkler (AT) found that the adrenal cortex appears to influence the peptide and protein content of the adrenal medulla including enkephalins and chromogranins(327-329). 

Klaus Unsicker (DE), Brigitte Krisch (DE), Uwe Otten (DE), Hans Thoenen (DE), Jose-Maria Trifaró (CA), and Raymond W.H. Lee (CA) reported that adrenal cortical hormones influence the shape of the adrenal chromaffin cells, somehow preventing them from extending processes, as do other post-ganglionic sympathetic neurons(330, 331).

Winifred M. Watkins (GB), Terry J. Painter (GB), and Walter Thomas James Morgan (GB) found that human blood type in the ABO system is determined by the terminal sugars of polysaccharides present on the surface of erythrocytes, e.g. type A has a terminal galactose unit while type B has a terminal N-acetylgalactosamine(332-334).

Baruch Samuel Blumberg (US) and Nancy M. Riddell (US) discovered an antibody present in the blood of a person infected with hepatitis which would react with the blood of an Australian aborigine. They named the antigen Australian antigen (Au) in the 1965 article(335, 336).

Baruch Samuel Blumberg (US), Betty Jane S. Gerstley (US), David A. Hungerford (US), W. Thomas London (US), and Alton Ivan Sutnick (US) identified and named the antigen with which this antibody reacted as HBV surface antigen (HBsAg) of the hepatitis B virus. The 1967 paper contains the first suggestion that Australia antigen (Au) is the hepatitis virus(337, 338).

Kazuo Okochi (JP), Seishi Murakami (JP), K. Ninomiya (JP), and M. Kaneko (JP) found that Australian antigen (Au) can be transmitted by transfusion and that it leads to the development of hepatitis in some of the people who receive it, and that some transfused patients develop anti-Au(339, 340).

Manfred E. Bayer (US), Baruch Samuel Blumberg (US), Barbara Werner (US), David Surrey Dane (GB), Colin H. Cameron (GB) and Moya Briggs (GB) isolated and identified the Au (hepatitis B virus) particle using the electron microscope(341, 342). Dane’s group identified 42nm particles. Bayer’s group identified particles of approximately 20nm size. Particles of both sizes contain Au antigen.

Baruch Samuel Blumberg (US) and Irving Millman (US) developed a vaccine against hepatitis B virus(343, 344).

William S. Robinson (US), David A. Clayton (US), Richard L. Greenman (US), and Larry I. Lutwick (US) determined that the hepatitis B virus is a double stranded DNA virus(345, 346).

Eberhardt Weiler (US), Benvenuto Pernis (IT), Gerolamo Chippino (IT), Andrew S. Kelus (US), and Philip George Houthem Gell (US) observed that when a lymphoid cell produces immunoglobulin, only one of its two possible allelic genes is expressed. This is called ‘allelic exclusion’(347, 348).

Robert Alan Good (US), Max Dale Cooper (US), Raymond D.A. Peterson (US), Michael J. Kellum (US), David E.R. Sutherland (US), Ann E. Gabrielsen (US), Jacques Francis Albert Pierre Miller (FR-AT-AU), Christine K. Wennersten (US), Katarina Isakovic (US), Stanley B. Smith (US), and Byron Halsted Waksman (US) discovered that the removal of the thymus gland from neonatal mice results in a severe reduction in immune response. This ushered in the modern era of the study of the cellular basis of the immune response(349-352).

Joseph S. Handler (US), Reginald William Butcher (US), Earl Wilbur Sutherland, Jr. (US), Jack Orloff (US), Jared J. Grantham (US), and Maurice B. Burg (US) demonstrated that vasopressin acts via intracellular cyclic AMP production(353, 354).

Michel Bouteille (FR), C. Fontaine (FR), C.L. Vedrenne (FR), J. Delarue (FR), Giuseppe Barbanti-Brodano (IT), Shinsaku Oyanagi (JP), Michael Katz (US), Hilary Koprowski (US), John H. Connolly (IE), Ingrid V. Allen (IE), Lewis J. Hurwitz (IE), J. Harold D. Millar (IE), Volker ter Meulen (DE), and Dieter Müller (DE) determined that subacute sclerosing panencephalitis (SSPE) is a slow infection of measles virus with reactivation years after the initial attack exhibiting production of incomplete viral particles in the central nervous system cells(355-359).

William E. Hathaway (US), Loretta P. Belhasen (US) and Helen S. Hathaway (US) discovered the human blood coagulation factor called Fletcher factor(360). This factor was later to be identified as plasma prekallikrein.

Olav Egeberg (NO) discovered the first known hereditary hypercoagulable disorder. He found a Norwegian family with a strong history of thrombosis. The affected individuals had plasma antithrombin concentrations that were 40-50% of normal(361). 

C. William Hall (US), William W. Akers (US), William O'Bannon (US), Domingo Liotta (AR), and Michael Ellis DeBakey (US) implanted an intraventricular artificial heart(362).

Adrian Kantrowitz (US), Tetsuzo Akutsu (US), Paul-Andre Chaptal (FR), Joseph C. Krakauer (US), Arthur R. Kantrowitz (US), and Robert T. Jones (US) implanted a mechanical auxiliary ventricle in a patient(363).

Willy Gepts (BE) suggested that insulin-dependent diabetes mellitus might be an autoimmune disease because of the presence of mononuclear cell infiltration in the pancreas and the presence of islet cell antibodies in affected individuals(364).

Richard K. Sibley (US), David E.R. Sutherland (US), Frederick C. Goetz (US), and Alfred F. Michael (US) proved that Gepts’ suggestion was correct(365).

John D. Utley (SE) and Arvid Carlsson (SE) discovered that dopamine is a neurotransmitter in the brain(366).

Kresimir Krnjevic (CA), Susan Schwartz (US) and Victor P. Whittaker (DE) discovered that the neural chemicals glutamate and gamma-amniobutyric acid (GABA) play more important roles in determining how information travels through the brain than was previously suspected. Glutamate plays a key excitatory function, while GABA has an opposite action as the main inhibitory neurotransmitter(367-369).

Norbert Hilschmann (DE) and Lyman Creighton Craig (US), using Bence Jones proteins as their material, discovered that the first 110-120 amino acid residues in light chains of antibody molecules represent a variable region(370).

Stanley A. Plotkin (US), David Cornfeld (US), and Theodore H. Ingalls (US) developed the rubella vaccine that is the only one in use in the United States and throughout most of the world(371).

André-Bernard Tonnel (FR), D. Dubois (FR), C. Blin (FR), Pierre Wattré (FR), and Jean Samaille (FR) developed the hemagglutination inhibition reaction and its application to biological diagnosis of rubella(372).

Alexander M. McPhedran (US), Raymond B. Wuerker (US), Elwood Henneman (US), George Somjen (US), David O. Carpenter (US), and Camille B. Olson (US) provided a detailed account of motor unit properties, motor neuron recruitment properties, and how the relationships between these two sets of properties could be summarized in terms of a unifying principle that they called the “size principle”(373-377).

Phil Gold (CA) and Samuel O. Freedman (CA) discovered a carcinoembryonic antigen (CEA) produced during growth of cancer cells of the digestive system(378). This antigen is produced in tumors and fetal embryonic gut, pancreas and liver cells, but not by normal adult cells. A blood test was developed that can indicate the presence, spread or reoccurrence of cancer(379). The CEA test has proved useful in assessing the extent of a cancer, its growth rate and response to treatment, but it is not reliable in testing for the presence of tumors, since early tumors do not produce enough CEA to be detected. The discovery of CEA opened the new field of onco-fetal antigens.

Paul Ichiro Terasaki (US), Thomas L. Marchioro (US), and Thomas Earl Starzl (US) described the hyperacute kidney rejection associated with antigraft lymphocytotoxic antibodies. They proposed that this could be prevented with cytotoxic crossmatching(380).

Flemming Kissmeyer-Nielsen (DK), Steen Olsen (DK), Villy Posborg Petersen (DK), and Ole Fjeldborg (DK) confirmed this proposal then extended it with the development of the leukoagglutinin test (Kissmeyer-Nielsen test)(381).

Roscoe O. Brady (US), Julian N. Kanfer (US), and David Shapiro (US) discovered the precise metabolic defect—a particular missing enzyme—which causes lipids to build up and destroy body tissues in such disorders as Gaucher's disease, Niemann-Pick disease, Fabry's disease, and Tay-Sachs disease(382, 383).

Peter G. Pentchev (US), Marcella E. Comly (US), Howard S. Kruth (US), Marie T. Vanier (US), David A. Wenger (US), Shutish Patel (US) and Roscoe O. Brady (US) demonstrated that Niemann-Pick disease type C is a disease of cholesterol metabolism(384).

Judith G. Pool (US) and Angela E. Shannon (US) discovered that slowly thawed frozen plasma yields deposits high in Factor VIII. The deposits, called cryoprecipitates, are further refined for treatment of hemophilia(385).

Forrest M. Bird (US) developed the first highly reliable, low-cost, mass-produced medical respirator in the world, the Bird Mark 7(386). In 1970, he introduced the first infant ventilators, the BABYbird, which reduced infant mortality by 60% for infants with Infant Respiratory Distress Syndromes (IRDS)(387).

Harry Angelman (GB) reported cases of a chromosome 15 disorder comprising microcephaly with mental and motor retardation, epilepsy, ataxic gait or complete inability to walk, muscle hypotonia, EEG abnormalities, and peculiar faces marked by a protruding jaw and tongue, occipital depression, and blue eyes(388). It is often called Angelman’s syndrome.

David H. Carr (CA) gave us some idea of the amount of fetal damage that was caused by chromosomal changes in spontaneously aborted fetuses. He showed that in 40-50% of all spontaneous abortions there was a major chromosomal abnormality occurring in the fetus(389).

Gunnar B. Stickler (DE-US), Paul G. Belau (US), Francis J. Farrell, Jr. (US), James D. Jones (US), David G. Pugh (US), Arthur G. Steinberg (US), and Louis E. Ward (US) described what was later called Stickler syndrome. It is a group of genetic disorders affecting connective tissue, specifically collagen(390). The syndrome is thought to arise from a mutation of several collagen genes during fetal development.

G. Cordier (FR), H. Garnier (FR), Jean-Pierre Clot (FR), M. Bertrand (FR), P. Camplez (FR), J.P. Gorin (FR), P.H. Clot (FR), J.P. Rassinier (FR), M. Nizza (FR), and R. Lévy (FR) observed that liver allografts in untreated pigs frequently were not rejected(391, 392).

Thomas Earl Starzl (US), Thomas L. Marchioro (US), Kendrick Arthur Porter (US), Paul D. Taylor (US), Tanous D. Faris (US), Thomas J. Herrmann (US), Charles J. Hlad, Jr. (US), and William R. Waddell (US) obtained the first greater than one year survival after liver replacement in any species (here mongrel dogs) with recognition of the liver’s unusual ability to induce tolerance under a 3- to 4-month course of azathioprine, or in this canine model after only a few perioperative injections of anti-lymphocyte serum or anti-lymphocyte globulin(393).

Henry Jay Heimlich (US) invented the flutter valve (Heimlich valve) which greatly facilitated the surgical removal of fluid and air from a collapsed lung(394, 395).

Michael Ellis DeBakey (US), E. Stanley Crawford (US), H. Edward Garrett (US), Arthur C. Beall, Jr. (US), Jimmy F. Howell (US), Robert D. Bloodwell (US), Grady L. Hallman (US), Denton A. Cooley (US), John E. Liddicoat (US), Szabolcs M. Bekassy (US), Pedro A. Rubio (MX-US), and George P. Noon (US) pioneered the successful surgical treatment of aneurysms of various parts of the human aorta(396-400).

Jose Maria Gil-Vernet (ES) introduced extended pyelolithotomy, a technique applicable for removal of most staghorn, and large pelvic and caliceal calculi(401).

Dame Cicely Mary Strode Saunders (GB) founded the modern hospice movement (St. Christopher’s hospice) during the early 1960s(402).

Lyndon B. Johnson, President of the United States, signed Medicare into law. Medicare is a medical and hospital insurance program for the aged in the United States of America.

John Langdon Brooks (US) and Stanley I. Dodson (US) hypothesized that size-dependent predation by fish determines the size structure of freshwater zooplankton. They observed that lakes seldom contained abundant large zooplankton (>0.5 mm) and small zooplankton (<0.5 mm) together. Large zooplankton did not coexist with plankton feeding fish(403).

Walter J. Bock (US) and Gerd von Wahlert (DE) distinguished the concepts of structure, function and biological role; extremely useful for those who think in terms of 'the target of selection' , i.e., what is actually being selected for(404).

Robert H. Whittaker (US) created a rank abundance curve or "Whittaker plot." This is a chart used by ecologists to display relative species abundance, a component of biodiversity. It can also be used to visualize species richness and species evenness. It overcomes the shortcomings of biodiversity indices that cannot display the relative role different variables played in their calculation(405).

Chester Gorman (US) found evidence to support Carl Ortwin Sauer’s (US) hypothesis of plant domestication by the Hoabinhian people. They lived at Spirit Cave in Northern Thailand and grew domesticated beans, peas, gourds and water chestnuts around 6000-9000 B.C.E.(406-409).

Esmond Ray Long (US) reported that from investigations on the mummies of ancient Egypt we know that bone tumors and tuberculosis of the spine occurred, that osteomyelitis and arthritis deformans were common, that, arteriosclerosis of the senile, atheromatous type with deposit of calcium salts, was at least as frequent as it is with us, and possibly more so, and that pneumonias, anthracosis, pleurisies, renal atrophies and abscesses, splenomegalies and gallstones troubled or cut off the Pharaohs and priests of Ammon, with the same kind of gross and microscopic change to be seen in the fresher human clay of the twentieth century (410).

J. William Schopf (US) Elso Sterrenberg Barghoorn (US), Morton D. Maser (US), and Robert O. Gordon (US) found microscopic formations that look very much like traces of cyanobacteria in 2 billion year old rock called Gunflint chert. The find was near Lake Superior in Canada(411). Cherts are rocks composed of minute interlocking grains of silica, occurring as the mineral quartz (SiO2).

Elso Sterrenberg Barghoorn (US) and J. William Schopf (US) discovered fossils of microorganisms in stromatolitic cherts of the Neoproterozoic Bitter Springs Formation of the Amadeus Basin of Central Australia(412, 413).

Other Precambriam fossil sites include: the Fig Tree Group, Africa; the Bulawayan Formation, Africa; the Gunflint Iron Formation, Minnesota/Canada; the Belcher Group, Hudson Bay; Bitter Springs, Australia; and the Ediacaran Sites, Australia.

Kenneth A. Kermack (GB), Patricia M. Lees (GB), and Frances Mussett (GB) describe the Early Cretaceous fossil Aegialodon dawsoni as the oldest known fossil to be a common ancestor to the marsupials and placentals(414).

Miklós Kretzoi (HU) and Laslo Vertes (HU), in 1964, found a portion of the fossil remains of a specimen of Homo erectus; Homo sapiens (archaic) near the village of Vértesszöllös west of Budapest, Hungary(415). The remains are dated at ca. 185,000 B.P.

Elwyn LaVerne Simons (US) announced the discovery of the 30,000,000-year-old skull of an ape, which he names Aegyptopithecus. Aegyptopithecus is at this time the earliest known primate that is definitely a part of the hominid line, the line that eventually led to Homo sapiens(416).


Reflecting on his study of salamanders blinded in order to study their homing instinct, Victor Chandler Twitty wrote, “Of the countless displaced newts that I have handled, I think none has made such an impact on me as the first one of these blinded animals to be recaptured. As I examined its empty eye sockets and emaciated body (many blinded newts do not feed at all!), and then looked downstream toward the heavy forest and rugged terrain it had transversed in coming home, my respect for its accomplishment came as near awe and reverence as can be inspired by lowly organisms or possibly even by their highly evolved descendents.” Victor Chandler Twitty(417).

“Only the genius or unsung hero can make an intellectual judgment when his feelings, emotions and beliefs are engaged.” William Bennett Bean(418).

Peyton Rous (US) for his discovery of tumor inducing viruses and Charles Brenton Huggins (US) for his discoveries concerning hormonal treatment of prostatic cancer shared the Nobel prize in physiology and medicine.

Craig Merrihue (US) and Granville Turner (US) presented the first 40Ar/39Ar dating results(419).

John G. Mitchell (GB), Kingsley C. Dunham (GB), Frank J. Fitch (GB), Peter R. Ineson (GB), and John A. Miller (GB) first applied the 40Ar/39Ar dating method to terrestrial rocks where they compared total fusion 40Ar/39Ar ages with conventional K-Ar ages(420, 421). The argon-argon technique had much to do with the proof of the theory of continental drift and sea floor spreading. It also helped scientists interpret the origin, history, age, and composition of the moon from lunar soil samples.

Csaba G. Horvàth (US) and Sandy R. Lipsky (US) developed and named high-pressure liquid chromatography (HPLC)(422). It did not catch on until the early 1970s, when the production of silanized silica yielded a packing material that allowed the use of smaller volume and longer columns with the pressurized solvents. Combined with the introduction of gradient elution in the 1950s by Arne Vilhelm Kaurin Tiselius and co-workers, the new packing materials proved the basis for HPLC. Note: HPLC was predicted in 1941 by Archer John Porter Martin (GB), in his famous paper with Richard Laurence Millington Synge (GB)(423).

Morris John Karnovsky (ZA-US) and Richard C. Graham (US) extended the horseradish peroxidase (HRP) tracer method of Werner Straus (US) to both the light and electron microscopic level, by introducing diaminobenzidine (DAB) as an electron donor. HRP oxidizes DAB in the presence of H2O2 and converts it to an insoluble primer which causes the reduction of added osmium tetroxide. The reduced osmium forms an insoluble electron opaque precipitate, localized to the site of the HRP(424, 425).

David T. Denhardt (CA) developed a membrane-filter technique for the detection of complementary DNA(426).

Robert Burns Woodward (US), Karl Heusler (CH), Jacques Gosteli (CH), Peter Naegeli (CH), Wolfgang Oppolzer (AT-CH), Robert Ramage (GB), Subramania Ranganathan (IN), and Helmut Vorbruggen (DE) carried out the total synthesis of cephalosporin C(427).

Toshio Ando (JP) and Koichi Suzuki (JP) determined the amino acid sequence of clupeine, a protamine of salmon(428-431). Protamines are very small, highly basic proteins with molecular weights ranging from about 4000 to 6000, which usually replace some or all somatic histone during spermatogenesis. They are highly variable and show few similarities in size or amino acid sequence between plants and animals or among major animal groups.

Gertrude Belle Elion (US), Aylene Kovensky (US), George Herbert Hitchings (US), Ts’ai-fan Yu (US), and Alexander B. Gutman (US) played a major role in the development of allopurinol (Zyloprim) for the treatment of gout(432, 433). 

Robert L. Letsinger (US) and Viswanath Mahadevan (IN) were among the first to accomplish the in vitro synthesis of oligodeoxyribonucleotides(434).

Ira Harry Pastan (US) and Jesse Roth (US), Vincenzo Macchia (IT), Robert Joseph Lefkowitz (US), and William Pricer (US) found that thyroid stimulating hormone (TSH) and adrenocorticotropic hormone (ACTH) specifically bind to receptors on the surface of cells(435-437).

M.B. Kemp (GB) and John R. Quayle (GB) discovered a bacterial pathway by which formaldehyde is converted into triose phosphate thus allowing their growth on a single carbon compound(438).

Benno Hess (DE), Rainer Haeckel (DE), Karl Brand (US), Christopher B. Taylor (GB), and E. Bailey (GB) reported that in the glycolytic pathway pyruvate kinase is stimulated by fructose-1,6-diphosphate, a phenomenon which can be thought of as positive feed-forward(439, 440).

John L. Hess (US) and N. Edward Tolbert (US) detected glycolate, glycine, serine, and glycerate formation during photosynthesis by tobacco leaves(441).

John L. Hess (US), N. Edward Tolbert (US), W.J. Bruin (US), and Edward B. Nelson (US) established that the glycolate pathway of metabolism is present in unicellular green algae(442, 443).

Arun Goyal (IN-US) and N. Edward Tolbert (US) associated glycolate oxidation with photosynthetic electron transport in plant and algal chloroplasts(444).

Rodney Robert Porter (GB), Ronald C. Weir (GB), Gerald Maurice Edelman (US) and Joseph A. Gally (US) described the structure and nature of antibodies(445-448).

Hugh R. Wallace (GB) and Max L. Birnstiel (CH) were the first to purify a eukaryotic chromosomal gene. It was amphibian ribosomal DNA(449).

Walter Gilbert (US) and Benno Müller-Hill (DE) isolated and purified the lactose repressor molecule. Their in vitro studies showed that the repressor binds to DNA that contains the lactose operon. Gilbert went on to determine the base sequence of the DNA region bound by the repressor. The repressor was shown to bind to the operator, preventing initiation of transcription by the RNA polymerase bound at the promoter (450).

Mark Steven Ptashne (US) isolated the lambda phage repressor shortly thereafter(451).

Mark Steven Ptashne (US), Walter Gilbert (US), and Benno Müller-Hill (DE) developed methods for purifying and testing repressor protein and proved that Jacob and Monod’s theory of the operon was correct; that repressor is the proteinaceous product of a repressor gene and interacts with a specific operator region on the DNA molecule(452, 453).

Karin Ippen (US), Jeffrey H. Miller (US), John Scaife (GB), and Jonathan Roger Beckwith (US) discovered the promoter for the lactose operon of Escherichia coli (reintroducing a term that had been used previously, with a different meaning, by Jacob, Ullman and Monod). They suggested that it is transcription that begins at the promoter. Moreover, as there was no evidence that the lacO region is translated, they proposed that translation begins just downstream of lacO, in a region that Jacob, Ullman and Monod had previously suggested was important for gene expression(454).

Larry Eron (US) and Ricardo Block (US) elegantly confirmed the promoter using an in vitro transcription system(455).

Walter Gilbert (US), Jay Gralla (US), John Majors (US), and Allan Maxam (US) determined that the Lac repressor functions by blocking access of the RNA polymerase to its initiation site(456).

Leonard Guarente (US), Jeffrey S. Nye (US), Ann Hochschild (US), Mark Steven Ptashne (US), and Nina Irwin (US) showed that the bacteriophage lambda repressor not only represses transcription at the lambda PR and PL promoters, but also activates transcription at the lambda PRM promoter. They proposed that activation required a protein–protein interaction between the lambda repressor and RNA polymerase(457, 458).

Mei Li (US), Henry Moyle (US), and Mariam M. Susskind (US) obtained compelling support for this proposed interaction and identified its target as a surface in the – sigma subunit of RNA polymerase holoenzyme(459).

Arthur Beck Pardee (US) crystallized and characterized a protein that appears to be the recognition part of the sulfate transport system of Salmonella typhimurium(460).

Anne Norris Baldwin (US) and Paul Berg (US) purified and determined the properties of isoleucyl ribonucleic acid synthetase from Escherichia coli. This enzyme recognizes tRNA for isoleucine and activates it by attaching a molecule of isoleucine(461).

Julien Marcot-Queiroz (FR) and Roger Monier (FR) isolated 18S ribosomal RNA (18SrRNA) from the ribosomes of Escherichia coli(462).

Radoslav J. Bachvaroff (RU-US) and Veniamin S. Tongur (RU) isolated 5S ribosomal RNA (5SrRNA) from mammalian tissue(463).

Jerry M. Adams (US) and Mario Renato Capecchi (US) determined that N-formylmethionyl transfer RNA is the initiator of protein synthesis in Escherichia coli(464). 

Alan E. Smith (GB) and Kjeld Adrian Marcker (DK) determined that N-formylmethionyl transfer RNA is the initiator of protein synthesis in yeast and rat liver mitochondria(465).

Philip S. Rudland (GB) and Shyam K. Dube (US) found that in Escherichia coli the initiator tRNA binds with the 30S fragment of the ribosome(466).

Douglas M. Fambrough (US) and James Frederick Bonner (US) discovered that there are only five different species of histones (each with its subspecies)(467).

Jean-Francois Petit (BE), Emilio Munoz (ES), Melina Leyh-Bouille (BE), Donald J. Tipper (US), Jack Leonard Strominger (US), Walther Katz (DE), Evanghelos Bricas (NL), Marvin Lache (US), Gerald D. Shockman (US), Philippe Dezélée (FR), Hans Heymann (US), Jacques Coyette (BE), and Jean-Marie Ghuysen (BE) described the complex matrix of the bacterial peptidoglycan—a closed net-like polymer of glycan strands and cross-linked peptides—and the biochemistry of the penicillin-binding proteins (PBPs), targets of a vast family of antibiotics capable of destroying bacteria by inhibiting cell wall synthesis(36, 468-476).

David Freifelder (US) determined that x-ray inactivation of bacteriophage T7 results primarily from double strand breakage in DNA(477).

Henry Seymour Kaplan (US) found that in Escherichia coli single-strand scissions caused by x-irradiation are usually repaired during reincubation(478).

R.A. McGrath (US) and R.W. Williams (US) demonstrated that Escherichia coli possesses a mechanism, probably enzymatic, to repair DNA damaged by x-rays(479).

David Freifelder (US), using phages T5, T4, T7, and lambda, calculated that mechanisms other than strand breakage (presumably base damage) were responsible for about half of the killing(480).

Bernard S. Strauss (US), T. Searashi (), and M. Robbins (US) showed that an extract of Micrococcus lysodeikticus acts like an endonuclease specific for DNA which contains radiation-induced lesions, most probably pyrimidine dimers(481). Note: Micrococcus lysodeikticus is now called Micrococcus luteus.

Yasuyuki Takagi (JP), Mutsuo Sekiguchi (JP), Shunzo Okubo (JP), Hiroaki Nakayama (JP), Kazunori Shimada (JP), Seiichi Yasuda (JP), Takeharu Nishimoto (JP), and Hajime Yoshihara (JP) discovered endonuclease V (five) in Micrococcus lysodeikticus. This enzyme recognizes and removes pyrimidine dimers(482).

Errol C. Friedberg (US) and John J. King (US) reported that phage T4 encodes an enzyme (ultraviolet endonuclease of  T4) that specifically recognizes pyrimidine dimers and incises the DNA at these sites(483).

Note: This endonuclease has been called variously, endonuclease V (five), ultraviolet endonuclease of T4, and denV endonuclease of phage T4—after the denV (dNA endonuclease V) gene (formally the v+gene) which encodes it.  

Jonathan Roger Beckwith (US) and Ethan R. Signer (US) described a technique for isolating transpositions of lac to specific regions of the Escherichia coli chromosome(484). This work signaled that chromosomes could be redesigned at will, and genes could be moved from one replicon to another. In many ways this represents the dawn of genetic engineering.

Dieter Söll (US), David S. Jones (US), Eiko Ohtsuka (US), R.D. Faulkner (US), Rolf Lohrmann (US), Hikoya Hayatsu (JP), Har Gobind Khorana (IN-US), Joseph D. Cherayil (US), Arnold E. Hampel (US), Rudolf M. Bock (DE), Susumu Nishimura (JP), Uttam L. RajBhandary (US), Richard E. Marshall (US), Charles Thomas Caskey (US), and Marshall Warren Nirenberg (US) presented evidence that the genetic code is universal, that there is remarkable similarity in codon-base sequences recognized by bacterial, amphibian, and mammalian AA-tRNA. This suggested that most, perhaps all, forms of life on the planet use essentially the same genetic language, and that the language is translated according to universal rules(217, 293-295, 485). 

William Meredith Stanley, Jr. (US), Margarita Salas (US), Albert J. Wahba (US), and Severo Ochoa (ES-US) established that in Escherichia coli there exists an initiation signal (AUG) for protein synthesis and that two factors (F1 and F2) other than the transfer enzymes are required for the translation of this signal(486).

Kentaro Iwasaki (US), Steven Sabol (US), Albert J. Wahba (US), and Severo Ochoa (ES-US) determined that a third factor (F3) is also necessary for initiation of the translation of mRNA in Escherichia coli(487).

Severo Ochoa (ES-US) determined that translation of the messenger RNA consists of three main phases, chain initiation, elongation, and termination. He enumerated all the chemical factors and enzymes necessary for the process(488).

Hans Georg Zachau (DE), Dieter Dütting (DE), Horst Feldmann (DE), Fritz Melchers (DE), and Wolfgang Karau (DE) proposed that all tRNAs have a clover-leaf type secondary structure(489).

John P. Richardson (US), using T7 bacteriophage, found that RNA polymerase has approximately 50 specific binding sites on a single T7 DNA molecule(490).

Peter Traub (US), Kei-ichi Hosokawa (JP), Masayasu Nomura (JP-US), and Dieter Söll (US) showed that the alteration of the 30 S ribosomal component as Escherichia coli mutates to streptomycin resistance occurs not in the RNA but rather in the protein fraction. They subsequenttly identified the specific protein and designated it P10(491-495).

Brian F.C. Clark (GB-DK), Kjeld Adrian Marcker (DK), Donald A. Kellogg (US), Bhupendra P. Doctor (US), Judith E. Loebel (US), and Marshall Warren Nirenberg (US) presented evidence that in Escherichia coli a non-dializable factor is necessary for the attachment of mRNA to a 30S ribosomal subunit. They also found that two additional non-dializable factors plus GTP are necessary for the binding of N-formyl-met-tRNA to the 30S ribosome-mRNA complex in response to an initiator codon (AUG or GUG)(290, 291). 

Keiichi Hosokawa (US), Robert K. Fujimura (US) and Masayasu Nomura (US) showed that reconstituted 30S and 50S ribosomal particles have activities comparable to the original intact particles. Any subunits of these particles such as 23S and 40S have no cell-free protein synthesizing ability(496).

Margit M.K. Nass (US) was the first to demonstrate the circularity of mitochondrial DNA(497).

René Thomas (BE) performed experiments suggesting that temperate virus is kept in the prophage state because a gene, N, is not being expressed. Gene N is itself blocked by a substance produced by gene cI plus(498).

Henryk Kubinska (US), Zofia Opara-Kubinska (US), Waclaw Szybalski (US), and Peter Sheldrick (US) postulated that DNA sites rich in cytosine are likely to act as initiation points for the transcription of RNA and if both strands contained such sites then both strands could be transcribed(499, 500).

Karol Taylor (PL), Zdenka Hradecna (CZ), and Waclaw Szybalski (US) confirmed this prediction with coliphage lambda, which provided the first example of in vivo transcription from both DNA strands, and went on to find that in the noninduced state the majority mRNA is transcribed from the W (light) strand, most probably being the product of gene cI. Upon induction or infection two regions adjoining the cI gene start to be transcribed: the predominant product is copied from strand W in the same direction as gene cI, through genes N-to-a, whereas the minority mRNA is copied in the opposite direction, i.e., from left-to-right, from strand C (dense) through the x-O operon(500, 501). 

Ora Mendelsohn Rosen (US) and Samuel M. Rosen (US) found that fructose 1,6-diphosphatase from Candida utilis possesses a site responsible for inhibition by AMP which is distinct from the site involved in its catalytic activity. This indicates that FDPase is an allosteric enzyme(502). 

Donald L. Schneider (US), Yasuo Kagawa (US), L.W. Johnson (US), M. Anne Kandrach (US), and Efraim Racker (PL-AT-US) developed a method for incorporating isolated transport enzymes into artificial vesicles made of phospholipids. They then went on to make membranes which incorporated the F0F1 complex. They were inverted with respect to normal mitochondria, that is, the F1 knobs were on the outer surface rather than the inner one. As a result the splitting of ATP by F0F1 complex transported protons inward(239, 250, 503, 504).

Richard G. Jensen (US) and James Al Bassham (US) demonstrated that isolated chloroplasts can carry out complete photosynthesis(505).

André Tridon Jagendorf (US) and Ernest G. Uribe (US) demonstrated that ATP can be generated in isolated chloroplasts by imposing an artificial pH gradient across the thylakoid membrane of the chloroplast(506). This experiment supported Peter Mitchell’s chemiosmotic theory of ATP synthesis.

Michael C.W. Evans (GB), and Bob B. Buchanan (US), and Daniel Israel Arnon (PL-US) discovered a new path of photosynthetic carbon dioxide assimilation in bacteria, the reductive carboxylic acid cycle (reverse of citric acid cycle)(507, 508).

Yasuo Kagawa (US), Youssef Hatefi (IR-US), Kerstin E. Stempel (US), Marietta L. Baginsky (US), Alessandro Bruni (US), Efraim Racker (PL-AT-US), John T. Penniston (US), Harold D. Vande Zande (US), David Ezra Green (US), and James F. Perdue (US) demonstrated that most of the electron carriers in the mitochondrial inner membrane, rather than existing individually, are combined with proteins into major complexes(239, 509-513).

Charles R. Hackenbrock (US) determined that mitochondria from rat livers alter their shape as their metabolic activity varies(514).

Robert S. Edgar (US) and William B. Wood (US) made the quite unexpected discovery that assembly of the T-even phage tail and its attachment to a preexisting, DNA-filled phage head can proceed spontaneously in vitro(515, 516). Along with Jonathan Alan King (US), Ilga Lielausis (US), and M.D. Henninger (US) they went on to formulate a pathway for intracellular assembly of bacteriophage T4(517, 518).

David Swenson Hogness (US), Walter Doerfler (US), J. Barry Egan (US), and Lindsey W. Black (US) were able to prove that the genetic map of the phage established by recombination experiments actually represents the arrangement of genes on the phage DNA molecule (519).

Marcus Morton Rhoades (US) and Ellen Dempsey (US) discovered that an abnormal form of chromosome 10 in maize possesses a unique system of meiotic drive. When this chromosome is heterologous with a normal chromosome 10 about 70% of female gametes will receive the abnormal form. About 50% of male gametes will receive it(520).

George Francis Cahill, Jr. (US), M. Guillermo Herrera (US), Alfred P. Morgan (US), John Stuart Soeldner (US), Jurgin Steinke (US), P.L. Levy (US), George A. Reichard, Jr. (US), and David Morris Kipnis (US) found that after the first few days of starvation, mammals have depleted their stores of glycogen and have begun to satisfy cerebral glucose needs by a gluconeogenic attack on body proteins. To offset this serious threat to body proteins, ketones substitute to an increasing degree for glucose, and body proteins are thereby spared(521).

Sir Ludwig Guttmann (DE-GB) and Hans L. Frankel (GB) established clean intermittent self-catheterization(522).

Carmia Borek (US) and Leo Sachs (US-IL) showed that x-irradiation can induce cell transformation(523).

Dorothea Zucker-Franklin (US), Zanvil A. Cohn (US), James Gerald Hirsch (US), and Martha E. Fedorko (US) discovered that the phagosomes of granulocytes move centripetally prior to fusion with lysosomal granules(524, 525).

Jane Mink Rossen (DK) and Majken Westergaard (DK) demonstrated conclusively that recombination takes place during prophase I of meiosis(526).

Pierre Baudhuin (BE), Russell L. Deter (US), and Christian Rene de Duve (GB-BE-US) discovered that autophagy is a process for the bulk degradation of proteins, in which cytoplasmic components of the cell are enclosed by double-membrane structures known as autophagosomes for delivery to lysosomes or vacuoles for degradation(527-529).

Roger Yate Stanier (CA), Norberto J. Palleroni (US), and Michael Doudoroff (RU-US) described 169 phenotypic characters of 267 strains of Pseudomonas. Their ability to utilize 146 different organic compounds as sources of carbon and energy was noted. RNA and DNA homologies were later used to refine relationships. They concluded by developing a practical scheme for the identification of twenty-nine species of Pseudomonas(530, 531).

S.K. Shome (IN) and Usha Shome (IN) found a fungus capable of trapping nematodes(532).

S.P. Flanagan (GB) described a homozygous recessive nude (nu) mutation on chromosome 11 in mice(533).

Evagoras Michael Pantelouris (GR-GB) would later report that nude mice are congenitally athymic. This lead to their widespread use in biomedical research(534).

Pinghui V. Liu (US) isolated a lethal, heat-labile exotoxin from Pseudomonas aeruginosa. Injection of the toxin into dogs resulted in hemodynamic and biochemical changes associated with shock and death. These changes included acidosis, elevated levels of catecholamines, an increased arterial-venous difference in oxygen saturation, circulatory collapse, and leucopenia. These observations were similar to those made in pseudomonas infections(535). This toxin was shown by others to inhibit protein synthesis just like the diphtheria toxin.

Warren Herbert Wagner, Jr. (US) and Florence S. Wagner (US) published a series of studies showing that ferns hybridize freely and that hybridization is a major source of new species in plants(536-540).

Sir Henry Harris (AU-GB), Richard Charles Lewontin (US), and Jack L. Hubby (US) established that a high level of polymorphism is the normal condition in populations of man and Drosophila(541, 542).

Jack L. Hubby (US) and Richard Charles Lewontin (US) introduced the use of electrophoresis as a tool for studying polymorphisms(543).

At the 1966 Chicago Conference: Standardization in Human Cytogenetics cytogeneticists recommended a standardized method for briefly representing the karyotype in publications. They suggested that p and q designate the chromosomal short and long arms respectively. A diagonal line is used to separate cell lines in a mosaic. A plus sign (+) or a minus sign (-) after an autosomal number or group letter indicates that a particular chromosome is extra or missing, respectively; when used immediately after an arm designation (p or q) it means that part is abnormally long or abnormally short. Satellite is referred to by s, translocation by t, isochromosome by i. Examples are:

45, X is the usual karyotype of Turner’s syndrome

47, XXY is the usual karyotype of Klinefelter’s syndrome

47, XX, G+ is the karyotype of a female with Down’s syndrome

45, X/46, XX/47, XXX is a triple line mosaic

46, XY, 5p- is the karyotype of a male with cri du chat syndrome

45, XX, D-,G-,t (DqGq)+ is the karyotype of a Down’s syndrome carrier

46, Xxqi is the karyotype of a female with Turner’s syndrome due to isochromosome of the long arm of one X chromosome(544).

Italo Testa-Bappenheim (IT), Anil K. Jain (IN-US), Salil Prabhakar (IN-US), and Sharath Pankanti; Sharathchandra U. Pankanti (IN-US) gave evidence that monozygotic twins share the same genetic makeup, meaning that their DNA is practically indistinguishable. However, a fingerprint is not entirely dependent on genetics. Along with other physical characteristics, the outcome is determined by the interaction of the individual's genes and the environment as it develops in the uterus. The ultimate shape of the fingerprints is believed to be influenced by environmental factors, such as blood pressure, nutrition, position in the womb and growth rate of the fingers at the end of first trimester. Therefore, you will find similar patterns of whorls and ridges in the fingerprints of identical twins, but there will also be differences(545, 546). There may be an earlier reference.

Alfred W. Bauer (US), William M.M. Kirby (US), John C. Sherris (US), and Marvin Turck (US) provided a standardized single disk method to test susceptibility of microorganisms to antibiotics (the Kirby-Bauer technique). This disk diffusion method could be used with ease and provide reliable results(547). The theoretical and practical studies of Hans Ericsson (SE) and Gunvor Svartz-Malmberg (SE) helped prepare the way for this advance(548). 

Henry Neumann Claman (US), Edward A. Chaperon (US), and R. Fraser Triplett (US) demonstrated that for an immune response to take place interactions between cells of bone marrow origin and those of thymus origin are required(549, 550).

Charlotte Friend (US), Maria Cecilia Patuleia (US), Etienne deHarven (US), Giovanni B. Rossi (IT), William Scher (US), J. Gilbert Holland (US), and Toru Sato (US) were able to establish permanent cell lines in culture from tumor cells and show that, even when cloned, these cultures consisted of undifferentiated cells and a small percentage of cells at various stages of erythroid maturation. They found that cancer cells can be induced to differentiate by exogenous agents such as dimethyl sulfoxide and, thereby, lose their ability to multiply. In other words the malignant phenotype can be reversed experimentally(551-555).

Robert I. Mishell (US), Richard William Dutton (US), John Marbrook (AU), William A. Robinson (AU), and Erwin Diener (AU) devised methods for generating primary antibody responses in vitro using tissue culture. The in vitro response closely parallels that observed in vivo with respect to size, early kinetics, antigen dose, and the inhibitory effect of passive antibody(556-560).

Lady Julia Bodmer (GB), Sir Walter Fred Bodmer (GB), Rose Payne (US), Paul Ichiro Terasaki (US), and Donna L. Vredevoe (US) were among the pioneers in human leucocyte antigen (HLA) cell typing(561).

John Rouben David (US), Barry R. Bloom (US), and Boyce Bennett (US) discovered that immune lymphoid cells stimulated by their corresponding antigen secrete a substance that inhibits the migration of macrophages, a characteristic of delayed hypersensitivity(562, 563). Both named this substance migration inhibitory factor (MIF).

Susumu Mitsuhashi (JP), Nobutaka Osawa (JP), Kazuko Saito (JP), Satonori Kurashige (JP), Frank M. Collins (US), George Bellamy Mackaness (US), and Robert Vincent Blanden (AU) discovered that macrophages must be activated before they can destroy the bacteria causing salmonellosis(564-566).

Eliezer Huberman (IL) and Leo Sachs (US-IL) demonstrated that there is a systematic relationship between dose of carcinogen and number of transformed colonies of cells(567).

Douglas E. Smith (US), Bruce Nathan Ames (US), Frank D. Lee (US), William E. Durston (US), Joyce McCann (US), Edmund Choi (US), Edith Yamasaki (US), and Kim Hooper (US) developed a rapid and inexpensive bacterial assay technique to test the mutagenicity of a chemical. This assay—now called the Ames test—also turned out to be a sensitive way to screen chemicals as potential carcinogenic agents(568-574).

Jacques Glowinski (FR) and Leslie L. Iversen (GB) made regional studies of catecholamines in the rat brain; determining the disposition of [3H]norepinephrine, [3H]dopamine and [3H]dopa in various regions of the brain(575).

Dennis M. Burley (GB) set up the first clinical trials testing the efficacy of rifampicin (rifampin, rifamycin, or rifaldazine) as an antituberculous drug. It turned out to be very efficient. Ref

P.J. Coletsos (), V. Nitti (), E. Catena (), A. Ninni (), A. Di Filippo (), A. Havel (CZ), J. Tousek (CZ), L. Trnka (CZ), A. Liener (DE), O. Jahn (DE), M. Lucchesi (), P. Mancini (), and M. Zubiani () introduced rifampin—a lipophilic ansamycin—into tuberculosis therapy(576-580).

Colin McDougall (GB) demonstrated that rifampicin is an excellent anti-leprosy drug(581).

Harry M. Meyer, Jr. (US), Paul Douglas Parkman (US), and Theodore Constantine Panos (US) developed a vaccine against rubella virus(582).

Max H. Weil (US), S. Herbert Shubin (US), and William M. Rand (US) introduced the first operational computer system for full-scale clinical monitoring in January 1965(583).

Kimishige Ishizaka (US), Teruko Ishizaka (US), and  Margaret M. Hornbrook (US) discovered the immunoglobulin epsilon (IgE) class of antibodies and linked their function with immediate hypersensitivity, i.e., reagin or atopic antibodies(584, 585).

Leif Wide (NO), Hans Bennich (NO), and S. Gunnar O. Johansson (NO-SE) developed the radioallergosorbent test (RAST) for the detection and quantification of allergen-specific IgE antibodies in human sera(586).

Kjell Aas (SE) and Stig Gunnar Olof Johansson (SE) showed the value of the radioallergosorbent test (RAST) as a diagnostic method(587).

Stuart Schlossman (US), Shlomo Ben-Efraim (IL), Arieh Yaron (IL), and Herbert A. Sober (US) produced studies on the antigenic determinants required to elicit delayed and immediate hypersensitivity reactions(588).

Paul Ichiro Terasaki (US), Donna L. Vredevoe (US), Max Ray Mickey (US), Kendrick Arthur Porter (US), Thomas L. Marchioro (US), Tanous D. Faris (US), and Thomas Earl Starzl (US) carried out the first prospective trial of HLA matching for donor selection(589).

Moses Judah Folkman (US), David M. Long, Jr. (US), and Richard Rosenbaum (US) were the first to report the use of silicone rubber implantable polymers for sustained drug release(590).

Elizabeth Caroline Crosby (US), Richard Coy Schneider (US), Bud R. DeJonge (US), and Paul Szonyi (US) reported that the basal ganglia and the cerebellum are critical for the acquisition of skills such as playing a violin or skating(591).

Vincent Paul Dole (US), Marie E. Nyswander (US), and Mary Jeanne Kreek (US) developed methadone treatment for heroin addiction(592-595).

Elliott F. Osserman (US) and Dolores P. Lawlor (US) found markedly elevated concentrations of the enzyme lysozyme in the serum and urine of patients with monocytic and monomyelocytic leukaemia(596).

Reuben Matalon (US) and Albert Dorfman (US) determined that elevated dermatan sulfate is characteristic of fibroblasts from Hurler’s syndrome patients(597).

Elizabeth Fondal Neufeld (US), Joseph C. Fratantoni (US), Clara W. Hall (US), Ulrich N. Wiesmann (US), Scot Hickman (US), Gideon Bach (US), Frank Eisenberg, Jr. (US), and Michael Cantz (DE) demonstrated that mucopolysaccharide storage disorders stem from defects in degradative enzymes, e.g. Hunter and Hurler syndromes. They also demonstrated that the excess mucopolysaccharides accumulate within lysosomes—the minute cellular organelles in which large molecules are broken down—thus, also defining these conditions a lysosomal storage disorders. Additionally they discovered the specific enzyme deficiencies involved in several diseases of this group(598-603).

Reuben Matalon (US) and Albert Dorfman (US) showed that fibroblasts of Hurler’s syndrome patients are deficient in alpha-L-iduronidase needed to degrade polysaccharides(604). This was the first enzyme defect established in the mucopolysaccharidoses.

Timple W. Lim (US), Irwin G. Leder (US), Gideon Bach (US), Elizabeth Fondal Neufeld (US), Inge Liebaers (DE), and Paola Di Natale (IT) developed the special methods and chemicals that now make it relatively easy to diagnose patients with these diseases and to perform prenatal diagnosis for these diseases. This work has also led to new concepts regarding the transport of enzymes to lysosomes, with implications for basic cell biology and for possible enzyme replacement(605-607). 

O. Suhren (), George W. Bruyn (NL), and J.A. Tuynman (NL) demonstrated that a defect in the inhibitory glycinergic pathway is responsible for the pathology of familial startle disease (hyperekplexia) in humans(608).

Francois Dessertenne (FR) was the first to describe torsade de pointes heart waves. This ia a specific form of dangerous ventricular tachycardia in which an undulating series of ventricular beats appear on the QRS axis(609).

Henry T. Lynch (US), Marjorie W. Shaw (US), Charles W. Magnuson (US), Arthur L. Larsen (US), Anne J. Krush (US), Milton J. Swartz (US), Jane F. Lynch (US), William A. Albano (US), Karen A. Biscone (US), Guy S. Schuelke (US), Avery Andren Sandberg (US), Martin Lipkin (US), Eleanor E. Deschner (US), and Yves B. Mikol (US) discovered familial predisposition to colorectal cancer with right-sided predominance. Predominantly early-onset proximal colon carcinomas (Lynch syndrome I) and familial predisposition for other primary cancers in addition to the predisposition for colon cancer; site is often female reproductive organs. Predominantly early onset proximal colon carcinoma associated with other extracolonic adenocarcinomas, particularly endometrial carcinoma (Lynch syndrome II)(610-613). Both disorders are inherited as autosomal dominant traits.

Robert H. Wilkins (US), James A. Alexander (US), Guy L. Odom (US), William Hollander (US), and Aram V. Chobanian (US) made outstanding contributions to the control of heart and blood vessel diseases through investigations into causes, diagnosis and treatment of hypertension(614-619).

Mark W. Steele (US) and William Roy Breg, Jr. (US) successfully cultured fetal cells obtained from amniocentesis, which allowed for karyotyping of the chromosomes and therefore for future diagnosis of aneuploidies such as trisomy 21, or Down's syndrome(620).

Henry L. Nadler (US) performed transabdominal amniocentesis on humans and succeeded in the intra-uterine detection of Down's syndrome, galactosemia, and mucopolysaccharidosis utilizing the cultivated amniotic fluid cells(621).

Maurice B. Burg (US), Jared J. Grantham (US), Maurice Abramow (BE), and Jack Orloff (US) developed the methodology for the preparation and study of perfused fragments of single rabbit nephrons(622). This paper ranks as one of the greatest advances in 20th century renal physiology.

James L. McGaugh (US) made observations indicating that the long-lasting trace of an experience is not completely fixed, consolidated, or coded at the time of the experience. Consolidation requires time, and under at least some circumstances the processes of consolidation appear to be susceptible to a variety of influences— both facilitating and impairing— several hours after the experience. There must be, it seems, more than one kind of memory trace process (31). If permanent memory traces consolidate slowly over time, then other processes must provide a temporary basis for memory while consolidation is occurring. The evidence clearly indicates that trial-to-trial improvement, or learning, in animals cannot be based completely on permanent memory storage. Amnesia can be produced by electroshock and drugs even if the animals are given the treatment long after they have demonstrated "learning" of the task(623).

Catherine Tchobroutsky (FR), M. Clauvel (FR) and D.N. Laurent (FR) provided long term support of puppies and fetal lambs in a controlled environment using extracorporeal circulation(624).

Robert B. Salter (CA) introduced the classic innominate osteotomy in the treatment of congenital dislocation and subluxation of the hip(625).

Richard H. Dyer, Jr. (US) pioneered a renewed interest in intraoperative autotransfusion leading to the development of the first commercial auto-transfusion apparatus(626). 

Ilyia I. Gokhman (RU) examined a skeleton (No. 6285-9) from the Vasilyevka II cemeteries with evidence that trepanation— surgical removal of bone from the cranial vault— had been performed during the Mesolithic period. The cemetery, excavated in 1953 by A.D. Stolyar (RU), has been dated to between 7,300-6,220 B.C.E., making this trepanned cranium the oldest known example of a healed trepanation yet discovered. The skull has a depression on its left side with a raised border of bone and 'stepping' in the center showing stages of healing during life. The complete closure indicates the survival of the patient, a man who was more than 50 years old at his death(627, 628).

Kurt W. Alt (DE) and his colleagues discovered a 5,000 B.C.E. burial at Ensisheim, in the French region of Alsace, which yielded unequivocal evidence for trepanation(629).

Elso Sterrenberg Barghoorn (US) and J. William Schopf (US) discovered fossilized cyanobacteria approximately 3.1 billion years old in Warrawoona Group rocks in Africa(630).

Harry Blackmore Whittington (GB), in 1966, began re-examining Burgess Shale fossils originally identified by Charles Doolittle Walcott (US) starting in 1909. Over the next two decades, Whittington, with the assistance of his graduate students Simon Conway Morris (GB) and Derek Briggs (GB), eventually overturned Walcott's theories that these organisms all belonged to modern phyla and proposed that most of the specimens are much more complex than originally believed, and have left no living relatives(631-634). It would appear that the Cambrian was a time of unparalleled innovation and experimentation in body designs. Note: On closer examination the Burgess fossils have been found to be not so different after all. Many of the Burgess specimens have now been assigned to living phyla—just where Walcott put them in the first place(635).

Henry De Lumley (FR), at Terra Amata, in the south of France, found red, purple, yellow, and brown ochre associated with Acheulian tools (ca. 300,000 B.C.E.). Lumps of the ochre showing signs of wear(De Lumley 1966; Rudgley 1999). Tribal peoples alive today use ochre to treat animal skins, as an insect repellent, to staunch bleeding, and as protection from the sun. Ochre may have been one of the first medicaments used by primitive man. Ochre is a naturally occuring iron oxide.

Charles Sutherland Elton (GB) described an ecological survey as an attempt “…to discover and measure the main dynamic relations between all organisms living on an area over some period of time”(636).

Richard Charles Lewontin (US) and L.C. Birch (AU) noted that hybridization is a major source of genetic variation for adapting species to new environments(637).

John Maynard-Smith (GB) initiated the development of mathematical models aiming to identify the conditions for sympatric speciation(638).

Robert T. Paine (US) showed that “local species diversity is directly related to the efficiency with which predators prevent monopolization of the major environmental requisites by one species.” He used an area of shore on the outer coast of Washington state where the seastar Pisaster ochraceus is the top carnivore(639).

George Christopher Williams (US) offers an excellent explanation for adaptation and a convincing defense of natural selection(640).

The Endangered Species Preservation Act of October 15, 1966 (P.L. 89-669, 80 Stat. 926) was passed by the U.S. Congress. The act was strengthened in 1973.


“Science advances but slowly, with halting steps. But does not therein lie her eternal fascination? And would we not soon tire of her if she were to reveal her ultimate truths too easily?” Karl von Frisch(641).

“When it is going well, it is like a quiet conversation with Nature. One asks a question and gets an answer, then one asks the next question and gets the next answer. An experiment is a device to make Nature speak intelligibly. After that one has only to listen.” George Wald, Nobel Lecture.

Ragnar Granit (FI-SE)), Haldan Keffer Hartline (US) and George Wald (US) were awarded the Nobel Prize in Physiology or Medicine for their discoveries concerning the primary physiological and chemical visual processes in the eye.

Arnold L. Shapiro (US), Eladio Vinuela (ES), and Jacob V. Maizel, Jr. (US) introduced the use of sodium dodecyl sulfate (SDS) for improving polyacrylamide-gel electrophoresis of proteins(642).

Jean-Paul Thiéry (FR) developed a way to demonstrate polysaccharides in thin sections by electron microscopy(643).

Edward P. Marbach (US) and Max Harry Weil (US) presented a simplified assay for lactate and pyruvate in blood(644).

Eijiro Ozawa (JP) and Setsuro Ebashi (JP) discovered the regulation of phosphorylase b kinase activity by calcium ions(645).

Roger Radloff (US), William Bauer (US), and Jerome R. Vinograd (US) introduced the dye-buoyant density method which allows the separation of covalently closed circular DNA molecules from linear and nicked circular molecules. These dye-DNA complexes can be separated in density gradients of the dense salt CsCl formed in the ultracentrifuge. Plasmid DNAs are easily isolated by this method(646).

Michael Bazaral (US) and Donald Raymond Helinski (US) used this technique to show that the colicine factors E1, E2, and E3 are circular DNA molecules of homogeneous molecular weights(647).

David W. Deamer (US), Robert Leonard (US), Annette Tardieu (FR), and Daniel Branton (US) created artificial membranes containing various ratios of phospholipids and proteins. Freeze-fractures of these membranes gave strong supporting evidence that the interpretation of natural membrane structure from freeze-fractures was correct(648-650).

George G. Brownlee (GB), Frederick Sanger (GB), and Barclay George Barrell (GB) determined the complete nucleotide sequence for 5S ribosomal RNA from Escherichia coli(651).

Berry E. Davidson (GB), Mihaly Sajgò (HU), Harry F. Noller, Jr. (US), and J. Ieuan Harris (GB) were the first to determine the primary structure of an intracellular enzyme, lobster muscle glyceraldehyde 3-phosphate dehydrogenase. This enzyme consists of 333 amino acid residues(652).

Amelia Agtarap (US), James W. Chamberlin (US), Mary Pinkerton (US), and Larry K. Steinrauf (US) isolated and determined the structure of monensic acid, a very close relative of the anticoccidial antibiotic monensin(653). Monensin is an ionophore produced by Streptomyces cinamonensis and has been used successfully to combat coccoidal infections in poultry and as an additive in cattle feed.

Herbert Röller (US), Karl H. Dahm (DE-US), Charles C. Sweeley (US), and Barry M. Trost (US) were the first to determine the structure of insect juvenile hormone (JH)(654).

Albrecht Fleckenstein (DE), Helmut Kammermeier (DE), H.J. Döring (DE), H.J. Freund (DE), Gisa Fleckenstein-Grün (DE), and A. Kienle (DE) reported on the fundamental actions of drugs that antagonize or potentiate the actions of calcium on muscle tissue. They designated some drugs as calcium antagonists. These agents inhibit transmembrane calcium supply to the contractile system so that the calcium dependent transformation of phosphate bond energy into mechanical work is restricted(655-657).

Albrecht Fleckenstein (DE), Helmut A. Tritthart (DE), B. Fleckenstein (DE), A. Herbst (DE), and Gisa Fleckenstein-Grün (DE) proved that iproveratrile (verapamil) and prenylamine reduce the flow of calcium ions into the muscle cells(658). Verapamil is an alkaloid found in raw opium from the Papaver somniferum plant.

Miklos Bodanszky (US), Nina J. Williams (US), Miguel A. Ondetti (AR-US), and Seymour D. Levine (US) synthesized the 27 residue secretin peptide by solution phase stepwise addition methods(659, 660).

Nicholas R. Cozzarelli (US), Malcolm L. Gefter (US), Martin Frank Gellert (US), Baldomero M. Olivera (US), Samuel Bernard Weiss (US), Andrew Becker (US), Charles Clifton Richardson (US), Jerard Hurwitz (US), Israel Robert Lehman (US), Norman E. Melechen (US), Thomas M. Jovin (DE), and Arthur J. Kornberg (US) discovered DNA ligase in Escherichia coli. This enzyme can, in fact, seal single stranded interruptions, or nicks, of the DNA double helix. It catalyzes the formation of the internucleotide phosphate diester bond between the 5´-phosphate and 3´-hydroxyl of two adjacent nucleotides of an interrupted DNA polynucleotide strand(661-665).

Ruth Sager (US) and Mary G. Hamilton (US) discovered ribosomes in the chloroplast of Chlamydomonas(666).

Kinichiro Oda (JP) and Wolfgang Karl Joklik (AT-AU-US) analyzed early and late vaccinia mRNAs, using hybridization and density gradient sedimentation. They found the following. 1) Early mRNAs are smaller than late mRNAs. 2) Early mRNAs are also transcribed late. 3) The pattern of transcription of early and late viral mRNAs in HeLa and L cells is quite different. In HeLa cells much more late mRNA is made than early mRNA; in L cells the reverse is true. 4) At 5 h after infection the mRNA molecules in polyribosomes contain all sequences characteristic of early mRNA; by 8 h after infection mRNA in polyribosomes is very significantly depleted with respect to early mRNA. 5) The large mRNA molecules transcribed late contain sequences also present in small early mRNA. Some small mRNA molecules are also transcribed late; they contain at least some sequences characteristic of late mRNA. 6) Early mRNA is very stable in HeLa cells. Late mRNA is significantly less stable, but late mRNA that contains some early sequences is as stable as early mRNA itself(667).

Leonard I. Malkin (US) and Alexander Rich (US) discovered that a portion of the newly synthesized polypeptide chain is buried in the ribosome. They determined that this nascent polypeptide chain contains an estimated 30-35 amino acids with an unfolded length of 100 angstroms(668). 

Seikichi Izawa (US) and Geoffrey Hind (US) provided evidence that two protons should be released to the interior of the thylakoid membrane for every electron flowing to NADP+ or to an alternate photosystem 1 acceptor(669).

William S. Brinigar (US), David B. Knaff (US), and Jui H. Wang (US) mixed a porphyrin, AMP, and inorganic phosphate with an imidazole group as a catalyst. Exposure of the mixture to ultraviolet or visible light resulted in the direct synthesis of ATP(670).

Christopher Reid (CA), Leslie Eleazer Orgel (GB-US), and Cyril Ponnamperuma (Ceylonese-US) found that nucleotides and dinucleotides can be formed by random processes alone. They have also demonstrated the formation of ATP through the ultimate agency of solar energy(671).

Christopher Reid (CA), Leslie Eleazer Orgel (GB-US) synthesized sugars in potentially prebiotic conditions(672).

Lionel V. Crawford (GB) and Michael J. Waring (GB) described supercoiling of polyoma virus DNA measured by its interaction with ethidium bromide(673).

Don B. Clewell (US) and Donald Raymond Helinski (US) described a supercoiled circular DNA-protein complex in Escherichia coli. They discussed its purification and induced conversion to an open circular DNA form(674).

Rafael D. Camerini-Otero (US) and Gary Felsenfeld (US) described a very simple model of a DNA superhelix in which twisting and bending forces are in balance. Closed circular DNA molecules in aqueous solution take the form of interwound superhelices over a wide range of superhelix densities(675).

William R. Bauer (US) reported that the DNA in all organisms is negatively supercoiled, and to about the same degree(676). The kinetoplastic DNA of certain unicellular eukaryotic parasites is the only known exception.

Reiji Okazaki (JP), Tuneko Okazaki (JP), Kiwako Sakabe (JP), Kazunori Sugimoto (JP), Akio Sugino (JP), Norio Iwatsuki (JP) and Yasuo Imae (JP) discovered that primers are laid down at short intervals in the synthesis of the lagging chain of DNA. This results in the synthesis of short fragments of DNA, now called Okazaki fragments. These fragments have been found in prokaryotes (Archaea or Bacteria), eukaryotes (Eucarya), and viruses(677-682).

William C. Summers (US) and Waclaw Szybalski (US) used bacteriophage T7 to show that only one strand of the DNA molecule acts as a template for RNA synthesis(683, 684). 

Mehran Goulian (US), Arthur J. Kornberg (US), and Robert L. Sinsheimer (US) were able to get DNA polymerase to assemble a 5000-nucleotide DNA chain with the identical form, composition, and genetic activity as DNA from a natural virus. This successful synthesis of the biologically active ϕX174 virus was the first time that the nucleic acid of an active virus was synthesized in the laboratory(685).

Jonathan R. Warner (US), Ruy Soeiro (US), Ming C. Liau (CN), Robert Palese Perry (US), Nessly C. Craig (US), Thoru Pederson (US), and Ajit Kumar (US) revealed the presence of ribosomal proteins and the assembly of nascent ribosomes in the nucleolus(686-690).

Giovanni B. Rossi (IT) and Charlotte Friend (US) showed that cancer cells can be induced to differentiate by an exogenous agent, such as a virus(552).

Joseph R. Kates (US), Brian R. McAuslan (US), William Munyon (US), Enzo Paoletti (US), and James T. Grace, Jr. (US) were the first to find a nucleic acid polymerase in a virion—the DNA-dependent RNA polymerase of vaccinia virus(691, 692).

Adam Kepes (FR), using Escherichia coli, presented evidence that the lactose operon is transcribed then translated in a linear sequential manner beginning with beta galactosidase (Z), followed by beta galactoside permease (Y), then beta galactoside transacetylase (A)(693). 

Hideyuki Ogawa (JP) and Jun-ichi Tomizawa (JP) found that single-strand breaks in lambda bacteriophage DNA induced by phosphorus 32 are rapidly repaired by a host cell mechanism(694). They found that simultaneous breaks in both strands are also repaired but at a much lower efficiency(695). 

Mario Renato Capecchi (US) found that the release of newly synthesized polypeptides from ribosomes depends on a release factor and a terminator codon(696).

Charles James Ingles (CA) and Gordon H. Dixon (CA) began work which would reveal how somatic histones are replaced by protamines in a regular series of biochemical changes(697).

Robin E. Monro (GB) determined that peptidyl transferase, which catalyzes peptide synthesis, is one of the constituent proteins of the 50S part of the ribosome in Escherichia coli(698).

George Alan Robison (US), Reginald William Butcher (US), Earl Wilbur Sutherland, Jr. (US) Joel Griffeth Hardman (US), Paul J. LaRaia (US), and Edmund H. Sonnenblick (US) concluded that beta andrenergic effects in general are mediated by cyclic AMP(699-701).

Jack Leonard Strominger (US), Jean-Marie Ghuysen (BE), and Donald J. Tipper (US) divided the bacteriolytic enzymes into three groups: 1) glycosidases such as lysozyme which catalyze hydrolysis within the glycan chain of the peptidoglycan, 2) endopeptidases such as lysostaphin which attack the interpeptide bridge portion of the peptidoglycan, and 3) acetylmuramyl-L-alanine amidases which attack the linkage between N-acetylmuramic acid and L-alanine(36, 475).

F. John Ballard (AU), Richard W. Hansen (US), and Gilbert A. Leveille (US) demonstrated that glyceride-glycerol is synthesized from pyruvate in adipose tissue via a pathway that involves both pyruvate carboxylase and phosphoenolpyruvate carboxykinase (PEPCK-C)(702).

Erela Gorin (IL), Z. Tal-Or (IL), and Eleazar Shafrir (IL) coined the term glyceroneogenesis to name the pathway described above(703).

Lea Reshef (IL), Richard W. Hanson (US), and F. John Ballard (AU) proposed that the glyceroneogenesis pathway is involved in the re-esterification of fatty acid to triacylglycerol in adipose tissue during fasting and that glyceroneogenesis from pyruvate is the source of the 3-phosphoglycerol required for triacylglycerol synthesis(704). 

John A. Rupley (US) discovered that lysozyme breaks the bond between carbon atom 1 of N-acetylmuramic acid and the oxygen attached to carbon 4 of N-acetylglucosamine in the glycosidic link(705).

Ronald John Gibbons (US) and Suzanne B. Banghart (US) reported that three enzymes at the bacterial surface deal in particular ways with the common sugar sucrose, which is composed of one molecule of glucose and one of fructose. The enzyme invertase splits the sucrose into its two components, both of which are released to become sources of energy for the cell. A second enzyme, glucosyltransferase, splits the sucrose and releases fructose as a nutrient but polymerizes the glucose into a long polysaccharide called a glucan, which is insoluble in water. A third enzyme, fructosyltransferase, builds the fructose into a similar but water-soluble polysaccharide and liberates glucose. The synthesis of extracellular dextrans by bacteria on the teeth contributes to the formation of dental plaque and encourages dental caries(706).

Morris John Karnovsky (ZA-US) and Thomas S. Reese (US) used the horseradish peroxidase (HRP) method to establish that the endothelial cells in the brain vasculature form the so-called blood brain barrier at the cellular level(707).

Helio Gelli Pereira (BR), Bela Tumova (CZ), and Robert G. Webster (NZ-US) described the recombination of avian and human influenza viruses involved in the generation of pandemic influenza(708).

William Graeme Laver (AU) and Robert G. Webster (NZ-US) formulated the concepts of antigenic drift and antigenic shift as well as theories of the origin of influenza virus strains responsible for pandemics that postulated the introduction of genome segments from influenza virus strains circulating in pelagic birds, horses, pigs, and chickens into influenza strains circulating in human populations(709-711).

Robert G. Webster (NZ-US), William Graeme Laver (AU), Bela Tumova (CZ) Judith R. Schäfer (US), Yoshihiro Kawaoka (US), William J. Bean (US), Jochen Süss (DE), Dennis Senne (US), and Robert G. Webster (NZ-US) found that serum from patients who had survived the 1957 influenza pandemic reacted with avian influenza viruses(712, 713). Later genetic analyses showed that the “Asian flu” virus had indeed received 3 of its 8 gene segments from birds.

Virginia S. Hinshaw (US), William J. Bean (US), Robert G. Webster (NZ-US), and G. Sriram (US) hypothesized that something like genetic reassortment (which had not yet been discovered) occurred to cause the big changes that appeared among human influenza viruses, driving pandemics(714).

Kennedy F. Shortridge (AU) and Charles H. Stuart-Harris (AU) hypothesized that Southern China is an epicenter for the emergence of pandemic influenza viruses, the seeds for which had been germinating for 4,500 years when it was believed the duck was first domesticated in that region(715).

Li L. Shu (CN), Yi P. Lin (CN), Stephen M. Wright (US), Kennedy F. Shortridge (AU) and Robert G. Webster (NZ-US) found evidence that interspecies transmission of influenza virus from humans to pigs has happened multiple times in pigs in Southern China(716).

Michael Gregor (US) notes that molecular and genetic studies point to the duck as the silent intestinal carrier of avian influenza viruses raised in close proximity to habitation. Large scale chicken production in Southern China introduces stressed and crowded chickens into this avian influenza milieu. Gregor highlights the role of man in creating the environment conducive to the spread of the avian influenza virus from duck to chickens to man(717).

Jack L. Pate (US) and Erling J. Ordal (US) discovered the mechanism of gliding motility in Cytophaga(718).

Lewis G. Tilney (US) and Keith R. Porter (US) presented a model of their interpretation of how in the heliozoan, Actinosphaerium nucleofilum, a 220-A microtubule from the axopodium transforms into a 340-A tubule and what this means in terms of the substructure of the untreated microtubules(719).

Thomas D. Brock (US) and Hudson Freeze (US) studied microorganisms from hot springs in Yellowstone National Park, where they observed growth of fungi at temperatures as high as 60°C, of cyanobacteria at 75°C, and bacteria at >90°C. This included a description of the bacterium Thermus aquaticus, which grows at an optimum temperature of 75°C(720-722). These papers stimulated renewed interest in extremophiles. Thermus aquaticus produces a heat stable DNA polymerase which became an indispensable tool in the polymerase chain reaction (PCR).

Marvin P. Bryant (US), Elizabeth A. Wolin (US), Meyer J. Wolin (US), and Ralph Stoner Wolfe (US), while studying the bacterial oxidation of ethanol, found two bacterial species acting in a symbiotic relationship. One converting the ethanol to hydrogen and acetate, the other utilizing the hydrogen to reduce carbon dioxide to methane. Excess hydrogen actually inhibits the first organism(723). This helps explain the interactions of anaerobes during the fermentation of complex organic compounds. This phenomenon is now known to be of great importance in anaerobic degradation in the rumen. It is also known to be even more importance in methanogenic ecosystems where more complete anaerobic degradation occurs, e.g., where products such as volatile and longer-chain fatty acids are largely converted to methane and carbon dioxide.

John Woodland Hastings (US) and Quentin Howieson Gibson (GB-US) found that Vibrio fischeri, a luminous species of bacterium, produces a diffusible compound, called an autoinducer, which accumulates in the medium during growth. This autoinducer allows the bacterium to sense its elevated density. The concept is analogous to the production of pheromones in higher organisms(724). 

Roger M. Spanswick (GB-US) and John W. Costerton (GB) demonstrated that many plant cells are directly connected by way of their cytoplasm(725).

David Koffler (US), Peter H. Schur (US), and Henry G. Kunkel (US) eluted anti-DNA and several other antinuclear antibodies from glomeruli of kidneys showing systemic lupus erythematosis (SLE) nephritis. Deposits of DNA antigen associated with immunoglobulin and complement were observed. These results suggest a pathogenic role for DNA-anti-DNA immune complexes(726). 

George Bellamy Mackaness (US), and Robert Vincent Blanden (AU) discovered that macrophages must be activated before they could digest the bacteria causing brucellosis(727).

Theodor Otto Diener (US) and William B. Raymer (US) proposed that the disease of plants called spindle-tuber is caused by an agent which is a naked RNA molecule(728). This represents the discovery and naming of viroids.

Charles B. Smith (US), Jose G. Canchola (US), and Robert Merritt Chanock (US) demonstrated parainfluenza 1 in tissue culture using the hemadsorption technique(729).

Akio Takeuchi (US) used the electron microscope to demonstrate that salmonellae invade epithelial cells of the guinea pig intestine by an endocytic process(730).

Theo M. Konijn (NL), J.G.C. van de Meene (NL), John Tyler Bonner (US), and David S. Barkley (US) discovered that bacterial 3´, 5´ cyclic AMP causes cellular slime molds to aggregate(731).

Shinya Inoué (US) and Hidemi Sato (JP) demonstrated that microtubules of the spindle apparatus are in dynamic equilibrium with a subunit pool(732).

Charles Allen Thomas, Jr. (US) proved that the DNA of T-even phages exists in a circular form(733).

Moshe Shilo (US) discovered myxobacteria which are specific in their ability to lyse cyanobacteria)(734).

A. Erling Porsild (CA), C. Richard Harrington (CA) and Gerry A. Mulligan (CA) germinated artic lupine (Lupinus arcticus) seeds from the Yukon which were known to be 10,000 years old(735).

The previous record was for seeds of the sacred lotus (Nelumbium nuciferum) that were 2,000 years old. 

Margaret B. Davis (US) developed a method for calculating absolute rates of pollen deposition(736).

Theodore Thomas Puck (US) and Fa-ten Kao (US) designed a very successful in vitro cell culture system specifically to detect auxotrophic mutants in animal cells(737).

Vincent M. Sarich (US) and Allan C. Wilson (NZ-US) shook the human family tree when they claimed, based on immunological comparisons of serum albumens, that humans, chimpanzees, and gorillas had a common ancestor five million years ago(738).

Vincent M. Sarich (US), Allan C. Wilson (NZ-US), Jack Lester King (US), Thomas H. Jukes (US), Richard Earl Dickerson (US),Walter Monroe Fitch (US), Richard Holmquist (US), Tomoko Ohta (JP), and Motoo Kimura (JP) supported the generalization that the rate of amino acid substitution within a given protein seems relatively constant over evolutionary time and that many of the amino acid changes occurring during the evolution of a protein are selectively unimportant ones which have been fixed by random process(738-746). This is often referred to as non-Darwinian evolution or the molecular clock. Emile Zuckerkandl (US) introduced the phrase molecular evolutionary clock(747).

Mary Weiss (US) and Howard Green (US) produced man-mouse hybrid cells which selectively eliminated human chromosomes. This asymmetric chromosome loss produced hybrid cells with partial human chromosome complements. By correlating the retention or loss of a specific human marker with the retention or loss of a particular chromosome they were able to assign the gene coding for the marker to an identifiable human chromosome. The gene locus coding for thymidine kinase was thus located to chromosome 17(748).

Olive S. Pettengill (US) and George D. Sorenson (US) succeeded in growing myeloma cells in suspension culture(749).

Hayden G. Coon (US) and Robert D. Cahn (US) were the first to obtain in vitro clones of euploid cells that retained their specialized function. They also showed that this specialized function can be stabilized(750, 751).

Wilbur H. Sawyer (US) determined that the volume of urine formed in mammals is regulated primarily through the antidiuretic hormone (ADH), arginine vasopressin, and lysine vasopressin(752).

Juha P. Kokko (US) and C. Craig Tisher (US) found that in mammals the effect of ADH is predominantly upon the water permeability of the collecting duct of the nephrons(753). 

Irving L. Weisman (US) demonstrated that thymocytes emigrate from the thymus to the "T cell domains" within peripheral lymphoid organs(754).

Nicholas Avrion Mitchison (GB) was among the first to suggest that a normal immune response requires co-operation of various types of lymphocytes(755).

Donald Mosier (US) was the first to show that lymphocytes must interact with nonlymphoid cells to be able to generate an antibody response(756).

Herman N. Eisen (US), J. Russell Little (US), C. Kirk Osterland (CA), Ernest S. Simms (US), and Michael Potter (US) observed that human and murine myeloma proteins are, in fact, monoclonal antibodies(757, 758).

Michael G. Davey (CA) and Ernst F. Lüscher (CH) found that thrombin is the most potent stimulator of platelet aggregation(759).

John Allen Clements (US), Don F. Tierney (US), Harold J. Trahan (US), and Jean Nellenbogen (US) defined and described the role of pulmonary surfactant(760-762).

Elwood Vernon Jensen (US), Eugene R. De Sombre (US), Daniel J. Hurst (US), T. Kawashima (JP), Peter Wilhelm Jungblut (DE), Tetsuro Suzuki (JP), Walter E. Stumpf (US), Masahiro Numata (JP), Sylvia Smith (US), Giovanni A. Puca (IT), Suresh Mohla (US), and Peter I. Brecher (US) performed pioneering studies of the mode of action of estrogenic hormones(763-774).

Sir Bernard Katz (RU-GB) and Ricardo Miledi (GB) proposed that the arrival of an action potential at the presynaptic terminal of the myoneural junction causes calcium influx that facilitates the binding of acetylcholine (ACh) packets to the presynaptic membrane which leads to the subsequent exocytotic release of multimolecular packets from the motor neuron terminal into the synaptic cleft. Each small packet of ACh produces a very brief signal in the muscle fiber(775-783).

Vincent Paul Dole (US) and Marie E. Nyswander (US) postulated the physiological basis of narcotic addiction(594, 595).

Saul Krugman (US), Joan P. Giles (US), and Jack Hammond (US) separated disease caused by the hepatitis A virus (HAV) from that caused by hepatitis B virus (HBV)(784). This led to virologic and serologic breakthroughs that have resulted in an increasing understanding of HBV, HBV infection and HBV disease.

F. Paul Alepa (US), R. Rodney Howell (US), James R. Klinenberg (US), and Jarvis Edwin Seegmiller (US) found that the increased rate of purine synthesis in patients with glycogen storage disease, Type 1 is attributed to the deficiency of glucose-6-phosphatase(785).

Mauricio B. Rosenbaum (AG) Marcelo V. Elizari (AG), and Julio O. Lazarri (AG) described intraventricular conduction disorders they called hemiblocks. They subdivided these blocks within Tawara branches into: unifascicular, bifascicular, and trifascicular blocks(786, 787). 

Dame Cicely Saunders (GB) and her colleagues opened St. Christopher’s Hospice in London, the world’s first modern hospice, where they combined clinical care, teaching, and research, seeking to achieve a “middle way” between too much and too little treatment(788).

William W. Rodman (US), Ralph C. Williams, Jr. (US), Paul J. Bilka (US), and Hans Joachim Müller-Eberhard (DE-US-DE) proved that rheumatoid factor is a 19S (IgM) antibody directed against 7S (IgG) gamma globulin(789).

Donald S. Waldorf (US), Harley A. Haynes (US), Peter L. Winters (US) and Eugene J. Van Scott (US) introduced the use of nitrogen mustard as a topical chemotherapy in the treatment of mycosis fungoides (T cell lymphoma)(790, 791).

Johannes Joseph van Rood (NL) proposed the creation of the first international organ exchange organization(792).

Folkert O. Belzer (US), B. Sterry Ashby (US), J. Engelbert Dunphy (US), Paul F. Gulyassy (US), and Malcolm Powell (US) discovered that the successful preservation of cadaver organs is aided by the development of a cold hypothermic solution that preserves organs before transplantation(793, 794).

Thomas Killip, II (US) and John T. Kimball (US) proved the importance of the specialized care administered in the coronary care unit (CCU) with their study of the treatment of myocardial infarction in a coronary care unit. Their two year experience tracked 250 patients(795).

Bernard Lown (LT-US) reported on sinus node dysfunction. He referred to it as “sick sinus syndrome”(796).

Edward Osborne Wilson (US) and Robert Helmer MacArthur (CA-US) authored The Theory of Island Biogeography, a study of islands which examines the relation between island size, the number of species contained, and their evolutionary balance. They theorized: 1) that an equilibrium number of species exists which characterizes any island of a given size and distance from its source of colonists, and 2) the exact composition of species present on an island should change over time and depend on the historical processes of immigration and extinction. This work established the discipline of theoretical ecology(797).

Daniel Solomon Simberloff (US) and Edward Osborne Wilson (US) tested the equilibrium theory in the Florida Keys and found it to be valid(798, 799).

Carl R. Woese (US), Francis Harry Compton Crick (GB), and Leslie Eleazer Orgel (GB-US) suggested that it would have been possible in a pre-DNA world to have a primitive replicating and catalytic apparatus devoid of both DNA and proteins and based solely on RNA molecules, i.e., an RNA world(800-802).

Manfred Eigen (DE), Manfred Sumper (DE), and Rudiger Luce (DE) reported that mixtures of nucleotide monomers and RNA replicase (ribozyme) will give rise to RNA molecules which replicate, mutate, and evolve(803, 804).

Sidney Altman (CA-US), Thomas Robert Cech (US), Mary Lou Pardue (US), Kelly Kruger (US), Paula J. Grabowski (US), Cecilia Guerrier-Takada (US), Kathleen Gardiner (US), Terry Marsh (US), Norman Richard Pace, Jr. (US), Arthur J. Zaug (US), Julie Sands (US), Daniel E. Gottschling (US), and Olke Cornelis Uhlenbeck (US) discovered a group of RNA molecules capable of acting as biological catalysts (ribozymes)(805-815).

Harold B. White, III (US), Bruce Michael Alberts (US), Walter Gilbert (US) and Antonio Lazcano (MX) proposed that DNA and proteins were originally derived from RNA-based cells or cell-like units(816-819). This is commonly referred to as the RNA world hypothesis.

Jennifer A. Doudna (US) and Jack William Szostak (GB-US) found that the Tetrahymena ribozyme can splice together multiple oligonucleotides aligned on a template strand to yield a fully complementary product strand. This reaction demonstrates the feasibility of RNA-catalysed RNA replications and supports the RNA world hypothesis(820).

Anne M. Teisman (GB) and Gina Geffen (GB) asked the question: "Does our limited capacity in selective listening tasks arise primarily in perception or in response organization?" Their experimental results clearly showed that the main limit is perceptual(821).

John L. Harper (GB) compares the contemporary accomplishments in plant ecology with the fundamental ecological questions brought about in Origin of Species by Charles Darwin(822).

Camille Arambourg (FR) and Yves Coppens (FR) discovered Paraustralopithecus aethiopicus: Australopithecus aethiopicus: Paranthropus aethiopicus in 1967 at a site named Koobi Fora. Their work would be largely ignored because of the scarcity of fossils found(823, 824).

Alan Cyril Walker (US), Richard Erskine Frere Leakey (KE), John Michael Harris (US), and Frank H. Brown (US) also discovered the hominid Paraustralopithecus aethiopicus: Australopithecus aethiopicus: Paranthropus aethiopicus, WT 17000, west of Lake Turkana in Kenya. This creature existed between 2.6 and 2.3 million years ago. This species is known from one major specimen, the Black Skull, and a few other minor specimens which may belong to the same species. It may be an ancestor of robustus and boisei, but it has a baffling mixture of primitive and advanced traits. The brain size is very small, at 410 cc, and parts of the skull, particularly the hind portions, are very primitive, most resembling A. afarensis. Other characteristics, like the massiveness of the face, jaws and single tooth found, and the largest sagittal crest in any known hominid, are more reminiscent of A. boisei(825).


“... the history of science bores most scientists stiff. A great many highly creative scientists . . . take it quite for granted, though they are usually too polite or too ashamed to say so, that an interest in the history of science is a sign of failing or unawakened powers.” Peter Brian Medawar(826).

“You will die but the carbon will not; its career does not end with you…it will return to the soil, and there a plant may take it up again in time, sending it once more on a cycle of plant and animal life.” Jacob Bronowski (PL-GB)(827).

“Life is very strange,” said Jeremy. “Compared to what?” replied the spider. Norman Moss(828).

Har Gobind Khorana (IN-US), Marshall Warren Nirenberg (US), and Robert William Holley (US), were awarded the Nobel Prize in Physiology or Medicine for their interpretation of the genetic code and its function in protein synthesis.

James R. Heirtzler (US), Geoffrey Owen Dickson (AU), Ellen M. Herron (US), Walter C. Pitman, III (US), and Xavier Le Pichon (FR) proposed that a geomagnetic polarity timescale (GPTS) can be constructed using oceanic magnetic anomaly record(s), assuming constant seafloor spreading rate(s), and interpolating between available radiometric ages(829-834). This method is most accurate in dating rocks 780,000 to 200,000 million years old. 

Kurt Wuethrich (CH) developed nuclear magnetic resonance spectroscopy for determining the three-dimensional structures of biological molecules(835-837).

For this work he was awarded the 2002 Nobel Prize in Chemistry.

Arnold Henry Kadish (US), Robert L. Litle (US), and James C. Sternberg (US) provided the first description of a polarographic method for the measurement of glucose in biological fluids(838).

Arne Bøyum (NO) presented methodology for isolation of mononuclear cells and granulocytes from human blood. Isolation of monuclear cells by one centrifugation, and of granulocytes by combining centrifugation and sedimentation at 1 gravity(839).

Robert Burns Woodward (US), Albert Eschenmoser (CH), and Claude E. Wintner (US) synthesized cyanocobalamin (vitamin B12)(840-843).

David M. Blow (GB) and Paul Sigler (GB) solved the tertiary structure of chymotrypsin(844-846).

Joel A. Huberman (US) and Arthur D. Riggs (US) combined the techniques of pulse-labeling and DNA autoradiography to analyze DNA replication in Chinese hamster and HeLa cells. Their results prove that the long fibers of which chromosomal DNA is composed are made up of many tandemly joined sections in each of which DNA is replicated at a fork-like growing point. In Chinese hamster cells most of these sections are probably less than 30 μ. long, and the rate of DNA replication per growing point is 2.5 μ per minute or less. In Chinese hampster cells replication seems to proceed in opposite directions at adjacent growing points. Furthermore, adjacent diverging growing points appear to initiate replication at the same time(847). 

Roy John Britten (US) and David E. Kohne (US) were the first to describe repetitive noncoding sequences of DNA in eukaryotic genomes. They went on to show that some sequence elements occur in millions of copies in eukaryotes (Eucarya)(848, 849).

Christine Guthrie (US) and Masayasu Nomura (JP-US) determined that the formation of an initiation complex involving the 30S ribosomal subunit, F-met-tRNA F, and mRNA is an obligatory step in the initiation of protein synthesis in bacterial extracts(850).

Jean Lucas-Lenard (US), Anne-Lise Haenni (US), Richard W. Erbe (US), Philip Leder (US), Lawrence Skogerson (US), and Kivie Moldave (US) found that in protein synthesis following the binding reaction, peptide bond formation ensues if the peptidyl site carries peptidyl-tRNA, or an aminoacyl-tRNA with a free or a blocked alpha-amino group on the amino acid(54, 55, 851).

Brian F.C. Clark (GB-DK), Bhupendra P. Doctor (US), Kenneth C. Holmes (GB), Sir Aaron Klug (ZA-GB), Kjeld Adrian Marcker (DK), S.J. Morris (GB), and Heinrich H. Paradies (DE) crystallized a transfer RNA molecule. The specific type was n-formyl-methionyltransfer RNA(852).

Raymond O. R. Kaempfer (US), Matthew Stanley Meselson (US), and Herschel J. Raskas (US), based on their experimental work with Escherichia coli, suggested that ribosomes must dissociate into their subunits between successive rounds of translation(853).

Friedrich Cramer (DE), H. Doepner (DE), Friedrich von der Haar (DE), Eckhard Schlimme (DE), and Hans-Peter Seidel (DE) proposed a general tertiary structure for tRNA molecules(854).

Brian F.C. Clark (GB-DK), Shyam K. Dube (US), and Kjeld Adrian Marcker (DK), using Escherichia coli, provided the first direct experimental evidence for the position of the anticodon sequence in the structure of a tRNA(855).

Peter Traub (US) and Masayasu Nomura (JP-US) completely reconstituted the 30S ribosomal subunit of Escherichia coli from 16S RNA and proteins(493).

Robert Palese Perry (US) and Dawn E. Kelley (US) were among the first to isolate 28S ribosomal RNA (28SrRNA)(856).

S. Riyasaty () and John F. Atkins (IE) showed that messenger RNA (mRNA) molecules are not always translated in a triplet manner(857).

Hisaji Yamazaki (JP), Satoshi Mizuno (JP), Kazuo Nitta (JP), Ryozo Utahara (JP) and Hamao Umezawa (JP) determined that streptovaricin inhibits RNA and protein synthesis in microorganisms, particularly in gram-positive bacteria(858).

Jan Drenth (NL), Johan N. Jansonius (NL), Roelof Koekoek (NL), H.M. Swen (NL), and Bert G. Wolthers (NL), determined the three-dimensional structure of papain(859).

Robert Lee Hill (US), Keith Brew (GB-US), Thomas C. Vanaman (US), Ian P. Trayer (GB), and P. Mattock (GB) reported the structure, function, and evolution of the milk protein, alpha-lactalbumin(860).

Aaron Jeffrey Shatkin (US) and Jean D. Sipe (US), working with reovirus, were the first to find a virion-bound RNA-dependent RNA polymerase(861).

Donald F. Summers (US), Jacob V. Maizel, Jr. (US), Michael F. Jacobson (US), and David Baltimore (US) demonstrated with polio virus that the proteolytic processing of RNA virus proteins can be mediated by a virus-encoded rather than cellular proteinase(862, 863).

Donald Arthur Walsh (US), John P. Perkins (US), Edwin Gerhard Krebs (US), Thomas R. Soderling (US), John P. Hickenbottom (US), Erwin M. Reimann (US), and Felix L. Hunkeler (US) discovered a protein kinase which is stimulated by cyclic AMP, and which is responsible not only for activating phosphorylase but also for inactivating glycogen synthetase(864, 865).

Earl Reece Stadtman (US), Bennett M. Shapiro (US), Henry S. Kingdon (US), Clifford A. Woolfolk (US), and Jerry S. Hubbard (US) discovered that glutamine synthetase of Escherichia coli is subject to rigorous control by at least four different mechanisms: (1) repression and derepression of enzyme formation, (2) cumulative feedback inhibition by multiple end-products of glutamine metabolism, (3) enzyme catalyzed alterations of preformed glutamine synthetase effecting modulation of glutamine synthetase activity, divalent ion specificity and feedback inhibitor responses, and (4) modulation of glutamine synthetase activity by variations in the ratios of ATP, manganese ions, and other nucleotide tri- and di-phosphates(866). 

Carl Schnaitman (US) and John W. Greenawalt (US) localized the following enzymes to rat liver mitochondrial membranes: outer membrane-monoamine oxidase, kynurenine hydroxylase, rotenone-insensitive NADH-cytochrome c reductase, nucleoside diphosphokinase; inner membrane plus matrix-succinate-cytochrome c reductase, succinate dehydrogenase, cytochrome oxidase, beta-hydroxybutyrate dehydrogenase, alpha-ketoglutarate dehydrogenase, lipoamide dehydrogenase, NAD- and NADH-isocitrate dehydrogenase, glutamate dehydrogenase, aspartate aminotransferase, ornithine transcarbamoylase; intramembranous space- nucleoside diphosphokinase, adenylate kinase(867).

Yasuchiro Anraku (US) isolated galactose-binding and leucine-binding proteins from the surface material of Escherichia coli K12 cells(868).

Howard Michael Goodman (US), John Abelson (US), Arthur Landy (GB), Sydney Brenner (ZA-GB), and John D. Smith (GB) reported their finding of a suppressor gene. In certain mutants a single base change alters the meaning of a messenger codon in such a way that, instead of spelling out an amino acid, it spells out chain termination. Mutants in a quite different gene, called a suppression gene, allow the chain terminating triplet to be read as an amino acid. Their experiments showed that this is caused by a mutated tRNA which carries a single base change in its anticodon. This allows it to read the chain-terminating codon as an amino acid(869). 

Stephen Cooper (US), Charles Helmstetter (US), Olga Pierucci (US), and Eras Revelas (US) established the rules for replication in the Escherichia coli life cycle(870, 871).

Misao Ohki (JP) and Jun-ichi Tomizawa (JP-US) demonstrated that during bacterial conjugation the donor DNA is transferred as a single strand with the 5 prime terminus leading the way(872).

Richard C. Weisenberg (US) and Edwin W. Taylor (US) were the first to describe the presence of nonaxonemal dynein within cells(873).

Richard C. Weisenberg (US), Gary G. Borisy (US), and Edwin William Taylor (US) identified tubulin as the protein subunit of microtubules (874).

Timothy J. Mitchison (US) and Marc Wallace Kirschner (US) described how tubulin polymerizes into microtubules, i.e., that microtubules coexist in growing and shrinking populations that interconvert infrequently - a state that the authors coined 'dynamic instability'(875). They also found that growth of microtubules from centrosomes is governed by dynamic instability(876).

C. Elizabeth Oakley (US) and Berl R. Oakley (US) discovered a third type of cellular tubulin which they named gamma-tubulin. They found it to be essential for nuclear division and microtubule assembly in Aspergillus nidulans(877).

Berl R. Oakley (US), C. Elizabeth Oakley (US), Yisang Yoon (US), and M. Katherine Jung (US) noted that gamma-tubulin has microtubule-nucleating properties(878).

Federico Leighton (CL), Brian Poole (BE), Henri Beaufay (BE), Pierre Baudhuin (BE), John W. Coffey (US), Stanley Fowler (US), and Christian Rene de Duve (GB-BE-US) described the first large-scale preparation of peroxisomes—a feat that made possible more conclusive and precise characterization of their biochemical and morphological properties(879).

Charles L. Fox, Jr. (US) combined silver with sulfadiazine to produce a mild, easily applied drug at least 50 times more active than sulfadiazine alone. Introduced to the market in 1968 as Silvadene R, it has proven to be the most efficacious topical (surface application) compound for controlling bacteria in open wounds of any size. The combination inhibits infection over extended periods of time allowing dermal structures to reconstruct themselves naturally, unimpeded by bacteria. The complete restoration of wound areas proceeds naturally and painlessly, avoiding the need for skin grafts. All the pre-existing functions of the damaged area are restored to their original fully functional state by natural reconstruction(880).

Surendra P. Shrivastava (US), Masuhisa Tsukamoto (JP), and John Edward Casida (US) reported a mechanism of insect resistance to carbamate insecticides in which hydroxylation occurs at various points on the molecule, not only the aromatic group but also the N-methyl on the carbamate, as well as some demethylation(881).

David Y. Thomas (GB) and David Wilkie (GB) demonstrated that in Saccharomyces cerevisiae erythromycin resistance was inherited in a non-Mendelian manner and was eliminated by conversion of the strain to ρ-. The discovery of an antibiotic-resistant marker residing on the ρ determinant ushered in the era of formal mitochondrial genetics, because these markers were phenotypically dissimilar and behaved as point mutations, thus allowing studies of recombination(882). 

William L. Brown, Jr. (US) describes a interspecific chemical signal as an allomone(883). If the benefit is to the recipient the substance is referred to as a kairomone, if both organisms benefit then it is a synomone.

Donald R. Forsdyke (GB) took the natural selection theory of immunity of Jerne, with its emphasis on natural antibody, and combined it with the clonal selection theory of Burnet, with its emphasis on cells, to produce a simple "two site" hypothesis of the mechanism of immune self-recognition in vivo. He made an analogy with a similar process occurring in liquid scintillation counters containing two photocells and a coincidence circuit(884).

Sir Gustav Joseph Victor Nossal (AU), Alistair J. Cunningham (CA), Graham Frank Mitchell (AU), Jacques Francis Albert Pierre Miller (FR-AT-AU), Niels Kaj Jerne (GB-DK), Albert A. Nordin (US) , Claudia Henry (US), Hiroshi Fuji (US), Aurelia M.C. Koros (US), and Ivan Lefkovits (CH) demonstrated that when stimulated by a specific antigen, each B cell becomes a plasma cell that secretes antibodies with a single specificity(885-888).

Hugh O’Neill McDevitt (US) and Marvin L. Tyan (US) found that if they transferred spleen cells from (C3H X C57B1/6) F1 mice, capable of responding to (T, G)-A--L, into irradiated C3H parental recipients, normally incapable of responding to (T,G)-A--L, that the ability to make either a primary or secondary immune response to this synthetic polypeptide antigen was transferred. This localizes the genetic control of the ability to respond to the spleen cell population and indicates that the genetic control is exerted upon a process directly related to antibody formation. Studies with congenic strains of mice and linkage studies in segregating backcross populations show that the ability to respond to (T,G)-A--L and (It,G)-A--L is linked to the H-2 locus and can thus be localized to the IXth mouse linkage group. Note: The antigens were composed of a polylysine backbone with side chains of poly-nL-alanine terminating in short, random sequences of either tyrosine and glutamic acid, [(T, G)-A--L], or histidine and glutamic acid, [(H, G)-A--L], or phenylalanine and glutamic acid, [(P, G)-A--L]. The multipolyalanyl-polylysine (A--L) part of these antigens is not antigenic by itself, and the antibody response to (T, G)-A--L is specific for the tyrosine, glutamic acid, and alanine at the end of each side chain(889).

Emil R. Unanue (US) and Brigette A. Askonas (GB) found that when peritoneal macrophages were cultured for several hours after uptake of mIhemocyanin. The cells degraded most of the mI-labeled protein within 2-5 hr. Their ability to prime lymphocytes of syngeneic mice for a secondary immune challenge remained unchanged for long periods of time despite the loss of more than 90 % of the original content of antigen. The persistence of immunogenicity was associated with a small percentage of antigen retained by the cell in a form which was protected from rapid breakdown and elimination(890).

Motoo Kimura (JP) proposed that genetic variability is maintained in a finite population due to mutational production of neutral and nearly neutral isoalleles(891). This is referred to as the neutral mutation theory of molecular evolution (the neutral theory).

Donald D. Brown (US), Igor Bert Dawid (US), and Joseph Grafton Gall (US) proved in the African clawed toad, Xenopus, that the rRNA genes just like the nucleoli are present in a 1000-fold excess in oocyte GVs, a phenomenon that they named specific gene amplification(892, 893).

Robert Tod Schimke (US), Frederik W. Alt (US), Rodney E. Kellems (US), Randal J. Kaufman (US), and Joseph R. Bertino (US) discovered gene amplification in mammalian cells(894, 895).

Donald D. Brown (US), Carl S. Weber (US), Pieter C. Wensink (US), and Eddie Jordan (US) found that 5 S RNA genes are not linked to the rDNA genes in Xenopus laevis. Tens of thousands of these 5 S RNA genes are arranged in tandem and distributed on many chromosomes(896, 897).

Nina Fedoroff (US), Donald D. Brown (US), J. Ross Miller (US), Elma M. Cartwright (US), and George G. Brownlee (US) subsequently sequenced an entire repeat from Xenopus laevis genomic 5 S DNA. This was the first time that a full-length eukaryotic gene had been sequenced(898).

Barbara R. Migeon (US) and Carol S. Miller (US) were the first to assign an autosomal gene to a particular human chromosome (thymidine kinase to chromosome 17) and proved the usefullness of the parasexual fusion-segregation approach to human gene mapping(899).

Jacques Francis Albert Pierre Miller (FR-AT-AU) and Graham F. Mitchell (Australia) demonstrated experimentally that antibody producing cells originate in the bone marrow(900, 901).

Arthur Cronquist (US) wrote The Evolution and Classification of Flowering Plants, outlining what became known as the Cronquist system. In this system he organized some 350 families of plants by their evolutionary relationships, describing which families are very closely related and which are more distantly related. Since its introduction the system has become the most widely used and accepted reference for botanists studying the evolution of plants(902).

Calaway H. Dodson (US), Robert L. Dressler (US), Harold G. Hills (US), Ralph M. Adams (US) and Norris H. Williams (US) found that some orchids have fragrances composed of 18-20 chemical compounds effective both as general and specific attractants for euglossine bees(903).

Abby Conway (US) and Daniel Edward Koshland, Jr. (US) discovered an example of negative cooperativity in enzymes. When glyceraldehyde 3-phosphate dehydrogenase binds one molecule of glyceraldehyde 3-phosphate this reduces its ability to bind a second molecule of the same substrate(904).

Antoinette Ryter (FR), Yukinori Hirota (JP), and Francois Jacob (FR) proposed that the bacterial DNA molecule is attached to the cell membrane and that the synthesis of new cell-membrane material during elongation of the rod shaped cell occurs in a narrow zone of growth that is situated between the points of attachment of the two partially replicated DNA molecules. Thus growth of the membrane between these points of attachment would cause the continuous separation of the two future genomes(905)

Ernst Hadorn (CH) discovered that cells retain an ability to differentiate in only one way (such as wing) for 100 generations or more, even though there are no known morphological or biochemical criteria by which they differ from other cells only able to differentiate in a different direction (such as leg). This is the state of determination(906).

William N. Lipscomb (US) solved the structure of carboxypeptidase(907).

Junko Hosoda (JP-US) and Cyrus Levinthal (US) used the term early genes to refer to the group of viral genes transcribed immediately following infection(908).

Karl W.A. Wirtz (NL), Donald B. Zilversmit (US) isolated a group of lipid transfer proteins which can promote the movement of lipid from one membrane to another within the cell(909, 910).

K. Theodor Brunner (CH), Jacques Mauel (CH), Jean-Charles Cerottini (CH), and Bernard Chapuis (CH) developed a quantitative assay of the lytic action of immune lymphoid cells(911). We now know that this was evidence for the presence of cytotoxic T lymphocytes (CTLs).

F. Rudolf Turner (US) studied spermatogenesis of the alga Nitella and found that it resembled animal spermatogenesis in many respects(912).

David Arthur John Tyrrell (GB), June D. Almeida (GB), D.M. Berry (GB), Charles H. Cunningham (US), Dorothy Hamre (GB), Melvin S. Hofstad (US), L. Mallucci (GB), Ken McIntosh (US), Walter R. Dowdle (GB), M. Tajima (GB), L.Y. Zakstelskaya (GB), Bernard C. Easterday (GB), Albert Z. Kapikian (GB), R.W. Bingham (GB), Dennis J. Alexander (GB), David J. Garwes (GB), John C. Hierholzer (GB), and Malcolm R. Macnaughton (GB) were the first to recognize and characterize the coronaviruses(913-915).

Robert Paul Hanson (US) and Richard F. Marsh (US) reported the physical and chemical properties of the transmissible mink encephalopathy agent(916).

Margaret J. Polley (US) and Hans Joachim Müller-Eberhard (DE-US-DE) identified C3 convertase, the enzyme responsible for activating the C3 component of complement(917).

Murray A. Matthews (US) found that there is a critical diameter for the initiation of myelin production ranging from 1-2 µm(918).

Stanley D. Beck (US) performed studies of photoperiodic and thermoperiodic regulation of insect diapause induction and development, cold hardiness, voltinism, and neuroendocrine regulation which culminated in his dual-system theory of insect time measurement(919-921).

Randall K. Cole (US), Joseph H. Kite, Jr. (US), and Ernest Witebsky (DE-US) established that the clinical symptoms in the Obese strain of chickens are attributable to a spontaneously arising thyroiditis which is autoimmune in nature(922).

Georg Wick (AT) characterized this avian model as the closest counterpart to human Hishimoto’s disease(923).

John W. Blunt (NZ), Hector F. DeLuca (US), and Heinrich K. Schnoes (US) isolated an active substance identified as 25-hydroxyvitamin D3 (25-hydroxycholecalciferol), which was later proved to be produced in the liver(924, 925).

Michael F. Holick (US), Heinrich K. Schnoes (US), Hector F. DeLuca (US), Anthony Westcott Norman (US), Ronald J. Midgett (US), James F. Myrtle (US), Henry G. Nowicki (US), V. Williams (US), George Joseph Popjak (US), D. Eric M. Lawson (GB), David R. Fraser (AU), Egon Kodicek (GB), H.R. Morris (GB), and Dudley H. Williams (GB) reported the existence of a second active metabolite (1, 25-dihydroxyvitamin D3 or 1, 25-dihydroxycholecalciferol) and showed that this second metabolite is produced in the kidney(926-931). It was now clear that the liver changes vitamin D3 (cholecalciferol) to 25-hydroxyvitamin D3, the major circulating form of the vitamin. The kidneys then convert 25-hydroxyvitamin D3 to 1,25-dihydroxyvitamin D3, the active form of the vitamin which accumulates in cell nuclei of the intestine, where it regulates calcium metabolism.

Hector F. DeLuca (US) summarized as follows: In response to low blood calcium, parathyroid hormone is secreted that in turn stimulates 1-hydroxylase in the kidney to produce the vitamin D hormone. The vitamin D hormone together with parathyroid hormone then provides for the mobilization of calcium from bone and renal reabsorption of calcium, and 1,25-(OH)2D3 by itself provides for the absorption of calcium and phosphorus(932). See Brumbaugh, 1975.

Philip Duryeé McMaster (US) and Robert E. Franzl (US) performed experiments strongly suggesting that antibody production is intimately associated with the proliferation and development of lymphoid elements(933). 

Stanley J. Dudrick (US), Douglas W. Wilmore (US), Harry M. Vars (US), and Jonathan Evans Rhoads (US) reported the successful maintenance of a young child by total parenteral nutrition (TPN)(934).

Joseph Frank Sambrook (GB-US-AU), Heiner Westphal (US), Parithychery R. Srinivasan (IN-US), and Renato Dulbecco (IT-US) discovered that Simian Virus 40 (SV40) can integrate into host DNA, becoming a provirus which is covalently bonded with the cellular DNA(935).

Kinichiro Oda (JP) and Renato Dulbecco (IT-US) found that as long as Simian Virus 40 (SV40) is integrated as a provirus it continues to be transcribed into messenger RNA, even hundreds of generations after the original integration and transformation event. They also established that in lytic infection with SV40 the entire viral genome is transcribed in two nearly equal parts, one early, before the inception of replication of the viral DNA, the other late after DNA replication has begun and that the early RNA is also present in transformed cells(936).

Dona M. Lindstrom (US) and Renato Dulbecco (IT-US) subsequently discovered that in SV40 the early and late messengers are transcribed from different strands of the viral DNA(937).

Joseph Frank Sambrook (GB-US-AU), Bill Sugden (US), Walter Keller (DE-US), Phillip A. Sharp (US), Brad Ozanne (US) Terri Grodzicker (US), Jim Williams (GB-US), Ulf Pettersson (SE), S.J. Flint (US), Yvonne Wewerka-Lutz (US), and Arthur S. Levine (US) produced physical, genetic, and transcriptional maps of the genomes of simian virus 40 and adenovirus 2(938-944). The 1974 Grodzicker paper contains the first use of restriction-fragment-length polymorphism (RFLP) analysis.

Masanori Daibata (JP), Takahiro Taguchi (JP), Yuiko Nemoto (JP), Hirokuni Taguchi (JP), Isao Miyoshi (JP), Philip E. Pellett (US), Dharam V. Ablashi (US), Peter F. Ambros (AT), Henri Agut (FR), Mary T. Caserta (US), Vincent Descamps (FR), Louis Flamand (CA), Agnès Gautheret-Dejean (US), Caroline B. Hall (US), Rammurti T. Kamble (US), Uwe Kuehl (DE), Dirk Lassner (DE), Irmeli Lautenschlager (FI), Kristin S. Loomis (US), Mario Luppi (IT), Paolo Lusso (US), Peter G. Medveczky (US), Jose G. Montoya (US), Yasuko Mori (JP), Masao Ogata (JP), Joshua C. Pritchett (US), Sylvie  Rogez (FR), Edward Seto (US), Katherine N. Ward (GB), Tetsushi Yoshikawa (JP), and Raymund R. Razonable (US) presented evidence that occasionally human herpesvirus 6 integrates its DNA into germ-line cells(945, 946).

A. Araujo (FR), Anne Pagnier (FR), Pierre Frange (FR), Isabelle Wroblewski (FR), Marie-José Stasia (FR), Patrice Morand (FR), and Dominique Plantaz (FR) presented evidence that in rare vertical transmission of herpesvirus 6 the viral genome is integrated into the human DNA in every cell in the infants body(947).

Rudolf Siegert (DE), Hsin Lu Shu (CN), and Werner Slenczka (DE) isolated and identified the Marburg virus. This was a new virus and the first filovirus to be identified(948-950). Ebola, the second filovirus to be identified caused its first known outbreak of hemorrhagic fever in the Sudan of Africa during 1976(951). All filoviruses are classified as biosafety level 4 (BSL 4) agents based on their high mortality rate.

Rainer F. Storb (US), Robert B. Epstein (US), Jean Bryant (US), Haakon Ragde (US), and E. Donnell Thomas (US), after developing dog typing sera, achieved survival of most histocompatibility matched, but not of unmatched, recipients of bone marrow from littermate donors. Recipients were cytoablated and treated with a short course of post-graft methotrexate(952).

Fritz H. Bach (US), Richard J. Albertini (US), Patricia Joo (US), James L. Anderson (US), and Mortimer M. Bortin (US) performed a partially successful allogeneic bone marrow engraftment in a child with Wiskott-Aldrich syndrome(953).

Elwood Vernon Jensen (US) identified estrogen receptor a (ERa)(954). It is found on human chromosome 6, and contains 595 amino acid residues.

George G. Kuiper (SE), Eva Enmark (SE), Markku Pelto-Huikko (SE), Stefan Nilsson (SE), and Jan Åke Gustafsson (SE) discovered estrogen receptor b (ERb)(955). It is found on chromosome 14 in humans and has 530 residues in its amino acid chain. The degree of similarity (homology) in the ligand-binding domain (LBD) between the two receptors is only 59 per cent. Breast cancer tumors are classed according to the type of receptor involved in cell proliferation as either ERa+ or ERa- (ERb+). Both receptors can be present in breast tumors, in different concentrations and playing different roles.

Richard A. Gatti (US), Hilaire J. Meuwissen (US), Hugh D. Allen (US), Richard Hong (US), and Robert Alan Good (US) performed the first completely successful bone marrow transplant in a child with otherwise uniformly lethal X-SCID [X-linked agammaglobulinemia, thymic alymphoplasia, and severe combined immunodeficiency disease](956).

C. Wayne Smith (US), Armond S. Goldman (US), Sylvia S. Crago (US), Shirley J. Prince (US), Thomas G. Pretlow (US), Jerry R. McGhee (US), and Jiri Mestecky (US) demonstrated that human milk contains a number of cell types including neutrophils, macrophages, and lymphocytes(957, 958).

C. Wayne Smith (US), Armond S. Goldman (US), and Robert D. Yates (US) found that many milk leucocytes are living, motile, and interactive(957, 959, 960). 

Dennis Bernard Amos (US), and Fritz H. Bach (US) showed that the mixed leucocyte culture reaction was detecting the HLA-D locus(961).

Graham F. Mitchell (AU) and Jacques Francis Albert Pierre Miller (AU) found that antibody secreting cells are derived from precursors in bone marrow and not in the thymus(962).

Sulo Toivonen (FI) and Lauri Saxén (FI) proposed a double gradient hypothesis to explain how the dorsal lip of the blastopore, when transplanted to the ventral side of a host embryo, could induce the host tissues to form a second embryo around the transplant. They suggested that there were two inducers, and that each inducer was setting up a gradient of inducing agent, and that the interactions between the two gradients allowed for the full induction of structures(963). 

Clarence Joseph Gibbs, Jr. (US), Daniel Carleton Gajdusek (US), David M. Asher (US), Michael P. Alpers (AU), Elizabeth Beck (GB), Peter M. Daniel (GB), and W. Bryan Matthews (GB) determined that Creutzfeldt-Jakob disease is transmissible with the long incubation period characteristic of slow infections(964).

Yuet Wai Kan (CN-US) and David Gordon Nathan (US) developed a way to detect beta-thalassemia trait at birth(965).

James Edward Cleaver (GB-US) observed that xeroderma pigmentosum cells are defective in unscheduled DNA synthesis and in repair synthesis of UV-irradiated DNA(966).

Jean Berger (FR) and Nicole Hinglais (FR) described a renal syndrome prevalent in males, characterized by glomerulonephritis associated with hematuria, extensive mesangial IgA deposits (the characteristic pathologic feature), and a variety of glomerular lesions. It is believed to be the most common form of primary glomerular disease throughout the world(967). It is often called Berger’s disease.

Max Samter (DE-US) and Ray F. Beers, Jr. (US) reported, “The clinical triad of nasal polyposis, bronchial asthma, and life-threatening reactions to acetylsalicylic acid is a disease entity, not a chance cluster of allergic symptoms and represents, in fact, the prototype of a syndrome that has not been previously described and deserves recognition.” This is referred to as aspirin idiosyncrasy syndrome(968).

Bruce S. McEwen (US), Jay M. Weiss (US), and Leslie S. Schwartz (US) reported that when rats were given intraperitoneal injections of radioactive corticosterone there was a higer uptake and longer retention of the corticosterone by the septum and hippocampus regions of the brain(969).

Sir John Charnley (GB) developed the technique for total hip replacement and pioneered arthrodeses (fusing joint surfaces) for the knee and hip(970, 971).

Frederick R. Cobb (US), Sarah D. Blumenschein (US), Will Camp Sealy (US), John P. Boineau (US), Galen S. Wagner (US), and Andrew G. Wallace (US) developed the first successful surgical treatment for cardiac arrhythmias(972, 973).

Adrian Kantrowitz (US), Steinar Tjonneland (US), Jesse C. Krakauer (US), Paul S. Freed (US), Steven J. Phillips (US), Adrian N. Butner (US), William Z. Yahr (US), Menachem Shapiro (), Dov Jaron (US), and Jacques L. Sherman, Jr. (US) pioneered the clinical use of intra-aortic balloon pumping(974, 975).

Ted Kolobow (US), Warren Zapol (US), Joseph E. Pierce (US), A.F. Keeley (US), Robert L. Replogle (US), and A. Haller (US) achieved partial extracorporeal gas-exchange in alert newborn lambs. They delivered premature fetal lambs connected to an extracorporeal membrane oxygenator by umbilical cord, and placed in a tank of artificial amniotic fluid with a membrane artificial lung, perfused via an A-V shunt for periods of up to 96 hours(976). This has been called "artificial placentation."

Hugh H. Bentall (GB) and Antony De Bono (MT) were the first to describe the technique of composite graft replacement of the ascending aorta and aortic valve, with reimplantation of the coronary arteries (977).

John Brereton Barlow (ZA), Chris K. Bosman (ZA), Wendy A. Pocock (ZA), and P. Marchand (ZA) reaffirmed that late systolic murmurs and mid-systolic clicks are intracardiac in origin(978). 

Norman Geschwind (US) and Walter Levitsky (US) discovered that in most human brains, the planum temporale is much larger in the left hemisphere than in the right. This was in accord with previous knowledge that the left hemisphere controls language(979).

C. Flanc (GB), V.V. Kakkar (GB) and M.B. Clarke (GB) investigated the use of 125-iodine labelled fibrinogen as a diagnostic tool in established thrombosis when the patients presented with suggestive symptoms and signs. The validity of their findings was confirmed by phlebography(980).

Susumu Ohno (JP-US), Ulrich Wolf (DE), and Niels Atkin (GB) presented strong circumstantial evidence to suggest that evolution from the fishes to the mammals was propelled primarily by gene duplication(981).


“Science is wonderfully equipped to answer the question ‘How?’ but it gets terribly confused when you ask the question ‘Why?” Erwin Chargaff, Columbia Forum.

“Twelve days ago, I reached the age conventionally regarded as the allotted span of human life…. I am an old man and…in a certain sense I am immortal. Nearly seventy-one years ago a genetic programme came into being in the zygote—the newly fertilized egg—from which there developed that fantastic four-dimensional clone of cells in spacetime, which is, has been, and always [will] be ME.” Frank Macfarlane Burnet(982).

"But, even for cancer, there is only one prime cause. Summarized in a few words, the prime cause of cancer is the replacement of the respiration of oxygen in normal body cells by a fermentation of sugar. All normal body cells meet their energy needs by respiration of oxygen, whereas cancer cells meet their energy needs in great part by fermentation." Otto Heinrich Warburg(983).

Alfred Day Hershey (US), Max Ludwig Henning Delbrück (DE-US) and Salvador Edward Luria (IT-US) were awarded the Nobel Prize in Physiology or Medicine for their discoveries concerning the replication mechanism and the genetic structure of viruses.

Klaus Weber (DE) and Mary Jane Osborn (US) popularized the reliable method of molecular weight determinations by dodecyl sulfate-polyacrylamide gel electrophoresis(984).

Ulrich K. Laemmli (CH) improved this technique which has now become a very popular method for polypeptide analysis and characterization(985).

Bernd Gutte (US), and Robert B. Merrifield (US), Ralph Hirshmann (US), Ruth F. Nutt (US), Daniel F. Veber (US), Ronald A. Vitali (US), Sandor L. Varga (US), Theodore A. Jacob (US), Frederick W. Holly (US), and Robert G. Denkewalter (US) accomplished the in vitro synthesis of ribonuclease A(986-988).

Elias James Corey (US) Ned M. Weinshenker (US), Thomas K. Schaaf (US), Willy Huber (US), Urs Koelliker (US), Ryoji Noyori (JP), and Xue-Min Cheng (US) developed a methodology for the synthesis of the hormones prostaglandin F2a (PGF2a) and prostaglandin E2 (PGE2)(989-993).

Norio Aimi (JP), Minoru Inaba (JP), Minroe Watanabe (JP), Shoji Shibata (US), Miyuki Kaneda (JP), and Yoichi Iitaka (JP) determined that the root of the Chinese peony, Paeonia lactiflora, is the source of paeoniflorin(994, 995).

Weici Wang (US), and Gerhard Eisenbrand (DE) reported that paeoniflorin exhibits sedative, anticoagulant, and anti-inflammatory activity(996).

Joe M. McCord (US) and Irwin Fridovich (US) isolated superoxide dismutase (SOD) from bovine erythrocytes(997).

Bernard B. Keele, Jr. (US), Joe M. McCord (US), and Irwin Fridovich (US) isolated superoxide dismutase (SOD) from Escherichia coli(998).

Joe M. McCord (US), Bernard B. Keele, Jr. (US), and Irwin Fridovich (US) surveyed microorganisms and found that aerobes contain abundant superoxide dismutase (SOD), whereas obligate anaerobes contain little or none. They suggested that SOD may have evolved to prevent unwanted oxidations within the cell(999). 

Richard A. Weisiger (US) and Irwin Fridovich (US) isolated superoxide dismutase from mitochondria(1000).

Fred J. Yost, Jr. (US) and Irwin Fridovich (US) isolated an iron containing SOD from Escherichia coli(1001).

 Thomas W. Kirby (US), Jack R. Lancaster (US), and Irwin Fridovich (US) isolated and characterized the iron-containing superoxide dismutase of Methanobacterium bryantii(1002).

Choh Hao Li (CN-US), Jonathan S. Dixon (US), and Wan-Kyng Liu (US) determined the primary structure of human growth hormone (HGH) from the pituitary(1003).

Denton A. Cooley (US), Domingo Liotta (AR), Grady L. Hallman (US), Robert D. Bloodwell (US), Robert D. Leachman (US), and John D. Milam (US) implanted a total artificial heart designed by Domingo Liotta into a human. The device served as a "bridge" for cardiac transplantation until a donor heart was found, 64 hours. The cardiac transplant functioned for an additional 32 hours until the patient died of pneumonia(1004).

Choh Hao Li (CN-US), Jonathan S. Dixon (US), Tung-bin Lo (TW), Knud D. Schmidt (DK), and Yuri A. Pankov (RU) determined the primary amino acid sequence of the sheep lactogenic hormone prolactin(1005, 1006).

Robert J. DeLange (US), Douglas M. Fambrough (US), Emil L. Smith (US), and James Frederick Bonner (US) showed that histone IVs from peas and cows have essentially the same amino acid sequence. This finding suggested that the sequence of histone IV has been conserved from a time before plants and animals diverged, possibly close to a billion years(1007, 1008).

Gerald Maurice Edelman (US), Bruce A. Cunningham (US), W. Einar Gall (US), Paul D. Gottlieb (US), Urs Rutishauser (US), and Myron J. Waxdal (US) determined the complete amino acid sequence of the immunoglobulin gamma (IgG) molecule(1009).

Donald Metcalf (AU) discovered colony stimulating factors (CSFs)(1010).

Antony W. Burgess (AU), James Camakaris (AU), and Donald Metcalf (AU) purified colony-stimulating factor which specifically stimulates mouse bone marrow cells to proliferate in vitro and generate colonies of granulocytes, or macrophages, or both. Analysis indicated that there was a single protein component. All of the colony-stimulating activity was coincident with the protein band. At high concentrations (>20 ng/ml) the factor stimulated the formation of granulocytic, macrophage, and mixed colonies from C57BL mouse bone marrow cells. As the concentration of purified colony-stimulating factor was decreased, the frequency of colonies containing granulocytes also decreased. At low concentrations of colony-stimulating factor (~70 pg/ml) only macrophage colonies were stimulated(1011).

Antony W. Burgess (AU) and Donald Metcalf (AU) and identified granulocyte-macrophage colony stimulating factor (GM-CSF)(1012).

They identified granulocyte colony stimulating factor (G-CSF) and macrophage colony stimulating factor(1013).

Donald Metcalf (AU) and Nicos A. Nicola (AU) discovered multi-colony stimulating factor (Multi-CSF)(1014). These agents are used to treat patients with cancer and diseases of blood cell formation.

Graham C. Brophy (AU), Janardanan Mohandas (AU), Michael B. Slaytor (AU), Sever Sternhell (AU), T.R. Watson (AU), and L.A. Wilson (AU) determined the structure of carpanone, a lignin found in the carpano tree(1015).

Susan Lowey (US), Henry S. Slater (US), Alan G. Weeds (GB), Gerhard Frank (CH), Harry Baker (GB), and Dennis Risby (US) characterized the myosin molecule(1016-1018).

Ivan Rayment (US) and Hazel M. Holden (US) determined the three-dimensional structure of myosin, a protein critical to generating force and motion in nearly all living things(1019).

Mark R. Adelman (US) and Edwin William Taylor (US) isolated actin and myosin from a non-muscle source, the slime mold Physarum(1020, 1021).

Bruce S. Hudson (US), William B. Upholt (US), Joseph Devinny (US), and Jerome R. Vinograd (US) discovered that bacterial F factor DNA is circular. This was made possible by the simultaneous discovery that ethidium will intercalate into linear DNA but not into circular DNA. Thus if ethidium is added to a solution containing both linear and circular DNA molecules of the same overall base composition, and hence of the same intrinsic buoyant density, the density of the linear molecules will be reduced much more than that of the circular molecules. That is to say, linear and circular DNA molecules of equal intrinsic density can be separated by centrifuging their mixture in a CsCl density-gradient solution containing an excess of ethidium. Vinograd realized that, in the course of the normal procedures of extracting DNA from Escherichia coli, the smaller circular plasmid DNA remains circular, whereas the larger circular bacterial chromosome is sheared into several linear fragments(1022).

R. Bruce Nicklas (US) and Carol A. Koch (US) found that kinetochore reorientation is the critical process ensuring normal chromosome distribution. Mal-oriented kinetochore-to-pole connections are corrected in a tension-dependent mechanism. They showed that the kinetochore-to-pole connection of a ‘maternal’ chromosome is stabilized by using a micro-needle to pull on the ‘paternal’ chromosome attached to it(1023).

Raymond E. Lockard (US) and Jerry B. Lingrel (US) isolated a 9 S RNA from rabbit reticulocytes and deduced it to be the mRNA for globin. This was the first identification of a eukaryotic mRNA(1024).

John Bertrand Gurdon (GB), Charles D. Lane (GB), Hugh R. Woodland (GB), and Gerard Marbaix (BE) injected globin mRNA into the cytoplasm of Xenopus laevis oocytes and demonstrated the synthesis of rabbit globin(1025).

Richard A. Finkelstein (US) and Joseph J. LoSpalluto (US) isolated, purified, tested and named choleragen, the exotoxin of Vibrio cholerae(1026). 

Monsanto Chemical Company introduced the herbicide alachlor, an acetanilide, useful in cotton (Gossypium spp.), soybeans (Glycine max), and peanuts (Arachis hypogaea). ref 

Hildegard Michalke (US) and Hans Bremer (US), exposed Escherichia coli strain B cells to ultraviolet light ranging from 500 to 10,000 erg/mm2. They found that: (1) Synthesis of RNA molecules is terminated and RNA polymerase molecules are liberated at the site of u.v. lesions on the DNA. (2) A dose of 1000 erg/mm2 produced about one transcription-terminating lesion per 1000 DNA bases. (3) Within 45 minutes after irradiation (dose greater than 1000 erg/mm2) the RNA synthesis rate is not significantly increased by photo- or dark repair. (4) With increasing doses of u.v. the rate of RNA chain initiation is reduced. (5) Most fragments and some complete molecules of ribosomal RNA synthesized after u.v. irradiation are broken down within 45 minutes after synthesis(1027).

Roman B. Khesin (RU), Zhosefine M. Gorlenko (RU), Michael F. Shemyakin (RU), Sergey L. Stvolinsky (RU), Sophia Z. Mindlin (RU), and T.S. Ilyina (RU) found evidence that the catalytic site of RNA polymerase and its ability to bind DNA both reside in its large component. The small subunit is believed to have a regulatory function and activate the large component(1028). 

Richard R. Burgess (US), Andrew A. Travers (US), John J. Dunn (US), Ekkehard K.F. Bautz (US), William C. Summers (US), and Ruth B. Siegel (US) purified Escherichia coli RNA polymerase on a phosphocellulose column and asked which combination of fractions, and then which factor in particular, conferred transcriptional activity to the core enzyme on T4 phage DNA. They identified that the selective fraction was a protein (they named it sigma) and discovered that some bacteriophages, including T-even and T7 coliphages, alter the sigma factor of RNA polymerase in such a way that instead of recognizing host DNA it recognizes viral DNA(1029, 1030).

Andrew A. Travers (US) and Richard R. Burgess (US) found that once initiation of RNA synthesis occurs the sigma factor, which is required for the initiation of RNA synthesis, is released from the RNA polymerase to be re-used in another initiation event(1031).

Andrew A. Travers (US) showed that some of the products of viral early genes helped endow RNA polymerase with specificity for viral genes(1032).

Joan W. Conaway (US), Jeanene P. Hanley (US), Karla Pfeil Garrett (US), and Ronald C. Conaway (US) fractionated rat liver and identified five distinct enzyme fractions that were essential for specific transcription: alpha, beta gamma, delta, epsilon and tau. Four of these could be replaced by purified proteins from rat liver: TFIIB (alpha), TFIIF (beta gamma), TFIIE (epsilon) and TFIIH (delta). With the purification of the final factor, TFIIE, and having in hand purified pol II, TFIIB, TFIIF and TFIIH, as well as recombinant TATA-binding protein (TBP), it was possible to show that promoter-specific transcription could be reconstituted in vitro with purified factors. With the purification of the final factor, TFIIE, and having in hand purified pol II, TFIIB, TFIIF and TFIIH, as well as recombinant TATA-binding protein (TBP), it was possible to show that promoter-specific transcription could be reconstituted in vitro with purified factors. Crucially, this allowed the definition of the minimal transcriptional machinery required for promoter-specific transcription in eukaryotes by pol II(1033, 1034).

Brian David Dynlacht (US), Timothy Hoey (US), and Robert Tjian (US) showed that Drosophila cells contain a complex of proteins, which they termed co-activators, that associate with the TATA-binding protein and are important for activation in vitro by specific transcription factors, such as Sp1 and NTF1(1035).

Young-Joon Kim (US), Stefan Bjorklund (US), Yang Li (US), Michael H. Sayre (US), and Roger D. Kornberg (US) purified the Mediator complex from yeast. They were able to reconstitute activated transcription in vitro with purified components, finally demonstrating the elusive Mediator activity. They found that the Mediator is a huge complex of about 20 subunits that associates with RNA polymerase II. Suppressors of RNA polymerase B (SRB) proteins are components of the Mediator complex(1036). 

Richard Marc Losick (US) and Abraham L. Sonenshein (US) found that as Bacillus subtilis enters sporulation a sigma-like factor is altered such that RNA polymerase is endowed with increased affinity for genes of sporulation(1037).

Don J. Brenner (US), George R. Fanning (US), Karl E. Johnson (US), Ronald V. Citarella (US), and Stanley Falkow (US) determined DNA relatedness by reacting denatured, labeled DNA fragments of one organism with similarly prepared unlabeled fragments of another(1038). Later, the definition of a species was made based on ≥70% DNA-DNA relatedness and a change in melting temperature ≤5°C. This process now allows an ideal taxonomy, i.e., one based on bacterial phylogeny.

Wallace L. McKeehan (US) and Boyd Hardesty (US) purified and partially characterized aminoacyl transfer ribonucleic acid binding enzyme. It catalyzes the guanosine triphosphate-dependent binding of phenylalanyl transfer RNA to ribosomes in the sequence of polyuridylic acid, has activity as a ribosome and aminoacyl transfer RNA-dependent guanosine triphosphatase, and is required for the synthesis of peptides from aminoacyl transfer RNA(1039).

James A. Shapiro (US), Lorne A. MacHattie (US), Larry Eron (US), Garret Ihler (US), Karin Ippen (US), Jonathan Roger Beckwith (US), Rita Arditti (US), William S. Reznikoff (US), and Ronnie MacGillivray (US) using an electron microscope became the first to see a particular gene—the lacZ gene(1040).

Takashi Kasai (US) and Ekkehard K.F. Bautz (US), using T4 bacteriophage and Escherichia coli strain BB, found that the synthesis of endolysin messenger RNA is under the control of an initiation site at or near the N-terminus of the endolysin gene(1041).

Izuru Yamamoto (JP), Ella C. Kimmel (US), and John Edward Casida (US) reported insect resistance to pyrethrin as due to an oxidation, occurring at the transmethyl group of the isobutenyl side-chain of the chrysanthemic acid(1042).

J. Michael Kehoe (US) and Michel Fougereau (US) suggested that the constant heavy 2 (CH2) region of the antibody molecule can bind complement(1043).

Viktor A. Bokisch (US), Hans Joachim Müller-Eberhard (DE-US-DE), and Charles G. Cochrane (US) isolated a fragment (C3a) of the third component of human complement containing anaphylatoxin and chemotactic activity and described an anaphylatoxin inactivator of human serum. This was the first time that a specific protein in the complement cascade was purified(1044).

Peter Perlmann (SE), Hedvig Perlmann (SE), Hans Joachim Müller-Eberhard (DE-US-DE), and Jorge A. Manni (AR) noted that cytotoxic effects of leucocytes can be triggered by complement bound to target cells(1045).

Ivan Maurice Roitt (GB), Melvyn Francis Greaves (US), Giorgio Torrigiani (GB), Jonathan Brostoff (GB), and John H.L. Playfair (GB) coined the terms B cells and T cells. B stood for bursa, and T for thymus. B cells soon came to mean bone marrow-derived cells(1046).

Pieter D. Nieuwkoop (NL) and Elze C. Boterenbrood (NL) demonstrated that the mesoderm is induced from ectoderm, under instructions from endoderm. By excising different portions of Ambystoma mexicanum (axolotl) blastulae, and culturing them alone or in combination with other portions, Nieuwkoop concluded that the mesoderm develops from the ectodermal (animal) part of the embryo, but requires contact with the endodermal (vegetal) part to do so(1047, 1048).

Jonathan M. W. Slack (GB), Barry G. Darlington (GB), Joan K. Heath (AU), and Susan F. Godsave (NL) published the results of testing various different growth factors on ectoderm explants from Xenopus blastulae. They found that, at low concentrations, basic fibroblast growth factor (bFGF) could induce mesoderm, as judged by histological criteria(1049).

David Kimelman (US) and Marc Kirschner (US) published the results of similar experiments. These authors used a different indicator of mesoderm induction — the levels of mRNA encoding cardiac actin — but they, too, found that bFGF can induce mesoderm. They also discovered that transforming growth factor-β (TGF-β) is required to boost cardiac actin expression to the level seen normally in embryos. Moreover, they found that FGF mRNA is present in early embryos(1050).

James C. Smith (GB), Brenda M.J. Price (GB), Kristien van Nimmen (BE), and Danny Huylebroeck (BE) discovered that in mammals, a likely mesoderm inducer is activin A — a protein that was best known until then for its roles in adult organisms, but which was now shown to have a similar sequence and activity to a member of the Xenopus TGF-β family that can induce mesoderm(1051).

David L. Barker (US) and William P. Jencks (US) proposed that in enzyme catalyzed reactions it might be possible to produce antibodies specific for the configuration of the substrate in its transition state(1052, 1053).

Henry C.P. Wu (US), Winfried Boos (DE), and Herman Moritz Kalckar (DK-US) isolated and characterized a specific galactose-binding protein used to transport galactose into Escherichia coli(1054).

Herman Moritz Kalckar (DK-US), Thomas J. Silhavy (US), and Winfried Boos (DE) showed that the galactose-binding protein is not only needed in transport but is also needed in the chemotaxis of galactose(1055).

Peter Eric Braun (US), Norman S. Radin (US), Pierre J. Stoffyn (BE-US), Jordi Folch-Pi (ES-US), David H. MacLennan (CA), Cecil C. Yip (CA), G.H. Iles (CA), and Philip Seeman (CA) determined that eukaryotes (Eucarya) normally possess proteins containing covalently bound long chain fatty acids(1056-1058).

Mutsuko Nishihara (US), Norman Friedman (US), and H. Vasken-Aposhian (US) reported that a group of bacteriophages, including Øe, contains 5-hydroxymethyluracil instead of thymine in their DNA and that following infection they alter the pathway of DNA production from host type to viral type(1059, 1060).

Ruth Arnon (IL) and Michael Sela (IL) demonstrated that conformation of a molecule can be important to its antigenicity(1061, 1062).

Paul Whur (CA), Annette Herscovics (CA), and Charles Philippe Leblond (CA) confirmed that the addition of carbohydrate groups to glycoproteins is coordinated in the endoplasmic reticulum and the Golgi complex(1063).

Susumu Ito (US) reported that one of the constant features of intestinal microvilli is the so-called fuzz, glycocalyx, or surface coat which is composed of glycoprotein(1064).

Marco Baggiolini (CH), James Gerald Hirsch (US), Christian Rene de Duve (GB-BE-US), Pierre L. Masson (BE), Joseph Felix Heremans (BE), Marilyn Gist Farquhar (US), and Dorothy Ford Bainton (US) characterized the two types of granules present in neutrophil polymorphonuclear leucocytes(1065-1068). 

Robert H. Whittaker (US) proposed that each living creature can be conveniently and logically placed in one of five kingdoms: Plantae, Animalia, Protista, Fungi, or Monera (prokaryotes)(1069). Whittaker's five kingdom taxonomic scheme.

John Hogg (GB) coined the word Protoctista (Gr. first created beings) to describe any organisms that were neither plant nor animal. Protista is a modification of this term(1070). 

Ernst Heinrich Philipp August Haeckel (Häckel) (Heckel) (DE) suggested that bacteria deserved to be placed in a separate kingdom, which he named Monera(1071, 1072).

H.C. Jones (US), Ivan L. Roth (US), Walter M. Sanders III (US), Ian W. Sutherland (GB), William D. Grant (GB), and John F. Wilkinson (GB) demonstrated carbohydrate fibers as part of the capsule or slime layers of aquatic bacteria(1073, 1074). This layer is now referred to as the glycocalyx.

Torbjörn Oskar Caspersson (SE), Lore Zech (SE), Edward J. Modest (US), George E. Foley (US), Ulhas V. Wagh (SE), E. Simonsson (SE), Gösta Gahrton (SE), Jan Lindsten (SE), Maj Hulton (SE), Gösta Lomakka (SE), Adrian T. Sumner (GB), H. John Evans (GB), Richard A. Buckland (GB), and Marina Seabright (GB) discovered and perfected a staining procedure by which chromosomes took on a characteristic banding pattern. The bands, corresponding to regions rich in AT pairs, were called Q bands if quinacrine was used and G bands if Giemsa stain was used. In most cases the banding pattern was so unique that individual chromosomes could be discriminated from all others in a karyotype(1075-1081).

Joseph Grafton Gall (US) and Mary Lou Pardue (US) were the first to localize a specific gene to a specific site on a chromosome. They used DNA-RNA hybridization to locate the gene for producing rRNA in Xenopus laevis. These experiments represent the first application of highly radioactive nucleic acid probes (RNA) to locate a complementary region (DNA) along a chromosome(1082, 1083). The regions to which the DNA probes annealed were also stained selectively by the Giemsa banding technique. See, above.

Renato Dulbecco (IT-US) described what he called topoinhibition, the in vitro inhibition of DNA synthesis seen in cells which had established extensive contacts with each other. The inhibition was released when a confluent layer was wounded(1084, 1085).

J.  Isobel Howell (GB) and Jack A. Lucy (GB) were the first to fuse plant protoplasts using a chemical, lysolecithin, to promote the union(1086).

Charles Novotny (US), Judith Carnahan (US), and Charles C. Brinton, Jr. (US) discovered that F+ and Hfr bacteria possess a superficial filamentous appendage, the F pilus, which is absent from F- cells. Because Brinton found that removal of its F pilus by physical or chemical means destroys the fertility of the donor cell until such time as a new pilus has been generated, he proposed that the F pilus serves as a conjugation bridge(1087).

Oscar L. Miller, Jr. (US) and Barbara R. Beatty (US) state that he presence of extrachromosomal nucleoli in amphibian oocytes has permitted isolation and electron microscopic observation of the genes coding for ribosomal RNA precursor molecules. Visualization of these genes is possible because many precursor molecules are simultaneously synthesized on each gene. Individual genes are separated by stretches of DNA that apparently are not transcribed at the time of synthesis of precursor rRNA in the extrachromosomal nucleoli(1088).

Gabriella Augusti-Tocco (IT) and Gordon Hisashi Sato (US) adapted a mouse nerve cell tumor (neuroblastoma) to tissue culture and isolated clones that were electrically excitable and that extended nerve processes. This was the first differentiated cell line to be isolated(1089).

S.R. Smithers (GB), R.J. Terry (GB), and David J. Hockley (GB) demonstrated that schistosomes absorb host antigens and, thus disguised, protect themselves against immune attack(1090).

Jean P. Nitsch (FR), Colette Nitsch (FR), and Brigit S. Norreel (FR) developed a technique that made it possible to culture microspores of Nicotiana and Datura, to double the chromosome number of their microspores, and to collect seeds from the homozygous diploid plants within a 5-month period(1091-1094).

Scott Murphy (US) and Frank H. Gardner (US) demonstrated the feasibility of storing blood platelets at room temperature, revolutionizing platelet transfusion therapy(1095).

James A. Miller (US) and Elizabeth Cavert Miller (US) were the first to demonstrate that normal metabolism can convert some harmless chemicals into cancer inducing chemicals(1096).

Priscilla J. Piper (GB) and Sir John Robert Vane (GB) demonstrated the first association between prostaglandin production and the actions of aspirin-like drugs(1097).

Sir John Robert Vane (GB) proposed that the mechanism of action of aspirin and the aspirin-like drugs or non-steroid anti-inflammatory drugs (NSAIDs) is through their inhibition of prostaglandin biosynthesis(1098). There is now general acceptance of the concept that these drugs work by inhibition of the enzyme cyclooxygenase (COX) or prostaglandin H2 synthase, now know to have two isoforms, COX-l and COX-2.

Hans Henriksen Ussing (DK), Cornelis L. Voûte (DK), R. Dirix (DK), Robert Nielsen (DK), Kjeld Mollgard (DK), Karen Eskesen (DK), and Jong J. Lim (DK) made important contributions to renal and electrolyte physiology and performed ingenious studies on the transport and hormonal regulation of sodium and water across isolated frog skin. This led to a new understanding of the transport processes that are basic to the functioning of the human kidney(1099-1108).

Charles D. Kelman (US) developed a technique for cataract removal by aspiration following ultrasonic emulsification of the lens(1109). 

Emil C. Gotschlich (US), Irving Goldschneider (US), Teh Y. Liu (US), and Malcolm S. Artenstein (US) developed a vaccine against Neisseria meningitidi (1110-1112).

David V. Reynolds (US) described the analgesic effect produced by electrical stimulation of the periaqueductal gray area(1113). 

Robert Joseph Huebner (US) and George Joseph Todaro (US) proposed the oncogene hypothesis to explain how RNA viruses can cause human cancer. According to this model, infection of cells by type C RNA viruses occurred millions of years ago during the course of evolution. Every cell is assumed to contain an oncogene, a region of DNA that is normally repressed (prevented from functioning). When the oncogene becomes derepressed, possibly by a virus, by a chemical carcinogen, or by radiation, it expresses itself by bringing about the formation of a transforming protein. A transforming protein of this type could change a normal cell into a malignant one even though no viruses could be recovered from it. They coined the term oncogene(1114).

John E. Dowling (US) and Frank S. Werblin (US) presented an anatomical and physiological analysis of the Necturus maculosus retina. The principles of synaptic organization of the Necturus retina are similar to those of other vertebrates(1115, 1116).

Lewis Wolpert (GB) proposed the French flag model as a conceptual definition of a morphogen. The French flag is used to represent the effect of a morphogen on cell differentiation. A morphogen affects cell states based on its concentration, with these states represented by the different colors of the French flag. High concentrations activate a "blue" gene, lower concentrations activate a "white" gene, while "red" serves as the default state in cells below the necessary concentration threshold(1117, 1118). Well-known morphogens include: Decapentaplegic /Transforming growth factor beta, Hedgehog /Sonic hedgehog, Wingless /Wnt, Epidermal growth factor, and Fibrobalst growth factor. See, Christiane Jani Nüsslein-Volhard, 1980.

Flemming Kissmeyer-Nielsen (DK), Arne Svejgaard (DK), Steen Ahrons (DK), and Lene Staub Nielsen (DK) were the first to describe a crossover between HLA-A and HLA-B, proving that HLA identified a chromosomal region and not a single locus(1119).

Hugh O’Neill McDevitt (US) and Allen Chinitz (US) found in inbred mice that the immune responses to a related series of three synthetic polypeptide antigens are genetically controlled traits which are closely correlated with the genotype for the major histocompatibility (H-2) locus(1120).

Roy Y. Calne (GB), Robert A. Sells (GB), João Rodrigues Pena, Jr. (GB), Duane R. Davis (GB), Peter R. Millard (GB), Basil M. Herbertson (GB), Richard M. Binns (GB), and David Allen L. Davis (GB) showed that spontaneously tolerant pig liver recipients were also tolerant to skin and kidney allografts from the same donor(1121).

Martin G. Lewis (US), Ruscho L. Ikonopisov (BG), Rodney C. Nairn (GB), Terry M. Phillips (GB), Gordon Hamilton Fairley (GB), Dennis C. Bodenham (GB), and Peter Alexander (GB) discovered tumor specific antibodies in patients with melanomas(1122).

Edmund Klein (US) developed a protocol for the application of a highly effective topical anticancer agent, 5-fluorouracil (5-FU), to superficial basal cell carcinoma(1123).

Natalie Hurwitz (GB) reported that there are significantly more adverse drug reactions in elderly patients than in young patients and more in women than in men(1124).

Edward D. Freis (US) demonstrated the life-saving effectiveness of the use of drugs in the treatment of moderate hypertension, and the dramatic reduction of deaths from stroke and congestive heart failure, which can be realized when blood pressure is kept within normal limits(1125-1131).

Juan Rosai (IT-AR-US) and Ronald F. Dorfman (US) described sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman syndrome). It is characterized by abundant histiocytes in the lymph nodes throughout the body(1132).

Richard C. Lillehei (US), Yasuo Idezuki (JP), William D. Kelly (US), Frederick K. Merkel (US), Richard L. Simmons (US), John S. Najarian (US), Richard Weil (US), Hisanori Uchida (JP), José Octavio Ruiz (MX), Carl M. Kjellstrand (US), Frederick C. Goetz (US), and Carlos J. Aquino () were the first to perform the successful allotransplantation of a pancreas(1133-1135).

Colin James Pennycuick (GB) discovered that many migratory birds have minimal energy reserves and must stop to feed at regular intervals. The destruction of the intermediate feeding places of these birds could lead to their extinction, even if their summer and winter quarters are conserved(1136, 1137).

Eugene Pleasants Odum (US) stated that ecological succession is regarded as orderly and directional, and therefore predictable, as a result of modifications of the physical environment by the community itself(1138).

Warren P. Porter (US) and David M. Gates (US) emphasized that animals must be in a thermodynamic equilibrium with their environment(1139).

Paul Ralph Ehrlich (US), and Peter Hamilton Raven (US) suggested that many, if not most, species are not evolutionary units, except in the sense that they (like genera, families, and so forth) are products of evolution. They argue that selection is both the primary cohesive and discruptive force in evolution, and that the selective regime itself determines what influence gene flow (or isolation) will have. They present evidence to support their thesis(1140).

Jürgen Haffer (DE) reasons that in the temperate regions, as well as in the tropics, climatic fluctuations caused pronounced changes in the vegetation cover and led to the isolation of comparatively small populations in refuge areas. The presumably small niche size (and lower population density) of tropical relative to temperate-zone forest animals and the correspondingly higher rate of speciation in the tropics under conditions of large-scale climatic fluctuations may explain the rapid differentiation of topical forest faunas during the Pleistocene(1141).

Margaret B. Davis (US), by identifying and counting  pollen grains at Rogers Lake in Conneticut, was able to construct a plant history of this area from 8,000 to 14,000 years ago(1142).

John Harold Ostrom (US) described the carnivorous dinosaur Deinonychus as an agile, active warm-blooded theropod who may have hunted in packs(1143).

Robert T. Bakker (US) strongly argues that dinosaurs were warm-blooded and that many were very agile runners(1144-1146).

F. Clark Howell (US), Lynn S. Fichter (US), Gerald G. Eck (US), and Bernard A. Wood (US) found fossil remains of Australopithecus africanus, Australopithecus boisei, Homo habilis, and Homo erectus in the lower basin of the Omo river, Southwest Ethiopia(1147-1150).

Michael H. Day (GB) discovered fossil Homo sapiens in the lower basin of the Omo river, Southwest Ethiopia(1151). It was dated at ca. 130K B.P.


“The idea of man as a dominant animal of the earth whose whole behavior tends to be dominated by his own desire for dominance gripped me. It seemed to explain almost everything.” Sir Frank Macfarlane Burnet(1152).

“Freedom to inquire into the nature of things is a rewarding privilege granted to a few by a permissive society.” Sterling Brown Hendricks, The Passing Scene.

“Within each cell a cybernetic network … guarantees the functional coherence of intracellular machinery … and in this system the elementary control operations are handled by specialized proteins (the allosteric proteins) acting as detectors and transducers of chemical information.” Jacques Lucien Monod(1153).

Luis Federico Leloir (AR) was awarded the Nobel Prize in Chemistry for his discovery of sugar nucleotides and their role in the biosynthesis of carbohydrates.

Sir Bernard Katz (DE-GB), Ulf Svante von Euler (SE) and Julius Axelrod (US) were awarded the Nobel Prize in Physiology or Medicine for their discoveries concerning the humoral transmitters in the nerve terminals and the mechanism for their storage, release and inactivation.

Paul J. Crutzen (NL) wrote an article explaining that nitrogen oxides can promote decomposition of atmospheric ozone(1154).

Witold Mechlinski (US), Carl P. Schaffner (US), Paolo Ganis (IT), and Gustavo Avitabile (IT) established the structure of amphotericin B by x-ray crystallographic analysis(1155, 1156). Amphotericin B is a widely used antifungal agent produced by Streptomyces nodosus. It is a member of a family of clinically important molecules called the polyene macrolides.

Ralph C. Dougherty (US), Harold H. Strain (US), Walter A. Svec (US), Robert A. Uphaus (US), and Joseph J. Katz (US) determined the chemical structure of chlorophyll c(1157).

S.E. Balegh (US) and O. Biddulph (US) showed that leaves do absorb and use much green light in photosynthesis, despite the common misconception that they reflect all green light(1158).

Thomas A. Bewley (US), Choh Hao Li (CN-US), and Jonathan S. Dixon (US) performed a comparison of amino acid sequences in human pituitary growth hormone, human chorionic somatomammotropin and ovine pituitary lactogenic hormone(1159-1161).

San-pin Wang (CN-US) and J. Thomas Grayston (US) developed the micro-immunofluorescence (micro-IF) test(1162).

Sergei E. Severin (RU), Alexander A. Boldyrev (RU), Vladimir B. Petukhov (RU), Alexander M. Dupin (RU), and Evgenia V. Pindel (RU) discovered that carnosine, found in the muscle, directly interacts with peroxides formed in the tissue that deteriorate the structure and function of membranes. Thus carnosine participates in maintaining the muscle in a functionally active state. The ascorbate-dependent peroxidation of lipid components of biological membranes is inhibited by the natural histidine-containing dipeptides, carnosine and anserine(1163-1165).

Shiro Kakiuchi (JP), Reiko Yamazaki (JP), and Hideki Nakajima (JP) were examining properties of a heat stable phosphodiesterase activating factor isolated from brain extract and Wai Yiu Cheung (US) was examining the necessity of a calcium binding activator for cyclic 3', 5'-nucleotide phosphodiesterase when they discovered calmodulin(1166, 1167).

Wai Yiu Cheung (US), Thomas J. Lynch (US), and Robert W. Wallace (US) named it calmodulin (1168, 1169).

D. Martin Watterson (US), Farida Sharief (US), and Thomas C. Vanaman (US) determined the primary amino acid structure of calmodulin(1170).

Tai Te Wu (CN-US) and Elvin Abraham Kabat (US) analyzed the amino acid sequences of the variable regions of Bence Jones proteins and myeloma light chains(1171).

Celso Bianco (BR), Richard Patrick (US), and Victor Nussenzweig (US) divided lymphocytes into two subpopulations: those carrying a complement receptor on their surface (CRL) and those not carrying a complement receptor on their surface (non-CRL). The two populations were physically separated using rosette formation and density gradient centrifugation. CRL cells carry immunoglobulin and adhere to nylon wool(1172). Later CRL cells became known a B lymphocytes and non-CRL cells as T lymphocytes.

John D. Crossland (GB), M.D. Pepper (GB), Carolyn M. Giles (GB), and Elizabeth W. Ikin (GB) discovered the MV blood antigen(1173).

Carolyn M. Giles (GB), J. Darnborough (GB), Peter Aspinall (GB), and M.W. Fletton (GB) identified the Cob blood antigen(1174).

Kan L. Agarwal (US), Henry Büchi (US), Marvin Harry Caruthers (US), Neera K. Gupta (US), Har Gobind Khorana (IN-US), Kjell Kleppe (NO), Ashok Kumar (IN), Eiko Ohtsuka (US), Uttam L. Rajbhandary (US), J. Hans Van deSande (DE-CA), Vittorio Sgaramella (IT), Hans Weber (US), and Tesshi Yamada (US) carried out the total synthesis of the gene for alanine transfer ribonucleic acid from yeast(1175).

Gertrudis DelaFuente (ES), Rosario Legunas (ES) and Alberto Sols (ES) used experiments with hexokinase to confirm the theory that enzyme catalysis depends on the enzyme being flexible(1176, 1177).

Takashi Murachi (JP) demonstrated that trypsin exhibits similar behavior(1178).

Thomas Kornberg (US), Malcolm L. Gefter (US), Robb E. Moses (US), Charles Clifton Richardson (US), and Rolf Knippers (DE) discovered DNA polymerase II (second polymerase recognized) of Escherichia coli(1179-1182).

Harvey A. Eisen (US), Philippe Brachet (FR), Luiz H. Pereira da Silva (BR), Francois Jacob (FR), using the lambda virus, were the first to define a genetic oscillatory system, cI and cro(1183).

David Baltimore (US), Alice S. Huang (US), and Martha Stampfer (US) found that there exists a large class of viruses, now called negative strand viruses, that carry a strand of RNA complementary to the messenger RNA as their genome and that carry an RNA polymerase able to copy the genome RNA to form multiple messenger RNAs(1184, 1185).

Masayasu Nomura (JP-US) and Volker A. Erdmann (DE) were the first to reconstitute the 50S ribosomal subunit. Their material was from Bacillus stearothermophilus(1186).

Robert Wesley Morris (US) and Edward Herbert (US) purified and characterized yeast nucleotidyl transferase. They investigated its role in the enzyme-transfer ribonucleic acid complex formation(1187).

John Michael Bishop (US), Warren E. Levinson (US), Nancy A. Quintrell (US), Drew Sullivan (US), Lois Fanshier (US), Jean Jackson (US), Thomas A. Walker (US), Norman Richard Pace, Jr. (US), Raymond L. Erikson (US) and F. Behr (US) associated signal recognition (SRP) RNA (then called 7S RNA) with retrovirus genomic RNA(1188, 1189).

Graham Warren (US) and Bernhard Dobberstein (DE) first noticed that a signal recognition particle (SRP) was operating when they realized that it restored the translocation activity of salt-extracted microsomes in vitro(1190). 

Peter Walter (US), Reid Gilmore (US), and Günter Klaus-Joachim Blobel (DE-US) isolated a signal recognition particle (SRP) which is used to attach protein secreting ribosomes to the endoplasmic reticulum(1191-1193).

Peter Walter (US) and Günter Klaus-Joachim Blobel (DE-US) found that the signal recognition particle (SRP) contains RNA essential to its function (SRP 7S scRNA)(1194).

Peter Walter (US), Reid Gilmore (US), and Günter Klaus-Joachim Blobel (DE-US) proposed a model that described the molecular mechanism of protein targeting to and translocation across the endoplasmic reticulum (ER) membrane(1195). “According to this model, signal sequences are recognized as they emerge as part of a nascent protein chain from the ribosome by the signal recognition particle (SRP), which binds to them in a direct protein-protein interaction. This recognition event occurs in intimate association with the ribosome, and, indeed, SRP can directly talk to the ribosome and slow the rate at which the polypeptide chain is elongated. This elongation arrest activity most likely serves to maintain the nascent chain as short as possible prior to its targeting to the membrane. Thus a targeting complex consisting of the ribosome with its signal-bearing nascent chain and the engaged SRP is formed, which next interacts with the SRP receptor, a membrane protein that is localized specifically to the ER. The ribosome-nascent chain is then released from SRP and the SRP receptor and, concomitantly, is handed over to a translocation complex, or translocon, in the membrane. Upon binding to the ribosome, the translocon opens an aqueous pore that allows the passage of the nascent protein across the hydrophobic core of the lipid bilayer. The ribosome thus stays attached to the ER membrane to complete the synthesis of the protein that it initiated in the cytosol, and it is these membrane-bound ribosomes that give the rough ER its characteristic appearance when viewed in the electron microscope”(1196).

Davis T.W. Ng (US), Jeremy D. Brown (GB), and Peter Walter (US) discovered a SRP-independent targeting to the ER membrane(1197).

Laust Østergaard (DK), Niels Larsen (DK), Henrik Leffers (DK), Jørgen Kjems (DK), Roger A. Garrett (DK), Elizabeth Suzanne Haas (US), James W. Brown (US), Charles J. Daniels (US), and John N. Reeve (US) found that in the archaebacteria Methanobacterium thermoautotrophicum and Methanothermus fervidus the single signal recognition particle (SRP) RNA gene resides together with a 5S rRNA gene and two tRNA genes within one of the organism's rRNA operons(1198, 1199).

Peter Walter (US) and Alexander E. Johnson (US) described the signal recognition particle (SRP)—the ribonucleoprotein machine that facilitates topologically correct protein synthesis into the endoplasmic reticulum (ER)—as containing a small RNA and six bound proteins(1200).

Adelaide T.C. Carpenter (US) discovered recombination nodules within the synaptonemal complex of Drosophila. This nodule is believed to be the location for recombination events. These nodules have not been found in organisms which do not exhibit recombination(1201-1203).

Ruth Sager (US) and Zenta Ramanis (US) produced a genetic map of non-Mendelian (chloroplast) genes in Chlamydomonas(1204).

Potu N. Rao (US) and Robert T. Johnson (US) merged mammalian cells in the S phase with cells in the G1 phase and found that the nuclei of the G1 cells began to make DNA long before they would normally have done so. This result clearly demonstrated that a cell in the S phase contains something that triggers DNA synthesis, whereas this something is absent from a cell that has not completed its G1 phase(1205). These results were the first indication in mammalian cells that the sequential and unidirectional phases of the cell cycle are controlled by a series of chemical signals that can diffuse freely between the nucleus and cytoplasm.

Leland Harrison Hartwell (US), Joseph Culotti (US), Marilyn Culotti (US), Brian J. Reid (US), John R. Pringle (US), and Robert K. Mortimer (US) pioneered genetic and molecular studies that revealed the universal machinery—cell division cycle or cdc genes— for regulating cell division in all eukaryotic organisms, from yeasts to frogs to human beings(1206-1212).

Yoshio Masui (CA) and Clement L. Markert (CA) discovered, but did not purify, a cytoplasmic factor which had the power to arrest Xenopus eggs at meiotic metaphase II. Cytostatic factor (CSF) was the name they gave it. It later became known as maturation-promoting factor (MPF), then mitosis-promoting factor(1213). MPF was later identified as cyclin B-CDC2. See below.

Sir Paul M. Nurse (GB), Pierre Thuriaux (GB), and Kim Nasmyth (GB), in the yeast Schizosaccharomyces pombe, “defined 14 unlinked genes which are involved in DNA synthesis, nuclear division and cell plate formation. The products from most of these genes complete their function just before the cell cycle event in which they are involved. Physiological characterisation of the mutants has shown that DNA synthesis and nuclear division form a cycle of mutually dependent events which can operate in the absence of cell plate formation. Cell plate formation itself is usually dependent upon the completion of nuclear division”(1214).

Sir Paul M. Nurse (GB) and Pierre Thuriaux (GB) found the first unambiguous evidence for the existence of a gene whose role is to trigger the Gap2-to-M- phase transition during mitosis in Schizosaccharomyces pombe(1215).

John C. Gerhart (US), Mike Wu (US), and Marc Wallace Kirschner (US) extracted MPF from Xenopus laevis eggs and oocytes and determined that this factor appears early during the cell cycle and then rapidly disappears during the first meiotic cycle. MPF then appears during the second meiotic cycle and disappears when maturation arrests. Therefore, MPF activity cycles throughout meiosis(1216).

John W. Newport (US) and Marc Wallace Kirschner (US) discovered the maturation promoting factor (MPF) which could be considered as part of a molecular clock in Xenopus; controlling its cleavage divisions(1217). MPF now means mitosis promoting factor because it was shown to be a mitotic inducer in most, if not all, eukaryotic cell types. MPF consists of two polypeptides which are the products of the cdc2 gene discovered in yeasts(1218).

Tom Evans (GB), Eric T. Rosenthal (US), James Youngblom (US), Dan Distel (US), and Richard Timothy Hunt (GB) discovered and named cyclin from sea urchin eggs. It is identical to the larger polypeptide(1219).

Robert T. Johnson (US) and Potu N. Rao (US) identified a soluble factor which promotes condensation of chromosomes(1220). It now seems likely that the condensation factor and mitosis-promoting-factor (MPF) are one and the same.

Manfred J. Lohka (US), Marianne K. Hayes (US), and James L. Maller (US) purified MPF from unfertilized Xenopus oocytes and postulated that it is composed of two components(1221).

Jean-Claude Labbé (FR), Melanie G. Lee (GB), Sir Paul M. Nurse (GB), André Picard (FR), Marcel Dorée (FR), Jean-Paul Capony (FR), Daniel Caput (FR), Jean-Claude Cavadore (FR), Jean Derancourt (FR), Mourad Kaghad (FR) and Jean-Michel Lelias (FR) showed that in starfish oocytes MPF is a heterodimer consisting of cyclin-dependent kinase (cdc2) and cyclin B(1222, 1223).

Noriyuki Sagata (JP), Nobumoto Watanabe (JP), George F. Vande Woude (US), and Yoji Ikawa (JP) discovered that the c-mos proto-oncogene product, pp39mos is the cytostatic factor (CSF), long known as an endogenous meiotic inhibitor in vertebrate eggs(1224).

Arthur Beck Pardee (US) proposed that cells go into a Gap 0 (G0) state, and that this is an equivalent state irrespective of the means by which it is induced. He showed that cells re-enter the cell cycle by transiting a 'restriction point' - after which they are committed to the cell cycle - and argued that this switch is defective in cancer cells. He proposed that the ‘restriction point’ allows normal cells to retain viability by a shift to minimal metabolism upon differentiation... when conditions are suboptimal for growth(1225, 1226).

Anders Zetterberg (SE) and Olle Larsson (SE) showed that a variable growth-factor-dependent phase preceded a growth-factor-independent phase(1227).

Viesturs Simanis (CH) and Sir Paul M. Nurse (GB) found that the cell cycle control gene cdc2+ of fission yeast encodes a protein kinase potentially regulated by phosphorylation(1228).

Paul Russell (GB) and Sir Paul M. Nurse (GB) found that in the fission yeast S. pombe the cdc25+ gene function is required to initiate mitosis. They demonstrated that cdc25+ functions as a dosage-dependent inducer in mitotic control, the first such mitotic control element to be specifically identified(1229).

Paul Russell (GB) and Sir Paul M. Nurse (GB) found that wee1+ functions as a dose-dependent inhibitor of mitosis, the first such element to be specifically identified and cloned(1230).

Melanie G. Lee (GB) and Sir Paul M. Nurse (GB) showed that the human gene encoding a cell cycle protein kinase (Cdc2) when expressed in yeast permitted the otherwise defective yeast strain to complete cell division. These data indicate that elements of the mechanism by which the cell cycle is controlled are likely to be conserved between yeast and humans(1231).

Ted A. Weinert (US) and Leland Harrison Hartwell (US) discovered that the RAD9 gene product in Saccharomyces cerevisiae arrests—acts as a checkpoint—the cells in G2 thus improving their opportunity to repair damage to DNA(1232).

Melanie G. Lee (GB), Christopher J. Norbury (GB), Nigel K. Spurr (GB), and Sir Paul M. Nurse (GB) proposed that phosphorylation of p34CDC2, the protein product of the CDC2 gene in mammals, serves as a regulatory mechanism generally in eukaryotic cells, while transcriptional control of the CDC2 gene in higher eukaryotes may be relevant to long term processes such as senescence and differentiation(1233).

Jean-Claude Labbé (FR), Melanie G. Lee (GB), Sir Paul M. Nurse (GB), André Picard (FR), and Marcel Dorée (FR) proposed that entry into meiotic and mitotic nuclear divisions involves activation of the protein kinase encoded by a homologue of cdc2+(1222).

Kathleen L. Gould (GB) and Sir Paul M. Nurse (GB) confirmed that cyclin-dependent kinase (cdc2) is, regulated by phosphorylation. Phosphorylation is lost as cells enter mitosis. These results indicate that cdc2 is negatively regulated by phosphorylation and that dephosphorylation is required for entry into mitosis(1234). Biochemical evidence later proved definitively that wee1 is the kinase and cdc25 is the phosphatase in question.

Bruce A. Edgar (US) and Pat H. O'Farrell (US) identified the cell-cycle regulator sting (stg ) in Drosophila and found that stg mRNA is expressed in a dynamic pattern that, importantly, anticipates the patterns of mitosis(1235, 1236). These studies gave insight into how cell-cycle regulation is carefully tuned and coordinated with other simultaneous events such as cell-fate determination and morphogenesis. The idea that the expression of a cell-cycle regulator, stg, might be regulated by the same genes that control embryonic patterning, rather than cyclins, provided a molecular mechanism that could explain the tight correlation between these two processes during development.

M. Andrew Hoyt (US), Laura Totis (US), B. Tibor Roberts (US), Rong Li (US), and Andrew Murray (US) identified the spindle checkpoint by showing the existence of a feedback-control mechanism in Saccharomyces cerevisiae that prevents cells from leaving mitosis if their mitotic spindle has been incompletely assembled(1237, 1238).

Sandra L. Holloway (US), Michael Glotzer (US), Randall W. King (US), and Andrew W. Murray (US) proposed "that chromosome segregation requires the ubiquitination and degradation of a protein that is not cyclin but is recognized by some of the same proteins that recognize cyclin and target its degradation"(1239).

Randall W. King (US), Jan-Michael Peters (AT), Stuart M. Tugendreich (US), Mark Rolfe (US), Philip Hieter (CA), and Marc Wallace Kirschner (US) isolated and named the anaphase-promoting complex (APC) and found that it could reconstitute destruction of cyclin B in interphase extracts(1240).

Valery Sudakin (IL), Dvora Ganoth (IL), Aviva Dahan (IL), Hanna Heller (IL), Judith Hershko (IL), Francis C. Luca (US), Joan V. Ruderman (US), and Avram Hershko (HU-IL) also isolated a complex, which they called the cyclosome (C), from their clam extracts(1241). We now know that the APC and the cyclosome are one and the same (APC/C).

Hironori Funabiki (JP), Hiroyuki Yamano (GB), Kazuki Kumada (JP), Koji Nagao (JP), Richard Timothy Hunt (GB), and Mitsuhiro Yanagida (JP) presented evidence that Pds1 might be a substrate of the APC/C when they found that destruction of Cut2, the fission-yeast orthologue of Pds1, is necessary for anaphase to occur(1242).

Chang Bai (US), Partha Sen (US), Kay Hofmann (CH), Lei Ma (US), Mark G. Goebl (US), J. Wade Harper (US), Stephen J. Elledge (US), Dorota Skowyra (US), Karen I. Craig (US), Mike Tyers (US), R.M. Renny Feldman (US), Craig C. Correll (US), Kenneth B. Kaplan (US), and Raymond J. Deshaies (US) shed considerable light on how phosphorylation and proteolysis link together to regulate the cell cycle(1243-1245).

Rafal Ciosk (AT), Wolfgang Zachariae (AT), Christine Michaelis (AT), Andrej Shevchenko (DE), Matthias Mann (DE), and Kim Nasmyth (AT) proposed that the APC promotes sister separation not by destroying cohesins but instead by liberating the "sister-separating" Esp1 protein from its inhibitor Pds1p(1246).

Christine Michaelis (AT), Rafal Ciosk (AT), Kim Nasmyth (AT), Vincent Guacci (US), Douglas Koshland (US), Alexander Strunnikov (US), Ana Losada (US), Michiko Hirano (US), Tatsuya Hirano (US), Frank Uhlmann (AT), and Friedrich Lottspeich (AT) described how a cohesin complex—which includes Scc1—keeps chromatids together as they are aligned at anaphase. During this time, separase (Esp1) is kept in check by securin (Pds1). At the start of anaphase, securin (Pds1) is destroyed and releases separase (Esp1), which goes on to cleave Scc1 and allows sister chromatids to spring apart(1247-1250). C. Michaelis and his colleagues coined the term cohesins.

Leland Harrison Hartwell (US), Richard Timothy Hunt (GB), and Sir Paul M. Nurse (GB) were awarded the 2001 Nobel Prize in Physiology or Medicine for their discoveries of “key regulators of the cell cycle.”

Otto Götze (US), Hans J. Müller-Eberhard (US), Sir Peter J. Lachmann (GB), and Ronald A. Thompson (GB) supplied information that identified the C5-C9 complement complex as the actual attack unit responsible for forcing a hole in the cell membrane and discovered that activation of this complex could occur in the absence of an antigen-antibody reaction(1251, 1252).

Jonathan William Uhr (US), Earl Wilbur Sutherland, III (US), Daniel H. Zimmerman (US), and Milton Kern (US) determined that most of the newly synthesized heavy and light chains of immunoglobulin molecules rapidly appear within the cisternae of the endoplasmic reticulum, are assembled into covalently linked molecules, and acquire carbohydrate(1253, 1254).

Paul M. Knopf (US) and Jonathan William Uhr (US) found that most of the immunoglobulin molecules are then secreted relatively rapidly. At the same time a small percentage of the newly synthesized immunoglobulin is inserted into the plasma membrane(1254, 1255).

Matthew Daniel Scharff (US) and Reuven Laskov (IL) discovered that the genes for the heavy and light chains of the imnmunoglobulin molecule are not linked and are translated onto separate messengers(1256).

Peter B. Moore (GB), Hugh Esmor Huxley (GB-US), and David J. DeRosier (GB-US) showed how myosin cross-bridges can interact with actin filaments. They suggested that myosin crossbridging supplied the power source for muscle contraction(1257, 1258).

Birdwell Finlayson (US), Richard W. Lymn (US), Edwin William Taylor (US) and George Moll (US), among others, worked out many of the biochemical details(1259-1262).

Akira Endo (JP), Kazuro Kakiki (JP), and Tomomasa Misato (JP) discovered that the fungicide polyoxin D interfers with chitin synthesis in several fungi by inhibiting chitin synthetase(1263).

Larry D. Frye (US), Michael Edidin (US) and Arthur Weiss (US) discovered that lipid molecules move very freely within their one-half of the lipid bilayer of a cell membrane(1264-1267).

Alan Bernheimer (US) proposed the terms cytotoxin or cytolytic toxin to describe the range of biological activity exhibited by the membrane-damaging toxins(1268).

Peter S. Carlson (US) developed in vitro methods to select biochemical mutants in tobacco(1269).

John B. Power (GB), Sharon E. Cummins (GB), and Edward C. Cocking (GB) took a first step towards in vitro somatic hybridization in plants when they achieved the fusion of isolated protoplasts(1270). 

Patricia A. Black-Cleworth (US) discovered that weakly electric fish use their electric organs for social communication such as aggressiveness, submission, and probably courtship(1271).

Maurice E. Shils (US), William L. Wright (US), Alan D. Turnbull (US), and Frank J. Brescia (US) were the first to attempt home parenteral nutrition (HPN) with a patient. The patient was a woman who had undergone massive small bowel resection for a recurrent desmoid tumor invading the superior mesenteric artery(1272).

The cyclosporins were discovered by workers in Switzerland at Sandoz Ltd. while looking for new antifungal agents. Crude extracts of two strains of fungi imperfecti (Cyclindrocapon lucidium Booth and Tolypocladium inflatum Gams) from the soil of Norway's Hardaanger Fjord showed marginal antifungal activity in vitro, but contained a compound that would revolutionize transplant surgery.

Jean-Francois Borel (CH), Camille Feurer (FR), Hans Ulrich Gubler (CH), Hartmann R. Stahelin (US), C. Magnée (), Robert M. Merion (US), David J.G. White (GB), Sathia Thiru (GB), Douglas B. Evans (US), and Sir Roy Y. Calne (GB) found that the substance, called cyclosporin (cyclosporine), appeared to have exquisite immuno-suppressant properties—controlling organ rejection without knocking out all resistance to infection(1273-1276).

Ray L. Powles (GB), A. John Barrett (US), Hugh M. Clink (GB), Humphrey E.M. Kay (GB), John P. Sloane (GB), Timothy J. McElwain (GB), Roy Y. Calne (GB), David J.G. White (GB), Sathia Thiru (GB), Douglas B. Evans (US), Paul McMaster (GB), David C. Dunn (GB), Graham N. Craddock (GB), Barry D. Pentlow (GB), and Keith Rolles (GB) confirmed that cyclosporin increased survival rate for both bone marrow and organ transplantation without immunosuppression(1277, 1278). Cyclosporine was the first immunosuppressive medication powerful enough to allow transplants to become life-saving treatments, rather than experimental research. 

Peter A. Bretscher (CA) and Melvin Cohn (US) proposed the two-signal theory of lymphocyte activation. This theory states that in order for an effector lymphocyte to become stimulated it must receive two signals, one from an antigen the other from a helper T cell(1279). This had already been demonstrated by Henry Neumann Claman (US), Edward A. Chaperon (US), and R. Fraser Triplett (US)(549, 550).

Nicholas Avrion Mitchison (GB), Klaus Rajewsky (DE-US), and Robert B. Taylor (US) proposed that a cell bound immunoglobulin of T cells is crucial in antibody production. This immunoglobulin serves as an antigen receptor which through cell-cell interaction presents antigenic determinants to cells capable of antibody production(1280).

Richard K. Gershon (GB) and Kazunari Kondo (JP) found that thymus dependent bone marrow derived B cells are incapable of becoming tolerant unless they interact with thymus dependent cells (T cells)(1281). 

Peter J. McCullagh (AU), Richard K. Gershon (GB), and Kazunari Kondo (JP) discovered suppressor T lymphocytes(1282, 1283).

Harvey I. Cantor (US) and Richard Marcy Asofsky (US) discovered that it is T cells which damage the host in the graft-versus-host response. The response was shown to involve two populations of T cells interacting synergistically, one from thymus tissue and the other from either spleen or lymph nodes(1284). 

Joseph H. Coggin, Jr. (US), Kathleen R. Ambrose (US), and Norman G. Anderson (US) discovered that when cells are transformed into cancer cells by Simian virus 40 (SV40) there occurs a reexpression of cellular genes normally expressed in a preceding state of differentiation, i.e., in fetal life(1285).

Beatrice Mintz (US), Karl Illmensee (US), Virginia E. Papaioannou (US), Michael W. McBurney (CA), Richard L. Gardner (GB), and Sir Martin J. Evans (GB), working with a teratoma (a tumor originating when cells from an early embryo are transplanted to an adult environment) found that when this tumor is transplanted back into a blastocyst, i.e., an early embryo, they return to normal(1286, 1287). This is sometimes referred to as the anachronistic origin of cancer.

Alice S. Huang (US), David Baltimore (US), and Martha Stampfer (US) discovered that the single stranded RNA genome of vesicular stomatitis virus behaves as a negative strand which generates positive strand mRNAs complementary to itself(1288).

Thomas Dean Pollard (US), Emma Shelton (US), Robert R. Weihing (US), and Edward David Korn (US) showed that amoeba cytoplasm contains actin filaments which form the typical arrowheads when reacted with rabbit heavy meromyosin(1289).

David J. DeRosier (GB-US), Peter B. Moore (US), Sir Aaron Klug (ZA-GB), R. Anthony Crowther (GB), Linda A. Amos (GB), and John T. Finch (GB) described techniques for the reconstruction of three-dimensional structures from electron micrographs(1258, 1290, 1291).

Robert L. Bennett (US), Michael H. Malamy (US), Harry Rosenberg (AU), Robert G. Gerdes (AU), Kenneth P. Strickland (CA), Kaye Chegwidden (AU), Gail R. Willsky (US), and Franklin M. Harold (US) discovered in studies of Escherichia coli a set of four phosphate transport systems, each of which carried 32Pi into the cell(1292-1296).

Hamilton Othanel Smith (US) and Kent W. Wilcox (US) isolated a new restriction enzyme from Haemophilus influenzae. The restriction activity of this enzyme, named HindII, differed from those previously discovered in two important ways. First, the restriction activity is separate from the modification activity. Second, it cleaves DNA predictably, cutting within its recognition sequence(1297).

Keith Robert Yamamoto (US), Bruce Michael Alberts (US), Ronald M. Evans (US), Neal C. Birnberg (US), Michael Geoffrey Rosenfeld (US), Bert W. O’Malley (US), Merry Rubin Sherman (US), David O. Toft (US), Jean-Claude Courvalin (FR), Marie-Madeleine Bouton (FR), Étienne Émile Baulieu (FR), Pierre Nuret (FR), and Pierre M. Chambon (FR), Marilyn I. Evans (US), Lisa J. Hager (US), G. Stanley McKnight (US), Eileen R. Mulvihill (US), Jean-Paul LePennec (FR), Alan W. Steggles (US), Thomas C. Spelsberg (US), Pierre Pennequin (FR), and Robert Tod Schimke (US) identified steroid hormone receptors and their functions. These hormones plus their receptor represent an active complex which functions by interacting with regulatory proteins which share the following. All of these proteins have at least three binding sites. One binds the hormone recognized by the receptor. Interacting with the hormone activates a second region on the protein which contains two zinc ions. This activated region binds the edges of bases exposed in the DNA major grooves. The recognized major groove base sequence is a control region. The third region directly or indirectly promotes initiation of transcription by RNA polymerase II or, in some cases, inhibits transcription(1298-1307).

Thomas J. Kelly, Jr. (US) and Hamilton O. Smith (US) determined the base sequence recognized by the restriction endonuclease, Hind II(1308).

George H. Sack, Jr. (US) and Daniel Nathans (US) were the first to use polyacrylamide gel electrophoresis as a simple and rapid means of separating DNA restriction fragments(1309). 

Morton Mandel (US) and Akiko Higa (US) found that Escherichia coli becomes markedly competent for transformation by foreign DNA when cells are suspended in cold calcium chloride solution and subjected to a brief heat shock at 42°C. They also found that cells in early to mid-log growth can be rendered more competent than can cells in other stages of growth(1310, 1311).

Kenneth H. Nealson (US), Terry Platt (US) and John Woodland Hastings (US) postulated that the enzyme luciferase is controlled not by some mechanism inside each bacterial cell but by a molecular messenger (autoinducer) that travels between cells as it accumulates in the growth medium(1312).

Anatol Eberhard (US) found that the autoinducer does exist(1313).

Choh Hao Li (CN-US), David Chung (US), Waleed Danho (DE-US), Kalman Kovacs (HU), and Yolande Kovacs-Petres (?) synthesized the pituitary human growth hormone (HGH) or somatatropin, the largest protein molecule yet put together in the laboratory(1314-1317).

Robert Huber (DE) determined the atomic structure of insect hemoglobin(1318).

Phillip Periman (US) was the first to demonstrate that antibody production persisted when a lymphoid cell was fused with an established cell line(1319).

L. Lim (US), Evangelos S. Canellakis (US), Mary Patricia Edmonds (US), Maurice H. Vaughan, Jr. (US), Hiroshi Nakazato (US), Se Yong Lee (US), Jozef Mendecki (US), and George Brawerman (US) discovered that in animal cells messenger RNA is terminated and perhaps stabilized by the addition of polyadenylic acid sequences(1320-1322).

Thomas W. Keenan (US), Wayne N. Yunghans (US), D. James Morré (US) , C.M. Huang (), Sally E. Nyquist (US), and Rita Barr (US), William D. Merritt (US), and Carole A. Lembi (US) showed that newly synthesized membrane lipids of plant and animal cells are first inserted into the endoplasmic reticulum and may later appear in the membranes of organelles such as mitochondria and the plasma membrane(1323-1327).

Herbert Röller (US) and Karl H. Dahm (DE-US) developed the methodology for in vitro culture of insect endocrine glands. This facilitated the extraction of hormones(1328).

John Harley Walsh (US), Rosalyn Sussman Yalow (US), and Solomon Aaron Berson (US) used radioimmunoassay to detect the Australian antigen associated with hepatitis(1329).

Behzad Mohit (US) and Kang Fan (US) discovered that if two cells of the same general lineage are fused they will both express genetic information(1330).

Sonja M. Buckley (US) and Jordi Casals-Ariet (ES-US) isolated and characterized the Lassa fever virus (named for the Nigerian town where it first appeared)(1331).

In 1973, biologists in Sierra Leone, aided by the Yale and Centers for Disease Control (CDC) teams, determined that Lassa virus spread from wild rats to humans(1332).

Bessel Kok (NL-US), Bliss Forbush III (), and Marion P. McGloin (US) proposed that the photolytic (water-splitting) reaction associated with photosystem 2 of photosynthesis uses two molecules of water and proceeds in four steps, each step liberating an electron. Oxygen being a waste product(1333).

Martin G. Weigert (US), Italo M. Cesari (VE), Shirlee J. Yonkovich (US), and Melvin Cohn (US) discovered hypermutation in the lambda light chain of mouse antibody DNA(1334).

Delia B. Budzko (BR) and Hans Joachim Müller-Eberhard (DE-US-DE) reported the cleavage of the fourth component of human complement (C4) by C1 esterase and isolation and characteristics of the low molecular weight product(1335).

Benvenuto Pernis (IT), Luciana Forni (IT), and Luisa Amante (IT) used immunofluorescence to show immunoglobulins on the membrane of bone marrow and not thymus lymphocytes. About one-half of lymphoid cells in blood and spleen have membrane immunoglobulins. The molecules show allelic exclusion, are oriented with the Fab toward the outside, and can bind antigens(1336).

Tsuneo Tomita (JP) showed that following the illumination of a retinal rod cell its membrane became hyperpolarized due to a decrease in permeability to sodium ions(1337).

Julie L. Schnapf (US), Robert N. McBurney (US), David R. Copenhagen (US), and Denis A. Baylor (US) determined that this hyperpolarization traveled along the membrane to the synaptic terminal at the other end of the cell where the nerve impulse arises(1338-1340). 

David Hunter Hubel (CA-US) and Torsten Niels Wiesel (SE-US) provided the first clue to how the brain circuits represent the shape of a given object, by demonstrating that neurons in the primary visual cortex are selectively tuned to respond to the edges oriented in various angles(1341, 1342).

Sir Bernard Katz (RU-GB) and Ricardo Miledi (GB) determined that acetylcholine changes the permeability on the receptor surface of the nerve synapse by opening ion gates(780).

Paul G. Lendvay (AU) and Earl R. Owen (AU) pioneered microsurgery techniques when they rejoined an amputated index finger(1343).

Lewellys F. Barker (US), N. Raphael Shulman (US), Roderick Murray (US), Richard J. Hirschman (US), Frank Ratner (US), William C. L. Diefenbach (US), and Herman M. Geller (US) noted that there is evidence that transmission of serum hepatitis is associated with transmission of virus-like particles, approximately, 20 millimicron in diameter, containing the Australia or serum hepatitis (SH) antigen, which is currently referred to as the hepatitis associated antigen (HAA)(1344).

Nils-Erik Birger Andén (SE), Sherrel G. Butcher (SE), Hans R. Corrodi (SE), Kjell Fuxe (SE), and Urban Ungerstedt (SE) reported that chlorpromazine and similar drugs (neuroleptics) block dopamine receptors but not noradrenaline receptors(1345).

Nils-Erik Birger Andén (SE), Arvid Carlsson (SE), Jüri Kerstell (SE), Tor Magnusson (SE), R. Olsson (SE), Björn-Erik Roos (SE), Bertil Steen (SE), Göran Steg (SE), Alvar Svanborg (SE), Georg Thieme (SE), and Bengt Werdinius (SE) carried out clinical trials for the treatment of Parkinsonism with L-dopa(1346).

Isaac Djerassi (US), Jung Sun Kim (US), Chulee Mitrakul (US), Udom Suvansri (US), and W. Ciesielka (US) invented leucocyte filtration (leukopheresis) and popularized leucocyte transfusions(1347, 1348).

Isaac Djerassi (US) and Jung Sun Kim (US) invented gravity leukopheresis(1349).

Jean Baptiste Gabriel Joachim Dausset (FR), Felix T. Rapaport (FR), Liliane Legrand (FR), Jacques Colombani (FR), and Aline Marcelli-Barge (FR) demonstrated the importance of HLA compatibility for the survival of skin grafts in unmodified human volunteers(1350). 

Thomas Earl Starzl (US), Kendrick Arthur Porter (US), Giuseppe A. Andres (US), Charles G. Halgrimson (US), Richard Hurwitz (US), Geoffrey Giles (US), Paul Ichiro Terasaki (US), Israel Penn (US), Gerhard T. Schroter (US), John R. Lilly (US), S.J. Starkie (US), Charles W. Putnam (US), Max Ray Mickey (US), Miguel Kreisler (ES), Ekkehard D. Albert (US), and N. Tanaka (US) found that zero-HLA mismatching gives human kidney allografts their best chance for function, good histologic appearance, and least dependence on immunosuppression(1351, 1352).

John L. Ziegler (US) and Victor Anomah Ngu (CM) made outstanding contributions toward increasing the cure rate of Burkitt's tumor by chemotherapy(1353-1356).

Alexander Breslow (US)  found from a retrospective study of 98 cutaneous melanomas that both tumor thickness and stage of invasion are of value in assessing prognosis. By combining these two criteria it was possible to identify a group of 45 patients only one of whom developed recurrent or metastatic disease. These criteria may be of value in selecting patients for prophylactic lymph node dissection(1357).

Alex S. Gallus (AU), John F. Cade (AU), John K. Clareborough (AU), Jack Hirsh (AU-CA), John H.N. Bett (AU), Peter A. Castaldi (AU), G.S. Hale (AU), James P. Isbister (AU), K.H. McLean (AU), E.F. O'Sullivan (AU), James C. Biggs (AU), Colin N. Chesterman (AU), I.G. McDonald (AU), J.J. Morgan (AU), and M. Rosenbaum (AU) did work on oral anticoagulants that led to the development of the International Normalized Ratio, an advance in laboratory diagnosis and to clinical trials that assessed the efficacy and risk: benefit ratio of anticoagulants in a variety of clinical situations(1358-1360).

Gene Elden Likens (US), Frederick Herbert Bormann (US), Noye M. Johnson (US), Donald W. Fisher (US), and Robert S. Pierce (US) undertook the large-scale manipulation of a forest ecosystem at Hubbard Brook Experimental Forest in the White Mountains of New Hampshire. This represents the first planned manipulations of an ecosystem to ascertain the importance of vegetation in regulating biogeochemical cycles. They concluded that vegetation is very important in influencing the processes governing the retention of essential nutrients in forest ecosystems. The biotic community is not simply a passive respondent to available abiotic resources, but instead seems instrumental in regulating that availability(1361).

Thomas H. Frazzetta (US) suggests that bolyerine snakes with their unusual anatomy may be an example of what Richard Goldschmidt meant when he said that every once in a while a macromutation might, by sheer good fortune, adapt an organism to a new mode of life, a "hopeful monster" in his terminology. Bolyerines are distinct from all known amniotes, both living and fossil, in that the maxillary bone is divided into anterior and posterior sections by a movable joint. Such a modification has mechanical characteristics adaptive for feeding(1362).

Daniel H. Janzen () and Joseph H. Connell (US) independently proposed that the maintenance of tree species biodiversity in tropical rainfores is due to a density- or distance-dependent factor in recruitment of seedlings from adults of tropical tree species due to host-specific predators or pathogens. These predators/pathogens that specifically target a species make the areas directly surrounding that parent tree (the seed producing tree) inhospitable for the survival of seedlings(1363, 1364). This is referred to as the Janzen-Connell Hypothesis. Subsequent research has demonstrated the applicability of the Janzen–Connell hypothesis in temperate settings as well.

J. Desmond Clark (US) attributed the great success of Homo sapiens sapiens over other hominids to the development of speech. “The achievement of awareness and integration, as with the transmission of knowledge, is in the main through speech”(1365).


“Well, the only thing I’d like to say at the end is that it has all been wonderful fun. I wouldn’t change a single thing; it has been a tremendous privilege, and I hope that in the next generation, where things are going to be more complicated, that it will still be possible for people to have as much fun and reward as I had.” William Barry Wood, Jr.(1366).

Earl Wilbur Sutherland, Jr. (US) was awarded the Nobel Prize in Physiology or Medicine for his discoveries concerning the mechanisms of the action of hormones.

Kyoyu Sasaki (JP), Yoshimasa Hirata (JP), Masaaki Toda (JP), and Shosuke Yamamura (JP) determined the structure of methyl homosecodaphniphyllate by x-ray crystallographic analysis(1367, 1368). This chemical is a member of a family of alkaloids originally extracted from the bark of the Yuzuriha tree, Daphniphyllum macropodum, and used to treat asthma.

Henry Arnold Lardy (US), David L. Garbers (US), W.D. Lust (US), and Neal L. First (US) found that caffeine increases respiration and dramatically induces whiplash-type motility in sperm by increasing cyclic AMP(1369).

Andrew L. Milkowski (US), Donner F. Babcock (US), and Henry Arnold Lardy (US) noted that the respiratory response is dependent on the utilization of acetylcarnitine(1370).

Stanislav Fakan (DE) and Wilhelm Bernhard (CH) found that nascent RNA is predominantly found in the interchromatin region. High-resolution autoradiography associates nascant RNA with perichromatin fibrils(1371).

Douglas Brutlag (US), Randy Schekman (US), Arthur J. Kornberg (US), and William Wickner (US) discovered that short RNA chains are synthesized onto DNA to act as primers during DNA replication(1372, 1373). 

Thomas Kornberg (US) and Malcolm L. Gefter (US) discovered DNA polymerase III (third polymerase recognized) of Escherichia coli(1374).

W. Dean Rupp (US), Charles E. Wilde III (US), Donna L. Reno (US), and Paul Howard-Flanders (US) showed that replication is used to repair or bypass DNA damage(1375).

Anne Marie Skalka (US) was the first to suggest that recombination can be used to complete DNA replication(1376).

Bénédicte Michel (FR), S. Dusko Ehrlich (FR), and Marilyne Uzest (FR) demonstrated fork breakage by replication arrest in E. coli(1377).

Andreas Luder (US) and Gisela Mosig (US) detailed the first clear elucidation that phage T4 initiates most of its DNA replication by a recombinational mechanism(1378).

Timothy Formosa (US) and Bruce M. Alberts (US) developed an in vitro DNA synthesis system that requires seven highly purified proteins encoded by the T4 bacteriophage: the DNA polymerase "holoenzyme" (four proteins), gene 32 protein, dda DNA helicase, and uvsX protein—an enzyme that catalyzes homologous DNA pairing and is functionally homologous to the recA protein. In the reaction observed, the 3'OH end of one single-stranded DNA molecule primes DNA synthesis using a double-stranded DNA molecule of homologous sequence as the template. They incorrectly surmized that DNA is synthesized by a conservative mechanism(1379).

Joing Liu (US), Liewei Xu (US), Steven J. Sandler (US), and Kenneth J. Marians (US) provided key evidence that recombination provides an important pathway for completing DNA replication in E. coli(1380).

Sophie Maisnier-Patin (SE), Kurt Nordström (SE), and Santanu Dasgupta (SE) directly measured how often (DnaC-dependent) replication restart is invoked during E. coli growth(1381).

Martin R. Singleton (GB), Sarah Scaife (GB), and Dale B. Wigley (GB) determined the structure of RecG helicase bound to a replication fork-like DNA molecule(1382).

Hisayuki Matsuo (JP), Akira Arimura (US), R.M.G. Nair (US), Andrew Victor Schally (PL-US) synthesized active porcine luteinizing hormone-releasing factor (LRF) with the following amino acid sequence: pGlu-His-Trp-Ser-Tyr-Gly-Leu-Arg-Pro-Gly-NH2(1383).

Orville L. Chapman (US), Michael Roy Engel (US), James P. Springer (US), and Jon C. Clardy (US) synthesized carpanone, a lignin from the carpano tree(1384).

William S. Johnson (US), Michael B. Gravestock (US), Brian E. McCarry (US), Ronald J. Parry (US), and Bruce E. Ratcliffe (US) synthesized progesterone, a hormone that prepares the lining of the uterus for implantation of the fertilized egg(1385, 1386).

Stephen Fahnestock (US) and Alexander Rich (US) were the first to use the cell’s protein synthesizing machinery to produce a polypeptide containing a nonnatural residue(1387, 1388).

Ramakrishnan Nagarajan (US), LaVerne D. Boeck (US), Marvin Gorman (US), Robert L. Hamill (US), Calvin E. Higgens (US), Marvin M. Hoehn (US), William M. Stark (US), and Joel G. Whitney (US) discovered the cephamycin antibiotics(1389). These antibiotics are produced by species of Streptomyces.

Richard E. Moore (US) and Paul J. Scheuer (US) were the first to isolate palytoxin(1390). This substance is produced by certain soft corals of the genus Polythoa and is one of the most toxic non-peptide substances known.

Daisuke Uemura (JP), Katsuhiro Ueda (JP), Yoshimasa Hirata (JP), Hideo Naoki (JP), Takashi Iwashita (JP), Richard E. Moore (US), Giovanni Bartolini (US), Joseph J. Barchi, Jr. (US), Aksel A. Bothner-By (US), Josef Dadok (CZ-US), and Joseph Ford (US) worked out the structure of palytoxin(1391-1393).

Ernst Richard Habermann (DE) found that palytoxin binds to Na/K pumps to generate nonselective cation channels (1394).

Susan N. Meloan (US), Linda S. Valentine (US), and Holde Puchtler (US) established the structure of carmine and its Ca++ and Al+++ lakes(1395).

Bayer Chemical Company introduced the herbicide metribuzin, a symmetrical triazine, useful in soybeans (Glycine max), sugar cane (Saccharum officinarum), and potatoes (Solanum tuberosum). ref 

Stratis Avrameas (FR), Brigitte Guilbert (FR), Eva Engvall (SE-US), Peter Perlmann (SE), Bauke K. Van Weeman (NL), and Anton H. W. M. Schuurs (NL) developed the enzyme immunoassay procedure to quantitate antigen and subsequently antibody(1396-1400).

Marina Seabright (GB) developed a rapid banding technique for human chromosomes(1080). The immediate application was to determine the location of break points in naturally occurring chromosome rearrangement in patients with congenital defects, and to study the lesions and patterns of exchange induced by X-irradiation. 

Giuseppe Attardi (IT-US), Barbara Attardi (IT-US), Yosef Aloni (US), Donald L. Robberson (US), Livia Pica-Mattoccia (IT), and Norman Davidson (US) made significant progress toward understanding the structure of the human mitochondrial genome and its role in human disease(1401-1406).

John W. Kebabian (US), Paul Greengard (US) and James A. Nathanson (US) discovered how dopamine and a number of other transmitters exert their action in the nervous system. The transmitter first acts on a receptor on the cell surface. This will trigger a cascade of reactions that will affect certain "key proteins" that in turn regulate a variety of functions in the nerve cell. The proteins become modified as phosphate groups are added (phosphorylation) or removed (dephosphorylation), which causes a change in the shape and function of the protein. Through this mechanism the transmitters can carry their message from one nerve cell to another(1407-1409).

Günter Klaus-Joachim Blobel (DE-US), David D. Sabatini (US), and Bernhard Dobberstein (DE) used data from experiments with in vivo and in vitro systems to predict that eukaryotic cells use signals to route proteins across membranes of the rough endoplasmic reticulum. This concept became part of the signal hypothesis (also referred to as topogenesis)(1410-1412).

César Milstein (AR-GB), George G. Brownlee (GB), Timothy M. Harrison (GB), Michael B. Mathews (GB), David Swan (US), Haim Aviv (IL), and Philip Leder (US) were the first to experimentally support the signal hypothesis. This was based on their studies of the manufacture and secretion of antibodies. The signal is a group of amino acid residues at the end of a nascent polypeptide with affinity for the membrane of the endoplasmic reticulum(1413-1415). Günter Klaus-Joachim Blobel (DE-US) and his colleagues extended this concept to other proteins destined to be secreted by the cell (see Blobel references).

Grant Fairbanks (US), Theodore L. Steck (US), and Donald F.H. Wallach (US) were the first to describe the proteins of erythrocyte ghosts(1416).

Lawrence Spatz (US) and Philipp Strittmatter (US) used detergents to isolate the complete cytochrome b5 molecule. This molecule contains an additional sequence of 40 amino acids more than the version isolated using hydrolytic agents. The additional sequence contains a predominance of hydrophobic side chains. They concluded that cytochrome b5 in its native form is anchored to the hydrophobic interior of a membrane(1417).

Clay M. Armstrong (US) provided the first general description of the K+ channel pore, including the fundamental ideas of a selectivity filter, a wider inner vestibule and a gate on the inside(1418, 1419).

Lars U. Lamm (DK), Arne Svejgaard (DK), and Flemming Kissmeyer-Nielsen (DK) assigned the human leucocyte antigen (HLA) region to chromosome 6(1420).

Tetsuo Hiyama (US) and Bacon Ke (US) examined spinach and several cyanobacteria where they identified pigment 430 as possibly the primary electron acceptor of photosystem 1(1421).

J. Murdoch Mitchison (GB) reported that the gap 1 (G1) and gap 2 (G2) phases of the eukaryotic cell cycle may vary considerably between organisms and cell types but the synthesis (S) phase is typically restricted to a small fraction of the cell cycle(1422).

Martin Rodbell (US), Lutz Birnbaumer (US), Stephen L. Pohl (US), and Hendrik Michiel Jan Krans (US) were the first to determine that G protein is involved in transmembrane signaling. They noted that hormonal activation of adenylyl cyclase requires GTP(1423). They also noted that GTP interfers with detection of hormone (glucagon) binding to receptors which regulate adenylyl cyclase activity(1424).

Michael E. Maguire (US), Pamela M. Van Arsdale (US), and Alfred Goodman Gilman (US) found that guanine nucleotides effected receptor binding for specific agonists by reducing their affinity for the receptor(1425).

Dan Cassel (DE), Zvi Selinger (DE), and Thomas Pfeuffer (DE) discovered that GTP protein-linked systems are activated upon binding GTP; hydrolysis of GTP initiates or is responsible for deactivation; dissociation of GDP is linked with the rate-limiting step and is controlled by receptor(1426-1428).

Joseph Orly (IL) and Michael Schramm (DE) demonstrated that components of the adenylyl cyclase system can be mixed and exchanged by cell fusion(1429).

Elliott M. Ross (US), Alfred Goodman Gilman (US), Allyn C. Howelett (US), Kenneth M. Ferguson (US), and Thomas Pfeuffer (DE) then reconstituted the adenylyl cyclase system in vitro(1430-1433).

John K. Northup (US), Paul C. Sternweis (US), Murray D. Smigel (US), Leonard S. Schleifer (US), Elliott M. Ross (US), and Alfred Goodman Gilman (US) purified G proteins associated with adenylyl cyclase(1434).

D. Michael Gill (US), Roberta Meren (US), Dan Cassel (DE), Thomas Pfeuffer (DE), Joel Moss (US), Martha Vaughn (US), Toshiaki Katada (JP), and Michio Ui (JP) discovered that cholera toxin and pertussis toxin possess ADP-ribosylate specific G proteins(1428, 1435-1438).

Robert G.L. Shorr (US), Robert Joseph Lefkowitz (US), and Marc G. Caron (US) purified the beta-adrenergic receptor(1439).

Thomas Pfeuffer (DE), Bernhard Gaugler (DE), and Heinz Metzger (DE) purified adenylyl cyclase(1440).

Bernard Kwok-Keung Fung (US), James B. Hurley (US), and Lubert Stryer (US) discovered that G proteins are necessary for flow of information in the light-triggered cyclic nucleotide cascade of vision in the retina(1441).

Robert D. Bremel (US), Annemarie Weber (DE-US), and John M. Murray (US) found that ATP hydrolysis in solutions containing actin filaments and heavy meromyosin subfragment (HMMS-1) units will proceed quite well even at low calcium ion levels, provided that the ATP level is also sufficiently low for rigor complexes to form. They found that the formation of rigor complexes could actually increase the affinity of troponin for calcium ions. They found that at high calcium ion levels when actin filaments should be in the on state the rate of ATP hydrolysis increased, provided the ATP level was low, to give what was called the potentiated state. This was found to be due to an increase in the rate of binding of subfragment-1 to actin. They found that potentiation by active complexes (i.e., force-producing) at high ATP levels was also observed provided the concentration of subfragment-1 in solution was abnormally high(1442-1447).

Werner Kundig (US) and Saul Roseman (US) isolated from Escherichia coli a phosphotransferase system which catalyzed the transfer of phosphate from phosphoenolpyruvate to sugars of the D-gluco and D-manno configurations, yielding pyruvate and the corresponding sugar 6-phosphate esters. This mechanism provides a way of concentrating sugars as their phosphates, against a gradient. Some of the components of this system are membrane associated while others are cytoplasmic(1448, 1449).

Thomas Ferenci (AU) and Hans Leo Kornberg (GB-US) were able to elucidate the main routes whereby E. coli utilizes fructose as a sole carbon source for growth(1450-1452).

Michael Abercrombie (GB), Joan E.M. Heaysman (GB), and Sue M. Pegram (GB) were the first to identify focal adhesions. They observed them in electron microscopic studies of cultured fibroblasts. Many cells grown in cell culture adhere tightly to the underlying substrate through discrete regions of the plasma membrane, referred to as adhesion plaques, focal contacts, or focal adhesions(1453).

Keith E. Summers (US) and Ian R. Gibbons (US) present evidence supporting the hypothesis that the propagated bending waves of live-sperm tails are the result of ATP-induced shearing forces between outer tubules which, when resisted by the native structure, lead to localized sliding and generate an active bending moment(1454).

Richard William Dutton (US), Reuben J.M. Falkoff (US), John A. Hirst (US), Michael Hoffmann (US), John W. Kappler (US), Jack R. Kettman (US), Jayne F. Lesley (US), and Douglas C. Vann (US) were the first to propose that helper functions of T cells may be mediated by soluble products released from T cells(1455). This was confirmed by Anneliese Schimpl (DE) and Eberhard Wecker (DE)(1456).

Otto Götze (DE) and Hans Joachim Müller-Eberhard (DE-US-DE) described the C3-activator system: an alternate pathway of complement activation(1457).

Michael Hoffmann (US) and Richard W. Dutton (US) found that depression of the in vitro immune response of mouse spleen cell suspensions to sheep erythrocytes by removal of macrophages can be reversed by the addition of supernatant fractions from peritoneal macrophage cultures. Supernatant fraction activity can be absorbed by the red cell antigen, and supernatant fraction-treated red cells are stimulatory in the absence of macrophages or supernatant fraction(1458).

Ivan J. Ryrie (US) and André Tridon Jagendorf (US) observed changes in the conformation of the CF1 unit of chloroplasts when the chloroplasts were illuminated or when the pH of the medium was changed from acidic to basic, creating a momentary pH gradient(1459).

Richard Kelly (US) reported the first successful in vitro cultivation of a spirochete. He grew Borrelia hermsi in a complex organic medium under microaerophilic conditions (1460).

Mark S. Bretscher (GB) pioneered work that established the overall organization and asymmetry of the erythrocyte polypeptides. He showed that most of the membrane proteins, including the most prevalent protein, spectrin, are associated with the cytoplasmic surface of the membrane. It was also recognized that spectrin is involved in maintenance of erythrocyte shape. Bretscher developed an important way of labeling cell membranes with nonpenetrating molecules such that the inside of the membrane could be distinguished from the outside(1461-1468).

Stanley E. Gordesky (US) and Guido V. Marinetti (US) demonstrated that nearly all phosphatidylserine and a minimum of seventy percent of phosphatidylethanolamine is on the inside surface of the human erythrocyte membrane, thus suggesting an asymmetric arrangement of membrane phospholipids(1469).

Knute A. Fisher (US) demonstrated that cholesterol in human erythrocytes is asymmetrically distributed across the plane of the cell membrane, being more prominent on the exterior side than on the interior side(1470).

Garth Lamb Nicolson (US), Serafeim P. Masouredis (US), Robert Hyman (US), Vincent T. Marchesi (US), and Seymour Jonathan Singer (US) demonstrated that the distribution of membrane proteins is asymmetric and were the first to suggest that there is likely to be an interrelation between protein array and membrane function in cells with a variable distribution of proteins(1471-1474).

 Harden Marsden McConnell (US), Roger D. Kornberg (US), Phillipe F. Devaux (FR), Mark G. McNamee (US), Kenneth L. Wright (US), and Betty Gaffney McFarland (US) used electron spin-resonance spectroscopy to show that lipid molecules move laterally and flip-flop within cell membranes(1475-1480).

Robert F.A. Zwaal (NL), Ben Roelofsen (NL), Paul Comfurius (NL), and Laurens L.M. van Deenen (NL) demonstrated an asymmetric phospholipid distribution in red cell membranes from humans(1481).

David Baltimore (US) defined all viral mRNAs as plus strand RNAs. In this same publication Baltimore presnted what is now called the Baltimore classification, a classification scheme that groups viruses into families, depending on their type of genome (DNA, RNA, single-stranded (ss), double-stranded (ds), etc.) and their method of replication(1482).

Peter I. Payne (GB) and Tristan A. Dyer (GB) isolated 5.8S ribosomal RNA (5.8SrRNA) from plant tissue(1483).

Pierre Tiollais (FR), Francis Galibert (FR), and Michel Boiron (FR) discovered 45S ribosomal RNA (45SrRNA), also called hnRNA(1484).

Asen A. Hadjiolov (BG), Georgui I. Milchev (BG) and others found that the 45SrRNA is cleaved into 18S, 28S, and 5.8S rRNAs(1485).

Max L. Birnstiel (BR-CH), Donald D. Brown (US), John Bertrand Gurdon (GB), and Kazunori Sugimoto (US) were the first to isolate and purify the genes coding for ribosomal RNAs (18S, 28S, and 5S)(1486-1488).

Kathleen J. Danna (US), Daniel Nathans (US), George H. Sack, Jr. (US), Stuart P. Adler (US), George Khoury (US), Malcolm A. Martin (US), Theresa N.H. Lee (US), and Hamilton O. Smith (US) used restriction endonucleases in the analysis and restructuring of DNA molecules. They used HindII to cut the purified DNA of Simian Virus 40 and separated the resulting restriction fragments by size using agarose gel electrophoresis. The order of the fragments was deduced (and corresponding restriction sites) in the 5000-nucleotide circular chromosome, creating a restriction map. In the 1972 paper they established that replication of SV40 DNA is bidirectional and proceeds symmetrically(1489-1494). These papers ushered in a new era in genetics.

Yasuji Oshima (JP) and Isamu Takano (JP), from genetic mapping data, predicted the physical arrangement of the yeast mating-type genes on a chromosome in Saccharomyces cerevisiae(1495).

 James B. Hicks (US), Ira Herskowitz (US), Amar J.S. Klar (US), Seymour Fogel (US), and David N. Radin (US) found that the two mating types of the yeast Saccharomyces cerevisiae can be interconverted in both homothallic and heterothallic strains. A defective alpha mating type locus can be converted to a functional a locus and subsequently to a functional alpha locus(1496, 1497). This has been called the "Cassette Model."

Jeffrey N. Strathern (US), James B. Hicks (US), and Ira Herskowitz (US) discovered that mating type switching during the haploid phase of the yeast, Saccharomyces cerevisiae, is controlled by three adjacent gene loci on chromosome 3. These loci determine whether the cell is one of two mating types, a or alpha. A gene designated MAT is flanked on one side by a silent copy of a, and on the other side by a silent copy of alpha. If the a gene is duplicated then inserted at the MAT locus the resulting cell is mating type a. If the alpha gene is duplicated then inserted at the MAT locus the resulting cell is mating type alpha(1498).

Jeffrey N. Strathern (US), Amar J.S. Klar (), James B. Hicks (US), Judith A. Abraham (US), John M. Ivy (US), Kim A. Nasmyth (GB), and Carolyn McGill (US) worked out many of the details of homothallic switching of yeast mating types in Saccharomyces cerevisiae(1499).

Alan Bender (US) and George F. Sprague, Jr. (US) determined that the alpha 1 product of the yeast alpha mating-type locus binds to homologous sequences within the control regions of the three known alpha-specific genes and there acts a transcription activator(1500).

Cynthia A. Keleher (US), Michael J. Redd (US), Janet Schultz (US), Marlan Carlson (US), and Alexander D. Johnson (US) found that Ssn6-Tup 1 proteins are a general repressor of transcription which influences many genes thereby resulting in a pleiotropic effect. Part of this effect involves alpha 2-mediated repression resulting in the a-specific STE phenotype(1501).

Jack A. Lucy (GB), Quet Fah Ahkong (CA), F.C. Cramp (GB), Derek Fisher (GB), and J.I. Howell (GB) pioneered in methods to induce cell fusion and the formation of hybrid cells(1502-1504).

Henry Harris (GB) observed that normal mouse cells are dominant to malignant cells when the two types are fused in the laboratory. This work cast doubt on the theory that (dominant) oncogenes are the general rule(1505).

David Comings (US) articulated a general framework for a role of tumor suppressor genes in all types of cancer: inherited tumors, he argued, are the result of a germline mutation in regulatory genes that suppresses tumorigenesis, followed by the somatic loss of the homologous allele. In non-heritable cancers, both alleles are affected in somatic cells(1506).

Uta Francke (US) showed that cells of retinoblastomas typically contained abnormalities involving chromosome 13(1507). Later Jorge J. Yunis (US), and Nora Ramsay (US) refined the location as a deletion in the long arm of chromosome 13(1508).

Christine Coulondre (FR), Jeffrey H. Miller (US), Philip J. Farabaugh (US), and Walter Gilbert (US) identified 5-methylcytosine as a mutational hotspot in Escherichia coli(1509).

Arthur D. Riggs (US) and Peter A. Jones (US) reported that in mammalian DNA most if not all 5-methylcytosine bases are found in the dinucleotide sequence CpG(1510).

Webster K. Cavanee (US), Thaddeus P. Dryja (US), Robert A. Phillips (CA), William F. Benedict (US), Roseline Godbout (US), Brenda L. Gallie (CA), A. Linn Murphree (US), Louis C. Strong (US), and Raymond L. White (US) localized the retinoblastoma gene (RB; also known as RB1) to a small region on chromosome 13 in man; they found that tumorigenesis may result from the development of homozygosity for the mutant allele at the Rb-1 locus(1511).

Alan Y. Sakaguchi (US), Peter A. Lalley (US), and Susan L. Naylor (US) found that a rearrangement of human c-myc (cellular myelocytomatosis) gene was observed in Burkitt's lymphoma cells possessing the t(8;14) translocation suggesting that human c-myc is located close to the breakpoint on chromosome 8 (q24) involved in the t(8;14) translocation. The mouse c-myc gene segregated concordantly with chromosome 15 in mouse-Chinese hamster cell hybrids. These gene assignments are noteworthy, as structural and numerical abnormalities of human chromosome 8 and mouse chromosome 15 are frequently associated with B-cell neoplasms(1512).

Andrew P. Feinberg (US) and Bert Vogelstein (US) compared gene methylation in DNA from primary human tumor tissues with DNA from adjacent normal cells. They found lowered DNA methylation in the tumor tissue DNA(1513).

Stephen H. Friend (US), Rene Bernards (US), Snezna Rogelj (US), Robert Allan Weinberg (US), Joyce M. Rapaport (US), Daniel M. Albert (US), and Thaddeus P. Dryja (US) isolated a human cDNA that mapped to the RB region and, importantly, was deleted at least partly in tumors. They were thus the first to discover a human tumor suppressor gene—retinoblastoma(1514).

Wen-Hwa Lee (US), Robert Bookstein (US), Frank Hong (US), Lih-Jiuan Young (US), Jin-Yuh Shew (TW-US), and Eva Y. Lee (US) found a fundamentally different type of oncogene associated with a rare childhood tumor, retinoblastoma. In this cancer, malignancy results from the absence of a functional copy of the retinoblastoma (Rb) gene, which is therefore said to be recessive-acting. Rb is an anti-oncogene, because its presence (even in a single copy) inhibits formation of this particular cancer(1515).

Wen-Hwa Lee (US), Robert Bookstein (US), Frank Hong (US), Lih-Jiuan Young (US), Jin-Yuh Shew (TW), Eva Y. H. P. Lee (US), Yuen-Kai T. Fung (US), A. Linn Murphree (US), Anne T'Ang (US), Jin Qian (US), Steven H. Hinrichs (US), and William F. Benedict (US) cloned RB by chromosome walking their way to a cDNA fragment that hybridized to transcripts in normal tissue, but was aberrantly expressed or deleted in retinoblastomas. This pointed to the inactivation of RB as being causative for cancer(1516, 1517).

Huei-Jen Su Huang (US), Jing-Kuan Yee (US), Jin-Yuh Shew (US), Phang-Lang Chen (US), Robert Bookstein (US), Theodore Friedmann (US), Eva Y.H.P. Lee (US), and Wen-Hwa Lee (US) confirmed this by rescuing the neoplastic phenotype of RB-mutant retinoblastoma cells with wild-type RB(1518).

James A. DeCaprio (US), John W. Ludlow (US), James Figge (US), Jin-Yuh Shew (TW), Chun-Ming Huang (US), Wen-Hwa Lee (US), Erika Marsilio (US), Eva Paucha (US), David M. Livingston (US), Peter Whyte (US), Karen J. Buchkovich (US), Jonathan M. Horowitz (US), Stephen H. Friend (US), Margaret Raybuck (US), Robert Allan Weinberg (US), Edward Harlow (US), Nicholas John Dyson (US), Peter M. Howley (US), and Karl Munger (US) found that the viral oncoproteins: E1A of adenovirus, large tumor (T) antigen of SV40, and E7 of papillomavirus bind to retinoblastoma protein (a tumor suppressor). This provided the first evidence of a physical link between oncoproteins and tumor suppressors(1519-1521).

Valerie Greger (DE), Eberhard Passarge (DE), Wolfgang Höpping (DE), Elmar Messmer (DE), and Bernhard Horsthemke (DE) showed that an unmethylated CpG island at the 5' end of the retinoblastoma gene becomes hypermethylated in tumors from retinoblastoma patients, leading the authors to speculate that methylation could contribute directly to the silencing of tumor suppressors(1522).

James A. DeCaprio (US), John W. Ludlow (US), Dennis Lynch (US), Yusuke Furukawa (US), James Griffin (US), Helen Piwnica-Worms (US), Chun-Ming Huang (US), David M. Livingston (US), Karen Buchkovich (US), Linda A. Duffy (US), and Ed Harlow (US) found that the product of the retinoblastoma susceptibility gene, retinoblastoma protein (RB), has properties of a cell cycle regulatory element(1523, 1524).

They reported, separately, that SV40 T antigen, which can drive G1-arrested cells into the cell cycle, only binds unphosphorylated RB — the first indication that this is the growth-suppressive form of RB. Therefore, they surmised that unphosphorylated RB acts to block exit from G1.

Note: Disruption of the pRb pathway liberates E2Fs and thus allows cell proliferation, rendering cells insensitive to antigrowth factors that normally operate along this pathway to block advance through the G1 phase of the cell cycle. The effects of the soluble signaling molecule TGFß (transforming growth factor beta) are the best documented. TGFß prevents the phosphorylation that inactivates pRb; in this fashion, TGFß blocks advance through G1.   

Jennifer A. Pietenpol (US), Roland W. Stein (US) (US), Elizabeth Moran (US), Peter Yaciuk (US), Richard Schlegel (US), Russette M. Lyons (US), Mark R. Pittelkow (US), Karl Münger (US), Peter M. Howley (US), and Harold L. Moses (US) reported that in some cell types, transforming growth factor beta (TGFß) suppresses expression of the c-myc (cellular myelocytomatosis)  gene, which  regulates the G1 cell cycle machinery(1525). Note: Malfunctions in the c-Myc gene have also been found in carcinoma of the cervix, colon, breast, lung and stomach.

Peter A. Jones (US), William M. Rideout, III (US), Jiang-Cheng Shen (US), Charles H. Spruck, III (US), and Yvonne C. Tsai (US) found 5-methylcytosine to be a source of genetic mutation in tumors(1526). These findings implied that altered DNA methylation could underlie oncogene activation.

Thomas M. Fynan (US) and Michael Reiss (US) discovered that the pRb signaling circuit, as governed by TGFß and other extrinsic factors, can be disrupted in a variety of ways in different types of human tumors(1527).

Gregory J. Hannon (US), David Beach (US), Michael B. Datto (US), Patrick Pei-Chih Hu (US), Timothy F. Kowalik (US), Jonathan Yingling (US), and Xiao-Fan Wang (US) reported that TGFß causes synthesis of p15INK4B and p21 proteins, which block the cyclin:CDK complexes responsible for pRb phosphorylation(1528, 1529).

Peter W. Laird (US), Laurie Jackson-Grusby (US), Amin Fazeli (US), Stephanie L. Dickinson (US), W. Edward Jung (US), En Li (US), Robert Allan Weinberg (US), and Rudolf Jaenisch (US) provided evidence linking DNA hypermethylation with cancer formation. Mice with the 'Min' mutation in the adenomatous polyposis coli (Apc) gene develop intestinal polyps early in life. They reduced DNA methylation in Min mice which led to a decreased number of polyps in the animals, lending support to the idea that tumor-suppressor genes are hypermethylated and silenced in cancer, and can be reactivated by inhibiting DNA methylation(1530).

Masanori Hatakeyama (JP) and Robert Allan Weinberg (US) relate that the retinoblastoma protein (pRb) is an inhibitor of cell cycle progression from the G1 to the S phase of the cell cycle. It acts through its ability to interact with cellular target molecules such as the E2F transcription factors. Recent evidence indicates that pRB inactivation is a key molecular event leading to the S-phase commitment at the G1 restriction point in the cell cycle. Deregulated inactivation of pRB in G1 phase may be a universal mechanism underlying cellular transformation(1531).

Carl R. Merril (US), Mark R. Geier (US), and John C. Petricciani (US) were the first to stably incorporate genes from bacterial viruses into mammalian cells and have them expressed(1532).

Peter C. Hinkle (US) and Lawrence L. Horstman (US) took isolated mitochondrial inner membranes and created some vesicles with the F0F1 ATPase facing inward and some with F0F1 ATPase facing outward. Protons were pumped in only one direction, depending on the direction in which the F0F1 ATPase faced(1533).

William B. Amos (GB) discovered two types of Ca++ binding contractile fibers in the stalks of Vorticella, these proteins are collectively called spasmin(1534).

J. Fevre () found these nanofilaments in the contractile organelles of the myonemes in acantharia(1535). Since then, these nanofilaments have been found to be the major constituents of the paraflagellar rod (PFR) in euglena, trypanosomes and dinoflagellates. They are also found in the rootlets of flagella and cilia in all eucaryotes studied so far and in mammalian cells. In the latter, they are associated with the centrosomes, which may suggest a crucial role in mitosis. 

Theodore Thomas Puck (US), Paul Wuthier (US), Carol Jones (US) and Fa-ten Kao (US) introduced the technique of selectively killing cells by using antisera directed against specific cellular surface markers. This simultaneously selected against the chromosome which likely coded for the marker(1536).

Tom J. Carew (US), Eric R. Kandel (US), Vincent F. Castellucci (CA), Harold M. Pinsker (US), and Wayne A. Hening (US), using the sea slug Aplysia as their subject, determined that learning seemed to change the nature of synapses between sensory and motor neurons. When the slug is sensitized to a stimulus the synapse is strengthened. When the slug habituates to a false alarm the synapse weakens(1537, 1538).

Eric R. Kandel (US), Marcello Brunelli (IT), Jack Byrne (US), and Vincent F. Castellucci (CA) found that cyclic AMP plays an important role in strengthening or weakening the synapse(1539).

Samuel M. Schacher (US), Vincent F. Castellucci (CA), and Eric R. Kandel (US) determined that the actions of cyclic AMP included the activation of cyclic-AMP response elements (CREBs)(1540). Animals which lack this activated form of CREB can still remember things, but cannot remember them for more than an hour or so.

Frank Hugh Ruddle (US), Verne M. Chapman (US), Florence C. Ricciuti (US), Mary J. Murnane (US), Robert J. Klebe (US), and P. Meera Kahn (NL) established the genetic linkage relationships of seventeen enzymes of humans(1541).

Bernard D. Stollar (US), Theodor Otto Diener (US), Roger H. Lawson (US), Heinz L. Sanger (DE), Gunther Klotz (Heinz L. Sanger), Detlev Riesner (DE), Hans J. Gross (DE), and Albrecht K. Kleinschmidt (DE) were among the first to describe infectious agents they called viroids. These were described as consisting only of infectious nucleic acid(1542-1544).

Ronald Duff (US) and Fred Rapp (US) showed that herpes simplex virus types 1 and 2 are capable of inducing host cell transformation in vitro(1545, 1546).

Janice Harumi Yen (US) and A. Ralph Barr (), Jeffrey L. Dean (US), and Stephen L. Dobson (US) found substantial numbers of Rickettsia-like microbes (Wolbachia type) in adults, eggs and embryos of the mosquitoes. Mating compatibility of mosquito strains seems to be correlated with the strain of the microbe present. Mosquitoes that carry different strains of the microbe exhibit cytoplasmic incompatibility; those that carry the same strain of microbe are interfertile(1547, 1548).

Roger Yate Stanier (CA) commenting on the blue-green algae said, “these organisms are not algae; their taxonomic association with eukaryotic groups is an anachronism.…Blue-green algae can now be recognized as a major group of bacteria”(1549).

George Henry Hepting (US) wrote, Diseases of Forest and Shade Trees in the United States, the most comprehensive text on these topics(1550).

Robert Lee Metcalf (US), Gurcharan K. Sangha (US), and Inder P. Kapoor (US) developed a model ecosystem for the evaluation of pesticide biodegradability and ecological magnification(1551).

Valerie Jane van Lawick-Goodall (GB), Frans B. M. de Waal (NL-US), and Geza Teleki (US) studied the social behavior of free-living chimpanzees. They showed that many human practices and potentials, from politics and child-rearing to violence and even morality, have parallels in the lives of our closest animal relatives. Between 1960 and 1997 Valerie Jane Goodall observed chimpanzees doing the following: eating as omnivores; toolmaking; planning; using man-made objects; suffering from polio and AIDS; expressing awe-(chimps spontaneously danced at the sight of a waterfall); participating in warfare between groups; cannibalism; establishing coalitions; transferring a female to a different group; adolescent female, adopted baby, after its mother died of pneumonia; males leading females away from the community and establishing short-term monogamous relationships. This is believed to be so the males can ensure that the offspring are theirs; transferring technology (chimps from one community modeled the toolmaking behavior of chimps in another community); giving birth to twins; chewing the plant Aspilia, a medicinal plant believed to relieve stomach pains or reduce internal parasites(1552-1555).

F. Giannelli (GB) showed that the defect in DNA repair exhibited by Xeroderma pigmentosum cells could be corrected when they were fused with normal fibroblasts(1556).

Eleanor E. Storrs (US), Waldemar F. Kirchheimer (US) and Chapman H. Binford (US) attempted to establish the nine-banded armadillo (Dasypus novemcinctus Linn.) as a model for the study of leprosy. They reported that 18-24 hours following inoculation the animals developed a systemic infection similar to lepromatous leprosy in humans(1557-1559).

Carolyn M. Giles (GB), John D. Crossland (GB), W.K. Haggas (GB), George H. Longster (GB) discovered the Rh 33 blood group antigen(1560).

Saul Krugman (US), Joan P. Giles (US), and Jack Hammond (US) produced the first vaccine to hepatitis B virus by extracting proteins from the virus, diluting them in water, and inactivating them by heat(1561).

Herbert L. Bonkowsky (US), Donald P. Tschudy (US), Annie Collins (US), Joyce M. Doherty (US), Irene C. Bossenmaier (US), Ruth Cardinal (US), Cecil James Watson (US), G. Jeelani Dhar (US), Zbyslaw J. Petryka (US), and Claus A. Pierach (US) discovered that acute porphyric attacks can be successfully treated by the infusion of hematin. They recognized that these attacks are associated with severe heme depletion in the liver(1562-1564).

Thomas Earl Starzl (US), Geoffrey R. Giles (US), John R. Lilly (US), Hiroshi Takagi (US), Gerard L. Martineau (US), Gerhard P.J. Schroter (US), Charles G. Halgrimson (US), Israel Penn (US), and Charles W. Putnam (US) corrected the metabolic abnormality of Wilson’s disease, first of more than two dozen liver-based inborn errors cured or ameliorated with liver replacement. These liver recipients and patients cured of mesoderm-based inborn errors by bone marrow transplantation were the first examples of effective genetic engineering(1565). 

Fritz Derom (BE), Fabrice Barbier (BE), Severin Ringoir (BE), Jacques Versieck (BE), Georges Rolly (BE), Guyla Berszenyi (BE), P. Vermeire (BE), and L. Vrints (BE) performed the first successful lung homotransplantation in man(1566).

Paul Ichiro Terasaki (US), Miguel Kreisler (ES), and Max Ray Mickey (US) developed the panel reactive antibody (PRA) test to identify presensitized patients at high immunologic risk for an allograft(1567).

Neil S. Painter (GB) and Denis Parsons Burkitt (GB) used geographical, historical, and physiological evidence to argue that diverticulosis coli is a preventable disease caused by the consumption of refined carbohydrates(1568).

Alfred G. Knudson, Jr. (US) proposed the "two-hit" theory of cancer causation, which explained the relationship between the hereditary and non-hereditary forms of a cancer and predicted the existence of anti-oncogenes (tumor suppressor genes) that can suppress cancer cell growth(1569-1572). This now-confirmed theory has advanced understanding of errors in the genetic program that turns normal cells into cancer cells. The “two hit” theory later merged with the concept of allelic loss of tumor-suppressor genes.

Raymond V. Damadian (US), in 1970, discovered that there is a marked difference in relaxation times between normal and abnormal tissues of the same type, as well as between different types of normal tissues. This discovery led Damadian, Lawrence Minkoff (US), Michael Goldsmith (US), and Jason A. Koutcher (US) to adapt nuclear magnetic resonance to the imaging of tissues. Magnetic resonance imaging (MRI), as it came to be called, utilizes the relaxation differences between diseased tissues, such as cancer, and normal tissues. These relaxation differences can not be exploited by any other type of imaging. The exceptional contrast of MRI (10 to 30 times that of x-ray) is responsible for the extraordinary detail of the MRI image. This technique, also called field-focusing nuclear magnetic resonance (FONAR), has produced a revolution in diagnostic medicine(1573, 1574).

Paul Christian Lauterbur (US), in 1972, conceived the theoritical basis for introducing gradients into the magnetic field thereby converting nuclear magnetic resonance information into 2D images. Along with David M. Kramer (US), Jeffrey S. Schneider (US), A. Markus Rudin (CH), and Ching-Ming Lai (US) he perfected the principle of zeugmatography—which adds to conventional NMR a three-dimensional gradient field, and is used as a system of landmarks to localize each signal. NMR or magnetic resonance imaging (MRI) today can show the differences between soft tissues, distinguish between fluid in motion and at rest, measure the extent of damage from heart disease and stroke, and visualize normal and diseased tissues in nearly every part of the body(1575-1578).

Sir Peter Mansfield (GB) and Peter K. Grannell (GB) developed the use of gradients in the magnetic field and showed how the signals could be mathematically analyzed, which made it possible to develop a useful 3D imaging technique.

Mansfield found that it is possible to selectively image a particular two-dimensional slice of an object held in a graded magnetic field by delivering the blast of radio waves at a particular frequency. He developed techniques to manipulate the applied magnetic fields and algorithms to interpret the resulting cacophony of radio signals that enabled images to be pieced together in just a matter of seconds.

Mansfield's work has allowed researchers and clinicians to take snapshots of fast-moving events, such as the beating of the heart. It has also been vital in the development of brain scanning by functional MRI, in which mental activity can be tracked by monitoring changes in blood flow(1579, 1580).

Paul Christian Lauterbur (US) and Sir Peter Mansfield (GB) would be awarded the 2003 Nobel Prize in Physiology or Medicine for their pioneering work in the development of magnetic resonance imaging (MRI).

Thomas W. Schoener (US) summarized the extant theory and created new theory for the field of feeding strategies. The theory is in four parts to explain why organisms select certain types of food from those encountered, where organisms feed, when organisms feed, and why organisms feed solitarily rather than in groups(1581).

Robert L. Trivers (US), in regard to human reciprocal altruism, shows that the details of the psychological system that regulates this altruism can be explained by a model. Specifically friendship, dislike, moralistic aggression, gratitude, sympathy, trust, suspicion, trustworthiness, aspects of guilt, and some forms of dishonesty and hypocrisy can be explained as important adaptations to regulate the altruistic system. Each individual human is seen as possessing altruistic and cheating tendencies, the expression of which is sensitive to developmental variables that were selected to set the tendencies at a balance appropriate to the local social and ecological environment(1582).  

Henry de Lumley (FR) discovered the earliest human remains of Homo erectus (upright man) from Europe, dated at c. 450,000 B.C.E. They were unearthed from the Caune de l'Arago cave (Tautavel, Pyrenees-Orientales, France) in 1971(1583, 1584).

Jean-Jacques Jaeger (FR) and M. Abdeslem Dakka (MA), in 1971, discovered fossil remains of Homo erectus near Rabat, Morocco(1585, 1586). It was dated to 400K B.P.

Michael H. Day (GB) reported the fossil remains of a Homo erectus found on the west side of Lake Turkana, Northern Kenya. It was dated to 1.6 M.Y.B.P.(1587).

The United States Congress passed and the President signed into law The National Cancer Act of 1971. This was the first mobilization of government and public support of basic biological research in the United States during the gene splicing age(1588).

ca. 1972

The azoles were introduced as systemic plant fungicides. They included triadimefon, propiconazole, prochloraz, epoxiconazole, fluquinconazole, and triticonazole. ref These fungicides act by inhibiting the synthesis of ergosterol, the major sterol component of fungal cell membranes.


Christian Boehmer Anfinsen (US) for his work on ribonuclease, especially concerning the connection between the amino acid sequence and the biologically active confirmation and Stanford Moore (US) and William Howard Stein (US) for their contribution to the understanding of the connection between chemical structure and catalytic activity of the active center of the ribonuclease molecule shared the Nobel Prize in Chemistry.

Gerald Maurice Edelman (US) and Rodney Robert Porter (GB) were awarded the Nobel Prize in Physiology or Medicine for their discoveries concerning the chemical structure of antibodies.

Preston Ercelle Cloud, Jr. (US) proposed a working model of the primitive Earth in which he related atmospheric-geologic-biologic history of the Precambrian(1589).

G. Adam () used thermoluminescence (TL) as a method for dating objects. This technique later proved useful for dating archaeological and paleoanthropological sites. The method is typically applied to dating samples of burned flint which is between 5,000 and 1,000,000 years old(1590).

Eli Lilly & Co., in 1972, synthesized fluoxetine hydrochloride and now sells this prescription product under the trade name Prozac. 

Ray W. Fuller (US), Harold D. Snoddy (US), A.M. Snoddy (US), Susan K. Hemrick (US), David T. Wong (US), and Byran B. Molloy (US) discovered that p-iodoamphetamine (fluoxetine hydrochloride) blocks the reuptake of serotonin but not of other neurotransmitters (acts as a depletor) in rats(1591). This led directly to the introduction, in 1987, of the anti-depressant (Prozac), the first selective-serotonin reuptake inhibitor (SSRI).

Gertrude Belle Elion (US) developed azathioprine (Imuran), an agent to prevent the rejection of kidney transplants(1592-1594).

Charles Gilvarg (US) demonstrated the existence of specific transport systems for metabolites (named permeases by Monod)(1595, 1596). See, Buttin, 1956

Sir James Whyte Black (GB), William A.M. Duncan (GB), Graham J. Durant (GB), C. Robin Ganellin (GB), and Michael E. Parsons (GB), while trying to discover a useful H2 antagonist, performed work leading to the production of cimetidine (Tagamet)(1597). The secretion of gastric acid is influenced by the hormone histamine. Histamine causes the release of chemicals when it interacts with points along cell membranes known as H-receptors. Black theorized that there are two types of H-receptors. H1-receptors cause allergic reactions and cold symptoms. Antihistamines suppress these symptoms, but fail to suppress the release of gastric acid, which occurs when histamine binds with the second type of H-receptor, called the H2-receptor.

Frederic Middlebrook Richards (US), Harold W. Wyckoff (US), William D. Carlson (US), Norma M. Allewell (US), Byungkook Lee (US), and Yukio Mitsui (US) solved the three-dimensional structure of ribonuclease-S(1598).

Howard K. Schachman (US) and John C. Gerhart (US) proved that the active site and inhibitor site on aspartate transcarbamylase are separate entities(1599).

Haim Aviv (IL) and Philip Leder (US) purified biologically active globin messenger RNA by chromatography on oligothymidylic acid-cellulose(1600).

Democleia Panagou (US), Malcolm D. Orr (US), John R. Dunstone (US), and Raymond L. Blakley (US) were the first to give experimental evidence for a single-chain protein— ribonucleotide reductase of Lactobacillus leichmannii —that has both a catalytic site and a regulatory site, i.e., allosteric(1601).

Earl Wilbur Sutherland, Jr. (US) and his colleagues demonstrated that when the enzyme phosphorylase is itself phosphorylated by ATP its sensitivity to regulatory compounds is altered. They further demonstrated that this covalent change is controlled by the hormone adrenaline (epinephrine) through its messenger, cyclic AMP(1602).

Joan E. Mertz (US) and Ronald W. Davis (US) discovered that one of the restriction enzymes of Escherichia coli cuts DNA asymmetrically to produce fragments with single-stranded termini in which the nucleotide sequences are complementary. Such termini, being cohesive, permits the annealing of any fragments of DNA that are cut by this enzyme. This observation can be regarded as the starting point of recombinant DNA technology(1603).

David Jackson (US), Robert H. Symons (US), and Paul Berg (US) ligated genes from the lambda bacteriophage and galactose operon of Escherichia coli into the circular DNA of Simian Virus 40. This complex was taken up by Escherichia coli and replicated(1604). This was the first man-made recombinant DNA.

Joe Hedgpeth (US), Howard Michael Goodman (US), and Herbert Wayne Boyer (US) determined the DNA nucleotide sequence restricted by the EcoRI endonuclease(1605).

Douglas Brutlag (US) and Arthur J. Kornberg (US) were the first to propose that some DNA polymerases may run in the 3’ to 5’ direction on DNA and carry out a proofreading function(1606).

Vittorio Sgaramella (IT) and Har Gobind Khorana (IN-US) found that T4 ligase brings about the joining of duplexes at their base-paired ends by a bimolecular type of reaction and that an intramolecular mechanism can be ruled out(1607).

Randolph Wall (US), Lennart Philipson (SE), Jeffrey L. Weber (US), Z. Gage (US), and James Edwin Darnell, Jr. (US) showed that cells copy viral genes into very large nuclear RNA molecules, too large to be mRNA, suggesting that some of the copied RNA ends up on the cutting room floor(1608, 1609).

Milton Adesnik (US), Marianne Salditt (US), W. Thomas (US), and James Edwin Darnell, Jr. (US) obtained the first direct evidence for RNA processing in messenger RNA formation, i.e., the addition of poly A to the 3' end of large nuclear RNA transcripts(1610).

James Dewey Watson (US) realized that because of the requirement for an RNA primer, DNA polymerases are unable to replicate the extreme 3’ end of a parental DNA strand of the linear T4 phage molecule. He accordingly proposed the presence of the end-replication problem(1611).

Alexy M. Olovnikov (RU) recognized that the end-replication problem would result in telomere shortening with each round of replication, he proposed that chromosome shortening might be a mechanism to limit the number of divisions of human diploid fibroblasts in culture and thus might make telomere shortening the basis for the Hayflick limit(1612). See, Hayflick, 1961.

Elizabeth H. Blackburn (US) and Joseph G. Gall (US) established that telomeres of Tetrahymena contain simple tandemly repeated sequences(1613).

Janis Shampay (US), Carol W. Greider (US), Elizabeth H. Blackburn (AU-US), Eric R. Henderson (US), Marina S. Lee (US), Dorothy Shippen-Lentz (US), and Jack William Szostak (GB-US) showed that replacement of the primer of the leading chain on a DNA molecule during replication depends on a group of repeated sequences that cap the ends, or telomeres, of all eukaryotic chromosomes. They revealed that a specialized ribonucleoprotein enzyme, telomerase, maintains the telomere sequences and, thereby, the length of the leading chain(1614-1618).

Robert K. Moyzis (US), Judy M. Buckingham (US), L. Scott Cram (US), Maria Dani (US), Larry L. Deaven (US), Myrna D. Jones (US), Julianne Meyne (US), Robert L. Ratliff (US), and Jung-Rung Wu (US) identified TTAGGG as the human telomere sequence(1619). 

Victoria Lundblad (US) and Jack William Szostak (GB-US) described a general assay designed to detect mutants of yeast that are defective for any of several aspects of telomere function. Using this assay, we have isolated a mutant that displays a progressive decrease in telomere length as well as an increased frequency of chromosome loss. This mutation defines a new gene, designated EST1 (for ever shorter telomeres). Null alleles of EST1 are not immediately inviable; instead, they have a senescence phenotype, due to the gradual loss of sequences essential for telomere function, leading to a progressive decrease in chromosomal stability and subsequent cell death(1620).

Titia de Lange (US), Lily Shiue (US), Richard M. Myers (US), David R. Cox (US), Susan L. Naylor (US), Ann M. Killary (US), Harold E. Varmus (US), Carol W. Greider (US), Calvin B. Harley (US), and A. Bruce Futcher (GB-US) proposed that telomere shortening serves as a mitotic clock that counts cell divisions and ultimately results in cellular senescence(1621-1624).

Christopher M. Counter (CA), Ariel A. Avilion (CA), Chatering E. LeFeuvre (CA), Nancy G. Stewart (CA), Carol W. Greider (CA), Carol B. Harley (CA), Silvia Bacchetti (CA) and Jerry W. Shay (US) showed that telomere maintenance is evident in virtually all types of malignant cells(1625, 1626).

Junli Feng (US), Walter D. Funk (US), Sy-Shi Wang (US), Scott L. Weinrich (US), Ariel A. Avilion (GB), Choy-Pik Chiu (US), Robert R. Adams (US), Edwin Chang (US), Richard C. Allsopp (GB), Jinghua Yu (US), Siyuan Le (US), Michael D. West (US), Calvin B. Harley (US), William H. Andrews (US), Carol W. Greider (US), and Bryant Villeponteau (US) determined that telomerases have a region composed of RNA. They also noted that human telomerase is a critical enzyme for the long-term proliferation of immortal tumor cells(1627).

Woodring E. Wright (US), Mieczyslaw A. Piatyszek (US), William E. Rainey (US), William Byrd (US), and Jerry W. Shay (US) found that telomerase activity is repressed in most human tissues during development(1628).

Joachim Lingner (CH), Timothy R. Hughes (US-CA), Andrej Shevchenko (RU), Matthias Mann (DK), Victoria Lundblad (US), and Thomas Robert Cech (US) found that the reverse transcriptase protein fold, previously known to be involved in retroviral replication and retrotransposition, is essential for normal chromosome telomere replication in diverse eukaryotes (Eucarya)(1629). Could telomerase be the ancestor of retroviruses and transposons?

Andrea G. Bodnar (US), Michel Ouellette (US), Maria Frolkis (US), Shawn E. Holt (US), Choy-Pik Chiu (US), Gregg B. Morin (US), Calvin B. Harley (US), Jerry W. Shay (US), Serge Lichtsteiner (US), and Woodring E. Wright (US) showed that overexpression of telomerase in primary fibroblasts causes telomeres to elongate and the cells with the elongated telomeres do not enter senescence(1630).

Tracy M. Bryan (AU) and Thomas R. Cech (US) reported that telomere maintenance is evident in virtually all types of malignant cell; 85%-90% of them succeed in doing so by upregulating expression of the telomerase enzyme, which adds hexanucleotide repeats onto the ends of telomeric DNA(1631).

Tom Vulliamy (GB), Anna Marrone (GB), Frederick Goldman (US), Andrew Dearlove (GB), Monica Bessler (US), Philip J. Mason (GB), and Inderjeet Dokal (GB) found that autosomal dominant dyskeratosis congenita results from a mutation in the RNA region of telomerase(1632).

Alfred L. Goldberg (US) showed that cells lacking lysosomes, such as bacteria and immature erythrocytes, can nonetheless destroy abnormal proteins(1633). This led the way to the eventual discovery of cellular structures called proteasomes.

Richard Cawthon Starr (US) was the first to discover a sexual pheromone in green plants (Volvox carteri f. nagariensis )(1634).

Richard Cawthon Starr (US) and Lothar Jaenicke (DE) purified and fully characterized the sexual pheromone produced by Volvox carteri f. nagariensis Iyengar(1635). Starr was honored by having Starria zimbabweensis, Chlorococcum starrii, and Cystomonas starrii named for him.

Richard Cawthon Starr (US), Franz Joseph Marner (DE), and Lothar Jaenicke (DE) reported that the male gametes of Chlamydomonas are attracted by a pheromone produced by female gametes(1636).

Lothar Jaenicke (DE) and Richard Cawthon Starr (US) described the lurlenes, a new class of plastoquinone-related mating pheromones from Chlamydomonas allensworthii (Chlorophyceae). Female cells temporarily or constantly excrete a luring signal into the medium to attract the male cells for mating(1637).

Antony Basten (AU), Jacques Francis Albert Pierre Miller (AU), Jonathan Sprent (AU), and J. Pye (AU) proved the existence of Fc receptors on the surface of B cells but not on T cells(1638).

Stuart F. Schlossman (DE-US) reported that T cell epitopes on protein antigens or polypeptides involve at least seven amino acids(1639).

J.A. Smith (), E.O. Ogunba (NG), T.I. Francis (), Alfred M. Prince (US), D. Metselaar (), George W. Kafuko (UG), Louis G. Mukwaya (UG), Chung-M. Ling (US), Lacy R. Overby (US), Francisco J. Muniz (AR), Don W. Micks (US), Baruch Samuel Blumberg (US), William Wills (US), Irving Millman (US), W. Thomas London (US), Gerard Saimot (Sengalese), Christian Brochard (US) and Rita Dechene (US) detected hepatitis B surface antigen (HbsAg) in mosquitoes collected in the field areas where HbsAg is common in the human population(1640-1644).

Alfred M. Prince (US), George F. Grady (US), Charles Hazzi (US), Betsy Brotman (US), William J. Kuhns (US), Richard W. Levine (US), and Stephen J. Millian (US) reported that most postransfusion hepatitis was due to a virus other than HBV or Hepatitis A (HAV)(1645).

Marianna M. Newkirk (US), Aylward E.R. Downe (CA-US), Jerome B. Simon (US), William Wills (US), Bernard Larouzé (FR), W. Thomas London (US), Baruch Samuel Blumberg (US), Irving Millman (US), M. Pourtaghra () and J. Coz () found that both the North American bedbug (Cimex lectularius) and the tropical bedbug (Cimex hemipterus) can be carriers of hepatitis B virus(1646, 1647).

Hermann Wagner (AU) and Marc Feldmann (AU) introduced a new in vitro system for the generation of cell-mediated cytotoxic activity(1648).

Margaret Oakley Dayhoff (US) observed that most amino-acid sequences can be classified into relatively few families(1649).

Walter Gilbert (US) later confirmed her observation(818).

Bo F. Oberg (US), Aaron Jeffrey Shatkin (US), George Jen (US), Claire H. Birge (US), Robert E. Thach (US), John L. Fakunding (US), William A. Held (US), Masayasu Nomura (JP-US), John W.B. Hershey (US), Michael J. Clemens (US), Brian Safer (US), Irving Myer London (US), William C. Merrick (US), William F. Anderson (US) Norton A. Elson (US), and Sherrill L. Adams (US) worked out the steps which occur during the initiation of protein synthesis in eukaryotes (Eucarya)(1650-1657).

Joseph A. Gally (US) and Gerald Maurice Edelman (US) hypothesized that immunoglobulin genes have arisen in evolution from those specifying the histocompatibility system(1658).

Diana F. Amsbaugh (US), Carl T. Hansen (US), Benjamin Prescott (US), Philip W. Stashak (US), David R. Barthold (US), and Philip J. Baker (US) described an X-linked recessive mutant in mice (xcid) which prevented them from developing a normal humoral response to certain antigens(1659).

Chung-Mei Ling (US) and Lacy R. Overby (US) were the first to apply radioimmunoassay technology to the detection of a viral antigen in serum. It was the hepatitis B surface antigen(1660). 

Bernice Kindred (AU), Donald Cecil Shreffler (US), David H. Katz (US), Toshiyuki Hamaoka (JP), Baruj Benacerraf (VE-US), Alan S. Rosenthal (US), Ethan Menahem Shevach (US), Rolf Martin Zinkernagel (CH-US), and Peter Charles Doherty (AU-US) discovered that T cells recognize only antigens that are present on the surfaces of other cells in the context of polymorphic cell-surface molecules encoded by the major histocompatibility complex (MHC), e.g. virus-specific CD8+ cytotoxic T lymphocytes (CTLs) recognize viral antigens presented by other cells only in the context of MHC molecules(1661-1666).

Howard B. Dickler (US) and Henry G. Kunkel (US) described a method for the detection of Fc-gamma receptors on the surface of human mononuclear cells(1667).

Mikael Jondal (SE), Göran Holm (SE), and Hans Wigzell (SE) concluded that sheep erythrocyte rosetting might be the first human T-lymphocyte marker and that it possibly could be used for T lymphocyte enumeration, classification of lymphoid malignancies, and fractionation of cells for experimental use(1668).  

Torkel Weis-Fogh (GB) and William B. Amos (GB) while studying vorticellids discovered that their stalk employed a new mechanism of cell motility which occurs without microtubules or microfilaments. It is based on calcium ion sensitive contractile proteins(1669).

Rochelle E. Esposito (US), Norman Frink (US), Paul Bernstein (US), and Michael S. Esposito (US) defined the first eleven sporulation-defective  (spo) genes affecting various stages of meiosis in budding yeast(1670). 

Manfred Martin Mayer (DE-US) proposed that the C5-C9 complement membrane attack complex (MAC) exists as a transmembrane doughnut shaped unit which allows free flow across the membrane and typically leads to explosive rupture of the cell. This bold suggestion turned out to be essentially correct(1671).

Eckhard R. Podack (US), Jürg Tschopp (CH), and Hans J. Müller-Eberhard (US) and others would later show that the MAC consists of polymerized C9(1672, 1673).

Elio Raviola (US) and Morris John Karnovsky (ZA-US) provided evidence for a blood-thymus barrier using electron-opaque tracers(1674).

J. Victor Small (AT), John M. Squire (GB), Catherine F. Shoenberg (GB), and John C. Haselgrove (GB) proved the existence of myosin filaments in smooth muscle cells(1675, 1676).

Mark S. Bretscher (GB) determined that phospholipids of the plasma membrane assume an asymmetrical distribution(1465).

William T. Friedewald (US), Robert I. Levy (US), and Donald S. Frederickson (US) pioneered a very popular method for estimation of the concentration of LDL-cholesterol (LDL-C) in both clinical and research laboratories(1677).

Rajko Igi (CS-US), Ervin G. Erdös (HU-US), H.S.J. Yeh (), K. Sorrells (), and T. Nakajima () discovered that angiotensin I converting enzyme (ACE) and kininase II are identical and that this enzyme exerts a dual effect on blood pressure by controlling two oppositely acting peptides. It activates the vasoconstrictor angiotensin, which raises blood pressure, while also inactivating bradykinin, which is a vasodilator(1678).

Igal Gery (US), Richard K. Gershon (US), and Byron Halsted Waksman (US) isolated a factor produced by monocytes which behaved as a mitogen for T-lymphocytes. This represents the discovery of the substance which would later be known as interleukin-1 (IL-1). The operational definition of IL-1 became a soluble substance of monocytic origin which augments murine thymocyte mitogenesis(1679, 1680).

Eugene B. Rosenberg (US), Ronald Bo Herberman (US), Paul H. Levine (US), Roger H. Halterman (US), James L. McCoy (US), John R. Wunderlich (US), F.C. Donnelly (US), C. Alford (US), Rolf Kiessling (SE), George Klein (SE), Hans L.R. Wigzell (SE), Gyösö G. Petranyi (SE), Myrthel E. Nunn (US), Howard T. Holden (US), David H. Lavrin (US), and John C. Roder (SE) discovered and described natural killer cells (NK) which were later defined as effector cells with spontaneous cytotoxicity against various target cells; these effector cells lack the properties of classical macrophages, granulocytes, or cytotoxic T lymphocytes (CTL); and the observed cytotoxicity does not show restriction related to the major histocompatibility complex (MHC)(1681-1683, 1684 18541, 1685-1689).

Inessa Yu Chernyakhovskaya (RU), Elena G. Slavina (RU), George J. Svet-Moldavsky (RU), Sylvia B. Pollack (US), Gloria Heppner (US), R. James Brawn (US), Karen Nelson (US), Robert K. Oldham (US), David R. Siwarski (US), James L. McCoy (US), Ernest J. Plata (US), Ronald Bo Herberman (US), and John R. Ortaldo (US) produced results indicating that natural killer cells (NK) may play important roles in natural host resistance against cancer and infectious diseases(1690-1693).

Gunther Dennert (US) cloned lines of natural killer cells(1694).

Derek C. Ellwood (GB) and David W. Tempest (NL) documented the capacity of bacterial cells to alter their wall chemistry in response to growth rate and nutritional conditions(1695).

Seymour Jonathan Singer (US), and Garth Lamb Nicholson (US) were the first to propose the fluid mosaic model to explain membrane structure(1696).

George Manolov (SE) and Yanka Manolova (SE) discovered that in most cells of freshly isolated Burkitt’s lymphoma there is an extra band at the end of the long arm of chromosome 14(1697).

Lore Zech (SE), Ulla Haglund (SE), Kenneth Nilsson (SE), and George Klein (SE) later suggested that this band is a translocation from chromosome 8(1698). Growing evidence indicated that the chromosomal translocation (8;14) was a consistent feature in both sporatic and endemic Burkitt lymphomas. 

Charlotte Boone (US), Tchaw-Ren Chen (US), and Francis Hugh Ruddle (US) located the human gene for thymidine kinase on the long arm of chromosome number 17(1699).

Eberhard Neumann (IL-DE), Kurt Rosenheck (IL), Ullrich Zimmerman (DE), J. Schulz (DE), and Gunther Pilwat (DE) discovered that when cells are exposed to high electric fields their membrane permeability increases and they are induced to fuse with one another (cell fusion and electroporation)(1700, 1701).

Peter S. Carlson (US), Harold H. Smith (US) and Rosemarie D. Dearing (US) obtained the first interspecific somatic hybrid by fusion of protoplasts between various species of tobacco (Nicotiana)(1702).

Elizabeth Anna de Weerd-Kastelein (NL), Wilma Keijzer (NL), and Dick Bootsma (NL) used somatic cell hybridization to show that there is a multi-step pathway for the repair of ultraviolet light damage inflicted on DNA and that Xeroderma pigmentosum could result from a fault at any one of these steps. Normal cells in the hybridization are complementing, thus compensating for, the abnormal cells(1703).

Efraim Racker (PL-AT-US) purified the calcium-pump from natural membrane, added it to artificial membrane, supplied it with ATP, and found that it would accumulate calcium against a concentration gradient(1704).

Robert R. Friis (US) concluded that tissue invasion by the elementary bodies of Chlamydia involves a phagocytic process(1705).

Albert Z. Kapikian (US), Richard G. Wyatt (US), Raphael Dolin (US), Thomas S. Thornhill (US), Anthony R. Kalica (), and Robert M. Chanock (US) associated a 27-nm particle in the stools of patients with acute infectious nonbacterial gastroenteritis. They suggested that the particle was the etiological agent of Norwalk gastroenteritis(Norwalk, Ohio)(1706).

Allan Jacobs (GB), F.M. Miller (GB), Mark Worwood (GB), Michael R. Beamish (US), and Charles A.J. Wardrop (GB) introduced a method for measuring the quantity of ferritin in serum(1707). This is especially important for patients suspected of having iron imbalance.

Porter Warren Anderson, Jr. (US) and David Hamilton Smith (US), Richard B. Johnston, Jr. (US), Michael E. Pichichero (US), Richard A. Insel (US), Robert Frank Betts (US), and Ronald J. Eby (US) made the first polysaccharide-conjugate vaccines against Haemophilus influenzae to be tested in adults and infants(1708, 1709). They went on to develop a vaccine which was a commercial success.

Louis P. Rodriques (US), John B. Robbins (US) Rachel Schneerson (US), James C. Parke, Jr. (US), C. Bell (US), James J. Schlesselman (US), Ann Sutton (US), Z. Wang (US), Gerald Schiffman (US), Arthur Karpas (US), and Joseph Shiloach (US) studied the antigenicity of the Hemophilus influenzae type b (Hib) polysaccharide then developed a clinically acceptable method of binding this polysaccharide to a medically useful protein, tetanus toxoid to form a conjugate vaccine. In sequential studies, their Hib-tetanus conjugate elicited protective levels in mice, rabbits, young rhesus monkeys and then in human adults, children and infants. Their achievement opened the door to their and others' development of conjugate vaccines for other bacterial pathogens whose surface polysaccharide could serve as a protective antigen(1710-1712).

Jack Hirsh (AU-CA), John F. Cade (AU), Alexander S. Gallus (AU), and Dilip Basu (US) noted the relationship between the in vitro anticoagulant activity of heparin and its efficacy in patients with venous thrombosis(1713, 1714). The superior clinical efficacy of low-molecular-weight heparin revolutionized anti-thrombotic treatment, allowing management on an outpatient basis.

John F. R. Kerr (AU), Alastair R. Currie (GB), and Andrew H. Wyllie (GB) coined the term apoptosis, outlined the cardinal characteristics of this program of cell death and articulated the significance of apoptosis in human disease. They coined the term to rhyme with necrosis, and also to mean literally a "falling off," as the petals fall off a flower or the leaves fall from a tree. The cell death machinery is a set of genes which stand ever ready to self-destruct. In the 1972 article the authors described massive apoptosis in the cells populating rapidly growing, hormone-dependent tumors following hormone removal and offered the suggestion that apoptosis serves as a barrier to cancer(1715-1719).

John E. Sulston (GB), H. Robert Horvitz (US), Einhard Schierenberg (DE), John G. White (GB-US), and J. Nicoll Thomson (GB) traced the embryonic cell lineage of the nematode Caenorhabditis elegans “from zygote to newly hatched larva, with the result that the entire cell lineage of this organism is now known. In every worm, out of 1,090 newborn cells, the same 131 cells die during development, resulting in a nematode of 959 cells exactly. The embryonic lineage is highly invariant, as are the fates of the cells to which it gives rise. In spite of the fixed relationship between cell ancestry and cell fate, the correlation between them lacks much obvious pattern. Thus, although most neurons arise from the embryonic ectoderm, some are produced by the mesoderm and a few are sisters to muscles; again, lineal boundaries do not necessarily coincide with functional boundaries. Nevertheless, cell ablation experiments (as well as previous cell isolation experiments) demonstrate substantial cell autonomy in at least some sections of embryogenesis. They concluded that the cell lineage itself, complex as it is, plays an important role in determining cell fate”(1720, 1721).

Hilary M. Ellis (US), H. Robert Horvitz (US), Michael O. Hengartner (US), Ding Xue (US), and Shai Shaham (US) described the genetic basis of programmed cell death, apoptosis, in the development of Caenorhabditis elegans (a nematode). They found many of the regulatory genes controlling apoptosis and showed that similar genes exist in humans. They identified genes that control the fate of doomed cells by screening for worms that — after mutagenesis of their genome — contained 'un-dead' cells (that is, cells that should have died, but survived instead). Tracing the mutations in these worms led them to two genes, ced-3 and ced-4 (called ced for cell death abnormal), which were both essential for cell death, and one, ced-9, which prevented death in cells that needed to survive. These experiments established a genetic basis for programmed cell death. Moreover, they showed that most developmental deaths are cell-autonomous — thereby establishing suicide rather than murder as the cause of death(1722-1725).

David Vaux (AU), Suzanne Cory (AU) and Jerry Adams (AU) showed that expression of the B cell lymphoma 2 (BCL2) gene can promote the survival of haematopoietic cells after the removal of growth factors. They also showed that the oncogene Myc cooperated with BCL2 to produce tumors in immunocompromised mice. They suggested that BCL2 provided a distinct survival signal that might contribute to neoplasia by allowing a clone to persist until other oncogenes, such as Myc, became activated. This provided evidence that cell survival is regulated independently of cell proliferation, and that impaired cell death, similar to enhanced proliferation, is indeed a key step in tumor development(1726).

Valerie A. Fadok (US), Dennis R. Voelker (US), Priscilla A. Campbell (US), J. John Cohen (US), Donna L. Bratton (US), and Peter M. Henson (US) discovered the exposure of phosphatidylserine at the lymphocyte’s outer surface during apoptosis triggering their recognition and removal by macrophages(1727).

Masayuki Miura (JP), Hong Zhu (US), Rocco J. Rotello (US), Erika A. Hartwieg (US), and Junying Yuan (CN-US) found that the activities of mammalian interleukin-1 beta-converting enzyme (ICE) suggests that it may function during mammalian development to cause programmed cell death (apoptosis). Interleukin-1 beta-converting enzyme (ICE) is a member of a group of cysteine-dependent, aspartate-specific proteases (caspases)(1728).

Curtis C. Harris (US) found that the functional inactivation of p53 protein (product of the p53 gene) is seen in greater than 50% of human cancers and results in the removal of a key component of the DNA damage sensor that can induce the apoptotic effector cascade(1729).

Arnold J. Levine (US) states that it is clear that the functioning of the p53 DNA damage signaling pathway is lost in most, if not all, human cancers(1730).

Joseph Lotem (IL), Leo Sachs (IL), Alison J. Butt (AU), Sue M. Firth (AU), and Robert C. Baxter (AU) suggested ligand/receptor molecules which serve to bind either survival or death factors. Examples of these ligand/receptor pairs include survival signals conveyed by IGF-1/IGF-2 through their receptor, IL-3R(1731, 1732). Note: IGF = insulin-like growth factor. IL-3R = interleukin 3 receptor.

Robert M. Pitti (US), Scot A. Marsters (US), David A. Lawrence (US), Margaret Roy (US), Frank C. Kischkel (US), Patrick Dowd (US), Arthur Huang (US), Christopher J. Donahue (US), Steven W. Sherwood (US), Daryl T. Baldwin (US), Paul J. Godowski (US), William I. Wood (US) , Austin L. Gurney (US), Kenneth J. Hillan (US), Robert L. Cohen (US), Audrey D. Goddard (US), David Botstein (US), and Avi  Ashkenasi (US) discovered a decoy receptor for Fas ligand which entices the death-inducing signal away from the Fas death receptor. The result is the abrogation of the Fas death signal. This decoy signal has been revealed in a high fraction of lung and colon carcinoma cell lines(1733). The Fas receptor is a death receptor on the surface of cells that leads to programmed cell death (apoptosis).

Avi Ashkenazi (IL-US) and Vishva M. Dixit (KE-US) determined that death signals are conveyed by the Fas ligand binding the Fas receptor and by TNF alpha binding TNF-R1(1734). Note: The Fas receptor is a death receptor on the surface of cells that leads to programmed cell death (apoptosis). TNF = tumor necrosis factor.

Gerard Evan (GB) and Trevor Littlewood (GB) noted that intracellular sensors monitor the cell's well-being and activate the death pathway in response to detecting abnormalities, including DNA damage, signaling imbalance provoked by oncogene action, survival factor insufficiency, or hypoxia(1735).

Douglas R. Green (US) and John C. Reed (US) reported that many of the signals that elicit apoptosis converge on the mitochondria, which respond to proapoptotic signals by releasing cytochrome C, a potent catalyst of apoptosis(1736).

Nancy A. Thornberry (US) and Yuri Lazebnik (US) determined the ultimate effectors of apoptosis to include an array of intracellular proteases termed caspases(1737).

Douglas Hanahan (US) and Robert Allan Weinberg (US) state that "collectively, the data indicate that a cell's apoptotic program can be triggered by an overexpressed oncogene. Indeed, elimination of cells bearing activated oncogenes by apoptosis may represent the primary means by which such mutant cells are continually culled from the body's tissues. Other examples strengthen the concensus that apoptosis is a major barrier to cancer that must be circumvented"(1738).                             

H. Robert Horvitz (US) and John E. Sulston (GB) would be awarded the 2002 Nobel Prize in Physiology or Medicine for their discoveries concerning genetic regulation of organ development and programmed cell death. 

G. Michael Besser (US), Lynne Parke (GB), Christopher R.W. Edwards (GB), Isabel A. Forsyth (GB), and Alan S. McNeilly (US) found that they could successfully treat galactorrhoea by reducing plasma prolactin levels using brom-ergocryptine(1739).

Sir Hedley J.B. Atkins (GB), John L. Hayward (GB), David J. Klugman (GB), and A.B. Wayte (GB), after 10 years of clinical trial, reported the superiority of radical mastectomy over wide excision (extended tylectomy) in patients with stage two breast cancer(1740).

William F. Bernhard (US), S. Bert Litwin (US), Willis W. Williams (US), Jimmy E. Jones (US), and Robert Edward Gross (US) pioneered operations on inborn cardiovascular defects found in infants during the first year of life(1741).

David J. H. Brock (GB) and Roger G. Sutcliffe (GB) found that amniotic alphafetoprotein in fetuses is common to cases of anencephaly and spina bifida(1742).

Malcolm A. Ferguson-Smith (GB) found that births with anencephalia and or spina bifida can be reduced by testing maternal serum for alphafetoprotein(1743).

Irwin R. Merkatz (US), Harold M. Nitowsky (US), James N. Macri (US), and Walter E. Johnson (US) noted that maternal serum levels of alphafetoprotein are lower in Down's syndrome pregnancies than in unaffected pregnancies(1744).  

Niles Eldredge (US) and Stephen Jay Gould (US) proposed punctuated equilibrium effects in evolution; stating that evolution often occurs in short bursts, followed by long periods of stability(1745-1747).

Henry S. Horn (US)  and Robert H. MacArthur (US) examined the qualitative behavior of differential equations in describing the potential for stable coexistence or competitive exclusion based on rates of migration and local extinction(1748). Their technique has subsequently been applied to questions about plant competition, landscape change, biodiversity maintenance, and parasite management.

Zofia Kielan-Jaworowska (PL) and Rinchen Barsbold (PL) with their team and Mongolian paleontologists discovered during 1971 the entwined skeletons of a Protoceratops and a juvenile Velociraptor in the Gobi Desert, most likely locked in mortal combat(1749).

Dietrich Mania (DE), in 1972, discovered the first fossil skull fragment of Homo erectus bilzingslebenensis; Homo erectus; Homo sapiens  near Bilzingsleben in Central Germany(1750). This fragment and those subsequently discovered have been dated to the Middle Pleistocene; ca. 400,000 B.P.

Maurice Taieb (FR), Yves Coppens (FR), Donald C. Johanson (US), Jon Kalb (US), and Raymonde Bonnefille (FR) discovered and described fossil remains of Australopithecus afarensis from the Hadar site in the Afar depression in the west central sedimentary basin, north-east of Addis Ababa, Ethiopia(1751-1754). These specimens were dated to ca. 2.9-3.0 M.Y.B.P.

Donald C. Johanson (US), Maurice Taieb (FR), Tim D. White (US), and Yves Coppens (FR) discovered a female fossil hominid at Hadar, Ethiopia (Australopithecus afarensis) and named her Lucy. Lucy's discovery established that hominids walked upright before developing large brains, overturning many long-held beliefs about hominid evolution. Australopithecus afarensis is considered to be the first human, but this is now being challenged by Meave G. Leakey’s discovery of Kenyanthropus in 2001(1755, 1756).

Donald C. Johanson (US) and Tim D. White (US) discovered more specimens of Australopithecus afarensis(1757). Australopithecus afarensis had an apelike face with a low forehead, a bony ridge over the eyes, a flat nose, and no chin. They had protruding jaws with large back teeth. Cranial capacity varied from about 375 to 550 cc. The skull is similar to that of a chimpanzee, except for the more humanlike teeth. The canine teeth are much smaller than those of modern apes, but larger and more pointed than those of humans, and shape of the jaw is between the rectangular shape of apes and the parabolic shape of humans. However their pelvis and leg bones far more closely resemble those of modern man, and leave no doubt that they were bipedal (although adapted to walking rather than running(1758).

Mary Douglas Nicol Leakey (GB-KE) and Richard L. Hay (US) reported hominid footprints preserved in Pliocene ash deposits in the Laetolil Beds at Laetoli, Northern Tanzania. These footprints, discovered by the geochemist Paul I. Abell (US) in 1978, constitute the earliest evidence of bipedalism in the hominid fossil record. This hominid was very likely Australopithecus afarensis(1759).

Carol V. Ward (US), William H. Kimbel (US) and Donald Carl Johanson (US) found fossil feet confirming that the A. afarensis foot was functionally like that of modern humans and support the hypothesis that this species was a committed terrestrial biped(1760).


“Nothing in biology makes sense except in the light of evolution.” Theodosius Grigorievich Dobzhansky(1761).

"One cannot necessarily assign a function to an enzyme merely on the basis of its in vitro properties or its abundance. A genetic approach using mutants makes meaningful in vivo correlates possible." Geoffrey L. Zubay and Marmur Julius.

Karl von Frisch (AT-DE), Konrad Zacharias Lorenz (AT) and Nikolaas Tinbergen (NL) were awarded the Nobel Prize in Physiology or Medicine for their discoveries concerning organization and elicitation of individual and social behavior patterns.

BASF Chemical Company introduced the herbicide bentazon, a benzothiadiazine, for the control of broadleaf weeds in soybeans (Glycine max), rice (Oryza sativa), corn (Zez mays), and peanuts (Arachis hypogaea). Ref

Giovanni Bucolo (US) and Harold David (US) introduced a simplified, highly specific enzyme-based method for serum triacylglycerol (TG) determination(1762).

Phillip Allen Sharp (US), Bill Sugden (US), and Joseph Sambrook (GB-US-AU) were the first to use agarose gel electreophoresis for rapid analysis of DNA restriction patterns and the first to use the fluorescent dye, ethidium bromide, to stain DNA bands in agarose(1763).

Marshall Elzinga (US), John H. Collins (US), W. Michael Kuehl (US), and Robert S. Adelstein (US) determined the amino acid sequence of G-actin(1764, 1765). This study represents the first complete determination of the amino-acid sequence of a myofibrillar protein. This protein polymerizes to form F-actin the main component of actin filaments.

Hans Leo Kornberg (GB-US) recognized that there exists a "pecking order" in the sequence in which different hexoses are taken up by E. coli. For example, as little as micromolar amounts of glucose will powerfully inhibit the continued uptake of fructose, even though the cells are fully induced for fructose utilization and that ketose is present in great excess(1766).

Cyril Jeremy Craven (GB) and Desmond J. Dawson (GB) showed that tetanus toxin prepared from cells consists of a single polypeptide chain of an approximate M.W. of 160,000 daltons(1767).

Frederick Sanger (GB), Alan R. Coulson (GB), Steve Nicklen (GB), Gillian M. Air (GB), Nigel L. Brown (GB), John C. Fiddes (GB), Clyde A. Hutchison III (US), Patrick M. Slocombe (GB), Michael Smith (CA), Barclay George Barrell (GB), Allan M. Maxam (US), and Walter Gilbert (US) developed rapid methods for sequencing the bases of  DNA(1768-1773). The 1977 article by Sanger et al., established the sites for initiation and termination of transcription and revealed that in some cases two genes are transcribed from the same DNA region using different reading frames.

Eugene D. Sverdlov (RU), Galina S. Monastyrskaya (RU), Arsenii V. Chestukhin (RU), and Edward I. Budowsky (RU-US) originated the methodology found in the Maxam-Gilbert method(1774). Their laboratory chief, Yuri A. Ovchinnikov (RU), thought the scheme would not work, so it was not tested.

Roger Cecil Burgus (US), Nicholas Ling (NZ), Madalyn Butcher (US), and Roger Charles Louis Guillemin (FR-US) determined the primary structure of somatostatin (somatotropin-release inhibiting factor), a hypothalamic peptide that inhibits the secretion of pituitary growth hormone as H-Ala-Gly-Cys-Lys-Asn-Phe-Phe-Trp-Lys-Thr-Phe-Thr-Ser-Cys-OH(1775).

John T. Rotruck (US), Arthur L. Pope (US), Howard E. Ganther (US), A.B. Swanson (US), Dean G. Hafeman (US), and William G. Hoekstra (US) discovered that selenium is a dietary essential because it is a component of glutathione peroxidase(1776).

Donald Yamashiro (US) and Choh Hao Li (CN-US) synthesized the entire human adrenocorticotropin hormone (ACTH) containing 39 residues. During the process they learned that as residues 19 through 26 were added the ACTH potency increased until at 26 it became as potent as the natural hormone(1777).

Sung-Hou Kim (US), Gray J. Quigley (US), Fred Leroy Suddath (US), Alexander McPherson (US), Daryll Sneden (US), Jung-Ja Park Kim (US), Jon Weinzierl (US), and Alexander Rich (US) determined the molecular structure of yeast transfer RNA Phe to a 4 angstrom resolution(1778). By 1974, together with Joel L. Sussman (US), Andrew H.J. Wang (US), and Nadrian C. Seeman (US) they had interpreted the three-dimensional tertiary structure of yeast transfer RNA Phe to a resolution of three angstroms(1779).

Shunji Natori (JP), Kazuyuki Takeuchi (JP), and Den’ichi Mizuno (JP) identified elongation factor SII (TFIIS) by its ability to stimulate transcription in vitro and to enable RNA polymerase II (pol II) to synthesize long transcripts(1780).

John Logan (US), Erik Falck-Pedersen (US), James Edwin Darnell, Jr. (US), Thomas Shenk (US), Sheila Connelly (US), and James L. Manley (US) established that polyadenylation and transcription termination are dependent on the same DNA sequences at the 3' ends of genes(1781, 1782).

Daniel Reines (US), Michael G. Izban (US) and Donal S. Luse (US) provided insights into the mechanism of SII activity. They noticed that the addition of elongation factor SII caused a shortening of transcripts associated with stalled RNA pol II. They found that, in the presence of SII, the RNA pol II complex can serve as a nuclease, cleaving its nascent transcript from the 3' end(1783, 1784).

Daguang Wang (US) and Diane K. Hawley (US) also presented evidence to support these observations, and proposed a possible proofreading role for the activity described. Surprisingly, it was noted that this process leaves the pol II complex intact and the remaining transcript can subsequently be elongated. The nuclease activity that is stimulated by SII helps pol II bypass specific blocks to elongation and therefore increases elongation efficiency(1785).

Richard E. McCarty (US), John Fagan (US), and Ronald P. Magnusson (US) showed that the reactivity of a chemical group in one subunit of chloroplast CF1 is enhanced when chloroplasts are illuminated(1786, 1787).

Walter Gilbert (US) and Allan M. Maxam (US) showed that the operator of the lac gene contains a highly symmetrical base sequence recognized by the lac repressor molecule(1788, 1789).

Stanley Norman Cohen (US), Paul Berg (US), John Anthony Carbon (US), John F. Morrow (US), Thomas E. Shenk (US), Herbert Wayne Boyer (US), Achilles Dugaiczyk (US), Howard Michael Goodman (US), Annie C.Y. Chang (US), Robert B. Helling (US), and Stephen Payne Goff (US) developed techniques for recombining DNA from two different sources using restriction endonucleases. Berg’s experiments showed that a restriction endonuclease can be used to cut DNA in a predictable manner and that DNA fragments from different organisms can be joined together. Foreign DNA could be recombined with plasmid DNA then maintained and replicated within Escherichia coli(1790-1795).

Stanley Norman Cohen (US) and Herbert Wayne Boyer (US) applied to patent this process(1796).

Eric H. Davidson (US) and Roy J. Britten (US) pioneered nucleic acid hybridization kinetics to study eukaryotic gene expression(1797).

Paul Delos Boyer (US), Richard L. Cross (US), William Momsen (US), B.O. Stokes (US), Richard G. Wolcott (US), and Chemda Degani (IL) presented the binding change hypothesis which suggests that at one time (a) ADP and Pi (inorganic phosphate) bind weakly at one site of the alpha-beta pair of the F1 part of the ATP synthase enzyme; (b) bound ATP is formed from bound ADP and Pi, without the use of energy at a second alpha-beta pair; and (c) the pH gradient energy is converted into rotational energy, mainly of the gamma subunit that extends up to the third alpha-beta pair, that is used to flip off the ATP free from the third alpha-beta binding site. These three sites alternate in time(1798-1803).

Roderick A. Capaldi (GB) demonstrated the rotation feature of the Boyer model directly by fluorescence microscopy and by photoselection and other experiments(1804).

Jan Pieter Abrahams (NL), Andrew G.W. Leslie (GB), René Lutter (NL), and John E. Walker (GB) deduced the atomic resolution structure of beef-heart mitochondrial F1 showing that the gamma subunit indeed looks all through the alpha-beta pairs; and in agreement with the Boyer model, the structure shows one alpha-beta pair site empty (as if ATP is released); another with bound ADP and Pi; and the third with an equivalent of bound ATP(1805).

Daniel J. Smith (US), Michael Gresser (US), Jeffrey W. Cardon (US), Gary Rosen (US), Paul Delos Boyer (US), Ian M. Fearnley (GB), Nicholas J. Gay (GB), Bradford W. Gibson (US), Frederick D. Northrop (GB), Steven J. Powell (GB), Michael J. Runswick (GB), Matti Saraste (DE), R.J. Todd (GB) and Victor L.J. Tybulewicz (GB) also contributed significantly to the elucidation of the enzymatic mechanism underlying the synthesis of adenosine triphosphate (ATP)(1806-1812).

Miklós Müller (HU-US), and Donald G. Lindmark (US) characterized, within the trichomonads, a completely new type of cytoplasmic particle, with the capacity of converting pyruvate to acetate, carbon dioxide, and molecular hydrogen, the hydrogenosome(1813-1816).

Bertil Hille (US) explained the functional and structural architecture of ion channel proteins, which govern the electrical potential of membranes. These channels are critical to generating nerve impulses, controlling muscle contraction, cardiac rhythm, and hormone secretion(1817-1823). 

Ronald J. Hill (AU), Kinsey G. Maundrell (CH), and Harold Garnet Callan (GB) found that the length of the S phase of cell division in the amphibian Triturus varies, depending on the stage of embryonic development. They observed that the variations are correlated with differences in the distances that separate replicating segments in the DNA(1824, 1825).

K. Nakamuro (), Nobuyuki Tanigaki (US), and David P. Pressman (US) observed that the beta microglobulin protein is the light polypeptide chain of histocompatibility antigen (HLA)(1826).

Dilruba Yasmeen (AU), James R. Ellerson (), Keith J. Dorrington (US), and Robert H. Painter (CA) found that the constant heavy chain 3 (CH3) domain of the antibody molecule can bind macrophage membranes(1827).

Sydney Brenner (ZA-GB) pioneered the use of the nematode Caenorhabditis elegans as a tool for genetics. It is especially useful because it is highly tractable genetically, simple, and virtually invariant in its cellular anatomy(1828, 1829).

Sydney Brenner (ZA-GB) would be awarded the 2002 Nobel Prize in Physiology or Medicine for his discoveries concerning genetic regulation of organ development and programmed cell death (apoptosis). 

Howard Curtis Berg (US) and Robert A. Anderson (US) determined that bacteria swim by rotating their flagellar filaments(1830).

Michael R. Silverman (US) and Melvin I. Simon (US) dramatically demonstrated this by tethering flagellated bacteria to a glass slide coated with antiflagellar antibodies. When this was done the cells rotated both clockwise and counterclockwise(1831).

Klaus Hantke (DE) and Volkmar Braun (DE) found that proteins with covalently bound fatty acids occur in the prokaryotes(1832).

Mark S. Bretscher (GB) proposed that cell membranes contain protein flippases which facilitate the flip-flopping of some lipids from the interior of the membrane to the exterior(1467).

Harvey Franklin Lodish (US), James Edward Rothman (US), Flora N. Katz (US), David M. Knipe (US), Jonathan M. Backer (US), and Eliezar A. Dawidowicz (US) performed experiments which supported Mark S. Bretscher’s hypothesis(1833-1837).

Michel Bitbol (FR) and Philippe F. Devaux (FR) described an ATP-dependent flippase in erythrocytes. It transports aminophospholipids and cholinephospholipids from the inner to outer leaflet(1838).

Urs-Peter Roos (CH) determined that kinetochores represent the points of attachment of chromosomes to the spindle and are vital to the correct segregation of chromosomes during anaphase(1839).

Edwin Morton Bradbury (GB), Robert J. Inglis (GB), Harry R. Matthews (GB), and Nitza Sarner (GB) presented evidence that the rise in phosphorylation of histone H1 coincides with the beginning of chromosome condensation and represents a major controlling event that shifts cells from G2 to mitosis(1840, 1841).

Ralph F. Kampschmidt (US), Herbert F. Upchurch (US), Carl L. Eddington (US), and Larry A. Pulliam (US) discovered that a factor released from leucocytes stimulates the acute-phase response. This mediator would later be called interleukin-1(1842).

Jim Patrick (US) and Jon Lindstrom (US) induced experimental autoimmune myasthenia gravis (EAMG) by injecting rabbits with nicotinic acetylcholine receptors from fish electric organs(1843).

Dharam P. Singal (CA) and Morris A. Blajchman (CA) made the first known association of the major histocompatibility complex (MHC) markers with insulin-dependent diabetes mellitus. They associated HLA-B with increased incidence of insulin-dependent diabetes mellitus(1844). Insulin-dependent diabetes mellitus is also known as type-1 diabetes.

Arne Svejgaard (DK), Per Platz (DK), and Lars Peter Ryder (DK) demonstrated that HLA-B markers are not as strongly associated with insulin-dependent diabetes mellitus as are HLA-DR markers(1845).

Kenneth J. Judy (US), David A. Schooley (US), M. Sharon Hall (US), B. John Bergot (US), and John B. Siddall (US) discovered and isolated insect juvenile hormone III from an organ culture of tobacco hornworm (Manduca sexta)(1846).

Hans Leo Kornberg (GB-US), Anne K. Soutar (GB), Pelin Faik (GB), Jacques M. Pouyssegur (FR), and Brigitte Bächi (CH) were able to elucidate the main routes whereby E. coli utilizes gluconate as a sole carbon sources for growth(1847-1851).

Bernadette Bouges-Bocquet (FR), Bruno R. Velthuys (NL-US), and Jan Amesz (NL) showed that there is a two electron gate on the acceptor side of photosystem 2(1852, 1853).

André Vermeglio (FR), Roderick K. Clayton (US), and Colin A. Wraight (GB) discovered a similar gate in anoxygenic photosynthetic bacteria(1854, 1855).

Dieter Oesterhelt (DE) and Walther Stoeckenius (DE-US) discovered a new photosynthetic mechanism powered by a different pigment (bacteriorhodopsin), one that is closely related to rhodopsin. They discovered this system in the archaebacterium, Halobacterium halobium and found that it functions as a light driven proton pump in the bacterial plasma membrane(1856).

Efraim Racker (PL-AT-US) and Walther Stoeckenius (DE-US) incorporated bacteriorhodopsin into a liposome membrane along with the F1Fo-ATPase from bovine heart. They found that upon illumination bacteriorhodopsin pumped protons out. These protons subsequently flowed back through the F1Fo-ATPase generating ATP from ADP and inorganic phosphate. This experiment confirmed Peter Mitchell’s chemiosmotic hypothesis and tied together the mechanism of ATP formation in mitochondria, chloroplasts, and the bacterial plasma membrane(1857).

Dean R. Hewish (AU) and Leigh A. Burgoyne (AU), Ada L. Olins (US), Donald E. Olins (US)  and Jennifer Mobbs (AU) took electron photomicrographs and used DNA endonucleases to cut chromatin and found that the pieces which resulted were roughly 200 base pairs long or a multiple of this length. This was strong evidence suggesting that eukaryotic DNA is organized into nucleosome units which occur along the DNA molecule like beads on a string(1858-1860).

Roger D. Kornberg (US) and Jean O. Thomas (US) discovered the histone tetramer, (H3)2 (H4)2 , then proposed a model for the basic unit of chromatin (the nucleosome) as a bead of about 100 A diameter, containing a stretch of DNA 200 base pairs long condensed around a protein core made out of 8 histone molecules, namely the (H3)2 (H4)2 tetramer and 2 each of H2A and H2B. The fifth histone, H1, was somehow associated with the outside of each nucleosome. They conceived that eukaryotic DNA is tightly packaged around a core of structural proteins — histones — to generate a nucleosome array that is fundamental for controlling gene expression, i.e., the nucleosome hypothesis(1861, 1862).

John T. Finch (GB), Leonard C. Lutter (GB), Daniela Rhodes (GB), Raymond S. Brown (GB), Barbara Rushton (GB), Michael Levitt (GB), Sir Aaron Klug (GB), Karolin Luger (CH), Armin W. Maeder (CH), Robin K. Richmond (CH), Davd F. Sargent (CH), Timothy J. Richmond (CH), Curt A. Davey (CH), and Armin W. Maeder (CH) reported the x-ray crystal structure of the nucleosome complex(1863-1865).

Oliver H. Lowry (US) developed the methodology to isolate, prepare, weigh and chemically study single nerve cells and subcellular particles(1866). 

Howard R. Six (US) and Sidney Harshman (US) isolated two stable forms of Staphylococcus aureus alpha-toxin from broth cultures of the Wood 46 strain. Alpha-toxin was later found to be a potent hemolysin and leucocidin(1867).

Charles E. Lankford (US) states that microorganisms combat biological shortages of iron in aerobic environments—at neutral pH iron exists almost exclusively in the form of insoluble ferric hydroxide—by producing low molecular weight iron-chelating compounds known as siderophores(1868).

Peter Lobban (US) and Armin Dale Kaiser (US) developed a technique for adding cohesive ends to DNAs which had been cut with an endonuclease which cleaves straight across(1869).

Armin Dale Kaiser (US), Michael Syvanen (US), and Terrie Masuda (US), found that the DNA molecule extracted from the Escherichia coli phage lambda can combine with the phage-precursor proteins present in a cell extract of lambda-infected bacteria to form infectious particles(1870).

Paul Wuthier (US), Carol Jones (US), and Theodore Thomas Puck (US) established a linkage between human cell surface antigen AL and the lactic dehydrogenase A gene(1871).

P.R. Dendy (GB) and Henry Harris (AU-GB) showed that diphtheria toxin, which is about 100,000 times more lethal to human than to mouse cells, can be used as a selective system for man-mouse hybrid cells(1872).

Arthur Karlin (US), David A. Cowburn (US), Cheryl L. Weill (US), and Mark G. McNamee (US) purified acetylcholine receptor (AChR) from Electrophorus electricus and Torpedo californica. They determined that it contains four different types of polypeptide subunits(1873, 1874). It turned out that these subunits are common to all vertebrate striated muscle-type AChRs.

Leslie D. Gottlieb (US) documented the speciation of Stephanomeira malheurensis. He found a single small population (< 250 plants) among a much larger population (> 25,000 plants) of S. exigua in Harney Co., Oregon. Both species are diploid and have the same number of chromosomes (N = 8). S. exigua is an obligate outcrosser exhibiting sporophytic self-incompatibility. S. malheurensis exhibits no self-incompatibility and self-pollinates. Though the two species look very similar, Gottlieb was able to document morphological differences in five characters plus chromosomal differences. F1 hybrids between the species produce only 50% of the seeds and 24% of the pollen that conspecific crosses produce. F2 hybrids show various developmental abnormalities(1875).

Frank L. Graham (CA) and Alex J. van der Eb (NL) showed that human adenovirus 5 can be transferred to cells in culture, with retention of function, if the viral DNA is precipitated onto the cells by means of calcium phosphate. The particulate complex of viral DNA and calcium phosphate is apparently taken into the cells by endocytosis, and the DNA is then released in a functional state(1876).

Robert E. Weibel (US), Victor M. Villarejos (US), Gloria Hernandez (ES), Joseph Stokes, Jr. (US), Eugene B. Buynak (US), and Maurice Ralph Hilleman (US) developed a combined live measles-mumps virus vaccine(1877).

Elaine G. Diacumakos (US) developed microinjection techniques accurate enough to deliver foreign molecules into mammalian cells(1878).

Andrew G. Szent-Gyorgyi (US), Eva M. Szentkiralyi (US), Robert M. Simmons (GB) and others worked out the mechanism which controls the ability of myosin to bind actin and proceed through the crossbridging cycle(1879-1882).

Thomas Dean Pollard (US) and Edward David Korn (US) discovered an unconventional myosin called myosin-1(1883).

Vincent Gaston Dethier (US), while studying the swallowtail butterfly, became the first to prove that caterpillars select their food by the plant’s taste and smell, not its nutritional value(1884).

Theodor Otto Diener (US) and Roger H. Lawson (US) found that the etiologic agent of chrysanthemum stunt is a viroid(1543).

George Laver (US) and Robert G. Webster (US) demonstrated that the genomes of influenza virus strains responsible for pandemics possess genome fragments acquired by genome segment reassortment from influenza strains circulating in animals(710).

E.A. Bevan (GB), A.J. Herring (GB), and Diane J. Mitchell (GB) noted that the non-Mendelian phenotype, "killer," is controlled by cytoplasmic nucleic acids, which constitute the family of L-A double-stranded RNA viruses(1885).

Joël Bockaert (FR), Christian Roy (FR), Rabary Rajerison (FR), and Serge Jard (FR) demonstrated, in cell membrane fractions from kidney medulla, the presence of molecular receptors which stereospecifically bind vasopressin molecules and are coupled to adenylate cyclase(1886).

Sally H. Zigmond (US) and James Gerald Hirsch (US), in their study of leucocyte locomotion and chemotaxis, described new methods for evaluation, and demonstration of a cell-derived chemotactic factor(1887).

William P. Kolb (US), James A. Haxby (US), Carlos M. Arroyave (US), and Hans Joachim Müller-Eberhard (DE-US-DE) described the membrane attack mechanism of complement and reversible interactions among the five native components in free solution(1888).

Andrew G. Engel (US) and Corrado I. Angelini (IT) discovered carnitine deficiency of human skeletal muscle with associated lipid storage myopathy: a new syndrome(1889).

Jean-Paul Butzler (BE), Paul J. Dekeyser (BE), M. Detrain (BE), F. Dehaen (BE), Victor D. Bokkenheuser (US), Neville J. Richardson (US), John H. Bryner (US) Daniel J. Roux (US), Awie B. Schutte (US), Martin B. Skirrow (GB), Trevor W. Steele (AU), Suzanne McDermott (US), Chik H. Pai (CA), Simon Sorger (CA), Lynn Lackman (CA), Roberto E. Sinai (FR-CA-US), Melvin I. Marks (CA), Signe Ringertz (NO), Robert C. Rockhill (US), Olof Ringertz (NO), Arini Sutomo (ID), Martin J. Blaser (US), Joy G. Wells (US), Roger A. Feldman (US), Robert A. Pollard (US), and James R. Allen (US) found that Campylobacter jejuni is the leading cause of acute gastroenteritis in humans throughout the world(1890-1896).

Ruth F. Bishop (AU), Geoffrey P. Davidson (AU), Ian H. Holmes (AU), Brian J. Ruck (AU), Thomas H. Flewett (GB), A.S. Bryden (GB), and Heather A. Davies (GB) gave the first descriptions of rotavirus in association with a human disease—diarrhea in infants and young children(1897, 1898).

Geoffrey P. Davidson (AU), Ruth F. Bishop (AU), R. Rugely W. Townley (AU), and Ian H. Holmes (AU) demonstrated rotavirus, the cause of acute sporadic enteritis in children, using electron microscopy(1899). 

Stephen M. Feinstone (US), Albert Z. Kapikian (US), and Robert H. Purcell (US) identified a viral agent in the stool of patients with hepatitis A(1900). This discovery quickly led to the development of tests to accurately detect antibodies to hepatitis A virus in the blood of those infected.

Alice S. Huang (US) defined defective interfering viral particles as follows: (1) they are deletion mutants and therefore lack large amounts of the genetic material present in the standard virus; (2) they contain the same viral structural proteins as standard virus; (3) they are unable to replicate alone; however, they are replicated in cells co-infected with standard virions; and (4) at the same time as they require standard virus to replicate, they inhibit the replication of standard virus and hence are interfering(1901).

Michael Stuart Brown (US) and Joseph Leonard Goldstein (US) worked out the steps involved in the uptake of cholesterol, in the form of low-density lipoprotein (LDL), in blood plasma by the cells of the body. The LDL particles bind to their receptors and are then internalized by endocytosis. An endocytotic vesicle forms which subsequently fuses with a lysosome where the lipoprotein is degraded. The receptors return to the cell membrane. They discovered that the gene mutated in familial hypercholesterolaemia is the gene for low density lipoprotein-receptors (LDL-receptors). They found that individuals with inherited high cholesterol levels have either low levels or deficient forms of the low-density lipoprotein receptor (LDL-receptor) involved in the removal of cholesterol from the blood(1902-1907). This discovery led to the development of new drugs that lower blood cholesterol levels and reduce the risk of heart disease.

Russell W. Schaedler (US) states that after birth, an important microbial ecosystem develops in the digestive tract. The major source of this microflora is normally the mother(1908).

Ralph M. Steinman (US) and Zanvii A. Cohn (US) reported a new cell type from mouse peripheral lymphoid organs (spleen, lymph node, Peyer's patch). Present in small numbers (0.1-1.6 % of the total nucleated cells) the cells have distinct morphological features. The nucleus is large, refractile, contorted in shape, and contains small nucleoli (usually two). The abundant cytoplasm is arranged in processes of varying length and width and contains many large spherical mitochondria. In the living state, the cells undergo characteristic movements, and unlike macrophages, do not appear to engage in active endocytosis. The term, dendritic cell, was proposed for this novel cell type(1909).

Adriana van Leeuwen (DK), H. Riek Schuit (DK), and Johannes Joseph van Rood (NL) identified the first sera that could be used for HLA-DR typing. This formed the basis on which HLA-DR serology was developed(1910).

Armond S. Goldman (US), C. Wayne Smith (US), Larry W. Thorpe (US), Randall M. Goldblum (US), and Lars Å. Hanson (US) found that human milk contains a complex immune system consisting of direct-acting antimicrobial agents, anti-inflammatory factors, immunomodulating agents, and living cells(1911-1913).

Sir James Whyte Black (GB) and Brian N.C. Prichard (GB) explored the activation and blockade of beta adrenoceptors in common cardiac disorders, i.e., role of beta-blockers(1914).

John C. Liebeskind (US), Gisèle Guilbaud (FR), Jean-Marie Besson (FR), and Jean-Louis Oliveras (FR) discovered that stimulation of the midbrain area called the PAG (periaqueductal gray) produced pain in animals, but reducing the stimulation produced analgesia(1915).

Huda Akil (US), David J. Mayer (US), and John C. Liebeskind (US) went on to show the effect was blocked by the opioid antagonist naloxone(1916).

Hanan Frenk (IL), Brad C. McCarty (US), and John C. Liebeskind (US) suggested that the effect was similar to the analgesia produced by opiates(1917).

Eric J. Simon (US) and Lars Terenius (SE), Candace B. Pert (US), and Solomon Halbert Snyder (US) proposed then demonstrated opioid receptors in the brain(1918-1921). This would lead to the discovery of encephalins by other workers.

John Hughes (GB), Hans W. Kosterlitz (GB), Terry W. Smith (GB), Barry A. Morgan (GB), and Linda A. Fothergill (GB), from pig brain, discovered and named enkephalin, a natural ligand for opiate receptors(1922, 1923).

John Hughes (GB), Terry W. Smith (GB), Hans W. Kosterlitz (GB), Linda A. Fothergill (GB), Barry A. Morgan (GB), and Howard R. Morris (GB) determined the amino acid sequences of two morphinomimetic pentapeptides, the enkephalines, to be H-Tyr-Gly-Gly-Phe-Met-OH and H-Tyr-Gly-Gly-Phe-Leu-OH (1924). The term enkephalin (meaning literally "in the head") is also applied to endorphins, but usually refers to smaller molecules that have pain-relieving properties. This work strongly supported a long-standing theory that there are normally opiate-like substances in the brain which are neurotransmitters of messages relating to pain and emotional behavior.

Eric J. Simon (US), in 1975, proposed the name endorphin (synthesized from endogenous and morphine) for endogenous substances which bind with opiate receptors in the brains of mammals(1925).

Choh Hao Li (CN-US) and David Chung (US) found a 31 residue peptide which consisted of residues 61-91 of beta-lipotropin from the camel. They named this 31 residue sequence beta-endorphin (beta-EP)(1926, 1927).

Brian M. Cox (US), Avram Goldstein (US), and Choh Hao Li (CN-US) reported the opioid activity of the peptide, beta-lipotropin-(61-91), derived from beta-lipotropin(1928). 

Choh Hao Li (CN-US), Simon Lemaire (US), Donald Yamashiro (US), and Byron A. Doneen (US) synthesized and reported the opiate quality of beta-endorphin(1929).

Nabil G. Seidah (CA), N. Dragon (CA), Suzanne Benjannet (CA), Richard Routhier (CA), and Michel Chretien (CA) determined the complete sequence of sheep beta-endorphin(1930).

Roger Charles Louis Guillemin (FR-US) isolated several large peptides, called endorphins, from extracts of the hypothalamus or pituitary(1931).

P.R. Loe (US), David L. Tomko (US) G. Werner (US) , Cesar Fernandez (US) and Jay M. Goldberg (US) provided the first complete characterization of the physiology of the mammalian peripheral otolith system, which senses linear accelerations, including gravity and the inertial motion of the head in space(1932-1935).  

Kenneth L. Jones (US), David W. Smith (US), Christy N. Ulleland (US), and Ann Pytkowicz Streissguth (US) described fetal alcohol syndrome in the following manner: “Eight unrelated children and three different ethnic groups, all born to mothers who were chronic alcoholics, have a similar pattern of craniofacial, limb, and cardiovascular defects associated with prenatal-onset growth deficiency and developmental delay”(1936).

Roscoe O. Brady (US) John F. Tallman (US) William G. Johnson (US), Andrew E. Gal (US), William R. Leahy (US), Jane M. Quirk (US), and Anatole S. Dekaban (US) pioneered in the use of enzyme replacement therapy to treat genetic diseases(1937).

Herbert L. Needleman (US), Philip Graham (US), Charles Gunnoe (US), Alan Leviton (US), Robert Reed (US), Henry Peresie (US), Cornelius Maher (US), and Peter Barrett (US) conducted studies that yielded strong evidence that lead, even at very low levels, can affect a child's IQ. By measuring levels of lead in children’s teeth, Needleman provided the first evidence that low level lead exposure not only reduces IQs, but also shortens attention spans and delays acquisition of language proficiency. In studies that followed, he determined that lead poisoning had long term implications for a child's attentiveness, behavior, and academic success(1938-1941).

After extensive scientific review, Needleman's findings were instrumental in convincing the Centers for Disease Control (CDC) to issue guidelines for the diagnosis and management of lead poisoning in children, in goading the Environmental Protection Agency (EPA) to mandate the removal of lead from gasoline, and inducing the Consumer Product Safety Commission to ban lead from interior paints. Needleman's research also helped cause the Department of Housing and Urban Development (HUD) to remove lead from thousands of housing units across the US.

Howard E. Skipper (US) and Frank M. Schabel, Jr. (US) showed that a single malignant cell can divide and eventually form enough cells to kill the host, emphasizing that it is essential to destroy every such cell. They also found that the immune system plays little or no part in the therapy of malignant disease, and a given dose of drug will kill a fixed proportion of cancer cells regardless of the total size of the malignancy(1942).

Anthony Martin Halliday (GB), William I. McDonald (GB), and Joan Mushin (GB) introduced a visual evoked response in diagnosis of multiple sclerosis(1943).

Renate Huch (DE), Albert Huch (DE), and Dietrich Lübbers (DE) demonstrated that when skin is heated to 42-45° C, it is possible to measure transcutaneously a reasonable value for arterial PO2, especially in newborn babies(1944). Shortly afterward, transcutaneous electrodes were developed for measuring PCO2.

R.N.H. Pugh (GB), Iain M. Murray-Lyon (GB), J.L. Dawson (GB), M.C. Pietroni (GB), and Roger Williams (GB) found that emergency ligation of bleeding oesophageal varices (extremely dilated sub-mucosal veins in the lower third of the esophagus) using the Milnes Walker technique resulted in an overall 6-month survival of 32 per cent. In patients with good preoperative liver function this rose to 71 per cent, and the simple scoring system for grading the severity of disturbance of liver function was found to be of value in predicting the outcome of surgery(1945).

John Terborgh (US) proposed the geographical area hypothesis. It asserts that the tropics are the largest biome and that large tropical areas can support more species. More area in the tropics allows species to have larger ranges, and consequently larger population sizes. Thus, species with larger ranges are likely to have lower extinction rates(1946).

Leigh M. van Valen (US) formulated what he termed a new evolutionary law. He hypothesized that because of antagonistic interactions such as predation and parasitism, evolution would continue in the absence of environmental change(1947). This concept has been dubbed the Red Queen effect because in Lewis Carroll’s Alice Through the Looking Glass the Red Queen states of her country that: “… Now here, you see, it takes all the running you can do to keep in the same place. If you want to get somewhere else, you must run at least twice as fast as that”(1948).

The United States Congress passed the Endangered Species Act, a much strengthened version of a 1966 omnibus bill. This is the first U.S. law concerned exclusively with wildlife. It specifically prohibits federally funded projects from jeopardizing endangered species or their habitats(1949). 


“Looking back... the facts have been far better than the dreams. In the long course of cell life on this earth it remained for our age, for our generation, to receive the full ownership of our inheritance. We have entered the cell, the mansion of our birth, and started the inventory of our acquired wealth.” Albert Claude(1950). 

Albert Claude (BE-US), Christian Rene de Duve (GB-BE-US) and George Emil Palade (RO-US) were awarded the Nobel Prize in Physiology or Medicine for their discoveries concerning the structural and functional organization of the cell.

William M. Bonner (GB) and Ronald A. Laskey (GB) showed that tritium can be detected in polyacrylamide gels using a solution of the scintillator PPO in dimethyl sulphoxidethem(1951).

Hermann Karl Felix Blaschko (DE-GB) discovered the role of monoamine oxidase in the metabolism of catecholamines(1952).

Yoram Salomon (IL), Constantine Londos (IL), and Martin Rodbell (US) developed a highly sensitive assay for adenylate cyclase(1953).

Charles C. Allain (US), Lucy S. Poon (US), Cicely S.G. Chan (US), W. Richmond (US), and Paul C. Fu (US) developed an automated method for total serum cholesterol using three enzymes: cholesteryl ester hydrolase was used for hydrolysis of cholesteryl esters, cholesterol oxidase for oxidation of cholesterol to form hydrogen peroxide, and peroxidase for oxidative coupling to develop color with 4-aminoantipyrine and phenol(1954).

Knud H. Nierhaus (DE) and Ferdinand Dohme (DE) carried out the total reconstitution of functionally active 50S ribosomal subunits from Escherichia coli(1955).

Hubert Guilley (AT), Gerard Jonard (AT), and Léon Hirth (AT) were among the first to determine some of the base sequences in the RNA of tobacco mosaic virus(1956).

Pieter C. Wensink (US), David J. Finnegan (US), John E. Donelson (US), and David S. Hogness (US) cloned fragments of Drosophila genomic DNA(1957). 

Takashi Kasai (US-IT) analyzed the effects of deletions that ended in the leader region of the his operon of Salmonella. Kasai concluded that the his operon leader region may contain a regulated site of transcription termination. He introduced the term transcription attenuation to describe the mechanism of transcription regulation that presumably occurs at this site(1958).

Charles Yanofsky (US) and Robert Kolter (US) while studying the tryptophane operon of Escherichia coli discovered a type of operon control mechanism called attenuation(1959, 1960).

Frank Lee (US), Catherine L. Squires (US), Craig Squires (US), and Charles Yanofsky (US) found that the trp leader transcript of the tryptophan operon can fold to form alternative hairpin structures, each of which plays an essential role in determining whether transcription will be completed(1961).

Charles Yanofsky (US) reported that one mRNA hairpin serves as a transcription terminator; it directs RNA polymerase to terminate transcription. The second, alternative mRNA hairpin functions as an antiterminator. Which of the alternative hairpin structures would form would depend on the cell's ability to translate the two Trp codons in the 14-residue leader peptide coding region. When these two tryptophan codons are translated, the antiterminator would not form; this would allow the terminator to form and terminate transcription(1959, 1962). Gerard Zurawski (US), George Stauffer (US), Dirk Elseviers (US), Keith Brown (US), and Dale Oxender (US) all contributed to this knowledge.

Bob Landick (US), Robert F. Fisher (US), Malcolm E. Winkler, (US), Robert Kolter (US), Anathbandhu Das (US), and Charles Yanofsky (US) established the role of a third hairpin structure that can form in the trp leader transcript, a structure that precedes and is an alternative to the antiterminator. This structure, which also serves as an anti-antiterminator, causes the transcribing RNA polymerase to pause during transcription of the leader region. This pause allows sufficient time for a ribosome to bind to and initiate translation of the leader peptide coding region(1963-1966).

Roger E. Fenna (US) Brian W. Matthews (US), John M. Olson (US), and Elizabeth K. Shaw (US) determined the structure of a bacteriochlorophyll-protein from the green photosynthetic bacterium Chlorobium limicola: crystallographic evidence for a trimer(1967).

Elias Lazarides (US) and Klaus Weber (PL-DE-US) developed a technique whereby they could visualize actin filaments in non-muscle cells(1968).

Russell Ross (US), John A. Glomset (US), Beverly Kariya (US), Laurence Harker (US), Nancy Kohler (US), and Allan Lipton (US) demonstrated that platelets contain a potent mitogen for cells such as fibroblasts. It is called platelet-derived growth factor (PDGF)(1969, 1970).

Alan T. Nurden (FR) and Jacques P. Caen (FR) made observations on platelet membrane glycoproteins which provided the basis for important advances in understanding hemostasis and prevention of thrombosis(1971). 

Charles D. Taylor (US) and Ralph Stoner Wolfe (US) were the first to describe coenzyme M. It was isolated from a methanogenic bacterium(1972).

Robert Nyfeler (CH) and Walter Keller-Schierlein (CH) reported the isolation of an antifungal agent, echinocandin B, from Aspergillus nidulans var. echinulatus. It inhibits beta glucan synthase activity(1973).

John M. Taylor (US), William M. Mitchell (US), and Stanley Norman Cohen (US) discovered epidermal growth factor(1974).

Charles J. Arntzen (US), Claudie Vernotte (FR), Jean-Marie Briantais (FR), Paul A. Armond (US), Kenneth R. Miller (US), Gayle J. Miller (US), and Katherine R. McIntyre (US) produced experimental evidence that photosystem 2 is found within a large chlorophyll-protein complex (CP II) which spans the thylakoid membrane(1975, 1976).

Ivo Zaenen (BE), Nicolas A. Van Larebeke (BE), H. Teuchy (BE), Marc Van Montagu (BE), Jozef Stephen Schell (BE), Gilbert Engler (BE), Marcelle Holsters (BE), S. Van den Elsacker (BE), and Robbert A. Schilperoort (NL) discovered that the circular DNA strand of the Ti plasmid of Agrobacterium tumefaciens is the tumor inducing principle in crown gall(1977, 1978).

Thomas Peter Maniatis (US), Mark Steven Ptashne (US), Bart Barrell (GB), and John Donelson (US) determined the base sequence of the binding site in the left operator of the lambda virus DNA that had the highest affinity for the repressor protein(1979).

Henri Beaufay (BE), Alain Amar-Costesec (BE), Denise Thines-Sempoux (BE), Maurice Wibo (BE), Mariette Robbi (BE), and Jacques Berthet (BE) determined that many proteins are common to both the smooth and rough endoplasmic reticulum(1980, 1981).

Barry A. Palevitz (US), John F. Ash (US), and Peter K. Hepler (US) suggested that active streaming in Nitella is generated by myosin molecules attached to chloroplasts, which walk by forming crossbridging cycles(1982, 1983).

Johan Stenflo (SE), Gary L. Nelsestuen (US), Thomas H. Zytkovicz (US), James Bryant Howard (US), Staffan Magnusson (SE), Lars Sottrup-Jensen (SE), Torben E. Petersen (DK), Howard R. Morris (GB), and Anne Dell (GB) discovered gamma-carboxyglutamic acid, a modified amino acid, while studying bovine prothrombin(1984-1986). 

Stephen Coplan Harrison (US), Anthony Jack (GB), Daniel A. Goodenough (US), and Bartholomew M. Sefton (US) determined the structure of two small spherical viruses(1987).

Loretta Leive (US) has drawn attention to the fact that many bacterial envelope mutants have been shown to possess dramatically altered permeability characteristics which influence their antibiotic susceptibility(1988).

Robert W. Hedges (GB) and Alan E. Jacob (GB), Naomi Datta (GB), and Jack N. Coetzee (ZA) postulated that resistance to ampicillin in bacteria is carried by a DNA element that can be transposed or moved from one DNA molecule to another. They called this element a transposon. This was the first direct evidence that such a transfer is by a procedure analogous to the insertion of IS (insertion sequence) elements(1989, 1990).

Steven H. Larsen (US), Julius Adler (US), J. Jay Gargus (US), and Robert W. Hogg (US) showed that a proton gradient is the driving force behind flagellar movement in bacteria(1991).

Steven H. Larsen (US), Robert W. Reader (US), Edward N. Kort (US), Wung-Wai Tso (US), and Julius Adler (US) found that change in direction of flagellar rotation is the basis of the chemotactic response in Escherichia coli(1992).

John Shine (AU) and Larry Dalgarno (AU) while studying mRNA translation in Escherichia coli discovered a ribosome-binding site upstream from the AUG initiation codon. This binding site consisted of a group of six to eight purine-rich nucleotides(1993).

Jim Speirs (CH) and Max J. Birnstiel (BR-CH) demonstrated that in Xenopus laevis the 5.8 S RNA is cleaved from the same precursor as 18 and 28 S RNA(1994).

Rolf Martin Zinkernagel (CH-US) and Peter Charles Doherty (AU-US) discovered that killer T cells are not stimulated unless they simultaneously recognize the antigen and the antigen-presenting MHC molecule(1995).

Hiroshi Shiku (US) and Pawel Kisielow (US) discovered that the CD8 receptor protein was unique to killer T cells and could be used to distinguish them from other lymphocytes(1995).

Harry Van Someren (NL), Andries Westerveld (NL), Anne Hagemeijer (NL), J.R. Mees (NL), P. Meera Kahn (IN-NL), and Oscar Brocades Zaalberg (NL) assigned the HLA histocompatibility gene to human chromosome 6(1996).

Howard O. Nornes (US) and Gopal D. Das (US) determined the precise timing of neuron formation in the rat spinal cord(1997).

Dorothy A. Miller (US), Orlando J. Miller (US), Vaithllingam G. Dev (US), Shahnaz Hashmi (US), Ramana V. Tantravahi (US), Leandro Medrano (US), and Howard Green (US) found a gene coding for a poliovirus virus receptor in humans located on chromosome 19(1998).

Jon Robertus (US), Jane E. Ladner (GB), John T. Finch (GB), Daniela Rhodes (GB), Ray S. Brown (GB), Brian F.C. Clark (GB-DK), and Sir Aaron Klug (ZA-GB) described the detailed three-dimensional structure of yeast phenylalanine tRNA. It was determined by x-ray diffraction at a resolution of three angstroms(1999).

Timothy C. Hall (US), Ronald K. Wepprich (US), Jeffrey W. Davies (US), Lewis G. Weathers (US), and Joseph S. Semancik (US) showed that the etiological agent of exocortis, an infectious disease of citrus trees, previously assumed to be caused by a virus, is in fact a viroid(2000).

Francis J. Tedesco (US), Robert W. Barton (US), and David H. Alpers (US) found a significant association between patients receiving clindamycin and the development of pseudomembraneous colitis (PMC)(2001).

John G. Bartlett (US), Te-Wen Chang (US), Marc Gurwith (US), Sherwood Leslie Gorbach (US), and Andrew B. Onderdonk (US) provided evidence that the etiological agent of pseudomembraneous colitis (PMC) is Clostridium difficile(2002). 

Ronald Berezney (US) and Donald S. Coffey (US) developed a technique for treating cells in such a way as to reveal what was called the nuclear matrix. Detergent, RNAases, DNAases, and concentrated salts were used(2003, 2004).

Monsanto Chemical Company introduced the herbicide glyphosate, a substituted glycine, for the control of perennial broadleaved weeds and grasses. ref

Friedrich G. Constabel (CA), Kuo Nan Kao (CA), Morris R. Michayluk (CA), Kutty K. Kartha (CA), and Oluf L. Gamborg (CA) discovered that polyethylene glycol is extremely efficient at promoting the fusion of cellular protoplasts(2005-2007).

Peter G. Shepherd (GB), B. Fraissignes (GB), W.A. Peet (GB) discussed a fermentation process designed for the production of single cell protein from hydrocarbons(2008).

Rolf Martin Zinkernagel (CH-US) and Peter Charles Doherty (AU-US) discovered how the immune system recognizes cells that must be eliminated because they have been infected by a virus(2009).

Jean David Rochaix (CH), Adrian Peter Bird (GB), Aimee Bakken (US), Debra J. Wolgemuth-Jarashow (US), Georgiana M. Jagiello (US), Ann S. Henderson (US), Robert W. Old (GB), Harold Garnet Callan (GB), Kenneth W. Gross (US), Lynn Golden (), Ulrich Schaefer (DE), Michael Rosbash (US), Manuel O. Diaz (UY-US), and Joseph Grafton Gall (US) performed experiments establishing that the appearance of the unusual lampbrush chromosomes probably represents a specialization for the intensive transcription of mRNAs, 5S rRNA, and tRNAs required for growth of the oocyte cytoplasm during diplotene(2010-2015).

Harold Garnet Callan (GB), Joseph Grafton Gall (US), and Celeste A. Berg (US) published the first physical maps of the Xenopus laevis lampbrush chromosomes(2016). 

J. J. Strange (GB), R. J. Kenworthy (GB), Adam J. Webb (GB), and C.M. Giles (GB) discovered Wka (Weeks), a new antigen in the Kell blood group system (also known as Kell-Cellano system)(2017).

Denis Parsons Burkitt (GB), Alec R. Walker (ZA), and Neil S. Painter (GB) became convinced that a diet high in roughage prevents many ailments. Their efforts encouraged scientists and the public to think differently about nutrition(2018).

Hans-Udo Schweikert (DE) and Jean D. Wilson (US) reported on the necessity of steroid hormones for normal hair development(2019, 2020).

Pernilla Lindahl (FR), Patricia Leary (FR), and Ion Gresser (FR) found that interferon preparations in the mouse enhanced the expression of histocompatibility antigens on thymocytes from mice of different ages, but of splenic lymphocytes only from young mice. Interferon did not alter the experession of the theta antigen of thymocytes or splenic lymphocytes(2021).

Pernilla Lindahl (FR), Ion Gresser (FR), Patricia Leary (FR), and Michael Tovey (FR) found that treatment of young and mature mice with potent preparations of interferon results in a marked enhancement of the expression of histocompatibility antigens on the surface of thymocytes and splenic lymphocytes(2022).

H. Robson MacDonald (CH), Howard D. Engers (CA), Jean-Charles Cerottini (CH), and K. Theodor Brunner (CH) generated mouse cytotoxic T lymphocytes (CTL) in unidirectional mixed leucocyte cultures (MLC) using normal C57BL/6 spleen cells as responding cells and irradiated DBA/2 spleen cells as stimulating cells(2023).

Michael J. Brownstein (US), Juan M. Saavedra (US), Julius Axelrod (US), Gary H. Zeman (US), and David O. Carpenter (US) were able to show the coexistence of several neurotransmitters in single identified neurons of Aplysia californica, the California sea slug(2024).

Tomas Hökfelt (SE), Olle Johanssen (SE), Ake Ljungdahl (SE), Jan M. Lundberg (SE), and Marianne Schultzberg (SE) demonstrated the coexistence of more than one neurotransmitter in single neurons within the mammalian brain(2025).

Kuzuo Fujikawa (US), Michael H. Coan (US), Mark E. Legaz (US), and Earl W. Davie (US) linked the intrinsic pathway with the extrinsic pathway of blood coagulation at the level of Stuart factor(2026).

Peter C. Elwood (GB), Archie L. Cochrane (GB), Michael L. Burr (GB), Peter M. Sweetnam (GB), G. Williams (GB), E. Welsby (GB), S. Janie Hughes (GB), and Ross Renton (GB) discovered that aspirin may be useful in the secondary prevention of mortality from myocardial infarction(2027).

The Steering Committee of the Physician’s Health Study Research Group (US) concluded that aspirin definitely reduces the risk of myocardial infarction but stated that the effect on cardiovascular morbidity remains inconclusive(2028).

Gian Franco Bottazzo (IT), Alejo Florin-Christensen (AR), Jim I. Mann (GB), Margaret Thorogood (GB), J. David Baum (GB), Deborah Doniach (CH-GB) suggested that an autoimmune factor may contribute to juvenile diabetes and that such autoimmune diabetes has a tendency to run in families and may be more likely to cause complications(2029, 2030). 

Yuet Wai Kan (CN-US), Andree-Marie Dozy (NL-US), John M. Taylor (US), Harold E. Varmus (US), Luan Eng Lie-Injo (US), J. Ganesan (), David Todd (CN), and Janice P. Holland (US) discovered that deletion of the gene for alpha-globin—a component of hemoglobin—causes alpha-thalassemia, a blood disorder that has a high incidence in people of Mediterranean and Asian descent(2031, 2032).

Yuet Wai Kan (CN-US), Mitchell S. Golbus (US), and Andree-Marie Dozy (NL-US) ushered in the era of human genetic testing when they used information about the missing alpha-globin gene to develop a DNA test to diagnose alpha-thalassemia in an unborn fetus(2033).

Yuet Wai Kan (CN-US), Andrée-Marie Dozy (NL-US) using restriction endonuclease mapping of the human globin genes revealed a genetic variation in a Hpa I recognition site about 5000 nucleotides from the 3' end of the beta-globin structural gene(2034, 2035).

E. Müller (CH), H.R. Marti (CH), J. Bach (CH), J.L. Michell (CH), C. Gasser (CH), John J. Hutton (US), and Robert R. Chilcote (US) reported cases of non-spherocytic hemolytic anemia caused by glucose-6-phosphate isomerase deficiency(2036, 2037).

William H. Sweet (US) and James G. Wepic (US) developed the most frequently used procedure for the treatment of trigeminal neuralgia (radiofrequency lesioning of the trigeminal ganglion)(2038).

Takuo Aoyagi (JP), Micho Kishi (JP), Kazuo Yamaguchi (JP), and Shinichi Watanabe (JP) invented the pulse oximeter to measure blood oxygen saturation. It is based on the equation they derived that makes it possible to compute arterial oxygen saturation without precalibration, independent of ear thickness, skin pigment, hemoglobin concentration, and light intensity(2039, 2040).

Eugene J. Van Scott (US) and Ruey J. Yu (US) introduced the use of alpha hydroxy acids to control keratinization(2041-2043). These substances are administered routinely by dermatologists, and they are an ingredient in countless antiaging products marketed by the cosmetics industry.

Susan P. Baker (US), Brian O'Neill (US), William Haddon, Jr. (US), and William B. Long (US) indicated that the Injury Severity Score represents an important step in solving the problem of summarizing injury severity, especially in patients with multiple trauma. The score is easily derived, and is based on a widely used injury classification system, the Abbreviated Injury Scale. Use of the Injury Severity Score facilitates comparison of the mortality experience of varied groups of trauma patients, thereby improving ability to evaluate care of the injured(2044).

William F. House (US) pioneered the development of cochlear implants(2045, 2046).

Robert L. Trivers (US) published on parent–offspring conflict and the genetics of offspring solicitation and parental response. ... genetic interests of parents and offspring(2047).

Marvin J. Allison (US), Alejandro Pezzia (PE), Ichiro Hasegawa (US), Enrique Gerszten (AR), Ronald F. Giffler (US), Dandl Mendoza (US), Harry P. Dalton (US) and Vincent A. Sawicki (US) presented evidence that an individual from the Huari culture in pre-columbian Peru exhibited an array of ailments at the time of his death (890-950 A.D.). Radiological diagnosis revealed aspiration pneumonia which was possibly initiated during the course of a systemic salmonellosis such as typhoid fever. His health was further jeopardized by the presence of two helminthic infestations, hookworm and trichinosis(2048-2050).

Richard Charles Lewontin (US) in his book, The Genetic Basis of Evolutionary Change, promotes the study of protein polymorphisms to measure the amount of genetic variation present in natural populations. The methods described here make possible studies of population genetics in natural populations of animals on a large scale(2051).


“For him [the scientist], truth is so seldom the sudden light that shows new order and beauty; more often, truth is the uncharted rock that sinks the ship in the dark.” Sir John Warcup Cornforth(2052). Speech given in 1975.

Sir John Warcup Cornforth (AU-GB) for his work on the stereochemistry of enzyme-catalyzed reactions and Vladimir Prelog (BA-CH) for his research into the stereochemistry of organic molecules and reactions shared the Nobel Prize in Chemistry.

David Baltimore (US), Renato Dulbecco (IT-US) and Howard Martin Temin (US) were awarded the Nobel Prize in Physiology or Medicine for their discoveries concerning the interaction between tumor viruses and the genetic material of the cell.

Benoit B. Mandelbrot (PL-FR-US) originated and named fractal geometry. He emphasized the use of this geometry to model many "rough" phenomena in the real world. Natural fractals include the shapes of mountains, coastlines, and river basins; the structures of plants, blood vessels, and lungs; the clustering of galaxies; and Brownian motion. Fractals are found in human pursuits, such a music, painting, architecture, and stock market prices. Mandelbrot believed that fractals, far from being unnatural, were in many ways more intuitive and natural than the artificially smooth objects of traditional Euclidean geometry(2053-2055).

Michel M. Ter-Pogossian (US), Michael E. Phelps (US), Edward J. Hoffman (US), and Nizar A. Mullani (US) developed the first positron-transmission-transaxial (PET) scanner(2056).

Patrick H. O’Farrell (US) devised a two-dimensional gel system for analyzing protein mixtures in which SDS polyacrylamide-gel electrophoresis is combined with separation according to isoelectric point(2057).

Peter Nigel Tripp Unwin (GB), Richard Henderson (GB), Andrew D. McLachlan (GB), Gebhard F.X. Schertler (AT), Joyce M. Baldwin (GB), Thomas A. Ceska (GB), Friedrich Zemlin (DE), Erich Beckmann (DE), and Kenneth H. Downing (US) used computer-based reconstruction from electron micrographs of unstained samples to determined the structure of bacteriorhodopsin. They established that this protein contains seven alpha-helical rods spanning the membrane(2058-2064).

Mats Hamburg (SE), Jan Svensson (SE), and Bengt Ingemar Samuelsson (SE) were the first to explain the physiological and pathological roles for the prostaglandin-thromboxane system in man(2065).

Elizabeth A. Carswell (US), Lloyd John Old (US), Robert L. Kassel (US), Saul Green (US), Nancy C. Fiore (US), and Barbara D. Williamson (US) coined the phrase tumor necrosis factor (TNF) and defined it as “an activity produced by activated macrophages that led to hemorrhagic necrosis of transplanted tumors in mice and killed certain transformed cell lines in culture”(2066).

Diane Pennica (US), Glenn E. Nedwin (US), Joel S. Hayflick (US), Peter H. Seeburg (US), Rik M. Derynck (US), Michael A. Palladino (US), William Jack Kohr (US), Bharat B. Aggarwal (US), and David VanNorman Goeddel (US) purified tumor necrosis factor (TNF) to homogeneity, and identified cDNA clones for human TNF(2067).

Diane Pennica (US), Joel S. Hayflick (US), Timothy S. Bringman (US), Michael A. Palladino (US), and David VanNorman Goeddel (US) cloned cDNA for murine tumor necrosis factor and expressed it in Escherichia coli(2068). 

Bruce A. Beutler (US), David A. Greenwald (US), Jeffrey D. Hulmes (US), May Chang (US), Yu-Ching E. Pan (US), John C. Mathison (US), Richard Joel Ulevitch (US), and Anthony Cerami (US) reported a high degree of homology between the N-terminal sequence of mouse cachectin and the N-terminal sequence of human tumor necrosis factor (TNF). Purified cachectin also possesses potent TNF activity in vitro. Evidence strongly suggests that cachectin and tumor necrosis factor (TNF) activities in mice are attributable to a single protein, which modulates the metabolic activities of normal as well as neoplastic cells through interaction with specific high-affinity receptors(2069).

Bruce A. Beutler (US), John R. Mahoney, Jr. (US), Nguyen Le Trang (US), Phillip H. Pekala (US), and Anthony Cerami (US) purified cachectin. The isolated protein has an isoelectric point of 4.7 and a subunit molecular weight of 17,000(2070).

Kevin J. Tracey (US), Bruce A. Beutler (US), Stephen F. Lowry (US), James P. Merryweather (US), Stephen D. Wolpe (US), Ian W. Milsark (US), Robert J. Hariri (US), Thomas J. Fahey, 3rd (US), Alessandro Zentella (US), James D. Albert (US), G. Tom Shires (US), and Anthony Cerami (US) infused recombinant human cachectin (tumor necrosis factor) into rats in an effort to determine whether cachectin, by itself, can elicit the derangements of host physiology caused by administration of endotoxin. When administered in quantities similar to those produced endogenously in response to endotoxin, cachectin causes hypotension, metabolic acidosis, hemoconcentration, and death within minutes to hours, as a result of respiratory arrest. Hyperglycemia and hyperkalemia were also observed after infusion. At necropsy, diffuse pulmonary inflammation and hemorrhage were apparent on gross and histopathologic examination, along with ischemic and hemorrhagic lesions of the gastrointestinal tract, and acute renal tubular necrosis. Thus, it appears that a single protein mediator (cachectin) is capable of inducing many of the deleterious effects of endotoxin(2071).

Robert H. Waldmann (US), John W. Rebuck (US), Hidehiko Saito (US), Joseph P. Abraham (US), June Caldwell (US), and Oscar D. Ratnoff (US) discovered the previously unrecognized human blood coagulation factor they named Fitzgerald factor(2072, 2073). Fitzgerald factor, Williams trait, Fleaujeac trait and Reid trait were all later determined to be high-molecular-weight kininogen.

Claude Vézina (CA), Alicia Kudelski (CA), Surenda Nath Sehgal (IN-CA), and Harold Baker (CA) found that Streptomyces hygroscopicus, a bacterial species indigenous to the soil of Rapa Nui (Easter Island), produces rapamycin (sirolimus, Rapamune), a potent immunosuppressive antibiotic, with cytotoxic properties(2074, 2075).

R.R. Martel (CA), J. Klicius (CA), S. Galet (CA) reported that rapamycin, a new antifungal antibiotic, was found to inhibit the immune response in rats(2076).

D.C. Neil Swindells (CA), Peter S. White (CA), and John A. Findlay (CA) used spectroscopic and x-ray crystallographic analysis to determine the structure of the antibiotic rapamycin(2077, 2078).

Kyriacos Costa Nicolaou (CY-US), Tushar K. Chakraborty (IN), Anthony D. Piscopio (US), Nobuto Minowa (JP), Peter Bertinato (US), and Kazunori Koide (US) carried out the total synthesis of the antibiotic rapamycin(2079-2081).

Eric J. Brown (US), Mark W. Albers (US), Tae Bun Shin (US), Kazuo Ichikawa (US), Curtis T. Keith (US), William S. Lane (US), Stuart Lee Schreiber (US), David Domingo Sabatini (US), Hediye Erdjument-Bromage (US), Mary Lui (US), Paul Tempst (US), and Solomon Halbert Snyder (US) found that the FKBP12-rapamycin complex binds to FRAP, a protein kinase in mammalian cells. This leads to immunosuppression(2082, 2083). Rapamycin is an immunophilin (a soluble, intracellular molecule which binds a powerful and specific immunosuppressant).

Laura Beretta (FR), Ann-Claude Gingras (CA), Yuri V. Svitkin (CA), Michael N. Hall (CH), and Nahum Sonenberg (CA) found that the immunosuppressant drug rapamycin blocks progression of the cell cycle at the G1 phase in mammalian cells and yeast by inhibiting cap-dependent, but not cap-independent, translation in NIH 3T3 cells. This inhibition is causally related to the dephosphorylation and consequent activation of 4E-BP1, a protein recently identified as a repressor of the cap-binding protein, eIF-4E, function(2084).

Breck Byers (US) and Loretta Goetsch (US) provided a largely accurate description of the structure of the spindle-pole body (SPB) and its changes during the life cycle, considerable detail about the organization and behavior of the spindle microtubules (sMTs), the first descriptions of the cytoplasmic microtubules (cMTs) and their behavior during the life cycle, and the first views of the septin-associated "neck filaments"(2085).

Barbara F. Sloat (US), Alison E.M. Adams (US), and John R. Pringle (US) found that chitin is randomly destributed over the entire cell surface of Saccharomyces cerevisiae in growing unbedded cells. They suggested that the CDC24 gene product seems to be involved in selection of the budding site, formation of the chitin ring at that site, the subsequent localization of new cell wall growth to the budding site and the growing bud, and the balance between tip growth and uniform growth of the bud that leads to the normal cell shape(2086).

John V. Kilmartin (GB) and Alison E.M. Adams (US) found actin present in cytoplasmic cables and cortical patches, both of which were strikingly associated with regions of localized cell surface growth, both during the normal cell cycle and in various morphogenetic mutants(2087). This suggested that actin was involved in the polarized delivery of secretory vesicles during both bud growth and cytokinesis.

Charles W. Jacobs (US), Alison E.M. Adams (US), Paul J. Szaniszlo (US), and John R. Pringle (US) presented evidence that microtubules (cytoplasmic, intranuclear, or both) appear to be necessary for the migration and proper orientation of the nucleus, as well as for spindle-pole body (SPB) separation, spindle function, and nuclear division. Cytoplasmic microtubules are apparently not essential for the establishment of cell polarity and the localization of cell-surface growth(2088).

Michael P. Rout (GB) and John V. Kilmartin (GB) defined at least three components of the spindle-pole body (SPB) and spindle in Saccharomyces cerevisiae. Two of the components were localized exclusively to the SPB region, and the other (a 90 k-D component) was localized both to the SPB region and to particulate dots in short spindles. The 90-kD component was also found in an inner nuclear layer close to where spindle microtubules emerge. This work provided a preliminary molecular map of the spindle-pole body (SPB) which pointed the way to the corresponding genes to be isolated(2089).

John Chant (US) and Ira Herskowitz (US), using Saccharomyces cerevisiae, identified four genes, BUD1-BUD4, necessary for the axial pattern of bud formation by isolating mutants of alpha cells that do not exhibit this pattern. These observations indicate the existence of a basal budding pattern, requiring no BUD products, that is random; BUD1 and BUD2 act on this basal pattern to create the bipolar pattern; the further action of BUD3 and BUD4 leads to the axial pattern. These studies thus identify a set of gene products that directs cell morphogenesis to a genetically programmed site(2090).

Daniel Julio Lew (US) and Steven I. Reed (US), in Saccharomyces cerevisiae, found that in the case of pre-bud site assembly following START (see below), the actin rearrangement could be triggered by Cln/Cdc28 activation in the absence of de novo protein synthesis, suggesting that the kinase may directly phosphorylate substrates (such as actin-binding proteins) that regulate actin distribution in cells(2091). Analysis of cell cycle regulation in the budding yeast Saccharomyces cerevisiae had shown that a central regulatory protein kinase, Cdc28, undergoes changes in activity through the cell cycle by associating with distinct groups of cyclins that accumulate at different times. The various cyclin/Cdc28 complexes control different aspects of cell cycle progression, including the commitment step known as START and mitosis.

Harvey I. Cantor (US) and Edward Arthur Boyse (US) described the cooperation between subclasses of Ly+ cells in the generation of killer cell activity(2092, 2093).

At the Asilomar Conference Center near Monterey, California more than 100 internationally respected molecular biologists met and voluntarily agreed to restrict cloning of DNA to organisms that had been specifically genetically disabled so that they would not grow well outside of the test tube. Government guidelines followed in 1976 but were relaxed in 1979 when cloning of cancer genes began(2094-2096).

The National Institutes of Health issued guidelines for the conduct of NIH supported research using recombinant DNA technology. The guidelines define physical and biological containment levels for research(2097).

Hiroaki Sawai (JP) and Leslie Eleazer Orgel (GB-US) showed that RNA can replicate without RNA-replicase and that zinc aids this replication(2098).

Argiris Efstratiadis (GR-US), Thomas Peter Maniatis (US), Fotis Constantine Kafatos (DE), Andrea Jeffrey (US), and John N. Vournakis (US) optimized conditions for synthesis and characterization of full-lenght single-stranded cDNA molecules from globin mRNAs using reverse transcriptase(2099).

Theresa N.H. Lee (US) and Daniel Nathans (US) identified early and late genes of SV40 and demonstrated that they are transcribed in divergent directions(2100).

Melanie I. Oakes (US), Michael W. Clark (US), Eric Henderson (US), Andrew Scheinman (US), T. Atha (US), Anna Marie A. Aguinaldo (US), Lawrence Kahan (US), G. Shankweiler (US), James A. Lake (US), Georg Stöffler (AT), Gilbert W. Tischendorf (DE), Heinz Zeichhardt (DE), Reinhard Luhrmann (DE), Marina Stöffler-Meilicke (DE), Harry F. Noller, Jr. (US), Seth Stern (US), Gloria M. Culver (US), Gabriele M. Heilek (US), Simpson Joseph (US), Bryn Weiser (US), Walter E. Hill (US), Anchalee Tassanakajohn (US), Dimitri M. Graifer (RU), Alexander A. Malygin (RU), Natalia B. Matasova (RU), Dmitri A. Mundus (RU), Marina A. Zenkova (RU), Galina G. Karpova (RU), Peter B. Moore (US), Albert E. Dahlberg (US), James E. Dahlberg (US), Michael J.R. Stark (GB), Richard J. Gregory (US), Richard L. Gourse (US), David L. Thurlow (US), Robert A. Zimmerman (DE), Christian W. Zwieb (DE), Carola Glotz (DE), Piotr Gornicki (US), Barbara Greuer (DE), Philip Mitchell (DE), Monika Osswald (DE), Jutta Rinke-Appel (DE), Dierk Schuler (DE), Katrin Stade (DE), and Richard L.C. Brimacombe (DE) were some of the pioneers in discovering where various proteins and rRNA molecules are located within the ribosome(2101-2116).

Marcia J. Ensinger (US), Scott A. Martin (US), Enzo Paoletti (US), and Bernard Moss (US) elucidated the three enzyme pathway by which eukaryotic and viral mRNA receives a 5’ cap. Their experimental subject was vaccinia virus(2117). The cap structure consists of 7-methyl guanosine linked via an inverted 5’-5’ triphosphate bridge to the initiating nucleoside of the transcript.

Richard D. Kolodner (US) and Krishna K. Tewari (US) demonstrated that the mechanism of DNA replication in chloroplasts is somewhat different from DNA replication in both the mitochondrium and in the eukaryotic nucleus. Here the replication begins at two points of origin, runs in opposite directions around the circle (each going 5’ to 3’) until completion(2118).

Frederick Sanger (GB), Alan R. Coulson (GB), Steve Nicklen (GB), Gillian M. Air (GB), Barclay George Barrel (GB), Nigel L. Brown (GB), John C. Fiddes (GB), Clyde A. Hutchison III (US), Patrick M. Slocombe (GB), and Michael Smith (GB) developed the first method for sequencing long sections of DNA nucleotides(1771-1773, 2119, 2120).

Arthur D. Riggs (US), Robin Holliday (GB), and John E. Pugh (GB) suggested that DNA methylation might control gene expression during cellular differentiation or cancer progression by changing the affinity of sequence-specific DNA-binding proteins for their target sites(2121, 2122).

Peter A. Jones (US) and Shirley M. Taylor (US) introduced the use of cytidine analogues to prevent the methylation of cytosine residues in DNA, and directly linked changes in the patterns of methylation with changes in the differentiated state of the treated cells. The analogue 5-azacytidine was shown to be a potent inhibitor of DNA methylation(2123). It is now used routinely to reactivate genes that are silenced by methylation. It has also entered the clinic as a treatment for myelodysplastic syndrome.

Adrian Bird (GB), Mary Taggart (GB), Marianne Frommer (AU), Orlando J. Miller (US), and Donald Macleod (GB) characterized the small fraction of the mouse genome that is frequently cleaved by a methylation-sensitive restriction enzyme. These sequences, which would come to be known as CpG islands, are CpG-rich fragments with low or undetectable levels of methylation. The available literature indicated that CpG islands were typically located near the 5' ends of genes, and the authors predicted correctly that genes might be associated with “methylation-free zones near sequences of regulatory significance”(2124).

Xinsheng Nan (GB), Huck-Hui Ng (GB), Colin A. Johnson (GB), Carol D. Laherty (US), Bryan M. Turner (GB), Robert N. Eisenman (GB), Adrian Bird (GB), Peter L. Jones (US), Gert C. Jan Veenstra (US), Paul A. Wade (US), Danielle Vermaak (US), Stefan U. Kass (BE), Nicoletta Landsberger (IT), John Strouboulis (US), and Alan P. Wolffe (US) showed that the methyl-CpG-binding protein 2 (MeCP2) which had been shown to bind to methylated DNA and repress transcription, does so by recruiting a histone deacetylase complex that alters chromatin structure(2125, 2126).

David Baltimore (US) coined the term retrovirus(2127).

Antonio Garcia-Bellido (ES) named and described homeotic selector genes(2128). 

Edward B. Lewis (US) discovered while studying the bithorax gene complex (BX-C) of Drosophila melanogaster that wild-type and mutant segmentation patterns are consistent with an antero-posterior gradient in repressor concentration along the embryo and a proximo-distal gradient along the chromosome in the affinities for repressor of each gene's cis-regulatory element(2129). This feature, called spatial collinearity, would turn out to be a defining feature of both vertebrate and invertebrate homeotic genes. Lewis showed remarkable vision by arguing that the identity of an individual body segment is produced by the particular combination of BX-C genes, and that these were activated in response to an anterior-posterior gradient.

William J. McGinnis (US), Richard L. Garber (CH), Johannes Wirz (CH), Atsushi Kuroiwa (JP), Michael S. Levine (US), Ernst Hafen (CH), Walter Jakob Gehring (CH), Matthew P. Scott (CH), Amy J. Weiner (US), Andrés E. Carrasco (AR), Edward Michael De Robertis (UY-US), and John C.W. Shepherd (CH) discovered a 184-bp DNA base sequence common to many of the Drosophila melanogaster genes which determine the particular character of each body segment. They named this the homeobox sequence and discovered that it is common among many other metazoans. It was discovered that the homeobox sequence is translated into a 60-amino-acid DNA-binding motif — the homeodomain — by which homeobox (Hox) genes control transcription of target genes, i.e., all homeotic genes are genes for switching other genes on or off(2130-2134).

Alexandra L. Joyner (US), Roger V. Lebo (US), Yuet W. Kan (US), Robert Tjian (CN-US), David R. Cox (US), and Gail R. Martin (US) defined conserved homeobox genes in mouse and man(2135).

Urban Deutsch (DE), Gregory R. Dressler (DE), and Peter Gruss (DE) found paired box (Pax) genes in segmented structures of the mouse during embryonic development. Paired box (Pax) proteins are important in early animal development for the specification of specific tissues, as well as during epimorphic limb regeneration in animals capable of such(2136). 

Denis Duboule (FR) and Pascal Dollé (FR) showed by in situ hydridization that mouse and fly Hox clusters showed a similar spatial and functional organization. Not only did genes in vertebrate and invertebrate clusters have spatial collinearity, but they were expressed in a temporal order that matched their physical order on the chromosome (that is, they showed 'temporal collinearity'). In addition, fly Hox genes—which map to two adjacent clusters, BX-C and ANT-C—could, by and large, be matched up with genes at similar positions on each of the four paralogous vertebrate clusters(2137). This was confirmation of Lewis' belief that all homeotic genes are evolutionarily related.

Alfred Walz (CH) and Vincenzo Pirrotta (US), using lambda virus, demonstrated that in the absence of repressor the enzyme RNA polymerase binds tightly to, and protects from DNAase digestion, a 45-base-pair sequence that includes most of the repressor binding sites(2138).

Michael Gottlieb (US), Bernard David Davis (US), and Robert C. Thompson (US) discovered that ribosome initiation factor 3 (IF-3) acts as a dissociation factor for maintaining 30S and 50S subunits(2139).

Thomas Peter Maniatis (US), Andrea Jeffrey (US), and J. Hans van deSande (DE-CA) showed that small DNA fragments can be separated according to size on denaturing polyacrylamide gels with the electrophoretic mobilities of the single-stranded DNA fragments exhibiting a linear function of the logarithm of their chain lengths. They found it possible to separate DNA fragments that differ by only a single nucleotide(2140).

Thomas Peter Maniatis (US), Andrea Jeffrey (US), and Dennis G. Kleid (US) established the base sequence of most of the right operator in lambda virus(2141).

Thomas Peter Maniatis (US), Mark Steven Ptashne (US), Keith C. Backman (US), Dennis G. Kleid (US), Stuart M. Flashman (US), Andrea Jeffrey (US), and Russell Maurer (US) noted that both operators in lambda virus contain sequences of bases which are strikingly similar. Presumably they are the sites recognized by the repressor molecules(2142).

Cha Mer Wei (US), Bernard Moss (US), Yasuhiro Furuichi (JP), Maureen A. Morgan (US), Subbaratnam Muthukrishnan (US), and Aaron Jeffrey Shatkin (US) discovered that the messenger RNAs (mRNAs) of a DNA virus (vaccinia) and of a double stranded RNA virus (reovirus) possess at their 5’ termini the structure m7GpppGmpCp-(2143, 2144). This capping was subsequently found to be common in cells and to promote mRNA activity.

Errol C. Friedberg (US), Ann K. Ganesan (US), and Kenneth Minton (US) detected in crude extracts of Bacillus subtilis an N-glycosidase activity which catalyzes the release of free uracil from DNA of the subtilis phage PBS2. Phage DNA contains deoxyuridine instead of thymidine(2145).

Tomas Lindahl (SE) determined the precise mechanism of action of the uracil-specific enzyme. This discovery led to the recognition of a new class of repair enzymes, now called DNA glycolylases, and his discovery of base excision repair(2146, 2147). 

Zhigang Wang (US) and Dale W. Mosbaugh (US) found that the uracil-DNA glycosylase inhibitor gene of bacteriophage PBS2 encodes a binding protein specific for uracil-DNA glycosylase(2148).

Robert W. Old (GB), Kenneth Murray (GB), and Gerard Roizes (GB) determined the recognition sequence of restriction endonuclease III from Haemophilus influenzae(2149).

Miroslav Radman (BE), Evelyn M. Witkin (US), Martine Defais (BE), Perrine Caillet-Fauquet (BE), and Maurice S. Fox (US) first suggested the SOS DNA repair mechanism in bacteria(2150-2154).

Edwin M. Southern (GB) developed a technique for identifying specific DNA fragments following their separation by agarose gel electrophoresis. The technique is called the Southern blot method (2155).

Roger D. Sloboda (US), Stephen A. Rudolph (US), Joel L. Rosenbaum (US), and Paul Greengard (US) discovered microtubule-associated proteins (MAPs). These are proteins which stabilize microtubules and reduce their tendency to separate into individual heterodimers(2156).

Murray D. Weingarten (US), Arthur H. Lockwood (US), Shu-Ying Hwo (US), and Marc Wallace Kirschner (US) isolated a protein, tau, which appears to act on the 6S tubulin dimer, activating it for polymerization. The unique ability of tau to restore the normal features of in vitro microtubule assembly makes it likely that tau is a major regulator of microtubule formation in cells(2157).

Thomas P. Stossel (US) and John H. Hartwig (US) found that actin and myosin of rabbit pulmonary macrophages are influenced by two other proteins. A protein cofactor is required for the actin activation of macrophage myosin Mg2 ATPase activity, and a high molecular weight actin-binding protein aggregates actin filaments(2158).

Thomas P. Stossel (US) and John H. Hartwig (US) provided findings suggesting that the actin-binding protein initiates a cooperative interaction of contractile proteins to generate cytoplasmic gelation, and that phagocytosis influences the behavior of the actin-binding protein(2159).

Stephen Meier (US) and Elizabeth D. Hay (US)  undertook to determine whether or not physical contact with the substratum is essential for the stimulatory effect of extracellular matrix (ECM) on corneal epithelial collagen synthesis. A role of cell surface-ECM interaction in the stimulation of extracellular matrix (ECM) synthesis by the reacting tissue(2160). 

Daniel Israel Arnon (PL-US) and Richard K. Chain (US) found that under aerobic conditions, in the presence of ferredoxin and NADP, cyclic photophosphorylation operated concurrently with noncyclic photophosphorylation, producing an ATP: NADPH ratio of about 1.5. An unexpected discovery was that the operation of cyclic photophosphorylation by itself was also regulated by a back reaction of NADPH and ferredoxin with two components of chloroplast membranes, component C550 and cytochrome b559(2161).

Henry H. Hagedorn (US), John D. O'Connor (US), Morton S. Fuchs (US), Becky A. Sage (US), Dorothy A. Schlaeger (US), and M.K. Bohm (US) were the first to report that ecdysone (a molting hormone) stimulates vitellogenin synthesis in the fat body of an insect. Their subject was the mosquito(2162). Vitellogenins are proteins synthesized outside the ovaries that become the major egg yolk proteins. 

Richard P. Creagan (US), Suzie Chen (US), and Francis Hugh Ruddle (US) located the gene for diphtheria toxin receptor on human chromosome 5 in human cells in mouse-human somatic cell hybrids. This work also indicated that entry of toxin into cells seems to be a two-step process involving: (1) binding of toxin to the cell surface, and (2) endocytotic uptake of toxin(2163).

Upon attempting to figure out why opium affected people the way that it does, scientists, 

Solomon H. Synder and Candace B. Pert at Johns Hopkins University School of Medicine, Lars Tereniun of the University of Uppsala, and Eric J. Simon of the New York University School of Medicine discovered the receptor-labeling technique and stumbled upon the idea of the opiate receptor in the brain.

In nineteen seventy-five, John Hughes and Hans W. Kosterlitz of the University of Aberdeen managed to isolate peptides found occurring naturally within the brain. These peptides were called endorphins, meaning morphine from within, and were found to have pain reducing effects

Carl R. Woese (US), George E. Fox (US), Kenneth R. Pechman (US), Lawrence Zablen (US), Tsuneko Uchida (JP), Linda Bonen (US), Bobby J. Lewis (US), David Stahl (US) and Linda J. Magrum (US) pioneered the analysis of ribosomal RNAs as a means of identifying organisms and inferring their natural relationships. This is possible because these molecules are universally distributed, constant in function, slow to change in sequence and easily manipulated. Their examination of many bacteria suggested that the methanogens are older than any other bacterial group. Methanogenic metabolism (the reduction of carbon dioxide) is ideally suited to the kind of atmosphere thought to have existed on the primitive earth. These methanogens were named Archaebacteria (Archaea) to emphasize that they were the dominant ones in the primeval biosphere. This work showed that the prokaryotes are composed of two distinct groups: the Bacteria and the Archaea. In the 1977 article the tree of life was redrawn with three domains, Bacteria, Archaea and Eukarya(2164-2167).

Carl R. Woese (US) proposed that the halophilic archaebacteria (Archaea) are a group of aerobic or microaerophilic organisms that evolved from a strictly anaerobic and nonhalophilic methanogen ancestor. Woese also constructed a trifurcated, unrooted, universal evolutionary tree in which all known organisms can be grouped in one of three major lineages: eubacteria (Bacteria), the archaebacteria (Archaea), and the eukaryotic (Eucarya) nucleocytoplasm. This is often referred to simply as the three kingdom scheme(2168).

Carl R. Woese (US), Otto Kandler (US), and Mark L. Wheelis (US), based primarily on ribosomal RNA (rRNA) comparisons, proposed that all biological diversity falls into three primary groupings, or domains: Archaea (formerly archaebacteria), Bacteria (eubacteria), and Eucarya (eukaryotes)(2169). 

Georges Jean Franz Köhler (DE), César Milstein (AR-GB) introduced the methodology for generating monoclonal antibodies(2170, 2171).

Knud E. Mogensen (FI), Liisa Pyhälä (FI), Kari Cantell (FI) produced antibodies to human leucocyte interferon(2172).

Shlomo Z. Ben-Sasson (US), William E. Paul (US), Ethan M. Shevach (US), and Ira Green (US) obtained specific selection of antigen-responsive guinea pig peritoneal exudate lymphocytes (PELs) using a selective culture procedure. These selected cells were largely T lymphocytes and could be maintained in culture(2173).

Pawel Kisielow (PL), John A. Hirst (US), Hiroshi Shiku (US), Peter C.L. Beverly (GB), Michael K. Hoffmann (US), Edward A. Boyse (US), and Herbert F. Oettgen (US) reported experiments with mice showing that antisera to different Ly alloantigens can identify functionally-distinct subpopulations of thymus-derived lymphocytes (T cells)(2174).

Erik Svedmyr (SE) found that in vitro he could induce up to 4 months of long-term maintenance of human T cells by repeated exposure to the same stimulator cells(2175).

Gunther Dennert (US) and Margaret De Rose (US) found that BALB/c (H-2d) thymus derived lymphocytes sensitized to C57BL/6 (H-2b) alloantigens could be propagated in vitro for over 9 months. These T lymphocytes are specifically cytotoxic to H-2b target cells but are stimulated to proliferate by both H-2b and H-2k spleen cells. This indicates that for these selected cells the antigen requirements for cell proliferation are different from those for cell-mediated cytotoxicity(2176).

Jan Rosing (NL), Edward Charles Slater (AU-GB), David A. Harris (NL), and A. Kemp, Jr. (NL) found that the CF1 unit of chloroplasts and the F1 unit of mitochondria have ADP and ATP firmly bound to them(2177).

George Emil Palade (RO-US), Alan M. Tartakoff (US), James D. Jamieson (US), and George A. Scheele (US) used pulses of radioactive amino acids to demonstrate that proteins synthesized on the endoplasmin reticulum typically move from there to the Golgi apparatus and, depending on the protein, to the cell surface or into the cytoplasm(2178, 2179).

Pierre Oudet (FR), R. Douglas Carlson (US), Christopher L.F. Woodcock (US), Ling-Ling Y. Frado (US), Christopher L. Hatch (US), Luigi Ricciardiello (US), Donald E. Olins (US), Maria Gross-Bellard (FR), Pierre M. Chambon (FR), and Jack D. Griffith (US) showed that chromatin fibers occur as linear arrays of spherical particles, about 100 A° in diameter, connecting apparently naked strands of DNA(2180-2183).

Alexander Tzagoloff (US), Anna Akai (US), Richard B. Needleman (US), and George Zulch (US) isolated mit- mutants (mit = mitochondrial) with single and multiple deficiencies from Saccharomyces cerevisiae.   

Kyung June Kwon-Chung (US) described sexual reproduction in the fungus Cryptococcus neoformans(2184).

Roy R. Gould (US) and Gary Guy Borisy (US) found that isolated pericentriolar material of eukaryotes (Eucarya), and not the centriole, acts as a center for microtubule assembly if supplied with tubulin under polymerizing conditions. It now appears that centrioles are merely passengers during astral spindle formation. Their distribution ensures that daughter cells receive centrioles and are capable of generating the 9+2 system of microtubules of flagella, which seems to be the primary or exclusive function of centrioles(2185-2187).

Taiji Nakae (US) and Hiroshi Nikaido (US) introduced the concept of pore-forming proteins (porins) in the outer membrane of gram-negative bacteria. These porins go a long way toward explaining the ability of low molecular weight hydrophilic nutrients to penetrate the outer membrane (2188). 

Carol Jones (US), Paul Wuthier (US), and Theodore Thomas Puck (US) placed the human lactic dehydrogenase gene and the AL gene on the same chromosome 11(2189).

Carol Jones (US), Fa-Ten Kao (US), B. Moore (US), David Patterson (US), and Theodore Thomas Puck (US) identified the AL gene’s product as a glycophorin(2190).

Peter F. Brumbaugh (US) and Mark R. Haussler (US) confirmed the discovery of a protein receptor that binds the active vitamin D metabolite (1,25-dihydroxyvitamin D3) to the nucleus of cells in the intestine(2191, 2192).

Walter Jakob Gehring (CH), Gerold Schubiger (US), Welcome W. Bender (US), Pierre Spierer (CH), David Swenson Hogness (US), Pierre M. Chambon (FR), Sean B. Carroll (US), Robert A. Laymon (US), Mark A. McCutcheon (US), Peter D. Riley (US), Matthew P. Scott (US), Amy J. Weiner (US), Valerie K.L. Merrill (US), F. Rudolf Turner (US), and Thomas C. Kaufman (US) analyzed three homeotic mutants of Drosophila melanogaster with respect to their time of expression, aristapedia (ssa and ssa-UCl) and Nasobemia (Ns) which involve antenna-leg transformations.

The DNA associated with homeotic genes of the bithorax complex was localized.

Sequence homology between the antennapedia, ultrabithorax, and fushi tarazu loci of Drosophila was noted and it was concluded that Dfd is a homeotic gene necessary for proper specification of both the embryonic and the adult head(2133, 2193-2196).

Peter N. Goodfellow (GB), Elizabeth A. Jones (GB), Veronica van Heyningen (GB), France Ellen Solomon (GB), Roger H. Kennet (GB), Martin Bobrow (GB), and Sir Walter Fred Bodmer (GB) located the gene for human ß2-microglobulin on chromosome 15(2197).

Richard P. Creagan (US), and Francis Hugh Ruddle (US) introduced the technique of screening panels of hybrid cell clones selected to provide a maximally informative representation of human chromosomes. This became the standard technique for determining synteny, the correlation of gene activity with the presence or absence of a specific chromosome in hybrid cells(2198).

Stephen J. Goss (GB) and Sir Henry Harris (AU-GB) used hybrids of rodent cells and lethally irradiated human cells to devise the first systematic method for determining the order of human genes along the chromosome and the distances between them(2199).

Michael Grunstein (US) and David Swenson Hogness (US) developed colony hybridization, a technique to transfer bacterial colonies to filters, lyse, and fix the DNA. Labeled probes of single stranded DNA, complementary to the fixed DNA, can be applied to determine the identity of the unknown bacterium(2200).

Philip John (GB) and F. Robert Whatley (GB) found evidence that the non-sulfur purple bacteria (Proteobacteria) are the closest contemporary bacterial relatives of mitochondria(2201).

Francois Rougeon (FR), Philippe Kourilsky (FR), and Bernard Mach (FR) were the first to insert an identifiable mammalian gene, rabbit ß-globin, into a plasmid(2202).

Dorothy E. Schumm (US) and Thomas E. Webb (US) found that export of ribonucleoprotein materials through nuclear pores requires an energy expenditure in the form of ATP or GTP(2203).

D. Michael Gill (US) and Carolyn A. King (GB) established that choleragen, the exotoxin of Vibrio cholerae, mimics the effects of hormones which activate the release of adenylate cyclase leading to the production of intracellular cyclic AMP (cAMP)(2204).

Dan Cassel (DE) and Thomas Pfeuffer (DE) presented evidence that choleragen stimulates G proteins to cause the ultimate release of cAMP(1428).

Guido Pontecorvo (IT-GB) was the first to fuse animal cells using polyethylene glycol(2205).

Joseph William Sanger (US) found actin present in the nucleoli, kinetochore and centriolar regions, and in the mitotic spindle of kangaroo rat (Dipodomys) cells. The specific localization of actin in chromosomal spindle fibers suggests an actin-myosin interaction as the force-producing mechanism for chromosomal movement(2206).

Joseph Kuc (US), Gary Shockley (US), and Karen Kearney (US) demonstrated that plants can be immunized against microbial diseases by using a restricted infection with fungi, bacteria, or viruses. Pathogens stopped by this method included fungi, local lesions and systemic viruses, fungal and bacterial wilts. Immunization was systemic and required a lag period. Immunization can be enhanced with booster inoculations(2207-2209).

According to the World Health Organization three-year-old Rahima Banu of Bangladesh was, on October 16, 1975, the last known case of smallpox in the world. This brought to a close a 10-year vaccination campaign costing approximately $83 million. Smallpox is considered by many medical experts to be the most devastating and feared pestilence in human history(2210).

William J. McAleer (US), Eugene B. Buynak (US), Robert E. Weibel (US), Victor M. Villarejos (US), Edgar M. Scattergood (US), Hermann E. Wasmuth (US), Arlene A. McLean (US), and Maurice Ralph Hilleman (US) developed measles, mumps and rubella virus vaccines prepared from virus produced by the unit process(2211).

Charles P. Romaine (US) and Ralph K. Horst (US) identified the etiologic agent of chrysanthemum chlorotic mottle as a viroid(2212).

Yvonne E. Cossart (AU-GB), Anne M. Field (GB), B. Cant (GB), and D. Widdows (GB) demonstrated Parvovirus-like particles in human sera(2213).

Yvonne E. Cossart (AU) identified Parvovirus B19 as the etiological agent of slapped cheek, erythema infectiosum or fifth disease (there were six childhood rashes recognized at the turn of the century and this was number five)(2214).

Douglas M. Watts (US), Somsak Pantuwatana (TH), Thomas M. Yuill (US), Gene R. DeFoliart (US), Wayne H. Thompson (US), and Robert Paul Hanson (US), working with mosquito larvae, discovered the transovarial transmission of La Crosse virus (a bunyavirus)(2215).

Barry J. Beaty (US) and Wayne H. Thompson (US) grew the La Crosse virus in suckling mice(2216).

Richard P. Blakemore (US) discovered that some bacteria are sensitive to the geomagnetic field of the earth (2217). Later analysis revealed that these bacteria contain particles of magnetic iron oxide which behave as a compass.

Alexander Tomasz (US) and Susan Waks (US) found that most bacteria, including the pneumococcus, disintegrate as they die in a fascinating process that involves the dissolution of the cell wall. Penicillin takes advantage of this suicidal tendency by triggering lysis, a process that involves a bacterium’s own enzymes, which normally nip and tuck the wall into a perfect fit. Penicillin destroys the controls that restrain the enzymes, so the enzymes tear the cell wall to pieces(2218).

Ronald John Gibbons (US) and Johannes van Houte (US) state that the evolution of specific adhesion mechanisms by a wide spectrum of bacterial species furnishes evidence of the general importance of such interactions and may account, at least in part, for the specific distribution of organisms in different habitats(2219).

Kenneth Gould (US), Carlos H. Ramirez-Ronda (PR), Randall K. Holmes (US), and Jay P. Sanford (US) documented the significance of bacterial adhesion in the pathogenesis of streptococcal endocarditis (2220).

George A.M. Cross (US) characterized the glycoprotein surface coat of Trypanosoma brucei(2221).

Kamla K. Pandey (NZ) used irradiated pollen of tobacco (Nicotiana tabacum) to realize interspecific crossings. One theory to explain this is that a high dose of ionizing irradiation "pulverizes" the generative nucleus to produce a mass of chromatin fragments. The generative nucleus then fails to divide and the fragmented nuclear material is discharged into the egg, with some of these fragments possibly being incorporated into the DNA of the stimulated egg nucleus (2222).

Anthony E. Butterworth (GB), Robert F. Sturrock (AU), Vaclav Houba (KE), Adel A.F. Mahmoud (US), Alan Sher (US), P.H. Rees (KE), John Rouben David (US), David Franks (US), Peter H. David (US), and Heinz G. Remold (US) demonstrated that schistosomules coated with IgG antibody attract and bind eosinophils that attack the parasites(2223-2225).

Elsa Bello-Reuss (US), Romulo E. Colindres (US), Enrique Pastoriza-Munoz (US), Robert A. Mueller (US), Daniel L. Trevino (US), and Carl W. Gottschalk (US) found by direct measurements that denervation of the kidney decreases sodium reabsorption by the proximal tubules and that stimulation of renal sympathetic nerves increases the rate of sodium reabsorption(2226, 2227).

Lyndall Molthan (US) and Carolyn M. Giles (US) discovered Yk-a (York), a new blood group antigen(2228).

George J. Miller (GB) and Norman E. Miller (GB) discovered the relationship between coronary heart disease and plasma levels of high-density lipoprotein. The body cholesterol pool increases with decreasing plasma-high-density-lipoprotein (HDL.) but is unrelated to the plasma concentrations of total cholesterol and other lipoproteins. They proposed that a reduction of plasma-HDL concentration may accelerate the development of atherosclerosis, and hence ischemic heart-disease by impairing the clearance of cholesterol from the arterial wall(2229).

Chulee Mitrakul (TH), Vinai Suvatte (TH), Chularatana Mahasandana (TH), Vichai Tamphaichitr (TH), and Soodsarkorn Tuchinda (TH) were the first to describe acquired platelet dysfunction with eosinophilia or nonthrombocytopenic purpura with eosinophilia. This acquired disorder presents with bleeding of unknown etiology associated with platelet dysfunction and eosinophilia(2230, 2231).

Joseph Leonard Goldstein (US) and Jean D. Wilson (US) reported that phenotypic sexual differentiation during embryogenesis is a complex process involving the action of at least 18 genes. These genes regulate gonadal differentiation, gonadal hormone formation, and in the male the cellular action of three necessary hormones, namely mullerian regression factor, testosterone, and dihydrotestosterone. Two androgens testosterone and dihydrotestosterone have separate and specific roles in virilization of the male urogenital tract, testosterone stimulating wolffian duct development and dihydrotestosterone mediating development of the urogenital sinus and external genitalia. In the disorder familial incomplete male pseudohermphroditism, type 2, deficient dihydrotestosterone formation is associated with a selective failure of virilization of the urogenital sinus and external genitalia, whereas the wolffian duct derivatives develop normally. On the other hand, in the testicular feminization syndrome there is a complete failure in the development of the male phenotype, indicating that the primary defect involves an abnormality in some biochemical step that is common to the action of both androgens(2232).

A. Malcolm R. Taylor (GB), David G. Harnden (GB), Colin F. Arlett (GB), Susan A. Harcourt (GB), Alan R. Lehmann (GB), S. Stevens (GB), and Bryn A. Bridges (GB) discovered that ataxia-telangiectasia cells are abnormally sensitive to being killed by X rays, an obversation suggesting a relationship between the disease and DNA repair(2233).

Carmel M. McConville (GB), Caroline J. Formstone (GB), D. Hernandez (GB), J.A. Thick (GB), and A. Malcolm R. Taylor (GB) used fine mapping of the human chromosome 11q22-23 region to localize the gene for ataxia telangiectasia to a 5cM region flanked by NCAM/DRD2 and STMY/CJ52.75, phi 2.22(2234).

James Edward Cleaver (US), Dirk Bootsma (DK), and Errol C. Friedberg (US) were the first to provide molecular evidence that DNA damage is a direct cause of cancer(2235).

Henry Jay Heimlich (US), Karol A. Hoffman (US), and Felix R. Canestri (US) noted that applying subdiaphragmatic compression has been used successful in saving victims of food-choking and drowning by expelling the asphyxiating bolus or aspirated water. Sudden elevation of the diaphragm compresses the lungs, which explosively forces air out through the trachea, ejecting the obstructing object(2236, 2237). This became known as the Heimlich maneuver.

Ronald Levy (IL), Esther Hurwitz (IL), Ruth Maron (IL), Ruth Arnon (IL), Michael Sela (IL), Meir Wilchek (IL), Yutaka Tsukada (JP), Rina Kashi (IL), Nozomu Hibi (JP), Akihiko Hara (JP), and Hidematsu Hirai (JP) found that immunotargeting could focus the supply of a drug exclusively to a cancer area. They bound daunomycin and adriamycin via a dextran bridge to antibodies against antigens of leukaemia, lymphoma, and plasmacytoma cells. They showed that these are effective as "guided missiles" both in vitro and in vivo. Daunomycin linked to anti-tumor antibodies penetrated the cell membrane at a higher rate than daunomycin linked to dextran or to normal immunoglobulin. They could show a chemotherapeutic effect against hepatoma in the rat(2238-2240).

Norman C. Staub (US), Richard D. Bland (US), Kenneth L. Brigham (US), Robert Demling (US), A. John Erdmann III (US), and William C. Woolverton (US) noted that the majority of lung lymph in the sheep drains through a large caudal mediastinal lymph node. At a preliminary operation, they removed the systemic lymph contamination. They obtained lung lymph by cannulating the efferent duct of the node. They used a physiologic test in which they elevated systemic and pulmonary venous pressures separately to show that the origin of the lymph is from the lung. The overall success rate in obtaining lung lymph flow for periods longer than 1 week is less than 50%. Successful animals are excellent models in which to study net lung fluid and protein flow(2241).

James G. Rheinwald (US) and Howard Green (US) succeeded in developing a procedure by which large amounts of human skin could be cultured(2242, 2243).

Nathan Sternberg (IL), Y. Becker (IL), Jacob Golan (IL), and Nahum Ben-Hur (IL) developed tissue culture of human skin for grafting(2244).

G. Gregory Gallico, III (US), Nicholas E. O'Connor (US), Carolyn C. Compton (US), Olaniyi Kehinde (US), and Howard Green (US) developed the methodology for culturing epithelium as a skin substitute and applying it to patients with severely burned skin(2245, 2246).

Allan C. Wilson (NZ-US) and Mary-Claire King (US) surveyed protein and nucleic acid studies and found that the average human protein was more than 99% identical to its chimpanzee counterpart; the coarse DNA hybridization methods of the time showed that the average nucleic acid sequence was almost as similar. They concluded, humans and chimpanzees were genetically as similar as sibling species of other organisms, such as fruit flies or mice(2247, 2248).

Jorge J. Yunis (US) and Om Prakash (US) performed a comparative analysis of high-resolution chromosomes from orangutan, gorilla, chimpanzee, and man. The results suggested that 18 of 23 pairs of chromosomes of modern man are virtually identical to those of our "common hominoid ancestor", with the remaining pairs slightly different. From this lineage, gorilla separated fist, and three major chromosomal rearrangements presumably occurred in a progenitor of chimpanzee and man before the final divergence of these two species. A precursor of the hominoid ancestor and orangutan is also assumed(2249).

Edward Osborne Wilson (US) wrote Sociobiology: The New Synthesis, in which he analyzes social behaviors at all phylogenetic levels(2250).

Colin Groves (AU) and Vratislav Mazák (CZ) proposed the name Homo ergaster (man the workman). The type specimen for ergaster is KNM-ER 992 (2251).


"Je cherche à comprendre" [I try to understand] Jacques Lucien Monod(2252). Agnes Ullmann (letter of Nov. 21, 1994 to Benno Müller-Hill) reports that Monod said this sentence to his doctor, Gerard Mantoux, near the time of Monod's death in 1976.

“In all human affairs … there is a single dominant factor—time. To make sense of the present state of science, we need to know how it got like that: we cannot avoid an historical account …. To extrapolate into the future we must look backwards a little into the past.” John M. Ziman(2253).

“We are survival machines—robot vehicles blindly programmed to preserve the selfish molecules known as genes. This is a truth that still fills me with astonishment.” Clinton Richard Dawkins(2254).

Baruch Samuel Blumberg (US) and Daniel Carleton Gajdusek (US) were awarded the Nobel Prize in Physiology or Medicine for their discoveries concerning new mechanisms for the origin and dissemination of infectious diseases.

Gilbert Stork (US), Stanley Raucher (US), Takashi Takahashi (US), Isao Kawamoto (US), and Toshio Suzuki (US) synthesized the hormones prostaglandin A2 (PGA2) and prostaglandin F2a (PGF2a)(2255, 2256).

Ursula Dähn (DE), Hanspaul Hagenmaier (DE), Hildegard Hohne (DE), Wilfried A. Konig (DE), G. Wolf (DE), and Hans Zahner (DE) were the first to isolate the antifungal antibiotic nikkomycin. It is produced by Streptomyces tendae(2257).

Akira Endo (JP), in 1976, became the first to discover a statin (compactin). These are drugs (3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors) which are important in the pharmacologic management of hypercholesterolemia(2258).

Michael Botchan (US), William C. Topp (US), and Joseph Frank Sambrook (GB-US-AU) provided detailed descriptions of the organization of viral DNA sequences integrated into the genomes of an isogenic set of 11 rat cell lines transformed by simian virus 40. The junctions between viral and cellular sequences map at different places on the viral genome(2259). They speculated that integration was a cellular process that might operate on any foreign DNA. It is now known that integration of SV40 DNA is the result of cellular mechanisms that evolved to repair damaged chromosomal DNA and that randomly broken viral DNA is joined together and linked to the chromosome to eliminate free ends.

Richard Olding Hynes (GB-US), Antonia T. Destree (US), Vivien Mautner (US), Kenneth D. Noonan (US), D.S. Lindberg (US), J.A. McClure (US), Jorma Keski-Oja (FI), Antti Vaheri (FI), Pentti Kuusela (FI), Erkki Ruoslahti (FI-US), and Eva Engvall (SE-US), identified the extracellular glycoprotein fibronectin (LETS protein or fibroblast surface antigen)(2260-2263).

Jorma Keski-Oja (FI), Antti Vaheri (FI), and Erkki Ruoslahti (FI) showed that cross-linking of a major fibroblast surface-associated glycoprotein (fibronectin) is catalyzed by blood coagulation factor XIII(2262).

Richard Olding Hynes (GB-US), Antonia T. Destree (US), Margaret E. Perkins (US), and Denisa D. Wagner (US) found that cell surface fibronectin is reduced in amount or absent on transformed cells and in many cases its loss correlates with acquisition of tumorigenicity and, in particular, metastatic ability(2264).

Erkki Ruoslahti (FI-US) found that cell-matrix interactions are important in development and neoplasia(2265).

Michael D. Pierschbacher (US), Edward G. Hayman (US), and Erkki Ruoslahti (FI-US) showed that the interaction of fibronectin with cells is restricted to a defined portion of the fibronectin molecule and is independent of the direct involvement of the known affinities toward other macromolecules(2266). Fibronectin is the best-characterized extracellular adhesive protein.

Michael D. Pierschbacher (US) and Erkki Ruoslahti (FI-US) reported that the ability of fibronectin to bind cells can be accounted for by the tetrapeptide L-arginyl-glycyl-L-aspartyl-L-serine, a sequence which is part of the cell attachment domain of fibronectin and present in at least five other proteins. This tetrapeptide may constitute a cellular recognition determinant common to several proteins(2267).

Jean E. Schwarzbauer (US), John W. Tamkun (US), Ihor R. Lemischka (US), and Richard Olding Hynes (US) found that three different fibronectin mRNAs arise by alternative splicing within the same coding region and are probably all encoded by a single gene(2268). In humans about 20 different messenger RNAs are produced, each encoding a somewhat different fibronectin subunit. This form of splicing allows a cell to produce the type of fibronectin most suitable for its needs at a particular time and place.

John W. Tamkun (US), Jean E. Schwarzbauer (US), and Richard Olding Hynes (GB-US) found that a single rat fibronectin gene generates three different mRNAs by alternative splicing of a complex exon(2269). 

John W. Tamkun (US), Douglas W. DeSimone (US), Deborah Fonda (US), Ramila S. Patel (US), Clayton Buck (US), Alan F. Horwitz (US), and Richard Olding Hynes (GB-US) reported the structure of integrin, a glycoprotein involved in the transmembrane linkage between fibronectin and actin(2270).

Charles French-Constant (GB), Livingston Van de Water (US), Harold F. Dvorak (US), and Richard Olding Hynes (GB-US) found that an embryonic pattern of fibronectin splicing reappears during wound healing in the adult rat(2271).

Kenneth B.M. Reid (GB) and Rodney Robert Porter (GB) discovered that the subunit composition and structure of subcomponent C1q of the first component of human complement is rich in repeats of the sequence —Gly—Gly—Pro— ordinarily seen in collagen. The authors proposed that these are the basis for a triple helix (such as exists in collagen itself), which binds three C1q subcomponents together into an overall trimeric structure(2272).

Rudolph L. Juliano (US), Victor Ling (CA), Paul G. Debenham (GB), Norbert Kartner (CA), Louis Siminovitch (CA), and John (Jack) R. Riordan (CA) discovered P-glycoprotein, which is encoded by the multidrug resistant gene (MDR)(2273-2275).

Stephen C. Hyde (GB), Paul Emsley (GB), Michael J. Hartshorn (GB), Michael M. Mimmack (GB), Uzi Gileadi (GB), Stephen R. Pearce (GB), Maurice P. Gallagher (GB), Deborah R. Gill (GB), Roderick E. Hubbard (GB), and Christopher F. Higgins (GB) found that P-glycoprotein is not only important clinically, as it confers multidrug resistance in many cancers, it also can protect the brain from poisonous substances. P-glycoprotein is the first protein discovered in humans that belongs to a group of membrane transport proteins called the ATP Binding Cassette (ABC) proteins. ABC is very important in maintaining normal cell functions. Mutations in this group of proteins cause many well known diseases. One example is the cystic fibrosis transmembrane regulator (CFTR), which is responsible for cystic fibrosis(2276).

Barbara M. F. Pearse (GB) identified and named clathrin (clathratus = lattice) as a unique protein associated with intracellular transfer of membrane by coated vesicles(2277).

Robert Palese Perry (US), James P. Calvet (US), and Thoru Pederson (US) determined that the genes for 5S rRNA lie outside the nucleolus in higher plant and animal cells, but 5.8S rRNA arises from processing of the pre-rRNA primary transcript and ends up base-paired with 28S rRNA in the nucleolus(2278, 2279).

Roger Charles Louis Guillemin (FR-US), Nicholas Ling (US), Roger Cecil Burgus (US), from a crude extract of porcine neurohypophysis-hypothalamus, isolated several peptides called endorphins which mimic opiads in a classical bioassay for morphine. The primary structure of alpha-endorphin is H-Tyr-Gly-Gly-Phe-Met-Thr-Ser-Glu-Lys-Ser-Gln-Thr-Pro-Leu-Val-Thr-OH(2280).

Artur Ruegger (CH), Max Kuhn (CH), Heinz Lichti (CH), Hans-Rudolf Loosli (CH), René Huguenin (CH), Charles Quiquerez (CH), and Albert von Wartburg (CH) discovered the antibiotic and immunosuppressive agent, cyclosporin A which is produced by Trichoderma polysporum(2281).

Alice Chien (US), David B. Edgar (US), and John M. Trela (US) discovered that the extreme thermophile, Thermus aquaticus, contained a DNA polymerase with a temperature optimum of 72°C. The enzyme is routinely used in biotechnology where it goes by the name Taq DNA polymerase(2282).

John J. Byrnes (US), Kathleen M. Downey (US), Vicky L. Black (US), and Antero G. So (US) discovered eukaryotic DNA polymerase delta. This enzyme has a 5’ to 3’ polymerizing ability and a 3’ to 5’exonuclease activity for proofreading(2283).

Francis Harry Compton Crick (GB), Sydney Brenner (ZA-GB), Sir Aaron Klug (ZA-GB), and George Pieczenik (US) proposed that the assignment of codons to particular amino acids was simply an historical accident. There being no special reasons why a particular codon stands for a given amino acid(2284).

Bart G. Barrell (GB), Gillian M. Air (US), and Clyde A. Hutchison III (US) discovered overlapping genes in bacteriophage phiX174(2285).

Argiris Efstratiadis (GR-US), Fotis Constantine Kafatos (DE), Allan M. Maxam (US), and Thomas Peter Maniatis (US) performed the in vitro synthesis of globin genes(2286).

Thomas Peter Maniatis (US), Sim Gek Kee (US), Argiris Efstratiadis (GR-US), Fotis Constantine Kafatos (DE), Richard M. Lawn (US), Edward F. Fritsch (US), Richard C. Parker (US), Geoffrey Blake (US), and Chris O’Connell (US) isolated and determined the nucleotide sequence of the gene which produces the human beta globin protein(2287-2289).

Terence H. Rabbitts (GB), Thomas Peter Maniatis (US), Sim Gek Kee (US), Argiris Efstratiadis (GR-US), and Fotis Constantine Kafatos (DE) made in vitro cDNA from the messenger RNA for beta-globin then cloned a full copy of the gene into bacteria(2287, 2290).

César Milstein (AR-GB), Leroy Edward Hood (US), William R. Gray (US), and Bob G. Sanders (US), and William J. Dreyer (US) concluded that each immunoglobulin chain is specified by two genes, a V gene and a C gene(2291, 2292). Although not quite correct they were very close.

Nobumichi Hozumi (CH), Susumu Tonegawa (US), Christine Brack (US), Minoru Hirama (US), Rita Lenhard-Schuller (US), Jonathan G. Seidman (US), Edward E. Max (US), Philip Leder (US), Hitoshi Sakano (US), Konrad Hüppi (US), Günther Heinrich (US), Philip W. Early (US), Henry V. Huang (US), Mark Davis (US), Kathryn Calame (US), Leroy Edward Hood (US), Nicholas M. Gough (US), Ora Bernard (US), Patricia J. Gearhart (US), Nelson D. Johnson (US), Richard Douglas (US), Erik Selsing (US), Ursula Beate Storb (US), Frederick Wayne Alt (US), David Baltimore (US), Wendy D. Cook (US), Stuart Rudikoff (US), Angela M. Giusti (US), Matthew Daniel Scharff (US), Daniel F. Bogenhagen (US), Charles Wood (US), Tim Manser (US), Shu Y. Huang (US), Malcolm L. Gefter (US), Claudine Schiff (FR), Michèle Milili (FR), and Michel Fougereau (FR) discovered how the diversity of antibodies produced by B cells of vertebrates could be explained by the recombination of a relatively small number of alleles. The intact linear code for the heavy chains of antibody molecules does not pre-exist in the fertilized egg, rather four sets of mini-genes located in widely separated parts of the nucleus combine in many different ways(2293-2307).

Nils Kaj Jerne (GB-DK) proposed the concept of the control of antibody synthesis by means of a network of idiotypes and anti-idiotypes(2308).

Klaus Radsak (DE), Karl-Werner Knopf (DE), Arthur Weissbach (US), Arthur Bolden (US), Guido Pedrali Noy (IT), Michiyuki Yamada (JP), William J. Adams, Jr. (US), and George F. Kalf (US) demonstrated that the DNA polymerase alpha of mitochondria is different from that in the nucleus because it can act as a polymerase in the 5’ to 3’ direction and as an exonuclease in the 3’ to 5’ direction(2309-2312).

Nancy B. Kinderman (US) and Arthur LaVelle (US) named and described coiled bodies as structures frequently attached to nucleoli in facial motor neurons of the golden hamster. These round-to-oval structures were seen at 15, 19, and 24 days post-natal and in the adult, both in normal neurons and in chromatolytic neurons which had been axotomized 4 days previously. With one exception, the coiled bodies were seen to be attached via fibrillar material to the nucleolar periphery(2313).

Kevin Struhl (US), John R. Cameron (US), and Ronald W. Davis (US) integrated genetic material from Saccharomyces cerevisiae into the lambda virus which was used as a vector to transfer the yeast material to Escherichia coli where it was expressed(2314). 

Louise Clarke (US) and John Anthony Carbon (US) sheared the total Escherichia coli genome into fragments of 8.5 X 106 dalton average size. These fragments were inserted into hybrid Col El plasmids constructed in vitro by the poly(dA•dT) connector method then used to transform a F+ recA E. coli strain (JA200) with transformants selected by resistance to colicin. Over 80 hybrid Col El-DNA (E. coli) plasmid-bearing clones were identified(2315).

Nguyen Van Cong (FR), Dominique Weil (FR), Catherine C. Finaz (FR), C. Cochet (FR), Regis Rebourcet (FR), Jan De Grouchy (FR), and Jean Frézal (FR) assigned the ABO-nail patella-adenylate kinase (ABO-Np-AK1) linkage group to chromosome 9 in man-hamster hybrids(2316). The ABO locus produces galactosyl transferase.

John T. Finch (GB) and Sir Aaron Klug (ZA-GB), using X ray diffraction analysis, proposed that nucleosomes coil into a structure of higher complexity which they called a solenoid. A string of solenoids forms the chromatin fiber(2317).

Brad W. Baer (US) and Roger D. Kornberg (US) described and defined the nucleosome(2318).

Ada L. Olins (US), Donald E. Olins (US), Hans Zentgraf (DE), Werner W. Franke (DE), Henri A. Levy (US), Richard C. Durfee (US), Stephen M. Margle (US), Ed P. Tinnel (US), Christopher L.F. Woodcock (US), Ling-Ling Y. Frado (US), Jerome B. Rattner (US-CA), and Joachim Frank (US) prepared electron photomicrographs of eukaryotic chromatin which suggested that it is organized into a string of spherical units called nucleosomes(2319-2323).

Sir Aaron Klug (ZA-GB), P. Jo G. Butler (GB), Roger D. Kornberg (US), John T. Finch (GB), Daniela Rhodes (GB), John Smith (GB), Dame Jean O. Thomas (GB), Ray S. Brown (US), Tim Richmond (US), Barbara Rushton (US), and Leonard C. Lutter (US) determined the location of the individual histone proteins within the core octomer of nucleosomes(2324-2327).

George Poste (US), Demetrios P. Papahadjopoulos (US), and William J. Vail (CA) discovered that macromolecules can be artificially delivered into cells by placing the macromolecules into unilamellar liposomes and then encapsulating the cells with these(2328).

Paul B. Lazarow (US) and Christian Rene de Duve (GB-BE-US) discovered that microbodies can carry out fatty acid oxidation(2329).

Archie R. Portis, Jr. (US) and Richard E. McCarty (US) found that the rate of phosphorylation in chloroplasts is critically dependent on magnitude of the pH gradient across the chloroplast’s membrane(2330).

Doris A. Morgan (US), Francis W. Ruscetti (US), and Robert Charles Gallo (US) showed that a cell-free supernatant fraction from phytohemagglutinin stimulated human peripheral lymphocytes could induce continuous proliferation of human T cells. It was called T cell growth factor (TCGF)(2331).

Lucien A. Aarden (CH), K. Theodor Brunner (CH), and Jean Charles Cerottini (CH) later agreed that a single class of molecules was responsible for activity in a number of in vitro immune response assay systems including the antibody response and further agreed that this molecule (TCGF), which could trigger T cell replication, should be referred to as interleukin-2 (IL-2)(2332).

Yadin Dudai (US), Yuh Nung Jan (US), Duncan Byers (US), William G. Quinn (US), and Seymour Benzer (US) discovered the dunce mutation in Drosophila. This mutation rendered its bearers incapable of learning simple tasks such as a certain smell is always followed by an electrical shock(2333). Other learning mutations were soon discovered in Drosophila.

James P. Hoeffler (US), Terry E. Meyer (US), Gerard Waeber (CH), and Joel F. Habener (US) localized the human CREB-327/341 gene to chromosome 2(2334).

Tim Tully (US), Thomas Preat (US), Susan C. Boynton (US), Maria Del Vecchio (US), and Josh Dubnau (US) removed the cyclic AMP response binding protein gene (CREB) from Drosophila resulting in a fly with an extremely short term memory. They also produced flies which learned very rapidly, i.e., with a photographic memory(2335, 2336).

Xiao-Ning Chen (US) and Julie R. Korenberg (US) used a cDNA probe for the mouse CREB binding protein gene to localize the gene CREBBP to human chromosome 16p13.3(2337). The protein product of this gene facilitates the functioning of the CREB-327/341 protein. The protein products of CREB-327/341 and CREBBP promote learning in humans.

Craig H. Bailey (US), Dusan Bartsch (US), and Eric R. Kandel (US) reported that these learning mutations resulted from molecular damage to a mechanism for making or responding to cyclic AMP(2338).

Michael S. Grotewiel (US), Christine D.O. Beck (US), Kwak Hang Wu (US), Xin-Ran Zhu (US), and Ronald L. Davis (US) discovered volado, a new memory mutant of Drosophila. The locus encodes two isoforms of a new alpha-integrin, a molecule that dynamically mediates cell adhesion and signal transduction. The volado gene is expressed preferentially in mushroom body cells, which are neurons known to mediate olfactory learning in insects. Volado proteins are concentrated in the mushroom body neuropil, brain areas that contain mushroom body processes in synaptic contact with other neurons. Volado mutants display impaired olfactory memories within 3 min of training, indicating that the integrin is required for short-term memory processes. Conditional expression of a volado transgene during adulthood rescues the memory impairment. This rescue of memory is reversible, fading over time along with expression of the transgene. Thus the volado integrin is essential for the physiological processes underlying memory. They proposed a model in which integrins act as dynamic regulators of synapse structure or the signaling events underlying short-term memory formation(2339).

Dominique Stehelin (FR), Ramareddy V. Guntaka (US), Harold Elliot Varmus (US), John Michael Bishop (US), and Peter Klaus Vogt (US) found that DNA related to the transforming gene(s) of avian sarcoma viruses is present in normal avian DNA(2340, 2341).

Peter H. Duesberg (DE-US), Lu-Hai Wang (US), Karen Beemon (US), Sadaaki Kawai (JP), Hidesaburo Hanafusa (JP) identified a cluster of three sarcoma gene (src)-specific oligonucleotides within the sarcoma virus RNA(2342). The src genes represent the first known oncogenes.

G. Steven Martin (US) was the first to identify src (sarcoma) genes(2343).

Gerald Maurice Edelman (US), Cheng-Ming Chuong (US), Warren J. Gallin (CA), Annie Delouvée (FR), Bruce A. Cunningham (US), and Jean-Paul Thiery (FR) developed the concept of what they called cell adhesion molecules (CAMs). These molecules were seen as important in adhesion and morphogenesis. It was realized that CAMs appear in a definite sequence of expression during embryogenesis and histiogenesis. Their appearance reflecting the formation of cell collectives and boundaries having morphological and functional significance(2344-2356).

Samuel J. Leibovich (US) and Russell Ross (US) discovered macrophage derived growth factor (MDGF), a potent mitogen(2357).

Janet M.D. Plate (US) found that following antigenic stimulation soluble factors are produced by T-helper cells which promote differentiation of committed cytotoxic T-killer cells into T-effector (T-killer) cells(2358).  

Saul Green (US), Areta Dobrjansky (US), Elizabeth A. Carswell (US), Robert L. Kassel (US), Lloyd J. Old (US), Nancy Fiore (US), and Morton K. Schwartz (US) achieved partial purification of a serum factor that causes necrosis of tumors (TNF)(2359).

Garth Lamb Nicolson (US) provided evidence that some transmembrane proteins and glycoproteins are held in a cluster by a protein which is joined to all of them on the inside of the membrane(2360).

William S. Bowers (US), Tomihisa Ohta (US), Jeanne S. Cleere (US), and Patricia A. Marsella (US) discovered precocene, an anti-juvenile hormone, in plants. It induces irreversible precocious metamorphosis and sterilization in some insects (such as grasshoppers and locusts) by suppressing the function of the corpora allata gland. which plays a major role in vitellogenin synthesis(2361).

Erwin Neher (DE) and Bert Sakmann (DE) recorded single-channel currents from membranes of denervated frog muscle fibers(2362).

Jorma Keski-Oja (FI), Deane F. Mosher (FI), and Antti Vaheri (FI) found that the cross-linking of fibroblast cell surface fibronectin by blood coagulation factor XIIIa (plasma protransglutaminase) requires highly specific enzyme-substrate and protein-protein interactions, and may be an important physiological reaction(2363). 

E. Donnall Thomas (US), David W. Golde (US), Robert E. Ramberg (US), George E. Sale (US), and Robert S. Sparkes (US) demonstrated that lung macrophages are derived from bone marrow stem cells(2364, 2365).

Max Ferdinand Perutz (AT-GB) and Joyce M. Baldwin (GB) presented the details of how hemoglobin performs its physiological functions(2366-2368).

Richard Mathies (US), Allan R. Oseroff (US), Lubert Stryer (US), Alfred Goodman Gilman (US), Michael A. Lochrie (US), Melvin I. Simon (US), Michael Freissmuth (AT), and Patrick J. Casey (US) worked out many of the steps in the visual cascade including the finding that metarhodopsin II interacts with a G-protein, transducin, which activates phosphodiesterase molecules which regulate cyclic GMP levels in photoreceptor cells. Cyclic GMP somehow opens the sodium channels in the outer membrane of retinal cone cells and hydrolysis of cyclic GMP leads to their closing. Their closing leads to hyperpolarization. Membrane voltage of the photoreceptor cell is therefore related to cyclic GMP levels and modulates neurotransmitter release(2369-2374).

Evgeniy E. Fesenko (RU), Stanislav S. Kolesnikov (RU), and Arkadly L. Lyubarsky (RU) determined that the sodium channels are directly opened by cyclic GMP(2375).

Eveline Schneeberger (US) and Morris John Karnovsky (ZA-US) determined the substructure of intercellular junctions in freeze-fractured alveolar-capillary membranes of the mouse lung, i.e., the blood-air barrier of the lungs(2376).

John W. Randles (AU), Erlinda P. Rillo (PH), and Theodor Otto Diener (US) found evidence that the etiological agent of cadang-cadang disease of coconuts is a viroid(2377).

Walter Charles Cornelius Fiers (BE), Roland R. Contreras (BE), Fred Duerinck (BE), Guy Haegemann (BE), Dirk Iserentant (BE), Joseph Merregaert (BE), Willy Min Jou (BE), Francis Molemans (BE), Alex Raeymaekers (BE), Antoon Vandenberghe (BE), Guido Volckaert (BE), and Maarten Ysebaert (BE) worked out the entire nucleotide sequence for the RNA bacteriophage MS2 (2378).

Tony R. Hunter (GB-US), Tim Hunt (GB), John Knowland (GB), and David Zimmern (GB) found that tobacco mosaic virus (TMV) RNA is not an efficient template for translation of the viral coat protein, in spite of containing nucleotide sequences coding for the protein. Efficient translation requires the prior synthesis within infected cells of a smaller RNA (messenger) carrying only a portion of the information encoded in the whole genome(2379).

John N. Champness (GB), Anne C. Bloomer (GB), Gerard Bricogne (GB), P. Jo G. Butler (GB), and Sir Aaron Klug (ZA-GB) elucidated the three dimensional structure of tobacco mosaic virus using crystallographic electron microscopy. Their work showed that the assembly of TMV starts with one disk of protein surrounding the nucleation or initiation region of a strand of RNA, the initial disk serves as a center for the assembly of a stack of 100 such disks composed of a total of 2,200 identical protein molecules that make up the complete virus(2380, 2381).

David Zimmern (GB) isolated the nucleation region and determined that it represents approximately 60 nucleotides near the middle of the viral RNA molecule(2382, 2383).

Richard B. Sykes (US) and Margaret J. Matthew (US) discovered that some bacteria are resistant to penicillins and cephalosporins because they produce beta-lactamases which can split the lactam ring found in these types of molecules (2384).

Hiroshi Nikaido (US) reported that gram-negative bacteria are usually insensitive to antibiotics that are effective against gram-positive bacteria because the antibiotics have difficulty penetrating the gram-negative outer membrane (2385).

L.H. San-Noeum (FR) made the first successful in vitro culture of non-fertilized ovaries of barley(2386).

William Trager (US) and James B. Jensen (US) discovered a simple method to grow the pathogenic human malaria, Plasmodium falciparum, in continuous culture inside erythrocytes(2387).

Paul D. Shirk (US), Karl H. Dahm (US), and Herbert Röller (US) discovered that the accessory sex glands of the male Cecropia moths (Hyalophora cecropia, giant silk moth) have the ability to sequester insect juvenile hormone (JH)(2388).

Ji-Won Yoon (US), Abner L. Notkins (US), Rainer Gladisch (DE), Werner Hofmann (DE), and Rüdiger Waldherr (DE) presented evidence that viruses play a role in the pathogenesis of insulin-dependent diabetes mellitus(2389, 2390).

Robert Austrian (US), Robert M. Douglas (US), Gerald Schiffman (US), A. Maureen Coetzee (ZA), Hendrik J. Koornhof (ZA), Stanley Hayden-Smith (ZA), and R.D.W. Reid (ZA) developed a pneumococcal vaccine, during the process of which they established that of 83 known types of pneumococci, 14 types were responsible for 80% of the pneumococcal infections in man, and that the outer coatings or capsules of these 14 types should be included in an effective vaccine(2391, 2392). Austrian also played a major role in the successful clinical trials which resulted in the vaccine's licensure.

Yuet Wai Kan (US), Mitchell S. Golbus (US), and Andree-Marie Dozy (US) diagnosed alpha-thalassemia in a prenatal human using DNA-DNA hybridization on cells cultured from amniotic fluid. This approach is based on the finding that the molecular defect in these syndromes is due to deletion of the gene that determines the structure of the alpha globin (alpha globin structural gene). A non-thalassemic person has four alpha globin structural genes per diploid cell; in alpha-thalassemia-1 and hemoglobin-H disease, two and one alpha globin genes are left intact respectively, and in homozygous alpha-thalassemia associated with hydrops fetalis, no alpha globin genes remain intact. The hybridization test can detect the number of intact globin structural genes(2033). 

Roger Harold Unger (US) gave clear experimental evidence that the control of glucose levels within the body involves a homeostatic system which is capable of augmentating glucose outflow from the extracellular space to compensate for increases in inflow of glucose(2393). Any extra glucose is stored as glycogen or fat.

Nemat O. Borhani (US), Manning Feinleib (US), Robert J. Garrison (US), Joe C. Christian (US), and Ray H. Rosenman (US) presented evidence that the variability of both systolic and diastolic blood pressure within the total human population can be attributed to genetic differences. They calculated that the "heritability" indexes were 0.82 and 0.64 respectively for systolic and diastolic blood pressures(2394).

Peter C. Nowell (US) gave strong support to the hypothesis of tumor stemlines that describe neoplastic progression in terms of sequential selection of mutant subpopulations derived from a common progenitor(2395).

Philip K. Hench (US) coined the phrase fibromyalgia syndrome (FMS)(2396).

Peter Davies (US) and Anthony J.F. Maloney (GB) reported that there is selective loss of central cholinergic neurons in Alzheimer's disease(2397).

A Conference of the Medical Royal Colleges and Their Faculties in the United Kingdom established brain death as: “All of the following [conditions] should coexist [for considering a diagnosis of brain death]. The patient is deeply comatose…. The patient is being maintained on a ventilator because spontaneous respiration had previously become inadequate or had ceased altogether…. There should be no doubt that the patient's condition is due to irremediable structure brain damage. The diagnosis of a disorder which can lead to brain death should have been fully established…. All brainstem reflexes should be absent”(2398).

Meyer Friedman (US) and Ray H. Rosenman (US) developed the theory that Type A behavior (chronically angry and impatient people) increases the likelihood of heart disease(2399, 2400).

Clinton Richard Dawkins (GB), in his book The Selfish Gene, suggested that organisms are designed by evolution as vessels by which genes project themselves through the generations, i.e., to have the greatest chance of perpetuation genes exhibit a selfish quality(2254).

Charles B. Beck (US) reported that the original arborescent plant bore planated lateral branch systems with helically arranged simple leaves very similar to those of some modern conifers(2401).

J. William Schopf (US) found rock bearing 3.5 billion year old microfossils in the Onverwacht formation in South Africa(2402). The microfossils were interpreted to be prokaryotes(2403, 2404).

Leif Størmer (NO) reported that arthropods likely invaded the land during late Silurian and early Devonian times(2405, 2406).

Richard Erskine Frere Leakey (KE) reported on Bernard Ngeneo’s (KE) discovery of Homo ergaster (Homo erectus), KNMER 3733, at Koobi Fora in Kenya(2407). Its estimated age is 1.7 Ma.

On July 20, 1976 the Viking 1 space-lander from earth came to rest in the Chryse Planitia region of Mars. Its test results strongly suggested that life did not exist on Mars(2408).


“Species differ in their nutrition: if species are delimited by their genes, then genes must control the biosynthetic steps which are reflected in nutritional patterns.” Joshua Lederberg(2409).

“An organism is a molecular society, and biological order is a kind of social order.” André Michel Lwoff(2410).

“The way to capture a student's attention is with a demonstration where there is a possibility the teacher may die." Attributed to:  Jearl Walker, Cleveland State University, ca. 1977(2411).

Roger Charles Louis Guillemin (FR-US), and Andrew Victor Schally (PL-US) for their discoveries concerning the peptide hormone production of the brain and Rosalyn Sussman Yalow (US) for the development of radioimmunoassays of peptide hormones shared the Nobel prize in physiology and medicine.

Koscak Maruyama (JP), Saburo Matsubara (JP), Reiji Natori (JP), Yoshiaki Nonomura (JP), Sumiko Kimura (JP), Kazuyo Ohashi (JP), Fumiko Murakami (JP), Shizuo Handa (JP), Goro Eguchi (JP) Kuan Wang (US), Janela McClure (US), and Ann Tu (US) independently discovered titin (connectin), a giant protein molecule in muscle cells(2412, 2413).

John Trinick (GB) determined that titin functions as a molecular scaffold for myosin, keeping it properly aligned. It is also an elastic protein which can exist in both an extended and a compact form. In the extended form it determines the maximum allowable movement of the myofibril(2414). 

Richard E. Reeves (US), Harland Goff Wood (US), Nancy A. Robinson (US), and Neil H. Goss (US) found that there are some cellular reactions in which inorganic pyrophosphate and polyphosphate replace ATP as a source of energy(2415-2418).

Catherine A. Pepin (US) and Harland Goff Wood (US) showed that a bacterial glucokinase utilizes polyphosphate much more effectively than ATP in the reaction with glucose(2419).

Kuniaki Nagayama (JP), Kurt Wüthrich (CH), Peter Bachmann (DE), and Richard R. Ernst (CH) were the first to use two-dimensional nuclear magnetic resonance to solve the structure of biological macromolecules, amino acids and a protein, the basic pancreatic trypsin inhibitor(2420).

Sir John Warcup Cornforth (AU-GB) Scott A. Reichard (US), Paul Talalay (US), Horace L. Carrell (US), and Jenny P. Glusker (US) determined the absolute configuration at the sulfonium center of S-adenosyl-methionine(2421).

Choh Hao Li (CN-US), Donald Yamashiro (US), Liang-Fu Tseng (US), and Horace H. Loh (US) synthesized human beta-endorphin and found that when it is applied centrally, beta h-endorphin is 17-48 times more potent than morphine(2422).

Toshiro Itoh (JP) and Hiroshi Kaneko (JP) isolated pyrophosphatidic acid from the yeast Cryptococcus neoformans and found that it, through phosphatidic acid, plays a role in phospholipid metabolism(2423).

John M. Essigmann (US), Robert G. Croy (US), Alex M. Nadzan (US), William F. Busby, Jr. (US), Vernon N. Reinhold (US), George Hermann Büchi (CH-US), and Gerald N. Wogan (US) obtained chemical data which indicates that the major product of the interaction of metabolically activated aflatoxin B1 (a potent carcinogen) and DNA is 2,3-dihydro-2-(N7-guanyl)-3-hydroxyaflatoxin B1 with the guanine and hydroxyl functions possessing a trans configuration. The structural data support the hypothesis that the putative 2,3-oxide of aflatoxin B1 is quantitatively important as an intermediate in the binding of aflatoxin B1 to the guanine of nucleic acids(2424).

William R. Hargreaves (US), Sean J. Mulvihill (US), and David W. Deamer (US) found that fatty acids and glycerol combine spontaneously to produce phospholipids when heated to dryness at 65°C, as they might have been in an evaporating tidepool along a primitive sea(2425).

James R. Paulson (US) and Ulrich K. Laemmli (CH) found that histone-depleted chromosomes consist of a scaffold or core, which has the shape characteristic of a metaphase chromosome, surrounded by a halo of DNA; the halo consists of many loops of DNA, each anchored in the scaffold at its base; most of the DNA exists in loops at least 10–30 μm long (30–90 kilobases). These results suggest a scaffolding model for metaphase chromosome structure in which a backbone of nonhistone proteins is responsible for the basic shape of metaphase chromosomes, and the scaffold organizes the DNA into loops along its length(2426).

James J. Champoux (US) discovered the topoisomerases which introduce negative supercoils to prokaryotic DNA(2427).

E. Stephen-Sherwood (US), A. Joshi (US), and Joan Oró (ES-US) produced polynucleotide polymers under primitive Earth conditions(2428).

John P. Devlin (CA), Oliver E. Edwards (CA), Paul R. Gorham (CA), N.R. Hunter (CA), R.K. Pike (CA), and B. Stavric (CA) identified a toxin they derived from Anabaena flos-aquae, and named it anatoxin-a. It turned out to be an alkaloid neurotoxin(1549, 2429). These poisons, which periodically and fatally contaminate the water supplies of wild and domestic animals, can also harm humans.

Carol Saunderson Huber (CA) had previously determined the chemical structure of the cyanobacterial toxin (anatoxin-a) for the first time(2430).

K. Peter C. Vollhardt (US) synthesized estrone(2431, 2432).

James C. Alwine (US), David J. Kemp (US), and George R. Stark (US) developed a technique for identifying specific RNA fragments following their separation by agarose gel electrophoresis. The technique is called the northern blotting method(2433).

Patricia S. Thomas (US) improved this method considerably by electrophoresing the RNA in a denaturing agent to prevent the RNAs from spontaneously folding back and interacting with themselves or bonding to other RNAs(2434).

Peter W.J. Rigby (GB), Marianne Dieckman (US), Carl Rhodes (US), and Paul Berg (US) originated the nick translation reaction as a rapid and efficient method for uniformly labeling double stranded DNA suitable for hybridization studies such as Northern and Southern blots and in situ hybridizations(2435).

Salvador Moncada (GB), E. Annie Higgs (GB), and Sir John Robert Vane (GB) discovered that prostacyclin is generated in human arteries and venous tissue. It is postulated that prostacyclin is important for prevention of deposition of platelets on the vessel wall and that the inhibition or prevention of the generation of prostacyclin is important in the genesis of diseases, especially those in which increased lipid peroxidation occurs, such as atherosclerosis(2436).

Gertrude Belle Elion (US), Phillip A. Furman (US), James A. Fyfe (US), Paulo de Miranda (US), Lilia Beauchamp (US), and Howard J. Schaeffer (US) synthesized 9-(2-hydroxyethoxymethyl) guanine called acyclovir and Zovirax(2437). It was subsequently shown to inhibit several of the herpes viruses.

Carl S. Parker (US) and Robert Gayle Roeder (US) reconstructed in a cell-free Xenopus laevis system the correct initiation of transcription by RNA polymerase III(2438).

Keiichi Itakura (US), Tadaaki Hirose (US), Roberto Crea (US), Arthur D. Riggs (US), Herbert L. Heynker (NL), Francisco Bolivar (MX), and Herbert Wayne Boyer (US) synthesized the mammalian gene for somatostatin then fused it to the beta-galactosidase gene of Escherichia coli on the plasmid pBR322. Cells of Escherichia coli were then transformed using this chimeric plasmid which led to the in vivo synthesis of a large polypeptide which included somatostatin. Active somatostatin was then cleaved from the large chimeric protein using cyanogen bromide(2439). This represents the first synthesis of a functional polypeptide product from a gene of chemically synthesized origin. 

Francisco Bolivar (MX), Raymond L. Rodriquez (US), Patricia J. Greene (US), Mary C. Betlach (US), Herbert L. Heynker (NL), Herbert Wayne Boyer (US), Jorge H. Crosa (US), and Stanley Falkow (US) used in vitro recombination techniques to construct the cloning vehicle pBR322. This plasmid quickly became one of the most popular cloning vehicles(2440).

William G. Burton (US), Richard J. Roberts (US), Phyllis A. Myers (US), and Ruth Sager (US) discovered a site-specific single-stranded endonuclease from the eukaryote Chlamydomonas(2441).

Argiris Efstratiadis (GR-US), Fotis Constantine Kafatos (DE), and Thomas Peter Maniatis (US) sequenced an entire cDNA insert, which confirmed the faithful propagation of the cDNA in E. coli, and provided the first complete nucleotide sequence of an mRNA(2442).

Gek Kee Sim (US), Argiris Efstratiadis (GR-US), C. Weldon Jones (US), Fotis Constantine Kafatos (DE), M. Koehler (US), Henry Morris Kronenberg (US), Thomas Peter Maniatis (US), Jerome C. Regier (US), B.F. Roberts (US), and Nadia Rosenthal (US) constructed a cDNA library and demonstrated the feasibility of using cDNA libraries of complex mRNA populations to obtain individual mRNAs(2443). 

Elisabeth Ljungquist (SE) and Ahmad Iqbal Bukhari (PK-US) stated that a segment of DNA can transpose from one chromosomal location to another without leaving the original location, and that replicas flit to new sites in the genome without having a discernible independent existence(2444).

Marie Lagueux (FR), Michel H. Hirn (FR), and Jules A. Hoffman (FR) found that ecdysone (a molting hormone) not only stimulates molting and metamorphosis in adult insects, but also regulates molts of the developing embryo. These observations “probably represent the best documented example of a transfer of steroid hormones of maternal origin to the embryo in egg-laying animals”(2445).

Holger W. Jannasch (US), Carl O. Wirsen (US), and Edward G. Ruby (US) retrieved undecompressed microorganisms from the deep sea and determined their physiological characteristics(2446-2448).

Per Hellung-Larsen (NL), Sune Frederiksen (NL), Lester Goldstein (US), Gary E. Wise (US), Christine Ko (US), Bernhard J. Benecke (NL), and Sheldon Penman (US) presented evidence for the presence of small nuclear RNA (snRNA)(2449-2451).

Eric Cundliffe (US) and Julian E. Davies (US) discovered that trichothecene fungal toxins inhibit initiation, elongation, and termination of eukaryotic protein synthesis(2452).

James Edward Rothman (US), John Lenard (US) and Eugene Patrick Kennedy (US) showed that in Bacillus megaterium newly synthesized cell membrane phospholipids are all added first to the membrane’s cytoplasmic side then some are flipped to the exterior side(2453-2455).

Rosalind Coleman (US) and Robert M. Bell (US) had similar results with eukaryotes (Eucarya)(2456, 2457).

Tom D. Petes (US) and David Botstein (US) determined the mode of inheritance of ribosomal DNA by tetrad analysis in Saccharomyces cerevisiae. Of 14 tetrads analyzed, 12 clearly showed the ribosomal DNA forms segregating as a single Mendelian unit. Their interpretation of this result is that all of the approximately 100 copies of the ribosomal DNA genes of the yeast cell are located on one chromosome and that meiotic recombination within these genes is suppressed(2458). This paper showed the way to locating a gene within a genome. One can use differences (polymorphisms) in DNA sequence as "DNA-sequence-based markers" to map genes. Restriction fragment length polymorphism (RFLP) was used for the first genetic mapping and positional cloning of human disease genes (cystic fibrosis, Duchenne muscular dystrophy, and Huntington's disease)(2459-2462).

Tom D. Petes (US went on to map the location of Saccharomyces cerevisiae ribosomal DNA genes to the left arm of chromosome 12(2463, 2464).

Philip J. Farabaugh (US), Ursula Schmeissner (CH), Murielle Hofer (CH), Jeffrey H. Miller (US), Donald Ganem (US), Ponzy Lu (US), and Albert Schmitz (CH) altered the amino acid composition of the lac repressor protein to determine which amino acids are necessary for the various functions of the complete protein(2465, 2466).

Leona Samson (US), Hugh John Forster Cairns (GB-US-GB), Penelope Jeggo (US), Martine Defais (US), and Paul Schendel (US) measured the accumulation of mutants in Escherichia coli cells growing continuously in the presence of very low concentrations of mutagens. They showed that the cells could adapt to low levels of alkylating agents and manifest an increased resistance (adaptation) to killing and to mutagenesis by subsequent and higher concentrations of the alkylating. A model of chemically induced mutagenesis based on these findings is presented. It maintains that the observed mutation frequency is dependent on a "race" between these two error-free systems and the two mutagenic pathways agents(2467-2469). Peter Robins (GB) was an outstanding technician during this work.

Peter Karran (SE), Tomas Lindahl (SE), Beverly Griffin (GB), Bruce Demple (US), Barbara Sedgwick (GB), Peter Robins (GB), Nicholas F. Totty (GB), Michael D. Waterfield (GB), Ian Teo (GB), B. Li (), Michael W. Kilpatrick (GB), Tommie V. McCarthy (GB), Hiroko Kataoka (JP), Yoko Yamamoto (JP), Mutsuo Sekiguchi (JP), Yusaku Nakabeppu (JP), Toshiyuki Miyata (JP), Hidemasa Kondo (JP), Sadaaki, Iwanaga (JP), Shun-ichiro Kawabata (JP), and Yoshiyuki Mine (JP) showed that adaptation to killing results from the enhanced repair of alkylating damage by a DNA glycosylase, one that specifically recognizes certain alkylated bases and is encoded by a gene called alkA. The gene ada (for adaptive response) turned out to be novel in the DNA repair world. Ada protein is endowed with the ability to specifically recognize O6-methylguanine and O4-methylthymine in DNA. It plucks methyl groups from these (and only these) two positions of these (and only these) two alkylating bases in DNA, transferring them to a specific amino acid residue in the polypeptide. Expression of the ada and alkA genes, both of which are involved in the adaptive response of Escherichia coli to alkylating agents, is positively controlled by Ada protein, the product of the ada gene(2470-2480). 

Randi Leavitt (US), Sondra Schlesinger (US) Stuart Kornfeld (US), Trudy G. Morrison (US), Catherine O. McQuain (US), Dwight Simpson (US), Ron Gibson (US), Carolyn E. Machamer (US), Robert Z. Florkiewicz (US), John K. Rose (US), Robert W. Doms (US), Aino Ruusala (SE), Jonne Helenius (FI-US-CH), and Ari Helenius (FI-US-CH) have indicated that the glycosylation of proteins within the endoplasmic reticulum is important to their proper folding and intracellular transport(2481-2487).

James Edward Rothman (US) and Harvey Franklin Lodish (US) demonstrated that glycosylation of proteins in the endoplasmic reticulum occurs almost immediately as they appear on the lumenal side of the membrane(1833).

Robert Brackenbury (US), Jean-Paul Thiéry (FR), Urs Rutishauser (US), and Gerald Maurice Edelman (US) isolated the neural cell adhesion molecule (NCAM), the first cell-cell adhesion molecule to be purified and characterized(2488, 2489).

Bruce A. Cunningham (US), John J. Hemperly (US), Ben A. Murray (US), Ellen A. Prediger (US), Robert Brackenbury (US), and Gerald Maurice Edelman (US) analyzed the cDNA and cloned the gene for neural cell adhesion molecule (NCAM)(2490).

Susumu Tonegawa (US), Christine Brack (CH), Nobumichi Hozumi (CH), and Rita Schuller (CH) cloned an immunoglobulin variable region gene from mouse embryo(2491).

Ora Bernard (CH), Nobumichi Hozumi (CH), and Susumu Tonegawa (US) determined the nucleotide sequences of the germ line gene as well as a corresponding somatically mutated and rearranged gene coding for a mouse immunoglobulin A, type light chain(2492). 

Arnold Kaplan (US), Daniel T. Achord (US), and William S. Sly (US) were the first to demonstrate that a hexose phosphate, specifically mannose-6-phosphate, is essential for the high affinity and saturable endocytosis of lysosomal hydrolases by cultured cells(2493).

Rodolfo R. Llinas (US) demonstrated a direct linkage between the inflow of calcium and the release of neurotransmitter at axon terminals(2494-2496).

Richard G.W. Anderson (US), Michael S. Brown (US), and Joseph L. Goldstein (US) indicate that the coated regions of plasma membrane are specialized structures of rapid turnover that function to carry receptor-bound low density lipoprotein (LDL), and perhaps other receptor-bound molecules, into the cell(2497). 

Frank F. Vincenzi (US) and Martha L. Farrance (US) discovered calmodulin, the calcium activated regulatory protein(2498).

Robert P. Casey (US), David Lars Njus (US), Sir George Karoly Radda (GB), P. John Seeley (GB), Peter A. Sehr (GB), Michael F. Beers (US), Sally E. Carty (US), Robert Gahagen Johnson (US) and Antonio Scarpa (US) demonstrated that ATPase actively drives protons into the chromaffin vesicle and the proton gradient (creating pH and electrical gradients across the vesicle membrane) in turn drives catecholamine uptake(2499-2503). This was the first demonstration of a chemiosmotic mechanism operating in any mammalian organelle other than the mitochondrion.

Brigit Rose (US), Ian Simpson (US), and Werner R. Loewenstein (US) demonstrated that calcium ions regulate gap junction permeability in leaves of the simple water plant Egeria densa(2504).

Wolfgang Schwarz (US), Philip T. Palade (US), and Bertil Hille (US) introduced the concept of use-dependant block of ion channels by local anesthetics(2505). The finding strongly influenced clinical medicine.

Enid W. Silverton (US), Manuel A. Navia (US), and David R. Davies (GB-US) used x-ray crystallographic diffraction data to produce a three dimensional picture of the myeloma protein(2506).

Lorenzo Moretta (IT), Susan R. Webb (US), Carlo E. Grossi (IT), Peter M. Lydyard (GB), and Max D. Cooper (US) give the first dissection of human T lymphocytes into phenotypically and functionally distinct subpopulations. They found that peripheral T lymphocytes express either receptors for the Fc portion of IgM or for the Fc portion of IgG. This made it possible to separate cells exerting helper or suppression functions on antibody production(2507).  

Alan F. Williams (AU), Giovanni Galfrè (IT), and César Milstein (AR-GB) were the first to identify a CD4 (clusters of differentiation) antigen. They used W3/25 monoclonal antibody to identify this antigen on rat lymphocytes(2508).

Robert A.H. White (GB), Donald W. Mason (GB), Alan F. Williams (GB), Giovanni Galfrè (IT), and César Milstein (AR-GB) identified the W3/25 antigen as a CD4 marker on a particular subpopulation of lymphocytes, the T helper lymphocytes. This was also a first such identification(2509).

Ellis L. Reinherz (US), Patrick C. Kung (US), Gideon Goldstein (US), and Stuart F. Schlossman (US) were the first to identify a CD4 antigen on human lymphocytes(2510).

Guenter Albrecht-Buehler (DE-CH-US) developed a technique he called a biological "cloud chamber" in which he studied cells as they migrated on a glass surface coated with colloidal gold particles. Because sister cells made symmetrical patterns (mirror image tracks) following division it suggested that cell migration is programmed(2511). 

Howard Michael Goodman (US), Maynard V. Olson (US), Benjamin D. Hall (US), Pablo Valenzuela (CL-US), Alejandro Venegas (CL), Fanyela Weinberg (US), Robert Bishop (US), and William J. Rutter (US) discovered transfer RNA (tRNA) introns in yeast(2512, 2513).

Louise T. Chow (CN-US), Richard E. Gelinas (US). Tom R. Broker (US), Richard John Roberts (US), Daniel F. Klessig (US), Ashley R. Dunn (AU), John A. Hassell (US), James B. Lewis (US), Carl W. Anderson (US), John F. Atkins (IE), Susan M. Berget (US), Claire Moore (US), Phillip Allen Sharp (US), B. Sayeeda Zain (US), Arnold J. Berk (US), and Timothy J. Harrison (GB) all played a part in the fascinating discovery that in adenovirus 2, coding regions (exons) of genes may be interrupted by non-coding regions (introns). This was the first indication that normal genes can exist as several, well separated segments. The gene would produce a large mRNA which prior to translation must be cut and spliced(2514-2521). This work represents the discovery of the intron and mRNA splicing.

Richard Breathnach (FR), Jean-Louis Mandel (FR), and Pierre M. Chambon (FR) discovered that eukaryotic genes have their coding sequences (exons) interrupted by noncoding sequences (introns)(2522).

Matthew A. Harmey (GB), Gerhard Hallermayer (DE), Harald Korb (DE), and Walter Neupert (DE) discovered how proteins are transported into mitochondria(2523, 2524).

Gottfried Schatz (AT-CH), Maria-Luisa Maccecchini (US), and Yvonne Rudin (CH) discovered how proteins are transported into mitochondria(2525, 2526).

Clay M. Armstrong (US) and Francisco Bezanilla (US) proposed a model, which became known as the ball-and-chain hypothesis, to explain the three dimensional structure of voltage-gated channels in cell membranes(2527).

Gerry C. Johnston (US), John R. Pringle (US), and Leland Harrison Hartwell (US) found in Saccharomyces cerevisiae that growth is integrated with the division cycle prior to budding, at the CDC28 and CDC33 (cell division cycle genes 28 and 33) step. This suggested that the growth cycle coupled to the cell cycle precisely at the initiation of the cell cycle (G1 phase). They demonstrated that in yeast the cell cycle depends on the growth cycle and that the reverse dependency does not operate. In addition, they showed that at least one step in the cell cycle—the initiation step, or the G1-S transition—depended on the cell's attaining a certain size(2528).

Roy Curtiss III (US), Matsuhisa Inoue (US), Dennis A. Pereira (US), J. Charles Hsu (US), Laura Alexander (US), and L. Rock (US) developed the first safe strain of bacteria for use in recombinant DNA biotechnology. It was a strain of Escherichia coli K12 designated c1776 in honor of the American bicentennial (2529).

Hugh Platt (GB), J.G. Atherton (GB), D.J. Simpson (GB), C.E.D. Taylor (GB), R.O. Rosenthal (GB), Derek F.J. Brown (GB), and Tim G. Wreghitt (GB) isolated a previously unknown bacterium responsible for a major outbreak of a highly contagious genital infection in thoroughbred horses. The disease was christened Contagious Equine Metritis (CEM). To date it has not been found to fit any known taxonomic group(2530).

Frederick Sanger (GB), Gillian M. Air (GB), Barclay George Barrel (GB), Nigel L. Brown (GB), Alan R. Coulson (GB), John C. Fiddes (GB), Clyde A. Hutchison III (US), Patrick M. Slocombe (GB), Michael Smith (CA), and Theodore Friedmann (GB) determined the nucleotide base sequence of the bacteriophage phi chi 174. This was the first genome to be sequenced completely(1772, 2531).


Mary-Dell Matchett Chilton (US), Martin H. Drummond (US), Donald J. Merlo (US), Daniela Sciaky (US), Alice L. Montoya (US), Milton P. Gordon (US), and Eugene W. Nester (US) found that genes on the Agrobacterium tumefaciens plasmid are transferred into infected plant cells(2532).

Steven Gillis (US) and Kendall A. Smith (US) reported they had succeeded in establishing long-term cultures of T cells using a lymphocyte-conditioned medium(2533).

Giovanni Galfrè (IT), Shirley C. Howe (GB), César Milstein (AR-GB), Geoffrey W. Butcher (GB), and Jonathan C. Howard (GB) were the first to demonstrate the usefulness of monoclonal antibodies for identification, and eventually purification, of specific antigens(2534).

Gordon Hisashi Sato (US), Sharon E. Hutchings (US), Reen Wu (US), Jennie P. Mather (US), David W. Barnes (US), and Richard A. Wolfe (US) showed that different cell lines require different mixtures of hormones and growth factors to grow in serum-free medium(2535-2541).

Axel Ullrich (US), John Shine (US), John Chirgwin (US), Raymond Pictet (US), Edmund Tischer (US), William J. Rutter (US), and Howard Michael Goodman (US) constructed recombinant bacterial plasmids containing complementary DNA prepared from rat islets of Langerhans messenger RNA, i.e., rat insulin genes(2542).

Lydia Villa-Komaroff (US), Argiris Efstratiadis (GR-US), Stephanie Broome (US), Peter Lomedico (US), Richard Tizard (US), Stephen P. Naber (US), William L. Chick (US), and Walter Gilbert (US) cloned double-stranded cDNA copies of a rat pre-proinsulin messenger RNA in Escherichia coli X1776 with the result that it was expressed as proinsulin(2543).

Scientists at Genentech and City of Hope inserted synthetic genes carrying the genetic code for human insulin, along with the necessary control mechanism, into an E. coli bacterial strain which is a laboratory derivative of a common bacteria found in the human intestine. Once inside the bacteria, the genes were "switched-on" by the bacteria to translate the code into either "A" or "B" protein chains found in insulin. The separate chains were then joined to construct complete insulin molecules. This is from a 1978 press release.

David VanNorman Goeddel (US), Dennis G. Kleid (US), Francisco Bolivar (MX), Herbert L. Heynker (NL), Daniel G. Yansura (US), Roberto Crea (US), Tadaaki Hirose (US), Adam Kraszewski (US), Keiichi Itakura (US), and Arthur D. Riggs (US) induced Escherichia coli, a bacterium that normally populates the human intestinal tract, to produce human insulin. Unfortunately, their method could not produce insulin in quantities sufficient for commercial manufacturing(2544).

Karen Talmadge (US), James F. Kaufman (US), and Walter Gilbert (US) were able to insert the gene for rat pre-proinsulin into Escherichia coli in such a way that the bacterium expressed the gene then processed the pre-proinsulin to proinsulin as it was excreted(2545).

Human insulin (Humulin) became the first recombinant DNA drug approved by the FDA(2546).

Humalog, a fast acting, chemically modified human insulin was introduced in 1996. Humalog differs from human insulin in that the amino acids at positions 28 and 29 on the insulin-chain are reversed.

Fredrick R. Blattner (US), Bill G. Williams (US), Ann E. Blechl (US), Katherine Denniston-Thompson (US), Harvey E. Faber (US), Lesley-Anne Furlong (US), David J. Grunwald (US), Delight O. Kiefer (US), David D. Moore (US), James W. Schumm (US), Edward L. Sheldon (US), Oliver Smithies (GB-US), Philip Leder (US), David C. Tiemeier (US), and Lynn W. Enquist (US) were the first to use disabled lambda virus as a vector for cloning foreign DNA(2547, 2548).

Mario Rizzetto (IT), Maria G. Canese (IT), Sarino Arico (IT), Osvaldo Crivelli (IT), Ferruccio Bonino (IT), Christian G. Trepo (IT), and Giorgio Verme (IT) discovered hepatitis delta virus (HDV) infections while studying chronic carriers of hepatitis B virus(2549).

Karl M. Johnson (US), James V. Lange (US), Patricia A. Webb (US), and Frederick A. Murphy (US) isolated and partially characterized a new virus causing acute hemorrhagic fever in Zaire, Africa(2550). This virus would later be called Ebola.

Joyce E. Heckman (US), Lanny I. Hecker (US), Steven D. Schwartzbach (US), W. Edgar Barnett (US), Barbara R. Baumstark (US), and Uttam L. RajBhandary (GB-US), using Neurospora crassa, were the first to sequence nucleic acid from mitochondria. Unique features of initiator tRNA were revealed(2551). This work foreshadowed the discovery of numerous unexpected features of mitochondrial genomes.

Peter Upcroft (AU), F. Ziemer (), Hagit Skolnik (IL), and George C. Fareed (US) used papovaviruses as vehicles for the transduction of foreign genes into mammalian cells(2552).

Robert A. Swanson (US), a venture capitalist, and biochemist Dr. Herbert W. Boyer (US), after a meeting in 1976, decided to start the first biotechnology company, Genentech.

Anton Lang (RU-US), Mikhail Khristoforovich Chailakhyan (RU), and I.A. Frolova (RU) demonstrated that graft-transmissible inhibitors of flower formation (antiflorigens) are formed in non-induced leaves(2553).

William Martin (US), Gina M. Villani (US), Desingarao Jothianandan (US), Kazuki Matsunaga (US), Robert F. Furchgott (US), Carl A. Gruetter (US), Barbara K. Barry (US), Dennis B. McNamara (US), Philip J. Kadowitz (US), Louis Joseph Ignarro (US), Darlene Y. Gruetter (US), William H. Baricos (US), Albert L. Hyman (US), Shoji Katsuki (JP), William P. Arnold (US), Chandra K. Mittal (US), Robert M. Rapoport (US), and Ferid Murad (US) began research which led to discoveries concerning nitric oxide as a signaling molecule in the cardiovascular system(2554-2562).

Shoji Katsuki (US), William P. Arnold (US), Chandra K. Mittal (US), and Ferid Murad (US) tested the hypothesis that nitroglycerin acts through the release of nitric oxide by allowing NO gas to bubble through a tissue preparation containing guanylylcyclase. The production of cGMP increased. A new mode of action for drugs, to activate enzyme function was discovered. After more than 100 years of successful treatment of angina with nitroglycerin, the woking principle was finally revealed(2554, 2563).

John G. Bartlett (US), Andrew B. Onderdonk (US), Ronald L. Cisneros (US), and Dennis L. Kasper (US) carried out animal studies implicating Clostridium difficle as the major cause of antibiotic-associated colitis. It was later shown by others that this is also true in humans. This organism produces a protein cytotoxin whose cytopathology is poorly understood. Colitis is one of the most frequent and potentially severe adverse reactions associated with antibiotic therapy. Vancomycin is the drug of choice in treatment (2564).

Michael R. Jacobs (ZA), Hendrik J. Koornhof (ZA), Roy M. Robins-Browne (AU), Carolyne M. Stevenson (ZA), Zoe A. Vermaak (GB), Ida Freiman (ZA), G. Bennie Miller (ZA), Maurice A. Witcomb (ZA), Margaretha Isaacson (ZA), Joel I. Ward (US) and Robert Austrian (US) reported pneumococci resistant to multiple antibiotics in Johannesburg, South Africa during July of 1977(2565).

Robert E. Weibel (US), Philip P. Vella (US), Arlene A. McLean (US), Allen F. Woodhour (US), Wallace L. Davidson (US), and Maurice Ralph Hilleman (US) developed a polyvalent pneumococcal vaccine(2566).

David Warshauer (US), Elliot Goldstein (US), Thomas G. Akers (US), William Lippert (US), M. Kim (US), George J. Jakob (US), Glenn A. Warr (US), and Mardel E. Knight (US) reported that influenza A viral infections can cause increased susceptibility to bacterial and fungal superinfections coincident with depressed metabolic and bactericidal activities of circulating and alveolar phagocytic cells(2567, 2568).

David W. Fraser (US), Theodore R. Tsai (US), Walter A. Orenstein (US), William E. Parkin (US), H. James Beecham (US), Robert G. Sharrar (US), John M. Harris (US), George F. Mallison (US), Stanley M. Martin (US), Joseph E. McDade (US), Charles C. Shepard (US), Philip S. Brachman (US), Martha A. Redus (US), and Walter R. Dowdle (US) isolated and named Legionella pneumophila as the causative agent of legionellosis; Legionnaires disease. The bodies of dead legionaires was the source(2569, 2570). 

Dhiman Barua (IN) and A.S. Paguio (PH) found that cholera appears more frequently among people with type O blood(2571). 

A. JA. Lysenko (RU), Andrei E. Beljaev (RU), and V.M. Rybalka (RU) formulated a theory on the polymorphism of Plasmodium vivax sporozoites(2572-2574).

Christoph Bernoulli (CH), Jean Siegfried (CH), G. Baumgartner (CH), Franco Regli (CH), Theodore Rabinowicz (US), Daniel Carleton Gajdusek (US), Clarence Joseph Gibbs, Jr. (US), David M. Asher (US), Paul W. Brown (US), Arwind Diwan (US), Paul M. Hoffman (US), George Nemo (US), Robert Rohwer (US), and Lon White (US) reported that Creutzfeldt-Jakob disease (CJD) was iatrogenically transmitted to patients undergoing brain surgery by electrodes previously used on a CJD patient. The electrodes had been sterilized(2575, 2576).

Elias E. Manuelidis (US), Jean N. Angelo (US), Edward J. Gorgacz (US), Jung H. Kim (US), and Laura Manuelidis (US) reported that CJD had been transmitted via a corneal transplant(2577).

John S. Najarian (US), David E. R. Sutherland (US), Arthur J. Matas (US), Michael W. Steffes (US), Richard L. Simmons (US), and Frederick C. Goetz (US) performed the first transplantation of human, insulin producing, islet cells(2578).

Thomas Dale Stewart (US), at Shanidar cave in Iraq, discovered that Shanidar I, a ca. 47,000 B.C.E. Neanderthal male, had an underdeveloped right shoulder blade, collar bone, and upper right arm bone. He believes that Shanidar I was crippled, with a useless right arm, which had been amputated in life just above the elbow(2579). This is surely one of the earliest examples of surgery. 

David Hunter Hubel (CA-US), Torsten Niels Wiesel (SE-US), and Simon LeVay (US) identified in neonatal animals a critical period during which deprivation of visual stimulation may induce permanent blindness. The length and timing of critical periods differ among species, which suggests that throughout the brain each functional unit has a unique program of development. This type of blindness is associated with changes in the functional architecture in layer IVc of the brain’s striate cortex(2580, 2581).

James F. Fixx (US) popularized jogging as a way to promote physical fitness(2582).

Sir Thomas Richard Edmund Southwood (GB) reasoned that since ecological strategies evolve from the interaction of the habitat and organisms “a sort of ecological periodic table” might be constructed with a set of key habitat characteristics, or “habitat templets,” as the organizing elements(2583).

Rupert Riedl (AT) discusses a systems-analytical approach to complex systems/phenotype/constraint theory(2584). 

Francois Jacob (US) wrote a 'perspective' essay that puts together many modern themes around the notion of "hierarchy" in evolutionary biology. He sees much of evolution as "tinkering," that is, working with available traits. "Tinkering" includes (but is not limited to) shifts in function(2585).

Joseph H. Connell (US) and Ralph O. Slatyer (US) attempted a codification of mechanisms of succession in natural communities and their role in community stability and organization. They proposed that there were 3 main modes of successional development. These sequences could be understood in the context of the specific life-history theories of the individual species within an ecological community. The key factor distinguishing the three models is how the process of succession affects the original, pioneer species (i.e. their relative success in later-successional stages)(2586).

John Philip Grime (GB) suggested that evolution in plants may be associated with the emergence of three primary strategies, each of which may be identified by reference to a number of characteristics including morphological features, resource allocation, phenology, and response to stress. The competitive strategy prevails in productive, relatively undisturbed vegetation, the stress-tolerant strategy is associated with continuously unproductive conditions, and the ruderal strategy is characteristic of severely disturbed but potentially productive habitats(2587). This is known as the CSR theory of plant strategies.

Marvin J. Allison (US), Enrique Gerszten(US), A. Julio Martinez (US), David M. Klurfeld (US), and Alejandro Pezzia (PE) discovered that a young female pre-columbian mummy of the Huari culture, ca. 900, in Peru seems to represent one of the earliest cases of collagen disease, with many aspects compatible with systemic lupus erythematosus (SLE)(2588).

Tom D. Dillehay (US), from 1977 to 1985, excavated at Monte Verde, some 31 miles (50 km) inland from the Pacific Ocean in Southern Chile. He found evidence of a known site of human habitation in the Americas at ~10,500 B.C.E.(2589, 2590).

Don W. Davis (CA), J. Gray (CA), George L. Cumming (CA), and Halfdan Baadsgaard (CA) determined the time constant for the decay of rubidium 87 to strontium 87. This became one of the standard radiometric dating methods. It has a 48.9 ± 0.4 billion year half-life(2591).


“The question of interest is no longer whether human social behavior is genetically determined; it is to what extent.” Edward Osborne Wilson(2592).

Peter D. Mitchell (GB) was awarded the Nobel Prize in Chemistry for his contribution to the understanding of biological energy transfer through the formulation of the chemiosmotic theory.

Werner Arber (CH), Daniel Nathans (US), and Hamilton O. Smith (US) were awarded the Nobel Prize in Physiology or Medicine for the discovery of restriction enzymes and their application to problems of molecular genetics.

Juan Oró (US), E. Stephen-Sherwood (US), Joseph Eichberg (US), and Dennis E. Epps (US) reported the synthesis of phospholipids under primitive Earth conditions(2593).

Noam Lahav (IL), David White (US), and Sherwood Chang (US) experimentally produced peptide bonds under conditions where clay, water, and amino acids were subjected to cyclic variations in temperature and water content(2594). 

James Ephraim Lovelock (GB) and Lynn Margulis (US) proposed what became known as the Gaia hypothesis, suggesting that life stabilizes the Earth’s atmosphere which otherwise contains an extraordinary and unstable mixture of gases. Life on Earth not only contributes to the atmosphere, but also helps stabilize it—keeping it at a constant composition, and at a level favorable for life(2595-2599).

David Shortle (US) and Daniel Nathans (US) developed a method for generating viral mutants with base substitutions in preselected regions of the viral genome: local mutagenesis(2600).

Dietmar Kamp (DE), Regine Kahmann (DE), David Zipser (US), Tom R. Broker (US), and Louise T. Chow (CN-US) discovered that the host range of bacteriophage Mu is determined by G-loop inversion(2601).

Louis Sokoloff (US), Martin Reivich (US), David E. Kuhl (US), Alfred P. Wolf (US), Tibor Farkas (US), Joel H. Greenberg (US), Michael Phelps (US), Tatsuo Ido (JP), Vito Casella (US), Joanna S. Fowler (US), Edward Hoffman (US), Abass Alavi (US), Prantika Som (US), Harold L. Atkins (US), Debashis E. Bandoypadhyay (), Robert R. MacGregor (US), David R. Christman (US), K. Matsui (), Zvi H. Oster (US), Donald F. Sacker (US), Chyng-Yann Shiue (US), H. Turner (), C.-N. Wan (), and S.V. Zabinski () developed a method to visualize the simultaneous biochemical activity of an entire network of neural pathways in the brain and central nervous system. This new method maps and measures their functioning, both as a whole and in localized areas, under both normal and abnormal conditions. The technique involves measuring the brain's utilization of glucose, since glucose is the primary fuel for the central nervous system. But since glucose itself metabolizes too quickly for adequate study, analogues of glucose, 2-deoxy-D-glucose and 2-deoxy-2-[18F]-fluoro-D-glucose, (18FDG), a radiotracer, are used. These analogues differ infinitesimally from glucose itself, but can be trapped in brain tissue long enough for chemical analysis and tomography, thus serving as a marker for central nervous system metabolism. 18FDG remains the most sensitive tracer to image tumors and tumor metastases, and it has provided the means of directly studying the effects of drugs on the human brain(2602-2608). These methods led the way to the development of Positron Emission Transverse Tomography (PETT); often shortened to (PET).

Francis P. Tally (US), Nilda V. Jacobus (US), Sherwood Leslie Gorbach (US), Susanne S. Weaver (US), Gerald Paul Bodey (US), Barbara M. LeBlanc (US), Jean S. Kahan (US), Frederick M. Kahan (US), Robert T. Goegelman (US), Sara A. Currie (US), Marion Jackson (US), Edward O. Stapley (US), Thomas W. Miller (US), A.K. Miller (US), David Hendlin (US), Sagrario Mochales (ES), S. Hernandez (US), Harold Boyd Woodruff (US), Jerome Birnbaum (US), Georg Albers-Schönberg (US), Byron H. Arison (US), Otto D. Hensens (US), Jordan Hirshfield (US), Karst Hoogsteen (US), Edward A. Kaczka (US), Robert E. Rhodes (US), Frederick M. Kahan (US), Ronald W. Ratcliffe (US), Edward Walton (US), Linda J. Ruswinkle (US), Robert B. Morin (US), and Burton G. Christensen (US) determined the properties and the structure of the beta-lactam antibiotic thienamycin. It is a natural product of Streptomyces cattleya and shows activity against Pseudomonas and beta-lactamase-producing species(2609-2612).

Elias James Corey (US), Eugene J. Trybulski (US), Lawrence S. Melvin, Jr. (US), Kyriacos Costa Nicolaou (CY-US), John A. Secrist (US), Robert Lett (US), Peter W. Sheldrake (US), John R. Falck (US), Daniel J. Brunelle (US), Martin F. Haslanger (US), Sunggak Kim (US), and Sung-eum Yoo (US) synthesized erythronolide B, an antibiotic produced by the bacterium Streptomyces erythreus. This antibiotic is a member of a group of antibiotics collectively called the erythromycins(2613, 2614).

A. González (), Antonio Jimenez (), D. Vazquez (), Julian E. Davies (CA), and Daniel Schindler (US), discovered the mode of action of hygromycin B, an inhibitor of translocation in eukaryotes (Eucarya)(2615).

Sir Aaron Klug (ZA-GB) determined the three-dimensional structure of chromatin by using high resolution electron microscopy and x-ray crystallographic analysis of the nuclease digests of chromosomes(2616).

Aharon Ciechanover (IL), Yaacov Hod (IL), Avram Hershko (IL), Keith D. Wilkinson (IL), Michael K. Urban (IL), Arthur L. Haas (US), Hanna Heller (IL), Irwin A. Rose (US), Alexander Varshavsky (RU-US), Daniel Finley (US), Esther Eytan (IL), Dvora Ganoth (IL), Tamar Armon (IL), Wolfgang Dubiel (DE), Katherine Ferrell (US), Greg Pratt (US), and Martin Rechsteiner (US) discovered that a small heat-stable polypeptide, ATP-dependent proteolysis factor1 (APF-1), is an essential component of the ATP-dependent proteolytic system of rabbit reticulocytes. They proposed that ubiquitin is the ATP-dependent proteolysis factor which conjugates with cellular proteins and suggested that such conjugates are the active intermediates in ATP-dependent proteolysis. They found that in eukaryotic cells proteins with abnormal structure are more readily conjugated to ubiquitin than most normal proteins and that these ubiquitin conjugates decayed more extensively than the corresponding average labeled cellular proteins(2617-2623).

Jack W. Lawler (US), Henry S. Slayter (US), and John E. Coligan (US) isolated, characterized, and named thrombospondin from human blood platelets. Platelet thrombospondin is an adhesive protein known to play a central role in the development of platelet aggregates(2624).

Stephanie Broome (US) and Walter Gilbert (US) developed a very sensitive method to detect as antigens the presence of specific proteins within phage plaques or bacterial colonies(2625). This is especially useful in DNA recombinant experiments in which one might desire to identify a bacterial cell containing a fragment of a gene from a higher cell.

Peter L. Ey (AU), Stephen J. Prowse (AU), and Charles R. Jenkin (AU) isolated pure IgG1, IgG2a, and IgG2b immunoglobulins from mouse serum using protein A-sepharose(2626).

Frederick Wayne Alt (US), Rodney E. Kellems (US), Joseph R. Bertino (US), and Robert Tod Schimke (US) purified cDNA sequences complementary to didydrofolate reductase mRNA of murine origin then used them to probe, to quantitate dihydrofolate reductase mRNA and gene copies in a number of different cell lines. When unstable cell lines were grown in the absence of 4-amino analogs of folic acid, e.g. methotrexate, loss of resistance to the drug was associated with a decrease in didydrofolate reductase gene copy number(2627).

Howard J. Edenberg (US), Stephen Anderson (US), and Melvin L. DePamphilis (US) were among the first to point out that eukaryotic DNA polymerase alpha is important in DNA replication(2628).

Dominic L. Poccia (US), D. LeVine (US), and James Chuo Wang (US) discovered DNA topoisomerase I which nicks the unwinding DNA during replication to allow relief of the positive supercoils(2629).

Robert Tjian (CN-US) reported the first detailed mapping of DNA sequences bound by a transcription factor. He used an adenovirus–simian-virus-40 (SV40) hybrid, which supported higher expression of a protein functionally similar to SV40 T antigen. He noted that the transcription-factor-binding site contained palindromic sequences(2630).

David R. Engelke (US), Sun-Yu Ng (US), Barkur S. Shastry (US), James J. Bieker (US), Paul L. Martin (US), Marcus D. Kretzschmar (US), Michael Meisterernst (DE), and Robert Gayle Roeder (US) were the first to isolate a eukaryotic chromosomal gene-specific transcription factor. It was from extracts of oocytes added to an egg cell-free system. They described many of the complex array of protein factors involved in transcription, e.g., transcription factors IIIA, IIIB, IIIC, and IIID, (TFIIIA), (TFIIIB), (TFIIIC), (TFIIID)(2631-2634).

Urs Rutishauser (US), Robert Brackenbury (US), Jean-Paul Thiery (FR), and Gerald Maurice Edelman (US) discovered cell adhesion molecules(2635).

Horst T. Witt (DE) showed that an electrical potential is created across the chloroplast inner membrane in less than 10-8 second after illumination(2636).

Rial D. Rolfe (US), David J. Hentges (US), Benedict J. Campbell (US), and James T. Barrett (US) determined that the oxygen tolerance of anaerobes is due in large part to their possession of Fe- and Mn-containing superoxide dismutase enzymes(2637).

Annie C.Y. Chang (US), Jack N. Nunberg (US), Randal J. Kaufman (US), Henry A. Erlich (US), Robert Tod Schimke (US), and Stanley Norman Cohen (US) constructed a bacterial plasmid that contained and phenotypically expressed the mammalian genetic sequence for mouse dihydrofolate reductase. The Escherichia coli host for this vector was rendered resistant to the antimetabolic drug trimethoprim(2638).

Albert Hinnen (US), James B. Hicks (US), and Gerald R. Fink (US) transformed a stable leu2- yeast strain to Leu2+ by using a chimeric ColE1 plasmid carrying the yeast leu2 gene. The ColE1DNA together with the yeast DNA integrated into the yeast chromosomes and once there behaved as a simple Mendelian element(2639).

Jean D. Beggs (GB) constructed chimaeric plasmids containing a yeast plasmid and fragments of yeast nuclear DNA linked to pMB9, a derivative of the ColEl plasmid from E. coli. These plasmids were used to develop a method for transforming a leu2 strain of S. cerevisiae to Leu+ with high frequency. The yeast transformants contained multiple plasmid copies which were recovered by transformation in E. coli. The yeast plasmid sequence recombined intramolecularly during propagation in yeast(2640).

Kevin Struhl (US), Dan T. Stinchcomb (US), Stewart Scherer (US), Ronald W. Davis (US), Chu-Lai (US), and John Anthony Carbon (US), using the methodology above provided the first evidence of replicators (DNA sequences required to direct replication initiation) in eukaryotic chromosomes(2641, 2642).

Gert Kreibich (DE-US), Belinda L. Ulrich (US), David Domingo Sabatini (US), Milton Bernard Adesnik (US), Alain Amar-Costesec (BE), John A. Todd (US), Victoria M. Harnik-Ort (US), Kulkarni Prakash (US), Eugene E. Marcantionio (US), David R. Colman (US), Michael Geoffrey Rosenfeld (US), Cristina Crimaudo (US). Michael Hortsch (DE), Heinrich Gausepohl (DE), David I. Meyer (DE ), Leander Lauffer (US), Pablo D. Garcia (US), Richard N. Harkins (US), Lisa M. Coussens (US), Axel Ullrich (US), Peter Walter (US), Marie-Madeleine Galteau (FR), Bénédicte Antoine (FR), and Hubert Reggio (FR) found that in the endoplasmic reticulum certain proteins are largely restricted to either the rough or smooth membranes(2643-2649).

Hao Wang Lee (KR), Pyung Woo Lee (KR), and Karl M. Johnson (US) isolated hantavirus, the etiological agent of Korean hemorrhagic fever, also referred to as hemorrhagic fever with renal syndrome(2650). Dr. Lee named it Hantaan virus for the Hantan river in Korea near where the prototype strain was obtained.

Hans J. Gross (DE), Horst Domdey (DE), Christine Lossow (DE), Peter Jank (DE), Manfred Raba (DE), Heidemarie Alberty (DE), and Heinz L. Sanger (DE) determined the nucleotide sequence and secondary structure of potato spindle tuber viroid. PSTV was the first pathogen of a eukaryotic organism for which the complete molecular structure has been established(2651).

Walter Charles Cornelius Fiers (BE), Roland R. Contreras (BE), Guy Haegemann (BE), Raphaël Rogiers (BE), André Van de Voorde (BE), Hugo Van Heuverswyn (BE), Jacqueline Van Herreweghe (BE), Guido Volckaert (BE), Maarten Ysebaert (BE), Vermuri B. Reddy (US), Bayar Thimmappaya (US), Ravi Dhar (US), Kiranur N. Subramanian (US), B. Sayeeda Zain (US), Julian Pan (US), Prabhat K. Ghosh (US), Maria L. Celma (US), and Sherman M. Weissman (US) determined the entire nucleotide sequence, 5243 bases, for the genome of Simian Virus 40(2652, 2653).

Norman Edwin Gibbons (CA) and Robert George Everitt Murray (CA) proposed that all prokaryotes be subdivided into four divisions: Gracilicutes (typical gram negative cell wall), Firmicutes (gram positive cell wall), Tenericutes (lacking a cell wall), and Mendosicutes (lacking peptidoglycan in their walls)(2654).

Jon G. Seidman (US), Marshall H. Edgel (US) and Philip Leder (US) cloned mouse immunoglobulin light chain structural gene sequences in a bacterial plasmid(2655).

Julian Davies (US) and David I. Smith (US) discovered that bacteria may become resistant to aminoglycosides by adenylating, phosphorylating, and acetylating sensitive enzymes(2656).

Ernest Robert Sears (US) and Lotti M. Steintz-Sears (US) made available an almost complete set of twenty-one 44-chromosome lines in which each wheat chromosome was represented by a pair of telocentrics for both arms of the chromosome(2657). This material was of great benefit to wheat geneticists.

Robert Peter Gale (US), Robert S. Sparks (US), and David W. Golde (US) showed that liver macrophages originate from stem cells in the bone marrow(2365, 2658).

T. Stuart Walker (US) and Herbert H. Winkler (US) proposed that Rickettsia prowazekii is internalized by a process termed induced phagocytosis. Active rickettsia can trigger the phagocytic process carried out by the host cell(2659).

Arthur J. Kornberg (US), John F. Scott (US), and LeRoy L. Bertsch (US) presented evidence for an unwinding enzyme in prokaryotes as part of the DNA replication mechanism. The enzyme would be named helicase(2660).

Georg Melchers (DK-DE), Maria Dolores Sacristán (DE), and Anthony A. Holder (DE) were the first to produce hybrid plants derived from fused protoplasts involving two species so different that they were genetically incompatible, e.g., potato and tomato(2661).

Benjamin C. Stark (US), Ryszard Kole (US), Emma J. Bowman (US), and Sidney Altman (CA-US) demonstrated the presence of a discrete RNA component in RNase P which appears to be essential for its enzymatic function(2662).

John Collins (US) and Barbara Hohn (US) created cloning vectors which were hybrids of lambda virus and plasmids. They called them ‘cosmids’(2663, 2664).

Steven Gillis (US), Mary M. Ferm (US), Winny Ou (US), Kendall A. Smith (US), and Paul E. Baker (US) described for the first time the biological and biochemical characteristics of the T cell growth factor (TCGF) now known as interleukin-2(2665-2668).

Erwin Neher (DE), Bert Sakmann (DE), and Joe Henry Steinbach (US) developed the extracellular patch clamp: a method for resolving currents through individual open channels in biological membranes(2669).

Kunihiro Matsumoto (JP), Akio Toh-e (JP), and Yasuji Oshima (JP) found that in Saccharomyces cerevisiae the polypeptide Gal80, the product of the gene GAL80, does not regulate Gal4, the product of gene GAL4. They found that Gal4 is preexisting, prior to the induction by galactose. These studies also demonstrated that nt all gene regulation is controlled by a repressor-operator relationship. 

Edwin D. Murphy (US), John B. Roths (US), and Eva M. Eicher (US) described the (lpr) lymphoproliferation, (gld) generalized lymphoproliferation, and (Yaa) Y chromosome-linked autoimmune accelerator mutations in mice. These single gene mutations mimic systemic lupus erythematosis (SLE) in man and are therefore valuable for biomedical research(2670-2673).

Francis Wiener (SE), Jack Spira (SE), Shinsuke Ohno (SE), Nechama Haran-Ghera (IL), and Georges Klein (SE) discovered that a trisomy for chromosome number 15 (and occasionally chromosome 17) is a common feature in mouse leukaemias induced by radiation or by chemicals(2674-2676).

Antony G. Searle (GB), Colin V. Beechey (GB), James McGrath (US), Davor Solter (DE), Bruce M. Cattanach (GB), M. Kirk (GB), M. Azim Surani (GB), Sheila C. Barton (GB), Michael L. Norris (GB), Jeffrey R. Mann (US), Robin H. Lovell-Badge (GB), Jean-Paul Renard (FR), Charles Babinet (FR), Wolf Reik (GB), and Marilyn Monk (GB) demonstrated that a genomic contribution from both the mother and the father is essential for successful development during mammalian embryogenesis, e.g., paternal genes inherited from the father, are responsible for making the placenta; maternal genes, inherited from the mother, are responsible for making the greater part of the embryo, especially the head and brain. This sovereignty of the paternal genes over the development of the placenta was named paternal imprinting (also called genomic imprinting)(2677-2692). 

Marisa Bartolomei (US), Sharon Zemel (US), Shirley M. Tilghman (US), Denise P. Barlow (GB-AT), Reinhard Stöger (AT), Bernhard G. Hermann (DE), K. Saito (US), Norbert Schweifer (AT), Thomas M. DeChiara (US), Elizabeth J. Robertson (US), and Argiris Efstratiadis (GR-US) reported that, in the mouse, three different genes are specifically and consistently expressed from only one parental copy: H19 and Igf2r from the maternal copy and Igf2 from the paternal copy(2693-2695).

Michael H. Wigler (US), Angel Pellicer (US), Saul J. Silverstein (US), and Richard Axel (US) developed an efficient method for introducing single copy mammalian genes into cultured-cells(2696).

Alexander W. Clowes (US) and Morris John Karnovsky (ZA-US) discovered that heparin, a well known anticoagulant, also inhibits the proliferation of smooth muscle cells(2697).

Steven Gillis (US), Paul E. Baker (US), Francis Ruscetti (US), and Kendall A. Smith (US) maintained long-term culture of human antigen-specific cytotoxic T cell lines(2698). 

Jørn Dyerberg (DK), Hans Olaf Bang (DK), Erik Stoffersen (DK), Salvador Moncada (GB), and Sir John Robert Vane (GB) hypothesized that eicosapentaenoic acid (EPA) plays a role in prevention of thrombosis and atherosclerosis(2699).

Jana Havrankova (CA), Donald E. Schmechel (US), Jesse Roth (US), Michael J. Brownstein (US), James L. Rosenzweig (US), Maxine A. Lesniak (US), Derek Le Roith (US), S. Anne Hendricks (US), S. Rishi (US), and Karin L. Becker (US) discovered that insulin (which was supposed to be produced only in the pancreas) is also made in the brain, as well as in one-celled organisms outside the human body(2700-2702).

Douglas L. Coleman (US) identified obese (ob/ob) and diabetes (db/db): two mutant genes causing diabetes-obesity syndromes in mice. Cross-circulation (parabiosis) experiments suggested that the ob/ob gene encodes a circulating factor that regulates the nutritional state and that the db/db gene encodes the receptor for this factor(2703). The syndrome produced by either or both homozygous recessive genotypes resembles morbid human obesity. 

Patricia R. Bergquist (NZ) wrote an authorative textbook on sponges(2704). She is the leading authority on the systematics of Keratose sponges (Orders Dictyoceratida, Dendroceratida and Verongida). Recently (1994) Professor Bergquist was knighted in recognition of her important scientific and academic work. She is commemorated by Acarnus bergquistae Van Soest et al., 1991, Halichondria bergquistae Hooper et al., 1995, Monosyringia patricae Lévi, 1993, and Xestospongia bergquistia Fromont, 1992.

James M. Hughes (US), Dannie G. Hollis (US), Eugene J. Gangarosa (US), and Robert E. Weaver (US) recognized Vibrio cholera non O-group 1 (non-O1) as a human pathogen(2705). It does not agglutinate in cholera O-group 1 antiserum(2706).

Anthony F. Purchio (US), Eleanor Erikson (US), Joan S. Brugge (US), Raymond L. Erikson (US), Marc S. Collett (US), Joan S. Brugge (US), and Paula J. Steinbaugh (US) were the first to isolate and define a polypeptide coded by an oncogene, the enzyme coded by the avian sarcoma virus src oncogene (this was after it was established that cancer-causing retroviruses carry oncogenes)(2707-2710). The protein product of this oncogene which is a unique enzyme drastically alters the biochemistry of the cell and diminishes its capacity for responding to regulatory signals from hormones. Of all the oncogenes now know, a substantial number seem to act in a similar way.

Arthur D. Levinson (US), Hermann Oppermann (US), Leon Levintow (US), Harold E. Varmus (US), and J. Michael Bishop (US) provided evidence that the transforming gene of avian sarcoma virus encodes a protein kinase (pp60) associated with a phosphoprotein(2711).

Walter Eckhart (US), Mary Anne Hutchinson (US), Tony Hunter (US), Owen N. Witte (US), Asim Dasgupta (US), David Baltimore (US), and Bartholomew M. Sefton (US) identified phosphotyrosine kinase activity associated with polyoma virus middle T antigen, Abelson murine leukaemia viral oncogene (Abl), and Rous sarcoma virus oncogene Src. They showed that these enzymes are essential for the malignant transformation of cells by the oncogenic proteins(2712-2714). As viral Src was derived from an evolutionarily conserved c-SRC cellular proto-oncogene, logic dictated that all vertebrate cells must contain at least one protein kinase that phosphorylates tyrosine.

Michael D. Waterfield (GB), Geoffrey T. Scrace (GB), Nigel Whittle (GB), Paul Stroobant (US), Ann Johnsson (SE), Ake Wasteson (SE), Bengt Westermark (SE), Carl-Henrik Heldin (SE), Jung-San Huang (TW-US), Thomas F. Deuel (US), Russell F. Doolittle (US), Michael W. Hunkapiller (US), Leroy E. Hood (US), Sushilkumar G. Devare (US), Keith C. Robbins (US), Stuart A. Aaronson (US), and Harry N. Antoniades (US) identified the putative transforming protein of simian sarcoma virus as platelet-derived growth factor (PDGF)(2715, 2716).

James Todd (US), Mark Fishaut (CA-US), R. Frank Kapral (US), and Thomas R. Welch (US) coined the phrase toxic-shock syndrome to describe an acute illness characterized by rapid onset of fever, hypotension, headache, myalgia, vomiting and diarrhea, mucous membrane hyperemia, laboratory evidence of multiple organ system dysfunction, and an erythematous rash with subsequent desquamation particularly on the palms and soles. This syndrome is consistently associated with Staphylococcus aureus (2717).

Peter G. Sargeaunt (GB), John E. Williams (GB), and J.D. Grene (GB) differentiated invasive from non-invasive Entamoeba histolytica by using isoenzyme electrophoresis(2718).

Matthias Leippe (DE), Egbert Tannich (DE), Rosa Nickel (DE), F. Gisou van der Goot (CH), Franc Pattus (FR), Rolf D. Horstmann (DE), and Hans Joachim Müller-Eberhard (DE-US-DE) discovered marked DNA differences between pathogenic and non-pathogenic isolates of Entamoeba histolytica(2719).

Hans Joachim Müller-Eberhard (DE-US-DE) showed that absence of the C3 complement component in blood predisposes an individual to recurrent infections(2720).

Andre  De Léan (CA), Peter J. Munson (US), and David Rodbard (US) developed a general computerized method to describe the dose-response curves to hormones, drugs, and neurotransmitters in terms of basal and maximal responses, ED50, and curve shape or steepness(2721).

Elaine K. Perry (GB), Bernard E. Tomlinson (GB), Garry Blessed (GB), Klaus Bergmann (GB), P.H. Gibson (GB), and Robert H. Perry (GB) obtained results suggesting a close relationship between changes in the cholinergic system within the brain and Alzheimer's dementia(2722).

Gerald Maurice Edelman (US) and Vernon B. Mountcastle (US) proposed the theory called neural Darwinism or the theory of neural group selection (TNGS). It assumed that morphogenesis of the brain with its myriad connections was initially constrained by homeotic genes and the like but then was subject to epigenetic events that resulted in enormous individual variation at the finest ramifications of neuroanatomy(2723, 2724).

Joseph H. Connell (US) proposed that the commonly observed high diversity of trees in tropical rain forests and corals on tropical reefs is a nonequilibrium state which, if not disturbed further, will progress toward a low-diversity equilibrium community. This may not happen if gradual changes in climate favor different species(2725).

Edward Osborne Wilson (US) wrote On Human Nature, a study of evolution and sociobiology for which he won the 1979 Pulitzer Prize for General Nonfiction(2592).

Richard Charles Lewontin (US) presents one of the best single treatments of the concept of adaptation(2726).


“The only solid piece of scientific truth about which I feel totally confident is that we are profoundly ignorant about nature. Indeed, I regard this as the major discovery of the past hundred years of biology.” Lewis Thomas(2727).

“A good laboratory, like a good bank or a corporation or government, has to run like a computer. Almost everything is done flawlessly, by the book, and all the numbers add up to the predicted sums. The days go by. And then, if it is a lucky day, and a lucky laboratory, somebody makes a mistake; the wrong buffer, something in one of the blanks, a decimal misplaced in reading counts, the warm room off by a degree and a half, a mouse out of its box, or just a misreading of the day’s protocol. Whatever, when the results come in, something is obviously screwed up, and then the action can begin.

The misreading is not the important error; it opens the way. The next step is the crucial one. If the investigator can bring himself to say, “But even so, look at that!” then the new finding, whatever it is, is ready for snatching. What is needed, for progress to be made, is the move based on the error.” Lewis Thomas(2727).

“The history of medicine has never been a particularly attractive subject in medical education and one reason for this is that it is so unbelievably deplorable a story … Bleeding, purging, cupping and the administration of infusions of every known plant, solutions of every known metal, every conceivable diet including total fasting, most of them based on the weirdest imaginings about the cause of disease, concocted out of nothing but thin air—this was the heritage of medicine until a little over a century ago.” Louis Thomas(2727).

“The aim of molecular biology is to find, in the structures of macromolecules, interpretations of the fundamentals of life.”Jacques Lucien Monod(2728).

Alan MacLeod Cormack (ZA-US) and Sir Godfrey Newbold Hounsfield (GB) were awarded the Nobel Prize in Physiology or Medicine for the development of computer assisted tomography (CAT scan).

John Edward Heuser (US), Thomas Sargent Reese (US), Michael J. Dennis (US), Yuh Nung Jan (US), Lily Yeh Jan (US), and Louise Evans (US) developed a high-resolution, deep-etching freeze-fracture technique using very rapidly frozen specimens(2729).

Harry Towbin (CH), Theophil Staehelin (CH), and Julian Gordon (CH) devised a method for the electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets. The method allows detection of proteins by autoradiography and is simpler than conventional methods(2730).

John M. Chirgwin (US), Alan E. Przybyla (US), Raymond J. MacDonald (US), and William J. Rutter (US) developed a method for isolation of RNA from tissue which contains a high level of RNAnase. The procedure entails rapid denaturation of nucleases with guanidinium thiocyanate and sedimentation of RNA through a CsCl cushion. The dense RNA is pelleted in the bottom of the tube, the DNA bands in the CsCl and proteins band in the top phase. The DNA may be saved and is not denatured during treatment. This is the method of choice when tissue is not limiting and large amounts of RNA are required(2731).

H. Chaim Birnboim (CA) and Janine Doly (CA) devised a simple, rapid procedure for extracting plasmid DNA from bacterial cells. The principle of the method is selective alkaline denaturation of high molecular weight chromosomal DNA while covalently closed circular DNA remains double-stranded(2732).

Michael C. Pirrung (US) carried out the total synthresis of isocomene, a tricyclic sesquiterpene from the rayless goldenrod, Isocoma wrightii(2733, 2734).

Gert J. Kruger (ZA), Pieter Streicher Steyn (ZA), Robert J. Vleggaar (ZA), and Christiaan J. Rabie (ZA) had isolated asteltoxin and determined its structure(2735).

Michel Satre (FR) found that asteltoxin, produced by Aspergillus stellatus, exerts a potent inhibitory effect on the adenosine triphosphatase activity of Escherichia coli BF1(2736).

Stuart Lee Schreiber (US) and Kunio Satake (US) carried out the complete synthesis of asteltoxin(2737-2739).

Al Claiborne (US), Douglas P. Malinowski (US), and Irwin Fridovich (US) discovered that Escherichia coli makes two catalases. One of these is only a catalase whereas the other is a dual catalase/peroxidase. These were named hydroperoxidase I and II respectively(2740, 2741).

W. Clark Still (US) carried out the total synthesis of periplanone B, a sex pheromone found in the female American cockroaches of the species Periplaneta americana(2742).

George Schmid (US), Tohru Fukuyama (JP), Kazuaki Akasaka (US), Yoshito Kishi (US), C.-L.J. Wang (US), Donald S. Karanewsky (US), David B. Collum (US), John H. McDonald III (US), W. Clark Still (US), Robert E. Ireland (US), Joseph D. Armstrong III (US), Jacques Lebreton (US), Robert S. Meissner (US), and Mark A. Rizzacasa (US) reported the first total synthesis of the ionophoric antibiotic, Monensin(2743-2750).

Avram Goldstein (US), Shinro Tachibana (US), Louise I. Lowney (US), Michael W. Hunkapiller (US), and Leroy Edward Hood (US) described the opioid properties of a tridecapeptide, the sequence of which corresponds to the NH2-terminal sequence of dynorphin, a novel porcine pituitary endorphin. They named it dynorphin-(1-13)(2751).

Andrew H.-J. Wang (US), Gray J. Quigley (US), Francis J. Kolpak (US), James L. Crawford (US), Jacques H. van Boom (NL), Gijs A. van der Marel (NL), and Alexander Rich (US) discovered the Z (left-handed) form of DNA (named for the zigzag backbone)(2752).

Fritz M. Pohl (DE) and Thomas M. Jovin (DE) had earlier suspected that such a form of DNA might exist(2753).

Wesley M. Brown (US), Matthew George, Jr. (US), Allan C. Wilson (NZ-US), Ellen M. Prager (US), and Alice Wang (US) found that mammalian and bird mitochondrial DNA mutates more rapidly than nuclear sequences(2754, 2755).

Shirley Gillam (CA) and Michael Smith (GB-CA) determined the optimum conditions and minimum oligodeoxyribonucleotide length of synthetic oligodeoxyribonucleotide necessary to produce a single defined point mutation in the DNA of the phage øX174(2756). This technique, called site-specific mutagenesis or site-directed mutagenesis, has become a very important method for determining the function of a particular protein or gene, by using single strands of viral DNA to mutate the genetic code at precise locations.

Patrick O. Brown (US), Craig L. Peebles (US), Alan Morrison (US), and Nicholas R. Cozzarelli (US) solved the problem of replicating circular DNA forming interlocking rings by their discovery of the enzyme topoisomerase II. This enzyme can cut both strands of a piece of DNA, pass another piece of DNA between the two ends, and then join the broken ends together again(2757, 2758).

P. Anthony Weil (US), Donal S. Luse (US), Jeffrey Segall (US), and Robert Gayle Roeder (US) reconstructed a cell-free system capable of the correct initiation of transcription by RNA polymerase II(2759).

Michael Rush Lerner (US) and Joan Argetsinger Steitz (US) discovered small nuclear ribonucleoproteins (snurps)(2760).

Michael Rush Lerner (US), John A. Boyle (US), Stephen M. Mount (US), Sandra L. Wolin (US), Joan Argetsinger Steitz (US), John Rogers (US) and Randolph Wall (US) proposed that the small nuclear RNA (snRNA) known as U1 is the recognition component of the nuclear RNA splicing enzyme of eukaryotic organisms and forms base pairs with both ends of an intron so as to align them for cutting and splicing(2761, 2762).

Michael Rush Lerner (US), John A. Boyle (US), John A. Hardin (US), and Joan Argetsinger Steitz (US) presented evidence that patients with lupus erythematosus develop autoantibodies that completely inhibit the splicing reaction in which small nuclear RNA (snRNA) remove introns(2763).

Edward M. De Robertis (UR-GB-CH-US), Susanne Lienhard (CH), and Ruth F. Parisot (CH) found that 5S RNA becomes concentrated in the nucleolus. Studies with lupus erythematosus antibodies showed that the migrating RNAs become associated with RNA-binding proteins(2764).

Philip R. Evans (GB), Peter J. Hudson (GB), and George W. Farrants (NO) worked out the molecular mechanism underlying allosteric regulation of the enzyme phosphofructokinase(2765, 2766).

Günter Klaus-Joachim Blobel (DE-US), Peter Walter (US), Chung Nan Chang (US), Barbara M. Goldman (US), Ann H. Erickson (US), and Vishwanath R. Lingappa (US) proposed the existence within integral membrane proteins of a stop-transfer sequence which serves to interrupt translocation and thereby to retain the polypeptide chain in the lipid bilayer. They also proposed the existence of specific sorting-sequences which would serve to route proteins to their final destination following translocation across or orientation within the membrane(2767).

C. Spencer Yost (US), Joe Hedgpeth (US), and Vishwanath R. Lingappa (US) presented experimental evidence for the existence of such stop-transfer sequences(2768).

Hans Peter Hauri (CH) presented experimental evidence in support of the existence of sorting-sequences(2769).

Lawrence W. Bergman (US), W. Michael Kuehl (US), Alan M. Tartakoff (US), Pierre Vassalli (CH), Sune Kvist (DE), Klas Wiman (SE), Lena Claesson (SE), Per A. Peterson (SE), Bernhard Dobberstein (DE), David G. Bole (US), Linda M. Hendershot (US), John F. Kearney (US), Barry E. Carlin (US), John Paul Merlie (US), Mary-Jane Gething (US), Karen McCammon (US), Joseph Frank Sambrook (GB-US-AU), Constance S. Copeland (US), Robert W. Doms (US), Eva M. Bolzau (US), Robert G. Webster (US), Ari Helenius (FI-US-CH), Klaus-Peter Zimmer (DE), Krystn R. Wagner (US), Glenn A. Healey (US), Ira Mellman (US), Thomas E. Kreis (US), Harvey Franklin Lodish (US), David S. Keller (US), William E. Balch (US), Juha Koivu (FI), and Raili Myllylä (FI) determined that assembly of most oligomeric proteins occurs prior to their exit from the endoplasmic reticulum. Some oligomers are assembled cotranslationally and some posttranslationally(2770-2780).

Hamilton O. Smith (US) reported that the sites recognized by many restriction endonucleases have a twofold symmetry(2781).

Martin Frank Gellert (US), Kiyoshi Mizuuchi (US), Mary H. O'Dea (US), Haruki Ohmori (JP), and Jun-ichi Tomizawa (JP-US) discovered DNA topoisomerase II (DNA gyrase) an enzyme which introduces breaks in both DNA strands simultaneously as a way to relieve the positive supercoils during unwinding associated with DNA replication(2782). 

Giuseppe Attardi (IT-US), Stephen T. Crews (US), Jerry Nishiguchi (US), Davin K. Ojala (US), James W. Posakony (US), Julio Montoya (ES), Thomas Christianson (US), David Levens (US), Murray Rabinowitz (US), James E. Hixson (US), William Walter Hauswirth, (US), David D. Chang (US), David A. Clayton (US), Enid F. Applegate (US), Barbara K. Yoza (US), and Daniel F. Bogenhagen (US) discovered that transcription in animal mitochondria, rather than initiating at each gene, begins at one promoter for each nucleotide chain of the DNA circle and transcribes the entire chain as a unit. In this sense, animal mitochondrial genomes consist of only two operons, one for each of the two nucleotide chains of the DNA circle(2783-2789).

Thomas A. Kunkel (US), Ralph R. Meyer (US), Lawrence A. Loeb (US), Roel M. Schaaper (US), and Robert A. Beckman (US) performed experiments which demonstrated that DNA polymerases are involved in the proofreading of DNA in eukaryotes (Eucarya)(2790, 2791).

Fred Heffron (US), Brian John McCarthy (US), Hisako Ohtsubo (JP), and Eiichi Ohtsubo (JP) reported that the genetic information contained within a transposon includes a transposase gene involved in a reaction cutting the transposon from one location in the genome and inserting it into a new one(2792).

Yoshimi Takai (JP), Akira Kishimoto (JP), Ushio Kikkawa (JP), Terutoshi Mori (JP), and Yasutomi Nishizuka (JP) described a protein kinase (now protein kinase C) requiring calcium, phosphatidylserine, and diacylglycerol for complete activation(2793).

Randy L. Bell (US), Donald A. Kennerly (US), Nancy Stanford (US), and Philip Warren Majerus (US) provided evidence that arachidonate release from stimulated platelets involves a diglyceride lipase acting on the diglycerides produced by a phosphatidylinositol-specific phospholipase C(2794).

Jørn Dyerberg (DK) and Hans Olaf Bang (DK) suggested for the first time a close relationship between platelet aggregation, bleeding time, and n-3 polyunsaturated fatty acids(2795).

Joseph A. Martial (US), Robert A. Hallewell (US), John D. Baxter (US), and Howard Michael Goodman (US) used mRNA to clone complementary DNA for human growth hormone, i.e., chorionic somatomammotropin. The cloned DNA was inserted into E. coli using a plasmid vehicle with the result that the bacteria produced human growth hormone(2796). 

Roger D. Kornberg (US), Brad W. Baer (US), Paul Berg (US), Richard J. Bram (US), and Yahli Lorch (US) performed pioneering studies of the components involved in the regulation of eukaryotic gene expression(2318, 2797-2801).

Lynna Hereford (US), Karen Fahrner (US), John Woolford, Jr. (US), Michael Rosbash (US), David B. Kaback (US), M. Mitchell Smith (US), Ólafur S. Andrésson (GB), and Kenneth Murray (GB) cloned the Saccharomyces cerevisiae genes encoding the four core histones, H2A, H2B, H3, and H4(2802-2804).

Yahli Lorch (US), Janice W. LaPointe (US), and Roger D. Kornberg (US) presented evidence that nucleosomes inhibit the initiation of transcription but allow chain elongation with displacement of histones(2805).

Paul S. Kayne (US), Ung-Jin Kim (US), Min Han (US), Janet R. Mullen (US), Fuminori Yoshizaki (US), and Michael Grunstein (US) found evidence that chromatin structure plays a key role in transcriptional silencing in Saccharomyces cerevisiae. These studies demonstrated that histone H4 mutants lacking their amino-terminal tails fail to silence HML and HMR(2806). This study led to the understanding that histone acetylation has a key role in transcriptional silencing.

Myeong-Sok Lee (US) and William T. Garrard (US) presented evidence that nucleosomes unfold to expose DNA during the transcription process(2807).

Joel N. Hirschhorn (US), Steven A. Brown (US), Chris D. Brown (US), and Fred Winston (US) found that the transcriptional activators Snf2/Swi2 and Snf5 activate transcription in yeast by altering chromatin structure. These proteins were envisioned to "function by removing or otherwise modifying nucleosomes" to allow transcription factors such as TATA-binding protein accessibility to their sies.(2808).

Brian D. Stahl (US) and C. David Allis (US) expressed the popular concept that multiple types of histone modifications control transcription(2809).

Michael D. Grove (US), Gayland F. Spencer (US), William K. Rohwedder (US), Nagabhushanam B. Mandava (US), Joseph F. Worley (US), J. David Warthen, Jr. (US), George L. Steffens (US), Judith L. Flippen-Anderson (US), and J. Carter Cook, Jr. (US) discovered brassinosteroids (BRs), or brassins, which are a group of plant hormones. These steroid compounds were first found in rapeseed plant (Brassica napus) pollen. The best known example of the brassinosteroids is brassinolide which controls plant development in response to light(2810).

Takao Yokoda (JP) proposed a pathway for the synthesis of brassinosteroids(2811).

Jianming Li (US) and Joanne Chory (US) identified a plasma membrane receptor (BRI1) involved in brassinosteroid signal transduction(2812).

William G. Burton (US), Constance T. Grabowy (US), and Ruth Sager (US) showed that chloroplast DNA of Chlamydomonas is methylated and paternal DNA is not methylated(2813).

Rolf Martin Zinkernagel (CH-US) and Peter Charles Doherty (AU-US) determined that infected host cells usually present microbial antigens on their surface in association with host structures encoded by the major histocompatibility (MHC) gene complex(2814).

Har Gobind Khorana (IN-US) was the first to accomplish in vitro synthesis of a complete gene (tyrosine tRNA suppressor gene)(2815).

Michael H. Wigler (US), Raymond Sweet (US), Gee Kee Sim (US), Barbara Wold (US), Angel Pellicer (US), Elizabeth Lacy (US), Thomas Peter Maniatis (US), Saul J. Silverstein (US), and Richard Axel (US) made a conceptual breakthrough as they demonstrated that when a selectable gene is transfected into a mammalian cell together with a gene that is not subject to selection, both genes are incorporated into the genome of the host cell at the one site; and when selection for the selectable gene is applied, both genes are amplified synchronously(2816).

James F. Gusella (US), Aviva Varsanyi-Breiner (IL), Fa-Ten Kao (US), Carol Jones (US), Theodore Thomas Puck (US), Cheryl Keys (US), Stuart Holland Orkin (US), and David Housman (US) determined the precise localization of the human beta-globin gene complex on human chromosome 11(2817).

C. Richard Madeley (GB) demonstrated the Calicivirus using electron microscopy(2818). Calicivirus infections commonly cause acute gastroenteritis in humans.

John B. Corliss (US), Jack Dymond (US), Louis Gordon (US), John M. Edmond (US), Richard von Herzen (US), Robert Ballard (US), Kenneth Green (US), David Williams (US), Arnold Bainbridge (US), Kathy Crane (US), and Tjeerd van Andel (US) discovered hydrogen sulfide oxidizing bacteria (chemolithotrophs) acting as primary producers at a depth of 2500 meters in an oceanic trench northwest of the Galápagos Islands. They noted that deep ocean, hot water vents in this area are surrounded by a community of giant clams and tube worms feeding on the sulfur oxidizing bacteria(2819).

Jacob J. Blum (US), Irwin Fridovich (US), Bridget E. Laue (US), and Douglas C. Nelson (US) reported that sulfur oxidizing bacterial endosymbionts are housed within the specialized spongy tissue organs (trophosome) of the tube worm, Riftia pachyptila, and gill filaments of the crab, Calyptogena magnifica. In these deep sea hydrothermal environments the microbes oxidize the hydrogen sulfide to obtain energy, converting carbon dioxide into organic compounds, which then are available for the nourishment of the invertebrates which lack digestive tracts(2820-2822). 

Dan T. Stinchcomb (US), Kevin Struhl (US), Ronald W. Davis (US), Bonita J. Brewer (US), Walton L. Fangman (US), Joel A. Huberman (US), Loretta D. Spotila (US), Kevin A. Nawotka (US), Suflan M. el-Assouli (SA), and Leslie R. Davis (US) identified autonomously replicating sequences (ARS). These are short DNA elements that are capable of directing replication of linked DNA molecules, and that therefore have the properties expected of replication origins(2823-2825).

Stephen P. Bell (US) and Bruce Stillman (US) discovered a complex of six proteins, known as origin recognition complex (ORC) which binds to yeast replication origins in an ATP-dependent fashion, providing an essential platform on which further steps in DNA replication are based(2826).

John F.X. Diffley (GB) and Julie H. Cocker (GB) provided evidence that a multiprotein pre-replicative complex accumulates on yeast replication origins in the G1 phase of the cycle(2827).

John F.X. Diffley (GB), Julie H. Cocker (GB), Simon J. Dowell (GB), and Adele Rowley (GB) show here that yeast replication origins exist in two chromatin states during the cell cycle. In the postreplicative state, genomic footprints closely resemble those produced in vitro by the purified ORC and ABF1 proteins, indicating that the binding of these proteins to replication origins is not sufficient to drive the initiation of DNA replication. The prereplicative state is characterized by an additional region of protection overlapping the ORC footprint. This prereplicative complex appears near the end of mitosis and persists through G1. After entry into S phase, origins return to the postreplicative state. Similarities in temporal regulation of the prereplicative state and the Xenopus licensing factor suggest that mechanisms limiting DNA replication to once per cell cycle may be conserved among eukaryotes(2828).

Paul E. Baker (US), Steven Gillis (US), and Kendall A. Smith (US) established the first monoclonal cytotoxic T cell lines(2829).

Steven Gillis (US), Gerald R. Crabtree (US), and Kendall A. Smith (US) produced results which indicate that a major mechanism of glucocorticoid mediated immunosuppression may occur at the level of the T cell growth factor (TCGF)-producing cell, resulting in the control of clonal expansion of activated T cells via inhibition(2830).

Goro Eguchi (JP) was among the first to show that genomic DNA does not undergo irreversible changes in most cases of cell differentiation(2831). Antibody forming cells are an exception to this rule.

Kunio Yamazaki (US), Masahiro Yamaguchi (JP), L. Baranoski (US), Judith Bard (US), Edward A. Boyse (US), and Lewis Thomas (US) found that urine is a potent source of the major histocompatability complex (MHC)-determined odors that distinguish individual mice. They observed that mice are able to distinguish other mice that have the same genes for the major histocompatibility complex, a part of the immune system that identifies "self" as opposed to “nonself”(2832).

Felipe Cabello (CL) and Kenneth N. Timmis (DE) realized that the genetic determinants for certain virulence characteristics, such as hemolysins, toxins and adhesive factors, can be carried by plasmids(2833).

Mapuera virus (MPRV) was isolated from the salivary glands of an apparently healthy fruit bat (Sturnira lilium) captured in the tropical rain-forest of Brazil in 1979(2834).

G.W. Henderson (GB), Carol Laird (GB), Evelyn Dermott (GB), and Bert K. Rima (GB) characterized the Mapuera virus(2835).

Thomas L. Hale (US) and Peter F. Bonventre (US) used transmission electron microscopy to demonstrate that Shigella flexneri is internalized by epithelial cells via an active endocytic process (2836).

Carol C. Halpern (US), William S. Hayward (US), and Hidesaburo Hanafusa (US) found that retroviruses with an incomplete, defective src oncogene can still produce tumors in animals. Viruses subsequently isolated from the malignant tumors had assembled a complete src gene, indicating that they had become oncogenic by capturing the missing portion of the src gene from the host-cell DNA(2837).

E. Tokunaga (JP), S. Sasakawa (JP), K. Tamaka (JP), H. Kawamata (JP), Carolyn M. Giles (GB), Elizabeth W. Ikin (GB), Joyce Poole (GB), David J. Anstee (GB), William J. Mawby (GB), and Michael J.A. Tanner (GB) report two Japanese blood donors who are the first homozygous MkMk individuals described; their red cells lack, as expected, known antigens of the MNSs blood group system and also have no demonstrable MN-active and Ss-active glycoproteins. Both MkMk individuals have a naturally occurring atypical antibody in their serum(2838).

Malarial resistance to chloroquine spreads in Africa.

Richard W. Ashford (GB) found an unidentified coccidian in patients in Papua New Guinea (confirmed as Cyclospora cayetanensis in 1993)(2839).

Rosemary Soave (US), Jitender P. Dubey (US), Leticia J. Ramos (US), and M. Tumings (US) found the same parasite (Cyclospora cayetanensis) in the stools of patients with HIV(2840).

Ynés R. Ortega (US), Charles R. Sterling (US), Robert H. Gilman (PE), Vitaliano A. Cama (US), and Fernando Diaz (PE) named the organism Cyclospora cayetanensis(2841). Since then it has been identified as the cause of a number of outbreaks of diarrhea and fatigue in both immunocompetent and immunosuppressed individuals. Cyclospora infections are known to be transmitted in water and on fruit, but the original source is not known.

Isao Arita (JP), as chief medical officer of the WHO World Smallpox Eradication Office, declares that smallpox (variola) is officially eliminated; the last natural case was seen in Somalia in 1977(2842). This represents the only microbial disease ever completely defeated.

Donald A. Henderson (US) also comments on this momentous accomplishment(2843).

Ernest Beutler (US) and Carol West (US) introduced a new anticoagulant preservative, citrate-phosphate-dextrose-adenine (CPDA-1), which extends the shelf life of whole blood and erythrocytes to 35 days(2844).

Ernest Beutler (US) and Carol West (US) found they could modify this solution to get a shelf life of  42-49 days(2845).

Jack Hirsh (AU-CA), Michael R. Buchanan (CA), Gregory W. Albers (US), John E. Atwood (US), David G. Sherman (US), Richard A. Hughes (GB), and Stuart J. Connolly (CA) established the value of aspirin in the prevention of stroke(2846-2849).

Herschel R. Harter (US), John W. Burch (US), Philip Warren Majerus (US), Nancy Stanford (US), James Albert Delmez (US), Charles B. Anderson (US), and Carol A. Weerts (US) discovered the ability of low-dose aspirin to prevent thrombosis by blocking thromboxane synthesis in the treatment of people at risk of heart attack, stroke, and other ailments associated with blood clots(2850). Thromboxane is a platelet-made molecule that causes the constriction of blood vessels and aggregation of platelets.

Philip Warren Majerus (US) found that aspirin blocks the thrombin-stimulated production of the icosanoid mediator thromboxane A2 in platelets by a unique mechanism. The acetyl group of aspirin covalently acetylates the enzyme cyclooxygenase, thereby permanently inactivating it. This effectively blocks production of all icosanoids(2851). 

Robert T. Giaquinta (US) provided strong evidence for the phloem loading of sucrose being coupled to a proton transport mechanism driven by a vectorial plasmalemma ATPase(2852).

G.Y. Wang (CN), T.A. Yin (CN), and H. Guanqing (CN) reported that the level of selenium in the diet is related to prevention of Keshan disease(2853-2858).

Judy C. Chang (US) and Yuet Wai Kan (CN-US) identified a gene mutation that causes beta-thalassemia(2859).

Richard Anthony Flavell (GB-US), René Bernards (NL), Jan M. Kooter (NL), Ernie de Boer (NL), Peter F.R. Little (AU), Gillian Annison (GB), Robert Williamson (AU), Lex H.T. Van der Ploeg (NL), Antonius W.T. Konings (NL), M. Oort (NL), Dirk Roos (NL), and Luigi F. Bernini (NL) showed that thalassemia, a group of inherited anemias, are the result of genetic defects. They went on to describe the exact nature of these genetic defects and the abnormal type of globin chain(s) they form(2860-2862). 

Yuet Wai Kan (CN-US), Kathleen Y. Lee (US), Mario Furbetta (IT), Andrea Angius (IT), and Antonio Cao (IT) then developed prenatal DNA tests for beta-thalassemia that are responsible for a dramatic reduction in the incidence of this disease in the Mediterranean region(2863).

Sven Hammarstrom (SE), Robert C. Murphy (US), Bengt Ingemar Samuelsson (SE), David A. Clark (US), Charles Mioskowski (FR), and Elias James Corey (US) determined the structure of leukotriene C(2864).

Robert A. Lewis (US), K. Frank Austen (US), Jeffrey M. Drazen (US), David A. Clark (US), Anthony Marfat (US), and Elias James Corey (US) identified the slow reacting substances (SRS) released during an anaphylactic reaction as leukotrienes(2865). These slow-acting but extremely potent substances cause blood vessels to constrict and lung tissue to contract.

Sven-Erik Dahlén (SE), Per Hedqvist (SE), Sven Hammarström (SE), and Bengt Ingemar Samuelsson (SE) announced that slow reacting substance (SRS-A) is a combination of the leukotrienes LTC4, LTD4 and LTE4. They hypothesized SRS-A to be a biochemical mediator of the asthma response(2866). 

James W. Weiss (US), Jeffrey M. Drazen (US), E. Regis McFadden, Jr. (US), Peter F. Weller (US), Elias James Corey (US), Robert A. Lewis (US), and K. Frank Austen (US) conducted the first human experiments on themselves, proving that leukotrienes caused the biological reactions of asthma(2867). This work stimulated a new class of asthma medications, leukotriene inhibitors, to be developed.

Jon Lindstrom (US) and many other workers demonstrated that both myasthenia gravis (MG) and experimental autoimmune myasthenia gravis (EAMG) are caused by an antibody-mediated autoimmune response to acetylcholine receptors(2868).

Hans R. Brunner (CH), Haralambos P. Gavras (US), Bernard Waeber (CH), Glen R. Kershaw (US), Gustave A. Turini (CH), Robert A. Vukovich (US), Doris N. McKinstry (US), and Irene M. Gavras (US) found that chronic inhibition of the angiotensin-converting enzyme with captopril offers an efficient and well-tolerated approach to the treatment of hypertension(2869).

David W. Cushman (US), Hong Son Cheung (US), Emily F. Sabo (US), Bernard Rubin (US), and Miguel A. Ondetti (US) developed Captopril (Capoten), a remarkably effective antihypertensive drug designed and developed as a potent and specific inhibitor of angiotensin-converting enzyme, a zinc metallopeptidase that participates in the synthesis of a hypertensive peptide, angiotensin II, and in the degradation of a hypotensive peptide, bradykinin(2870, 2871). Captopril is a powerful oral agent for the treatment of high blood pressure, heart failure, and diabetic kidney disease. The ACE (angiotensin converting enzyme) inhibitors prevent the formation in the blood of a naturally occurring substance, angiotensin II, which raises blood pressure. An ACE inhibitor called bradyknin potentiating factor (BPF), from the venom of snakes, was found to reduce blood pressure in rats. When eventually it could be purified, BPF was also shown to reduce blood pressure in patients. Various synthetic preparations were tested in rats, resulting in the introduction of captopril.

Gerald F.M. Russell (GB) described and named bulimia nervosa(2872).

Ellen Solomon (GB) and Sir Walter Fred Bodmer (GB) estimated that the sickle variant gene first appeared 2785 generations (or about 69,625 years BP). This suggests that the origin of the sickle allele might well predate the origin of the major human racial groups, although its striking increase in frequency was much more recent(2873). 

Andreas R. Gruentzig (DE) and David A. Kumpe (US) described recanalization of superficial femoral artery occlusions and of stenoses in the superficial femoral and pelvic arteries using the Gruentzig balloon catheter (angioplasty)(2874).

Andreas R. Gruentzig (DE), Ake Senning, (SE) and Walter E. Siegenthaler (CH) described their technique of percutaneous transluminal coronary angioplasty (PTCA) as used in 50 patients(2875).

Karl Victor Hall (NO), Robert L. Kaster (US), and Arne Wøien (NO) developed a pivotal disc prosthetic heart valve. This prosthetic valve has no welds, joints, or bends that can eventually weaken the valve's structure(2876). The Medtronic-Hall Valve.

Stephen P. Hubbell (US) studied patterns of tree abundance and dispersion in a tropical deciduous (dry) forest. He concluded that all species were either clumped or randomly dispersed, with rare species more clumped than common species. Breeding system was unrelated to species abundance or dispersion, but clumping was related to mode of seed dispersal(2877).

Richard D. Alexander (US), John L. Hoogland (US), Richard D. Howard (US), Katharine M. Noonan (US), and Paul W. Sherman (US) explained that species in which sexes are the same size tend, with some exceptions such as horses, not to have harems. Species in which males are markedly bigger than females tend to have harems, or to practice some other form of polygyny(2878).

Pere Alberch (US), Stephen Jay Gould (US), George F. Oster (US), and David B. Wake (US) formalized the notion of ‘ontogenetic trajectories’and proposesed a formal lexicon of heterochrony terms(2879).

Stephen Jay Gould (US) and Richard C. Lewontin (US) wrote this paper which marks the beginning of the modern era of constraint theory and a critique of the adaptationist programme(2880).

Richard Evans Schultes (US) and Albert Hofmann (US) wrote Plants of the Gods: Origins of Hallucinogenic Use, a very influential book(2881). 

Mark E. Barley (AU), John S.R. Dunlop (AU), Joseph John Edmund Glover (AU), David I. Groves (AU), and Roger Buick (AU) concluded from their studies of sedimentary rocks in Western Australia that near 3.5 Ga there existed a shallow marine environment dominated by episodic island volcanism and hydrothermal activity(2882, 2883).

Luis Walter Alvarez (US), Walter Alvarez (US), Frank Asaro (US), Helen Michel (US), and Alessandro Montanari (IT) found convincing physical and chemical evidence that the great extinctions which terminated the age of the dinosaurs were related to the high-speed impact on Earth of a great asteroid estimated to have been about 10 km in diameter. The element of catastrophe was thus introduced into the studies of the evolution of life forms(2884-2886).

Alan K. Hildebrand (US), Glen T. Penfield (US), David A. Kring (US), Mark Pilkington (CA), Z. Antonio Camargo (MX), Stein B. Jacobsen (US), and William V. Boynton (US) discovered the Chicxulub (shick-zoo-loob) crater in the Yucatán Peninsula, supporting the asteroid impact theory(2887-2889).

Digby J. McLaren (CA) and Wayne D. Goodfellow (CA) presented a model for the environmental effects of large asteroid and comet impacts and some evidence for large impact events at most of the major extinction horizons(2890).

Tamara Anastasevna Ishchenko (RU) and R.N. Shylokov (RU) discovered fossil Marchantiales in lower Middle Devonian material from the USSR providing evidence that some major bryophyte divisions were well established by the Lower Devonian and that the bryophytes in general must have played a part in the initial colonization of land by plants(2891).

John R. Horner (US) and Robert Makelar (US) found several fossilized dinosaur nests, which proved to them that some dinosaur parents cared for their young and even led to more evidence for the warm bloodedness theory(2892).

John R. Horner (US) presented evidence of colonial nesting and 'site fidelity' among ornithischian dinosaurs. This suggests that they may have moved about in a herd(2893).

Francois Lèvèque (FR) and Bernard Vandermeersch (FR), in 1979, found fossil remains of a Homo sapiens neanderthalensis; Homo neanderthalensis near Saint-Césaire in Southwestern France. The specimen has been dated between 34,000 and 31,000 B.P.(2894). This may well be the most recent Neandertal known.

Knut R. Fladmark (CA) has been one of the most vocal supporters of the proposal that humans from Siberia may have traveled along the Pacific coastlines as they populated North and South America(2895).


“Nothing in biology is understandable except in the light of genetics.” Francisco José Ayala(2896).

"I feel that much of the work is done because one wants to impose an answer on it. They have the answer ready, and they [know what they] want the material to tell them... [Anything else it tells them] they don't really recognize as there, or they think it's a mistake and throw it out... If you'd only just let the material tell you." Barbara McClintock(2897).

“I am, somehow, less interested in the weight and convolutions of Einstein’s brain than in the near certainty that people of equal talent have lived and died in cotton fields and sweatshops.” Stephen Jay Gould(2898).

Paul Berg (US) for his fundamental studies of the biochemistry of nucleic acids, with particular regard to recombinant-DNA and Walter Gilbert (US) and Frederick Sanger (GB) for their contributions concerning the determination of base sequences in nucleic acids shared the Nobel Prize in Chemistry.

Baruj Benacerraf (VE-US), Jean Baptiste Gabriel Joachim Dausset (FR) and George Davies Snell (US) were awarded the Nobel Prize in Physiology or Medicine for their discoveries concerning genetically determined structures on the cell surface that regulate immunological reactions.

Joseph P. Pinto (US), G. Randall Gladstone (US), Yuk Ling Yung (US), Akiva Bar-Nun (IL), Sherwood Chang (US), and James F. Kasting (US) showed that photochemistry in an atmosphere containing carbon dioxide or a mixture of carbon monoxide and carbon dioxide yielded formaldehyde as a major product(2899-2901).

Keith Burridge (GB-US) and James R. Feramisco (US) discovered the cell adhesion protein vinculin(2902).

Thomas N. Salzmann (US), Ronald W. Ratcliffe (US), F. Aileen  Bouffard (US), and Burton G. Christensen (US) carried out the total synthesis of the antibiotic thienamycin(2903, 2904).

Edith Kolb (GB), Peter J. Hudson (GB), and J. Leuan Harris (GB) determined the complete amino acid sequence of phosphofructokinase from Bacillus stearothermophilus(2905). 

J. Clark Lagarias (US) and Henry Rapoport (US) determined the structure of phytochrome chromophore attached to an undecapeptide, deduced from NMR spectra(2906).

Akira Endo (JP) discovered monacolin K (lovastatin), a drug which inhibits the synthesis of cholesterol and lowers cholesterol levels in the blood(2907).

Karl August Folkers (US), Peter H. Langsjoen (US), Richard Willis (US), Philip Richardson (US), Li-Jun Xia (CN), Chun-Qu Ye (CN), and Hiroo Tamagawa (JP) found that lovastatin decreases coenzyme Q levels in rats and humans(2908).

Ada Yonath (IL) , Jutta Mussig (DE), Bernd Tesche (DE), Siegfried Lorenz (DE), Volker A. Erdmann (DE), and Heinz Guenter Wittmann (DE) crystallized the large ribosomal subunits from Bacillus stearothermophilus(2909). They were the first to crystallize a ribosomal type.

Richard M. Wing (US), Horace R. Drew (US), Tsunehiro Takano (JP), Chris Broka (US), and Shoji Tanaka (US) gave hard evidence that the base sequence in DNA can have a pronounced effect on its structure(2910).

Louise Clarke (US), John Anthony Carbon (US), and Chu-Lai Hsiao (US), using Saccharomyces cerevisiae, were the first to isolate DNA specific to the centromere region of chromosomes(2911-2913).

Johannes Lechner (DE) and John Anthony Carbon (US) identified a 240-kDa multisubunit complex, CBF3, which is a major component of the budding yeast centromere(2914).

Graeme I. Bell (US), Raymond L. Pictet (US), William J. Rutter (US), Barbara Cordell (US), Edmund Tischer (US), Howard Michael Goodman (US), David Owerbach (US), and Thomas B. Shows (US) determined the nucleotide sequence of the human insulin gene and located it on chromosome 11(2915, 2916).

Shigekazu Nagata (JP), Hideharu Taira (JP), Alan Hall (GB), Lorraine Johnsrud (CH), Michel Streuli (US), Josef Ecsödi (CH), Werner Boll (CH), Kari Cantell (FI), and Charles Weissman (US) cloned double stranded cDNA for interferon (IF)-producing human leucocytes into Escherichia coli using the pBR322 vector. This clone produced a polypeptide with strong biological activity(2917).

John S. Emtage (GB), William C.A. Tacon (GB), Graham H. Catlin (GB), Brian Jenkins (GB), Alan G. Porter (GB), and Norman H. Carey (GB) demonstrated the feasibility of producing controlled amounts of influenza antigenic determinants by genetic engineering(2918).

Fred Sherman (US), John W. Stewart (US), and Ann Marie Schweingruber (US), working with Saccharomyces cerevisiae established that there is no absolute requirement for a particular sequence 5′ to the initiation codon, consistent with their previous suggestion that translation starts at the AUG codon closest to the 5′ end of the mRNA(2919).

William J. Adams, Jr. (US) and George F. Kalf (US) determined that DNA polymerase of mitochondria can act in the forward direction as a 5’ to 3’ polymerase and has a 3’ to 5’ exonuclease and proofreading capacity(2312).

Leonard Guarente (US), Thomas M. Roberts (US), and Mark Steven Ptashne (US) described methods allowing for the efficient expression in Escherichia coli of cloned eukaryotic genes(2920). 

Martin G. Low (US) and Donald B. Zilversmit (US) demonstrated that alkaline phosphatase is attached to membranes of Staphylococcus aureus by a strong interaction with phosphatidylinositol(2921). This discovery of anchor molecules had an impact on several areas of cell biology.

Ananda M. Chakrabarty (US) filed for a U.S. patent on strains of the bacteria Pseudomona aeruginosa and Pseudomonas putidas which had been genetically engineered to degrade crude oil. The patent was awarded to General Electric in 1980 by the U.S. Supreme Court and issued in 1981(2922).

David L. Rimm (US), Debra Horness (US), Jacky Kucera (US), and Frederick R. Blattner (US) reported the construction of three new lambda phage cloning vectors, Charons (Ch) 27, 28, and 30. Ch27 and Ch30, are suitable for cloning small and large DNA fragments, respectively, cut with BamHI, BglII, BclI, MboI, Sau3A, EcoRI, HindIII, SalI, and XhoI(2923). 

Dagmar E. Büchel (CH), Bruno Gronenborn (FR), and Benno Müller-Hill (DE) determined the nucleotide sequence of the lacY gene coding for lactose permease (M protein) in Escherichia coli and predicted that the enzyme would consist of 417 residues with a molecular weight of 46,504(2924).

Leland Harrison Hartwell (US) defined seven genes that function in two cell types of Saccharomyces cerevisiae (MATa and alpha) to control the differentiation of cell type and one gene, STE2, that functions exclusively in MATa cells to mediate responsiveness to polypeptide hormone(2925).

Arlene R. Wyman (US) and Ray White (US) discovered a locus in the human genome, not associated with any specific gene, which is a site of restriction fragment length polymorphism. The polymorphism was found by hybridizing a 16-kilobase-pair segment of single-copy human DNA, selected from the human genome library cloned in phage lambda CH4A, to a Southern transfer of total human DNA digested with EcoRI. DNAs from a number of individuals from within Mormon pedigrees as well as random individuals have been examined. The locus is highly variable, with at least eight alleles present, homozygotes accounting for less than 25% of the individuals examined. The polymorphism appears to be the result of DNA rearrangements rather than base-pair substitutions or modifications. Examination of the DNA from seven members of a family revealed fragment lengths that are consistent with their inheritance as Mendelian alleles through three generations(2926).

Alec John Jeffreys (GB), Polly Weller (GB), Victoria Wilson (GB), Alain Blanchetot (US), and Swee Lay Thein (GB) found two core DNA sequences common to the repeated sequences described by Arlene R. Wyman (US) and Ray White (US) in 1980. They developed complements to these core sequences to probe for the core sequences in partially digested and electrophoresed human DNA. The banding patterns which appear upon electrophoresis and probing are inherited in a Mendelian fashion. One half of the bands in a child’s DNA fingerprint is inherited from the mother and one half from the father(2927, 2928). The highly repetitious DNAs with the same core sequence are referred to as minisatellites.

Alec John Jeffreys (GB), Vicky Wilson (GB), Swee Lay Thein (GB), John F.Y. Brookfield (GB), Robert Semeonoff (GB), Peter Gill (GB), David J. Werrett (GB) Päivi Helminen (FI), Christian Ehnholm (FI), Marja-Liisa Lokki (FI), and Leena Peltonen (FI) described methodology for doing DNA fingerprinting. It was Jeffreys who coined the term DNA fingerprinting and was the first to use DNA polymorphisms in paternity, immigration, and murder cases(2929-2932).

Mauri E. Krouse (US), Menasche N. Nass (US), Jeanne M. Nerbonne (US), Joel Nargeot (FR), Henry A. Lester (US), Nigel J.M. Birdsall (GB), Jane Stockton (US), Norbert H. Wassermann (US), and Bernard F. Erlanger (US) compared the activation of cell membrane ion channels via nicotinic and muscarinic acetylcholine receptors (AChRs). They found the muscarinic response to be about a thousand times slower than the nicotinic response(2933, 2934).

W. Ford Doolittle (CA) and Carmen Spienza (CA) state that natural selection operating within genomes will inevitably result in the appearance of DNAs with no phenotypic expression whose only function is survival within genomes. Prokaryotic transposable elements and eukaryotic middle-repetitive sequences can be seen as such DNA's and thus no phenotypic or evolutionary function need be assigned to them(2935). As Matt Ridley puts it, “Genes do behave as if they have selfish goals, not consciously, but retrospectively: genes that behave in this way thrive and genes that don’t don't”(2936).

Kristin Eiklid (NO) Sjur Olsnes (NO), and Alexander Pihl (NO) reported on the mechanism by which the plant toxins abrin from the Indian licorice seed, ricin from the castor bean, and modeccin from Wild Granadilla (Adenia digitata) enter cells(2937, 2938).

Rockford K. Draper (US), Melvin I. Simon (US), Kristen Sandvig (NO), and Sjur Olsnes (NO) discovered how the toxic portion of the diphtheria toxin enters the cell cytoplasm by translocation across the cell membrane(2939, 2940).

Günter Klaus-Joachim Blobel (DE-US) expanded the signal hypothesis to say that topogenic sequences within discrete segments of targeted proteins are decoded by specific receptors, either during (cotranslational) or shortly after (post-translational) their biosynthesis. The specificity of such signal sequence-receptor interactions targets the proteins to the correct intracellular membranes where they are fed into translocons that move them across the hydrophobic core of the lipid bilayer. Similarly, it has been proposed that another class of topogenic sequences—termed stop-transfer sequences—interacts with the translocon to arrest further transport and thereby achieve an asymmetric transmembrane orientation of integral membrane proteins(2941).

Peter J. Novick (US), Charles Field (US), and Randy Schekmann (US) found that electron microscopy of Saccharomyces cerevisiae sec mutant cells reveals, with one exception, the temperature-dependent accumulation of membrane-enclosed secretory organelles. They suggested that these structures represent intermediates in a pathway in which secretion and plasma membrane assembly are colinear(2942).

Antti Salminen (FI) and Peter J. Novick (US) found that their analysis of SEC4 in Saccharomyces cerevisiae predicts a protein product of 23.5 kd molecular weight that shares 32% homology with ras proteins and is essential for growth. They proposed that the SEC4 product is a GTP-binding protein that plays an essential role in controlling a late stage of the secretory pathway(2943).

Hugh R.B. Pelham (GB), Kevin G. Hardwick (GB), and Michael J. Lewis (GB) reported that luminal endoplasmic reticulum (ER) proteins carry a signal at their C terminus that prevents their secretion; in S. cerevisiae this signal is the tetrapeptide HDEL. Indirect evidence suggests that HDEL is recognized by a receptor that retrieves ER proteins from the secretory pathway and returns them to the ER(2944, 2945). 

Michael J. Lewis (GB), Deborah J. Sweet (GB), and Hugh R.B. Pelham (GB) show here that presumptive endoplasmic reticulum (ER) proteins from the budding yeast Kluyveromyces lactis can terminate either with HDEL or, in the case of BiP, with DDEL. They concluded that ERD2 encodes the receptor that sorts luminal ER proteins(2946).

Peter V. Schu (US), Kaoru Takegawa (JP), Michael J. Fry (US), Jeffrey H. Stack (US), Michael D. Waterfield (US), and Scott D. Emr (US) discovered that VPS34 of Saccharomyces cerevisiae encodes a 110-kD protein with two regions of 33% sequence identity to a comparable carboxy-terminal domain of the bovine PI-3 kinase. Functional and genetic analyses demonstrated the catalytic identity of the yeast protein and the role of this enzyme reaction in the sorting of vacuolar proteins in vivo(2947).

Elliott M. Ross (US) and Alfred Goodman Gilman (US) described the hormone-regulated adenylate cyclase system which represents the origin of our understanding of the role of G proteins within the cell(2948).

Linda D. Rhein (US) and Robert H. Cagan (US) found that fish possess olfactory cilia with binding sites for amino acids that the fish smell, providing evidence for the existence of receptors for odorants(2949).

Linda B. Buck (US), Richard Axel (US), Nina S. Levy (US), Heather A. Bakalyar (US), Randall R. Reed (US), Marc Parmentier (BE), Frédéric Libert (BE), Stéphane Schurmans (BE), Serge Schiffmann (BE), Anne Lefort (BE), Dominique Eggerickx (BE), Catherine Ledent (BE), Catherine Mollereau (BE), Catherine Gérard (BE), Jason Perret (BE), Anton Grootegoed (BE), Gilbert Vassart (BE), Nissim Ben-Arie (IL), Doron Lancet (IL), Clare Taylor (GB), Miriam Khen (IL), Naoml Walker (IL), David H. Ledbetter (US), Romeo Carrozzo (US), Katen Patel (GB), Denise Sheer (GB), Hans Lehrach (GB), and Michael A. North (GB) determined that the initial step in olfactory discrimination requires the interaction of odorous ligands with a family of seven-transmembrane-domain receptors on olfactory sensory neurons. The repertoire of mammalian olfactory receptors is extremely large and consists of about 1000 different genes(2950-2953).

Andrew Chess (US), Michael M. Dowling (US), Linda B. Buck (US), Richard Axel (US), John Ngai (US), Kerry J. Ressler (US), and Susan L. Sullivan (US) obtained in situ hybridization results suggesting that each cell expresses only one or a small number of receptor genes, such that individual olfactory neurons are functionally distinct(2954-2956).

Anthony D. Mills (GB), Ronald A. Laskey (GB), P. Black (GB), and Edward M. DeRobertis (US) presented evidence of selective entry of nucleoplasmin (a protein) through the nuclear envelope(2957).

Bob B. Buchanan (US) discovered that thioredoxin, a small protein earlier found in bacteria by others, functions in regulating photosynthesis. In fulfilling this function, thioredoxin, in effect, acts as an "eye," allowing chloroplasts, the site of photosynthesis, to distinguish light from dark. The chloroplast thioredoxin system functions by breaking critical intrachain disulfide bonds on key enzymes thereby altering their activity in the light. In this way, the plant is able to maximize the energy obtained from the sun(2958).

Jean-Pierre Hernalsteens (BE), Francoise Van Vliet (BE), Marc De Beuckeleer (BE), Ann Depicker (BE), Gilbert Engler (BE), Michel Lemmers (BE), Marcelle Holsters (BE), Marc Van Montagu (BE), and Jeff Schell (DE) discovered the gene transfer mechanism between Agrobacterium and plants, which resulted in the development of methods to alter Agrobacterium into an efficient delivery system for gene engineering and to create transgenic plants. They inserted the bacterial transposon Tn7 into the Ti-plasmid of Agrobacterium tumefaciens. The inserted Tn7 DNA segment became part of the T DNA. The Tn7 segment was transferred to, and maintained in, the DNA of tumor tissue cultures induced by this mutant strain(2959).

Annick J. de Framond (US), Michael W. Bevan (US), Kenneth A. Barton (US), Richard B. Flavell (US), and Mary-Dell Chilton (US) created transgenic tobacco plants when they inserted kanamycin resistance bacterial genes(2960).

Josef Schell (BE) and Marc Van Montagu (BE), Marcelle Holsters (BE), Patricia Zambryski (BE), Henk Joos (BE), Dirk Inze (BE), Luis Herrera-Estrella (BE), Anna Depicker (BE), Marc de Block (BE), Allan Caplan (BE), Patrick Dhaese (BE), E. Van Haute (BE), Jean-Pierre Hernalsteens (BE), Henri de Greve (BE), Jan Leemans (BE), Rolf Deblaere (BE), Lothar Willmitzer (BE), Joachim Schroder (BE), and Leon Otten (BE) produced transgenic tobacco plants resistant to kanamycin and to methotrexate, a drug used to treat cancer and rheumatoid arthritis(2961).

Robert Fraley (US), Stephen Rogers (US), and Robert Horsch (US) produced transgenic petunia plants resistant to kanamycin(2962).

Norimoto Murai (US), Dennis W. Sutton (US), Michael G. Murray (US), Jerry L. Slightom (US), Donald J. Merlo (US), Nancy A. Reichert (US), Champa Sengupta-Gopalan (US), Carolyn A. Stock (US), Richard F. Barker (US), John D. Kemp (US) and Timothy C. Hall (US) inserted a bean gene into a sunflower plant(2963).

Peggy J. Farnham (US), Terry Platt (US), Howard B. Gamper (US), John E. Hearst (US), Peter H. von Hippel (US), David G. Bear (US), William D. Morgan (US), James A. McSwiggen (US), and Thomas D. Yager (US) established the bubble paradigm to describe the transcription of RNA from DNA(2964-2969).

Christiane Jani Nüsslein-Volhard (DE), Eric F. Wieschaus (US), Gerd Jürgens (DE), and Hildegard Kluding (DE), using Drosophila as their experimental material, discovered that during embryonic development homeotic genes act hierarchically, parceling up the embryo into smaller and smaller sections to create ever more detail. They proposed that gap genes help establish large-scale body patterns, whereas the segment-polarity and pair-rule genes control segmentation. The two-segment expression pattern of pair-rule genes, they suggested, could reflect an initial segmentation into seven double segments that later divide in half — perhaps avoiding errors that could arise in dividing the relatively few cells of the blastoderm evenly into 14 segments(2970-2972).

Hans Georg Fronhöfer (DE), Christiane Jani Nüsslein-Volhard (DE), and Wolfgang Driever (DE) discovered the first classic morphogen in Drosophila melanogaster, Bicoid (Bcd). Bcd is a maternal effect gene involved in anterior development in the fruit fly, and it controls the expression of zygotic segmentation genes, such as hunchback, in the developing embryo. This 55 KDa protein is localized in a visible gradient (with the highest concentration at the anterior) within the nuclei of cleaving embryos. This was the first work to identify a protein gradient in Drosophila embryos and led the authors to conclude that the protein was indeed a morphogen which had long-range effects on neighboring cells(2973-2976). 

Thomas Berleth (DE-CA), Maya Burri (DE), Gudrun Thoma (DE), Daniel Bopp (CH), Sibyll Richstein (DE), Gabriella Frigerio (DE), Markus Noll (CH), Wolfgang Driever (DE), and Christiane Jani Nüsslein-Volhard (DE) determined that the egg of the fruit fly, Drosophila melanogaster, is already marked front and rear, top and bottom, before it is fertilized. The mother in the very process of egg formation deposits at one location strands of messenger RNA—not a gene, but the gene’s transcript—for a protein called Bicoid. The Bicoid protein is distributed in a broad anterior-posterior gradient, with peak levels present at the anterior pole(2973, 2977-2979). This gradient controls the differentiation of head structures, and is also important for initiating the segmentation cascade.

Tommaso Meo (FR), Judith P. Johnson (DE), Colin V. Beechey (GB), Sandra J. Andrews (GB), Jürgen Peters (GB), and Anthony G. Searle (GB) discovered that in mice the genes coding for the production of the immunoglobulin heavy chain and serum prealbumin were located on chromosome 12(2980).

Tai-Kin Wong (DE), Claude Nicolau (FR), and Peter H. Hofschneider (DE) were the first to introduce a foreign gene into a mammalian cell using electroporation. The gene was bacterial beta-lactamase(2981).

J. Gregor Sutcliffe (US), Thomas M. Shinnick (US), Nicola Green (US), Fu-Tang Liu (US), Henry L. Niman (US), and Richard Alan Lerner (US) discovered previously unknown viral proteins of the Moloney leukaemia virus by starting with the viral nucleic acid sequence, synthesizing a protein from a particular nucleic acid segment, making rabbit antibodies to this protein, reacting the antibodies with Moloney infected cells. The result was the precipitation of two previously unidentified viral proteins(2982, 2983).

Harriet Harris (GB) suggested that genes can be controlled either at the level of transcription (DNA copying into RNA) in the nucleus or at the level of translation (protein production) in the cytoplasm after the messenger RNA has been exported from the nucleus. Harris performed an experiment in which he showed that once mRNA is formed and exported to the cytoplasm, the control mechanism for translation is then in the cytoplasm. If transcription is blocked by an antibiotic, mammalian cells continue to synthesize specific proteins for long periods in culture(2984).

David Botstein (US), Raymond L. White (US), Mark H. Skolnick (US), and Ronald W. Davis (US) launched a program to construct a genetic linkage map of the human genome(2985).

Richard Grantham (FR) articulated the genome hypothesis as, “The genetic code is used differently by different kinds of species. Each type of genome has a particular coding strategy, that is, choices among degenerate bases are consistently similar for all genes therein. This uniformity in the selection between degenerate bases within each taxonomic group has been discovered by applying new methods to the study of coding variability. It is now possible to calculate relative distances between genomes, or genome types, based on use of the codon catalog by the mRNAs therein”(2986).

Bernard J. Poiesz (US), Francis W. Ruscetti (US), Adi F. Gazdar (US), Paul A. Bunn, Jr. (US), John D. Minna (US), Marvin S. Reitz (US), Vaniambadi S. Kalyanaraman (US), Samuel Broder (US), Elaine S. Jaffe (US), William Blattner (US), Flossie Wong-Staal (CN-US), Thomas A. Waldmann (US), Vinvent T. DeVita, Jr. (US), Robert Charles Gallo (US), Mitsuaki Yoshida (JP), Isao Miyoshi (JP), Yorio Hinuma (JP), Takashi Uchiyama (JP), Junji Yodoi (JP), Kimitaka Sagawa (JP), Kiyoshi Takatsuki (JP), and Haruto Uchino (JP) were the first to discover a virus which causes cancer in humans; a human retrovirus. The virus, named Human T Lymphocyte Virus-1 (HTLV-1), causes a rare form of adult T cell leukaemia by integrating upstream of a cellular regulatory gene and causing it to over express itself leading to excess production of T cell growth factor, which stimulates proliferation of T lymphocytes(2987-2991).

Ruth Arnon (IL), Michael Sela (IL), Monique Parant (IL), Louis Chedid (FR), Francoise Audibert (FR), and Michel Jolivet (FR) prepared totally synthetic antigens, and these led to neutralization of a virus, MS2, as well as to protection against diphtheria and cholera(2992, 2993).

Christian Brechot (FR), Christine Pourcel (FR), Anna Louise (FR), Bernadette Rain (FR), and Pierre Tiollais (FR) reported that hepatitis B virus (HBV) DNA frequently integrates into the genome of human primary liver cancer cells(2994, 2995).

Robert F. Furchgott (US) and John V. Zawadzki (US) demonstrated that relaxation of isolated preparations of rabbit thoracic aorta and other blood vessels by acetylcholine requires the presence of endothelial cells, and that acetylcholine, acting on muscarinic receptors of these cells, stimulates release of a substance(s) that causes relaxation of the vascular smooth muscle(2996). The substance released by the endothelium was later found to be nitric oxide.

Kendall A. Smith (US), Kevin J. Gillbride (US), and Margaret F. Favata (US) provided evidence that lymphocyte activating factor (LAF) promotes the concentration-dependent release of T cell growth factor (TCGF). The extent to which T cells proliferate is determined by the concentration of TCGF. Thus a mechanism to control the extent of T cell clonal expansion is provided(2997).

Kendall A. Smith (US), Lawrence B. Lachman (US), Joost J. Oppenheim (US), and Margaret F. Favata (US) found that lymphocyte activating factor 1 (LAF1) = interleukin 1 (IL1) promotes the production of T cell-derived T cell growth factor (TCGF) = interleukin 2 (IL2)(2998).

Donald Bunjes (DE), Conny Hardt (DE), Martin Rollinghoff (DE), and Hermann Wagner (DE) found that cyclosporin A suppresses the production of cytotoxic T cells by impairing the release of interleukin 1 and interleukin 2(2999).

Richard J. Robb (US), Allan Munck (US), and Kendall A. Smith (US) determined that TCGF interacts with activated T cells via a receptor through which it initiates the T cell proliferative response(3000).

Richard J. Robb (US) and Kendall A. Smith (US) discovered that T cell growth factor (TCGF) is a protein which exists in various forms due to variable glycosylation(3001).

Warren J. Leonard (US), Joel M. Depper (US), Takashi Uchiyama (JP), Kendall A. Smith (US), Thomas A. Waldmann (US), and Warner C. Greene (US) partially characterized the membrane receptor for human interleukin-2(3002).

Constance A. Crowley (US), John T. Curnutte (US), Richard E. Rosin (US), Janine André-Schwartz (US), John I. Gallin (US), Mark Klempner (US), Ralph Snyderman (US), Frederick S. Southwick (US), Thomas P. Stossel (US), and Bernard M. Babior (US) discovered an inherited abnormality of neutrophil adhesion. It exhibits X-linked genetic transmission and it is associated with a missing protein of 110,000 mol. wt.(3003).

Wolf Szmuness (PL-US), Cladd E. Stevens (US), Edward J. Harley (US), Edith A. Zang (US), William R. Oleszko (US), Daniel C. William (US), Richard Sadovsky (US), John M. Morrison (US), and Aaron Kellner (US), between 1973 and 1980, designed and executed what has been described as the finest clinical field trial in the history of medicine, one that tested a vaccine for hepatitis B(3004).

D. Barth (US), Edwin S. Brokken (US), L.S. Blair (US), and William C. Campbell (US) discovered the antiparasitic nature of ivermectin(3005, 3006).

David E.R. Sutherland (US), Frederick C. Goetz (US), and John S. Najarian (US) performed the world's first living-donor (segmental) pancreas transplant(3007). 

William F. House (US) and Aziz Belal, Jr. (EG) pioneered the early diagnosis and translabyrinthine removal of schwannomas(3008).

Larry R. Brown (US), Robert S. Langer (US), Michael V. Sefton (US), Halimena M. Creque (US), Judah Folkman (US), Kam W. Leong (US), and Brigitta C. Brott (US) pioneered the field of controlled drug release delivery systems (slow release oral systems, transdermal patches, injectable microspheres, and slow release implants). These delivery systems involve macromolecules that have been incorporated into solid polymers from which they are released at controlled rates(3009-3012). This development has revolutionized medical therapy, permitted new therapies for patients, and by reducing the dose administered, has avoided complications and reduced costs. Examples of current drug applications include nitroglycerin, nicotine, cancer chemotheraputics, hormones and vaccines. In subsequent work, they determined the mechanism of release of drugs from polymers and then identified the factors that could be used to control the rate of release.

Charles C. Shepard (GB), Richard J.W. Rees (GB), Celia Lowe (GB), Philip Draper (GB), Morton Harboe (NO), Harvindar Kaur Gill (NO-MY), Abu Salim Mustafa (NO), Juraj Ivanyi (GB), and Tore Godal (NO) played important roles in the production of a vaccine for leprosy. It was licensed to the Wellcome drug company in England(3013-3016).

Barry R. Bloom (US) directed clinical efficacy trials of this vaccine for leprosy under the auspices of the World Health Organization(3017).

Victor Bruce Darlington Skerman (AU), Vicki F. McGowan (AU), and Peter Henry Andrews Sneath (GB) edited the Approved List of Bacterial Names. This publication had a major impact on bacteriology throughout the world and marked the culmination of an ambition to reform the nomenclature of the bacteria(3018).


“The reasons that have led professionals without exception to accept the hypothesis of evolution are in the main too subtle to be grasped by layman.” Sir Peter Brian Medawar(3019).

“He pondered a while and said ‘Of course, I have made mistakes—many of them. The only way to avoid making any mistakes is never to do anything at all. My biggest mistake was to get much to much involved in controversy. Never get involved in controversy. It’s a waste of time. It isn’t that controversy itself is wrong. No, it can be even stimulating. But controversy takes too much time and energy. That’s what is wrong about it. I have wasted my time and energy in controversy, when I should have been going on doing new experiments.” Birgit Vennesland quoting Otto Heinrich Warburg(3020).

Nicolaas Bloembergen (NL-US) and Arthur L. Schawlow (US) for their contribution to the development of laser spectroscopy and Kai M. Siegbahn (SE) for his contribution to the development of high- resolution electron spectroscopy were awarded the Nobel Prize in physics.

Roger Wolcott Sperry (US) for his discoveries concerning the functional specialization of the cerebral hemispheres and David Hunter Hubel (CA-US) and Torsten Niels Wiesel (SE-US) for their discoveries concerning information processing in the visual system shared the Nobel Prize in physiology and medicine.

W. Neal Burnette (US) developed western blotting: The electrophoretic transfer of proteins from sodium dodecyl sulfate-polyacrylamide gels to unmodified nitrocellulose followed by radiographic detection with antibody and radioiodinated protein A(3021).

John B. Corliss (US), John A. Baross (US), and Sarah E. Hoffman (US) proposed a thermophilic origin of life(3022).

Robert Day Allen (US), Jeffrey L. Travis (US), Nina Strömgren Allen (US), and HüSeyin Yilmaz (US) perfected video-enhanced contrast polarization (AVEC-POL) microscopy(3023). Robert and Nina were awarded U.S. Patent Number 4,412,246.

James R. Hawker, Jr. (US) and Juan Oró (US) synthesized peptides under plausible primitive Earth conditions(3024).

John Alan Kiernan (GB-CA) reported that formaldehyde fixes tissues by reacting with water to form methylene hydrate HOCH2OH, this then reacts with various parts of proteins to form methylene cross-links(3025).

Richard B. Sykes (GB), Christopher M. Cimaresti (US), Daniel P. Bonner (US), Karen Bush (US), David M. Floyd (US), Nafsika H. Georgopapadakou (US), William H. Koster (US), Wen-Chih Liu (US), William L. Parker (US), Pacifico A. Principe (US), Marlene L. Rathnum (US), William A. Slusarchyk (US), William H. Trejo (US), and Jerry Scott Wells, Jr. (US) described and named a novel group of monocyclic, bacterially produced beta-lactam antibiotics(3026).

Yong-Yeng Lin (US), Martin Risk (US), Sammy M. Ray (US), Donna Van Engen (US), Jon Clardy (US), Jerzy Golik (US), John C. James (US), Koji Nakanishi (US), Min S. Lee (US), Daniel J. Repeta (US), Koji Nakanishi (US), and Michael G. Zagorksi (US) discovered brevitoxin B, the potent lipid-soluble neurotoxin produced by dinoflagellates such as Ptycodiscus brevis Davis (Gymnodynium breve Davis) and associated with red tide. They also determined the molecular structure of this neurotoxin. It exerts its biological effect by binding to sodium channels of neurons, keeping them open, thereby causing depolarization of the cell membrane(3027, 3028).

Hirofumi Nakano (JP), Yuzuru Matsuda (JP), Kunio Ito (JP), Shuji Ohkubo (JP), Makoto Morimoto (JP), and Fusao Tomita (JP) discovered the gilvocarcins; new antitumor antibiotics. Gilvocarcin V and gilvocarcin M, with a novel skeleton, were discovered in culture broths of Actinomycete DO-38. (3029). Gilvocarcin V is a potent antitumor agent with low toxicity. It intercalates into DNA causing single-strand cleavage of duplex DNA when activated with low-energy light.

Takashi Matsumoto (JP), Takamitsu Hosoya (JP), Keisuke Suzuki (JP), and Eiji Takashiro (JP) carried out the complete synthesis of gilvocarcin M and gilvocarcin V(3030, 3031).

W.F. Becker (DE), Gebhard von Jagow (DE), Timm Anke (DE) and Wolfgang Steglich (DE) determined that the strobilurins and the related natural products oudemansin and myxothiazol inhibit respiratory electron transport between cytochrome b and cytochrome c1 of ubiquinol cytochrome c reductase. All of these are used to treat plants infected with fungi(3032).

Tsuyoshi Kihara (JP), Hiroo Kusakabe (JP), Goto Nakamura (JP), Tosio Sakurai (JP), and Kiyoshi Isono (JP) isolated, determined the structure, and reported the antineoplastic activity of cytovaricin which is produced by Streptomyces diastatochromogenes(3033, 3034).

Wylie Vale (US), Joachim Spiess (DE), Catherine Rivier (CH-US), and Jean E.F. Rivier (CH-US) purified corticotropin-releasing factor (CRF)(3035).

Ronald Bach (US), Yale Nemerson (US), William H. Konigsberg (US), George J. Broze, Jr. (US), Joseph E. Leykam (US), Benjamin D. Schwartz (US), and Joseph P. Miletich (US) purified tissue factor, the substance which initiates the blood clotting cascade(3036, 3037).

George J. Broze, Jr. (US), Ronald Bach (US), Rodney D. Gentry (US), Yale Nemerson (US), Daryl S. Fair (US), Marsha J. MacDonald (US), Toshiyuki Sakai (US), Torben Lund-Hansen (DK), Lisa R. Paborsky (US), Anders H. Pederson (US), and Walter Kisiel (US) found that tissue factor is an integral membrane glycoprotein located in the tissue adventitia and functions as a receptor for blood clotting factor VII (or VIIa) circulating in blood(3038-3041).

Hugo E. Jasin (US) and John T. Dingle (US) discovered a factor released from monocytes which promotes cartilage resorption. This substance would later be known as interleukin-1(3042).

Pennina R. Langer (US), Alex A. Waldrop (US), and David C. Ward (US) produced biotin-labeled polynucleotides which proved to be useful affinity probes for the detection and isolation of specific DNA and RNA sequences(3043).

Sandra L. Spurgeon (US) and John W. Porter (US) described the pathway to isopentyl diphosphate (IPP) in mammals and yeasts. This pathway starts from acetyl-CoA and proceeds through the intermediate mevalonic acid (MVA)(3044). IPP units condense to give rise to isoprenoids of various types.

Lionel V. Crawford (GB), David C. Pim (IT), Elizabeth Tucker G. Gurney (US), Peter Goodfellow (GB), Joyce Taylor-Papadimitriou (GB), Gilbert Jay (US), George Khoury (US), Albert B. DeLeo (US), Wolfgang G. Dippold (US), Lloyd J. Old (US), Samuel Benchimol (CA), Moshe Oren (IL), Nancy C. Reich (US), Arnold J. Levine (US), Sir David Lane (GB), and Ed Harlow (GB) discovered TP53 which was thought to be an oncogene but later found to be a tumor suppressor gene producing p53 which induces apoptosis among cells whose growth is out of control(3045-3050).

Suzanne J. Baker (US), Eric R. Fearon (US), Janice M. Nigro (US), Stanley R. Hamilton (US), Antonette C. Preisinger (US), J. Milburn Jessup (US), Peter vanTuinen (US), David H. Ledbetter (US), David F. Barker (US), Yusuke Nakamura (JP), Raymond White (US), and Bert Vogelstein (US) reported that two colon carcinoma cell lines contain deletions of chromosome 17p, causing loss of one TP53 allele, and that the remaining allele contains mutations in a highly conserved region. The authors proposed that normal p53 functions to suppress neoplastic growth, and that this suppression is relieved when TP53 is mutated or deleted(3051).

Janice M. Nigro (US), Suzanne J. Baker (US), Antonette C. Preisinger (US), J. Milburn Jessup (US), Richard Hostetter (US), Karen R. Cleary (US), Sandra H. Signer (US), Nancy Davidson (US), Stephen Baylin (US), Peter Devilee (US), Thomas Glover (US), Francis S. Collins (US), Ainsley Weslon (US), Rama Modali (US), Curtis C. Harris (US), and Bert Vogelstein (US) concluded that mutations in the p53 gene play a role in the development of many common human malignancies(3052).

Michael B. Kastan (US), Onyinye Onyekwere (US), David Sidransky (US), Bert Vogelstein (US), Ruth W. Craig (US), Steven J. Kuerbitz (US), Beverly S. Plunkett (US), William V. Walsh (US), Qimin Zhan (US), Wafik S. El-Deiry (US), France Carrier (US), Tyler Jacks (US), William V. Walsh (US), Beverly S. Plunkett (US),  and Albert J. Fornace, Jr. (US) described the role of p53 in the DNA damage-checkpoint response by showing that the G1-checkpoint arrest correlates with p53 protein induction. Cells with mutant or no p53 did not arrest in G1 after gamma-irradiation. GADD45 is described as one of the genes targeted by p53(3053-3055). p53 has emerged as a crucial guardian of the genome.

Elisheva Yonish-Rouach (IL), Dalia Resnitzky (IL), Joseph Lotem (IL), Leo Sachs (US-IL), Adi Kimchi (IL), and Mosha Oren (IL) suggested that products of tumor suppressor genes such as p53 could be involved in restricting precursor cell populations by mediating apoptosis(3056).

Holly Symonds (US), Leonard Krall (US),  Lee Remington (US), Mayte Saenz-Robles (US), Scott Lowe (US), Tyler Jacks (US),  and Terry Van Dyke (US) reported that p53-dependent apoptosis suppresses tumor growth and progression in vivo(3057).

Don Craig Wiley (US), Ian A.Wilson (GB-US), and John J. Skehel (GB) elucidated the structure of the influenza virus (Hong Kong) hemagglutinin glycoprotein(3058, 3059).

Joachim Messing (US), Roberto Crea (IT-US), and Peter H. Seeburg (DE) developed a method for the “shotgun” sequencing of DNA(3060).

Ronald Berezney (US), Linda A. Buchholtz (US), Scott C. Henderson (CA), David L. Spector (US), and Ray T. O´Keefe (GB) found that rather than being distributed evenly throughout the nucleus, replication appears to be concentrated in some 50 to 250 localized sites in eukaryotic nuclei(3061-3063).

Mark D. Matteucci (US), Marvin Harry Caruthers (US), Serge L. Beaucage (US), Christopher Becker (US), J. William Efcavitch (US), Eric F. Fisher (US), Gerald R. Galluppi (US), Ronit Goldman (IL), Pieter deHaseth (US), Lincoln McBride (US), et al., devised a way to synthesize strands of DNA of any desired base sequence(3064-3066).

Pierre Moreau (FR), Rene Hen (FR), Bodhan Wasylyk (FR), Roger Everett (FR), Marie-Pierre Gaub (FR), and Pierre M. Chambon (FR) discovered the DNA regulatory element—called the enhancer—that amazingly has the ability to increase the volume of transcription of genes from a very great distance(3067).

Christophe Benoist (US), Pierre M. Chambon (FR), Annette M. Healy (US), Terry L. Helser (US), and Richard S. Zitomer (US) found that the TATA box region is apparently involved in fixing the initiation of transcription precisely within a narrow area. They also found that gene expression in eukaryotes can be influenced by DNA elements remote from the TATA box(3068, 3069).

Julian Banerji (CH), Sandro Rusconi (CH), and Walter Schaffner (CH) provided further evidence that regulation by remote elements might be a general phenomenon. They showed that the SV40 72-bp repeats, which they called 'enhancers', could drive the expression of the heterologous rabbit hemoglobin 1 gene in HeLa cells. In addition, these enhancers could exert their effect even when placed thousands of base pairs upstream or downstream of the transcription-initiation site, independent of the orientation of the enhancer(3070).

Winship Herr (US-CH) and Yakov Gluzman (IL) found that damage to an enhancer region can be overcome (reverted) by simple tandem duplications in the enhancer region, which includes the 'core' element(3071). 

Winship Herr (US-CH) and Jennifer Clarke (US) described the modularity and redundancy (plasticity) of eukaryotic transcriptional regulatory elements(3072).

Rebecca Kellum (US) and Paul Schedl (US) demonstrated in Drosophila that chromatin is organized into domains that constitute transcription units, in which regulatory elements outside the domains have no effect on the gene activity within them. They described insulator DNAs as those DNA sequences that prevent enhancers and silencers located in one gene domain from interacting with promoters in neighboring domains(3073).

Edward L. Kuff (US), Leonard A. Smith (US), Kira K. Lueders (US), and John H. Rogers (GB) reported the existence of retrotransposons or retroposons. A retroposon is transcribed into an RNA copy that is subsequently used to produce a cDNA copy by reverse transcriptase. The cDNA copy is then inserted into the genome at a new location, leaving the original copy undisturbed and in place(3074, 3075).

Stephen Anderson (GB-US), Agnes T. Bankier (HU-GB-AU), Barclay George Barrell (GB), Maarten H.L. de Bruijn (GB), Alan R. Coulson (GB), Jacques Drouin (GB-CA), Ian C. Eperon (GB), Donald P. Nierlich (GB-US), Bruce A. Roe (GB-US), Frederick Sanger (GB), Peter H. Schreier (GB-DE), Andrew J.H. Smith (GB), Roger Staden (GB), Ian G. Young (GB-AU), Maureen J. Bibb (US), Richard A. van Etten (US), Catharine T. Wright (US), Mark W. Walberg (US), and David A. Clayton (US) sequenced the entire human mitochondrial genome providing evidence that the mammalian mitochondrial genome possesses an extremely compact organization; comparable to that of viral genomes. The mammalian mtDNA lacks introns and is completely saturated with genes except near the origin(3076-3078).

Michael Rosbash (US), Peter K.W. Harris (US), John L. Woolford, Jr. (US), and John L. Teem (US) discovered that genes for ribosomal proteins in yeast cells contain introns(3079).

George Klein (SE) discovered that the gene coding for the light chain of murine immunoglobulin molecules resides on chromosome number 6(3080).

Richard C. Mulligan (US) and Paul Berg (US) produced the first shuttle vector, Simian Virus 40 (SV40)-pBR322-derived deoxyribonucleic acid (DNA) vectors carrying the Escherichia coli gene (Ecogpt, or gpt) coding for the enzyme xanthine-guanine phosphoribosyltransferase (XGPRT). Cultured monkey kidney cells synthesized the bacterial enzyme after being infected(3081, 3082).

Jeffrey C. Edman (US), Robert A. Hallewell (GB), Pablo Valenzuela (CL-US), Howard Michael Goodman (US), and William J. Rutter (US) constructed plasmids capable of expressing the genes for hepatitis B surface and core antigens (HBsAg and HBcAg respectively). This promised to provide large quantities of the antigens necessary for a vaccine to this debilitating and potentially fatal disease(3083). 

Sidney V. Suggs (US), R. Bruce Wallace (US), Tadaaki Horose (US), Eric H. Kawashima (US), and Keiichi Itakura (US) synthesized labeled oligodeoxyribonucleotide probes to locate a small portion of the beta2-microglobulin. These were used to screen bacterial clones containing cDNA sequences primed with oligo(dT) and inserted into the plasmid vector pBR322(3084).

Jacques Perrault (US), Robert A. Lazzarini (US), Jack D. Keene (US), and Manfred Schubert (US) found that defective interfering (DI) RNAs , which represent one of several classes of symptom-modulating RNAs identified in association with RNA plant virus infections, are derived from, and represent mutant forms of, the viral genome(3085, 3086).

Bradley I. Hillman (US), David E. Schlegel (US), and Thomas J. Morris (US) were the first to definitively identify of a plant virus DI RNA when they described one associated with the small positive-sense RNA icosahedral virus, tomato bushy stunt virus(3087).

Richard A. Collins (US), Lori L. Stohl (US), Michael D. Cole (US), and Alan M. Lambowitz (US) discovered mitochondrial plasmids with base sequences unrelated to those of mitochondrial DNA(3088).

Georgiana May (US) and John W. Taylor (US) found horizontal transfer of mitochondrial plasmids, independently of mitochondrial DNA(3089). 

Bruno Gronenborn (DE), Richard C. Gardner (US), Sabine Schaefer (DE), and Robert J. Shepherd (US) reported the successful propagation of foreign DNA in plants using cauliflower mosaic virus as vector(3090). 

Eli Keshet (IL), Amit Rosner (IL), Yael Bernstein (IL), Marian Gorecki (IL), and Haim Aviv (IL) constructed a hybrid plasmid containing beta-lactamase gene of plasmid pBR322 and cloned coding sequences of bovine growth hormone (BGH). The constructed plasmid contains all DNA sequences required to encode BGH, and when used as a hybridization probe it detects one growth hormone gene in the bovine genome. The cloned DNA sequences are inserted into the beta-lactamase gene in the correct reading frame for BGH synthesis. The hybrid gene is expressed in bacteria and the product, a fused beta-lactamase-bovine growth hormone protein, is specifically immunoprecipitated with anti-serum to BGH(3091). Beginning in the 1930s BGH, usually in the form of pituitary gland material, had been injected into cows to increase milk yields. Biotechnology of the type mentioned above made BGH available in sufficient quantities for commercial use.

Marilyn Gist Farquhar (US) was the first to propose that vesicles budded off the surface of one cisterna in the Golgi too subsequently fuse with an adjacent cisterna. In this fashion material was moved via shuttle vesicles from the cis cisterna to the trans cisterna where it was released into secretory vesicles(3092). The implication was that individual cisternae remain more or less fixed in position, a concept which Erik Fries (US) and James Edward Rothman (US) supported experimentally(3093, 3094).

Peter Novick (US), Susan Ferro-Novick (US), William Hansen (US), Irene E. Schauer (US), Randy W. Schekman (US), Gregory S. Payne (US), Mitchell Bernstein (US), Werner Hoffmann (US), Gustav Ammerer (AT-US), Pamela C. Esmon (US), Brent E. Esmon (US), Alice B. Taylor (US), Richard I. Feldman (US), Tilman Achstetter (FR), Alex Franzusoff (US), C. Field (US), Akihiko Nakano (JP), Daniela Brada (US), Susie K. Lyman (US), Thomas Yeung (US), Akihiko Nakano (JP), and Charles Barlowe (US) initiated studies on the mechanism of protein secretion using the model eukaryotic cell, Saccharomyces cerevisiae. A classic genetic approach was developed to illuminate the processes of polypeptide import into the endoplasmic reticulum, protein sorting, and packaging into transport vesicles to acceptor membrane compartments. Secretory or SEC genes that encode the proteins implicated in these processes were cloned and shown to be evolutionarily conserved. Mammalian orthologs of the yeast SEC genes are now known to define most aspects of normal and specialized secretory processes. Schekman's group developed complementary biochemical approaches to define the exact roles of SEC proteins. Novel insights included the discovery of the major subunit of the polypeptide translocation channel of the endoplasmic reticulum (sec61p), the demonstration that cytosolic hsp70 promotes the post-translational translocation of secretory and mitochondrial precursor polypeptide, and the isolation of a novel coat protein complex, COPII, responsible for secretory and membrane cargo sorting and anterograde vesicle budding from the endoplasmic reticulum(3095-3106).

John E. Bergmann (US), Kiyoteru T. Tokuyasu (US), Seymour Jonathan Singer (US), Jon Green (GB), Gareth Griffiths (US), Daniel Louvard (FR), Paul S. Quinn (), Graham Warren (US), Jaakko Saraste (FI), and Esa Kuismanen (FI) using immunoelectron microscopy and viral membrane proteins as markers, demonstrated that proteins move from the endoplasmic reticulum through the Golgi cisternae(3107-3109).

Norifumi Hirota (JP), M. Kitada (JP) and Yasuo Imae (JP) found that in the bacterial genus Bacillus a sodium gradient substitutes for the proton gradient as the driving force behind flagellar rotation(3110, 3111).

Hajime Tokuda (JP), Makoto Asano (JP), Yoshiki Shimamura (JP), Tsutomu Unemoto (JP), Shigeru Sugiyama (JP), and Yasuo Imae (JP) found that in the bacterium Vibrio alginolyticus some flagella are driven by a proton gradient while others are driven by a sodium gradient(3112).

Joseph S. Tash (US) and Anthony R. Means (US) showed that flagellar motion in sperm and other flagellated cells is initiated by phosphorylation of flagellar polypeptides. Cyclic AMP-dependent protein kinase adds the phosphate groups(3113).

Mark C. Willingham (US), Ira Harry Pastan (US), G. Gary Sahagian (US), George W. Jourdian (US), and Elizabeth Fondal Neufeld (US) found that enzymes destined for a lysosome are marked in the Golgi by a post-insertion sorting signal that consists of a mannose sugar with a phosphate group added to its 6-carbon(3114).

Robert L. Margolis (FR-US) and Leslie Wilson (US) proposed microtubular treadmilling as a mechanism to explain the translocation of chromosomes during cell division and as a mechanism to move cellular organelles from one location within the cell to another(3115, 3116).

Sari Brenner (US), Daniel Pepper (US), Michael W. Berns (US), Eng M. Tan (US), and William R. Brinkley (US) demonstrated in eukaryotes (Eucarya) that centromeres of sister chromatids have duplicated by the G2 stage of mitosis(3117). 

Paul R. Dragsten (US), Robert Blumenthal (US), and Joseph S. Handler (US) found that tight junctions between cells block lateral movement of proteins and lipids(3118, 3119).

Peter C. Agy (US), Gary D. Shipley (US), and Richard G. Ham (US) introduced a defined, serum-free medium able to support the clonal growth of certain mammalian cells(3120).

Christopher Scot Henney (US), Kagemasa Kuribayashi (JP), Donald E. Kern (US), and Steven Gillis (US) reported that the activity of natural killer (NK) cells is stimulated by interleukin-2(3121).

Peter J. Rizzo (US) and David C. Sigee (GB) presented evidence that the dinoflagellates have a nuclear system intermediate in structural complexity between prokaryotes and eukaryotes (Eucarya)(3122, 3123).

H. Ernest Schnepf (US) and Helen Riaboff Whiteley (US) cloned the Bacillus thuringiensis toxin (Bt toxin) gene in Escherichia coli(3124).

Richard C. Parker (US), John Michael Bishop (US), Harold Elliot Varmus (US), Alan M. Schultz (US), Louis E. Henderson (US), Stephen Oroszlan (US), Ellen A. Garber (US), Hidesaburo Hanafusa (US), Gregory S. Payne (US), and Ronald Swanstrom (US) used DNA copies of the Rous sarcoma virus oncogene v-src to probe the cellular DNA of various animals. A closely related homolog, cellular c-src, was found in the DNA from normal chickens, fish, mammals, humans, and even Drosophila. Subsequently, other viral oncogenes were shown to have related cellular forms that have been conserved from species to species during the course of evolution. These retroviral oncogenes appear to be modified cellular genes captured by the virus from genomes of their vertebrate hosts. During provirus integration, all or part of the coding region of a cellular gene may be integrated within the sequences of the viral genome. Thus, the virus acts like a transducing phage, removing the cellular gene as part of its genome as it excises from the host DNA. The cellular gene is then packaged, along with viral sequences, into an infectious virus particle(3125-3129).

Ralph Lawrence Brinster (US), Howard Y. Chen (US), Myrna E. Trumbauer (US), Allen W. Senear (US), Raphael Warren (US), and Richard Deforest Palmiter (US) injected a plasmid, pMK, containing the structural gene for thymidine kinase from herpes simplex virus into the pronucleus of fertilized one-cell mouse eggs. The eggs were reimplanted into a pseudopregnant female and allowed to come to term. Of the adult mice resulting from this procedure 10 percent exhibited somatic expression of thymidine kinase(3130). 

Helmut Hahn (DE), and Stefan H.E. Kaufmann (DE) found that intracellular niches seem to be particularly useful for long-term survival of microbial pathogens in the face of an ongoing immune response because many diseases caused by intracellular microorganisms take a chronic course. Bacteria which have chosen macrophages as their preferred habitat include the following pathogens: Listeria monocytogenes, Mycobacterium tuberculosis, Mycobacterium leprae, Legionella pneumophila, and Salmonella typhimurium(3131).

Louis A. Magnarelli (US), John F. Anderson (US), Robert N. Philip (US), Elizabeth A. Caspar (US), Willy Burgdorfer (US), Alan G. Barbour (US), Stanley F. Hayes (US), Jorge L. Benach (US), Edgar Grunwaldt (US), and Jeffrey P. Davis (US) detected a treponema-like spirochete in and isolated it from adult Ixodes dammini, the incriminated tick vector of Lyme disease and showed antibody formation in patients with clinically diagnosed Lyme disease(3132, 3133).

Allen C. Steere (US), Robert L. Grodzicki (US), Arnold N. Kornblatt (US), Joseph E. Craft (US), Alan G. Barbour (US), Willy Burgdorfer (US), George P. Schmid (US), E. Johnson (US), and Stephen E. Malawista (US) described the causative agent and named it Borrelia burgdorferi in honor of Willy Burgdorfer(3134). See Arvid Afzelius, 1910.

Ruth L. Satter (US), Arthur W. Galton (US), Mary Jane Morse, (US), Youngsook Lee (US), Richard C. Crain (US), Gary G. Coté (US), and Nava Moran (IL) proposed that, following its interaction with light energy, phytochrome affects calcium ion release, which in turn alters other cellular processes(3135, 3136).

Richard Cawthon Starr (US) and Charles E. Miller (US) described the control of sexual morphogenesis in Volvox capensis(3137).

Tuomo Timonen (US), John R. Ortaldo (US), and Ronald Bo Herberman (US) discussed the characteristics of human large granular lymphocytes and their relationship to natural killer and K cells(3138).

Pat Levitt (US), M. Lee Cooper (US), and Pasko Rakic (US) found that neuronal and glial precursor cells coexisted in the cerebral ventricular zone of the fetal monkey(3139).

Sue Hockfield (US) and Ronald D.G. McKay (GB-US) generated monoclonal antibodies that distinguish among major cell types present during mammalian neurogenesis. These antibodies were used to analyze the development of cellular organization in the early nervous system(3140).

Urban Lendahl (SE), Lyle B. Zimmerman (US), and Ronald D.G. McKay (GB-US) describe a gene whose expression distinguishes the stem cells from the more differentiated cells in the neural tube. This gene was named nestin because it is specifically expressed in neuroepithelial stem cells my its production of the intermediate filament protein, nestin(3141).

Shigeo Okabe (JP), Karin Forsberg-Nilsson (SE), A. Cyril Spiro (US), Menahem Segal (IL), and Ronald D.G. McKay (GB-US) found that neuronal precursor cells can be isolated from embryonic stem cells and that these cells can efficiently differentiate into functional post-mitotic neurons of diverse central nervous system structures(3142).

Diana Boraschi (IT) and Aldo Tagliabue (IT) noted that large amounts of type 1 (alpha and beta) interferon can activate macrophages to express cytotoxicity against tumor cells(3143).

Judith L. Pace (US), Stephen W. Russell (US), Robert D. Schreiber (US), Amnon Altman (US), and David H. Katz (US) determined that relatively small amounts of type 2 (gamma) interferon are capable of priming macrophages for tumoricidal activity(3144).

Martin J. Evans (GB) and Matthew H. Kaufman (GB) showed that, by delaying implantation, they could obtain slightly enlarged mouse blastocysts, and that cells from these blastocysts could be used to establish embryonic stem (ES) cell cultures. These cultured cells were capable of differentiating in vitro and in vivo(3145-3150).

Gail R. Martin (US) established an embryonic stem (ES) cell line directly from normal pre-implantation mouse embryos and confirmed its pluripotency by showing that individual cells of this line could differentiate to form a wide variety of cell types in vitro and in vivo. She obtained the embryonic stem (ES) cell line by culturing cells isolated from blastocysts in a medium that had previously been conditioned by an established teratocarcinoma stem-cell line(3151).

James A. Thomson (US), Joseph Itskovitz-Eldor (IL), Sander S. Shapiro (US), Michelle A. Waknitz (US), Jennifer J. Swiergiel (US), Vivienne S. Marshall (US), and Jeffrey M. Jones (US) established a human pluripotent cell line which they derived from human blastocysts. The description of the cells is that they, “have normal karyotypes, express high levels of telomerase activity, and express cell surface markers that characterize primate embryonic stem cells but do not characterize other early lineages. After undifferentiated proliferation in vitro for 4 to 5 months, these cells still maintained the developmental potential to form trophoblast and derivatives of all three embryonic germ layers, including gut epithelium (endoderm); cartilage, bone, smooth muscle, and striated muscle (mesoderm); and neural epithelium, embryonic ganglia, and stratified squamous epithelium (ectoderm). These cell lines should be useful in human developmental biology, drug discovery, and transplantation medicine” (3152).

Peter J. Meier (CH), Urs Giger (CH-US), Otto Brändli (CH), and Jutta Fehr (DE) found that the therapeutic efficacy of pyridoxine (vitamin B6) in treating primary sideroblastic anemia is due to its effect on defective delta-aminolevulinic acid synthetase (ALAS). More generally, the data support the view that almost all features of primary sideroblastic anemia can be ascribed to a disturbance of heme synthesis in erythroblasts(3153).

Jean D. Wilson (US), James E. Griffin (US), Mark Leshin (US), and Fredrick W. George (US) report that male and female embryos develop in an identical fashion during the initial portion of gestation. If the indifferent gonad differentiates into an ovary (or if no gonad is present), a female phenotype is formed. Male phenotypic differentiation, however, requires the presence of an endocrinologically active testis. Two secretions of the fetal testis, Mullerian inhibiting substance and testosterone, are responsible for male development(3154, 3155).

Acquired immune deficiency syndrome (AIDS) was first defined by epidemiologists working at the Centers for Disease Control in Atlanta, GA, U.S.A. Many researchers contributed information which lead to the recognition and confirmation of this previously undescribed disease(3156-3171). Notables include: Michael S. Gottlieb (US), Howard M. Schanker (US), Peng Thin Fan (US), Andrew Saxon (US), Joel D. Weisman (US),  Robert A. Wolf (US), Irv Pozalski (US), Robert Schroff (US), Alvin E. Friedman-Kien (US), Linda J. Laubenstein (US), Pablo Rubenstein (US), Elena Buimovici-Klein (US), Michael Marmor (US), Rosalyn Stahl (US), Ilya Spigland (US), Kwang Soo Kim (US), Susan Zolla-Pazner (US), Henry Masur (US), Mary Ann Michelis (US), Jeffrey B. Greene (US), Ida M. Onorato (US), Robert A. vande Stouwe (US), Robert S. Holzman (US), Gary Wormser (US), Lee Brettman (US), Michael Lange (US), Henry W. Murry (US), Frederick P. Siegal (US), Carlos Lopez (US), Glenn S. Hammer (US), Arthur E. Brown (US), Stephen J. Kornfeld (US), Jonathan Gold (US), Joseph Hassett (US), Shalom Z. Hirschman (US), Charlotte Cunningham-Rundles (US), Bernard R. Adelsberg (US), David M. Parham (US), Marta Siegel (US), Susanna Cunningham-Rundles (US), Donald Armstrong (US), Anthony Stephen Fauci (US), Michael M. Lederman (US), Oscar D. Ratnoff (US), James Jay Scillian (US), Paul K. Jones (US), Bernice Schacter (US), James W. Curran (US), Dale N. Lawrence (US), Harold Jaffe (US), Jonathan E. Kaplan (US), Mary E. Chamberland (US), Ronald Weinstein (US), Kung-Jong Lui (US), Lawrence B. Schonberger (US), Thomas J. Spira (US), Lawrence D. Zyla (US), Joseph R. Bove (US), Gwendolyn B. Scott (US), Billy E. Buck (US), Joni G. Leterman (US), Floyd L. Bloom (US), Wade P. Parks (US), Nathan Clumeck (BE), Jean Sonnet (BE), Henri Taelman (BE), Francoise Mascart-Lemone (BE), Marc De Bruyere (BE), Philippe Vandeperre (BE), Jean Dasnoy (BE), Luc Marcelis (BE), Monique Lamy (BE), Claude Jones (BE), Luc Eyckmans (BE), Henri Noel (BE), Michel Vanhaeverbeek (BE), Jean-Paul Butzler (BE), John Leslie Fahey (US), Harry E. Prince (US), Michael Weaver (US), Jerry Groopman (US), Barbara R. Visscher (US), Kendra Schwartz (US), and Roger Detels (US).

Giancarlo Ghiselli (IT-US), Ernst J. Schaefer (US), Pere Gascon (ES), and H. Bryan Brewer, Jr. (US) found that patients with type 3 hyperlipoproteinemia develop premature atherosclerosis which may be due to an absence or striking deficiency of apolipoprotein E (apoE)(3172).

William K. Summers (US), John O. Viesselman (US), Gary M. Marsh (US), K. Candelora (US) found that tacrine (THA; 1,2,3,4-tetrahydro-9-aminoacridine) a centrally acting anticholinesterase, gives some relief of the symptoms of Alzheimer’s disease, especially in the more advanced cases(3173). This was one of the first drugs to show promise in the treatment of Alzheimer’s.

Adolfo J. de Bold (AR-CA), Harold Bernard Borenstein (CA), Anthony T. Veress (CA), Harald Sonnenberg (CA), and T. Geoffrey Flynn (CA) were the first to demonstrate that the heart has an endocrine function in addition to its role as a pump in the circulatory system. They discovered and isolated a hormone called atrial natriuretic factor (ANF), named thus because it is produced in the heart's atria and has very powerful diuretic and hypotensive properties. In general, de Bold explains, ANF counteracts the renin-angiotensin-aldosterone system in the body, which increases blood pressure and blood volume(3174, 3175). The discovery of an endocrine link between the heart and the kidneys has its basis in the electron microscopic finding that the striated muscle cells of the cardiac atria in mammals are differentiated both as contractile and as endocrine cells.

T. Geoffrey Flynn (CA), Mercedes L. de Bold (CA), and Adolfo J. de Bold (AR-CA) determined the amino acid sequence of an atrial natriuretic factor(3176).

Brian P. Kennedy (CA), Julian J. Marsden (CA), T. Geoffrey Flynn (CA), Adolfo J. de Bold (AR-CA) and Peter L. Davies (CA) isolated and sequenced a clone of cDNA which codes for the C-terminal 62 residues of the precursor molecule for the atrial natriuretic factor, cardionatrin(3177).

Judy C. Chang (US) and Yuet Wai Kan (CN-US) diagnosed sickle cell anemia antenatally, directly at the gene level, by restriction enzyme analysis of the DNA. This was the first disease to be so diagnosed(3178).

Susan Malcolm (GB), Paul Barton (GB), C. Murphy (GB), and Malcolm A. Ferguson-Smith (GB) localized the human beta globin genes on the short arm of chromosome 11 using in situ hybridization to fixed chromosomes(3179).

Susan Malcolm (GB), Paul Barton (GB), C. Murphy (GB), Malcolm A. Ferguson-Smith (GB), David L. Bentley (GB), and Terence H. Rabbitts (GB) located the human kappa light chain variable region genes on the short arm of chromosome 2 near the centromere(3180).

David H. Ledbetter (US), Vincent M. Riccardi (US), Susan D. Airhart (US), Richard J. Strobel (US), Bruce S. Keenan (US), and John Douglas Crawford, II (US) discovered a deletion in human chromosome 15 as the cause of Prader-Willi syndrome(3181).

Susan Lenz (DK), Jörgen G. Lauritsen (DK), and Merete Kjellow (DK) demonstrated for the first time that eggs can be obtained from ovarian follicles directly under ultrasound control(3182, 3183).

William G. Hayward (US), Benjamin G. Neel (US), Harriet Robinson (US), and Susan Astrin (US) were the first to associate the c-myc gene with B cell neoplasia when they found that the avian leukosis virus (ALV), which induces lymphomas in chickens, is associated with retroviral insertion into the 5’ end of the c-myc gene(3184).

Philip M.K. Leung (CA), Walter D. Rider (CA), Henry P. Webb (CA), Hélène Aget (CA), and Harold E. Johns (CA) invented and developed the Cobalt-60 machine which had an immediate impact on the cancer survival rate. Prior to the Cobalt-60, cancer therapy radiation could be used to treat superficial tumors but not those deep seated(3185).

Peter T. Boag (CA) and Peter R. Grant (GB-CA-US) found that survival of Darwin's finches through a drought on Daphne Major Island was nonrandom. Large birds, especially males with large beaks, survived best because they were able to crack the large and hard seeds that predominated in the drought. Selection intensities, calculated by O'Donald's method, are the highest yet recorded for a vertebrate population(3186). 

Joseph Felsenstein (US) created evolutionary trees using rRNA sequences and a maximum likelihood approach. He concluded that the Plantae, Animalia, and Fungi along with two new evolutionary assemblages (alveolates and stramenophiles) diverged nearly simultaneously(3187). Alveolates include dinoflagellates, apicomplexans, and ciliated protozoans. The stramenophiles include brown algae, labyrinthulids, chrysophytes, xanthophytes, diatoms, and oomycetes(3188).


“These are the gentle giants

Who walk softly through our lives.

No shrill demand for recognition

Commands our attentive admiration.

No blinding glare of brilliance

Announces their presence among us.

They are the quietly courageous ones

Who plant for future generations.

They are the creators and searchers

Who teach and celebrate the truth.” Solomon Spiegelman(3189).

Sir Aaron Klug (ZA-GB) was awarded the Nobel Prize in Chemistry for his development of crystallographic electron microscopy and his structural elucidation of biologically important nuclei acid-protein complexes.

Karl Sune Detlof Bergström (SE), Bengt Ingemar Samuelsson (SE) and Sir John Robert Vane (GB) were awarded the Nobel Prize in Physiology or Medicine for their discoveries concerning prostaglandins and related biologically active substances.

Kyriacos Costa Nicolaou (CY-US), Nicos A. Petasis (GR-US), Robert E. Zipkin (US), and Junìchi Uenishi (JP) carried out the complete synthesis of endiandric acids A-D. They are secondary metabolites from the Australian plant Endiandra introrsa(3190-3194).

Dawie P. Botes (ZA), Cornelis C. Viljoen (ZA), Helene Kruger (ZA), Philippus L. Wessels (ZA), and Dudley Howard Williams (ZA) determined the chemical structure of a hepatotoxin produced by the cyanobacterium, Microcystis aeruginosa (3195).

Ronald M. Wenger (CH) worked out the complete structural analysis and synthesis of cyclosporin A and cyclosporin H(3196, 3197).

Yuri A. Ovchinnikov (RU), Paul A. Hargrave (US), J. Hugh McDowell (US), Donna R. Curtis (US), Janet K. Wang (US), Elizabeth Juszczak (US), Shao-Ling Fong (US), J.K. Mohana Rao (US), and Patrick Argos (US) determined the complete amino-acid sequence of bovine rhodopsin. The molecule’s seven hydrophobic regions connected by hydrophilic loops suggested seven transmembrane alpha-helices(3198, 3199).

Andreas Pfaltz (CH), Bernhard Jaun (CH), Alexander Fässler (CH), Albert Eschenmoser (CH), Rolf Jaenchen (CH), Hans-Harald Gilles (DE), Gabriele Diekert (DE), and Rudolf K. Thauer (DE) isolated the nickel-containing cofactor F430 used by methyl coenzyme M reductase to generate methane. This is the way in which swamp gas is generated. They determined the structure of the methyl ester of cofactor F430M(3200, 3201).

Harland Goff Wood (US), Harold L. Drake (DE), Shou-Ih Hu (US), and Lars G. Ljungdahl (US) discovered and defined a novel pathway for carbon monoxide (CO) fixation in acetogens—a group of anaerobic bacteria that synthesize acetate from carbon monoxide or carbon dioxide and hydrogen(3202-3204).

The cluster of differentiation (CD) nomenclature was proposed and established in the 1st International Workshop and Conference on Human Leucocyte Differentiation Antigens (HLDA), which was held in Paris in 1982. This is a protocol used for the identification and investigation of cell surface molecules present on white blood cells.

Ursula Wilden (DE), Hermann Kühn (DE), Jeffrey L. Benovic (US), Ruth H. Strasser (US), Marc G. Caron (US), and Robert Joseph Lefkowitz (US), while exploring desensitizing or ‘shutting off’ of receptors, discovered that there exists a universal mechanism for regulation of the receptor superfamily (heptahelical G-protein-coupled receptors)(3205, 3206). Subsequently two families of protein regulators were described.

Julia A. Pitcher (US), Neil J. Freedman (US), and Robert Joseph Lefkowitz (US) discovered one of these families, the G-protein-coupled receptor kinases (GRKs 1-6) which phosphorylate only the activated form of the receptors(3207).

Robert Joseph Lefkowitz (US) discovered the second which are called arrestins. These bind the phosphorylated receptors and interdict further signaling to the G proteins(3208). 

Hartmut Michel (DE) prepared highly ordered crystals of the photosynthetic reaction center from a purple bacterium(3209).

Johann Deisenhofer (DE-US), Robert Huber (DE), Hartmut Michel (DE), Otto Epp (DE), Kunio Miki (JP), James P. Allen (US), George Feher (US), Todd O. Yeates (US), and Douglas C. Rees (US) performed x-ray analysis of three-dimensional crystals of the photosynthetic reaction center from the purple bacteria Rhodopseudomonas sphaeroides and Rhodopseudomonas viridis at 3 angstroms. The protein subunits of the complexes were identified and compared(3210, 3211).

Johann Deisenhorfer (DE-US), Hartmut Michel (DE), Robert Huber (DE), Otto Epp (DE), and Kunio Miki (JP) determined the details of the photosynthetically active components of protein, quinone, and iron(3212, 3213).

R. Glenn Hammonds, Jr. (US), Pierre Nicolas (FR), and Choh Hao Li (CN-US) identified a high molecular weight beta-endorphin complex (receptor) in extracts of rat brain membrane(3214).

R. Wayne Davies (GB), Richard B. Waring (GB), John A. Ray (GB), Terence A. Brown (GB), and Claudio Scazzocchio (FR) proposed a model for intron removal in which the three dimensional structure of the intron brings the ends of each intron together allowing an internal guide RNA sequence to pair with exon bases adjacent to the splice junctions. By this mechanism an intron is promoting its own excision(3215, 3216). They then proposed that this type of catalytic intron be called a ribozyme(3217).

Hiroto Okayama (JP) and Paul Berg (US) developed a high efficiency method for obtaining cDNA segments which contain the entire nucleotide sequence of the corresponding mRNA(3218). 

Jack William Szostak (GB-US) and Elizabeth H. Blackburn (AU-US) cloned yeast telomeres on linear plasmid vectors(3219).

Ilkka Palva (FI), Matti Sarvas (FI), Paivi Lehtovaara (FI), Mervi Sibakov (FI), and Leevi Kääriäinen (FI) constructed secretion vectors from the plasmid pUB110 and the promoter and signal sequence region of the alpha-amylase gene of Bacillus amyloliquefaciens. The Escherichia coli beta-lactamase gene was then inserted into the vector and used to transform non-secreting Bacillus subtilis cells into secretors of beta-lactamase(3220).

Leonard Guarente (US), R. Rogers Yocum (US), and Paula Gifford (US) demonstrated a Saccharomyces cerevisiae promoter element called an upstream activation site (UAS). This work demonstrates that the S. cerevisiae GAL UAS confers regulation in a gene fusion to the S. cerevisiae CYC1 gene thus demonstrating the autonomous function of a S. cerevisiae UAS(3221).   

Richard Hawkes (CA), Evelyn Niday (CA), and Julian Gordon (CA) developed a dot-immunobinding assay for monoclonal and other antibodies(3222). 

Michael Mackett (GB), Geoffrey L. Smith (GB), Bernard Moss (US), Dennis Panicali (US) and Enzo Paoletti (US) constructed a recombinant vaccinia virus expressing a foreign gene, the thymidine kinase (TK) gene of herpes simplex virus (HSV), which was inserted into the nonessential regions of the virus genome by homologous recombination(3223, 3224). 

Forrest A. Spencer (US), F. Michael Hoffmann (US), and William M. Gelbart (US) described the decapentaplegic gene complex in Drosophila melanogaster as a series of allelic mutations affecting imaginal disk development with the decapentaplegic (dpp) gene complex involved in the elaboration of positional information within developing epidermal tissue(3225).

William S. Dynan (US) and Robert Tjian (US) isolated the eukaryotic transcription factor Sp1 which works with RNA polymerase II(3226).

Rudolf Grosschedl (DE-US) and Max L. Birnstiel (BR-CH) reconstructed a cell-free system from sea urchin (Psammechinus miliaris) material in which they carried out the correct initiation of transcription by RNA polymerase I(3227).

Catherine M. Houck, (US), Carl W. Schmid (US), and Warren R. Jelinek (US) discovered the moderately repetitive nonfunctional sequence of DNA called Alu(3228, 3229).

Joachim Messing (US) and Jeffrey Vieira (US), and Celeste Yanisch-Perron (US) pioneered in the development of single stranded cloning vectors called pUC plasmids. These were derived from a single stranded filamentous DNA virus, M13, and were particularly valuable for DNA sequencing(3230-3232)

Joachim Messing (US) and Jeffrey Vieira (US) constructed single stranded DNA bacteriophage vectors, M13mp8 and M13mp9 containing a group of restriction sites. Because of their unique content of restriction sites DNA fragments whose ends corresponded to two of these restriction sites could be force cloned by ligation to one of these M13 cloning vehicles. M13mp8 and M13mp9 have their restriction site region arranged in opposite orientations relative to the M13 genome. Thus, a given restriction fragment can be directly orientated by forced cloning. This procedure guarantees that each strand of the cloned fragment will become the (+) strand in one or the other of the clones and thus be extruded as single stranded DNA in phage particles(3230).

Pablo Valenzuela (CL-US), Angelica Medina (US), William J. Rutter (US), Gustav Ammerer (AT), and Benjamin D. Hall (US) cloned the gene for hepatitis Hbs (surface) Ag into Saccharomyces cerevisiae thus providing a way of producing large quantities of the protein for use in a vaccine(3233). In 1986 the U.S. Food and Drug Administration approved a new vaccine containing yeast HBsAg.

Charles Weissmann (CH), Shigekazu Nagata (JP), Werner Boll (US), Michael Fountoulakis (CH), Atsuko Fujisawa (CH), Jun-ichi Fujisawa (CH), Joel Haynes (CA), Karsten Henco (DE), Ned Mantei (CH), Hermann Ragg (DE), Catherine H. Schein (CH), Jurg Schmid (CH), Gray D. Shaw (CH), Michael Streuli (US), Hideharu Taira (JP), Kazuo Todokoro (JP), and Ulrich Weidle (DE) fractionated poly(A)+ RNA by size on a sucrose gradient and cloned interferon cDNA from the active mRNA fraction assayed by injection into Xenopus laevis oocytes(3234). This was the first application of expression cloning.

Howard Curtis Berg (US), Michael D. Manson (US), and M. Patricia Conley (US) determined that flagellar rotation in prokaryotes is powered by a proton gradient across the cell membrane(3235).

Peter C. Isakson (US), Ellen Puré (US), Ellen S. Vitteta (US), and Peter H. Krammer (DE) provided experimental evidence that lymphokines produced by T cells can induce B cell differentiation. In the presence of lipopolysaccharide (LPS), this B cell differentiation factor(s) (BCDF) enhances IgG secretion by surface immunoglobulin (sIgG-) cells(3236).

Maureen Howard (US), John Farrar (US), Mary Hilfiker (US), Barbara Johnson (US), Kiyoshi Takatsu (JP), Toshiyuki Hamaoka (JP), and William E. Paul (US), in the mouse, identified a T cell-derived B cell growth factor distinct from interleukin 2. It interacts with B cells to maintain proliferation(3237).

Peter Nigel Tripp Unwin (GB) and Ronald A. Milligan (US) described some of the molecular architecture of the eukaryotic nuclear pore(3238).

Stamatis N. Alahiotis (GR) and George Kilias (GR) exposed Drosophila melanogaster populations to different temperature and humidity regimens for several years. They performed mating tests to check for reproductive isolation. They found some sterility in crosses among populations raised under different conditions. They also showed some positive assortative mating. These things were not observed in populations which were separated but raised under the same conditions. They concluded that sexual isolation was produced as a byproduct of selection(3239). This is an example of sexual isolation as a byproduct of adaptation to environmental conditions in Drosophila melanogaster.

Andrew L. Mellor (GB-US), Lynn Golden (GB), Elisabeth H. Weiss (GB), Hilary Bullman (GB), Jane L. Hurst (GB), Elizabeth Simpson (GB), R.F. James (GB), Alain R. Townsend (GB), Patricia M. Taylor (GB), Wilhelm Schmidt (DE), J. Ferluga (GB), Louise Leben (GB), Manuel Santamaria (GB), Gladys Atfield (GB), Hilliard Festenstein (GB), and Richard Anthony Flavell (GB-US) observed that expression of the murine H-2Kb gene product on the L-cell surface is sufficient to make it a target for killing by allospecific anti-H-2Kb cytotoxic T cells(3240).

Alain R. Townsend (GB), Frances M. Gotch (GB), and John Davey (GB) demonstrated that viral pathogens are degraded inside antigen presenting cells, and ultimately pieces of the virus derived from its core associate with Class I products of the Major Histocompatibility Complex (MHC)(3241).

Simon J. Powis (GB), Alain R. Townsend (GB), Edward V. Deverson (GB), Judy Bastin (GB), Geoffrey W. Butcher (GB), and Jonathan C. Howard (GB) established the essential role of these components in the assembly and surface expression of MHC Class I molecules themselves, leading to the discovery of peptide transporters in the endoplasmic reticulum(3242).

Werner W. Franke (DE), Christine Grund (DE), Caecilia Kuhn (DE), Brian W. Jackson (CH), Karl Illmensee (CH), Roland Moll (DE), Dorothea L. Schiller (DE), Erika Schmid (DE), Jürgen Kartenbeck (DE), Helga Mueller (DE), Monika Schmelz (DE), Rainer Duden (GB), and Pamela Cowin (US) identified desmogleins, desmoplakin I, and desmoplakin II as part of animal desmosomes(3243-3245).

Terrell Hill (US) and Marc Kirschner (US) described how the free energy of hydrolysis of ATP could be converted into mechanical work if actin polymerized against a resisting force(3246). This has elegantly been shown to account both for the extension of the leading edge of motile cells and the intracellular motility of Listeria and other infectious organisms that capture the cell's actin-based motility apparatus.

Frederick Sanger (GB), Alan R. Coulson (GB), Guofan F. Hong (CN), Diane F. Hill (GB), and George B. Petersen (GB) determined the nucleotide sequence of lambda virus DNA(3247).

Carl R. Woese (US) originally described the progenote as the last common ancestor for archaebacteria (Archaea), eubacteria (Bacteria), and eukaryotes (Eucarya). It contained informational polymers, could synthesize polypeptides and was still evolving a link between genotype and phenotype(2168, 3248).

Harald Huber (DE), Michael Thomm (DE), Helmut König (DE), Gesa Thies (DE), and Karl O. Stetter (DE) isolated hydrothermophilic microorganisms (Archea) with optimal growth at 105 degrees C, first from shallow marine springs and later from deep sea smokers(3249).

Katherine E. Steinback (US), Salil Bose (IN), David J. Kyle (CA), John Bennett (GB), L. Andrew Staehelin (CH-US), Charles J. Arntzen (US), Peter Horton (GB), Christine H. Foyer (GB), and John F. Allen (SE) discovered that movement of electrons through the Z pathway in photosynthesis is optomized by keeping its two photosystems in balance and operating at very near the same speed. The redox state of plastoquinone and the activity of a protein kinase maintain this control(3250-3254). 

Gerald Mayer Rubin (US) and Aaron C. Spalding (US) produced transgenic fruit flies. They introduced the gene for rosy eye color into a line of flies lacking a normal form of the gene. The normal rosy gene was inserted into a P element by recombinant DNA techniques, cloned in bacteria, then injected into Drosophila embryos. Adults exhibited the normal rosy eye color(3255, 3256).

Oliver Smithies (GB-US), Ronald G. Gregg (US), Sallie S. Boggs (US), Michael A. Koralewski (US), and Raju S. Kucherlapati (US) devised a method to find cells in which gene integration occurred at a chosen location. A rescuable plasmid containing globin gene sequences allowing recombination with homologous chromosomal sequences enabled them to produce, score and clone mammalian cells with the plasmid integrated into the human beta-globin locus. The planned modification was achieved in about one per thousand transformed cells whether or not the target gene was expressed. Their discovery showed that specific planned modification of native genes is possible. The DNA dart had found its corresponding sequence in the vast tangle of chromosomal DNA; they had targeted a specific gene(3257).

Kirk R. Thomas (US), Kim R. Folger (US), and Mario Renato Capecchi (US) corrected a defective gene residing in the chromosome of a mammalian cell by injecting into the nucleus copies of the same gene carrying a different mutation. They determined how the number, the arrangement, and the chromosomal position of the integrated gene, as well as the number of injected molecules influence the gene-targeting frequency. This is called high frequency targeting of genes to specific sites in the mammalian genome(3258, 3259).

Kirk R. Thomas (US) and Mario Renato Capecchi (US) succeeded in showing that the Hprt (hypoxanthine phosphoribosyl transferase) gene could be knocked out in embryonic stem (ES) cells. This revolutionary technique had the potential to be used to introduce any type of mutation in every gene and for the mutant cells to then be stably propagated(3260). Mutant ES cells could, in turn, be used to generate germ-line chimaeras, thereby allowing targeted knockouts or insertions, which could alter the expression of particular genes in the whole animal.

Kent G. Golic (US), Tian Xu (US), and Gerald Mayer Rubin (US) devised the FLP-FRT system of mosaic clone analysis. Andrea H. Brand (US) and Norbert Perrimon (US) devised the Gal4 system of mosaic clone analysis — two key techniques for disrupting gene expression in a small subset of cells, and for expressing genes ectopically in your cells of choice(3261-3263).

Carolyn A. Napoli (US), Christine Lemieux (US), Richard A. Jorgensen (US), Paul D. Cluster (IT), James English (GB), and Qiudeng Que (US), in an attempt to deepen the purple color of petunia flowers, introduced a pigment-producing gene under the control of a powerful promoter. Instead of the expected deep purple color, many of the flowers appeared variegated or even white. Jorgensen named the observed phenomenon cosuppression, since the expressions of both the introduced gene and the homologous endogenous gene were suppressed(3264, 3265). This was the discovery of a phenomenon now called post-transcriptional gene silencing (PTGS). PTGS appears to be a normal mechanism of eukaryotic cells.

Lander Ingelbrecht (BE), Helena van Houdt (BE), Marc van Montagu (BE), and Anna Depicker (BE) found that in PTGS the homologous RNA transcript is made, but that it is rapidly degraded in the cytoplasm and does not accumulate(3266).

Lori L. Wallrath (US) and Sarah C. Elgin (US) provided data suggesting that altered chromatin packaging plays a role in position effect variegation (PEV)(3267). A euchromatic gene placed in the vicinity of heterochromatin by a chromosomal rearrangement generally exhibits position effect variegation (PEV), a clonally inherited pattern showing gene expression in some somatic cells but not in others.

Scott M. Hammond (US), Amy A. Caudy (US), and Gregory J. Hannon (US) found that the trans-acting factor responsible for PTGS in plants is double stranded RNA (dsRNA)(3268).

Andrew Fire (US), SiQun Xu (CN-US), Mary K. Montgomery (US), Steven A. Kostas (US), Sam E. Driver (US), and Craig C. Mello (US) injected dsRNA — a mixture of both sense and antisense strands — into the nematode Caenorhabditis elegans. This injection resulted in much more efficient silencing than injection of either the sense or the antisense strands alone. Indeed, injection of just a few molecules of dsRNA per cell was sufficient to completely silence the expression of the homologous gene. Furthermore, injection of dsRNA into the gut of the worm caused gene silencing not only throughout the worm, but also in its first generation offspring(3269). This represents the discovery of RNAi, the i standing for interference.

Thomas A. Volpe (US), Catherine Kidner (US), Ira M. Hall (US), Grace Teng (US), Shiv I. S. Grewal (US), and Robert A. Martienssen (US) proposed that double-stranded RNA (dsRNA) arising from centromeric repeats targets formation and maintenance of heterochromatin through interference RNA (RNAi)(3270).

Stephen C. Meuer (DE), Rebecca E. Hussey (US), Ann C. Penta (US), Kathleen A. Fitzgerald (US), Beda Martin Stadler (CH), Stuart F. Schlossman (DE-US), and Ellis L. Reinherz (US) determined the cellular origin of interleukin 2 (IL 2) in man to be T4+ and T8+ T lymphocytes(3271).

Edouard M. Bevers (NL), Paul Comfurius (NL), Jan L.M.L. van Rijn (NL), H. Coenraad Hemker (), and Robert F.A. Zwaal (NL) reported that the activation of blood platelets triggers a change in the distribution of lipids in the plasma membrane: molecules of phosphatidylserine become exposed at the outer surface(3272).

A foreign gene incorporated into the cells of a tobacco (Nicotiana tabacum) plant was shown to be transmitted in ordinary Mendelian fashion through the gametes. ref

Richard Deforest Palmiter (US), Ralph Lawrence Brinster (US), Robert E. Hammer (US), Myrna E. Trumbauer (US), Michael Geoffrey Rosenfeld (US), Neal C. Birnberg (US), Ronald M. Evans (US), and Jean L. Marx (US) took a DNA fragment containing the promoter of the mouse metallothionein-I gene fused to the structural gene of rat growth hormone and microinjected it into the pronuclei of fertilized mouse eggs. The rat growth hormone gene was expressed giving rise to some supermice(3273, 3274).

Philip Goelet (GB), George P. Lomonossoff (GB), Peter J.G. Butler (GB), Michael E. Akam (GB), Michael J. Gait (GB), and Jonathan Karn (US) completed analysis of the entire nucleotide base sequence of the tobacco mosaic virus genome(3275). 

Norman D. Levine (US) completely revised the taxonomy of the coccidia which included placing the coccidia in the phylum Apicomplexa(3276).

Monique Castagna (FR), Yoshimi Takai (JP), Kozo Kaibuchi (JP), Kimihiko Sano (JP), Ushio Kikkawa (JP), and Yasutomi Nishizuka (JP) discovered that the phorbol esters (plant substances) immitate diacylglycerol thus activating protein kinase C. This resulted in increased growth and tumor formation(3277). 

Janet Davison Rowley (US) located the chromosomal regions involved with human chronic myeloid leukaemia (long arm of 9 translocates to 22), acute myeloblastic leukaemia (long arm of 21 translocates to 8), and acute promyelocytic leukaemia (long arm of 17 translocates to 15)(3278).

Peter N. Goodfellow (GB), Peter W. Andrews (GB), Robert P. Erickson (US), Kay E. Davies (GB), Hans-Hilger Ropers (NL), Vincent R. Harley (AU), Robin Lovell-Badge (GB), Jamie W. Foster (GB), Paul S. Burgoyne (GB), Marina A. Dominguez-Steglich (GB), Silvana Guioli (GB), Cheni Kowk (GB), Polly A. Weller (GB), Milena Stevanovic (CS), Jean Weissenbach (FR), Sahar Mansour (GB), Ian D. Young (GB), Jennifer A. Marshall Graves (AU), J. David Brook (GB), Alan J. Schafer (GB), Andrea Pontiggia (IT), Rebecca Rimini (IT), Marco E. Bianchi (IT), Jérôme Collignon (GB), Shanthini Sockanathan (GB), Adam Hacker (GB), Michel Cohen-Tannoudji (FR), David Norris (GB), Sohaila Rastan (GB), Karin Schmitt (GB), Ricky Critcher (GB), Mark Bouzyk (GB), Nigel K. Spurr (GB), Tsutomu Ogata (JP), Joe J. Hoo (US), Leonard Pinsky (CA), Giorgio Gimelli (IT), Linda M. Pasztor (US), Nikola Arsic (CS), Tamara Rajic (CS), and Slavica Stanojcic (CS) did pioneering work on the genetic basis of sex determination in humans(3279-3290).

Wojciech A. Krotoski (US), William E. Collins (US), Robert S. Bray (AU-GB), Percy Cyril Claude Garnham (GB), Frank B. Cogswell (US), Robert W. Gwadz (BE), Robert Killick-Kendrick (US), Robert E. Wolf (US), Robert E. Sinden (GB), Louis C. Koontz (US), and Peggy S. Stanfill (US) proposed that some Plasmodium vivax sporozoites in the liver remain latent (hypnozoites) for several months, causing relapses later on(3291).

Elizabeth H. Nardin (US), Victor Nussenzweig (US), Ruth Sonntag Nussenzweig (US), William E. Collins (US), Khunying Tranakchit Harinasuta (TH), Pramuan Tapchaisri (TH), and Yaovamarn Chomcharn (TH) characterized the first defined malaria antigen, the circumsporozoite protein(3292). The circumsporozoite proteins of Plasmodium falciparum and Plasmodium vivax play a role in protection from the host's immune system.

George R. Merriam (US) and Kenneth W. Wachter (US) developed algorithms for the study of episodic hormone secretion(3293).

Jean Clark Dan (US), Donner F. Babcock (US), Neal L. First (US), Henry Arnold Lardy (US), and Ryuzo Yanagimachi (JP-US) found that calcium ion promotes lysis of the acrosomal membrane of the sperm head (acrosomal reaction) of both invertebrates and vertebrates(3294-3296).

Gerald A. Rufo (US), Jai Pal Singh (US), Donner F. Babcock (US), and Henry Arnold Lardy (US) discovered that seminal fluid contains a calcium transport inhibitor that they termed caltrin(3297). Sperm bound caltrins prevent calcium movement into the acrosome and thus prevent a premature acrosome reaction. When a sperm coated with transport inhibitor caltrins contacts the egg the inhibitor forms are converted to enhancer forms. The enhancer forms of caltrin then stimulate calcium uptake at the acrosome where it activates membrane discomposition and at the tail where it induces whiplash movement of the sperm tail.

Chiaho Shih (US), Robert Allan Weinberg (US), Mitchell Goldfarb (US), Kenji Shimizu (JP), Manuel Perucho (US), Michael Wigler (US), Simonetta Pulciani (US), Eugenio Santos (US), Anne V. Lauver (US), Linda K. Long (US), Keith C. Robbins (US), and Mariano Barbacid (US) all cloned the first oncogene, it came from bladder carcinoma lines. These cloned cellular genes had the same transforming properties as the oncogenes from retroviruses(3298-3300). This is the discovery of oncogenes in humans.

Luis F. Parada (US), Clifford  J. Tabin (US), Chiaho Shih (US), Robert Allan Weinberg (US), Eugenio Santos (US), Steven R. Tronick (US), Stuart A. Aaronson (US), Simonetta Pulciani (US), Mariano Barbacid (US), Channing J. Der (US), Theodore G. Krontiris (US), and Geoffrey M. Cooper (US) determined that the oncogenes in question are the cellular homologues of the ras genes from the Harvey and Kirsten sarcoma viruses(3301-3303).

Clifford J. Tabin (US), Scott M. Bradley (US), Cornelia I. Bargmann (US), Robert Allan Weinberg (US), Alex G. Papageorge (US), Edward M. Scolnick (US), Ravi Dhar (US), Douglas R. Lowy (US), Esther H. Chang (US), E. Premkumar Reddy (US), Roberta K. Reynolds (US), Eugenio Santos (US), Mariano Barbacid (US), Elizabeth J. Taparowsky (US), Yolande Suard (US), Ottavio Fasano (US), Kenji Shimizu (US), Mitchell Goldfarb (US), and Michael H. Wigler (US) identified the difference between the normal cellular human c-Ha-RAS1 gene and its transforming counterpart from the carcinoma lines. They discovered the same single amino-acid change: glycine to valine at position 12(3304-3306). Subsequent research has shown that this change alters the structure of the RAS protein to make it constitutively active.

Esther H. Chang (US), Mark E. Furth (US), Edward M. Scolnick (US), and Douglas R. Lowy (US) discovered the ras oncogene in humans(3307).

James R. Feramisco (US) Michell Gross (US), Tohru Kamata (US), Martin Rosenberg (US), and Raymond W. Sweet (US) showed that microinjection of the activated human Ras protein into quiescent mammalian fibroblasts transiently stimulated cell growth in the absence of growth factors(3308).

Linda S. Mulcahy (US), Mark R. Smith (US), and Dennis W. Stacey (US) found that microinjection of antibodies inhibited serum-stimulated growth of cultured fibroblasts(3309).

Dafna Bar-Sagi (US) and James R. Feramisco (US) found that the same Ras oncogene protein that stimulated cell growth is also capable of triggering cel differentiation(3310).

The Centers for Disease Control in Atlanta, Georgia received reports on 19 cases of biopsy-confirmed Kaposi’s sarcoma (named for Moriz Kohn Kaposi, a 19th century Hungarian dermatologist) and/or Pneumocystis carinii pneumonia among previously healthy homosexual male residents of Los Angeles and Orange Counties, California. These symptoms would later be recognized as diagnostic of acquired immune deficiency syndrome (AIDS)(3157).

Kurt Semm (DE), on 13 September 1980, performed the first laproscopic appendectomy(3311).

Patrick C. Walsh (US) developed a nerve-sparing method of prostate removal. The procedure, in its refined form, dramatically reduces the risk of post-surgical impotence and incontinence(3312).

John J. Gallagher (US), Robert H. Svenson (US), Jackie H. Kasell (US), Lawrence D. German (US), Gust H. Bardy (US), Archer Broughton (AU), Giuseppe Critelli (IT), Melvin M. Scheinman (US), Fred Morady (US), David S. Hess (US), and Rolando Gonzalez (US) were the first to perform noninvasive His bundle ablation on a human(3313, 3314).

Toshio Mitsui (JP), H. Jima (JP), Kenji Okamura (JP), and Motokazu Hori (JP) had reported successful transvenous electrocautery of the atrioventricular connection in dogs(3315). 

Lura Harrison (US), John J. Gallagher (US), Jackie H. Kasell (US), Robert H. Anderson (US), Eileen Mikat (US), Donald B. Hackel (US), Andrew G. Wallace (US), Will C. Sealy (US), Roger Millar (US), Ronald W.F. Campbell (US), Edward L.C. Pritchett (US), and Andrew G. Wallace (US) used intraoperative mapping and cryosurgical ablation of the A-V node-His bundle to produce A-V blockage(3316, 3317).

Farooq Azam (US), Tom Fenchel (DK), John G. Field (ZA), John S. Gray (NO), Lutz-Arend Meyer-Reil (DE), and Frede Thingstad (NO) introduced the concept of the "Microbial Loop" and catalyzed a new perception of marine food webs. In this concept heterotrophic and phototrophic bacteria and small eucaryotic phytoplankton are consumed by heterotrophic nanoflagellates, which are themselves consumed by larger protozoa and then metazoa, linking the energy lost as dissolved organic matter back (loop) to copepods and other consumers of net plankton(3318).

Elaine Morgan (US) proposed that man descended from apes that adapted to an aquatic environment then returned to a terresterial lifestyle. Man is seen as retaining aquatic adaptations such as weeping, loss of body hair, bipedalism, face-to-face copulation, and the diving reflex(3319).

Russell Lande (US) developed a dynamic theory of life history evolution by synthesizing population demography with quantitative genetics(3320).

William D. Hamilton (US) and Marlene Zuk (US) found that in North American passerines (sometimes known as perching birds or, less accurately, as songbirds) there exists a highly significant association over species between incidence of chronic blood infections (five genera of protozoa and one nematode) and striking display (three characters: male "brightness," female "brightness," and male song). This result conforms to a model of sexual selection in which (i) coadaptational cycles of host and parasites generate consistently positive offspring-on-parent regression of fitness, and (ii) animals choose mates for genetic disease resistance by scrutiny of characters whose full expression is dependent on health and vigor(3321).

Stephen Jay Gould (US) and Elisabeth S. Vrba (ZA-US) explained the notion of exaptation, which refers to when a trait which evolved for one purpose gets used for another (such as feathers, which were originally evolved for warmth then later used for flying)(3322).


Henry Taube (CA-US) was awarded the Nobel Prize in Chemistry for his work on the mechanisms of electron transfer reactions, especially in metal complexes.

Barbara McClintock (US) was awarded the Nobel Prize in Physiology or Medicine for her discovery of mobile genetic elements.

David J. Stevenson (US), Takafumi Matsui (JP), and Yutaka Abe (JP) reasoned that the Earth, a planet with a metallic core, highly convective mantle, molten surface, and massive steam atmosphere, formed as a direct result of accretion(3323-3325).

Immaunel Kant (DE) had proposed much earlier that the Earth formed by condensation(3326, 3327).

Preston Ercelle Cloud, Jr. (US) and Stanley L. Miller (US) made the argument that the Earth’s primitive atmosphere was virtually devoid of oxygen(3328, 3329).

J. William Schopf (US), John M. Hayes (US), and Malcolm R. Walter (US), speculated that life on Earth may have arisen as early as 3.9 Ga(3330).

Stanley M. Awramik (US), J. William Schopf (US), Malcolm R. Walter (US), and Bonnie M. Packer (US) found rock bearing 3.5 billion year old microfossils within early Archean stromatolites (Gk. archaios=ancient)(3331-3333). The microfossils were interpreted to be prokaryotes and represent the oldest fossils known (2403).

Keith Burridge (GB-US) and Laurie Connell (US) discovered talin, one of the cell adhesion proteins(3334).

Choh Hao Li (CN-US), Donald Yamashiro (US), Denis Gospodarowicz (US), Selna L. Kaplan (US), and Guy Van Vliet (US) accomplished the total synthesis of insulin-like growth factor I (somatomedin C)(3335).

Mark D. Biggin (GB), Toby J. Gibson (DE), and Guofan F. Hong (CN) described two methods for increasing the length of DNA sequence data that can be read off a polyacrylamide gel. First they describe a way to pour a buffer concentration gradient gel that, by altering the vertical band separation on an autoradiograph, allows more sequence to be obtained from a gel and second show that the use of deoxyadenosine 5'-(alpha-[35S]thio)triphosphate as the label incorporated in dideoxynucleotide sequence reactions increases the sharpness of the bands on an autoradiograph and so increases the resolution achieved(3336).

Donald R. Senger (US), Stephen J. Galli (US), Ann M. Dvorak (US), Carole A. Perruzzi (US), V. Susan Harvey (US), Harold F. Dvorak (US), Yuen Shing (US), Moses Judah Folkman (US), Robert Sullivan (US), Catherine Butterfield (US), Jacqueline Murray (US), and Michael Klagsbrun (US), discovered vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF); molecules which mediate angiogenesis(3337, 3338).

Karen A. Magnus (US) and Eaton E. Lattman (US) discovered the structural motif common to many regulatory proteins called helix-turn-helix(3339).

Robert S. Fuller (US) and Arthur J. Kornberg (US) isolated a protein in Escherichia coli which appears necessary for the initiation of DNA unwinding at the replication origin (oriC)(3340).

Hiroto Okayama (JP) and Paul Berg (US) described the pcDV1 and pL1 plasmid vectors for cloning cDNAs in Escherichia coli; the same vector promotes expression of the cDNA segment in mammalian cells(3341).

Donna L. Daniels (GB), Frederick Sanger (GB), and Alan R. Coulson (GB) reported the analysis of the complete 48,502 base pair sequence of the DNA of bacteriophage lambda(3342).

Scott D. Putney (US), Walter C. Herlihy (US), Paul Reinhard Schimmel (US), Robert J. Milner (US), and J. Gregor Sutcliffe (US) sequenced fragments of DNA by the shotgun approach discovered by Schimmel and Sutcliffe. The technique was later dubbed expressed sequence tags (ESTs)(3343, 3344).

Michael W. Bevan (GB), Richard B. Flavell (GB), and Mary-Dell Matchett Chilton (US) inserted genetic material conferring resistance to the antibiotic G418 into the T-DNA region of Agrobacterium tumefaciens tumor-inducing plasmid. Plant cells transformed by this plasmid could grow in the presence of otherwise lethal levels of the antibiotic. Disarmed T-DNA vectors can be regenerated into entire plants, whose sexual progeny contain unaltered copies of the inciting T-DNA(3345).

Luis Herrera-Estrella (MX), Ann Depicker (BE), Marc Van Montagu (BE), and Jozef Stephen Schell (BE) modified a Ti-plasmid of Agrobacterium tumefaciens in such a way that it could transfer foreign genes into plant cells and have them expressed(3346).

Gale E. Smith (US), Max D. Summers (US), and Malcolm J. Fraser (US) produced human beta interferon in insect cells (Spodoptera frugiperda, fall armyworm) infected with a baculovirus expression vector(3347).

Douglass J. Forbes (US), Frank D. McKeon (US), Daniel Caput (FR), Georg Krohne (DE), Elke Debus (DE), Mary Jane Osborn (US), Werner W. Franke (DE), Denny L. Tuffanelli (US), Satoru Kobayashi (JP), Kimie Fukuyama (US), John W. Newport (US), Marc Wallace Kirschner (US), and Klaus Weber (DE) used sequencing studies and antibody probes to identify nuclear envelope lamins as a form of intermediate filament closely related to cytoplasmic intermediate filaments(3348-3354).

Takashi Fujita (JP), Tadatsugu Taniguchi (JP), Hiroshi Matsui (JP), Chikako Takaoka (JP), Nikki J. Holbrook (US), Kendall A. Smith (US), Albert J. Fornace (US), Claudette M. Comeau (US), Robert L. Wiskocil (US), and Gerald R. Crabtree (US) determined the entire nucleotide sequence for the human interleukin-2 gene and flanking regions(3355, 3356).

Tadatsugu Tanaguchi (JP), Hiroshi Matsui (JP), Takashi Fujita (JP), Chikako Takaoka (JP), Nobukazu Kashima (JP), Ryota Yoshimoto (JP), Junji Hamuro (JP), Steven C. Clark (US), Suresh K. Arya (US), Flossie Wong-Staal (CN-US), Michiko M. Matsumoto-Kobayashi (US), and Robert M. Kay (US) cloned the gene which codes for human interleukin-2(3357, 3358).

Lawrence Greenfield (US), Michael J. Bjorn (US), Glenn Horn (US), Darlene Fong (US), Gregory A. Buck (US), R. John Collier (US), and Donald A. Kaplan (US) cloned and sequenced the structural gene for diphtheria toxin carried by corynebacteriophage beta(3359).

Kathryn Haskins (US), Ralph Kubo (US), Janice White (US), Michelle Pigeon (US), John Kappler (US), and Philippa Marrack (US) used monoclonal antibody to isolate the major histocompatibility complex-restricted antigen receptor on T cells(3360).

Bradley W. McIntyre (US) and James P. Allison (US) characterized the mouse T cell receptor. Their data indicated that the T cell-specific receptor heteroduplex has regions of constant and regions of variable structure consistent with the properties expected for the T cell antigen receptor(3361).

Stefan C. Meuer (DE), Kathleen A. Fitzgerald (US), Rebecca E. Hussey (US), James C. Hodgdon (US), Stuart F. Schlossman (US), and Ellis L. Reinherz (US), working in humans, found that clonotypic T cell receptors contain two molecules of molecular weight 49,000 and 43,000 respectively. These molecules are associated with, but distinct from the T3 molecule expressed on all mature T lymphocytes(3362).

Stefan C. Meuer (DE), James C. Hodgdon (US), Rebecca E. Hussey (US), Jeffrey P. Protentis (US), Stuart F. Schlossman (US), and Ellis L. Reinherz (US) found that anticlonotypic monoclonal antibodies to the 49/43-kD heterodimer of a given clone or antibodies to the 20/25-kD membrane associated monomorphic T3 molecule selectively induce proliferation and IL-2 secretion when linked to a solid support. The antibodies behave as antigen and support the idea that the T3-Ti molecular complex represents the antigen receptor on human lymphocytes(3363).

Stephen M. Hedrick (US), David I. Cohen (US), Ellen A. Nielsen (US), and Mark M. Davis (US) used cDNA probes to locate a region in the murine T cell genome which encodes the antigen receptor on the surface of T lymphocytes(3364). 

Robert D. Schreiber (US), Judith L. Pace (US), Stephen W. Russell (US), Amnon Altman (US), and David H. Katz (US) provided biochemical and biosynthetic evidence indicating that the macrophage activating factor (MAF) produced by the murine T cell hybridoma clone 24/G1, which primes macrophages for nonspecific tumoricidal activity, is a form of gamma-interferon (IFN gamma)(3365).

Kendall A. Smith (US), Margaret F. Favata (US), and Stephen Oroszlan (US) described laboratory techniques useful in the production of monoclonal antibodies against human interleukin 2 (IL-2). These anti-lymphokines should be excellent tools to explore the molecular and biologic properties of these immunoregulatory molecules(3366).

Aziz Sancar (TR-US), W. Dean Rupp (US), Anthony T. Yeung (US), William B. Mattes (US), Euk Y. Oh (US), and Lawrence Grossman (US) discovered that proteins which mediate the individual steps in Escherichia coli nucleotide excision repair mechanism are encoded by the uvrA, uvrB, and uvrC genes. The UvrA, UvrB, and UvrC proteins act in a series of steps to first recognize and bind to the damaged site and then hydrolyze two phosphodiester bonds, one 7 nucleotides 5’ and the other 3 or 4 nucleotides 3’ of the modified nucleotide (3367, 3368).

Hanspeter Streb (DE), Robin F. Irvine (GB), Sir Michael John Berridge (GB), and Irene Schulz (DE) provided evidence that when phosphatidylinositol 4,5-biphosphate is hydrolyzed to yield inositol 1,4,5-triphosphate, the later serves as a second messenger mediator of calcium release from internal cellular reservoirs(3369, 3370).

Ulf Skoglund (SE), Kim Andersson (SE), Birgitta Björkroth (SE), Mary M. Lamb (US), and Bertil Daneholt (SE) characterized the growth and maturation of the transcription products on the Balbiani ring (BR) genes in Chironomus tentans by electron microscopy(3371).

John E. Walker (GB), Nicholas J. Gay (GB), Masamitsu Futai (JP), and Hiroshi Kanazawa (JP) successfully isolated the gene complex coding for the entire group of polypeptides forming the FoF1-ATPase in Escherichia coli(3372, 3373).

Patricia C. Zambryski (US), Henk Joos (BE), Chris Genetello (BE), Jan Leemans (BE), Marc van Montagu (BE), and Jozef Stephen Schell (BE) introduced foreign genes into plants by using Agrobacterium tumefaciens plasmid vectors(3374).

Robert T. Fraley (US), Stephen G. Rogers (US), Robert B. Horsch (US), Patricia R. Sanders (US), Jeffrey S. Flick (US), Steven P. Adams (US), Michael L. Bittner (US), Leslie A. Brand (US), Cynthia L. Fink (US), Joyce S. Fry (US), Gerald R. Galluppi (US), Sarah B. Goldberg (US), Nancy L. Hoffmann (US), and Sherry C. Woo (US) conferred resistant to aminoglycoside antibiotics upon petunia and tobacco (Nicotiana tabacum) plants by inserting the Agrobacterium tumefaciens tumor-inducing (Ti) plasmid into plant cells by in vitro transformation techniques. The plasmids were carrying antibiotic resistance genes of bacterial origin(3375).

Robert B. Horsch (US), Robert T. Fraley (US), Stephen G. Rogers (US), Patricia R. Sanders (US), Alan Lloyd (US), Joyce S. Fry (US), Nancy L. Hoffmann (US), and David A. Eicholtz (US) produced the first genetically engineered plants(3376, 3377).

Manfred J. Lohka (CA) and Yoshio Masui (CA) found that a cell-free preparation of the cytoplasm from activated eggs of Rana pipiens induces, in demembranated sperm nuclei of Xenopus laevis, formation of a nuclear envelope, chromatin decondensation, initiation of DNA synthesis, and chromosome condensation(3378).

Werner W. Franke (DE), Christine Grund (DE), Brian W. Jackson (CH), and Karl Illmensee (DE) discovered that during epidermal development, embryonic basal cells are the first to express detectable levels of the type 1 keratin K14 (50kD) and type 2 keratin (58kD)(3379).

Karl O. Stetter (DE), Helmut König (DE), and Erko Stackebrandt (DE) discovered Pyrodictium, a bacterium with an optimum growth temperature of 105 ° C and a maximum growth temperature of 110° C. These qualities placed it in a subgroup of the extremeophiles referred to as hyperthermophiles(3380).

Jean-Pierre Métraux (CH), Ilya Raskin (US), and Hans Kende (CH-US) examined the environmental and hormonal regulation of the growth response in deepwater rice and the cellular basis of rapid internodal elongation. They found that the plant hormone ethylene accumulates in submerged internodes because of enhanced synthesis under reduced partial pressures of O2 and because of its low rate of diffusion from the plant into the surrounding water(3381, 3382).

Ilya Raskin (US), Susanne Hoffmann-Benning (US) and Hans Kende (CH-US) found that the interaction of ethylene and two other plant hormones—abscisic acid (ABA), and gibberellin (GA)—determines the growth rate of deepwater rice. Ethylene renders the internode more responsive to GA, at least in part by lowering the level of endogenous ABA, a potent antagonist of GA action in rice. Growth of the internode is, ultimately, promoted by GA(3383, 3384).

Margret Sauter (US) and Han Kende (CH-US) determined that the primary target tissue of GA is the intercalary meristem of the internode, where GA enhances cell division activity. Cells are displaced from the intercalary meristem into the elongation zone, where they reach their final size(3384, 3385).

Reinhardt Møbjerg Kristensen (DK) and Robert P. Higgins (US) discovered, described, and named the phylum Loricifera(3386-3388). These metazoans are microscopic (meiofaunal) animals possessing spiny heads and unsegmented bodies encased in a vase-shaped anterior that can retract into the posterior trunk. Some are acoelomates and others are pseudocoelomates.

Roberto Danovaro (IT), Antonio Dell'Anno (IT), Antonio Pusceddu (IT), Cristina Gambi (IT), Iben Heiner (DK), and Reinhardt Møbjerg Kristensen (DK) discovered that at least three species of the Loriciferans are the first known multicellular organisms which spend their entire lives in an anoxic environment. They are able to do this because they rely on hydrogenosomes instead of mitochondria for energy(3389). 

Cambridge Life Sciences (GB) invented biosensors. ref check L.C.Clark Jr Biosens Bioelectron. 1993;8(1):iii-vii.

Robert S. Hikida (US), Robert S. Staron (US), Fredrick C. Hagerman (US), W. Michael Sherman (US) and David L. Costill (US) demonstrated that "the stresses and strains of violent effort" can lead to microscopic injury to the muscle fiber(3390, 3391). Archibald Vivian Hill (GB) had predicted this result.

William C. Byrnes (US), Priscilla M. Clarkson (US), John S. White (US), Sandy S. Hsieh (US), Peter N. Frykman (US), and Ronald J. Maughan (GB) found that muscle adapts to the stress of violent effort, noting that a single bout of eccentric exercise can protect against muscle soreness and damage from future bouts for up to 6 wk(3392). Archibald Vivian Hill (GB) had predicted this result.

George H.A. Clowes, Jr. (US), Barbara C. George (US), Claude Alvin Villee, Jr. (US), and Calvin A. Saravis (US) reported that a peptide in the circulation of patients with sepsis or trauma promoted muscle wasting. This peptide would later be known as interleukin-1(3393).

Ze’ev Trainin (IL), Dorothee Wernicke (DE), Hannah Ungar-Waron (IL), and Myron Essex (US) reported that a retrovirus responsible for feline leukaemia in feral cats also produces immunodeficiency in the same animals(3394).

Myron Essex (US), Mary Frances McLane (US), Tun-Hou Lee (US), Larry Falk (US), Craig W.S. Howe (US), James I. Mullins (US), Cirilo D. Cabradillo (US), Donald P. Francis (US), Edward P. Gelmann (US), Mikulas Popovic (US), Douglas Blayney (US), Henry Masur (US), Gurdip Sidhu (US), Rosalyn Stahl (US), Robert Charles Gallo (US), Prem S. Sarin (US), Marjorie Robert-Guroff (US), Ersell Richardson (US), Francoise Barré-Sinoussi (FR), Jean-Claude Chermann (FR), Francoise Rey (FR), Marie-Thérèse Nugeyre (FR), Sophie Chamaret (FR), Jacqueline Gruest (FR), Charlie Dauguet (FR), Claudine Axler-Blin (FR), Francoise Vezinet-Brun (FR), Christine Rouzioux (FR), A. Gérard Saimot (FR), Jean-Claude Gluckman (FR), David Klatzmann (FR), Etienne Vilmer (FR), Claude Griscelli (FR), C. Foyer-Gazengel (FR), Jean-Baptiste Brunet (FR), Willy Rozenbaum (FR), and Luc Montagnier (FR) produced empirical evidence for the hypothesis that AIDS is caused by one or more immunosuppressive T cell tropic retroviruses. The Americans initially referred to the viral agent as human T cell leukaemia virus type 3 (HTLV-III) while the French called it lymphadenopathy-associated retrovirus (LAV)(3395-3400). The name of the virus causing AIDS would shortly be changed to human immunodeficiency virus (HIV). It became HIV-1 after another strain, HIV-2, was isolated from West African patients(3401).

Abebe Haregewoin (ET-US), Tore Godal (NO), Abu Salim Mustafa (NO), Ayele Belehu (ET), and Tebebe Yemaneberhan (ET) demonstrated that patients with severe leprosy are not producing interleukin 2(3402).

Nadia Nogueira (US), Gilla Kaplan (US), E. Levy (), Euzenir Nunes Sarno (BR), Peter Kushner (US), Angela Granelli-Piperno (US), Leila Vieira (BR), Veronica F. Colomer-Gould (US) William R. Levis (US), and Ralph M. Steinman (US) discovered that there is a defective gamma interferon production in leprosy; reversible with antigen and interleukin 2(3403).

Lee W. Riley (US), Robert S. Remis (US), Steven D. Helgerson (US), Harry B. McGee (US), Joy G. Wells (US), Betty R. Davis (US), Richard J. Hebert (US), Ellen S. Olcott (US), Linda M. Johnson (US), Nancy T. Hargrett (US), Paul A. Blake (US), and Mitchell L. Cohen (US) were able to firmly link Escherichia coli serotype O157:H7 with a clinically distinctive gastrointestinal disorder later called EHEC (enterohemorrhagic Escherichia coli) diarrhea(3404).

Denise A. Galloway (US) and James K. McDougall (US) demonstrated that after herpes simplex initiated carcinogenesis the virus did not need to remain present to maintain the carcinogenic state(3405).

Gayle C. Bosma (US), R. Philip Custer (US), and Melvin J. Bosma (US) described a homozygous recessive mutation on chromosome 16 in mice called (scid) severe combined immunodeficiency disease which results in severely reduced populations of T cells and B cells(3406). These mice were found to lack mature T and B cells yet can survive up to a year in specific pathogen-free conditions and are therefore valuable for biomedical research.

Alexandre Fabiato (FR-US) used experiments performed in skinned cardiac cells (sarcolemma removed by microdissection) to support the hypothesis of a Ca2+-induced Ca2+ release (CICR) from the sarcoplasmic reticulum (SR)(3407). According to this hypothesis, the transsarcolemmal Ca2+ influx does not activate the myofilaments directly but through the induction of a Ca2+ release from the SR.

A. James Hudspeth (US) determined that the hair cells of the inner ear are exquisitely sensitive transducers that in human beings mediate the senses of hearing and balance. A tiny force applied to the top of the cell produces an electrical signal at the bottom(3408-3410).

Efrain O. Aceves-Pina (MX), Ronald Booker (US), Janet S. Duerr (US), Margaret S. Livingstone (US), William G. Quinn (US), R.F. Smith (US), Patricia P. Sziber (US), Bruce L. Tempel (US), Timothy P. Tully (US), Craig H. Bailey (US), Dusan Bartsch (DE), and Eric R. Kandel (AT-US) determined that the brain’s storage of long-term memory is associated with a cellular program of gene expression, altered protein synthesis, and the growth of new synaptic connections(2338, 3411).

Alfred Sommer (US), Ignatius Tarwotjo (ID), Gusti Hussaini (ID), and DJoKo Susanto (ID) demonstrated that low-dose vitamin A supplementation can prevent death from infectious diseases as well as blindness in millions of third world children(3412).

Joseph L. Melnick (US), Betty L. Petrie (US), Gordon R. Dressman (US), Joyce Burek (US), Charles H. McCollum (US), and Michael Ellis DeBakey (US) reported that evidence of cytomegalovirus (CMV), a common virus infecting a high percentage of people without causing symptoms, was present in the cells comprising the vessel walls of 11 patients with atherosclerosis, or hardening of the arteries. Cytomegalovirus, which causes cells to multiply, often becomes dormant in the body for years after infection. The study suggested that early in life, cytomegalovirus may initiate the lesions that later cause atherosclerosis(3413).

Ervin Adam (US), Joseph L. Melnick (US), Jeffrey L. Probstfield (US), Betty L. Petrie (US), Joyce Burek (US), Kent R. Bailey (US), Charles H. McCollum (US), and Michael Ellis DeBakey (US) reported that patients with heart disease have higher-than-normal levels of antibodies to cytomegalovirus. The report supported their earlier finding that cytomegalovirus may play a major role in the development of atherosclerosis(3414).

John E. Buster (US), Maria Bustillo (US), Ian H. Thorneycroft (US), James A. Simon (US), Stephen P. Boyers (US), John R. Marshall (US), John A. Louw (ZA), Randolph W. Seed (US), Richard G. Seed (US) had medical oversight of the first human pregnancy resulting from oocyte donation. Sperm from the male partner were introduced into the cervix of a female egg donor. When fertilization had taken place, the embryo was removed and replaced in the female partner. In the first instance, 2 pregnancies resulted from 5 embryo transfers(3415).

H. Weber (DE) and L. Schmitz (DE) reported the first treatment of a patient with type B Wolff-Parkinson-White (WPW) syndrome using catheter ablation(3416).

Francis Denis (US) introduced the concept of middle column or middle osteoligamentous complex between the traditionally recognized posterior ligamentous complex and the anterior longitudinal ligament. Major spinal injuries are classified into four different categories: compression fractures, burst fractures, seat-belt-type injuries, and fracture dislocations. He presents a correlation between the three-column system, the classification, the stability, and the therapeutic indications(3417).

Stevan J. Arnold (US) reported that it is possible to measure adaptive significance directly(3418). 

Andrew C. Scott (GB) and William Gilbert Chaloner (GB) provided the earliest fossil record of a gymnosperm—conifers from the Upper Carboniferous(3419).

Carl Gans (US) and Richard Glenn Northcutt (US) noted that vertebrate body organization differs from that of other chordates in a large number of derived features that involve all organ systems. Most of these features arise embryonically from epidermal placodes, neural crest, and a muscularized hypomere(3420, 3421).

Raúl Patrucco (PE), Raúl Tello (PE), and Duccio Bonavia (PE) found Ascaris lumbricoides eggs in human coprolites from Peru dating from 2277 B.C.E.(3422, 3423).

Hartmut Land (DE-US), Luis F. Parada (CO-US), Robert Allan Weinberg (US), H. Earl Ruley (GB-US), Douglas Hanahan (US), Peter Whyte (CA), Karen J. Buchkovich (US), Jonathan M. Horowitz (US), Stephen H. Friend (US), Maragret Raybuck (GB) and Edward Harlow (US) discovered the ability of different oncogenes to cooperate in producing cellular transformation(1520, 3424-3426).


Niels Kaj Jerne (GB-DK), Georges Jean Franz Köhler (DE) and César Milstein (AR-GB) were awarded the Nobel Prize in Physiology or Medicine for theories concerning the specificity in development and control of the immune system and the discovery of the principle for production of monoclonal antibodies.

James F. Kasting (US), James B. Pollack (US), and David Crisp (US) concluded that to keep the oceans from freezing on the primitive Earth a global greenhouse was necessary to offset the effects of a faint young Sun which was dimmer than today's by 25-30%. Climate models confirmed that 100-1,000 times the present atmospheric level of carbon dioxide would have been necessary(3427).

James F. Kasting (US), James B. Pollack (US), David Crisp (US), and John P. Grotzinger (US) used greenhouse calculations and the sedimentary record to suggest that before 3.8 Ga the Earth’s surface was a warm (80-100˚C), with a bicarbonate-rich ocean at a pH perhaps as low as 6(3427, 3428).

Michael W. Hunkapiller (US), Stephen Kent (US), Marvin Harry Caruthers (US), William J. Dreyer (US), Joseph R. Firca (US), C. Griffin (US), Suzanna J. Horvath (US), Tim Hunkapiller (US), Paul Tempst (US), and Leroy Edward Hood (US) developed a series of automated instruments that use state-of-the-art chemical methods for high-sensitivity protein sequencing, DNA synthesis, and peptide synthesis(3429).

Charles N. Serhan (US), Mats Hamberg (SE), and Bengt Samuelsson (SE) discovered a new biologically active class of compounds— lipoxins A and B —which are formed from arachidonic acid in leucocytes(3430).

Charles N. Serhan (US), Kyriacos Costa Nicolaou (CY-US), Stephen E. Webber (US), Chris A. Veale (US), Sven-Erik Dahlen (SE), Tapio J. Puustinen (SE), and Bengt Samuelsson (SE) described the structure and formation of various lipoxins by leucocytes(3431).

Shuichi Gomi (JP), Daishiro Ikeda (JP), Hikaru Nakamura (JP), Hiroshi Naganawa (JP), F. Yamashita (JP), Ken Hotta (JP), Shinichi Kondo (JP), Yoshiro Okami (JP), Hamao Umezawa (JP), Yoichi Iitaka (JP), and S. Kurasawa (JP) were the first to isolate the novel antibiotic indolizomycin which is generated by a bacterium resulting from the fusion of two non antibiotic producing strains of bacteria, Streptomyces tenjimariensis NM16 and Streptomyces grisline NP1-1(3432, 3433). 

James B. Hurley (US), Melvin I. Simon (US), David B. Teplow (US), Janet D. Robishaw (US), and Alfred Goodman Gilman (US) discovered similarities which suggested that G proteins and ras proteins may have analogous functions(3434). 

Yasutomi Nishizuka (JP) suggested that 1,2-diacylglycerol, one of the products resulting from the first messenger induced breakdown of inositol phospholipids, initiates the activation of protein kinase C(3435, 3436).

Gregg Duester (US), G. Wesley Hatfield (US), Rolf Buhler (US), John Hempel (US), Hans Jornvall (SE), and Moyra Smith (ZA-US) cloned and characterized cDNA for the beta subunit of human alcohol dehydrogenase (ADH)(3437).

Gregg Duester (US), G. Wesley Hatfield (US), and Moyra Smith (ZA-US) used a cDNA probe to locate the alcohol dehydrogenase 2 (ADH2) gene encoding the beta subunit of human ADH to human chromosome 4(3438).

Gregg Duester (US), Moyra Smith (ZA-US), Virginia Bilanchone (US), and G. Wesley Hatfield (US) analyzed the five distinct human alcohol dehydrogenase (ADH) subunits—each encoded by a separate gene—to determine their organization and regulation. In addition, they determined the nucleotide sequence of the gene encoding the beta subunit(3439).

William J. Brown (US) and Marilyn Gist Farquhar (US) detected a protein in the membranes of vesicles near the Golgi which binds mannose-6-phosphate. This modified sugar binds lysosomal proteins so that they may be transported within vesicles(3440, 3441).

Novozymes A/S of Denmark developed the first enzyme from a genetically modified organism for the starch industry—maltogenic amylase—it was marketed under the name Maltogenase®. They were given the U.S. Federal trademark serial number 73782780 for Maltogenase in 1991.

Gregory L. Gray (US), Douglas H. Smith (US), Jane S. Baldridge (US), Richard N. Harkins (US), Michael L. Vasil (US), Ellson Y. Chen (US), and Herbert L. Heyneker (US) cloned and sequenced the exotoxin A structural gene of Pseudomonas aeruginosa(3442).

Gerhard Heinrich (US), Henry M. Kronenberg (US), John T. Potts, Jr. (US), Joel F. Habener (US), Christine A. Weaver (US), David F. Gordon (US), Martin S. Kissil (US), David A. Mead (US), and Byron Kemper (US) sequenced the parathyroid hormone (PTH) gene(3443, 3444).

Gian Garriga (US) and Alan M. Lambowitz (US) were the first to demonstrate self-splicing by a mitochondrial intron(3445).

Fred K. Chu (US), Gladys F. Maley (US), Frank Maley (US), and Marlene Belfort (ZA-US) reported on the presence of an "intervening sequence" (intron) in the td gene, in the TS coding sequence, of the T4 phage(3446). They subsequently found the td intron to be a group 1 intron that self-splices by the guanosine-initiated pathway.

Susan M. Quirk (US), Deborah Bell-Pedersen (US), and Marlene Belfort (ZA-US) demonstrated hopping of the td and nrdD introns from intron-containing donor replicons of the T-even phages to cognate intronless recipients containing the td or nrdD homing sites(3447).

Nobuchika Suzuki (US), Hiromi Shimomura (JP), E. William Radany (US), Chodavarapu S. Ramarao (US), Gary E. Ward (US), J. Kelley Bentley (US), and David Lorn Garbers (US) discovered a peptide (resact) associated with the eggs of the sea urchin, Arbacia punctulata, which stimulates sperm respiration rates by 5-10-fold. It was purified and its amino acid sequence was determined. The sequence was found to be Cys-Val-Thr-Gly-Ala-Pro-Gly-Cys-Val-Gly-Gly-Gly-Arg-Leu-NH2. The peptide was subsequently synthesized. It appears that resact behaves as a sperm attractant(3448).

Dina Ralt (IL), Mordechai Goldenberg (IL), Peter Fetterolf (IL), Dana Kathryn Thompson (US), Jehoshua Dor (IL), Shlomo Mashiach (IL), David Lorn Garbers (US), and Michael Eisenbach (IL) indicate that a sperm attractant functions in humans(3449).

David F. Spencer (CA), Murray N. Schnare (CA), Michael W. Gray (CA), David Sankoff (CA), Robert J. Cedergren (CA), Dan Yang (JP), Yaeko Oyaizu (JP), Hiroshi Oyaizu (JP), Gary J. Olsen (US), and Carl R. Woese (US) demonstrated that mitochondrial rRNA genes are of direct eubacterial (Bacteria) ancestry(3450-3453).

Svend O. Freytag (US), Arthur L. Beaudet (US), Hans-George O. Bock (DE), and William E. O'Brien (US) presented evidence for the occurrence of alternative splicing of the argininosuccinate synthetase gene mRNA. The splicing of the argininosuccinate synthetase mRNA was found to be species specific in primates and variable among different human cell types(3454).

Barbara Ruskin (US), Adrian R. Krainer (US), Thomas Peter Maniatis (US), Michael R. Green (US), Richard A. Padgett (US), Maria M. Konarska (US), Paula J. Grabowski (US), Stephen F. Hardy (US), and Phillip Allen Sharp (US) worked out the mechanism of pre-mRNA splicing using human cells and for adenovirus 2(3455, 3456). 

Michael A. Blanar (US), Donald G. Kneller (US), Alexander E. Karu (US), Fred E. Cohen (US), Robert Langridge (US), Irwin D. Kuntz (US), Murty V.V.S. Madiraju (US), Ann Templin (US), and Alvin John Clark (US) identified the RecA enzyme in Escherichia coli. This enzyme can catalyze invasion of an intact DNA helix by a single nucleotide strand. The enzyme binds to the exposed single strand then catalyzes rewinding of the chain with its complement in the receiving molecule(3457, 3458).

Jack Coleman (US), Pamela J. Green (US), and Masayori Inouye (US) constructed a plasmid that produces a complementary RNA to the E. coli lpp mRNA (mic[lpp] RNA). Induction of the mic(lpp) gene efficiently blocked lipoprotein production and reduced the amount of lpp mRNA(3459). 

Sushilkumar G. Devare (US), Allan R. Shatzman (US), Keith C. Robbins (US), Martin Rosenberg (US), Stuart A. Aaronson (US), Steven F. Josephs (US), Chan Guo (US), Lee Ratner (US), Flossie Wong-Staal (CN-US), Ing-Ming Chiu (US), E. Premkumar Reddy (US), David Givol (IL), and Steven R. Tronick (US) provided the first link between an oncoprotein and biochemical signal transduction. The amino acid sequence of platelet-derived growth factor (PDGF), a powerful mitogen, is almost identical to that of the v-sis oncogene of Simian Sarcoma Virus. Virus transformed cells secrete a mimic PDGF protein which stimulates mitosis when it binds to a PDGF receptor. Alternatively, internal expression of the sis oncoprotein might stimulate replication in cell types lacking PDGF receptors(3460-3462).

Julian Downward (GB), Yosef Yarden (IL), Elaine L.V. Mayes (GB), Geoffrey T. Scrace (GB), Nicholas F. Totty (GB), Peter A. Stockwell (NZ), Axel Ullrich (DE), Joseph Schlessinger (US), and Michael D. Waterfield (GB) found that the amino acid sequence of the cell-surface receptor for epidermal growth factor (EGF) shares a remarkable homology with the predicted sequence of the v-erb-B oncogene protein of avian erythroblastosis virus. It appears that v-erb-B oncogene protein is an example of viral capture of an incomplete cellular gene(3463).

David B. Rhoads (US), Phang C. Tai (US), and Bernard David Davis (US) showed that the incorporation of protein into membrane vesicles requires the setting up of a membrane potential(3464).

Gloria Lee (US), Richard Olding Hynes (GB-US), Eric Schulze (US) and Marc Wallace Kirschner (US), using amphibians as a model, contributed greatly to the elucidation of the pathways that underlie morphogenesis(3465, 3466).

Jane Gitschier (US), William I. Wood (US), Teresa M. Goralka (US), Karen L. Wion (US), Ellson Y. Chen (US), Dennis H. Eaton (US), Gordon A. Vehar (US), Daniel J. Capon (US), and Richard M. Lawn (US) reported the complete isolation and characterization of the human blood coagulation factor VIII gene. Located on the X chromosome it was the largest gene characterized at the time (186kb)(3467). 

John J. Toole (US), John L. Knopf (US), John M. Wozney (US), Lisa A. Sultzman (US), Janet L. Buecker (US), Debra D. Pittman (US), Randal J. Kaufman (US), Eugene J. Brown (US), Charles Shoemaker (US), Elizabeth C. Orr (US), Godfrey W. Amphlett (US), W. Barry Foster (US), Mary Lou Coe (US), Gaylord J. Knutson (US), David N. Fass (US), and Rodney M. Hewick (US) cloned the cDNA for human antihemophilic factor—human blood coagulation factor VIII—into COS-1 cells using the plasmid vector pCVSVL. The cells expressed the gene and produced the polypeptide(3468).

Grant A. Bitter (US), Kenneth K. Chen (US), Allen R. Banks (US), and Por-Hsiung Lai (TW) constructed gene fusions between the alpha-factor leader region and two chemically synthesized genes. The fusions were cloned into various yeast—E. coli shuttle vectors and reintroduced into Saccharomyces cerevisiae with the result that the synthesized genes were expressed and excreted if correctly oriented to the alpha-factor gene(3469). 

Francisco Malpartida (ES) and Sir David A. Hopwood (GB) isolated a large continuous segment of Streptomyces coelicolor DNA which carries the complete genetic information for the synthesis of the antibiotic actinorhodin. Using a plasmid vector for this segment they transformed non-actinorhodin strains of Streptomyces coelicolor or Streptomyces parvulus to actinorhodin producers(3470).

G.M.S. Hooykaas-Van Slogteren (NL), Paul J.J. Hooykaas (NL), and Robbert A. Schilperoort (NL) reported that the Ti-plasmid of Agrobacterium tumefaciens may be used as a vector for transforming monocotyledonous plants with foreign DNA(3471). 

Jerszy (Jurek) Paszkowski (CH), Ray D. Shillito (US), Michael William Saul (CH), Vaclav Mandak (CH), Thomas Hohn (CH), Barbara Hohn (CH), and Ingo Potrykus (CH) constructed plasmids which they used as vectors to directly transfer foreign genes into protoplasts of Nicotiana tabacum(3472).

Roger D. Cone (US), and Richard C. Mulligan (US) reported the high-efficiency transfer of foreign genes into mammalian cells using a modified retrovirus with a broad mammalian host range(3473).

Nina V. Federoff (US) Douglas B. Furtek (US), Oliver Evans Nelson, Jr. (US), Robert J. Schmidt (US), Frances A. Burr (US), and Benjamin Burr (US) cloned the bronze locus of maize (Zea mays L.)(3474, 3475).  This was the first successful application of transposon tagging to gene cloning in plants.

Charles K. Paull (US), Barbara Hecker (US), A. Conrad Neumann (US), Elisabeth L. Sikes (US), James Hook (US), William Corso (US), Raymond P. Freeman-Lynde (US), Robert F. Commeau (US), Stjepko Golubic (US), and Joseph R. Curray (US), discovered oceanic cold seeps (cold vents) where entire communities of light independent organisms - known a extremophiles- develop in and around cold seeps, most relying on symbiotic relationship with chemoautotrophic bacteria. These prokaryotes, both Archaea and Eubacteria process sulfides and methane through chemosynthesis into a variety of energy rich organic molecules. Higher organisms, namely vesicomyid clams and siboglinid tube worms use this energy to power their own life processes, and in exchange provide both safety and a reliable source of food for the bacteria(3476, 3477).

Kenneth Bryan Raper (US) and Ann Worley Rahn (US) wrote the important monograph, The Dictyostelids(3478).

William J. McAleer (US), Eugene B. Buynak (US), Robert Z. Maigetter (US), D. Eugene Wampler (US), William J. Miller (US), and Maurice Ralph Hilleman (US) developed a hepatitis B vaccine of yeast cell origin. Vaccinated chimpanzees were completely protected when challenged. This is the first example of a vaccine produced from recombinant cells which is effective against a human viral infection(3479).

Tadeusz J. Wiktor (US), Roderick I. Macfarlan (AU), Kevin J. Reagan (US), Bernhard Dietzschold (US), Peter J. Curtis (US), William H. Wunner (US), Marie-Paul Kieny (CH), Richard Lathe (GB), Jean-Pierre Lecocq (FR), Michael Mackett (GB), Bernard Moss (US), and Hilary Koprowski (PL-US) produced a vaccine for rabies by creating a vaccinia virus recombinant containing the rabies virus glycoprotein gene(3480). 

Adrian Peter Bird (GB), William Robert A. Brown (GB), Susan Lindsay (GB), Richard R. Meehan (GB), Joe D. Lewis, (GB) Stewart McKay (GB), Elke L. Kleiner (AT), Francisco Antequera (ES), Donald MacLeod (GB), and Wendy A. Bickmore (GB) demonstrated that the process of DNA methylation provides a switching mechanism by which a cell can control the activity of specific genes in its nucleus. When sites within a gene are methylated the gene is inactivated; if unmethylated the gene returns to or remains active(3481-3488). This process is thought to be particularly important for cell differentation

Larry Gerace (US), C. Comeau (?), Margaret Benson (GB), and Brian Burke (US) determined that the nuclear envelope is a distinct organelle in that it contains membrane proteins not found in other cellular membranes, e.g. proteins which interact with nuclear lamins and signal proteins allowing it to reassemble following mitosis(3489, 3490).

Carl M. Feldherr (US), Ernst Kallenbach (US) and Nigel Schultz (US) gave direct evidence that eukaryotic nuclear pores are the route by which proteins are imported into the nucleus(3491).

Frances M. Finn (US), Gail Titus (US), Diane Horstman (US), and Klaus Hofmann (CH-US) isolated the insulin receptor of the human placenta(3492).

William A. Braell (US), William E. Balch (US), Darrell C. Dobbertin (US), James Edward Rothman (US), and William G. Dunphy (US) reconstituted and characterized protein transport between successive compartments of the Golgi apparatus in a cell-free system(3493-3495).

Michel Seigneuret (FR) and Philippe F. Devaux (FR) discovered in erythrocytes an ATP-dependent aminophospholipid-specific transporter (translocase) which transports phosphatidylserine and phosphatidylethanolamine from the outer to the inner leaflet of the plasma membrane(3496). 

Michael N. Hall (CH), Lynna M. Hereford (US), and Ira Herskowitz (US) described an amino acid sequence which could act as a signal for translocation of a nonnuclear protein into the cell nucleus(3497).

Manfred Schleyer (DE) and Walter Neupert (DE) were the first to demonstrate that proteins traverse the two mitochondrial membranes in an unfolded state(3498).

Martin Eiles (CH) and Gottfried Schatz (CH) presented data suggesting that dihydrofolate reductase must at least partly unfold in order to be transported across mitochondrial membranes(3499). 

Raymond J. Deshaies (US) and Randy Schekman (US) uncovered a new secretory mutant, sec61, that accumulates multiple secretory and vacuolar precursor proteins that have not acquired any detectable posttranslational modifications associated with translocation into the endoplasmic reticulum. Thus, the sec61 mutation defines a gene that is required for an early cytoplasmic or endoplasmic reticulum membrane-associated step in protein translocation(3500).            

Eckhard R. Podack (US) and Paula J. Konigsberg (US) found that dense granules of cytolytic T cells contain cytolytic proteins that polymerize to disulfide-linked tubular poly perforins in a Ca-dependent reaction and may cause cytolysis by membrane insertion and transmembrane channel. In the presence of Ca, these granules effect strong tumoricidal and hemolytic activity(3501).

Steven M. Block (US), Howard Curtis Berg (US), David F. Blair (US), Shahid Khan (Pakistani-US), Michaela Dapice (US), and Thomas Sargent Reese (US) proposed a model for the mechanism propelling the bacterial motor involving the M ring and the Mot proteins, found by genetic experiments to be necessary for flagellar function in prokaryotes(3502-3505).

Daniel Kalderon (GB-US), William D. Richardson (GB), Alexander F. Markham (GB), Alan E. Smith (US), Bruce L. Roberts (US), William Henry Colledge (GB), Michael D. Edge (GB), Peter Gillett (GB), and Eva Paucha (GB) identified a short sequence of predominantly basic amino acids Pro-Pro-Lys-Lys-Lys-Arg-Lys-Val from SV40 Large T as responsible for the normal nuclear location of the protein(3506, 3507).

Benjamin Harrison Landing (US) discussed factors in the distribution of butterfly color and behavior patterns(3508).

Daniel A. Portnoy (US), Hans Wolf-Watz (SE), Ingrid Bolin (SE), Ann B. Beeder (US), and Stanley Falkow (US) cloned the (inv) gene —confers invasive phenotype—from Yersinia pseudotuberculosis into the non-invasive strain HB101 of E. coli(3509). This was the first demonstration of the transfer of such a virulence property by a single gene. 

Bernard M. Babior (US) discovered that phagocytosis of pathogens by macrophages induces the macrophage to generate reactive oxygen intermediates(3510).

Toshio Nikaido (JP), Akira Shimizu (JP), Norio Ishida (JP), Hisataka Sabe (JP), Keisuke Teshigawara (JP), Michiyuki Maeda (JP), Takashi Uchiyama (JP), Junji Yodoi (JP), Tasuku Honjo (JP), Warren J. Leonard (US), Timothy A. Donlon (US), Roger V. Lebo (US), and Warner C. Greene (US) reported the isolation of a gene for the human interleukin-2 receptor(3511, 3512).

Frances J. Benham (GB), Nigel K. Spurr (GB), Sue Povey (GB), Bradford T. Brinton (GB), Peter N. Goodfellow (GB), Ellen Solomon (GB), and Tess J. Harris (AU-GB) assigned the tissue-type plasminogen activator gene to chromosome 8 in man(3513).

Reiko Takemura (JP) and Zena Werb (DE-CA) reported that mononuclear phagocytes can produce a number of extracellular proteases including collagenolytic, elastinolytic, and gelatinolytic hydrolases. These enzymes would allow them to clear themselves a path through the macromolecular barriers of basement membranes and other extracellular matrices(3514).

Michael J. Bastiani (US), Corey Scott Goodman (US), Chris Q. Doe (US), Sascha du Lac (US), Stephen L. Helfand (US), John Y. Kuwada (US), John B. Thomas (US), Allan L. Harrelson (US), Christian Klambt (US), J. Roger Jacobs (US), Alex L. Kolodkin (US), and David J. Matthes (US) contributed to developmental neurobiology, in particular to understanding the initial cellular and subsequent molecular and genetic mechanisms controlling the guidance of neuronal growth cones to find and recognize their correct targets(3515-3519).

Doreen A. Cantrell (GB), Kendall A. Smith (US), Stefan C. Meuer (DE), Rebecca E. Hussey (US), James C. Hodgdon (US), Oreste Acuto (GB), Thierry Hercend (FR), Stuart F. Schlossman (US), and Ellis L. Reinherz (US) discovered that after T cell stimulation by antigen the concentration of interleukin-2, the concentration of interleukin-2 receptors on T cells, and the duration of the interleukin-2 reaction with its receptor are all critical if the T cell is to be stimulated to divide(3520-3522).

Barry Toyonaga (US), Yusuke Yanagi (JP), Nicole Suciu-Foca (US), Mark D. Minden (CA), Tak W. Mak (CA), Carolyn A. Blanckmeister (US), Keith R. Yamamoto (US), Mark M. Davis (US), Gunter J. Hammerling (DE), Jerome Ritz (US), Thomas J. Campen (US), Reinhold E. Schmidt (DE), Hans Dieter Royer (DE), Thierry Hercend (FR), Rebecca E. Hussey (US), Ellis L. Reinherz (US), Stuart F. Schlossman (US), Andrea Biondi (IT), Paola Allavena (IT), Valentina Rossi (IT), Renato Bassan (IT), Tiziano Barbui (IT), Eric Champagne (FR), Alessandro Rambaldi (IT), and Alberto Mantovani (IT) discovered that the receptor molecule on the surface of T killer cells consists of one alpha and one beta polypeptide chain, each encoded by a separate gene(1995, 3523-3527).

Tak W. Mak (CA), Yusuke Yanagi (JP), Yasunobu Yoshikai (JP), Kathleen Leggett (CA), Stephen P. Clark (CA), Ingrid Aleksander (CA), Gerald Siu (US), Marie Malissen (FR), Erich C. Strauss (US), Leroy Edward Hood (US), Karyl I. Minard (US), Shelley Mjolsness (US), Mitchell Kronenberg (US), Joan Goverman (US), Timothy Hunkapiller (US), Michael B. Prystowsky (US), Frank W. Fitch (US), Sheryle Taylor (CA) cloned and sequenced the gene for the T cell receptor, a critical component of the body’s defense system against disease(3528-3532).

Kenji Nakanishi (JP), David I. Cohen (US), Marcia A. Blackman (US), Ellen A. Nielsen (US), Junichi Ohara (JP-US), Toshiyuki Hamaoka (JP), Marian E. Koshland (US), and William Erwin Paul (US) demonstrated that interleukin-2 helps B cells to start secreting antibodies(3533).

Eric Westhof (FR), Daniéle Altschuh (FR), Dino Moras (FR), Anne C. Bloomer (GB), Alfonso Mondragon (US), Sir Aaron Klug (ZA-GB), Marc H. van Regenmortel (FR), John A. Tainer (US), Elizabeth D. Getzoff (US), Yvonne Paterson (US), Arthur J. Olsen (US), and Richard Alan Lerner (US) showed that the mobility of a segment of an antigen molecule influences its antigenicity(3534, 3535).

Angus G. Dalgleish (GB), Peter C.L. Beverley (GB), Paul R. Clapham (GB), Dorothy H. Crawford (GB), Melvyn Francis Greaves (GB), Robin A. Weiss (GB), David Klatzmann (FR), Eric Champagne (FR), Sophie Chamaret (FR), Jacqueline Gruest (FR), Denise Guetard (FR), Thierry Hercend (FR), Jean-Claude Gluckman (FR), and Luc Montagnier (FR) concluded that the CD4 antigen is an essential and specific component of the receptor for the causative agent of AIDS(3536, 3537).

Ola Myklebost (NO), Sissel Rogne (NO), Bjørnar Olaisen (NO), Tobias Gedde-Dahl, Jr. (NO), and Hans Prydz (NO) determined that the apo CII (apolipoprotein CII) gene is situated on chromosome 19 of man, close to the apoE (apolipoprotein E) gene(3538).

Lee J. Siegel (US), Mary E. Harper (US), Flossie Wong-Staal (CN-US), Robert Charles Gallo (US), William G. Nash (US), and Stephen James O’Brien (US) located the human gene for interleukin-2 on chromosome 4q and the feline gene for interleukin-2 on chromosome B1(3539).

Eugene D. Weinberg (US) stressed that the body withholds iron from microorganisms as part of its natural defense mechanism. Lactoferrin, transferrin, and leucocyte endogenous mediator (LEM) are all useful for sequestering iron thus inhibiting microbial growth(3540).

Catherine D. O'Connell (US) and Maurice Cohen (US) discovered that the human genome contains endogenous retrovirus genes(3541).

Masao Ono (US) determined that the haploid human genome contains approximately 50 copies of the human endogenous retrovirus genes (HERV-K) (3542).

Cristophe Fraser (CA), R. Keith Humphries (CA), and Dixie L. Mager (CA) analyzed the chromosomal distribution of a large family of human endogenous retrovirus-like sequences termed RTVL-H. In situ hybridizations suggested that these sequences are found on all human chromosomes(3543).

Renato Mariani-Costantini (IT), Toby M. Horn (US), and Robert Callahan (US) suggested that the ancestral HERVII retrovirus(es) entered the genomes of Old World anthropoids by infection after the divergence of New World monkeys (platyrrhines) but before the evolutionary radiation of large hominoids(3544).

Roswitha Lower (DE), Johannes Lower (DE), and Reinhard Kurth (DE) proposed that human endogenous retroviruses (HERVs) are very likely footprints of ancient germ-cell infections. HERV sequences encompass about 1% of the human genome. HERVs have retained the potential of other retroelements to retrotranspose and thus to change genomic structure and function. The genomes of almost all HERV families are highly defective(3545).

David J. Griffiths (GB), Palle Villesen (DK), Lars Aagaard (DK), Carsten Wiuf (DK), and Finn Skou Pedersen (DK) reported that approximately 8% of human DNA represents fossil retroviral genomes. This does not include the LINE elements and other retrotransposons scattered throughout the genome(3546, 3547).

Robert E. Weibel (US), Beverly J. Neff (US), Barbara J. Kuter (US), Harry A. Guess (US), Carol A. Rothenberger (US), Alison J. Fitzgerald (US), Karen A. Connor (US), Arlene A. McLean (US), Maurice Ralph Hilleman (US), and Eugene B. Buynak (US) developed a live attenuated varicella (chickenpox) virus vaccine(3548).

Matthias Dürst (DE). Lutz Gissmann (DE), Hans Ikenberg (DE), Harald zur Hausen (DE), Michael Boshart (DE), Andreas Kleinheinz (DE), and Wolfram Scheurien (DE) linked human papillomavirus type 16 and type 18 to cervical cancer in humans(3549, 3550). 

Merceds L. de Bold (CA), Adolfo J. de Bold (AR-CA), and Jack Kraicer (CA) discovered stellate cells of the pars intermedia of the pituitary gland using a new silver impregnation technique(3551).

David Hunter Hubel (CA-US) and Margaret S. Livingstone (US) showed that some neurons in the brain’s primary visual cortex respond selectively to color but not shape(3552). 

William H. Jopling (GB) reports there is evidence that leprosy originated in Asia and was probably transported from India to Europe in the 4th century B.C.E. by soldiers returning from the Greek wars of conquest. From Greece it was spread slowly throughout Europe by trade and military expeditions(3553).

John Desmond Clark (US), Berhane Asfaw (US), Getaneh Assefa (ET), Jack W.K. Harris (US), Hiro Kurashina (GU), Robert C. Walter (CA), Tim D. White (US), and Martin A.J. Williams (AU), in 1981, discovered fossil remains of Australopithecus sp., dated to ca. 3.5 -4.0 M.Y.B.P. These remains are the earliest evidence of Australopithecus from anywhere in the world and the earliest evidence of hominid bipedalism yet discovered(3554). 


“The hypothalamus is without peer in its authority over body adjustments to our external and internal environments…[It] regulates body temperature, hunger, thirst, sexual activity, goal seeking behavior, endocrine functions, affective (emotional) behavior, and the activity of the visceral nervous system.” Marian Cleeves Diamond, Lawrence M. Elson, and Arnold C. Scheibel(3555).

Michael Stuart Brown (US) and Joseph Leonard Goldstein (US) were awarded the Nobel Prize in Physiology or Medicine for their discoveries concerning the regulation of cholesterol metabolism.

James C.G. Walker (US) and Peter Brimblecombe (GB) determined that in a oceanic hydrothermal system, precipitation of highly insoluble iron sulfides by abundant aqueous ferrous iron would have served as a highly effective sink for hydrogen sulfide(3556).

Sir Harold W. Kroto (GB), James R. Heath (US), Sean C. O’Brien (US), Robert F. Curl, Jr. (US), and Richard E. Smalley (US) discovered the unusual stability of the carbon-60 Buckminsterfullerene molecule and deduced its structure(3557).

Robert A. Wolf (US) and Richard W. Gross (US) were the first to demonstrate a plasmalogen selective phospholipase A2 in heart tissue(3558).

Michael A.J. Ferguson (GB), Martin G. Low (US), and George A.M. Cross (US) determined the composition and structure of a novel phosphatidylinositol-containing glycolipid, now known as membrane anchor. It was obtained from the protozoan, Trypanosoma brucei(3559).

Shripad S. Bhagwat (US), Philip R. Hamann (US), W. Clark Still (US), Stuart Bunting (US), and Frank A. Fitzpatrick (US) accomplished the synthesis and structure of the platelet aggregation factor thromboxane A2(3560).

Ken Richardson (GB), Keith W. Brammer (GB), Michael S. Marriott (GB), and Peter F. Troke (GB) introduced the antifungal UK-49,858, a difluorophenyl bis-triazole derivative, for the treatment of Candida albicans and Tricophyton mentagrophytes infections(3561). Trade name Diflucan.

Giorgio Bernardi (IT), Birgitta Olofsson (GB), Jan Filipski (FR), Marino Zerial (IT), Julio Salinas (ES), Gerard Cuny (FR), Michele Meunier-Rotival (FR), and Francis Rodier (FR) examined the proportion of guanine (G) and cytosine (C) after genome DNA was cut into large pieces. The GC content of these fragments in mammals and birds tended to fall into discrete fractions, with either higher or lower GC composition rather than lying near the overall mean of the genome. This meant that the genome is made up of large domains, some one million bases in length, which differ in GC content. Such regions they christened isochores(3562, 3563). 

Michael Berger (DE) and Michael F.G. Schmidt (DE) showed that fatty acylation of membrane proteins occurs before they leave the endoplasmic reticulum(3564).

Paul J. Pfaffinger (US), Jennifer M. Martin (US), Dale D. Hunter (US), Neil M. Nathanson (US), David J. Beech (GB), Laurent Bernheim (CH), Alistair Mathie (GB), Mark S. Shapiro (US), Lonnie P. Wollmuth (US), Humberto Cruzblanca (MX), Duk-Su Koh (US), and Bertil Hille (US) discovered the way that muscarinic acetycholine receptors in the heart, acting through G-proteins, turn on M-type Ca2+ channels and dissected the mechanism for modulation of K+ and N-type Ca2+ channels in sympathetic neurons(3565-3570).

Raymond S. Brown (DE), Christian Sander (DE), Patrick Argos (DE), Jonathan Miller (GB), Andrew D. McLachlan (GB), Mair Elisa Annabelle Churchill (US), Thomas D. Tullius (US), Sir Aaron Klug (ZA-GB), Alan D. Frankel (US), Carl O. Pabo (US), Jeremy M. Berg (US), Toby J. Gibson (DE), Pieter W. Postma (NL), Lora M. Green (US), Grace Parraga (CA), Susan Horvath (US), Leroy Edward Hood (US), Elton T. Young (US), Rachel E. Klevit (US) were among those who worked out the zinc-finger motif as one of the features common to many regulatory proteins(3571-3578).

Katherine M. Call (US), Tom Glaser (US), Caryn Y. Ito (US), Alan J. Buckler (US), Jerry Pelletier (US), Daniel A. Haber (US), Elise A. Rose (US), Astrid Kral (US), Herman Yeger (CA), William H. Lewis (CA), Carol Jones (US) and David E. Housman (US) isolated and characterized a zinc finger polypeptide gene from the human chromosome 11 Wilms' tumor locus(3579).

Michele Sawadogo (US) and Robert Gayle Roeder (US) found that three basic transcription factors, TFIIB, TFIID, and TFIIE, are absolutely required, in addition to the RNA polymerase II, for specific transcription initiation from the adenovirus major late promoter(3580).

Stanley Tabor (US) and Charles Clifton Richardson (US) cloned the RNA polymerase gene of bacteriophage T7 into the plasmid pBR322 under the inducible control of the lambda PL promoter. After induction, T7 RNA polymerase constitutes 20% of the soluble protein of Escherichia coli, a 200-fold increase over levels found in T7-infected cells. The overproduced enzyme has been purified to homogeneity(3581).

F. Ian Lamb (GB), Lynne M. Roberts (GB), and J. Michael Lord (GB) deduced from the nucleotide sequence of cloned DNA complementary to preproricin mRNA the primary structure of a precursor protein that contains the toxic (A) and galactose-binding (B) chains of the castor bean lectin, ricin(3582).

Rodney K. Tweten (US), Joseph T. Barbieri (US), and R. John Collier (US) found that the glutamic acid at position148 in diphtheria toxin is essential for the ADP-ribosylation of elongation factor 2. This is consistent with other data suggesting that this residue may be at or near the catalytic center of the toxin(3583). This glutamic acid residue is conserved in all ADP-ribosylating toxins like those of cholera, pseudomonas, and pertussis.

Roger Brent (US) and Mark Ptashne (US) postulated that in S. cerevisiae the Gal4 activator protein functions by directly contacting other proteins required for initiation of transcription(3584). 

Ronald G. Schoner (US), Lee F. Ellis (US), and Brigitte E. Schoner (US) found that Escherichia coli cells transformed into high-level bovine growth hormone producers possess distinct cytoplasmic granules which are nearly homogenous bovine growth hormone(3585).

Bruce P. Babbitt (US), Paul M. Allen (US), Gary Matsueda (US), Edgar Haber (US), and Emil R. Unanue (US) found that the small epitopic portion of hen-egg lysozyme (HEL) is physically associated with Ia (histompatibility) glycoproteins of macrophages and T cells during the antigen presentation process(3586).

Toshio Hirano (JP), Tetsuya Taga (JP), Naoko Nakano (JP), Kiyosi Yasukawa (JP), Shinichiro Kashiwamura (JP), Kazuo Shimizu (JP), Koichi Nakajima (JP), Kwang H. Pyun (JP), and Tadamitsu Kishimoto (JP) purified to homogeneity and characterized human B cell differentiation factor (BCDF or BSFp-2)(3587).

Toshio Hirano (JP), Kiyoshi Yasukawa (JP), Hisashi Harada (JP), Tetsuya Taga (JP), Yasuo Watanabe (JP), Tadashi Matsuda (JP), Shin-ichiro Kashiwamura (JP), Koichi Nakajima (JP), Koichi Koyama (JP), Akihiro Iwamatsu (JP), Susumu Tsunasawa (JP), Fumio Sakiyama (JP), Hiroshi Matsui (JP), Yoshiyuki Takahara (JP), Tadatsugu Taniguchi (JP), and Tadamitsu Kishimoto (JP) reported the molecular cloning, structural analysis and functional expression of the cDNA encoding human B cell differentiation factor (BSF-2). The primary sequence of BSF-2 deduced from the cDNA reveals that BSF-2 is a novel interleukin consisting of 184 amino acids. They named it interleukin 6 (IL-6). This factor was found to induce final maturation of B cells into antibody producing cells(3588). Since this work IL-6 has been found to be a multifunctional cytokine exerting a biological influence on various tissues and cells including hematopoietic progenitors, hepatocytes, nerve cells, epidermal keratinocytes and kidney mesangium cells.

Eckhard R. Podack (US), John Ding-E Young (US), and Zanvil A. Cohn (US) isolated then performed a biochemical and functional characterization of perforin 1 (P1) from cytolytic T cell granules(3589). Pl-mediated hemolysis is Ca2+-dependent and is inhibited by Zn2 ions. Lysis is accompanied by the polymerization of P1 to membrane associated tubular complexes (poly-Pl) that form large transmembrane pores. P1 causes a rapid membrane depolarization of cells in the presence of Ca2+. Purified P1 also induces transmembrane monovalent and divalent ion flow across lipid vesicles only in the presence of Ca2 .

Kiyoshi Takatsu (JP), Nobuyuki Harada (JP), Yoshinobu Hara (JP), Yousuke Takahama (JP), Gen Yamada (JP), Kunio Dobashi (JP), and Toshiyuki Hamaoka (JP) purified and determined the physicochemical characteristics of murine T cell replacing factor (TRF). The TRF is a extremely hydrophobic protein with an apparent m.w. of 50,000 to 60,000(3590). T cell replacing factor (TRF) has been shown to induce terminal differentiation of late-developing B cells to antibody-producing cells.

Eric M. Smith (US), Deborah Harbour-McMenamin (US), and J. Edwin Blalock (US) reported that the immune and neuroendocrine systems appear able to communicate with each other by virtue of signal molecules (hormones) and receptors common to both systems. They presented data concerning the production of one type of neuroendocrine hormone, endorphins (END), by stimulated lymphocytes(3591). These findings were very controversial at the time.

Peter N. Ray (CA), Bonnie Belfall (CA), Catherine Duff (CA), Cairine Logan (CA), Vanora Kean (CA), Margaret W. Thompson (CA), James E. Sylvester (US), Jerome L. Gorski (US), Roy D. Schmickel (US), and Ronald G. Worton (CA) located the Duchenne muscular dystrophy (DMD) X-linked recessive disorder gene within band Xp21 of the X chromosome(3592).

Susan M. Forrest (GB), Gareth S. Cross (GB), Astrid Speer (GB), David Gardner-Medwin (GB), John Burn (GB), and Kay E. Davies (GB) found that both Duchenne and Becker muscular dystrophy (DMD and BMD) genes are located in Xp21 on the short arm of the X chromosome(3593).

Eric P. Hoffman (US), Robert H. Brown, Jr. (US), and Louis M. Kunkel (US) produced antibodies to the mDMD and DMD gene protein products. They used these antibodies to study the protein product of the Duchenne muscular dystrophy locus, called dystrophin, in tissues isolated from both normal and dystrophic mice and humans(3594).

Kay E. Davies (GB), Terry J. Smith (GB), Sarah Bundey (GB), Andrew P. Read (GB), Tracey Flint (GB), Martyn V. Bell (GB), and Astrid Speer (GB) determined that mild and severe muscular dystrophy are associated with deletions in Xp21 of the human X chromosome(3595).

Peter Sicinski (US), Yan Geng (CN), Allan S. Ryder-Cook (US), Eric A. Barnard (GB), Mark G. Darlison (DE), and Pene J. Barnard (GB) found the molecular basis of muscular dystrophy in the mdx mouse to be a point mutation(3596).

Nguyen thi Man (GB), J.M. Ellis (GB), Donald R. Love (NZ), Kay E. Davies (GB), Kevin C. Gatter (GB), George Dickson (GB), and Glenn E. Morris (GB) identified a protein they called utrophin(3597). In early human life, Davies says, utrophin serves as a kind of infantile form of dystrophin, the crucial protein missing or deficient in the muscle cells of boys with Duchenne and Becker muscular dystrophies. However, as the organism reaches adulthood, the utrophin protein serves its own distinct function. "We think it's a stabilizing protein at the neuromuscular junction," Davies says.

Bernhard Moss (US) reported that interest in poxviruses has been sustained primarily by the unusual biology of the infection: these are the only DNA-containing viruses which replicate entirely in the cytoplasm of infected cells(3598).

Michael George Rossmann (US), Edward Arnold (US), John W. Erickson (US), Elizabeth A. Frankenberger (US), James P. Griffith (US), Hans-Jürgen Hecht (DE), John E. Johnson (US), Greg Kamer (US), Ming Luo (US), Anne G. Mosser (US), Roland R. Rueckert (US), Barbara Sherry (US), and Gerrit Vriend (NL) worked out the three dimensional structures of human rhinovirus (HRV) by x-ray crystallography(3599).

James M. Hogle (US), Marie Chow (US), and David J. Filman (US) worked out the three dimensional structure of poliovirus using x-ray crystallography(3600).

Isabelle Giri (FR), Olivier Danos (FR), and Moshe Yaniv (FR) determined the genomic structure of the cottontail rabbit (Shope) papillomavirus(3601).

Pekka Saikku (FI), San-Pin Wang (CN-US), Marjaana Kleemola (FI), Eljas Brander (FI), Eeva Rusanen (FI), and J. Thomas Grayston (US) reported outbreaks of a mild respiratory infection that began with coryza and usually affected young people, such as military recruits and college students(3602). 

J. Thomas Grayston (US), Cho-Chou Kuo (US), San-Pin Wang (CN-US), and Jeff Altman (US) subsequently identified a new organism, Chlamydia pneumoniae, as the cause of the infection mentioned above. They were able to show that the bacterium is distinct from its cousins Chlamydia trachomatis and Chlamydia psittaci(3603).

Richard A. Young (US), Vijay Mehra (US), Douglas Sweetser (US), Thomas Buchanan (US), Josephine Clark-Curtiss (US), Ronald W. Davis (US), and Barry R. Bloom (US) cloned genes for the major protein antigens of the leprosy parasite Mycobacterium leprae(3604).

Joe Cappello (US), Karl Handelsman (US), Stephen M. Cohen (US), and Harvey Franklin Lodish (US) described a retrotransposon in Dictyostelium discoideum(3605). The DNA of retrotransposons is transcribed then using a gene for reverse transcriptase which they carry make DNA copies and insert them back into the host DNA. In this way retrotransposons replicate without ever having to leave the host cell.

Takashi Toda (US), Isso Uno (JP), Tatsuo Ishikawa (JP), Scott Powers (US), Tohru Kataoka (US), Daniel Broek (US), Scott Cameron (US), James Broach (US), Kunihiro Matsumoto (JP), and Michael Wigler (US) found in Saccharomyces cerevisiae that RAS proteins are controlling elements of adenylate cyclase(3606).

Scott Cameron (US), Lonny Levin (US), Mark Zoller (US), and Michael Wigler (US) obtained results indicating that cAMP-independent mechanisms must exist for regulating glycogen accumulation, sporulation, and the acquisition of thermotolerance in S. cerevisiae, therefore, Ras is not alone in controlling cell growth in response to nutrients(3607).

Nik C. Barbet (CH), Ulrich Schneider (CH), Stephen B. Helliwell (CH), Ian Stansfield (GB), Michael F. Tuite (GB), and Michael N. Hall (CH) found that Saccharomyces cerevisiae cells treated with the immunosuppressant rapamycin or depleted for the targets of rapamycin TOR1 and TOR2 arrest growth in the early G1 phase of the cell cycle. They proposed that the TORs, two related phosphatidylinositol kinase homologues, are part of a novel signaling pathway that activates eIF-4E-dependent protein synthesis and, thereby, Gl progression in response to nutrient availability(3608). 

Charles P. Hart (US), Alexander Awgulewitsch (DE-US), Abraham Fainsod (IL), William McGinnis (US), and Francis Hugh Ruddle (US) reported findings that support the hypothesis that the homeo box is a 180 bp protein-coding domain found within homeotic genes of Drosophila and conserved in a variety of invertebrate and vertebrate species. It has been suggested that the mammalian homeo box sequences may play a role in controlling pattern formation during embryogenesis. They cloned three overlapping recombinant phage clones that cover a region of mouse chromosome 11 that contains a cluster of four homeo boxes (the Hox-2 locus). This locus encodes multiple transcripts that are expressed during embryogenesis. Forty kilobases of the Hox-2 region is devoid of repetitive elements and shows extensive homology with the human Hox-2 locus. These results provide direct evidence for genetic expression during embryonic development, a conserved organization in comparison to the cognate human locus, and a complexity of organization and transcript expression similar to that found in Drosophila(3609).

Matthew P. Scott (US) discussed how developmental fates along the anterior-posterior axes of animals are controlled by clustered homeotic genes which in vertebrates are called Hox genes. The gene clusters are similar and probably functionally homologous in animals as different as nematodes, flies, and mammals. A new set of names for Hox genes was recently agreed upon by many workers in the field. Remarkably, the order of the Hox genes along the chromosome reflects where they are expressed along the body axis. This simple principle is reflected in the new nomenclature system(3610).

Edward Brody (US) and John Norman Abelson (US) discovered and described the function of the spliceosome as an enzymatic complex used for the removal of introns during the processing of pre-messenger RNA(3611).

Randall K. Saiki (US), Kary Banks Mullis (US), Fred Faloona (US), Steven J. Scharf (US), Glen T. Horn (US), Henry A. Erlich (US), and Norman Arnheim (US) conceived that a fragment of DNA could be forced to replicate itself many times in a test tube. This was the origin of what is called the polymerase chain reaction (PCR)(3612-3615). This methodology was used in the 1985 paper to diagnose sickle cell anemia.

Randall K. Saiki (US), David H. Gelfand (US), Susanne Stoffel (CH-US), Steven J. Scharf (US), Russell Higuchi (US), Glen T. Horn (US), Kary Banks Mullis (US), and Henry A. Erlich (US) used a heat stable enzyme (DNA polymerase) from Thermus aquaticus to establish polymerase chain reaction technology(3616).

Thomas C. Sudhof (US), Joseph Leonard Goldstein (US), Michael Stuart Brown (US), David W. Russell (US), Ramila S. Patel (US), Erich Odermatt (US), Jean E. Schwarzbauer (US), and Richard Olding Hynes (GB-US) presented evidence for what would become known as exon shuffling, the exchange of exons between genes, and suggested that the process promotes evolution(3617, 3618).

Ronald D. Vale (US), Thomas Sargent Reese (US), Michael P. Sheetz (US), Bruce J. Schnapp (US), Timothy J. Mitchison (US), and Eric Steuer (US) identified kinesin as the "motor" moving organelles toward the plus ends of microtubules—toward axon tips—in eukaryotes (Eucarya)(3619-3624).

Paul B. Wolfe (US), Marilyn Rice (US), and William Wickner (US) determined that two membrane proteins of Escherichia coli, SecA and SecY, are very likely to promote passage of proteins through the membrane(3625).

Richard E. Greenblatt (US), Y. Blatt (US), Maurice Montal (US), H. Robert Guy (US), Peddaiahgari Seetharamulu (US), Bruce L. Tempel (US), Diane M. Papazian (US), Thomas L. Schwarz (US), Yuh Nung Jan (US), and Lily Y. Jan (US) hypothesized, based on experimental evidence, that potassium channels in cell membranes consist of proteins arranged such that they create an ion-conducting pore(3626-3628).

Phyllis J. Kanki (US), Mary F. McLane (US), Norval W. King, Jr. (US), Norman L. Letvin (US), Ronald D. Hunt (US), Prabhat Sehgal (US), Muthiah D. Daniel (US), Ronald C. Desrosiers (US), and Myron Essex (US) isolated a simian immunodeficiency virus (SIV) from nonhuman primates(3629). This virus shares many characteristics with human immunodeficiency virus (HIV). 

Joseph E. Varner (US) and Jychian Chen (TW) cloned cDNA of the carrot (Daucus carotus) cell wall protein extensin(3630).

Robert G. Knowlton (US), Odile Cohen-Haguenauer (FR), Nguyen Van Cong (FR), Jean Frézal (FR), Valerie A. Brown (US), David Barker (US), Jeffrey C. Braman (US), James W. Schumm (US), Lap-Chee Tsui (CN), Manuel Buchwald (CA), and Helen Donis-Keller (US) located a polymorphic DNA marker linked to cystic fibrosis on chromosome 7 in humans(2459).

Lap-Chee Tsui (CA), Stephanie Zengerling (DE), Huntington F. Willard (US), and Manuel Buchwald (CA) mapped the cystic fibrosis locus on chromosome 7 of humans(3631).

Lap-Chee Tsui (CN), Manuel Buchwald (CA), David Barker (US), Jeffrey C. Braman (US), Robert G. Knowlton (US), James W. Schumm (US), Hans Eiberg (US), Jan Mohr (DK), Dara Kennedy (US), Natasa Plavsic (US), Martha Zsiga (US), Danuta Markiewicz (US), Gita Akots (US), Valerie Brown (US), Cynthia Helms (US), Thomas Gravius (US), Carol Parker (US), Kenneth Rediker (US), Helen Donis-Keller (US), Stephanie Zengerling (DE), and Huntington F. Willard (US) mapped the cystic fibrosis (CF) gene to chromosome 7 in humans(2461, 3631).

David Barker (US), Philip Green (US), Robert G. Knowlton (US), James W. Schumm (US), Eric Lander (US), Arnold Oliphant (US), Huntington F. Willard (US), Gita Akots (US), Valerie Brown (US), Thomas Gravius (US), Cynthia Helms (US), Christopher Nelson (US), Carol Parker (US), Kenneth Rediker (US), Marcia Rising (US), Diane Watt (US), Barbara Weiffenbach (US), and Helen Donis-Keller (US) determined the genetic linkage map of human chromosome 7 with 63 DNA markers(3632).

Devra P. Rich (US), Matthew P. Anderson (US), Richard J. Gregory (US), Seng H. Cheng (US), Sucharita Paul (US), Douglas M. Jefferson (US), John D. McCann (US), Katherine W. Klinger (US), Alan E. Smith (US), Michael J. Welsh (US), Mitchell L. Drumm (US), Heidi A. Pope (US), William H. Cliff (US), Johanna M. Rommens (US), Sheila A. Marvin (US), Lap-Chee Tsui (CN), John (Jack) R. Riordan (CA), Francis Sellers Collins (US), Raymond A. Frizzell (US), and James M. Wilson (US) determined that in humans the cystic fibrosis (CF) gene regulates the passage of chlorine ions across plasma membranes. Mutations in this gene are common and lead to cystic fibrosis(3633-3635).

Daniel A. Portnoy (US), and Rafael J. Martinez (US) determined that all three Yersinia species pathogenic for man harbor closely related virulence plasmids(3636).

Michael M. Mueckler (US), Celso Caruso (BR), Stephen A. Baldwin (GB), Maria Panico (GB), Ian Blench (GB), Howard R. Morris (GB), W. Jeffrey Allard (US), Gustav E. Lienhard (US), and Harvey Franklin Lodish (US) determined the amino acid sequence and the structure of the glucose transport protein from human HepG2 hepatoma cells(3637).

Michelle M. Le Beau (US), Carol A. Westbrook (US), Manuel O. Diaz (US), Janet Davison Rowley (US), and Moshe Oren (IL) mapped the p53 gene to human chromosome 17(3638).

William R. Rice (US) and George W. Salt (US) presented experimental evidence in support of sympatric speciation in Drosophila melanogaster(3639-3641).

Hiroaki Mitsuya (JP-US), Kent J. Weinhold (US), Phillip A. Furman (US), Marty H. St. Clair (US), Sandra Nusinoff Lehrman (US), Robert Charles Gallo (US), Dani Bolognesi (US), David W. Barry (US), and Samuel Broder (US) demonstrated that 3'-azido-3'-deoxythymidine (AZT) inhibits the infectivity and cytopathic effects of the human immunodeficiency virus (HIV) in vitro(3642).

Alessandro Guidotti (US) Paola Ferrero (AR), and Erminio Costa (US) isolated a brain neuropeptide of 105 amino acid residues which influences the level of anxiety(3643). 

Stewart Shipp (GB) and Semir M. Zeki (GB) found that the brain regions receiving sensory information after the primary visual cortex did are specialized for the further processing of color or movement(3644).

Sofsite Contact Lens Laboratory (US) introduced the soft contact lens. ref

David C. Page (US), Albert de la Chapelle (FI-US), Jean Weissenbach (FR), and Mea Andersson (FI) reported that human 'XX males' are sterile males whose chromosomes seem to be those of a normal female yet contain portions of the Y chromosome. They speculated that maleness is probably due to the presence of the Y-encoded testis-determining factor (TDF)(3645, 3646).

Richard H. Schiappacasse (US), Dariouche Mohammadi (US), and Adrian J. Christie (US) reported that praziquantel is effective in treating human fasciolasis(3647).

David J. Durand (US), Ronald I. Clyman (US), Michael A. Heymann (US), John Allen Clements (US), Francoise Mauray (US), Joseph A. Kitterman (US), Philip L. Ballard (US), Roderic H. Phibbs (US), Roberta A. Ballard (US), John Allen Clements (US), David C. Heilbron (US), Ciaran S. Phibbs (US), Mureen A. Schlueter (US), Susan H. Sniderman (US), William H. Tooley (US), and Ann Wakeley (US) developed a life-saving artificial surfactant now used to treat the lungs of infants suffering from respiratory distress syndrome(3648, 3649).

Daniel Tranel (US) and Antonio R. Damasio (US) presented the neurological syndrome called prosopagnosia, where a patient has a stroke that damages the medial-inferior parts of both temperal lobes. Following the stroke, the patient may be mentally quite lucid, fluent, and attentive, but the surprising thing is that even though he can read the newspaper and score normally on the Snellen chart he is unable to recognize people by looking at their faces(3650, 3651).

Paul D. MacLean (US) proposed that the human brain can conveniently be thought of as three separate brains, each representing a distinct evolutionary stratum that has formed upon the older layer before it, like archaeological strata: He calls it the triune brain. These three brains are the neocortex or neo-mammalian brain, the limbic or paleo-mammalian system, and the reptilian brain, the brainstem and cerebellum. Each of the three brains is connected by nerves to the other two, but each seems to operate as its own brain system with distinct capacities(3652).

Xavier Martin (FR), Jean-Louis Mestas (FR), Dominique Cathignol (FR), Jacqueline Margonari (FR), Albert Gelet (FR), and Jean-Michel Dubernard (FR) initiated extracorporeal shockwave lithotripsy (crushing a calculus in the urinary system with ultrasonic waves)(3653).

Onik Gary (US), John Gilbert (US), William Hoddick (US), Roy Filly (US), Peter Callen (US), Boris Rubinsky (US), and Linda Farrel (US) performed surgeries suggesting that sonography is an effective and accurate means of monitoring the entire freezing and thawing cycle in hepatic cryosurgery(3654).

Joseph Felsenstein (US) used information on the evolutionary relationships of organisms (phylogenetic trees) to compare species. The most common applications are to test for correlated evolutionary changes in two or more traits, or to determine whether a trait contains a phylogenetic signal (the tendency for related species to resemble each other). This is the paper that really started the whole emphasis on 'comparative methods' in the sense of statistically controlling for the effects of evolutionary history/phylogeny(3655).

John Maynard-Smith (), Richard M. Burian (US), Stuart Kauffman (US), Pere Alberch (ES-US-ES), John Campbell (), Brian Carey Goodwin (CA-GB), Russell Scott Lande (US-GB), David M. Raup (US), and Lewis Wolpert (GB) wrote this often cited work on evolutionary/developmental constraint(3656).

Martha Allen Sherwood-Pike (GB) and Jane Gray (GB) reported finding fossil evidence of fungi (Ascoymcota) in material from the Silurian period (438-408 Ma)(3657).

Kamoya Kimeu (KE) discovered Turkana boy, a Homo ergaster: Homo erectus, KNMWT 15000, at Nariokotome near Lake Turkana in Kenya, in 1984. It has been dated to 1.6 M.Y.B.P.(3658-3661). In the 1988 video Mysteries of Mankind, produced by National Geographic, Richard Leakey said of this skeleton, "I think [the Turkana Boy] is remarkable because it's so complete, but perhaps another aspect that is often overlooked is that many people who don't like the idea of human evolution have been able to discount much of the work that we've done on the basis that it's built on fragmentary evidence. There have just been bits and pieces, and who knows, those little bits of bone could belong to anything. To confront some of these people with a complete skeleton that is human and is so obviously related to us in a context where it's definitely one and a half million years or even more is fairly convincing evidence, and I think many of the people who are fence-sitters on this discussion about creationism vs. evolution are going to have to get off the fence in the light of this discovery." 


Ernst Ruska (DE) for his fundamental work in electron optics, and for the design of the first electron microscope and Gerd Binnig (DE) and Heinrich Rohrer (CH) for their design of the scanning tunneling microscope shared the Nobel Prize in physics.

Stanley Norman Cohen (US) and Rita Levi-Montalcini (IT) were awarded the Nobel Prize in Physiology or Medicine for their discoveries of growth factors. 

Susan Solomon (US), Rolando R. Garcia (US), F. Sherwood Rowland (US), and Donald J. Wuebbles (US) reported on work done by a team of 16 scientists who made measurements of trace gases and physical properties of the atmosphere in Antarctica. The data showed conclusively that human-produced trace gases that contain chlorine and bromine are causing the ozone hole. Scientists from the National Aeronautics and Space Administration (NASA), National Oceanic and Atmospheric Administration (NOAA), and other organizations made the key measurements and analyses that showed the chlorofluorocarbons/ozone/polar stratospheric cloud theories of the ozone hole, and not other theories, are consistent with the observations(3662).

Franz Zinoni (DE), Angelika Birkmann (DE), Walfred Leinfelder (DE), and August Bock (DE) reported that the UGA codon could incorporate a new amino acid altogether: selenocysteine(3663). Selenocysteine, the 21st amino acid, has its own tRNA and is found in archaea, eubacteria and animals.

Bing Hao (US), Weimin Gong (CH), Tsuneo K. Ferguson (US), Cary M. James (US), Joseph A. Krzycki (US), and Michael K. Chan (US) found that genes encoding methanogenic methylamine methyltransferases within the archaeon  Methanosarcina barkeri all contain an in-frame amber (UAG) codon that is read through during translation. The electron density for the UAG-encoded residue is distinct from any of the 21 natural amino acids. Instead it appears consistent with a lysine in amide-linkage to (4R,5R)-4-substituted-pyrroline-5-carboxylate. They suggested that this amino acid be named l-pyrrolysine(3664). This brings the number of amino acids with their own tRNAs to 22.

Peter P. Mueller (US) and Alan G. Hinnebusch (US) found that in Saccharomyces cerevisiae multiple upstream AUG codons mediate translational control of the GCN4 gene(3665).

Jeremy Nathans (US), Darcy Thomas (US), and David S. Hogness (US) described the precise difference between the three opsins associated with blue, green, and red visual pigments in humans(3666). 

Nalin M. Kumar (US) and Norton B. Gilula (US) cloned and characterized human and rat liver cDNAs coding for a gap junction protein (connexin)(3667).

Francesco Losinno (IT), Fiorenza Busato (IT), Pietro Pavlica (IT), and F. Garofalo (IT) introduced percutaneous nephropyelolithotomy (PCN). This is a wide passage through the kidney percutaneously with the subsequent introduction of a 26 F nephroscope to remove kidney stones(3668).

Wolfgang Stremmel (DE), Georg Strohmeyer (DE), and Paul D. Berk (DE) provided evidence that movement of free fatty acids through hepatocyte plasma membrane is facilitated by a specific binding protein (FABP)(3669). 

Anton J.M. Roebroek (BE), Jack A. Schalken (NL), Jack A.M. Leunissen (BE), Carla Onnekink (NL), Henri P.J. Bloemers (NL), and Wim J.M. Van de Ven (BE-NL) discovered furin, the prototype of the novel family of endoproteolytic processing enzymes called proprotein convertases(3670). These enzymes are involved in the activation of a large variety of regulatory proteins like peptide hormones and their receptors, neuropeptides, growth and differentiation factors, blood coagulation factors, plasma proteins, and also exogenous proteins such as viral coat proteins (e.g. HIV-1 and Influenza virus), and bacterial toxins (e.g. diphtheria and anthrax toxin). See Steiner, 1967.

Lynn Y. Sakai (US), Douglas R. Keene (US), and Eva Engvall (US) discovered a new connective tissue protein, which they named fibrillin. It was isolated from the medium of human fibroblast cell cultures(3671).

Brendan Lee (US), Maurice Godfrey (US), Emilia Vitale (US), Hori Hisae (JP), Marie-Geneviéve Mattei (FR), Mansoor Sarfarazi (US), Petros Tsipouras (US), Francesco Ramirez (US), and David W. Hollister (US) linked Marfan’s syndrome and a phenotypically related disorder, congenital contractural arachnodactyly, to two different fibrillin genes(3672).

Harry C. Dietz (US), Garry R. Cutting (US), Reed E. Pyeritz (US), Cheryl L. Maslen (US), Lynn Y. Sakai (US), Glen M. Corson (US), Erik G. Puffenberger (US), Ada Hamosh (US), Elizabeth J. Nanthakumar (US), Sheila M. Curristin (US), Gail Stetten (US), Deborah A. Meyers (US), and Clair A. Francomano (US) found that Marfan’s syndrome is caused by a recurrent de novo missense mutation in the fibrillin gene(3673).

R. Ellen Magenis (US), Cheryl L. Maslen (US), Linda Smith (US), Leland Allen (US), and Lynn Y. Sakai (US) localized the human fibrillin (FBN) gene to chromosome 15, band q21.1(3674).

Andreas Bachmair (DE), Daniel Finley (US), and Alexander Varshavsky (US) encountered the N-end rule in experiments that explored the metabolic fate of a fusion between ubiquitin and a reporter protein such as E. coli beta-galactosidase (beta gal) in Saccharomyces cerevisiae(3675). The N-end rule relates the in vivo half-life of a protein to the identity of its N-terminal residue. In eukaryotes the N-end rule pathway is a part of the ubiquitin system.

Mark M. Hiller (DE), Andreas Finger (DE), Markus Schweiger (DE), and Dieter H. Wolf (DE) studied the endoplasmic reticulum (ER) degradation system with yeast mutants defective in the breakdown of a mutated soluble vacuolar protein, carboxypeptidase yscY (CPY*). The ubiquitin-conjugating enzyme Ubc7p participated in the degradation process, which was mediated by the cytosolic 26S proteasome. It is likely that CPY* entered the ER, was glycosylated, and was then transported back out of the ER lumen to the cytoplasmic side of the organelle, where it was conjugated with ubiquitin and degraded(3676).

Noboru Mizushima (JP), Takeshi Noda (JP), Tamotsu Yoshimori (JP), Yae Tanaka (JP), Tomoko Ishii (JP), Michael D. George (US), Daniel J. Klionsky (US), Mariko Ohsumi (JP) and Yoshinori Ohsumi (JP) isolated 14 autophagy-defective (apg) mutants of the yeast Saccharomyces cerevisiae and examined the autophagic process at the molecular level. They found that a unique covalent-modification system is essential for autophagy to occur. The carboxy-terminal glycine residue of Apg12, a 186-amino-acid protein, is conjugated to a lysine at residue 149 of Apg5, a 294-amino-acid protein. They discovered that Apg7 is a ubiquitin-E1-like enzyme. This is the first report of a protein unrelated to ubiquitin that uses a ubiquitination-like conjugation system. Furthermore, Apg5 and Apg12 have mammalian homologues, suggesting that this new modification system is conserved from yeast to mammalian cells(3677). See, Baudhuin, 1966.

Alfonso Tramontano (US), Kim D. Janda (US), Richard Alan Lerner (US), Scott J. Pollack (US), Jeffrey W. Jacobs (US), and Peter G. Schultz (US) produced antibodies specific for the transition state of substrates. These antibodies behaved as enzymes(3678-3681). Jean L. Marx (US) named them abzymes(3682). William P. Jencks (US) had predicted that it would be possible to make such molecules(1053).

Richard Alan Lerner (US), Alfonso Tramontano (US), Kevan M. Shokat (US), Christian J. Leumann (CH), Renee Joyce Sugasawara (US), and Peter George Schultz (US) produced antidodies which could function as enzymes(3683, 3684).

Maurice K. Gately (US), Darien E. Wilson (US), and Henry L. Wong (US) performed experiments suggesting that lymphokine-containing supernatant (LKS) fraction contains a late-acting factor(s), antigenically distinct from IL 2, which synergizes with IL 2 in facilitating human cytotoxic T lymphocyte (CTL) responses(3685).

Timothy R. Mosmann (US), Holly Cherwinski (US), Martha W. Bond (US), Martin A. Giedlin (US), and Robert L. Coffman (US) examined a panel of antigen-specific mouse helper T cell clones. They were characterized according to patterns of lymphokine activity production, and two types of T cell were distinguished. Type 1 T helper cells (TH1) produced IL 2, interferon-gamma, GM-CSF, and IL 3 in response to antigen + presenting cells or to Con A, whereas type 2 helper T cells (TH2) produced IL 3, BSF1, and two other activities unique to the TH2 subset, a mast cell growth factor distinct from IL 3 and a T cell growth factor distinct from IL 2. Examples of both types of T cell were also specific for or restricted by the I region of the MHC, and the surface marker phenotype of the majority of both types was Ly-1+, Lyt-2-, L3T4+. Both types of helper T cell could provide help for B cells, but the nature of the help differed. TH1 cells were found among examples of T cell clones specific for chicken RBC and mouse alloantigens. TH2 cells were found among clones specific for mouse alloantigens, fowl gamma-globulin, and keyhole limpet hemocyanin (KLH)(3686).

Ranjan Sen (US) and David Baltimore (US) found that NF-kappaB, a nuclear protein found only in cells that transcribe immunoglobulin light chain genes, interacts with a defined site in the kappa immunoglobulin enhancer. This protein can be induced in pre-B cells by stimulation with bacterial lipopolysaccharlde (LPS). The induction involves a post-translational activation. They interpreted these results to indicate that factors that control transcription of specific genes in specific cells may be activated by post-translatlonal modification of precursor factors present more widely(3687).

Julie B. Stern (US) and Kendall A. Smith (US) found that the activation of the T cell antigen receptor rendered the cells responsive to interleukin-2 (IL-2), but did not move them through the cell cycle. Interleukin-2 (IL-2) stimulated G1 progression to S phase, or lymphocyte blastic transformation. During IL-2 promoted G1 progression, expression of the cellular proto-oncogene c-myb was induced transiently at six to seven times basal levels, maximal levels occurring at the midpoint of G1(3688).

Barry J. Bowman (US), Emma Jean Bowman (US), Johann Peter Gogarten (US), Henrik Kibak (US), Peter Dittrich (DE), Lincoln Taiz (US), Morris F. Manolson (CA), Ronald J. Poole (CA), Takayasu Date (JP), Tairo Oshima (JP), Jin Konishi (JP), Kimitoshi Denda (JP), and Masasuke Yoshida (JP) showed that V-type direct action proton pumps, which produce proton gradients, appeared early in cellular evolution, before the divergence of archaebacteria (Archaea) and eubacteria (Bacteria)(3689, 3690).

Rob Benne (NL), Janny Van den Burg (NL), Just P. Brakenhoff (NL), Paul Sloof (NL), Jacques H. Van Boom (NL), and Marijke C. Tromp (NL) presented evidence that in the kinetoplast (a modified mitochondrium) DNA of Trypanosoma brucei and Trypanosoma fasciculata the coding sequence in mRNAs may be altered after transcription so that they do not complement the DNA from which they were transcribed. They named this process RNA editing and considered it to be an alternative means of handling genetic information(3691-3693). Others would later show that over 50% of the bases of the fully edited mature transcript of the cox III gene were introduced by the editing process with guide RNAs (gRNA) in some way insuring that the correct sequence appears in the mRNA.

Giuseppe Attardi (IT-US), Anne Chomyn (US), Paolo Mariottini (US), Michael W.J. Cleeter (GB), C. Ian Ragan (US), Marcia Riley (US), and Russell F. Doolittle (US) were the first to directly sequence genes found within mitochondria. Their presence was indicated by other researchers using different techniques(3694, 3695).

Mark E. Samuels (US) and Phillip Allen Sharp (US) isolated and purified a specific RNA polymerase II transcription factor(3696).

David M. Helfman (US), Stephen B. Cheley (US), Esa Kuismanen (FI), Linda A. Finn (US), Yuriko Yamawaki-Kataoka (JP) proposed that by variation in the intron exon splicing pattern of the pre-mRNA of tropomyosin, fibroblasts, and skeletal muscle cells are able to produce different mRNAs thus different tropomyosins. One gene is thereby coding for more than one type of polypeptide. This discovery altered forever the one gene-one enzyme paradigm(3697).

Maynard V. Olson (US), James E. Dutchik (US), Madge Y. Graham (US), Garrett M. Brodeur (US), Cynthia Helms (US), Mark Frank (US), Mia MacCollin (US), Robert Scheinman (US), and Thomas Frank (US) used global restriction mapping to define the physical arrangement of closely linked genes in the yeast genome(3698).

Timothy J.R. Harris (GB), Thakor P. Patel (GB), Fiona A.O. Marston (GB), Sheila P. Little (GB), John Spencer Emtage (GB), Ghislain Opdenakker (BE), Guido Volckaert (BE), Wilfried Rombauts (BE), Alfons Billiau (BE), and Piet DeSomer (BE) cloned cDNA coding for human tissue-type plasminogen activator into Escherichia coli and elicited its expression(3699).

June R. Scott (US), Susan K. Hollingshead (US), Kevin F. Jones (US), Vincent A. Fischetti (US), Shabbir A. Khan (US), and Bruce W. Erickson (US) cloned an M protein gene from type 6 streptococci. Using this gene they produced pure type 6 M protein and determined its amino acid sequence. From this sequence they were able to deduce that the primary job of the M protein is thwarting the immune system. Negative charges at the N-terminus may repel phagocytic white blood cells which also carry a negative charge. A portion of the M protein binds with factor H—a regulatory protein produced by the human host—which protects the M proteins most conserved regions from antibodies and complement enzymes. Only antibodies against the antigenically shifting hypervariable region at the N-terminus can clear an established streptococcal infection from the body(3700-3703).

Mitsuru Tsudo (JP), Robert W. Kozak (US), Carolyn K. Goldman (US), Thomas A. Waldmann (US), Keisuke Teshigawara (JP), Huey-Mei Wang (JP), Koichi Kato (JP), and Kendall A. Smith (US) independently discovered that the receptor for interleukin-2 (IL-2-R) is composed of two polypeptide chains. Both of these polypeptide chains are necessary for high-affinity binding of IL-2(3704, 3705).

Huey-Mei Wang (US) and Kendall A. Smith (US) found that the high-affinity receptor (IL-2-R) for interleukin-2 (IL-2) is formed by a unique cooperative functional interaction between the two separate and distinct binding sites expressed on the p75 alpha and p55 beta chains. The function of the p55 beta chain is as a helper binding site with no signaling capacity of its own. The p75 alpha chain, without assiatance from the p55 beta chain, is capable of promoting cell division within the T cell by triggering a second messenger system(3706).

Pawel Kisielow (PL), Hung Sia Teh (CA), Horst Blüthmann (CH), and Harald von Boehmer (DE-CH) provided evidence that positive selection of antigen-specific, class I MHC-restricted CD4-8+ T cells in the thymus requires the specific interaction of the alpha-beta T cell receptor with the restricting class I MHC molecule(3707).

Pawel Kisielow (PL), Horst Blüthmann (CH), Uwe D. Staerz (US), Michael Steinmetz (US), and Harald von Boehmer (DE-CH) examined the mechanism of self-tolerance in T cell-receptor transgenic mice expressing a receptor in many of their T cells for the male (H-Y) antigen in the context of class I H-2Db MHC antigens. Autospecific T cells are deleted in male mice. The deletion affects only transgene-expressing cells with a relatively high surface-density of CD8 molecules, including nonmature CD4+ CD8+ thymocytes, and is not caused by anti-idiotype cells(3708).

Hung Sia Teh (CA), Pawel Kisielow (PL), Bernadette Scott (CH), Hiroyuki Kishi (JP), Yasushi Uematsu (JP), Horst Blüthmann (CH), and Harald von Boehmer (DE-CH) found that the specific interaction of the T cell receptor on immature thymocytes with thymic major histocompatibility complex antigens determines the differentiation of CD4+8+ thymocytes into either CD4+8- or CD4-8+ mature T cells(3709). 

Richard A.F. Dixon (US), Brian K. Kobilka (US), David J. Strader (US), Jeffrey L. Benovic (US), Henrik G. Dohlman (US), Thomas Frielle (US), Mark A. Bolanowski (US), Carl D. Bennett (US), Elaine Rands (US), Ronald E. Diehl (US), Richard A. Mumford (US), Eve E. Slater (US), Irving S. Slater (US), Marc G. Caron (US), Robert J. Lefkowitz (US), and Catherine D. Strader (US) reported that beta 2-adrenergic receptor and rhodopsin share sequence homology and a presumed ‘seven member spanning’ topography, and that they are the first two members of what is probably a large gene family. Unexpectedly the gene for the beta 2-adrenergic receptor was found to be without introns(3710). This superfamily of receptors has grown to include: hormonal control of virtually all physiological functions, many instances of neurotransmission, the preception of light, taste, smell and pain, the effects of numerous therapeutic agents such as analgesic effect of opiates, the attraction of motile cells by chemotaxis, the stimulation and regulation of mitosis, and even the entry of viruses such as HIV into cells.

Patricia P. Abel (US), Richard S. Nelson (US), Barun De (US), Nancy L. Hoffmann (US), Stephen G. Rogers (US), Robert T. Fraley (US), and Roger N. Beachy (US) used a Ti plasmid of Agrobacterium tumefaciens from which tumor inducing genes had been removed to transfer cloned cDNA of the coat protein (CP) gene of tobacco mosaic virus (TMV) into tobacco cells to induce cross-protection against tobacco mosaic virus (TMV) in tobacco plants (Nicotiana tabacum). The results of these experiments indicate that plants can be genetically transformed for resistance to virus disease development(3711).

Alina C. Lopo (US), Susan E. MacMillan (US), John W. B. Hershey (US), Coralie C. Lashbrook (US), Dzintra Infante (US), and Anthony A. Infante (US) found that regulation of the initiation of protein synthesis in the sea urchin egg is associated with phosphorylation of initiation factor elF4F(3712-3714).

Rick L. Sharp (US), David L. Costill (US), William J. Fink (US), and Douglas S. King (US) demonstrated the increased buffer capacity of muscle brought on by sprint training(3715). These researchers credited Archibald Vivian Hill (GB) with putting forth the hypothesis that led to their study.

James W. Moulder (US) reported that the phagocytosis of microbial pathogens stimulates macrophages to acidify their phagosomes then fuse them with one or more lysosomes(3716).

David F. Bird (CA) and Jacob Kalff (CA) discovered that some algae phagocytize and digest bacteria. The most active alga they tested was the chrysophycean, Dinobryon sp(3717, 3718). 

George Kollias (GB), Nick Wrighton (GB), Jacky Hurst (GB), and Frank Grosveld (GB) introduced the human fetal gamma- and adult beta-globin genes into the germ line of mice. Analysis of the resulting transgenic mice shows that the human gamma-globin gene was expressed like an embryonic mouse globin gene; the human beta-globin gene was expressed like an adult mouse globin gene. These results imply that the regulatory signals for tissue- and developmental stage-specific expression of the globin genes have been conserved between man and mouse but that the timing of the signals has changed(3719).

Robert E. Hammer (US), Vernon G. Pursel (US), Caird E. Rexroad, Jr. (US), Robert J. Wall (US), Douglas J. Bolt (US), Richard Deforest Palmiter (US), and Ralph Lawrence Brinster (US) produced transgenic mice by linking the coding sequences of rat growth hormone gene to the mouse metallothionein promoter. This chimeric plasmid was injected into one of the two pronuclei of fertilized mouse eggs. The resulting transgenic mice grew faster than normal mice(3720, 3721).

Lance A. Liotta (US), Raya Mandler (US), Genesio Murano (US), David A. Katz (US), Richard K. Gordon (US), Peter K. Chiang (US), and Elliott Schiffmann (US) isolated, purified, and partially characterized a cell motility-stimulating factor from the serum-free conditioned medium of human A2058 melanoma cells. They term this activity "autocrine motility factor" (AMF)(3722).

Hideomi Watanabe (JP), Kenji Takehana (JP), Massayo Date (JP), Tetsuya Shinozaki (JP), and Avraham Raz (US) demonstrated that "autocrine motility factor" (AMF) is the previously cloned cytokine and enzyme designated as neuroleukin, and phosphohexose isomerase, which has been independently implicated in cell motility, and to be a cancer progression marker(3723).

Kang-Sheng Wang (US), Qui Lim Choo (US), Amy J. Weiner (US), Jing-Hsiung Ou (US), Richard C. Najarian (US), Richard M. Thayer (US), Guy T. Mullenbach (US), Katherine J. Denniston (US), John L. Gerin (US), Michael Houghton (US), A. Kos (NL), Rein Dijkema (NL), Annika C. Arnberg (NL), Peter H. van der Meide (NL), Huub Schellekens (NL), Pei-Jer Chen (TW), Ganjam Kalpana (US), Janet Goldberg (US), William Mason (US), Barbara Werner (US), and John Taylor (US) confirmed that the causative agent for delta hepatitis in mammals contains a circular, viroid-like RNA(3724-3726).

Patricia Kahn (DE), Lars Frykberg (SE), Claire Brady (DE), Irene Stanley (AU), Hartmut Beug (DE), Björn Vennström (SE), and Thomas Graf (DE) reported that during the generation of avian erythroblastosis, the erbA oncogene acts to prevent irreversible erythrocyte differentiation(3727). Note: ErbA oncoprotein is involved in neoplastic transformation leading to acute erythroleukemia and sarcomas.

Kenneth W. Kinzler (US) and Bert Vogelstein (US) reported that during human colon carcinogenesis, inactivation of the APC/ß-catenin pathway serves to block the egress of enterocytes in the colonic crypts into a differentiated, postmitotic state(3728).

Karla J. Matteson (US), James Picado-Leonard (US), Bon-Chu Chung (US), Thuluvancheri K. Mohandas (US), and Walter L. Miller (US) assigned the gene for adrenal P450c17 (steroid 17 alpha-hydroxylase/17,20 lyase) to human chromosome 10(3729). This gene is also called CYP17 and is important because its enzyme product is part of the pathway to convert cholesterol to cortisol, testosterone and estradiol.

Francois Clavel (FR), Denise Guetard (FR), Francoise Brun-Vezinet (FR), Sophie Chamaret (FR), Marie-Anne Rey (FR), Maria Odete Santos-Ferreira (FR), Anne G. Laurent (FR), Charles Dauguet (FR), Christine Katlama (FR), Christine Rouzioux (FR), David Klatzmann (FR), John L. Champalimaud (FR), and Luc Montagnier (FR) isolated human immunodeficiency virus type 2 from patients in West Africa. This virus causes AIDS(3401).

Bernard Lown (US), Raghavan Amarasingham (US), and Jose Neuman (US) introduced the use of synchronized capacitor discharge to terminate cardiac arrhythmias(3730).

Ralph Seal Paffenbarger, Jr. (US), Mary Elizabeth Laughlin (US), Alfred S. Gima (US), Rebecca A. Black (US), Robert T. Hyde (US), Alvin L. Wing (US), Dexter L. Jung (US), Chung-Cheng Hsieh (US), Susan P. Helmrich (US), David R. Ragland (US), and Rita W. Leung (US) beginning in 1960, performed the landmark College Alumni Health Study, investigating the exercise habits of over 50,000 University of Pennsylvania and Harvard University alumni and the San Francisco Longshoremen Study. The results of this study confirmed that more physically active people have a lower risk of coronary heart disease and live longer(3731-3734).

Steen M. Willadsen (GB) cloned sheep from early embryo cells(3735).

Katharine B. Payne (US), William R. Langbauer, Jr. (US), and Elizabeth M. Thomas (US) discovered that elephants frequently communicate using infrasound at frequencies below the level of human hearing. The frequency of a sound is measured in Hertz (Hz) and the infrasonic range is generally considered to be between 1 and 20 Hz(3736).

Zh Zhang (CN) discovered large (40-200 micrometer) spherical microfossils 1.8 to 1.9 billion years old in sedimentary rocks from China. These microfossils were interpreted to be the earliest know eukaryotes (Eucarya)(3737).


“Science is a search for repeated pattern.” Stephen Jay Gould(3738).

Susumu Tonegawa (US) was awarded the Nobel Prize in Physiology or Medicine for his discovery of the genetic principle for generation of antibody diversity. 

Rainer Grün (DE-AU) and Henry P. Schwarcz (CA) introduced electron spin resonance (ESR) dating of archaeological and palaeoanthropological materials. Fossil teeth are a ubiquitous component of prehistoric sites, and as a consequence, ESR dating of tooth enamel is very widely applicable tool for chronometric dating in the time range beyond the 40,000 yr. limit of radiocarbon and up to at least 2 Ma(3739, 3740).

Koichi Tanaka (JP), Yutaka Ido (JP), Satoshi Akita (JP), Yoshikazu Yoshida (JP), Tamio Yoshida (JP), and Hiroaki Waki (JP) developed electrospray ionization for the mass spectroscopy of large and fragile polar biomolecules important in biological systems (3741, 3742).

John B. Fenn (US), Matthias Mann (US), Chin Kai Meng (US), Shek Fu Wong (US), and Craig M. Whitehouse (US) independently developed the same technique(3743).

A. Mar (US), Jason P. Dworkin (US) and Juan Oró (US) synthesized uridine diphosphate glucose, cytidine diphosphate choline, other phosphorylated metabolic intermediates, the coenzymes adenosine diphosphate glucose (ADPG), guanosine diphosphate glucose (GDPG), and cytidine diphosphoethanolamine (CDP-ethanolamine) under primitive Earth conditions(3744, 3745).

Kyriacos Costa Nicolaou (CY-US), Tushar K. Chakraborty (IN), Robert A. Daines (US), and Yuji Ogawa (JP) carried out the total synthesis of amphotericin B(3746).

Kyriacos Costa Nicolaou (CY-US), Robert D. Groneberg (US), Tohru Miyazaki (JP), Nicolas A. Stylianides (CY), Thomas J. Schulze (US), Wilhem Stahl (DE), Adrian L. Smith (GB), Chan-Kou Hwang (US), Emmanuel N. Pitsinos (GR), Gerard R. Scarlato (US), Conrad W. Hummel (US), Masahisa Nakada (JP), Katsuhiro Shibayama (JP), Hiroyuki Saimoto (JP), Erwin P. Schreiner (AT), Toshio Suzuki (JP), Yoshiharu Iwabuchi (JP), Yukio Mizuno (JP), and Kai-Uwe Baldenius (DE) carried out a total synthesis of calicheamicin gamma(3747-3753). Calicheamicin gamma 1I is a recently discovered diyne-ene-containing antitumor antibiotic with considerable potency against murine tumors.

Gregory Prelich (US), Matthew Kostura (US), Daniel R. Marshak (US), Michael B. Mathews (US), and Bruce Stillman (US) reported the ring-shaped eukaryotic version of the "sliding clamp" used to keep a single DNA polymerase moving progressively along the same DNA template strand. This eukaryotic version of the clamp is called proliferating cell nuclear antigen (PCVA)(3754).

Peter T. Stukenberg (US), Patricia S. Studwell-Vaughn (US), and Mike O'Donnell (US) demonstrated that the prokaryotes use a homologous enzyme which forms around the DNA helix to keep the DNA polymerase tethered to the same molecule as it moves(3755).

Xiang-Peng (US), Rene Onrust (NL), Mike O'Donnell (US), and John Kuriyan (US) solved the three-dimensional structure of the beta subunit of one of these "sliding clamp" enzymes found in E. coli(3756).

Pamela J. Bjorkman (US), Mark A. Saper (US), Boudjema Samraoui (US), William S. Bennett (US), Jack L. Strominger (US), and Don C. Wiley (US) determined that the class I histocompatibility antigen (HLA-A2) from human cell membranes has two structural motifs: the membrane-proximal end of the glycoprotein contains two domains with immunoglobulin-folds that are paired in a novel manner, and the region distal from the membrane is a platform of eight antiparallel beta-strands topped by alpha-helices. A large groove between the alpha-helices provides a binding site for processed foreign antigens(3757).

Jean-Francois Brunet (FR), Francois Denizot (FR), Marie-Francoise Luciani (FR), Magali Roux-Dosseto (FR), Marie Suzan (FR), Marie-Genevieve Mattei (FR), and Pierre Golstein (FR) discovered a new member of the murine immunoglobulin superfamily; they named it CTLA-4. It consists of a V-like domain flanked by two hydrophobic regions, one of which has a structure suggestive of membrane anchoring. CTLA-4 is usually expressed in activated lymphocytes and is coinduced with T cell mediated cytotoxicity in inducible models of this process. The murine ctla-4 gene maps to the C band of chromosome 1(3758).

Yueh-hsiu Chien (US), Makio Iwashima (US), Kenneth B. Kaplan (US), John F. Elliott (US), and Mark M. Davis (US) discovered a new T cell receptor gene located within the alpha locus and expressed early in T cell differentiation(3759).

Paul D. Siebert (US) and Minoru Fukuda (JP) cloned the human glycophorin B gene and determined its genomic relationship to glycophorin A(3760). It is located on the long arm of chromosome 4 (4q28-q31) and has 5 exons. The peptide sequence of 72 amino acids had been determined earlier that year. Glycophorin A and B are major sialoglycoproteins of the human erythrocyte membrane which bear the antigenic determinants for the MN and Ss blood groups respectively.

Marc K. Jenkins (US) and Ronald H. Schwartz (US) found that antigen presentation by chemically modified splenocytes induces antigen-specific T cell unresponsiveness in vitro and in vivo(3761).

John W. Kappler (US), Neal Roehm (US), and Philippa Marrack (US) presented results showing that in normal animals tolerance to self-MHC is due to clonal elimination rather than suppression. In addition, they indicated that tolerance induction may occur in the thymus at the time immature thymocytes are selected to move into the mature thymocyte pool(3762).

Elwyn Y. Loh (US), Lewis L. Lanier (US), Christoph W. Turck (US), Dan R. Littman (US), Mark M. Davis (US), Yueh-hsiu Chien (US), and Arthur Weiss (US) identified and sequenced a fourth human T cell antigen receptor chain(3763).

Brad J. Brandhuber (US), Tom Boone (US), William C. Kenney (US), and David B. McKay (US) grew crystals of interleukin-2 and determined its three-dimensional structure(3764, 3765).

Daizo Koga (JP), Akira Isogai (JP), Shohei Sakuda (JP), Shogo Matsumoto (JP), Akinori Suzuki (JP), Shigeru Kimura (JP), and Akio Ide (JP) were the first to isolate allosamidin, an antibiotic which inhibits insect, nematode, and fungal chitinases(3766).

Takenori Ochiai (JP), Kazuaki Nakajima (JP), Matsuo Nagata (JP), Takao Suzuki (JP), Takehide Asano (JP), Takeshi Uematsu (JP), Takesada Goto (JP), Seiji Hori (JP), Takashi Kenmochi (JP), Toshio Nakagoori (JP), and Kaichi Isono (JP) reported the effect of a new immunosuppressive agent, FK 506 (tacrolimus), on heterotopic cardiac allotransplantation in the rat(3767). The agent was isolated from Streptomyces tsukubaensis.

Jeffrey E. DeClue (US), Ivan Sadowski (CA), G. Steven Martin (GB-US), and Anthony J. Pawson (GB-CA) discovered the Src homology 2 (SH2) domain and identified its role in intracellular signaling (all cytoplasmic protein-tyrosine kinases (PTKs) share a noncatalytic domain, termed SH2, which comprises approximately 100 residues located immediately N-terminal to the kinase domain). They established that modular protein interactions control signal transduction(3768). It is now widely recognized that SH2 domains control a series of protein-protein interactions by which the components of the signal transduction process activate one another. It now appears that these SH2-mediated interactions are very widespread, and play a central role both in normal cell signaling, and in the abnormal stimulation of cell growth induced by many oncogene products.

Palmer A. Orlandi, Jr. (US) and Sam J. Turco (US) isolated and characterized the lipid moiety of the lipophosphoglycan of Leishmania donovani as a novel lyso-alkylphosphatidylinositol(3769).

A human genome sequencing plan won unanimous approval in the United States(3770).

The U.S. Patent Office indicated that new higher life forms, animal or plant, are proper subjects of patents if they are not naturally occurring (and are not human, in the case of animals)(3771).

Walter Gilbert (US) proposed the Exon Theory of Genes which is the idea that the first genes were made of small pieces. The crucial elements of the theory are that the very first genes were exons represented by small polypeptide chains ≈ 15-20 amino acids long, that the basic method used by evolution to make new genes was to shuffle the exons, and that a major trend of evolution was then to lose introns and to fuse small exons together to make complicated exons(3772).

Walter Gilbert (US), Sandro J. de Souza (US), and Manyuan Long (US) supported the exon theory of genes with experimental evidence(3773).

Bruce Michael Alberts (US) and Kevin J. Hacker (US) proposed that during eukaryotic and prokaryotic DNA replication the lagging chain of DNA loops back over the DNA polymerase(3774, 3775).

Ada Yonath (IL), Kevin R. Leonard (DE) and Heinz Guenter Wittmann (DE) determined that the large subunit of the ribosome houses a tunnel extending from the area of the A and P sites to the area on the ribosome where the newly assembled polypeptide exits. Therefore, the nascent polypeptide is likely to pass down this tunnel during the translation process(3776).

Bernd Epe (DE), Paul Woolley (DE), and Horst Hornig (DE) established that tetracycline inhibits translation of mRNA by interacting with the ribosomal A site(3777).

Ditlev E. Brodersen (DK), Andrew P. Carter (GB), William M. Clemons, Jr. (GB), Robert J. Morgan-Warren (GB), Frank V. Murphy, 4th (GB), James M. Ogle (GB), Michael J. Tarry (GB), Brian T. Wimberly (US), and Venkatraman Ramakrishnan (IN-US-GB) confirmed, at the atomic level, that indeed the A site of the ribosome is where tetracycline attaches to inhibit translation(3778).

John E. Walker (GB), Alison L. Cozens (GB), Mark R. Dyer (GB), Ian M. Fearnley (GB), Steven J. Powell (GB), Michael J. Runswick (GB), David F. McCarn (US), Richard A. Whitaker (US), Jawed Alam (US), Jacqueline M. Vrba (US), and Stephanie E. Curtis (US) isolated and sequenced the genes coding for F0F1 ATPase in Anabaena and Synechococcus(3779-3782).

John P. Adelman (US), Chris T. Bond (US), James Douglass (US), and Edward Herbert (US) found two rat genes, one encoding gonadotropin-releasing hormone and the other an unidentified protein, that occupy opposite nucleotide chains of the same DNA segment(3783).

Ernst Hafen (CH), Konrad Basler (CH), Jan E. Edstroem (US), and Gerald M. Rubin (US) after sequencing the sevenless gene discovered that it encodes a predicted transmembrane protein bearing a tyrosine kinase domain that is highly related to domains that are present in viral oncogenes and hormone receptors. Based on this homology, they correctly prophesized that the molecular mechanisms of signaling would be the same in both cases — a prediction that came to fruition a few years later(3784).

Michael A. Simon (US), David D.L. Bowtell (AU), G. Steven Dodson (US), Todd R. Laverty (US), and Gerald M. Rubin (US) reported that two of the isolated enhancers of sevenless encoded known signaling molecules — the GTPase Ras, and its guanine nucleotide exchange factor, Cdc25(3785).

Hugh D. Campbell (AU), William Q.J. Tucker (AU), Yvonne Hort (AU), Mary E. Martinson (AU), Garry Mayo (AU), Elaine J. Clutterbuck (AU), Colin J. Sanderson (AU), and Ian G. Young (AU) carried out molecular cloning, nucleotide sequencing, and expression of the gene encoding human eosinophil differentiation factor (interleukin 5)(3786).

Paul Primakoff (US), Hilary Hyatt (US), and Joanne Tredick-Kline (US) discovered a sperm protein that promotes fusion of mammalian egg and sperm membranes. It was called PH-30(3787).

David T. Burke (US), Georges F. Carle (US), and Maynard V. Olsen (US) created yeast artificial chromosomes (YACs) which proved to be excellent cloning vectors for large pieces of DNA(3788).

Leland H. Johnston (GB), Julia H.M. White (GB), Anthony L. Johnson (GB), Giovanna Lucchini (IT), and Paolo L. Plevani (IT) described the control sequences responsible for co-ordinated expression in the yeast cell cycle of enzymes involved in DNA synthesis(3789).

Arthur Ashkin (US), Joseph M. Dziedzic (US), and T. Yamane () developed a new optical technique which made it possible to hold and move objects as small as individual microtubules and microtubule motors and measure forces generated by the motors. The technique, employing a powerful light microscope and a laser is referred to as optical tweezers(3790, 3791).

Gary J. Gorbsky (US), Douglas Edward Koshland, Jr. (US), Timothy J. Mitchison (US), Marc Wallace Kirschner (US), Paul J. Sammak (US), and Gary Guy Borisy (US) performed experiments indicating that, during anaphase A (reduction of kinetochore-to-pole distance) chromosomes move toward the cell poles by sliding over or along kinetochore microtubules(3792, 3793).

Theodore M. Klein (US), Edward D. Wolf (US), Ray Wu (US), Nelson Allen (US), and John C. Sanford (US) developed the biolistic or gene gun method for inserting foreign DNA into host plant cells. Magnesium tungsten or gold particles are coated with a DNA vector construct which can also contain a promoter and selectable genes. The coated particles are then blasted into plant cells using gunpowder detonation in a particle gun. The method works with both monocotyledonous and dicotyledonous plants(3794, 3795).

Theodore M. Klein (US), Michael E. Fromm (US), Arthur Weissinger (US), Dwight Tomes (US), Steve Schaaf (US), Margit Sletten (US), and John C. Sanford (US) successfully recovered stable transformants following transfer of foreign genes into intact maize cells with high-velocity microprojectiles(3796).

Katherine Gordon (US), Eric Lee (US), James A. Vitale (US), Alan E. Smith (US), Heiner Westphal (US), and Lothar Henninghausen (US) constructed a vector with which they transferred the human tissue plasminogen activator (t-PA) with its endogenous secretion signal sequence into mouse embryos. Milk obtained from lactating females was found to contain biologically active t-PA. This has medical significance since t-PA dissolves fibrin clots and thus may be used to treat myocardial infarction and other similar conditions(3797).

Thomas Ganz (US), Michael E. Selsted (US), and Robert I. Lehrer (US) discovered that the phagocytosis of microbial pathogens by macrophages stimulates the macrophages to release defensins (proteins with antimicrobial potential) into the lysosomes of neutrophils and alveolar macrophages(3798).

Roland Stocker (CH), Yorihiro Yamamoto (JP), Antony F. McDonagh (US), Alexander N. Glazer (US), and Bruce Nathan Ames (US) found that bilirubin, at micromolar concentrations in vitro, efficiently scavenges peroxyl radicals generated chemically in either homogeneous solution or multilamellar liposomes(3799).

Zlatko Dembic (CH), Werner Haas (CH), Rose Zamoyska (US), Jane Parnes (US), Michael Steinmetz (CH), and Harald von Boehmer (CH) showed that the CD8 coreceptor is actively involved in antigen recognition by killer T cells(1995, 3800).

Frank Emmrich (DE), Ulrike Strittmatter (DE), and Klaus Eichmann (DE) discovered that a killer T cell is activated most effectively when an alpha-beta T cell receptor and a CD8 coreceptor are bound by the same molecule(3801).

Ming Luo (US), Gerrit Vriend (NL), Greg Kamer (US), Iwona Minor (US), Edward Arnold (US), Michael George Rossmann (US), Ulrike Boege (CA), Douglas G. Scraba (CA), Gregory M. Duke (US), Ann C. Palmenberg (US), and Roland R. Rueckert (US) suggested that many spherical RNA viruses have evolved from a common viral ancestor. This was based on three-dimensional constructions of the viruses(3802, 3803).

Philippe Clerc (FR), and Philippe J. Sansonetti (FR) discovered that F-actin and myosin accumulate as aggregates subjacent to the cytoplasmic membrane in areas of the cell surface that interact with invasive shigellae. It can be concluded that S. flexneri has the capacity to induce epithelial cells to perform a phagocytic process similar to that observed in professional phagocytes(3804). 

Steven E. Lindow (US) produced a genetically altered bacterial strain of Pseudomonas syringae, designed to make plants resistant to frost damage(3805). It was first released in California.

That same year a version of Rhizobium meliloti (Sinorhizobium meliloti) dubbed RMBPC-2, was genetically engineered to contain antibiotic resistance as well as genes to enhance nitrogen-fixing ability. The Environmental Protection Agency (EPA) approved its use in 1997. It was first released in Wisconsin.

Lauri Saxén (FI) determined that glial cell line-derived neurotrophic factor (GDNF) controls ureteric branching and thereby a fundamental step in kidney development(3806).

Mary D. Lee (US), Theresa S. Dunne (US), Marshall M. Siegel (US), Conway C. Chang (US), George O. Morton (US), Donald B. Borders (US), George A. Ellestad (US), and William J. McGahren (US) discovered that calicheamicin gamma, produced by Micromonospora echinospora ssp calichensis, has a phenomenally high potency against tumor cells(3807-3809).

Shinichiro Sawada (JP), Gen Suzuki (JP), Yoshiko Kawase (JP), and Fumimaro Takaku (JP) reported results indicating that the novel immunosuppressive agent, FK506, affects T cell activation with mechanisms similar to those of cyclosporin A (CsA) but at considerably lower concentrations(3810).

Ralph R. Isberg (US), Deborah L. Voorhis (US), and Stanley Falkow (US) discovered that invasin, produced by Yersinia spp., triggers its engulfment by intestinal cells on their way to colonize lymph nodes of the gut(3811).

T. Hasegawa (JP), Fuminori Masugi (JP), Toshio Ogihara (JP), Yuichi Humahara (JP), Tadashi Inagami (US), Masaaki Tamura (US), Stephen S. Gottlieb (US), Amy C. Rogowski (US), Michelle Weinberg (US), Cathy M. Krichten (US), Bruce P. Hamilton (US), John M. Hamlyn (US), Mordecai P. Blaustein (US), Sergio Bova (IT), Donald W. DuCharme (US), Frederic Mandel (US), W. Rodney Mathews (US), James H. Ludens (US), Zhuo Ren Lu (US), Paolo Manunta (IT), Keizo Kimura (SE), Jui R. Shah (US), James Laredo (US), Jennifer P. Hamilton (US), Matthew J. Hamilton (US), Su-Qin Li (CN), Christian Eim (DE), Ulrike Kirch (DE), Rudolf E. Lang (DE), and Wilhelm Schoner (DE) presented evidence that ouabain is a new steroid hormone of the adrenal cortex and hypothalamus with qualities like digitalis. Ouabain-like immunoreactivity has been found in almost all tissues, including plasma, but the highest concentrations have been observed in the adrenal, hypophysis, and hypothalamus(3812-3817). See, Ringer, 1885.

Dmitry Goldgaber (US), Michael I. Lerman (RU-US), O. Wesley McBride (US), Umberto Saffiotti (IT-US), and Daniel Carleton Gajdusek (US) reported a gene associated with alzheimer’s disease. The gene is highly conserved in evolution and has been mapped to human chromosome 21(3818).

Thomas A. Stamey (US), Norman Yang (US), Alan R. Hay (US), John E. McNeal (US), Fuad S. Freiha (US) and Elise A. Redwine (US) concluded that prostate-specific antigen (PSA) is more sensitive than prostatic acid phosphatase (PAP) in the detection of prostatic cancer and will probably be more useful in monitoring responses and recurrence after therapy. However, since both PSA and PAP may be elevated in benign prostatic hyperplasia, neither marker is specific(3819).

Manuel Elkin Patarroyo (CO), Pedro Romero (CO), Martha L. Torres (CO), Pedro Clavijo (CO), Alberto Moreno (CO), Alberto Martinez (CO), Raul Rodriguez (CO), Fanny Guzman (CO), and Edelmira Cabezas (CO) developed the first synthetic vaccine against the Plasmodium falciparum parasite. Its efficacy is yet to be proved(3820).

Michael S. Hershfield (US), Rebecca H. Buckley (US), Michael L. Greenberg (US), Alton L. Melton (US), Richard Schiff (US), Christine Hatem (US), Joanne Kurtzberg (US), M. Louise Markert (US), Roger H. Kobayashi (US), Ai-Lan Kobayashi (US), and Abraham Abuchowski (US) treated two children who had adenosine deaminase (ADA) deficiency and severe combined immunodeficiency disease (SCID) by injecting bovine adenosine deaminase modified by conjugation with polyethylene glycol (PEG-ADA). The therapy was considered a success(3821).

Richard S. Schwalbe (US), Jack T. Stapleton (US), and Peter H. Gilligan (US) reported the emergence of vancomycin resistant coagulase-negative staphylococci(3822). This was an alarming development because at the time vancomycin was the antibiotic of last resort in treating methicillin-resistant-Staphylococcus aureus (MRSA).

Larry R. Squire (US) reported that the hippocampus region of the brain is integral to the learning of facts pertaining to people, places, and events(3823).

W. Ripley Ballou (US), James A. Sherwood (US), Franklin A. Neva (US), Daniel M. Gordon (US), Robert A. Wirtz (US), Gall F. Wasserman (US), Carter L. Diggs (US), Stephen L. Hoffman (US), Michael R. Hollingdale (GB), Wayne T. Hockmeyer (US), Imogene Schneider (US), James F. Young (US), Peter Reeve (US), and Jeffrey D. Chulay (US) reported on the first human trials of malaria vaccines based on recombinant or synthetic forms of the circumsporozoite protein(3824).

Brian H. Cummins (GB), M.L. Auckland (GB), and P. Cummins (GB) developed a cardiac-specific troponin-I radioimmunoassay capable of diagnosing acute myocardial infarction(3825).

James M. Robl (US), Randall Prather (US), Frank Barnes (US), Willard Eyestone (US), David L. Northey (US), B.G. Gilligan (US), and Neal L. First (US) cloned a bovine from a bovine early embryo cell(3826).

Frayed, fibrous chew sticks were being used by the ancient Egyptians as a form of tooth brush. Toothpaste was first used ca. 2000 B.C.E.(3827).

Rebecca L. Cann (US), Mark Stoneking (US), Allan C. Wilson (NZ), Linda Vigilant (US), Henry C. Harpending (US), Kristen Hawkes (US), Alan R. Templeton (US), S. Blair Hedges (US), Sudhir Kumar (IN), and Koichiro Tamura (JP) proposed that all mitochondrial DNA (mtDNA) types in contemporary humans originated in a common female ancestor present within an African population between 164,000 and 247,000 B.C.E., i.e., a mitochondrial eve. All the populations examined except the African population have multiple origins, implying that each area was colonized repeatedly. These results support and extend the African origin hypothesis of human mtDNA evolution(3828-3831).

Victor Almon McKusick (US) and Francis Hugh Ruddle (US) were searching for an appropriate title for a new journal which covered the newly developing discipline of mapping/sequencing (including analysis of the genetic information). Thomas H. Roderick (US) suggested the name Genomics(3832).

J. William Schopf (US), Bonnie M. Packer (US), Roger Buick (AU), and Stanley M. Awramik (US) presented evidence for a well established community of oxygenic photosynthesizers ca. 700 Ma(3332, 3833, 3834).

Peter R. Sheldon (GB) collected 15,000 trilobite specimens from the Ordivician
 stratum around Builth Wells, England. Their fossilized remains make a strong case for gradual evolutionary change(3835).


“What gives biological research its special flavor is the long continued operation of natural selection. Every organism, every cell, and all the larger biochemical molecules are the end result of a long intricate process, often stretching back several billion years.…Outside biology, we do not see the process of exact geometrical replication, which, together with the replication of mutants, leads to rare events becoming common.…Another key feature of biology is the existence of many identical examples of complex structures.…One type of protein molecule, on the other hand, usually exists in many absolutely identical copies. If this were produced by chance alone, without the aid of natural selection, it would be regarded as almost infinitely improbable.…Biology has its laws, such as those of Mendelian genetics, but they are often only rather broad generalizations, with significant exceptions to them.…Biologists must constantly keep in mind that what they see was not designed, but rather evolved.…Nature can only build on what is already there.” Francis Harry Compton Crick (3836).

“We are made of star stuff, processed through supernova, concentrated from the contracting solar nebula, spun into biochemical aggregates with a difference, and graced, during our tenure here, by the ability to imagine, to conceptualize, to hypothesize, to create science, poetry, music, and works of art and technology.” Preston Ercelle Cloud, Jr.(3837). 

Johann Deisenhofer (DE-US) , Robert Huber (DE) and Hartmut Michel (DE) were awarded the Nobel Prize in Chemistry for the determination of the three-dimensional structure of a photosynthetic reaction center.

Sir James Whyte Black (GB), Gertrude Belle Elion (US) and George Herbert Hitchings (US) were awarded the Nobel Prize in Physiology or Medicine for their discoveries of important principles for drug treatment.

Roger B. Ruggeri (US), Marvin M. Hansen (US), and Clayton H. Hathcock (US) carried out the complete synthesis of methyl homosecodaphniphyllate. This chemical, first discovered in a crude extract from the tree Daphniphyllum macropodum, was used to treat asthma(3838).

Toshikazu Oki (JP), Masakazu Konishi (JP), Kozo Tomatsu (JP), Koji Tomita (JP), Kyoichiro Saitoh (JP), Mitsuaki Tsunakawa (JP), Maki Nishio (JP), Takeo Miyaki (JP), and Hiroshi Kawaguchi (JP) discovered pradimicin, a novel class of potent antifungal antibiotics(3839).

Edward N. Baker (NZ) Sir Thomas L. Blundell (GB), John F. Cutfield (NZ), Susan M. Cutfield (NZ), Eleanor J. Dodson (GB), Guy G. Dodson (GB), Dorothy Mary Crowfoot-Hodgkin (GB-NZ), Roderick E. Hubbard (GB), Neil W. Isaacs (GB), Colin D. Reynolds (GB), Kiwako Sakabe (GB), Norioshi Sakabe (GB), and Numminate M. Vijayan (GB) used computer aided x-ray diffraction analysis to determine the three dimensional structure of 2 Zn pig insulin crystals at 1.5 A resolution(3840).

William H. Landschulz (US), Peter F. Johnson (US), and Steven Lanier McKnight (US) discovered the leucine finger, a structural motif common to many regulatory proteins(3841).

Jim Haseloff (AU) and Wayne L. Gerlach (AU) produced synthetic ribozymes and deduced general rules associated with the design of such molecules(3842).

Aleksey Zaks (US) and Alexander M. Klibanov (US) demonstrated that some enzymes can function in non-aqueous environments(3843).

Thomas F. Donahue (US), A. Mark Cigan (US), Edward K. Pabich (US), and Beatriz Amaral de Castilho-Valavicius (BR) showed that in Saccharomyces cerevisiae the 40S ribosome recognizes the AUG initiator codon by using the anticodon tRNAi Met along with contributions from elongation factors (elFs) 1, 2, and 5(3844).

A. Mark Cigan (US), Lan Feng (US), and Thomas F. Donahue (US) established that perfect base pairing between the anticodon of the initiator and the start codon in mRNA, regardless of their sequences, is a fundamental requirement for efficient initiation in yeast(3845).

A. Mark Cigan (US), Edward K. Pabich (US), Lan Feng (US), Thomas F. Donahue (US), and Beatriz Amaral de Castilho-Valavicius (BR)  cloned and sequenced the SU12 and SU13 genes which they found to encode the  alpha and beta subunits of elF2(3844, 3846).  

Jean Gautier (US), Chris Norbury (US), Manfred J. Lohka (US), Paul Nurse (US), and James L. Maller (US) found that a Xenopus p34cdc2 homolog is present in purified maturation-promoting factor (MPF) and suggest that p34cdc2 is a component of the control mechanism initiating mitosis generally in eukaryotic cells(3847). 

Kurt R. Gehlsen (US), Lena Dillner (US), Eva Engvall (US), and Erkki Ruoslahti (FI-US) reported identifying the receptor that allows a cell to attach to a specific protein called a laminin(3848). This discovery is important to understanding how nerves are formed and brings scientists closer to finding a way to repair them.

Steven I. Dworetzky (US) and Carl M. Feldherr (US) concluded that in Xenopus oocytes the nuclear translocation sites for gold particles coated with different classes of RNA are located in the centers of the nuclear pores and that particles at least 23 nm in diameter could cross the envelope. It was also determined that individual pores are bifunctional, that is, capable of transporting both proteins and RNA(3849).

Howard M. Grey (US), Stéphane Demotz (CH), Soren Buus (DK), Alessandro Sette (US), Emil R. Unanué (CU-US), Clifford V. Harding (US), Immanuel F. Luescher (CH), Richard W. Roof (US), Pamela J. Bjorkman (US), Mark M. Davis (US), Leslie J. Berg (US), Augustin Y. Lin (US), Barbara Fazekas de St. Groth (US), Brigitte Devaux (US), Charles G. Sagerstrom (US), John F. Elliott (US), Jerry H. Brown (US), Theodore Jardetzky (US), Mark A. Saper (US), Boudjema Samraoui (US), and Don Craig Wiley (GB-US) have helped reveal the mechanism by which cells transport and present peptides at their surface. They have shown that most peptides bind to major histocompatibility complex (MHC) molecules inside a cell. The molecules are of two types: class I MHC molecules, which displays peptides from proteins made inside the cell, and class II MHC molecules, which displays peptides from proteins that have entered the cell from the outside(1995, 3850-3853).

Steven Robinow (US), Ana Regina Campos (CA), Kwok-Ming Yao (CN), and Kalpana White (US) were among the first to describe a gene that encodes an RNA-binding protein implicated in neuronal development. The gene is elav of Drosophila(3854).

Yona Kassir (IL), David Granot (IL), and Giora Simchen (IL) concluded that in Saccharomyces cerevisiae IME1 (inducer of meiosis) is a positive regulator of meiosis that normally is repressed by RME1. RME is repressed by a complex of MATal and MATα2 gene products. IME1 is also regulated by the environment: no transcripts could be detected in glucose growing cells, in contrast to acetate growing cell. Starvation for nitrogen further induced (6- to 8-fold) transcription of IME1, but, as expected, the induction was found only in MATa/MATα or rmel-l/rme1-1 diploids. Furthermore, the IME1 multicopy plasmids promoted sporulation in rich media(3855).

W. Mark Toone (GB), Anthony L. Johnson (GB), Geoffrey R. Banks (GB), Jeremy H. Toyn (GB-US), David Stuart (US), Curt Wittenberg (US), and Leland H. Johnston (GB) demonstrated that the RME1 (regulator of meiosis) gene can bypass the normally essential requirement for the transcription factor SBF. RME1 encodes a zinc finger protein which is able to repress transcription of IME1 (inducer of meiosis) and thereby inhibit cells from entering meiosis. They present evidence to suggest that Rme1 may act both to promote mitosis, by activating CLN2 expression, and prevent meiosis, by repressing IME1 (inducer of MEiosis) expression(3856).

Henny W.M. van Straaten (NL), Johan W.M. Hekking (NL), Emilie L.M.J. Wiertz-Hoessels (NL), Frans Thor (NL), and Jan Drukker (NL) showed that the notochord — a rod-like structure of mesodermal tissue that is just ventral to the neural tube — can induce the development of a specialized structure along the ventral midline of the neural tube called the floor plate. The floor plate is known to have effects on the guidance of some spinal-cord axons, and, along with the notochord, it is implicated as a signaling center(3857).

Toshiya Yamada (AU), Marysia Placzek (GB), Hideaki Tanaka (AU), Jane Dodd (US), and Thomas M. Jessell (US) through grafting experiments in the chick embryo showed that both the notochord and the floor plate can induce ectopic patterns of ventral motor neuron layers. Furthermore, removal of the notochord or floor plate results in the loss of these ventral motor neurons. So, both notochord and floor-plate cells can release signals that are required for the initial dorsal-ventral (DV) patterning of the central nervous system (CNS). Induction by notochord and floor-plate explants resulted in distinct subsets of neuron types at defined distances from the ectopic tissue source. The authors proposed a model in which a diffusible signal produced in the notochord or floor plate results in a gradient of the signal across the DV axis, and this gradient is responsible for the pattern of neurons induced(3858, 3859).

Yann Echelard (US), Douglas J. Epstein (US), Benoit St. Jacques (US), Liya Shen (US), Jym Mohler (US), Jill A. McMahon (US), Andrew P. McMahon (US), Stefan Krauss (NO), Jean-Paul Concordet (FR), and Philip W. Ingham (GB) cloned mouse and zebrafish (Brachydanio rerio) homologues of the Drosophila segment polarity gene hedgehog (hh). In both cases, the expression pattern of one homologue in particular, sonic hedgehog (shh), implied that it might be involved in ventral central nervous system (CNS) patterning. Shh was expressed in both the notochord and the floor plate at the appropriate times in development that were expected for the inductive signal. Furthermore, ectopic expression of shh could induce floor-plate-specific genes. Shh was predicted to be a secreted protein, so it was an obvious candidate for the diffusible signal that was predicted by the earlier study of Jessell and colleagues(3860, 3861). Shh has come to be known as a classic example of a morphogen — a signal that regulates the spatial pattern of cell differentiation in a concentration-dependent manner.

Andre-Patrick Arrigo (US), Keiji Tanaka (JP), Alfred L. Goldberg (US-CA), and William J. Welch (US) found that cellular proteins are broken down by large, multienzyme complexes they named proteasomes(3862). An average body cell contains thousands of proteasomes, which chop proteins the cell wishes to remove (are tagged) into bits of various sizes.

Vickie E. Baracos (CA), Cynthia DeVivo (CA), Duncan H.R. Hoyle (CA), and Alfred L. Goldberg (US-CA) found that accelerated muscle proteolysis and muscle wasting in tumor-bearing rats result primarily from activation of the ATP-dependent pathway involving ubiquitin and the proteasome. The ubiquitin serving as the tag for destruction(3863).

Hirohisa Masuda (US), and W. Zacheus Cande (US) were the first to obtain experimental evidence that during anaphase B (lengthening of the entire spindle) the interpolar microtubules slide past one another(3864). This type of movement had first been proposed by Kent L. McDonald (US), J.D. Pickett-Heaps (US), J. Richard McIntosh (US), and D.H. Tippit (US)(3865).

Robert M. McCarroll (US) and Walton L. Fangman (US) showed that centromeres of sister chromatids are duplicated during the S phase of mitosis in Saccharomyces cerevisiae(3866).

Kenneth J. Kemphues (US), James R. Priess (US), Diane G.Morton (US), and Niansheng (Nick) Cheng (US) identified genes that are involved in cell-fate specification in Caenorhabditis elegans, a free-living, transparent nematode (roundworm). A study of maternal-effect lethal mutations led to the identification of the par (partitioning defective) genes par1–4. Wild-type C. elegans oocytes contain a uniform distribution of P granules — large ribonuclear particles that normally segregate into P1. Mutations in the four par genes led to abnormal positioning of the mitotic spindle and aberrant localization of the P granules, leading the authors to propose that the par genes encode products that are required for spindle placement and cytoplasmic localization(3867).

Su Guo (US) and Kenneth J. Kemphues (US) cloned the C. elegans par-1 and par-3 genes. PAR-1 is a conserved serine/threonine kinase, whereas PAR-3 turned out to be a novel protein. Both of these proteins are asymmetrically distributed in the zygote: PAR-1 is enriched at the posterior periphery, whereas PAR-3 is found at the anterior periphery. In early germ-line precursor cells, PAR-1 localization correlates strikingly with P granule distribution and requires the kinase activity of PAR-1. Meanwhile, the distribution of PAR-3 controls spindle orientation. PAR-3 localization depends on the par-2 gene, and PAR-3 is required for PAR-1 localization(3868).

Michelle S. Rhyu (US), Lily Yeh Jan (US), and Yuh Nung Jan (US) identified a protein in Drosophila sensory organs called Numb, which is localized within the sensory organ precursors (SOP) before cell division and segregates to only one of the daughter cells during division. These results demonstrated that the asymmetric segregation of a determinant during cell division could induce a specific fate in one of the two daughter cells(3869).

Rachel Kraut (CN), William Chia (CN), Lily Yeh Jan (US), Yuh Nung Jan (US), and Jüergen A. Knoblich (DE) showed that expression of the inscuteable gene is required for asymmetric segregation of Numb, as well as correct spindle orientation, in fly neuroblasts and epithelial cells. The Inscuteable protein localizes to the apical-cell cortex before mitosis and precedes the basal localization of Numb. These results indicated that asymmetric localization of Inscuteable establishes positional information for both spindle orientation and asymmetric localization of Numb. The Par proteins have also been shown to be involved in asymmetric Numb localization in neuroblasts(3870).

Bernadette Connolly (GB), Charles I. White (FR), and James E. Haber (US), in describing mating type switching in the yeast Saccharomyces cerevisiae, were among the first to report a natural recombination system involving double-strand DNA breaks(3871).

Dennis E. McCabe (US), William F. Swain (US), Brian J. Martinelli (US), and Paul Christou (CY-GB) transformed soybean cells by shooting into them tiny particles of gold coated with foreign DNA(3872). 

Suzanne L. Mansour (US), Kirk R. Thomas (US), and Mario Renato Capecchi (US) developed a method of gene targeting—homologous recombination of DNA sequences residing in the chromosome with newly introduced DNA sequences—in mouse embryo-derived stem cells which promises to provide a means to generate mice of any desired genotype(3873). This technique is referred to as reverse mammalian genetics.

Sallie W. Chisholm (US), Robert J. Olson (US), Erik R. Zettler (US), Ralf Goericke (US), John B. Waterbury (US), and Nicholas A. Welschmeyer (US) discovered that the bacteria-sized cyanobacterium, Prochlorococcus sp., is abundant in the open ocean, with counts of up to 20,000 cells per drop of seawater(3874).

John B. Hibbs, Jr. (US), Read R. Taintor (US), Zdenek Vavrin (CZ), and Elliot M. Rachlin (US) discovered that the phagocytosis of microbial pathogens by macrophages stimulates the macrophages to release reactive nitrogen intermediates such as nitric oxide(3875).

Elaine Tuomanen (US) discovered in animal models of meningitis that when a bacterium shatters, body defenses mistake the shrapnel for a burst of bacterial growth and respond accordingly. The bits of the cell wall activate the body’s defenses by setting off the cytokine alarms and clotting initiators. These events prepare a platform on a vessel wall to which white blood cells stick, giving them enough purchase to squeeze themselves through the blood brain barrier. The white blood cells, now esconced in the brain, enhance the production of cytokine alarms, accelerating the disruption of the barrier. More white blood cells migrate into the brain, further exacerbating inflammation, swelling and the immune response.

In short, the animal model taught an unexpected lesson: antibiotic therapy makes meningitis worse before it makes it better.

Tuomanen discovered that she could keep white blood cells from entering the brain using an antibody (anti-CD18) known to prevent white blood cells from sticking to the vessel walls. By combining antibiotic therapy with anti-CD18 therapy in animal cases of meningitis she was able to achieve a remarkable 100 percent survival rate(3876).

Jussi Mertsola (FI), Octavio Ramilo (ES), Mahmoud M. Mustafa (US), Xavier Saez-Llorens (PA), Eric J. Hansen (US), and George H. McCracken, Jr. (US) demonstrated that antibiotic therapy for meningitis in children causes bacteria to shatter, temporarily worsening the disease by accelerating inflammation within the central nervous system(3877, 3878).

Anthony E. Namen (US), Ann E. Schmierer (US), Carl J. March (US), Robert W. Overell (US), Linda S. Park (US), David L. Urdal (US), and Diane Y. Mochizuki (US) purified a previously uncharacterized murine lymphopoetic growth factor designated lymphopoetin 1 (LP-1). This factor is capable of stimulating the proliferation and extended maintenance of precursor cells of the B lineage. This factor was purified to a single 25-kD species from the culture supernatant fraction of an adherent stromal cell line. This material acts on immature lymphocytes, it binds to specific receptors on cells, and is distinct from previously described hematopoietic factors(3879).

Jeng-Pyng Shaw (US), Paul J. Utz (US), David B. Durand (US), J. Jay Toole (US), Elizabeth Ann Emmel (US), and Gerald R. Crabtree (US) identified a protein complex found within T cells which they named NFAT-1. Its characteristics suggest that it transmits signals initiated at the T cell antigen receptor which regulate early T cell activation genes(3880).

Kendall A. Smith (US) summarizes by saying that IL-2 was the first of a series of lymphocytotrophic hormones to be recognized and completely characterized. It is pivotal for the generation and regulation of the immune response. A product of T lymphocytes, IL-2 also stimulates T cells to undergo cell cycle progression via a finite number of interactions with its specific membrane receptors. Because T cell clonal proliferation after antigen challenge is obligatory for immune responsiveness and immune memory, the IL-2 cell system has opened the way to a broader understanding of such fundamental cellular phenomena(3881).

Günter Wächtershäuser (DE) presented a hypothesis supporting chemoautotrophy as the first form of metabolism to appear within life forms on the primitive Earth. He argued that these life forms were coatings that adhered to the positively charged surfaces of pyrite, a mineral composed of iron and sulfur. The formation of pyrite from hydrogen sulfide provides a source of electrons as an energy source(3882).

Ok-Ryun Choi (US) and James D. Engel (US) were the first to show that promoter competition is an important mechanism of gene regulation. They were analyzing the chicken globin locus(3883).

Colin Pitchfork (GB), a bakery worker in Leicestershire, England was the first person convicted and sentenced— in this case for two murders—using DNA fingerprint information(2936). The fingerprinting evidence also exonerated Richard Buckland (GB) who had confessed to one of the murders.

For the first time a person was convicted and given the death penalty on the strength of DNA fingerprint evidence. Randall Jones was convicted in Florida. State of Florida vs. Jones and Reesh.

Philip Leder (US) and Timothy A. Stewart (US) patented animal life, a transgenic mouse. They devised a method of introducing specific oncogenes (genes with the potential to cause other cells to become cancerous) into mice. The transgenic non-human eukaryotic animal is bred to contract breast cancer for medial research to facilitate carcinogen testing and development of cancer therapies(3884).

John H. Shaw (US) and Stanley Falkow (US) proposed a molecular version of Koch’s postulates which is used to assess whether or not a gene or its products are required for virulence(3885).

Dvora Teitelbaum (IL), Rina Aharoni (IL), Ruth Arnon (IL), Ruth Arnon (IL), and Michael Sela (IL) obtained results suggesting that Cop 1 (glatiramer acetate) may be effective in suppression of experimental allergic encephalomyelitis, the animal equivalent of multiple sclerosis(3886).

Dvora Teitelbaum (IL), Ruth Arnon (IL), and Michael Sela (IL), in phase III clinical trials, found that Cop-1 (glatiramer acetate) can slow progression of disability and reduce the relapse rate in exacerbating-remitting multiple sclerosis (MS)(3887).

Luigi Luca Cavalli-Sforza (IT-US), Alberto Piazza (IT), Paolo Menozzi (IT), and Joanna Mountain (US) used genetic, archaeological, and linguistic data to reconstruct human evolution. They concluded that the first split in the phylogenetic tree separates Africans from non-Africans, and the second separates two major clusters, one corresponding to Caucasoids, East Asians, Arctic populations, and American natives, and the other to Southeast Asians (mainland and insular), Pacific islanders, and New Guineans and Australians. Average genetic distances between the most important clusters are proportional to archaeological separation times. Linguistic families correspond to groups of populations with very few, easily understood overlaps, and their origin can be given a time frame. Linguistic superfamilies show remarkable correspondence with the two major clusters, indicating considerable parallelism between genetic and linguistic evolution. The latest step in language development may have been an important factor determining the rapid expansion that followed the appearance of modern humans and the demise of Neanderthals(3888).

Stan Wood (GB) discovered the 20 cm long fossilized remains of a burgess Westlothiana lizziae in East Kirkton, West Lothian, Scotland (near Edinburgh).

Tim R. Smithson (GB), Robert Lynn Carroll (US-CA), Alec L. Panchen (GB), S. Mahala Andrews (GB), Roberta L. Paton (GB), and Jennifer A. Clack (GB) clarified the taxonomic status of Westlothiana lizziae stating that it might be the oldest known reptile and thus the oldest known amniote(3889-3892).

Karl F. Hirsch (US), Kenneth L. Stadtman (US), Wade E. Miller (US), and James H. Madsen, Jr. (US) discovered a fossilized dinosaur egg that contains the oldest known embryo of any kind, probably the embryo of an allosaur from about 150 Ma. The embryo of approximately 2cm was detected by X raying the egg(3893).

Roy A. Norton (US), Patricia M. Bonamo (US), James D. Grierson (US), and William A. Shear (US) found that mites are among the oldest of all terrestrial animals, with fossils known from the early Devonian, nearly 400 Ma(3894).


“Wind back the tape of life to the early days of the Burgess Shale. Let it play again from an identical starting point, and the chance becomes vanishingly small that anything like human intelligence would grace the replay.” Stephen Jay Gould(3895).

Sidney Altman (CA-US) and Thomas Robert Cech (US) were awarded the Nobel Prize in Chemistry for their discovery of catalytic properties of RNA.

John Michael Bishop (US) and Harold Elliot Varmus (US) were awarded the Nobel Prize in Physiology or Medicine for their discovery of the cellular origin of retroviral oncogenes.

Bernard J. Wood (GB) and David Virgo (US) presented evidence that the primitive atmosphere was poised at a redox state buffered close to the fayalite-quartz-magnetite system consistent with a neutral redox atmosphere and characteristic of basalts throughout the geological record(3896).

Maureen D. Keller (US), Wendy K. Bellows (US), Robert R.L. Guillard (US), James Ephraim Lovelock (GB), Gordon V. Wolfe (US), and Michael Steinke (DE) reported that marine phytoplankton such as Emiliania huxleyi produce significant qualities of dimethyl sulfide (sulphide) which in the atmosphere is rapidly oxidized to non-sea salt sulfate (sulphate) NSS-SO4. Non-sea salt sulfate is one of the major sources of nuclei for cloud condensation(2598, 3897, 3898).

Robert W. Armstrong (US), Jean-Marie Beau (US), Seung Hoon Cheon (US), William J. Christ (US), Hiromichi Fujioka (US), Won-Hun Ham (US), Lynn D. Hawkins (US), Haolun Jin (US), Sung Ho Kang (US), Yoshito Kishi (US), Michael J. Martinelli (US), William W. McWhorter, Jr. (US), Masanori Mizuno (US), Masaya Nakata (US), Arnold E. Stutz (US), Francisco X. Talamas (US), Mikio Taniguchi (US), Joseph A. Tino (US), Katsuhiro Ueda (US), Jun-ichi Uenishi (US), James B. White (US), Masahiro Yonaga (US), and Edward M. Suh (US) carried out the total synthesis of palytoxin. This substance is produced by certain soft corals of the genus Polythoa and is one of the most toxic non-peptide substances known(3899-3903).

Hans van Tol (NL), Hans J. Gross (DE), and Hildburg Beier (DE) found that 5’ cleavage processing of pre-tRNAs is autocatylytic(3904).

Stanley Fields (US) and Ok-Kyu Song (US) provided a novel genetic system to detect protein-protein interactions by expressing them in yeasts(3905).

Robert A. Fromtling (US) and George K. Abruzzo (US) isolated a new antifungal agent from Zalerion arboricola(3906). It is referred to as a pneumocandin because of its action against Pneumocystis carinii.

John L. Hall (US), Zenta A. Ramanis (US), and David J. Luck (US) localized DNA in the basal bodies of Chlamydomonas reinhardtii(3907, 3908).

Shlomo Handeli (IL), Avihu Klar (US), Mark Meuth (US-GB), Howard Cedar (IL) were the first to identify DNA regions in higher eukaryotes (Eucarya) which behave as origins of replication(3909).

Daniel Kitsberg (GB-IL), Sara Selig (IL), Ilana Keshet (IL) and Howard Cedar (IL) located one origin of replication upstream of a beta globin gene in humans(3910). Rather than containing a specific sequence at which replication begins, these origins appear to be zones including thousands of base pairs in which replication is more likely to begin than in other regions.

Michael Altmann (CH), Nahum Sonenberg (CH), and Hans Trachsel (CH) established an essential role in Saccharomyces cerevisiae translation for elF4E and elF4A(3911).

Malcolm Whiteway (CA), Linda Hougan (CA), Daniel Dignard (CA), David Y. Thomas (CA), Leslie Bell (US), Gena C. Saari (US), Francis J. Grant (US), Patrick J. O'Hara (US), and Vivian L. MacKay (US), proposed that in Saccharomyces cerevisiae the products of the STE4 and STE18 genes comprise the beta and gamma subunits of a G protein complex coupled to the mating pheromone receptors. The genetic data suggest pheromone-receptor binding leads to the dissociation of the alpha subunit from beta gamma (as shown for mammalian G proteins), and the free beta gamma element initiates the pheromone response(3912).

Giulio Draetta (US), Frank Luca (US), Joanne Westendorf (US), Leonardo Brizuela (US), Joan V. Ruderman (US), and David Beach (US) used Schizosaccharomyces pombe to offer proof that cell division can look superficially different from one organism to another, but the basic apparatus is the same(3913).

Trevor C. Dale (GB), A.M. Ali Imam (GB), Ian M. Kerr (GB), and George R. Stark (GB) suggested that interferon-stimulated gene factor 3 (ISGF3) is the ligand-dependent transcriptional activator that, in response to interferon treatment, is assembled in the cell cytoplasm, is translocated to the nucleus, and binds the consensus DNA site, the interferon-stimulated response element(3914).

Xin-Yuan Fu (US), Daniel S. Kessler (US), Susan A. Veals (US), David E. Levy (US), and James Edwin Darnell, Jr. (US) purified ISGF3 and identified its constituent proteins: a DNA binding protein of 48 kD and three larger polypeptides (84, 91, and 113 kD), which themselves do not have DNA-binding activity. The multisubunit structure of ISGF3 most likely reflects its participation in receiving a ligand-dependent signal, translocating to the nucleus, and binding to DNA to activate transcription(3915).

Christian W. Schindler (US), Xin-Yuan Fu (US), Teresa Improta (US), Ruedi H. Aebersold (CA), Ke Shuai (US), Vincent R. Prezioso (US), and James Edwin Darnell, Jr. (US) discovered a direct signaling pathway from the cell surface to genes in the nucleus. Darnell's group discovered that a set of dual function proteins they named STATs (signal transducers and activators of transcription) remain quiescent in the cell until circulating polypeptides bind to their specific cell surface receptors. Specific STATs are then activated, pair and travel to the nucleus to activate appropriate genes. For example, some STATs switch on a group of interferon-responsive genes when interferon contacts cells(3916-3918).

Zhong Zhong (CN-US), Zilong Wen (CN), and James Edwin Darnell, Jr. (US) discovered the first STATs to be activated by polypeptides other than interferon. Zhong says that the significance of their work is that it shows the existence of "a large gene family that is heavily used for gene regulation by a number of cytokines and growth factors." They showed that one of these (STAT3) could be activated by epidermal growth factors and interleukin-6(3919, 3920).

Mathias Müller (DE), James Briscoe (GB), Carl Laxton (GB), Dmitry Guschin (US), Andrew Ziemiecki (GB-CH), Olli Silvennoinen (FI), Ailsa G. Harpur (GB), Giovanna Barbieri (FR), Bruce A. Witthuhn (US), Christian W. Schindler (US), Sandra Pellegrini (FR), Andrew F. Wilks (AU), James N. Ihle (US), George R. Stark (US), and Ian M. Kerr (GB) demonstrated the function of the JAK1 protein in the cellular responses to two different types of interferon signaling. The JAKs, are members of a "family of tyrosine kinases that were originally cloned by their homology to other tyrosine kinases, but without any idea as to what their function might be." Tyrosine kinases are a group of enzymes that activate various intracellular proteins by transferring phosphate groups to amino acids called tyrosines of these proteins, in response to signals from outside the cell. The initial lack of information about the JAKs is reflected in the name; JAK is an acronym for "just another kinase"(3921).

Carol Beadling (GB), Dmitry Guschin (GB), Bruce A. Witthuhn (US), Andrew Ziemiecki (CH), James N. Ihle (US), Ian M. Kerr (GB), and Doreen A. Cantrell (GB) investigated the activation of Janus protein tyrosine kinases (JAK kinases) and signal transducer and activator of transcription (STAT) proteins by interleukin-2 (IL-2). They noted an IL-2-induced increase in JAK1 and JAK3, but not JAK2 or Tyk2; tyrosine phosphorylation was observed. No induction of tyrosine phosphorylation of JAKs was detected upon stimulation of the T cell receptor (TCR). Interferon alpha (IFN alpha) induced the tyrosine phosphorylation of JAK1 and Tyk2, but not JAK2 or JAK3. IFN alpha activated STAT1, STAT2 and STAT3 in T cells, but no detectable activation of these STATs was induced by IL-2. Finally, in other cell types the correlation between JAK1 activation and the induction of STAT1 has suggested that JAK1 may activate STAT1(3922).

James Edwin Darnell, Jr. (US), Ian M. Kerr (GB), and George R. Stark (US), during their investigation of transcriptional activation in response to interferon alpha (IFN-alpha) and interferon gamma (IFN-gamma), discovered a previously unrecognized direct signal transduction pathway to the nucleus. Interferon-receptor interaction at the cell surface leads to the activation of kinases of the JAK family that then phosphorylate substrate proteins called STATs (signal transducers and activators of transcription). The phosphorylated STAT proteins move to the nucleus, bind specific DNA elements, and thereby direct transcription(3923).

Franco Felici (IT), Giovanni Cesareni (IT), and John M.X. Hughes (GB) isolated and sequenced a gene for small cytoplasmic RNA (scRNA) from Saccharomyces cerevisiae(3924).

Michael Litt (US), JeffreyA. Luty (US), Diethard Tautz (DE), James L. Weber (US), and Paula E. May (US) discovered microsatellite DNA. These are polymorphic DNA sequences made of tandemly repeated strings of short elements, usually two, three or four nucleotides in length, and occur scattered throughout the genomes of all eukaryotes (Eucarya)(3925-3927). They hold out great promise as a marker for DNA fingerprinting.

Alan R. Templeton (US), Hope Hollocher (US), Susan Lawler (US-AU), and J. Spencer Johnston (US) discovered that the cellular machinery in Drosophila mercatorum has the ability to differentiate between functional and non-functional ribosomal RNA genes(3928).

Michael S. Davies (GB), (), Simon C. Wallis (GB), Donna M. Driscoll (GB), Judy K. Wynne (GB), Gareth W. Williams (GB), Lyn M. Powell (US), James Scott (GB), San-Hwan Chen (US), Xiaoxia Li (US), Warren S. Liao (US), June H. Wu (US), and Lawrence Chan (US) discovered an example of nuclear RNA editing in pre-mRNA encoding apolipoprotein B, a cytosine is converted to uracil in intestinal but not in liver cells(3929, 3930).

Sharon Rugel Long (US) identified common and host specific nodulation (nod) genes which determine infection and nodulation of specific leguminous hosts(3931).

William D. Huse (US), Lakshmi Sastry (US), Sheila A. Iverson (US), Angray S. Kang (GB), Michelle Alting-Mees (CA), Dennis R. Burton (US), Stephen J. Benkovic (US), and Richard Alan Lerner (US) produced a bacteriophage lambda vector system which expressed in Escherichia coli a combinatorial library of fragment antigen binding (Fab) fragments of the mouse antibody repertoire. The system allows rapid and easy identification of monoclonal Fab fragments in a form suitable for genetic manipulation(3932).

Rosaria Orlandi (IT), Detlef H. Gussow (GB), Peter T. Jones (GB), and Greg Winter (GB) designed oligonucleotide primers used to amplify the cDNA of mouse immunoglobulin heavy and light chain variable domains by the polymerase chain reaction(3933).

Great Britain launched its human genome program(3934).

David W. Deamer (US) and Richard M. Pashley (AU) found membrane-forming nonpolar molecules within the Murchison carbonaceous chondritic meteorite(3935).

Keith A. Kvenvolden (US), James G. Lawless (US), Katherine Pering (US), Etta Peterson (US), Jose Flores (US), Cyril Ponnamperuma (LK-US), Isaac R. Kaplan (US), Carleton Moore (US) and John R. Cronin (US) examined the Murchison carbonaceous chondritic meteorite and found racemic mixtures of 74 different amino acids: 8 that are present in proteins, 11 with other biological roles (including, quite surprisingly, some neurotransmitters), and 55 that have been found almost exclusively in extraterresterial samples(3936-3938).

Qui Lim Choo (US), George Kuo (US), Amy J. Weiner (US), Lacy R. Overby (US), Daniel W. Bradley (US), Michael Houghton (US), Harvey J. Alter (US), Gary L. Gitnick (US), Allan G. Redeker (US), Robert Harry Purcell (US), Tatsuo Miyamura (US), Jules L. Dienstag (US), Miriam J. Alter (US), and Cladd E. Stevens (US), Gary E. Tegtmeier (US), Ferruccio Bonino (IT), Massimo Colombo (IT), W.-S. Lee (), C. Kuo (), Kim M. Berger (US), and Jeffrey R. Shuster (US)  identified the hepatitis C virus as the main causative agent of post-transfusion non-A, non-B hepatitis. This was the first infectious agent discovered entirely by cloning nucleic acid. A blood test to detect antibodies to hepatitis C soon followed(3939, 3940). 

Shyh-Cheng Lo (US), James Wai-Kuo Shih (US), Perry B. Newton III (US), Dennis M. Wong (US), Michael M. Hayes (US), Janet R. Benish (US), Douglas J. Wear (US), and Richard Yuan-Hu Wang (US) identified a pathogenic virus-like infectious agent (VLIA), originally reported in patients with AIDS but also known to be pathogenic in previously healthy non-AIDS patients and in non-human primates. They classified it as a member of the order Mycoplasmatales, class Mollicutes and named it Mycoplasma incognitus(3941).

Stuart K. Kim (US), Armin Dale Kaiser (US) and Adam Kuspa (US) found that independent cells of Myxococcus xanthus (a type of bacterium) congregate when facing starvation and or drought. Factor A secreted by the cells themselves causes cellular aggregation when its concentration reaches a threshold. Factor C on the surface of the cells allows them to signal one another that they are packed together in such a way that spore formation can take place(3942-3944).

Mitchell Lloyd Sogin (US), John H. Gunderson (US), Hillie J. Elwood (US), Rogelio A. Alonso (US), and Debra A. Peattie (US) determined that in the diplomonad Giardia lamblia 16S-like rRNA has retained many of the features that may have been present in the common ancestor of eukaryotes (Eucarya) and prokaryotes (Archaea or Bacteria). They concluded that it represents the earliest-branching eukaryotic lineage(3945).

Kam-Ha Anna Yeung (US), Mark A. Schell (US), and Peter G. Hartel (US) developed an ingenious three-nested-cup set-up for studying the rhizosphere(3946).

Gerald J. Spangrude (US), John Klein (US), Shelly Heimfeld (US), Ykoh Aihara (US), and Irving Lerner Weissman (US) used monoclonal antibodies to identify totipotent cells in mouse bone marrow. They found that these totipotent cells account for only about 0.1 percent of all bone marrow cells(3947). These totipotent cells came to be called stem cells.

David Haig (AU-US), Mark Westoby (AU), Tom Moore (GB), and Chris Graham (GB) predicted that in placental animals and in plants whose seed gain sustenance from the parent plant the paternal genes have been selected to be aggressive in their bid to obtain nourishment. This is called paternal imprinting(3948-3953)

Kevin S. Johnson (AU), Gavin L.B. Harrison (AU), Marshall W. Lightowlers (AU), Kim L. O'Hoy (AU), Wendy G. Cougle (AU), Robert P. Dempster (AU), Stephen B. Lawrence (AU), Jennifer G. Vinton (AU), David D. Heath (AU), and Michael D. Rickard (AU) used the first recombinant vaccine against a helminth worm to vaccinate sheep against Taenica ovis(3954).

David G. Wilkinson (GB), Sangita Bhatt (GB), Martyn Cook (GB), Edorado Boncinelli (IT), Robb Krumlauf (GB), Jarema Malicki (US), Klaus Schughart (DE), and William McGinnis (US) provided genetic evidence that the serial repetition of body parts is an ancient feature of animal design(3955, 3956).

Isidore Tepler (US), Cynthia C. Morton (US), Akira Shimizu (JP), Randall F. Holcombe (US), Roger L. Eddy (US), Thomas B. Shows (US), and Philip Leder (US) determined that the gene for human IgE receptor alpha chain is located on chromosome number one(3957).

David K. Grandy (US), Michael Litt (US), Lee Allen (US), James R. Bunzow (US), Mark A. Marchionni (US), Haripriya Makam (US), Leslie Reed (US), R. Ellen Magenis (US), and Olivier Civelli (US) identified and localized the dopamine D2 receptor to human chromosome 11(3958). Human dopaminergic neurons are involved in the control of hormone secretion, voluntary movement, and emotional behavior. Mediating these effects are the dopamine D1 and D2 receptors. These macromolecules belong to a large family of related sequences known as the G protein-coupled receptors.

Donald E. Staunton (US), Vincent J. Merluzzi (US), Robert Rothlein (US), Richard Barton (US), Steven D. Marlin (US), and Timothy Alan Springer (US) discovered that I-CAM-1 is the major surface receptor for the rhinoviruses (CAM=cell adhesion molecules)(3959).

Steven D. Marlin (US), Donald E. Staunton (US), Timothy Alan Springer (US), Christian Stratowa (AT), Wolfgang Sommergruber (AT), and Vincent J. Merluzzi (US) solubilized the I-CAM-1 receptor and found that it would block the normal rhinovirus receptor site. This could have promise as a prophylactic for the common cold(3960).

Siegfried Roth (DE), David Stein (DE), Christiane Jani Nüsslein-Volhard (DE), Christine A. Rushlow (US), Kyuhyung Han (US), James L. Manley (US), Michael Levine (US), and Ruth Steward (US) determined that in the early Drosophila embryo the Dorsal protein is uniformly distributed along the anterior-posterior axis of the body yet it is distributed in a broad ventral-to-dorsal gradient, with peak levels present along the ventral surface(3961-3963). The Dorsal gradient is responsible for initiating the differentiation of several embryonic tissues, including the mesoderm, neurogenic ectoderm, and the dorsal ectoderm.

Tomoyuki Yokota (JP), Kenji Konno (JP), Shuichi Mori (JP), Shiro Shigeta (JP), Masao Kumagai (JP), Yohko Watanabe (JP), and Haruhiko Machida (JP) described sorivudine (E-5-(bromovinyl) arabinofuranosyluracil), also called BVaraU, as the most potent inhibitor of Varicella zoster(3964).

George Streisinger (HU-US), Frank Coale (US), Cori Taggart (US), Charline Walker (US), and David Jonah Grunwald (US) demonstrated the clonal origins of cells in the pigmented retina of the zebrafish eye(3965).

Mariella Chaput (BE), Victor  Claes (BE), Daniel Portetelle (BE), Isabelle Cludts (BE), Alfredo Cravador (BE), Arsène Burny (BE), Hélène Gras (BE), and André Tartar (BE) cloned the gene for pig muscle phosphohexose isomerase (glucose-6-phosphate isomerase) which catalyses the conversion of glucose-6-phosphate to fructose-6-phosphate, an obligatory step in glycolysis, and determined its amino-acid sequence. Surprisingly, it is 90% homologous to the sequence of mouse neuroleukin(3966). Neuroleukin is a neurotrophic factor for spinal and sensory neurons and a lymphokine product of lectin-stimulated T-cells.

Stephan C. Meuer (DE), Hubert Dumann (DE), Karl-Hermann Meyer zum Buschenfelde (DE), and Hans Kohler (DE) demonstrated the safety and efficacy of treating humans with interleukin-2. This was determined during immunization trials with hepatitis B vaccine(3967).

Masanori Hatakeyama (JP), Mitsuru Tsudo (JP), Seijiro Minamoto (JP), Takeshi Kono (JP), Takeshi Doi (JP), Tomoko Miyata (JP), Masayuki Miyasaka (JP), and Tadatsugu Taniguchi (JP) were able to isolate the gene encoding for a second polypeptide making up the receptor for interleukin-2(3968).

Masaaki Eto (JP), Kiyoshi Watanabe (JP), and Isao Makino (JP) concluded that both epsilon 2 and epsilon 4 alleles of the apolipoprotein gene E (epsilon) are more associated with ischemic heart disease (IHD) than the epsilon 3 allele(3969).

Étienne Émile Baulieu (FR) developed RU 486, the first safe, effective contragestive medication. The drug also known as Mifepristone works by acting on the woman's body to block progesterone, a hormone needed to maintain pregnancy(3970).

William L. Gerald (US) and Juan Rosai (IT-AR-US) were the first to describe desmoplastic small-round-cell tumor, an agressive rare soft tissue sarcoma that primarily occurs as masses in the abdomen of children(3971).

Amanda J. Murphy (CA), Karen Bishop (CA), Carlos Pereira (CA), Susan Chilton-MacNeill (CA), Michael Ho (CA), Maria Zielenska (CA), and Paul S. Thorner (CA) found that DSRCT is associated with a unique chromosomal translocation (t11;22)(p13:q12) (3972).

William L. Gerald (US) and Daniel A. Haber (US) found that this translocation results in a EWS/WT1 transcript(3973).

Yi-Shuan Lee (CN) and Cheng-Hsiang Hsiao (CN) found that this transcript codes for a protein that acts as a transcriptional activator that fails to suppress tumor growth and is diagnostic of this tumor(3974).

Suzanne Fortney (US), Elizabeth Miescher (US), and Barbara Rolls (US) determined that body fluid homeostasis may be impaired with aging, such that older individuals compensate more slowly to changes in body water. Older subjects seem less able to sense changes in hydration and at a given body water deficit, they have greater difficulty maintaining plasma volume and osmolality(3975).

Victor Candas (FR) and Gabrielle Brandenberger (FR) found that progressive rehydration during exercise is more efficient than initial hyperhydration in reducing the homeostatic disturbances associated with exercise in the heat(3976).

Vijay K. Chaudhary (IN), Gary Queen (DE), Richard P. Junghans (US), Thomas A. Waldmann (US), David J. FitzGerald (US), and Ira Harry Pastan (US) produced a recombinant immunotoxin consisting of two antibody variable domains fused to Pseudomonas exotoxin A. The new chimeric protein was produced in E. coli and shown to selectively kill CD25-expressing cells(3977). This paper clearly shows that one can design and produce a powerful and specific cell-killing agent using a combination of protein design and genetic engineering.

Jorge E. Galán (US) and Roy Curtis III (US), using an in vitro system, isolated a genetic locus, inv, that confers to a noninvasive strain of Salmonella typhimurium the ability to penetrate tissue culture cells(3978).

Jorge E. Galán (US), Christine Ginocchio (US), and Paul Costeas (US) predicted the sequence of InvA and found it to be homologous to Caulobacter crescentus FlbF, Yersinia LcrD, Shigella flexneri VirH, and E. coli FlhA proteins. They suggested that these proteins may form part of a family of proteins with a common function, quite possibly the translocation of specific proteins across the bacterial cell membrane(3979).

Koné Kaniga (US), David Trollinger (US), and Jorge E. Galán (US) found that inv encodes a type 3 secretion system (TTSS)(3980).

Robert M. Mcnab (US), Gregory V. Plano (US), James B. Day (US), and Franco Ferracci (US) reported that the TTSS is a complex protein export pathway that is used by numerous gram-negative pathogens to export flagella or to secrete effector proteins into the extracellular milieu or into the membrane or cytosol of an infected host eukaryotic cell(3981, 3982).

Guy R. Cornelis (CH) found that pathogenic Yersinia species carry a plasmid-encoded TTSS required for counteracting immune defenses after the pathogen has penetrated host tissues(3983).

Fionula M. Brennan (GB), David Chantry (GB), Andrew Jackson (GB), Ravinder Maini (GB), and Marc Feldman (GB) found that tumor necrosis factor alpha (TNF-alpha) is the dominant inducer of IL-1 production in rheumatoid but not in osteoarthritic joints(3984).

Craig B. Thompson (US), Tullia Lindsten (US), Jeffrey A. Ledbetter (US), Steven L. Kunkel (US), Howard A. Young (US), Stephen G. Emerson (US), Jeffrey M. Leiden (US), and Carl H. June (US) showed that CD28 stimulation augments T cell immune responses by specifically inducing a 5- to 50-fold enhancement in the expression and secretion of interleukin 2 (IL-2), tumor necrosis factor type alpha, lymphotoxin, interferon gamma, and granulocyte-macrophage colony-stimulating factor in normal human T cells stimulated to proliferate by crosslinking of the T cell receptor/CD3 complex(3985). CD28 is a 44-kD glycoprotein expressed as a homodimer on the surface of a major subset of human T cells. Previous studies have demonstrated that the binding of monoclonal antibodies to the CD28 surface antigen can augment the proliferation of purified human T cells stimulated with suboptimal doses of mitogens or anti-T cell receptor/CD3 complex antibodies.

Cornelis L. Verweij (NL), Marlieke Geerts (NL), and Lucien A. Aarden (NL) demonstrated that costimulation of T cells via CD28 provides a signal which activates transcription of the IL-2 gene. A CD28-responsive element (CD28RE) in the IL-2 enhancer at position -162 to -152 was identified. Besides an effect on lymphokine mRNA stabilization, stimulation via CD28 acts at the level of transcription via coinduction of an NF-kB-like activity(3986).

David H. Ledbetter (US), Susan A. Ledbetter (US), Peter vanTuinen (US), Kim M. Summers (US), Terence J. Robinson (US), Yusuke Nakamura (US), Roger Wolff (US), Ray White (US), David F. Barker (US), Margaret R. Wallace (US), Francis S. Collins (US), and William B. Dobyns (US) discovered frequent submicroscopic deletions, evolutionarily conserved sequences, and a hypomethylated "island" in the Miller-Dieker chromosome region as the cause of the Miller-Dieker syndrome(3987).

Ronald Jaffe (US), Jonathan D.K. Trager (US), Adriana Zeevi (US), Enigul Sonmez-Alpan (US), Rene J. Duquesnoy (US), Satoru Todo (US), Marc Rowe (US), and Thomas Earl Starzl (US) reported the diagnostic surgical pathology of two children who underwent multivisceral abdominal transplantation; one survived for 1 month, the other for 6 months(3988).

Jerry A. Coyne (US) and H. Allen Orr (US) found that postzygotic isolation evolves at about the same rate as prezygotic isolation between allopatric species of Drosophila(3989, 3990). Note : many other studies ask whether any patterns characterize the evolution of reproductive isolation in a large group of species. One of the clearest lessons to emerge from this question is that biology matters: although postzygotic isolation, for instance, evolves at about the same rate as prezygotic between allopatric species of Drosophila, the same is not true in birds, where prezygotic isolation typically evolves long before postzygotic.

Joachim Wittbrodt (DE), Dieter Adam (DE), Barbara Malitschek (DE), Winfried Maueler (DE), Friedrich Raulf (DE), Agnes Telling (DE), Scott M. Robertson (DE), and Manfred Schartl (DE) found several genes that cause reproductive isolation have been identified and characterized. These genes are Xmrk-2, which causes inviability in backcross hybrids between the platyfish Xiphophorus maculatus and the swordtail Xiphophorus helleri(3991). 

Chau-Ti Ting (US), Shun-Chern Tsaur (US), Mao-Lien Wu (US), and Chung-I Wu (US) discovered that OdsH causes male sterility in backcross hybrids between the flies Drosophila simulans and Drosophila mauritiana(3992, 3993).

Daniel A. Barbash (GB), Dominic F. Siino (US), Aaron M. Tarone (US), and John Roote (GB), Hmr, which causes inviability in F1 hybrids between the flies Drosophila melanogaster and D. simulans(3994).

Daven C. Presgraves (US), Lakshmi Balagopalan (US), Susan M. Abmayr (US), and H. Allen Orr (US) discovered Nup96, which causes inviability in F2-like hybrids between D. melanogaster and D. simulans(3995).

Nicholas J. Brideau (US), Heather A. Flores (US), Jun Wang (US), Shamoni Maheshwari (US), Xu Wang (US), and Daniel A. Barbash (US) identified Lhr, which causes inviability in F1 hybrids between the flies D. melanogaster and D. simulans(3996).

Jerry A. Coyne (US) and H. Allen Orr (US) suggested that the genetics of speciation thus provides strong support for the traditional view that reproductive isolation evolves as an epiphenomenon of Darwinian adaptation, a result that has rightly received much attention(3990).

William Martin (DE), Alfons Gierl (DE), and Heinz Saedler (DE) report molecular evidence suggesting that angiosperm ancestors underwent diversification more than 300 Myr ago(3997).

Kenneth H. Wolfe (US), Manolo Gouy (US), Yau-Wen Yang (US), Paul M. Sharp (US), and Wen-Hsiung Li (US) estimated the date of the divergence between monocots and dicots by reconstructing phylogenetic trees from chloroplast DNA sequences, using two independent approaches: the rate of synonymous nucleotide substitution was calibrated from the divergence of maize, wheat, and rice, whereas the rate of nonsynonymous substitution was calibrated from the divergence of angiosperms and bryophytes. Both methods lead to an estimate of the monocot-dicot divergence at 200 million years (Myr) ago (with an uncertainty of about 40 Myr). This estimate is also supported by analyses of the nuclear genes encoding large and small subunit ribosomal RNAs. These results imply that the angiosperm lineage emerged in Jurassic-Triassic time, which considerably predates its appearance in the fossil record (approximately 120 Myr ago). They estimated the divergence between cycads and angiosperms to be approximately 340 Myr ago, which can be taken as an upper boundary for the age of angiosperms(3998). The two papers above suggest that the genomes of maize, rice, and wheat have been isolated for more than 60 million years.

Baruch Arensburg (IL), Anne-Marie Tillier (FR), Bernard Vandermeersch (FR), Henri Duday (FR), Lynne A. Schepartz (US), and Yoel Rak (IL) reported the discovery of a well-preserved human (Neanderthal) hyoid bone from Middle Palaeolithic layers of Kebara Cave, Mount Carmel, Israel, dating from about 60,000 years B.P. The bone is almost identical in size and shape to the hyoid of present-day Homo sapiens populations, suggesting that there has been little or no change in the visceral skeleton (including the hyoid, middle ear ossicles, and inferentially the larynx) during the past 60,000 years of human evolution. They concluded that the morphological basis for human speech capability appears to have been fully developed during the Middle Palaeolithic(3999).


“Often I am asked if I prefer chimpanzees to humans. The answer to that is easy—I prefer some chimpanzees to some humans, some humans to some chimpanzees!” Valerie Jane Goodall(4000).

Joseph Edward Murray (US) and E. Donnall Thomas (US) were awarded the Nobel Prize in Physiology or Medicine for their discoveries concerning organ and cell transplantation in the treatment of human disease.

Wolfgang Krätschmer (DE), Lowell D. Lamb (US), Konstantinos Fostiropoulos (DE), and Donald Huffman (US) synthesized the soccor-ball-shaped C60 fullerene(4001).

Jason D. Morrow (US), Kristina E. Hill (US), Raymond F. Burke (US), Tarek M. Nammour (US), Kamal F. Badr (LB), and L. Jackson Roberts, II (US) discovered new prostaglandin-like molecules which they named isoprostanes(4002).

Christopher E. Turner (US), John R. Glenney (US), and Keith Burridge (US) discovered paxillin, one of the cell adhesion proteins(4003).

David A. Evans (US), Stephen W. Kaldor (US), Todd K. Jones (US), Jon Clardy (US), and Thomas J. Stout (US) carried out the total synthesis of the antineoplastic macrolide antibiotic cytovaricin(4004).

Guncheol Kim (US), Margaret Y. Chu-Moyer (US), Samuel J. Danishefsky (US), and Gayle K. Schulte (US) carried out the total synthesis of indolizomycin(4005, 4006).

Edward E. Farmer (US) and Clarence A. Ryan (US) found that methyl jasmonate, a common plant secondary compound, when applied to surfaces of tomato plants, induces the synthesis of defensive proteinase inhibitor proteins in the treated plants and in nearby plants as well. The presence of methyl jasmonate in the atmosphere of chambers containing plants from three species of two families, Solanaceae and Fabaceae, results in the accumulation of proteinase inhibitors in leaves of all three species demonstrating that interplant communication can occur from leaves of one species of plant to leaves of another species to activate the expression of defensive genes(4007).

John M. Wozney (US), Vicki Rosen (US), Michael H. Byrne (US), Anthony J. Celeste (US), Ioannis K. Moutsatsos (US), and Elizabeth A. Wang (US) approached the study of growth factors affecting cartilage and bone development by investigating those factors present in bone which are able to initiate new cartilage and bone formation in vivo. They identified and cloned seven novel human factors which they named BMP-1 through BMP-7. Six of these molecules are related to each other, and are also distantly related to TGF-beta. The presence of one of these molecules, recombinant human BMP-2 (rhBMP-2) is sufficient to produce the complex developmental system of cartilage and bone formation when implanted subcutaneously in a rat assay system(4008). This factor, rhBMP-2, is now in clinical trials and showing remarkable promise as an agent to promote bone growth following surgery.

Manfred S. Weiss (DE), Thomas Wacker (DE), Jürgen Weckesser (DE), Wolfram Welte (DE), and Georg E. Schulz (DE) reported the structure of porin from Rhodobacter capsulatus at 3 Angstroms resolution(4009).

Beat Blum (CH), Norbert Bakalara (FR), and Larry Simpson (US) discovered what they called guide RNAs (gRNAs). These molecules serve as controls for RNA editing to determine the extent and positioning of editing(4010).

Barbara E. Bierer (US), Patricia K. Somers (US), Thomas J. Wandless (US), Steven J. Burakoff (US), and Stuart Lee Schreiber (US) appear to be the researchers who coined the term immunophilin to mean a soluble, intracellular molecule which binds a powerful and specific immunosuppressant(4011). 

Edward M. Golenberg (US), David E. Giannasi (US), Michael Tran Clegg (US), Charles J. Smiley (US), Mary Durbin (US), David Henderson (US), and Gerard Zurawski (US) isolated DNA from a 17 to 20 Ma (Miocene) Magnolia leaf; indicative of the resistance of DNA to degradation(4012).

Peter Lichter (DE), Chieh-Ju Chang Tang (US), Katherine Call (US), Gary Hermanson (US), Glen A. Evans (US), David Housman (US), and David C. Ward (US) performed a high resolution mapping of human chromosome 11 by in situ hybridisation with cosmid clones(4013). 

Alexander Hoffmann (US), Masami Horikoshi (JP), C. Kathy Wang (US), Stephanie C. Schroeder (US), P. Anthony Weil (US), and Robert Gayle Roeder (US) cloned the gene encoding transcription factor IID (TFIID)(4014). TFIID is considered to be the most important of the transcription factors.

Steven M. Block (US), Lawrence S. Goldstein (US), Bruce J. Schnapp (US), Scot C. Kuo (US), Jeff Gelles (US), Eric Steuer (US), Michael P. Sheetz (US), Karel Svoboda (US), and Christoph F. Schmidt (US) measured the force generated by a single kinesin motor using the optical tweezer technique(4015-4020).

William Donald Hamilton (GB) developed mathematical models to explain the evolution of sexual reproduction, models that relied upon a genetic arms race between parasites and their hosts, and resulted in what Hamilton called “the permanent unrest of many [genes]”(4021). Hamilton’s line of thinking went back to John Burdon Sanderson Haldane (GB-IN) who in 1949 wrote of genetic variation as a way of dealing with parasitic pressure. Others who continued this line included Suresh Jayakar (IN), 1970s, and Robert McCredie May (AU-GB) who demonstrated that there might be no equilibrium between parasite and host, only eternal chaotic motion(4022-4024).

Thomas J. Jentsch (DE), Klaus Steinmeyer (DE), and Gisela Schwarz (DE) discovered the first voltage-gated chlorine channel in cell membranes. It was found in the ray Torpedo(4025).

Susanna Cotecchia (IT-CH), Sabrina T. Exum (US), Marc G. Caron (US), and Robert Joseph Lefkowitz (US) were the first to report the results of mutations in G-protein-coupled receptors which make them constitutively active, specifically a mutagenized third cytoplasmic loop of the alpha1B-adrenergic receptor(4026).

Philippe Samama (US), Susanna Cotecchia (IT-CH), Tommaso Costa (IT), and Robert Joseph Lefkowitz (US) produced a mutation-induced activated state of the beta 2-adrenergic receptor. In this article they concluded that the ternary model needed to be extended to include an explicit isomerization of the receptor (R) to an active state (R*)(4027). A number of pathological conditions are now known to be the result of such constitutively active mutant G-protein-coupled receptors.

Andre De Léan (CA), Jeffrey M. Stadel (US), and Robert Joseph Lefkowitz (US) proposed the ternary model which postulates that receptor activation requires the agonist-promoted formation of an active, ternary complex consisting of agonist, receptor, and G protein(4028).

Peter E. Thorsness (US) and Thomas D. Fox (US) detected the movement of DNA between mitochondria and the nucleus in yeast(4029).

Pierre A. Coulombe (US), Yiu-Mo Chan (US), Kathryn M. Albers (US), Elaine V. Fuchs (US), Robert Vassar (US), Linda Degenstein (US), M. Elizabeth Hutton (US), Anthony G. Letai (US), Adelaide A. Hebert (US), and Amy S. Paller (US) demonstrated that as basal epidermal cells differentiate they reduce K5 and K14 keratin production and step-up K1 and K10 keratin production. In fully differentiated squamous cells these keratins constitute approximately 85% of total cellular protein.

They isolated and characterized human K5 and K14 genes, went on to modify their DNA, used it to transfect culture cells, and produce transgenic mice. The results indicate that mutated keratin genes can induce tissue conditions very similar to diseases such as epidermolysis bullosa simplex (EBS) and therefore, may serve as good animal models to study human skin disease(4030-4033). 

Toshiki Tsurimoto (JP), Thomas Melendy (US), and Bruce Stillman (US) prepared the first completely defined eukaryotic cell-free system for replicating DNA(4034).

Jacek Bielecki (US), Philip Youngman (US), Patricia Connelly (US), and Daniel Portnoy (US) cloned the structural gene for the Listeria monocytogenes haemolysin, hlyA, into an asporogenic mutant of Bacillus subtilis under the control of an IPTG-inducible promoter. After being internalized by the macrophage-like cell line J774, hemolytic B. subtilis disrupted the phagosomal membrane and grew rapidly within the macrophage cytoplasm. These results show that a single gene product is sufficient to convert a common soil bacterium into a parasite that can grow in the cytoplasm of a mammalian cell(4035).

Peter C. Sijmons (NL), Ben M.M. Dekker (NL), Barbara Schrammeijer (NL), Theo C. Verwoerd (NL), Peter J.M. van den Elzen (NL), and André Hoekma (NL) succeeded in creating transgenic potato plants which could produce human serum albumin useful as a blood extender(4036).

Andrew H. Paterson (US), Joseph W. DeVerna (US), Brenda Lanini (US), and Steven D. Tanksley (US) devised the technique of quantitative trait loci mapping (QTL) using the tomato as their test organism(4037). QTL is a type of linkage analysis involving a determination of the probability that specific DNA marker loci are situated near genes that control expression of the phenotype in question.

Bruce A. Sullenger (US), Humilidad F. Gallardo (US), Grace E. Ungers (US), and Eli Gilboa (US) isolated a gene from the HIV virus called tar that binds and blocks a protein the virus needs in order to replicate(4038).

David A. Relman (US), Jeffrey S. Loutit (US), Thomas M. Schmidt (US), Stanley Falkow (US), and Lucy S. Tompkins (US) used 16S rRNA analysis and polymerase chain reaction (PCR) to identify pathogens which had resisted culturing. They identified the causative agents of bacillary angiomatosis and cat-scratch disease as Bartonella henselae and Bartonella quintana respectively(4039).

Erhard Kranz (DE), Brigitte Krautwig (DE), Jaqueline Bautor (DE), and Horst Lörz (DE) accomplished in vitro fertilization with isolated single gametes resulting in zygotic embryogenesis and recovery of fertile maize plants(4040-4042).

Jean-Yves Exposito (FR) and Robert Garrone (FR) determined that sponges have collagen genes that are homologous to those of echinoderms and vertebrates. Since collagen is confined to animals this suggests that all metazoans belong to the same monophyletic clade(4043).

Edward Osborne Wilson (US) and Berthold Karl Holldobler (US) authored The Ants, possibly the most authoritative book to date on this important group of insects(4044).

Theodore G. Andreadis (US) and Ronald M. Weseloh (US) discovered a biological control of the gypsy moth, Lymantria dispar(4045).

Shawn J. Green (US), Sylvie Mellouk (US), Stephen L. Hoffman (US), Monte S. Meltzer (US), Carol A. Nacy (US), and John B. Hibbs, Jr. (US) determined that nitric oxide (NO) produced by cytokine-treated macrophages and hepatocytes plays a vital role in protective host responses to infectious pathogens(4046, 4047).

Dennis J. Stuehr (US), Hearn J. Cho (US), Nyoun Soo Kwon (US), Mary F. Weise (US), and Carl F. Nathan (US) purified soluble nitric oxide synthase from a mouse macrophage cell line activated with interferon gamma and bacterial lipopolysaccharide(4048).

Graham Le Gros (US), Shlomo Z. Ben-Sasson (IL), Robert Seder (US), Fred D. Finkelman (US), and William E. Paul (US) found that injection of anti-IgD into mice, a stimulus that leads to striking increases in serum levels of IgG1 and IgE, causes a striking increase in the IL-4 producing capacity of T cells. This increase is first observed 4 d after injection of anti-IgD. IL-4 production by T cells from anti-IgD-injected donors is mainly found among large- and intermediate-sized T cells. The capacity of T cells from anti-IgD-injected donors to produce IL-4 is enhanced by addition of IL-2(4049).

Marjorie A. Oettinger (US), David G. Schatz (US), Carolyn Gorka (US), and David Baltimore (US) found that recombination activating gene 1 (RAG-1), which is exclusively expressed in maturing lymphocytes, inefficiently induces V(D)J recombinase activity when transfected into fibroblasts. Co-transfection with an adjacent gene,  RAG-2 results in at least a 1000-fold increase in the frequency of recombination(4050).

The Recombinant Advisory Committee of the National Institutes of Health (U.S.A.) approved the first clinical trials of gene therapy. The proposed work would insert a normal gene for adenosine deaminase (ADA) into infants with severe combined immune deficiency (SCID)(4051, 4052). See Kenneth W. Culver, 1991. 

Qianjin Hu (US), Nicholas Dyson (US), and Edward Everett Harlow, Jr. (US) showed that the adenovirus E1A protein binds to the Rb protein. Sense Rb protein is the product of the anti-oncogene Rb. This suggested that dominant-acting oncogenes may bring about malignancy by interfering with anti-oncogene proteins required to suppress cell proliferation(4053).

Fumi-ichiro Yamamoto (US), Henrik Clausen (US), Thayer White (US), John Marken (US), and Sen-itiroh Hakomori (US) cloned and sequenced the gene controlling the ABO blood antigens. They found that the A and B genes differ in a few single-base substitutions, changing four amino-acid residues that may cause differences in A and B transferase specificity. A critical single-base deletion in the O gene resulted in the production of a faulty glycosyl transferase incapable of transfering a sugar unit to the correct site(4054).

Sir Henry Harris (AU-GB) discovered tumor-suppressor genes whose job is to detect excessive growth and shut it down(4055).

Eric R. Fearon (US) and Bert Vogelstein (US) amalgamated the findings that oncogenes and tumor-suppressor genes are altered in human cancer together with the idea of clonal evolution to produce a coherent molecular model of multistep tumorigenesis(4056).

Baya Cherif-Zahar (FR), Christian Bloy (FR), Caroline Le Van Kim (FR), Dominique Blanchard (FR), Pascal Bailly (FR), Patricia Hermand (FR), Charles Salmon (FR), Jean-Pierre Cartron (FR), and Yves Colin (FR) isolated cDNA clones encoding a human blood group Rh polypeptide from a human bone marrow cDNA library by using a polymerase chain reaction-amplified DNA fragment encoding the known common N-terminal region of the Rh proteins. The entire primary structure of the Rh polypeptide has been deduced from the nucleotide sequence of a 1384-base-pair-long cDNA clone(4057).

Andrew H. Sinclair (GB), Philippe Berta (FR), Mark S. Palmer (GB), J. Ross Hawkins (GB), Beatrice L. Griffiths (GB), Matthijs J. Smith (GB), Jamie W. Foster (FR), Anna-Maria Frischauf (GB), Robin Lovell-Badge (GB), and Peter N. Goodfellow (GB) searched for a 35-kilobase region of the human Y chromosome necessary for male sex determination and in the process identified of a new gene. This gene is conserved and Y-specific among a wide range of mammals, and encodes a testis-specific transcript. This gene has been termed SRY (for sex-determining region Y) and proposed to be a candidate for the elusive testis-determining gene, TDF(4058).

Eric R. Fearon (US), Kathleen R. Cho (US), Janice M. Nigro (US), Scott E. Kern (US), Jonathan W. Simons (US), J. Michael Ruppert (US), Stanley R. Hamilton (US), Antonette C. Preisinger (US), Giles Thomas (US), Kenneth W. Kinzler (US) and Bert Vogelstein (US) found that the Deleted in Colorectal Cancer (DCC) gene, located on chromosome 18, may play a role in the pathogenesis of human colorectal neoplasia, perhaps through alteration of the normal cell-cell interactions controlling growth(4059).

Craig A. Smith (US), Terri Davis (US), Dirk Anderson (US), Lisabeth Solam (US), M. Patricia Beckmann (US), Rita Jerzy (US), Steven K. Dower (US), David Cosman (US), and Raymond G. Goodwin (US) found that a receptor for tumor necrosis factor defines an unusual family of cellular and viral proteins(4060). 

Anthony F. Suffredini (US), Debra G. Reda (US), Steven M. Banks (US), Margaret M. Tropea (US), Jan M. Agosti (US), and Renee Miller (US) then led to way to discovering that tumor necrosis factor receptor is useful as a drug in the treatment of rheumatoid arthritis(4061). Enbrel is the trade name for the drug.

Walter Charles Cornelius Fiers (BE), Rudi Beyaert (BE), Elke Boone (BE), Wim Declercq (BE), Els Decoster (BE), Dirk Devalck (BE), Vera Goossens (BE), Johan Grooten (BE), Guy Haegemann (BE), Karen Heyninck (BE), Louis C. Penning (BE), Stéphane Plaisance (BE), Mark Van de Craen (BE), Peter Vandenabeele (BE), Eva A. van den Berg (BE), André Van de Voorde (BE), and Dominique Vercammen (BE) described the intracellular mechanism of action of tumor necrosis factor(4062).

Antonio Rafael Cabral (MX), Javier Cabiedes (MX), Donato Alarcón-Segovia (MX) reported a patient with hemolytic anemia who was producing antiphosphatidylcholine antibodies(4063).

Isabel Zuazu-Jausoro (ES), Arturo Oliver (ES), Montserrat Borrell (ES), Mercé Gari (ES), Isabel Pich (ES), Enric Grau (ES), and Jordi Fontcuberta (ES) reported on 30 cases of patients with lupus anticoagulant who possessed specific antibodies to phosphatidylserine(4064).

Eberhard Deltz (DE), W. Mengel (DE), and Horst Hamelmann (DE) reported one of the first cases of small bowel transplantation in humans(4065).

David R. Grant (CA), William J. Wall (CA), Richard Mimeault (CA), Robert A. Zhong (CA), Cameron N. Ghent (CA), Bertha M. Garcia (CA), Calvin R. Stiller (CA), John H. Duff (CA) reported a successful small-bowel/liver transplantation(4066).

Andreas G. Tzakis (US), Camillo Ricordi (US), Rodolfo Alejandro (US), Yijun Zeng (US), John J. Fung (US), Satoru Todo (US), Anthony J. Demetris (US), Daniel H. Mintz (US), and Thomas Earl Starzl (US) performed the first unequivocal example of successful clinical islet cell transplantation(4067).

Gary Onik (US), Barbara Porterfield (US), Boris Rubinsky (US), and Jeffrey Cohen (US) successfully performed percutaneous transperineal prostate cryosurgery using transrectal ultrasound guidance in the dog(4068).

Henry Brem (US) surgically implanted a quarter-size biodegradable polymer containing a chemotherapeutic drug directly into the site of a patient's brain tumor(4069). He first did this in 1987.

Henry Brem (US), M. Stephen Mahaley, Jr. (US), Nicholas A. Vick (US), Keith L. Black (US), Stanley C. Schold, Jr. (US), Peter C. Burger (US), Allan H. Friedman (US), Ivan S. Ciric (US), Theodore W. Eller (US), Jeffrey W. Cozzens (US), and James N. Kenealy (US) directed a Phase I-II study trial in which 21 patients with recurrent malignant glioma were treated with BCNU (carmustine) released interstitially by means of a polyanhydride biodegradable polymer implant. Implantation of the drug-impregnated polymer at the tumor site allows prolonged local exposure with minimal systemic exposure(4070). This is referred to as a polymer wafer implant.

Robert G.C. Teepe (NL), Robert W. Kreis (NL), Eline J. Koebrugge (NL), Johanna A. Kempenaar (NL), Adrianus F.P.M. Vloemans (NL), Rudy P. Hermans (NL), Han Boxma (NL), Jan Dokter (NL), Jo Hermans (NL), Maja Ponec (NL), and Bert J. Vermeer (NL) grafted seventeen patients with deep second- and third-degree burn wounds with cultured autologous epidermis. These epidermal cell sheets were cultivated according to the feeder layer technique as described by James G. Rheinwald (US) and Howard Green (US). Wound infection was the main cause of graft failure. Up to 4 years after grafting, the grafted areas showed continued stability and the regenerated skin became supple, smooth, and pliable(2242, 4071).

Malcolm R. Walter (US), Du Rulin (US), and Robert Joseph Horodyski (US) discovered the oldest known multicellular fossils. They were removed from Old Greyson Shale, Lower Belt Supergroup, in Montana, US, and from the similarly aged Gaoyuzhuang Formation, Upper Changcheng Group, in the Jixian Section, Northern China. The organism was identified as Grypania spiralis, a coiled ribbon-like creature. It was judged to most likely have been a multicellular eukaryotic alga(4072). Shale is rock formed by condensation of layers of clay or mud sedimented, along with phytoplankton and other debris, at the bottoms of lakes or ocean basins.

Scott D. Boden (US), David O. Davis (US), and Thomas S. Dina (US) performed magnetic resonance imaging on sixty-seven individuals who had never had low-back pain, sciatica, or neurogenic claudication. In view of the findings in asymptomatic subjects, they concluded that abnormalities on magnetic resonance images must be strictly correlated with age and any clinical signs and symptoms before operative treatment is contemplated(4073).

Jennifer A. Clack (GB) and Michael I. Coates (GB) reported on fossil specimens of the Devonian fish-like Acanthostega gunneri they collected during 1987 in Greenland. Their work strongly suggested that legs appeared in tetrapods well before they abandoned water and not vice-versa as had been suggested by the popular dry pond theory first articulated by Alfred Sherwood Romer (US)(4074-4077).


“The distinctive features of microbes are that they can make use of unusual and ingenious methods of obtaining energy in order to drive a fairly conventional metabolism, and that they can adjust themselves to run such a metabolism in circumstances that would be lethal to higher organisms. They can be found all over the planet, can grow and perform chemical transformations in what seem, from an anthropomorphic point of view, the most unlikely places. For this reason they have a profound, and often unrealized, effect, not only on the balance of nature but on the existence of mankind and on our economy.” John R. Postgate(4078).

Richard R. Ernst (CH) was awarded the Nobel Prize in Chemistry for his contributions to the development of the methodology of high resolution nuclear magnetic resonance (NMR) spectroscopy.

Erwin Neher (DE) and Bert Sakmann (DE) were awarded the Nobel Prize in Physiology or Medicine for their discoveries concerning the function of single ion channels in cells.

Hitoshi Matsushime (JP), Martine F. Roussel (US), Richard A. Ashmun (US), Charles J. Sherr (US), Yue Xiong (US), Tim Connolly (US), Bruce Futcher (US), David Beach (US), Daniel Julio Lew (US), Vjekoslav Dulic (FR), Steven I. Reed (US), Andrew Koff (US), Fred Cross (US), Alfred Fisher (US), Jill Schumacher (US), Katherine LeGuellec (US), Michel Philippe (US), James M. Roberts (US), Toru Motokura (JP), Theodora Bloom (US), Hyung Goo Kim (KR), Harald Jüppner (US), Joan V. Ruderman (US), Henry M. Kronenberg (US), and Andrew Arnold (US) independently identified, using a variety of techniques, a new class of cyclins—which consists of cyclins C, D and E—in mammals(4079-4083).

Elaine O. Davis (GB), Steven G. Sedgwick (GB), M. Joseph Colston (GB), Peter J. Jenner (GB), and Patricia C. Brooks (GB) described a novel mechanism of protein biosynthesis in mycobacteria(4084, 4085).

Sanford M. Simon (US) and Günter Klaus-Joachim Blobel (DE-US) presented direct evidence for the existence of protein-conducting channels in the endoplasmic reticulum(4086, 4087).

Hali A. Hartmann (US), Glenn E. Kirsch (US), John A. Drewe (US), Maurizio Taglialatela (IT), Rolf H. Joho (US), Arthur M. Brown (US) performed experiments which gave one of the first clues about the location of the channel pore in a potassium channel(4088).

Masatoshi Takeichi (JP) named calcium-dependent cell adhesion molecules (CAMS) cadherins(4089).

James B. Bliska (US), Kun-Liang Guan (CN-US), Jack E. Dixon (US), and Stanley Falkow (US) discovered that YopH is a type of enzyme which causes the removal of a phosphate group (phosphatase). YopH, produced by cells of Yersinia pestis, inhibits their being phagocytized by macrophages(4090).

Bernadette Connolly (GB), Hazel J. Dunderdale (GB), Fiona E. Benson (GB), Carol A. Parsons (GB), Gary J. Sharples (GB), Robert G. Lloyd (GB), and Stephen C. West (GB) identified the RuvC gene of Escherichia coli which codes for a nuclease capable of resolving Holliday intermediates(4091, 4092).

Gary G. Shutler (CA-US), Alex E. MacKenzie (CA), Han G. Brunner (NL), Berend Wieringa (NL), Pieter J. de Jong (US), Frans P. Lohman (NL), Suzanne Leblond (CA), Jane Bailly (CA), and Robert G. Korneluk (CA) mapped the myotonic dystrophy gene locus to the region of 19q13.2-13.3 lying distal to the gene for creatine kinase subunit M (CKM)(4093).

Charalampos Aslanidis (US), Gert Jansen (NL), Chris T. Amemiya (US), Gary G. Shutler (CA-US), Mani S. Mahadevan (CA), Catherine Tsilfidis (CA), Chira Chen (US), Jennifer Alleman (US), Nicole G.M. Wormskamp (NL), Marc Vooijs (US), Jessica Buxton (GB), Keith Johnson (GB), Hubertus J.M. Smeets (NL), Gregory G. Lennon (US), Anthony V. Carrano (US), Robert G. Korneluk (CA), Bé Wieringa (NL), Pieter J. de Jong (US), J. David Brook (US), Mila E. McCurrach (US), Helen G. Harley (GB), Alan J. Buckler (US), Deanna Church (US), Hiroyuki Aburatani (JP), Kent Hunter (US), Vincent P. Stanton (US), Jean-Paul Thirion (CA), Thomas Hudson (CA), Robert Sohn (US), Boris V. Zemelman (US), Russell G. Snell (US), Shelley A. Rundle (GB), Stephen Crow (GB), June Davies (GB), Peggy Shelbourne (GB), Clare Jones (GB),Vesa Juvonen (FI), Peter S. Harper (US), Duncan J. Shaw (GB), David E. Housman (US), Tracey Van Tongeren (GB), Maria Anvret (GB), Brien Riley (GB), Robert Williamson (GB), Ying-Hui Fu (US), Antonio Pizzuti (IT), Raymond G. Fenwick, Jr. (US), J. King (), S. Rajnarayan (), Patrick W. Dunne (US), Jacqueline R. Dubel (US), G.A. Nasser (), Tetsuo Ashizawa (JP-US), M. Benjamin Perryman (US), Henry F. Epstein (US), Charles Thomas Caskey (US), William Reardon (GB), Luc Sabourin (CA), Catherine E. Neville (CA), Monica A. Narang (CA), Juana M. Barceló (CA-US), Kim L. O'Hoy (AU), Suzanne Leblond (CA), and J. Earle-Macdonald (CA) discovered the myotonin-protein kinase (Mt-PK) gene, which contains a track of CTG trinucleotide repeats in the 3’-untranslated region. While normal individuals have 5-30 repeats of this trinucleotide, affected individuals exhibit repeats in the hundreds to thousands resulting in myotonic dystrophy(4094-4099).

Michael J. Kuranda (US) and Phillips W. Robbins (US) cloned and sequenced the gene responsible for producing chitinase in Saccharomyces cerevisiae. By disrupting this gene they demonstrated that chitinase is necessary for cell separation(4100). 

G. Moore (GB), H. Lucas (GB), N. Batty (GB), and Richard Anthony Flavell (GB-US) investigated the segregation of different phenotypes within identical genotypes using wheat(4101).

Charlotte E. Alford (US), Talmadge E. King, Jr. (US), Priscilla A. Campbell (US), Thomas F. Byrd (US), and Marcus A. Horowitz (US) reported that phagocytosis of microbial pathogens by macrophages includes the microbes being deprived of intracellular iron(4102, 4103).

Jacques Banchereau (FR), Paolo de Paoli (FR), Alain Valle (FR), Eric Garcia (FR), and Francoise Rousset (FR) found that resting B lymphocytes enter a state of sustained proliferation when incubated with both the mouse fibroblastic Ltk- cell line, that had been transfected with the human Fc receptor (Fc gamma RII/CDw32) and monoclonal antibodies to CD40(4104). CD40 is a 45-50 kD transmembrane glycoprotein expressed on B lymphocytes, epithelial cells, and carcinoma cell lines.

Susan H. Chan (US), Bice Perussia (US), Jean W. Gupta (US), Michiko Kobayashi (US), Miloslav Pospisil (CZ), Howard A.Young (US), Stanley F. Wolf (US), Deborah Young (US), Steven C. Clark (US), and Giorgio Trinchieri (US) showed that human natural killer cell stimulatory factor (NKSF) induces IFN-gamma production from both resting and activated human peripheral blood lymphocytes (PBL) and from freshly isolated murine splenocytes . Human T and NK cells produce IFN-gamma in response to NKSF, but resting PBL require the presence of nonadherent human histocompatibility leucocyte antigens DR+ (HLADR+) accessory cells to respond to NKSF. The ability of NKSF to directly induce IFN-gamma production and to synergize with other physiological IFN-gamma inducers, joined with the previously described ability to enhance lymphocyte cytotoxicity and proliferation, indicates that this lymphokine is a powerful immunopotentiating agent(4105). (NKSF), a heterodimeric lymphokine purified from the conditioned medium of human B lymphoblastoid cell lines, induces interferon gamma (IFN-gamma) production from resting peripheral blood lymphocytes (PBL) and synergizes with interleukin-2 (IL-2) in this activity.

Stefan Ehlers (DE) and Kendall A. Smith (US) compared neonatal and adult T cells revealing that both populations expressed the genes for interleukin 2 (IL2) and its receptor, but only adult T cells were capable of transcribing mRNAs for IL-3, IL-4, 1IL-5, IL-6, interferon gamma, and granulocyte/macrophage colony-stimulating factor. However, neonatal T cells could be induced to undergo functional differentiation in vitro, thereby acquiring the capacity to express the lymphokine gene repertoire characteristic for adult T cells. These data suggest that the T cells generated from neonatal blood by a primary stimulation in vitro are functionally indistinguishable from the T cells in adult blood that presumably have undergone primary stimulation in vivo(4106).

Hubert Schorle (DE), Thomas Holtschke (DE), Thomas Hünig (DE), Anneliese Schimpl (DE), and Ivan Horak (DE) found that mice homozygous for a IL-2 gene mutation are normal with regard to thymocyte and peripheral T cell subset composition, but that dysregulation of the immune system is manifested by reduced polyclonal in vitro T cell responses and by dramatic changes in the isotype levels of serum immunoglobulins(4107).

Paulo Vieira (PT-FR), Rene de Waal-Malefyt (US), Minh-Ngoc Dang (US), K.E. Johnson (US), Robert A. Kastelein (US), David F. Fiorentino (US), Jan E. de Vries (NL), Maria-Grazia Roncarolo, Timothy R. Mosmann (US), and Kevin W. Moore (US) demonstrated the existence of human cytokine synthesis inhibitory factor (CSIF) [interleukin 10 IL-10]. Human and murine IL-10 exhibit a strong sequence homology to the open reading frame in Epstein-Barr virus, BCRFI. Human IL-10 and the BCRFI product inhibit cytokine synthesis(4108).

Antanina Zmuidzinas (US), Harvey J. Mamon (US), Thomas M. Roberts (US), and Kendall A. Smith (US) found that interleukin-2-triggers Raf-1 expression, phosphorylation, and associated kinase activity increase through G1 and S in CD3-stimulated primary human T cells(4109).

Judith P. Johnson (DE) reported that changes in expression of cell-cell adhesion molecules (CAMs) in the immunoglobulin superfamily appears to play a critical role in the processes of invasion and metastasis(4110).

Ulrich Kaiser (DE), Bernhard Auerbach (DE), Marcus Oldenberg (DE) and Judith P. Johnson (DE) presented the case where neural cell adhesion molecule (N-CAM) undergoes a switch in expression from a highly adhesive isoform to poorly adhesive forms in Wilm's tumor, neuroblastoma, and small cell lung cancer(4110, 4111).

Paola Fogar (IT), Daniela Basso (IT), Claudio Pasquali (IT), Massimo De Paoli (IT), Cosimo Sperti (IT), Giovanni Roveroni (IT), Sergio Pedrazzoli (IT), and Mario Plebani (IT)  showed that in invasive pancreatic and colorectal cancers there is a reduction in overall expression level of neural cell adhesion molecule (N-CAM)(4112).

Judith A. Varner (US), David A. Cheresh (US), Matvey E. Lukashev (US), and Zena Werb (DE-CA-US) reported that carcinoma cells facilitate invasion by shifting their expression of integrins from those that favor the extracellular matrix (ECM) present in normal epithelium to other integrins (e.g., alpha3ß1 and alphaVß3) that preferentially bind the degraded stromal components produced by extracellular proteases(4113, 4114). 

Gerhard Christofori (DE) and Henrik Semb (DK) report on coupling between adjacent cells by E-cadherin bridges resulting in the transmission of antigrowth and other signals via cytoplasmic contacts with ß-catenin to intracellular signaling circuits that include the Lef/Tcf transcription factor. E-cadherin function is apparently lost in a majority of epithelial cancers, by mechanisms that include mutational inactivation of the E-cadherin or ß-catenin genes, transcriptional repression, or proteolysis of the extracellular cadherin domain. Forced expression of E-cadherin in cultured cancer cells and in a transgenic mouse model of carcinogenesis impairs invasive and metastatic phenotypes, whereas interference with E-cadherin function enhances both capabilities(4115). Therefore, E-cadherin serves as a widely acting suppressor of invasion and metastasis by epithelial cancers, and its functional elimination represents a key step in the acquisition of this capability. 

Yinghua Huang (US), Alexander M. Diner (US) and David F. Karnosky (US) produced the first transgenic plants of a conifer (Larix decidua), by Agrobacterium rhizogenes mediated transformation(4116).

Roderick MacKinnon (US) found that the K+ channels in membranes have a tetrameric structure. This is consistent with the sequence relationship between a K+ channel and each of the four internally homologous repeats of Na+ and Ca2+ channels(4117).

Roderick MacKinnon (US), Steven L. Cohen (US), Anling Kuo (US), Alice Lee (US), Brian T. Chait (ZA-US), Declan A. Doyle (GB), João Morais Cabral (PR-US), Richard A. Pfuetzner (CA), and Jacqueline M. Gulbis (AU) found that membrane K+ channels have “four identical subunits creating an inverted teepee, or cone, cradling the selectivity filter of the pore in its outer end. The narrow selectivity filter is only 12 angstroms long, whereas the remainder of the pore is wider and lined with hydrophobic amino acids. A large water-filled cavity and helix dipoles are positioned so as to overcome electrostatic destabilization of an ion in the pore at the center of the bilayer. Main chain carbonyl oxygen atoms from the K+ channel signature sequence line the selectivity filter, which is held open by structural constraints to coordinate K+ ions but not smaller Na+ ions. The selectivity filter contains two K+ ions about 7.5 angstroms apart. This configuration promotes ion conduction by exploiting electrostatic repulsive forces to overcome attractive forces between K+ ions and the selectivity filter.” They also showed that a prokaryotic K+ channel has the same pore structure as eukaryotic K+ channels(4118, 4119).

Youxing Jiang (CN-US), Alice Lee (US), Jiayun Chen (US), Martine Cadene (FR), Brian T. Chait (ZA-US), and Roderick MacKinnon (US) determined the crystal structure of a K+ channel (MthK) from Methanobacterium thermoautotrophicum in the Ca(2+)-bound, opened state. Eight RCK domains (regulators of K+ conductance) form a gating ring at the intracellular membrane surface. The gating ring uses the free energy of Ca(2+) binding in a simple manner to perform mechanical work to open the pore(4120).

Roderick MacKinnon (US) would be awarded the 2003 Nobel Prize in Chemistry for structural and mechanistic studies of ion channels.

Jun Liu (US), J. Dean Farmer, Jr. (US), William S. Lane (US), Jeffrey M. Friedman (US), Irving Lerner Weissman (US), and Stuart Lee Schreiber (US) found that both cyclophilin-cyclosporin and FKBP12-FK506 bind and inactivate calcineurin, a ubiquitious protein phosphatase. This leads to immunosuppression(4121). Cyclophilin and FKBP12 are immunophilins (a soluble, intracellular molecule which binds a powerful and specific immunosuppressant).

H. Yamasaki (JP), Chitoshi Itakura (JP), and Makoto Mizutani (JP) presented the first evidence that neurofilaments are the primary determinant of axonal caliber. This came from the identification of a mutant Japanese quail (quiver or Quv) that accumulates no neurofilaments in its axons(4122).

 Charles H. Streuli (GB), Nina Bailey (GB) and Mina J. Bissell (GB) provided evidence for a central role of basement membrane in the induction of tissue-specific gene expression(4123).

Peter Koopman (GB), John Gubbay (GB), Nigel Vivian (GB), Peter N. Goodfellow (GB), and Robin H. Lovell-Badge (GB) discovered the sex determining gene in mice(4124).

Sam J. McCullough (GB), Francis McNeilly (GB), Gordon M. Allan (GB), Seamus Kennedy (GB), Joan A. Smyth (US), S. Louise Cosby (GB), Stephen McQuaid (GB), and Bert K. Rima (GB) isolated and characterized porpoise morbillivirus (PMV) from harbor porpoises (Phocoena phocoena) that died along the Irish coast in 1988(4125).

Kenneth W. Culver (US), R. Michael Blaese (US), Lauren Chang (US), W. French Anderson (US), Craig A. Mullen (US), Arthur W. Nienhuis (US), Charles S. Carter (US), Cynthia E. Dunbar (US), Susan F. Leitman (US), Melvin Berger (US), A. Dusty Miller (US), Richard Morgan (US), Thomas Fleisher (US), Roger Kobyashi (US), Ai Lan Kobyashi (US), Harvey Klein (US), Gene Shearer (US), Mario Clerici (US), Gerald McGarrity (US), and Aliza Cassell (US) treated severe combined immune deficiency (SCID) patients with CD34+ selected autologous peripheral blood cells transduced with a human adenosine deaminase (ADA) gene. The white-cell count of patients trebled, and they made about one-quarter of the ADA that a normal person makes(4126, 4127). This represents the first case of gene therapy to clinically treat a disease in humans.

Laryssa N. Kaufman (US), Mary M. Peterson (US), and Stephen M. Smith (US) demonstrated that, “Male Sprague-Dawley rats fed either a high-fat or a glucose enriched diet developed higher blood pressure than rats fed a control diet.… Rats fed the high-fat diet developed hypertension only when they were allowed to overeat and become obese and hyperinsulinemic. But when their feeding was restricted to prevent obesity… they remained normotensive”(4128).

Arnold I. Caplan (US), Stephen E. Haynesworth (US), Jun Goshima (US), Victor M. Goldberg (US), Mark F. Pittenger (US), Alastair M. Mackay (US), Stephen C. Beck (US), Rama K. Jaiswal (US), Robin Douglas (US), Joseph D. Mosca (US), Mark A. Moorman (US), Donald W. Simonetti (US), Stewart Craig (US) and Daniel R. Marshak (US) characterized the mesenchymal stem cells (MSC) of the bone marrow as having the potential to differentiate to all mesenchymal cell types, including osteocytic, chondrocytic, adiocytic, myocytic, tenocytic, and also dermal and stromal lineages(4129-4131).

David Gailani (US), George J. Broze, Jr. (US), Koji Naito (JP), and Kazuo Fujikawa (US) found that the activation of factor XI by thrombin triggers the intrinsic pathway of coagulation that also takes place on the surface of the activated platelets(4132, 4133).

In 1991, 100 years after cholera was vanquished from South America, there was an outbreak in Peru that spread across the continent, killing 10,000 people. It was a similar strain to the pandemic that petered out more than a decade earlier in Japan and the South Pacific. ref

Wesley W. Parke (US) has shown that when spinal nerve compression occurs that it is the impairment of the less resilient venous return system that produces the clinical symptoms. This means that surgeons can not merely "unroof" nerves in treating lateral spinal stenosis but must also relieve tension and stretch on the structure to allow return to a normal state(4134).

Erich Mühe (DE) performed the first laproscopic cholecystectomy in 1985 but it was not reported until 1991(4135). 

Jerome M. Siegel (US), Robert Nienhuis (US), Heidi M. Fahringer (US), Richard Paul (US), Priyattam Shiromani (US), William C. Dement (US), Emmanuel Mignot (US), and Charles Chiu (US) discovered that unusual activity in the medial medulla region of the brain could bring a cataplectic episode such as those commonly experienced by narcoleptics(4136). Horace W. Magoun (US), in the 1940s, discovered that when he electrically stimulated the medial medulla (a part of the brain stem), muscle tone vanished. He did not connect this with narcolepsy.

Felix Eijgenraam (NL) and Alun Anderson (GB) described a 4,000 year old Bronze Age man found frozen since his death in the Italian Alps. It is hoped that this body—found by Helmut and Erika Simon— will shed light on the racial structure and culture of early Europe(4137).

Leopold Dorfer (AT), Maximilian Moser (AT), Frank Bahr (DE), Konrad Spindler (AT), Eduard Egarter-Vigl (IT), Sonja Giullen (PE), Gottfried Dohr (AT), and Thomas Kenner (AT) reported that the Bronze Age “Ice Man,” found in the Italian Alps near the Austrian border, possesses many "tattoos" corresponding very near or precisely to acupuncture points and meridians, including the 'master point for back pain'. If these are acupuncture sites then this is the oldest known example of such treatment(4138).


“One reason why medical history is not much taught in medical schools is that so much of it is an embarrassment.” Lewis Thomas(4139).

Edmond H. Fischer (US) and Edwin Gerhard Krebs (US) were awarded the Nobel Prize in Physiology or Medicine for their discoveries concerning reversible protein phosphorylation as a biological regulatory mechanism.

Kenneth R. Ludwig (US), Kathleen R. Simmons (US), Barney J. Szabo (US), Isaac J. Winograd (US), Jurate M. Landwehr (US), Alan C. Riggs (US), and Ray J. Hoffman (US) were among the first to use mass spectrometric uranium series dating (MS/U-series) of calcite. The technique is typically applied to calcite or tooth materials intercalated into archaeological or paleoanthropological sites and works well for samples between 1,000 and 400,000 yeas old(4140). 

Kimiko Murakami-Murofushi (JP), Masaki Shioda (JP), Kazuhiko Kaji (JP), Shonen Yoshida (JP), and Hiromu A. Murofushi (JP) were the first to describe the parent compound, cyclic phosphatidic acid, which they found in myxoamoebae of a true slime mold, Physarum polycephalum(4141).

Tetsuyuki Kobayashi (JP), Rieko Tanaka-Ishii (JP), Ryo Taguchi (JP), Hiroh Ikezawa (JP), and Kimiko Murakami-Murofushi (JP) found cyclic phosphatidic acid later in the human serum albumin fraction where it may have biological activities related to the inhibition of cell proliferation(4142).

Gifford H. Miller (US), Peter B. Beaumont (ZA), Anthony J.T. Jull (CA), and Beverly J. Johnson (US) discovered that degradation of polypeptides, including hydrolysis to smaller peptide fragments and eventual release of free amino acids, decomposition, and racemization and epimerization occur at regular, predictable rates dependent on ambient temperature. This provided a method of dating materials of biological origin(4143). The method is accurate from 500 to 300,000 years ago.

Gifford H. Miller (US), John W. Magee (AU), Beverly J. Johnson (US), Marilyn L. Fogel (US), Nigel A. Spooner (AU), Malcolm T. McCulloch (AU), and Linda K. Ayliffe (AU) used this dating technique to determine that the large flightless bird Genyornis newtoni became extinct in the late pleistocene, some 50,00 years ago. They reasoned that extinction was the result of human impact(4144).

Seunghyon Choe (Korean-US), Melanie J. Bennett (US), Gary Fujii (US), Paul M.G. Curmi (AU), Katherine A. Kantardjieff (US), R. John Collier (US), and David Eisenberg (US) solved the three dimensional structure of diphtheria toxin(4145).

J. Fernando Bazan (US) determined the tertiary structure of interleukin-2 (IL-2)(4146).

Anne Kallioniemi (FI), Olli P. Kallioniemi (FI), Damir Sudar (US), Denis Rutovitz (GB), Joe W. Gray (US), Frederic Waldman (US), and Dan Pinkel (US) introduced "comparative genome hybridization" (CGH). This is a form of reverse chromosome painting used to detect chromosome deletions and duplications from a patient's total genomic DNA rather that from his or her karyotype. The patient's DNA is labeled in one color and mixed with control DNA labeled in another color. Both are mixed and hybridized to normal metaphases and the ratio of the two colors determined along the length of each chromosome. Duplications are recognized by the predominance of the subject DNA color, whereas deletions are revealed by the predominance of the control DNA color. CGH has been useful both in screening for small constitutional chromosome aberrations in patients and in detecting aberrations in cancer cells(4147).

Christophe Caux (FR), Colette Dezutter-Dambuyant (FR), Daniel Schmitt (FR), and Jacques Banchereau (FR) found that in man, cooperation between granulocyte-macrophage-colony-stimulating factor (CM-CSF) and tumor necrosis factor-alpha (TNF-alpha) is crucial for the generation of human dendritic Langerhans cells from haematopoietic progenitors(4148). Dendritic cells are highly efficient antigen presenting cells which initiate immune responses such as the sensitization of T cells restricted by major histocompatibility complex molecules, the rejection of organ transplants and the formation of T cell-dependent antibodies. Dendritic cells are found in non-lymphoid tissues, such as skin (Langerhans cells) and mucosa, and they migrate after antigen capture through the afferent lymph or the bloodstream to lymphoid organs, where they efficiently present antigen to T cells.

Kayo Inaba (JP), Ralph Steinman (US), Margit Witmer Pack (US), Hikeki Aya (JP), Muneo Inaba (JP), Tesuo Sudoo (JP), Stephen Wolpe (US), and Gerold Schuler (AT) found that murine blood contains GM-CSF-dependent, proliferating progenitors that give rise to large numbers of dendritic cells with characteristic morphology, mobility, phenotype, and strong T cell stimulatory function(4149).

Carlos J. Gimeno (US), Per O. Ljungdahl (US), Cora A. Styles (US), and Gerald R. Fink (US) rediscovered that yeast cells, and the colonies that they produced, could adopt a mode of growth different from the vegetative style familiar to yeast researches. Instead of forming ovoid buds that separate cleanly from the mother cell, under conditions of nutrient limitation, yeast cells grew as filaments in which the daughter cells remain adhered to the mother cell. They carefully described the physiological events that characterize the phenomenon and investigated the underlying molecular mechanisms(4150). See, Guilliermond, 1920.

Brian J. Stevenson (US), Nelson Rhodes (US), Beverly Errede (US), and George F. Sprague, Jr. (US) recognized a protein kinase cascade in Saccharomyces cerevisiae that appears to be an essential feature of the pheromone response pathway and probably connects the receptor/G protein to an identified transcription factor, Ste12. STE12 is a gene that encodes a protein kinase activity essential for mating(4151).

Kang-Yell Choi (KR), Brett Satterberg (US), David M. Lyons (US), and Elaine A. Elion (US) produced results using Saccharomyces cerevisiae to substantiate a novel signal transduction component, Ste5, that physically links multiple kinases within a single cascade(4152). 

Yasumasa Ishida (JP), Yasutoshi Agata (JP), Keiichi Shibahara (JP), and Tasuku Honjo (JP) provided evidence to suggest that activation of the PD-1 gene (a member of the immunoglobulin gene superfamily) may be involved in the classical type of programmed cell death(4153).

Seth Lederman (US), Michael J. Yellin (US), Alexander Krichevsky (US), John Belko (US), Julie J. Le (US), and Leonard Chess (US) discovered 5c8 Ag, a novel, activation-induced surface T cell protein that is involved in mediating a contact dependent element of the helper effector function of CD4+ T lymphocytes(4154). CD4+ T lymphocytes provide contact-dependent stimuli to B cells that are critical for the generation of specific antibody responses in a process termed T helper function.

Randolph J. Noelle (US), Meenakshi Roy (US), David M. Shepherd (US), Ivan Stamenkovic (US), Jeffrey A. Ledbetter (US), and Alejandro Aruffo (US) discovered that a  39-kD protein on activated helper T cells binds CD40 and transduces the signal for cognate activation of B cells(4155). 

Toshikazu Takeshita (JP), Kiyoshi Ohtani (JP), Hironobu Asao (JP), Satoru Kumaki (JP), Masataka Nakamura (JP), and Kazuo Sugamura (JP) produced results which suggested the possibility that p64 (a membrane molecule) associates with IL-2R beta and has an important role in formation of the functional IL-2R complex(4156).

Richard O. Williams (GB), Marc Feldmann (GB), and Ravinder N. Maini (GB) showed that anti-tumor necrosis factor ameliorates joint disease in murine collagen-induced arthritis(4157). This research was in response to the considerable evidence implicating tumor necrosis factor (TNF-a) in the pathogenesis of rheumatoid arthritis.

Joseph G. Naglich (US), James E. Metherall (US), David W. Russell (US), Leon Eidels (US) determined that the receptor for diphtheria toxin is a membrane bound growth factor precursor that the toxin exploits as a receptor(4158).

Simon McQueen-Mason (GB), Lian-Chao Li (US), Daniel M. Durachko (US), and Daniel J. Cosgrove (US) discovered the expansin gene family which produces expansins; proteins that allow plant cell walls to grow while maintaining their rigidity(4159, 4160).

Harry F. Noller, Jr. (US), Vernita Hoffarth (US), and Ludwika Zimniak (US) confirmed that the ability to catalyze the formation of a covalent bond between adjacent amino acids—the peptidyl bond—lies in rRNA and not in proteins associated with the ribosome(4161).

Poul Nissen (DK), Jeffrey L. Hansen (US), Nenad Ban (Crotian-US-CH), Peter B. Moore (US), and Thomas A. Steitz (US) used the atomic structures of the large ribosomal subunit from Haloarcula marismortui (Archaea) and its complexes with two substrate analogs, to establish that the ribosome is a ribozyme and explored the catalytic properties of its all-RNA active site(4162).

Swapan K. Datta (PH), Karabi Datta (PH), Nouchine Soltanifar (CH), Günter Donn (DE), and Ingo Potrykus (CH) produced herbicide resistant rice plants through polyethylene glycol (PEG) mediated transformation of protoplasts(4163).

Edward F. DeLong (US), Jed A. Fuhrman (US), Kirk McCallum (US), Alison A. Davis (US), Tohru Ueda (JP), Yuko Suga (JP), and Tatsuhiko Matsuguchi (JP) discovered numerous crenarchaeal ribosomal RNA (rRNA) genes in low-temperature marine and terresterial environments. This destroyed the notion that all Crenarchaeota (a major subdivision of the Archaea) were from high-temperature geothermal environments(4164-4166).

Susan K. McLaughlin (US), Peter J. McKinnon (US), and Robert F. Margolskee (US) discovered gustducin, a taste cell expressed G protein(4167). Their subsequent work has demonstrated that gustducin is critical to the transduction of compounds that humans consider bitter or sweet.

Siegfried Burggraf (DE), Gary J. Olsen (US), Karl O. Stetter (DE), Carl R. Woese (US), Gertrud Huber (DE), Elisabeth Drobner (DE), Harald Huber (DE), Robert Huber (DE), Thomas Wilharm (DE), Antonio Trincone (IT), Helmut König (DE), Reinhard Rachel (DE), Ingrid Rockinger (DE), and Hans Fricke (DE) discovered and characterized Aquifex pyrophilus as a deeply branching, eubacterial (Bacteria) hyperthermophile whose optimum environment is marine and near 85˚C, where it uses small amounts of oxygen to oxidize hydrogen(4168-4170).

Stephen George Oliver (GB), Quirina J.M. van der Aart (NL), Maria Luisa Agostoni-Carbone (IT), Michel Aigle (FR), Lilia Alberghina (IT), Despina Alexandraki (GR), G. Antoine (FR), R. Anwar (GB), Juan P. Garcia Ballesta (ES), P. Benit (FR), G. Berben (BE), E. Bergantino (IT), N. Biteau (IT), A. Bolle (BE), Monique Bolotin-Fukuhara (FR), Jean-Marie Buhler (FR), C. Carcano (IT), Giovanna Carignani (Italy), H. Cederberg (DE), R. Chanet (FR), Roland Contreras (BE), M. Crouzet (FR), Bertrand Daignan-Fornier (FR), E. Defoor (BE), M. Delgado (ES), J. Demolder (BE), C. Doira (FR), Edu Dubois (BE), Bernard Dujon (FR), A. Dusterhof (DE), D. Erdmann (DE), M. Esteban (ES), F. Fabre (FR), Cecile Fairhead (FR), G. Faye (FR), Horst Feldmann (DE), W. Fiers (BE), M.C. Francingues-Gaillard (FR), L. Franco (ES), L. Frontali (IT), Hiroshi Fukuhara (FR), L.J. Fuller (GB), P. Galland (Cretean), M.E. Gent (GB), D. Gigot (BE), V. Giliquet (BE), Nicolas Glansdorff (BE), Andre Goffeau (BE), M. Grenson (BE), P. Grisanti (IT), Les A. Grivell (NL), M. de Haan (NL), M. Haasemann (DE), D. Hatat (FR), J. Hoenicka (ES), J. Hegemann (DE), G.J. Herbert (FR), Francois Hilger (BE), S. Hohmann (DE), Cornelis P. Hollenberg (DE), K. Huse (DE), F. Iorra (FR), K.J. Indge (GB), K. Isono (Japan), Claude Jacq (FR), Michel Jacquet (FR), C.M. James (GB), Jean-Claude Jauniaux (BE), Y. Jia (FR), Antonio Jimenez (ES), A. Kelly (GB), U. Kleinhans(DE), P. Kreisl (DE), G. Lanfranchi (IT), C. Lewis (GB), C.G. van der Linden (NL), Giovanna Lucchini (IT), K. Lutzenkirchen (DE), M.J. Maat (NL), Laurent Mallet (FR), G. Mannhaupt (DE), E. Martegani (IT), A. Mathieu (FR), C.T.C. Maurer (NL), M. Muzi-Falconi (IT), David McConnell (GB), Andrew McKee (GB), Francine Messenguy (BE), H.W. Mewes (DE), F. Molemans (BE), M.A. Montague (GB), L. Navas (ES), Carol S. Newlon (US), D. Noone (GB), C. Pallier (FR), L. Panzeri (IT), B.M. Pearson (GB), J. Perea (FR), Peter Philippsen (DE), Andre Pierard (BE), Rudi J. Planta (NL), Paolo Plevani (IT), B. Poetsch (DE), F. Pohl (DE), Benedicte Purnelle (BE), Massoud Ramezani-Rad (DE), Soren W. Rasmussen (Dannish), Raynal (FR), M. Remacha (ES), P. Richterich (DE), A.B. Roberts (GB), F. Rodriguez (IT), E. Sanz (ES), I. Schaaff-Gerstenschlager (DE), B. Scherens (BE), B. Schweitzer (DE), Y. Shu (FR), J. Skala (BE), Piotr P. Slonimski (FR), Frederic Sor (FR), C. Soustelle (FR), R. Spiegelberg (DE), L.I. Stateva (GB), H. Yde Steensma (NL), S. Steiner (DE), A. Thierry (FR), Georges Thireos (Cretean), M. Tzermia (Cretean), L. Antonio Urrestarazu (BE), G. Valle (Italy), I. Vetter (DE), J.C. van Vliet-Reedij (NL), M. Voet (BE), Guido Volckaert (BE), P. Vreken (NL), H. Wang (GB), J.R. Warmington (GB), Dietter von Wettstein (Dannish), B.L. Wicksteed (GB), C. Wilson (IT), H. Wurst (DE), G. Xu (DE), A. Yoshikawa (JP), F.K. Zimmermann (DE), and John G. Sgouros (DE) determined the entire DNA sequence of chromosome III of the yeast Saccharomyces cerevisiae. This was the first complete sequence analysis of an entire chromosome from any organism(4171).

Michael J. Dawson (GB), J.E. Farthing (GB), P.S. Marshall (GB), R.F. Middleton (GB), M.J. O’Neill (GB), Alan Shuttleworth (GB), C. Stylli (GB), Robert M. Tait (GB), P.M. Taylor (GB), Howard G. Wildman (GB), Antony D. Buss (GB), D. Langley (GB), Michael V. Hayes (GB), P.J. Sidebottom (GB), R.M. Highcock (GB), S.J. Lane (GB), Panayiotis A. Procopiou (GB), N.S. Watson (GB), J.D. Bergstrom (GB), M.M. Kurtz (GB), D.J. Rew (GB), A.M. Amend (GB), J.D. Karkas (GB), R.G. Bostedor (GB), V.S. Bansal (GB), C. Dufresne (GB), F.L. Van Middlesworth (GB), O.D. Hensens (GB), J.M. Liesch (GB), D.L. Zink (GB), K.E. Wilson (GB), J. Onishi (GB), J.A. Milligan (GB), G. Bills (GB), L. Kaplan (GB), M. Nallin Omstead (GB), R.G. Jenkins (GB), L. Huang (GB), M.S. Meinz (GB), L. Quinn (GB), R.W. Burg (GB), Y.L. Kong (GB), S. Mochales (GB), M. Mojena (GB), I. Martin (GB), F. Pelaez (GB), M.T. Diez (GB), and A.W. Alberts (GB) announced the discovery of a new class of natural products they found in two different fungi. Each research group gave the family a different name—squalestatins and zaragozic acids respectively(4172-4174).

Allan Baxter (GB), Belinda J. Fitzgerald (GB), Julie L. Hutson (GB), Alun D. McCarthy (GB), Joanne M. Motteram (GB), Barry C. Ross (GB), Meenu Sapra (GB), Michael A. Snowden (GB), Nigel S. Watson (GB), Robert J. Williams (GB), and Carolyn Wright (GB) discovered that zaragozic acid A (squalestatin S1) has a very high affinity for squalene synthase and could lower serum cholesterol levels in the marmoset(4175).

Kyriacos Costa Nicolaou (CY-US), Alan Nadin (US), James E. Leresche (US), Susan La Greca (US), Tatsuo Tsuri (US), Eddy W. Yue (US), Zhen Yang (US), Yoshimitsu Naniwa (US), and Francesco De Riccardis (US) carried out the total synthesis of zaragozic acid A, a potent reducer of serum cholesterol(4176-4179).

Xing-Wang Deng (CN-US), Minami Matsui (JP), Ning Wei (US), Daniel S. Wagner (US), Angela M. Chu (US), Kenneth A. Feldmann (US), Peter H. Quail (US), and Brian P. Dilkes (US) pioneered the development of T-DNA-tagged Arabidopsis mutant populations(4180, 4181). This resource led to many important discoveries such as cloning of the first Arabidopsis homeotic gene (AG), important in flower development, and the first photomorphogenetic gene (COP1).

Francois Rousset (FR), Didier Bouchon (FR), Bernard Pintureau (FR), Pierre Juchault (FR), and Michel Solignac (FR) found that the pill bug, Armadillidium vulgare, frequently associates with bacteria of the genus Wolbachia as a symbiont. These bacterial symbionts convert all hosts to females if they are not already females. The bacterium is passed from one generation of pill bug to the next by the transovarian route(4182). 

Duncan A. Veal (AU), Joseph E. Trimble (AU), and Andrew J. Beattie (AU) discovered that bull ants, Myrmecia gulosa, possess a gland on the dorsal aspect of the thorax which contains potent antibiotics(4183).

Hugh S. Mason (US), Dominic M. Lam (US), and Charles J. Arntzen (US) genetically transformed tobacco plants with the gene encoding hepatitis B surface antigen (HBsAg) and concluded that transgenic plants hold promise as low-cost vaccine production systems(4184).

Tariq A. Haq (US), Hugh S. Mason (US), John D. Clements (US), and Charles J. Arntzen (US) orally immunized mice with potato tubers transgenic for Escherichia coli heat-labile enterotoxin (LT-B)(4185).

Carol O. Tacket (US), Hugh S. Mason (US), Genevieve Losonsky (US), John D. Clements (US), Myron M. Levine (US), and Charles J. Arntzen (US) demonstrated immunogenicity in humans for a recombinant bacterial antigen delivered orally in a transgenic potato(4186).

Gregory M. Preston (US), Tiziana Piazza Carroll (US), William B. Guggino (US), and Peter Agre (US) developed a striking assay for a water channel gene. He prepared synthetic mRNA from the previously unknown cDNA, injected it into Xenopus laevis oocytes, and then watched them swell and rupture(4187).

The discovery of a new species of the cholera bacteria (O139) in Bangladesh. It has since been detected in 11 countries raising the possibility of future pandemics. ref

Jeff M. Hall (US), Lori S. Friedman (US), C. Guenther (US), Ming K. Lee (US), James L. Weber (US), Donald M. Black (GB), and Mary-Claire King (US) found linkage of early-onset familial breast and ovarian cancer to 11 markers on chromosome 17q12-q21 which defines an 8-cM region which is very likely to include the disease gene BRCA-1(4188).

Riitta Saario (FI), Rauli Leino (FI), Riitta Lahesmaa (FI), Kaisa Granfors (FI), Auli Toivanen (FI), Timo Yli-Kerttula (FI), Reijo Luukkainen (FI), Riitta Merilahti-Palo (FI), and Jouko Seppälä (FI) found that mild or inapparent infections of Yersinia enterocolitica may trigger autoimmune disorders such as thyroiditis and reactive arthritis, especially in individuals harboring the HLAB27 histocompatability allele(4189, 4190).

Wilfred Niels Arnold (US) presented evidence that Vincent van Gogh, the great Dutch painter, suffered from acute intermittent porphyria. This disease makes sufferers more sensitive to the neurotoxicity of absinthe (the active ingredient of absinthe is alpha-thujone)(4191).

Michael M. Davis (US), Philip M. McCabe (US), Neil Schneiderman (US), Theodore W. Jarrell (US), Christopher G. Gentile (US). Alan H. Teich (US), Ray W. Winters (US), and David R. Liskowsky (US) determined that the neural pathways involved in fear conditioning include sensory pathways transmitting the signal to the amygdala where specific internal connections ultimately project to motor systems. The amygdala is involved in fear conditioning regardless of the sensory modality of the conditioned stimulus and independent of which motor response is used(4192, 4193).

Olivier J. Goulet (FR), Yann Revillon (FR), Nicole Brousse (FR), Dominique Jan (FR), Danielle Canion (FR), Caroline Rambaud (FR), Nadine Cerf-Bensussan (FR), Christianne Buisson (FR), Philippe Hubert (FR), Sophie de Potter (FR), et al. performed the first successful small bowel transplantation in humans(4194).

Tsu-Ming Han (US) and Bruce N. Runnegar (AU-US) found fossils of the multicellular Grypania spiralis (probably an alga) in the 2.1 Ga Negaunee Iron Formation in Michigan, U.S.A(4195). Malcom R. Walter (US), Du Rulin (US), and Robert Joseph Horodyski (US) had previously discovered multicellular fossil (ca.1.4 Ga) in old Greyson Shale, lower Belt Supergroup, in Montana, US, and from the similarly aged Gaoyuzhuang Formation, upper Changcheng Group, in the Jixian section, Northern China. The organism was identified as Grypania spiralis, a coiled ribbon-like creature. It was judged to most likely have been a multicellular eukaryotic alga(4072). Shale is rock formed by condensation of layers of clay or mud, along with phytoplankton and other debris, sedimented at the bottoms of lakes or ocean basins.


“Very difficult decisions will have to be made if we are to have a sustainable human society in a sustainable environment. Many of those decisions will require extensive knowledge of biology. We have reached the point in history, therefore, when biological knowledge is the sine qua non for a viable human future.” John Alexander Moore(4196).

“To discover nature’s true order, the mind must be purified of all its internal obstacles, purged of its habitual tendencies to produce rational or imaginary wish fulfillments in advance of empirical investigation.” Richard Tarnas(4197).

"In science and elsewhere there are two types of truth: (1) The truth everyboby already knows, and (2) the truth that is not yet discovered.…The second type of truth is different. At first it looks to bizarre to be true, and it may be as dangerous as fire. If you are not clever it may destroy you." Benno Müller-Hill(4198).

All is Fair in Love and Warts 

 “He proclaimed she had given him warts

 Of the most ignominious sorts

 Said that her papilloma

 Had entered his soma

 And the issue was clearer than quartz 

 She denies having given him warts

 Says that "His allegation distorts.

 It's incredibly plain

 That they differ by strain

 As shown in my doctor's reports.

And despite his assertion of torts

 On the issue of giving him warts,

 She was quickly acquitted

 Of having transmitted

 (And upheld in the lowest of courts).” Robert D. Siegel, November 16, 1993

Kary Banks Mullis (US) for his invention of the polymerase chain reaction (PCR) method and Michael Smith (GB-CA) for his fundamental contributions to the establishment of oligonucleotide-based, site-directed mutagenesis and its development for protein studies shared the Nobel Prize in Chemistry.

Richard John Roberts (GB) and Phillip Allen Sharp (GB-US) were awarded the Nobel Prize in Physiology or Medicine for their independent discoveries of split genes.

Elias James Corey (US) and Yong-Jin Wu (US) carried out the total synthesis of paeoniflorigenin and paeoniflorin(4199).

Edward J. Weinman (US), Deborah Steplock (US), Shirish Shenolikar (US), and Yu Wang (US) discovered, purified, and characterized a molecule called sodium-hydrogen exchanger regulatory factor (NHERF) that binds to adrenergic receptors to begin the internal fight-or-flight signaling process(4200, 4201). Prior to this finding G-protein was the only molecule known to have this binding property. This is an entirely new signaling model for the cell's internal machinery.

Leu-Fen H. Lin (US), Daniel H. Doherty (US), Jack D. Lile (US), Susan Bektesh (US), and Frank Collins (US) were the first to isolate glial cell line-derived neurotrophic factor (GDNF). It functions as a survival and differentiation factor for midbrain dopaminergic neurons(4202).

Mary Sym (US), JoAnne Engebrecht (US), and G. Shirleen Roeder (US) proposed that ZIP1 is a novel meiosis-specific gene which acts as a molecular zipper to bring homologous chromosomes in close apposition in Saccharomyces cerevisiae(4203).

Michel Rohmer (FR), M’hamed Knani (FR), Pascale Simonin (FR), Bertrand Sutter (FR), and Hermann Sahm (FR) described the glyceraldehyde-3-phosphate (GAP)-pyruvate pathway to the production of isopentyl diphosphate (IPP). The IPP is synthesized by the condensation of pyruvate and glyceraldehyde-3-phosphate, via 1-deoxyxylulose-5-phosphate (DXP) as the first intermediate(4204). The isoprenoids are composed of repeating five-carbon, isopentenyl diphosphate (IPP) subunits.  Eubacterial hopanoids and plastid-associated isoprenoids of algae and higher plants are produced via this pathway.

Craig M. Thompson (US), Anthony J. Koleske (US), David M. Chao (US), and Richard A.  Young (US) defined the Saccharomyces cerevisiae Mediator complex in detail and provided evidence for its role in the regulation of transcription(4205). The Mediator complex appears in all eukaryotes. It is a protein complex physically associated with RNA polymerase II during transcription.

Edward M. Brown (US), Gerardo Gamba (MX), Daniela Riccardi (US), Michael Lombardi (US), Robert Butters (US), Olga Kifor (US), Adam Sun (US), Matthias A. Hediger (US), Jonathan Lytton (US), and Steven C. Hebert (US) reported the cloning of complementary DNA encoding an extracellular Ca(2+)-sensing receptor from bovine parathyroid with pharmacological and functional properties nearly identical to those of the native receptor(4206).

Carol Beadling (US), Kirk W. Johnson (US), and Kendall A. Smith (US) isolated interleukin 2-induced immediate-early genes(4207).

Ramsay Fuleihan (US), Narayanaswamy Ramesh (US), Richard Loh (US), Haifa Jabara (US), Fred S. Rosen (US), Talal Chatila (US), Shu Man Fu (US), Ivan Stamenkovic (US), and Raif S. Geha (US) obtained results suggesting that defective expression of the CD40 ligand underlies the failure of isotype switching in X chromosome-linked immunoglobulin deficiency disease(4208).

Paritosh Ghosh (US), Tse-Hua Tan (US), Nancy R. Rice (US), Antonio Sica (US), and Howard A. Young (US) found that the interleukin 2 CD28-responsive complex contains at least three members of the NF-kB family: c-Rel, p50, and p65(4209).

Steven E. Macatonia (US), Chyi-Song Hsieh (US), Kenneth M. Murphy (US), and Anna O'Garra (US) discovered that dendritic cells and macrophages are required for T-helper 1(Th1) development of CD4+ T cells. They also determined that interleukin 12 (IL-12) substitution for macrophages to stimulate IFN-gamma production is IFN-gamma-dependent(4210).

Patricia G. McCaffrey (US), Chun Luo (US), Tom K. Kerppola (US), Jugnu Jain (US), Tina M. Badalian (US), Andrew M. Ho (US), Emmanuel Burgeon (US), William S. Lane (US), John N. Lambert (US), Tom Curran (US), Gregory L. Verdine (US), Anjana Rao (US), and Patrick G. Hogan (US) purified NFATp from murine T cells and isolated a complementary DNA clone encoding NFATp(4211). Nuclear factor of activated T cells (NFAT) is a transcription factor that regulates expression of the cytokine interleukin-2 (IL-2) in activated T cells. The DNA-binding specificity of NFAT is conferred by NFATp, a phosphoprotein that is a target for the immunosuppressive compounds cyclosporin A and FK506.

Demetrius Moskophidis (CH), Franziska Lechner (CH), Hanspeter Pircher (CH), and Rolf M. Zinkernagel (CH) found that some strains of non-cytopathic lymphocytic choriomeningitis virus (LCMV) persist after acute infection because they induce most of the specific antiviral CD8+ cytotoxic T cells so completely that they all disappear within a few days and therefore neither eliminate the virus nor cause lethal immunopathology(4212).

Masayuki Noguchi (US), Huafang Yi (US), Howard M. Rosenblatt (US), Alexandra H. Filipovich (US), Stephen Adelstein (US), William S. Modi (US), O. Wesley McBride (US), and Warren J. Leonard (US) localized the IL-2R gamma gene to human chromosome Xql3. Genetic linkage analysis indicates that the IL-2R gamma gene and the locus for X-linked severe combined immunodeficiency (XSCID) appear to be at the same position. These data establish that XSCID is associated with mutations of the IL-2R gamma gene product(4213). The interleukin-2 (IL-2) receptor gamma chain (IL-2R gamma) is a component of high and intermediate affinity IL-2 receptors that is required to achieve full ligand binding affinity and internalization.

Julia M. Turner (GB) found that IL-2-dependent induction of G1 cyclins in primary T cells is not blocked by rapamycin or cyclosporin A. These observations suggest that cyclins D2 and D3 may monitor the interleukin 2 receptor (IL-2R) signal but that their induction does not guarantee entry into S phase(4214).

William R. Jacobs, Jr. (US), Raúl G. Barletta (US), Rupa A. Udani (US), John Chan (US), Gary Kalkut (US), Gabriel Sosne (US), Tobias Kieser (GB), Gary J. Sarkis (US), Graham F. Hatfull (GB-US), and Barry R. Bloom (US) developed luciferase reporter phages with which they could assess drug susceptibility based on the efficient production of photons by viable mycobacteria infected with specific reporter phages expressing the firefly luciferase gene. Cells killed by a drug would not emit light(4215).

Galina A. Dubinina (RU), Natalia V. Leshcheva (RU), and Margarita Yu Grabovich (RU) reported that the colorless sulfur bacterium Thiodendron is actually a symbiotic association of spirochetes and sulfidogens(4216, 4217).

Friedrich Widdel (DE), Sylvia Schnell (DE), Silke Heising (DE), Armin Ehrenreich (DE), Bernhard Assmus (DE), and Bernhard Schink (DE) discovered that ferrous ions may serve as the electron donors for certain purple nonsulfur phototrophs(4218). This provides an explanation for the banded iron oxide geological formations which were deposited when the earth's atmosphere was anoxic: anoxic phototrophs very likely did it.

Marc Stadler (DE), Timm Anke (DE), Johannes Dasenbrock (DE), and Wolfgang A. Steglich (DE) described a new hirsutane derivative, phellodonic acid (1), isolated from fermentations of Phellodon melaleucus strain 87113. Its structure was elucidated by spectroscopic methods. The compound exhibits antibiotic activities towards bacteria and fungi. It is the first bioactive metabolite from cultures of a species belonging to the family Thelephoraceae(4219).

Esther R. Angert (US), Kendall D. Clements (NZ), and Norman Richard Pace, Jr. (US) isolated the largest (600 microns by 80 microns) bacterium to be described so far. It is the morphologically peculiar microorganism Epulopiscium fishelsoni which inhabits the intestinal tract of Acanthurus nigrofuscus, a brown surgeonfish (family Acanthuridae), from the Red Sea. Similar microorganisms have been found in surgeonfish species from the Great Barrier Reef. They are considered to be specific symbionts of surgeonfish, although the nature of the symbiosis is unclear(4220).

Esther R. Angert, (US), Austin E. Brooks (US), and Norman Richard Pace, Jr. (US) presented ribosomal RNA (rRNA) phylogenetic evidence placing this organism nearest the cellulolytic Clostridia(4221).

Vincent Falanga (US) and Robert S. Kirsner (US) were the first to obtain vigorous growth and multiplication of isolated single euploid animal cells. They did this by reducing the oxygen tension from the usual 20% down to 2%(4222).

René H. Medema (NL) and Johannes L. Bos (NL) found that Ras proteins are present in structurally altered forms that enable them to release a flux of mitogenic signals into cells, without ongoing stimulation by their normal upstream regulators(4223).

Douglas Hanahan (US) and Robert Allan Weinberg (US) suspect that growth signaling pathways suffer deregulation in all human tumors(1738).

Lee W. Janson (US) and D. Lansing Taylor (US) proposed that amoeboid motion can be explained by contraction of the cortical gel in mid-regions and near the rear of an advancing amoeba(4224).

Julie R. Pear (US), Rick A. Sanders (US), Kristin R. Summerfelt (US), Belinda Martineau (US), and William Hiatt (US) produced the first genetically engineered vegetables to reach the market. They were tomatoes in which the action of polygalacturonase (PG), a pectinase contributing to normal ripening, was blocked by the insertion of an antisense gene(4225).

Kenichi Higo (JP), Yusuke Saito (JP), and Hiromi Higo (JP) created transgenic tobacco plants capable of producing epidermal growth factor; a mitogen(4226).

Cynthia J. Kenyon (US), Jean Chang (US), Erin Gensch (US), Adam Rudner (US), Ramon Tabtiang (US), Kui Lin (CN), Jennie B. Dorman (US), and Aylin Rodan (US) found mutants of the hermaphroditic nematode Caenorhabditis elegans with reduced activity of the gene daf-2, a homolog of the insulin and insulin-like growth factor receptors, which live more than twice as long as wild-type. These mutants are active and fully fertile and have normal metabolic rates. The life-span extension caused by daf-2 mutations requires the activity of the gene daf-16. daf-16 appears to play a unique role in life-span regulation and encodes a member of the hepatocyte nuclear factor 3(HNF-3)/forkhead family of transcriptional regulators(4227, 4228).

Honor Hsin (US) and Cynthia J. Kenyon (US) demonstrated that signals from the reproductive system influence the lifespan of the nematode Caenorhabditis elegans. This study demonstrates an inherent relationship between the reproductive state of this animal and its lifespan, and may have implications for the co-evolution of reproductive capability and longevity(4229).

Claude Lévi (FR) introduced the use of reproductive characters for the higher classification of Demosponges(4230, 4231). He is commemorated by Acarnus claudei Van Soest et al., 1991; Acarnus levii Vacelet, 1960; Diacarnus levii Kelly-Borges & Vacelet, 1995; Levinella Borojevic & Boury-Esnault, 1986; Levinellidae Borojevic & Boury-Esnault, 1986; Microciona levii Sarà & Siribelli, 1960; Paresperella levii Uriz, 1989; Tethya levii Sarà, 1988; Lekanesphaera levii Argano & Ponticelli, 1981; and Seguenzia levii B.A. Marshall, 1991.

James C. Smith (GB) discovered mesoderm inducing factors in Xenopus embryos(4232).

John A. Eisman (AU), Paul J. Kelly (AU), Nigel A. Morrison (AU), Nicholas A. Pocock (AU), Rosanna Yeoman (AU), Joan Birmingham (AU), and Philip N. Sambrook (AU) found that the vitamin D receptor is associated with a variability in susceptibility to osteoporosis(4233).

The landmark national collaborative study called the DCCT (Diabetes Control and Complications Trial) was published. The DCCT conclusively demonstrated the value of tight glucose control in type 1 diabetes. The study clearly revealed that better control leads to better outcomes(4234).

David M. Danks (AU) located the gene for Huntington’s disease on the short arm of chromosome number 4(4235).

Huntington's Disease Collaborative Research Group (US), Huntington G. Willard (US), Russell G. Snell (GB), John C. MacMillan (GB), Jeremy P. Cheadle (GB), Iain Fenton (GB), Lazarus P. Lazarou (GB), Peter Davies (GB), Marcy E. MacDonald (US), James F. Gusella (US), Peter S. Harper (GB), Duncan J. Shaw (GB), Anne Norremolle (DK), Olaf Riess (DK), Jörg T. Epplen (DK), Kristen Fenger (DK), Liz Hasholt (DK), and Sven A. Sorensen (DK) found that near the middle of the gene associated with Huntington’s disease the trinucleotide CAG is repeated 9-34 times in the normal allele and 30-70 times in the disease allele(4236-4239). The Danish group determined that the normal allele produces a protein called Huntingtin.

Akitada Ichinose (JP) and Earl W. Davie (US) reported the complete amino acid sequences of all the known blood coagulation factors and the DNA sequences coding for the genes for all the clotting factors(4240).

Elaine Tuomanen (US) found that the agent of whooping cough, Bordetella pertussis, fools the body’s defense mechanisms by producing a chemical signal which interferes with the ability of patrolling white blood cells to recognize the address at their destination. (see Tuomanen, 1988) (4241). This chemical might be useful as a highly selective anti-inflammatory agent to treat inflammation in the brain, joints, eyes and other sites where the surrounding tissues must be protected from the immune system as well as from invaders.

Alan T. Hudson (GB) reported that atovaquone, a member of the hydroxynaphthoquinone family, is an outstanding antimalarial drug(4242).

Yael Katz-Levy (IL), Susan L. Kirshner (IL), Michael Sela (IL), and Edna Mozes (IL) synthesized two immunodominant myasthenogenic T cell epitopes (p195–212 and p259–271) derived from an alpha-subunit of the nicotinic acetylcholine receptor (AchR)(4243).

Miri Paas-Rozner (IL), Molly Dayan (IL), Yoav Paas (FR), Jean-Pierre Changeux (FR), Itzhak Wirguin (IL), Michael Sela (IL), and Edna Mozes (IL) found that when administered orally, the dual analog (p195–212 and p259–271) could treat experimental allergic myasthenia gravis (EAMG) induced in mice by immunization with the multideterminant native Torpedo AChR (TACHR)(4244). Torpedo is a genus of electric ray fishes.

Maria Victoria Valero (CO), Luis Roberto Amador (CO), Claudia Galindo (CO), Jorge Figueroa (CO), Mary Stella Bello (CO), Luis Angel Murillo (CO), Ana Lucia Mora (CO), Gloria Patarroyo (CO), Claudia Lucia Rocha (CO), Mauricio Rojas (CO), John Jairo Aponte (CO), Luis Eduardo Sarmlento (CO), Diana M. Lozada (CO), Carlos Gustavo Coronell (CO), Norella M. Ortega (CO), Jaiver E. Rosas (CO), Manuel Elkin Patarroyo (CO), and Pedro Luis Alonso (ES) reported on the first successful large scale malaria vaccine trial in South America(4245).

Richard J. Cristiano (US), Louis C. Smith (US), Mark A. Kay (US), William R. Brinkley (US), Savio L.C. Woo (US), Steven Rothenberg (US), Charles N. Landen (US), Dwight A. Bellinger (US), Francis Leland (US), Carol Toman (US), Milton Finegold (US), Arthur R. Thompson (US), Marjorie S. Read (US), and Kenneth M. Brinkhous (US) announced that gene therapy in dogs with hemophilia B has provided short-term relief from bleeding, an important first step toward a permanent cure(4246-4248).

Jeffrey B. Ulmer (US), John J. Donnelly (US), Suezanne E. Parker (US), Gary H. Rhodes (US), Philip L. Felgner (US), Varavani J. Dwarki (US), Stanisiaw H. Gromkowski (US), R. Randall Deck (US), Corrille M. DeWitt (US), Arthur Friedman (US), Linda A. Hawe (US), Karen R. Leander (US), Douglas Martinez (US), Helen C. Perry (US), John W. Shiver (US), Donna L. Montgomery (US),  and Margaret A. Liu (US) were among the first to successfully vaccinate animals with plasmid DNA encoding a specific gene, in their case influenza A nucleoprotein. They generated nucleoprotein-specific cytotoxic T lymphocytes and protection from a subsequent challenge with a heterologous strain of influenza A virus(4249). This technology is now being used to generate immunity to a host of antigens, from malaria to cancer.

Scott W. Lowe (US), H. Earl Ruley (US), Tyler E. Jacks (US), and David E. Housman (US) proposed that the cytotoxic action of many anticancer agents involves processes subsequent to the interaction between drug and cellular target and indicate that divergent stimuli can activate a common cell death program, i.e., the production of p53. Consequently, the involvement of p53 in the apoptotic response suggests a mechanism whereby tumor cells can acquire cross-resistance to anticancer agents(4250).

Georg Gosztonyi (DE) Bernhard Dietzschold (US), Moujahed Kao (DE), Charles E. Rupprecht (US), and Hilary Koprowski (US) determined that during rabies viral antigens are almost exclusively found on neurons(4251).

Jeffrey Travis (US), Digamber S. Borgaonkar (IN-US), L.C. Schmidt (US), S. Eric Martin (US), Michael D. Kanzer (US), Lanny Edelsohn (US), John H. Growden (US), and Lindsay A. Farrer (US) found a linkage of late-onset Alzheimer's disease with apolipoprotein E type 4 on chromosome 19(4252, 4253).

Antonio Torroni (IT), Rem I. Sukernik (RU) , Yelena B. Starikovskaya (RU), Margaret F. Cabell (US), Michael H. Crawford (US), Anthony G. Comuzzie (US), James van Gundia Neel (US), Ramiro Barrantes (CR), Theodore G. Schurr (US) and Douglas C. Wallace (US) compared several DNA markers found in modern Native Americans and modern Siberians and estimated that if the Amerindians entered the New World as a single group, that entry would have occurred approximately 20,000-27,000 B.C.E.(4254, 4255).

Johanna Nichols (US) argues that the diversity of languages among Native Americans could have arisen only after humans had been in the New World for at least 20,000-30,000 years(4256).


Alfred Goodman Gilman (US) and Martin Rodbell (US) were awarded the Nobel Prize in Physiology or Medicine for their discovery of G-proteins and the role of these proteins in signal transduction in cells.

Kenneth M. Towe (US) made a compelling case for Earth’s early atmosphere to have contained significant quantities of oxygen(4257).

Kyriacos Costa Nicolaou (CY-US), Zhen Yang (US), Jin-Jun Liu (US), Hiroski Ueno (US), Philippe G. Nantermet (US), Rodney Kiplin Guy (US), Christopher F. Claiborne (US), Johanne Renaud (GR), Elias A. Couladouros (GR), Kumarapandian Paulvannan (US), and Erik J. Sorensen (US) carried out the total synthesis of taxol, an anticancer agent(4258, 4259).

The Environmental Protection Agency (EPA) of The United States government compiled a Public Review Draft of its Dioxin Reassessment. It covers dioxin, dioxin-like PCBs and furans. The report concludes that these chemicals cause harm at levels similar to those seen in the general public. In addition to cancer, potential damage is seen to the immune, nervous and reproductive systems. This report was not released due to pressure from the chemical industry(4260).

Daniel Picot (FR), Patrick J. Loll (US), and R. Michael Garavito (US) presented the x-ray crystal structure of the membrane protein prostaglandin H2 synthase-1(4261). 

Aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) like ibuprofen and indomethacin work by inhibiting prostaglandin H2 synthase that produces prostaglandins—hormone-like messenger molecules that trigger many processes in the body, including inflammation. 

Patrick J. Loll (US), Daniel Picot (FR), R. Michael Garavito (US) reported that aspirin splits into two parts and affixes one part to prostaglandin H2 synthase-1, permanently altering its chemical structure and blocking the reaction that produces prostaglandins(4262). Aspirin is the only NSAID known to work in this manner.

Antonio Lazcano (MX) theorizes that DNA evolved to replace RNA as the repository of hereditary information because, 1) DNA is much more resistant to harsh environmental conditions, 2) DNA is less prone to mutations which cannot be repaired, 3) cytosines in DNA are not as prone to spontaneously deaminate to uracil as they are in RNA, and 4) the duplex nature of DNA offered redundancy, which when coupled with repair mechanisms had a distinct advantage over simplex RNA without a repair mechanism(4263).

Saulius Klimasauskas (LT), Sanjay Kumar (US), Richard J. Roberts (US), and Xiaodong Cheng (US) found that HhaI methyltransferase flips its target base out of the DNA helix thus exposing it for methylation(4264).

R. Pat Bucy (US), Angela Panoskaltsis-Mortari (US), Guo-qiang Huang (US), Jimin Li (US), Laurel Karr (US), Martha Ross (US), John H. Russell (US), Kenneth M. Murphy (US), and Casey T. Weaver (US) discovered heterogeneity of single cell cytokine gene expression in clonal T cell populations(4265).

Jack D. Burton (US), Richard N. Bamford (US), Christian Peters (US), Angus J. Grant (US), Gloria Kurys (US), Carolyn K. Goldman (US), Jennifer Brennan (US), Erich Roessler (US), and Thomas A. Waldmann (US) discovered a lymphokine, provisionally designated interleukin T (IL-T), which stimulates T cell proliferation and the induction of lymphokine-activated killer cells(4266).

Michael J. Elliott (GB), Ravinder N. Maini (GB), Marc Feldmann (GB), Alice Long-Fox (GB), Peter Charles (GB), Hanny Bijl (GB), and James N. Woody (GB) reported that a chimeric monoclonal antibody to tumor necrosis factor alpha (cA2) may be useful therapy in the control of acute disease flares in rheumatoid arthritis and treatment programs including cA2 may be effective in the long term treatment of this disease(4267).

Paul A. Garrity (US), Dan Chen (US), Ellen V. Rothenberg (US), and Barbara J. Wold (US) found that interleukin-2 transcription is regulated in vivo at the level of coordinated binding of both constitutive and regulated factors(4268).

Kenneth H. Grabstein (US), June Eisenman (US), Kurt Shanebeck (US), Charles Rauch (US), Subhashini Srinivasan (US), Victor Fung (US), Courtney Beers (US), Jane Richardson (US), Michael A. Schoenborn (US), Minoo Ahdieh (US), Lisabeth Johnson (US), Mark R. Alderson (US), James Dewey Watson (US), Dirk M. Anderson (US), and Judith G. Giri (US) cloned a T cell growth factor (IL-15) that interacts with the beta chain of the interleukin-2 receptor(4269).

Larry L. Green (US), Margaret C. Hardy (US), Catherine E. Maynard-Currie (US), Hirohisa Tsuda (US), Donna M. Louie (US), Michael J. Mendez (US), Hadi Abderrahim (US), Masato Noguchi (US), Douglas H. Smith (US), Yongjun Zeng (US), Nathaniel E. David (US), Hitoshi Sasai (US), Dan Garza (US), Daniel G. Brenner (US), Joanna F. Hales (US), Ryan P. McGuinness (US), Daniel J. Capon (US), Sue Klapholz (US), and Aya Jakobovits (US) engineered antigen-specific human monoclonal antibodies from mice using human Ig heavy and light chain yeast artificial chromosomes (YACS)(4270).

James A. Johnston (US), Masaru Kawamura (US), Robert A. Kirken (US), Yi-Qing Chen (US), Trevor B. Blake (US), Kyoichi Shibuya (US), John R. Ortaldo (US), Daniel W. McVicar (US), and John J. O'Shea (US) reported that a new member of the Janus family of kinases (JAK-3) is coupled to the interleukin 2 receptor (IL-2R) in human peripheral blood T cells and natural killer cells. Interaction with interleukin 2 (IL-2) leads to the phosphorylation and activation of JAK-3(4271).

Jamison Nourse (US), Eduardo Firpo (US), W. Michael Flanagan (US), Steve Coats (US), Kornella Polyak (US), Mong-Hong Lee (US), Josan Massague (US), Gerald R. Crabtree (US), and James M. Roberts (US) reported that interleukin 2 (IL-2) allows cyclin-dependent kinase (Cdk) activation by causing the elimination of the Cdk inhibitor protein p27klp1 and that this is prevented by rapamycin(4272).

Nikolaus Romani (AT), Stefan Gruner (DE), Daniela Brang (AT), Eckhart Kampgen (DE), Angela Lenz (AT), Bettina Trockenbacher (AT), Günther Konwalinka (AT), Peter O. Fritsch (AT), Ralph M. Steinman (US), and Gerold Schuler (AT) found that large numbers of dendritic cells can be mobilized by specific cytokines from progenitors in the blood stream(4273).

Federica Sallusto (IT-CH) and Antonio Lanzavecchis (CH) found that efficient presentation of soluble antigen by cultured human dendritic cells is maintained by granulocyte/macrophage colony-stimulating factor plus interleukin 4 and downregulated by tumor necrosis factor alpha(4274).

Diana L. Sylvestre (US), and Jeffrey V. Ravetch (US) found a murine strain deficient in Fc receptor expression could respond normally to other stimuli yet their inflammatory response to immune complexes was markedly attenuated. These results suggest that immune complex-triggered inflammation is initiated by cell bound Fc receptors and is then amplified by cellular mediators and activated complement(4275). 

Karl O. Stetter (DE) concluded that the origin of life probably took place under conditions of high temperature because the hyperthermophiles are grouped around and occupy all of the deepest branches of the three kingdom phylogenetic scheme. He also concluded that an anaerobic hyperthermophilic autotroph was very likely the original cell type(4276).

Mitchell Lloyd Sogin (US) declared that some microbial lineages seem never to have had mitochondria and chloroplasts, so may have diverged from the eukaryotic (Eucarya) line of descent prior to the incorporation of these organelles(4277).

Howard Ochman (US) and Eduardo A. Groisman (US) used multilocus electrophoresis and nucleotide sequence analysis to reevaluate the phylogenetic relationships within the genus Salmonella. Two species, Salmonella bongeri and Salmonella enterica emerged(4278, 4279). S. enterica has been further divided into subspecies designated by Roman numerals. S. enterica I is isolated almost exclusively from warm-blooded animals and is by far the most common clinical isolate. Among the S. enterica I, certain subtypes, like Typhi and Pullorum, show a remarkable host species preference (for humans and fowl, respectively). The other S. enterica subspecies and S. bongeri are isolated mainly from cold-blooded animals.

Bradley D. Jones (US), Nafisa Ghori (US), and Stanley Falkow (US) determined that Salmonella typhimurium initiates murine infection by penetrating and destroying the specialized epithelial M cells of the Peyer's patches(4280).

An outbreak of cholera occured within Rwandan refugee camps in the Democratic Republic of the Congo killing tens of thousands. ref

Stephen A. Wharton (GB), Robert B. Belshe (US), John J. Skehel (GB), and Alan J. Hay (GB) discovered the first virus ion channel(4281). The M2 protein enables hydrogen ions to enter the viral particle lowering the pH inside of the virus, thus causing dissociation of the viral matrix protein M1 from the ribonucleoprotein RNP. This is a necessary step in uncoating of the virus and exposing its content to the cytoplasm of the host cell.

Ken R. Schneider (US), Rebecca L. Smith (US), and Erin K. O'Shea (US) identified Pho81 as a cyclin kinase inhibitor (CKI) in Saccharomyces cerevisiae(4282). CKIs modulate cyclin-dependent kinases (CDKs) which regulate two important cell cycle transitions, from G1 to S phase and G2 to M phase.

Akio Toh-e (JP), Yoshinami Ueda (JP), Sei-Ichiro Kakimoto (JP), and Yasuji Oshima (JP) had earlier identified Pho81 as a genetic entity involved in the regulation of phosphate, however, they did not recognize it as a CKI(4283).

Christine Guthrie (US) presented circumstantial evidence that the splicesome is, at least in part, a ribozyme(4284). 

Werner Kühlbrandt (DE), Da Neng Wang (DE), and Yoshinori Fujiyoshi (JP) determined the atomic level structure of the largest antenna of photosystem 2, the light-harvesting complex II b(4285).

Geery McDermott (GB), Steve M. Prince (GB), Andy A. Freer (GB), Anna M. Hawthornthwaite-Lawless (GB), Miroslav Z. Papiz (GB), Robert J. Cogdell (GB), Neil W. Isaacs (GB), Thomas Walz (CH), and Robin Ghosh (CH) have provided the atomic level structures of two light-harvesting antenna complexes of anoxygenic photosynthetic bacteria(4286, 4287).

Eckhard Hofmann (DE), Pamela M. Wrench (AU), Frank P. Sharples (AU), Roger G. Hiller (AU), Wolfram Welte (DE), and Kay Dietrichs (DE) have provided the atomic level structure of the peridinin-chlorophyll protein complex of the dinoflagellate Amphidinium carterae(4288).

Ralf Kölling (DE) and Cornelis P. Hollenberg (DE) found in yeast cells that membrane protein Ste6 is mainly associated with internal membranes and not with the cell surface. Ste6 is localized in the Golgi. The Ste6 protein is in contact with the cell surface, as demonstrated by the finding that Ste6 accumulates in the plasma membrane in endocytosis mutants. The Ste6 protein which accumulates in the plasma membrane in endocytosis mutants is ubiquitinated(4289). The Ste6 protein is a member of the ABC-transporter family and is required for the secretion of the yeast mating pheromone a-factor.

Etienne Schwob (AT), Thomas Böhm (AT), Michael D. Mendenhall (US), and Kim Nasmyth (GB-AT-GB) found that in Saccharomyces cerevisiae DNA replication requires activation of Cdc28 protein kinase by B-type (Clb) cyclins. A sextuple clb1-6 mutant arrests as multibudded G1 cells that resemble cells lacking the Cdc34 ubiquitin-conjugating enzyme. cdc34 mutants cannot enter S phase because they fail to destroy p40SIC1, which is a potent inhibitor of Clb but not Cln forms of the Cdc28 kinase. In wild-type cells, p40SIC1 protein appears at the end of mitosis and disappears shortly before S phase. Proteolysis of a cyclin-specific inhibitor of Cdc28 is therefore an essential aspect of the G1 to S phase transition(4290).

Zhen Zhu (CN), Karen W. Hughes (US), Leaf Huang (CN-US), Baolin Sun (CN), Chunming Lui (CN), Yuing Li (CN), Yunde Hou (CN) and Xianghui Li (CN) produced transgenic rice plants capable of manufacturing alpha-interferon which has potential use for viral protection and as an anti-cancer agent(4291).

D. Bosch (), J. Smal (), and E. Krebber () created transgenic tobacco plants which could produce trout growth factor; a mitogen(4292).

Jerry C.P. Yin (US), Jonathan S. Wallach (US), Maria Del Vecchio (US), Elizabeth L. Wilder (US), Hong Zhou (US), William G. Quinn (US), and Tim Tully (US) obtained results suggesting that long term memory formation in Drosophila requires de novo gene expression; probably mediated by CREB family genes(4293, 4294). CREB (cAMP response element-binding protein) is a cellular transcription factor. It binds to certain DNA sequences called cAMP response elements(CRE), thereby increasing or decreasing the transcription of the downstream genes.

Yiying Zhang (CN-US), Ricardo Proenca (US), Margherita Maffei (US), Marisa Barone (US), Lori Leopold (US), and Jeffrey M. Friedman (US) cloned and characterized the ob gene from mice. They confirmed that it encodes a novel adipocyte-derived hormone which they named leptin (Gr. leptos, thin)(4295). The wild-type obese allele is necessary for the production of leptin. The wild-type allele at another locus diabetes is necessary to produce a receptor for leptin.

Margherita Maffei (US), Hon Fei (US), Gwo-Hwa Lee (US), Christian Dani (US), Pascale Leroy (US), Yiying Zhang (CN-US), Ricardo Proenca (US), Raymond Negrel (US), Gérard Ailhaud (FR), and Jeffrey M. Friedman (US) studied the action of leptin and found that body fat content is regulated by a negative feedback loop centered in the hypothalamus and elsewhere. They suggested that weight is regulated by a set point mechanism and that weight is set at different levels among different individuals. When at the set point, a state of energy balance in which food intake equals energy expenditure is maintained. Increasing adipose tissue mass leads to an increase in the production of leptin(4296).

Margherita Maffei (US), Jeffrey L. Halaas (US), Eric Ravussin (US), Richard E. Pratley (US), Gwo-Hwa Lee (US), Yiying Zhang (CN-US), Hon Fei (US), Sharon Kim (US), Roger L. Lallone (US), Subramanian Ranganathan (CA), Philip A. Kern (US), and Jeffrey M. Friedman (US) found that the plasma level of leptin is highly correlated with adipose mass and falls in both humans and mice after weight loss(4297).

Rebecca Quiring (CH), Uwe Walldorf (CH), Urs Kloter (CH), and Walter Jakob Gehring (CH) took the gene that controls development of the mouse’s eye and inserted it into the larva of a fruit fly. The mouse-eye gene not only made a viable eye in the fruit fly, it made a fly’s eye(4298).

Walter Jakob Gehring (CH) reported that eyeless (Pax-6) is the master control gene for eye morphogenesis. The finding of Pax-6 from flatworms to humans suggests that eyeless is a universal master control gene and that the various types of eyes in the various animal phyla may have evolved from a single prototype(4299).

Pascal Bailly (FR), Patricia Hermand (FR), Isabelle Callebaut (FR), Hans H. Sonneborn (FR), Samir Khamlichi (FR), Jean-Paul Mornon (FR), and Jean-Pierre Cartron (FR) cloned the human LW (Landsteiner-Wiener) blood group genes and found their glycoprotein products to be homologous to intercellular adhesion molecules(4300).

Barbara L. Smith (US), Gregory M. Preston (US), Frances A. Spring (US), David J. Anstee (US), and Peter Agre (US) found that the Colton blood group antigens are located on the water channel protein, Aquaporin(4301).

Peter Agre (US) would be awarded the 2003 Nobel Prize in Chemistry for his discovery of water channels.

Dominic A. Fantozzi (US), Alec T. Harootunian (US), Wei Wen (US), Susan S. Taylor (US), James R. Feramisco (US), Roger Y. Tsien (US), and Judy L. Meinkoth (US) demonstrated that a very small sequence of amino acids embedded in protein kinase inhibitor (PKI) constitutes a signal that instructs the catalytic (C) subunit to leave the cell nucleus and move out into the cytoplasm, where it becomes available for binding to a regulatory (R) subunit(4302). This nuclear export signal (NES) is the first such signal identified.

Peter J. Svensson (SE) and Björn Dahlbäck (SE) discovered an autosomal dominant hereditary condition in which venous thrombosis results because of resistance to anticoagulant activated protein C (APC). The condition is due to a deficiency in a previously unrecognized anticoagulant factor that functions as a cofactor to activated protein C(4303).

Richard Wooster (GB), Susan L. Neuhausen (US), Jonathan Mangion (GB), Yvette Quirk (GB), Deborah Ford (GB), Nadine Collins (GB), Kim Nguyen (US), Sheila Seal (GB), Thao Tran (US), and David B. Averill (US) localized a second breast cancer susceptibility locus, BRCA2, to chromosome 13q12-13. Preliminary evidence suggests that BRCA2 confers a high risk of breast cancer but, unlike BRCA1, does not confer a substantially elevated risk of ovarian cancer(4304).

Rita Shiang (US), Leslie M. Thompson (US), Ya-Zhen Zhu (US), Deanna M. Church (US), Thomas J. Fielder (US), Maureen Bocian (US), Sara T. Winokur (US), and John J. Wasmuth (US) found that achondroplasia (ACH), the most common genetic form of dwarfism, is caused by alteration of the normal gene localized to 4p16.3. The ACH candidate region includes the gene encoding fibroblast growth factor receptor 3 (FGFR3)(4305).

Mitsuharu Hattori (JP), Hideki Adachi (JP), Masafumi Tsujimoto (JP), Hiroyuki Arai (JP), and Keizo Inoue (JP) found that the gene for the Miller-Dieker form of lissencephaly encodes a subunit of the heteromeric platelet-activating factor, paf(4306). Paf affects neuronal growth cone morphology.

Alexander Sasha Kamb (US) pointed out the role of a cell cycle regulator (CDKN2A ) in hereditary and sporadic cancer(4307).

S. Blair Hedges (US) analyzed DNA sequences from four slow-evolving genes (mitochondrial 12S and 16S rRNA, tRNAVal, and nuclear alpha-enolase) and found strong statistical support for a bird-crocodilian evolutionary relationship(4308).

Henry A. Feldman (US), Irwin Goldstein (US), Dimitrios G. Hatzichristou (US), Robert J. Krane (US), and John B. McKinlay (US) provided normative data on the prevalence of impotence, and its physiological and psychosocial correlates in a general population using results from the Massachusetts Male Aging Study. Blood samples, physiological measures, socio-demographic variables, psychological indexes, and information on health status, medications, smoking and lifestyle were collected by trained interviewers in the subject's home. A self-administered sexual activity questionnaire was used to characterize erectile potency. The combined prevalence of minimal, moderate and complete impotence was 52%. The prevalence of complete impotence tripled from 5 to 15% between subject ages 40 and 70 years. Subject age was the variable most strongly associated with impotence. After adjustment for age, a higher probability of impotence was directly correlated with heart disease, hypertension, diabetes, associated medications, and indexes of anger and depression, and inversely correlated with serum dehydroepiandrosterone, high density lipoprotein cholesterol and an index of dominant personality. Cigarette smoking was associated with a greater probability of complete impotence in men with heart disease and hypertension. They concluded that impotence is a major health concern in light of the high prevalence, is strongly associated with age, has multiple determinants, including some risk factors for vascular disease, and may be due partly to modifiable para-aging phenomena(4309).

Tim D. White (US), Gen Suwa (Ethiopian), and Berhane Asfaw (Ethiopian) discovered hominid fossil remains of Ardipithecus ramidus at Aramis in Ethiopia dated at 4.4 million years. Most remains are skull fragments. Indirect evidence suggests that it was possibly bipedal, and that some individuals were about 122 cm (4'0") tall(4310, 4311).

Yohannes Haile-Selassie (US) reported new hominid specimens from the Middle Awash area of Ethiopia that date to 5.2-5.8 Myr and are associated with a wooded palaeoenvironment. These Late Miocene fossils are assigned to the hominid genus Ardipithecus and represent the earliest definitive evidence of the hominid clade(4312).

Hagen Hass (DE), Thomas N. Taylor (US), Winfried Remy (PL-DE), and Hans Kerp (DE) found fossil hyphae in association with wood decay and fossil chytrids and Glomales-Endogenales representatives associated with plants of the Rhynie Chert from the Devonian Period (408-360 Ma)(4313-4317). These findings strongly suggest that the ability to form an arbuscular-mycorrhizal symbiosis occurred early in the evolution of vascular plants.


“Our bodies were designed over the course of millions of years for lives spent in small groups hunting and gathering on the plains of Africa. Natural selection has not had time to revise our bodies for coping with fatty diets, automobiles, drugs, artificial lights, and central heating. From this mismatch between our design and our environment arises much, perhaps most, preventable modern disease. The current epidemics of heart disease and breast cancer are tragic examples.” Randolph M. Neese(4318).

Edward B. Lewis (US), Christiane Jani Nüsslein-Volhard (DE) and Eric F. Wieschaus (US) shared the Nobel Prize in Physiology or Medicine for their discoveries concerning the genetic control of early embryonic development.

Rosamund M. J. Cleal (GB), Karen E. Walker (GB), and Richard Montague (GB) radiocarbon dated the first phase of Stonehenge, the outer ditch, which lies far outside the iconic stone structure. The ditch forms a nearly complete circle with an earthen bank on the inner side. (Now the bank is almost level with the ground due to age.) Radiocarbon dating of material found in the ditch in 1993-94 suggests it was built more than five thousand years ago, somewhat before 3000 B.C.E.(4319).

Kyriacos Costa Nicolaou (CY-US), Emmanuel A. Theodorakis (Greek-US), Floris P.J.T. Rutjes (NL), Jorg Tiebes (DE), Mitsunobu Sato (JP), Edouard Untersteller (FR), X.-Y. Xiao (US) carried out the total synthesis of brevitoxin B, the potent lipid-soluble neurotoxin produced by dinoflagellates such as Ptycodiscus brevis Davis (Gymnodynium breve Davis) and associated with red tide(4320, 4321).

Subhash C. Sinha (IL) and Ehud Keinan (IL) achieved the first total synthesis of a natural product via antibody catalysis(4322).

So Iwata (GB), Christian Ostermeier (DE), Bernd Ludwig (DE), and Hartmut Michel (DE) determined the structure of cytochrome c oxidase (a membrane embedded protein) from Paracoccus denitrificans at 2.8 A resolution(4323).

Eva Nogales (US), Sharon Grayer Wolf (US), Israr A. Khan (US), Richard F. Luduena (US), and Kenneth H. Downing (US) presented a three-dimensional reconstruction of tubulin to a 6.5 A resolution with a location of the taxol-binding site. It was obtained by electron crystallography of zinc-induced two-dimensional crystals of the protein(4324).

Norman Richard Pace, Jr. (US) indicated that the Archaea and Bacteria diverged from one another near the time that life arose on Earth. This changed the notion of evolutionary unity among prokaryotes. The phylogenetic data support the very early appearance of the eukaryotic nuclear line of descent. The Eucarya is as old as the prokaryotic lines Archaea and Bacteria. The idea that eukaryotes resulted from the fusion of two prokaryotes and are late arrivals on the evolutionary stage (1-1.5 billion years ago) is incorrect(2822). 

Robert D. Fleischmann (US), Mark D. Adams (US), Owen White (US), Rebecca A. Clayton (US), Ewen F. Kirkness (US), Anthony R. Kerlavage (US), Carol J. Bult (US), Jean-Francois Tomb (US), Brian A. Dougherty (US), Joseph M. Merrick (US), Keith McKenney (US), Granger G. Sutton (US), William FitzHugh (US), Chris Fields (US), Jeannine D. Gocayne (US), John Scott (US), Robert Shirley (US), Li-Ing Liu (US), Anna Glodek (US), Jenny M. Kelley (US), Janice F. Weidman (US), Cheryl A. Phillips (US), Tracy Spriggs (US), Eva Hedblom (US), Matthew D. Cotton (US), Teresa R. Utterback (US), Michael C. Hanna (US), David T. Nguyen (US), Deborah M. Saudek (US), Rhonda C. Brandon (US), Leah D. Fine (US), Janice L. Fritchman (US), Joyce L. Fuhrman (US), Neil S.M. Geoghagen (US), Cheryl L. Gnehm (US), Lisa A. McDonald (US), Keith V. Small (US), Claire M. Fraser (US), Hamilton O. Smith (US), and J. Craig Venter (US) published the first complete DNA sequence of a free-living organism, Haemophilus influenzae. They solved the sequence using a technique known as whole-genome random sequencing and assembly(4325).

Claire M. Fraser (US), Jeannine D. Gocayne (US), Owen White (US), Mark D. Adams (US), Rebecca A. Clayton (US), Robert D. Fleischmann (US), Carol J. Bult (US), Anthony R. Kerlavage (US), Granger G. Sutton (US), Jenny M. Kelley (US) Janice L. Fritchman (US), Janice F. Weidman (US), Keith V. Small (US), Mina Sandusky (US), Joyce Fuhrmann (US), David Nguyen (US), Teresa R. Utterback (US), Deborah M. Saudek (US), Cheryl A. Phillips (US), Joseph M. Merrick (US), Jean-Francois Tomb (US), Brian A. Dougherty (US), Kenneth F. Bott (US), Ping-Chuan Hu (US), and Thomas S. Lucier (US) determined the minimal gene complement of Mycoplasma genitalium(4326).

Valerie C. Wasinger (AU), Stuart J. Cordwell (AU), Anne Cerpa-Poljak (AU), Jun X. Yan (AU), Andrew A. Gooley (AU), Marc R. Wilkins (AU), Mark W. Duncan (AU), Ray Harris (AU), Keith L. Williams (AU) and Ian Humphrey-Smith (AU), during their study of Mycoplasma genitalium, coined the term proteome to mean that portion of the genomic library that creates proteins(4327).

Andreas Hecht (US), Thierry Laroche (CH), Sabine Strahl-Bolsinger (US), Susan M. Gasser (CH), and Michael Grunstein (US), provided the first clue that gene-regulatory proteins directly interact with chromatin. In Saccharomyces cerevisiae, histones are packaged into regions of transcriptionally silent, inaccessible heterochromatin by repressor proteins, such as the silent information regulators SIR3 and SIR4. The N termini of histones H3 and H4 are bound by the SIRs, showing for the first time that histones interact with gene-regulatory proteins. Importantly, further analysis revealed that acetylation of the N terminus of H4 prevented its interaction with SIR3(4328). The amino (N)-terminal tails of histones are subject to a range of covalent modifications, which provide binding sites for regulatory proteins that drive specific patterns of gene expression.

Stefan Irniger (AT), Simonetta Platti (AT), Christine Michaelis (AT), and Kim Nasmyth (AT) found that 13-type cyclin destruction is necessary for exit from mitosis and the initiation of a new cell cycle in Saccharomyces cerevisiae. Through the isolation of mutants, they identified three essential yeast genes, CDC16, CDC23, and CSE1, which are required for proteolysis of the B-type cyclin CLB2 but not of other unstable proteins. cdc23-1 mutants are defective in both entering and exiting anaphase. Their failure to exit anaphase can be explained by defective cyclin proteolysis. CDC23 is required at the metaphase/anaphase transition to separate sister chromatids. They speculated that CDC23 might promote proteolysis of proteins that hold sister chromatids together. Proteolysis of CLB2 is initiated in early anaphase, but a fraction of CLB2 remains stable until anaphase is complete(4329).

Feizhou Liu (US), Jack D. Thatcher (US), José Moreno (US), and Henry F. Epstein (US) discovered the glycolate cycle in the nematode Caenorhabditis elegans(4330).

Kimberley A. Gavin (US), Masumi Hidaka (US), and Bruce Stillman (US) suggested that origin recognition complex (ORC) subunits are conserved and that the role of ORC is a general feature of eukaryotic DNA replication(4331).

Shinga Matsumoto (JP), Koji Ikura (JP), Makoto Ueda (JP), and Ryuzo Sasaki (JP) created transgenic tobacco cells capable of producing human erythropoietin; a mitogen for blood cells(4332).

Mark Schena (US), Dari Shalon (US), Ronald W. Davis (US) and Patrick O. Brown (US) invented a high-capacity system which allowed them to monitor the expression of 45 Arabidopsis genes in parallel. Microarrays prepared by high-speed robotic printing of complementary DNAs on glass were used for quantitative expression measurements of the corresponding genes. This 'array' was probed with a mixture of fluorescently labeled cDNAs that were derived from the reverse transcription of mRNAs extracted from a tissue sample(4333). Today this is referred to as a DNA microarray.

Paul T. Spellman (US), Gavin Sherlock (US), Michael Q. Zhang (US), Vishwanath R. Iyer (US), Kirk Anders (US), Michael B. Eisen (US), Patrick O. Brown (US), David Botstein (US), and Bruce Futcher (US) used microarrays to monitor the expression of 800 genes throughout the yeast cell cycle. Subtle changes in overall gene-expression patterns over time were revealed. These could not have been detected by other methods(4334).

Charles M. Perou (US), Therese Serlie (US), Michael B. Eisen (US), Matt Van De Rijn (US), Stefanie S. Jeffrey (US), Christian A. Rees (US), Jonathan R. Pollack (US), Douglas T. Rossi (US), Hilde Johnsen (US), Lars A. Akslen (US), Oystein Fluge (US), Alexander Pergamenschikov (US), Cheryl Williams (US), Shirley X. Zhu (US), Per E. Lenning (US), Anne-Use Berresen-Dale (US), Patrick O. Brown (US), and David Botstein (US) used microarrays to study the expression of more than 8,000 genes in 65 human breast tumors. They generated 'molecular portraits' of gene expression that allowed them to distinguish between different classes of breast tumor and to identify two new categories that had been overlooked by traditional classification tools. They were also able to identify expression patterns that predicted the response to chemotherapy(4335).

Detlef Weigel (DE), Ove Nilsson (SE), Frederick D. Hempel (US), M. Alejandra Mandel (AR), Gary Ditta (US), Patricia C. Zambryski (US), Lewis J. Feldman (US), Martin F. Yanofsky (US), Miguel A. Blázquez (ES), Lara N. Soowal (US), Ilha Lee (Korean), Roland Green (US), Michael R. Sussman (US), Francois Parcy (FR), and Maximilian A. Busch (DE) identified a gene (LEAFY) that appears to be a key regulator in flowering; with the hormone gibberellin controlling its expression. They demonstrated that over expression of LFY protein causes early flowering. LFY also induces some of the homeotic genes that specify floral organ identity. LFY protein is transported between meristem cells and exhibits activity in the cells to which it has moved(4336-4340).

Dana L. Parmenter (CA), Joseph G. Boothe (CA), Gijs J.H. van Rooijen (NL-CA), Edward C. Yeung (CA), and Maurice M. Moloney (GB-CA) created transgenic canola plants capable of producing hirudin, a useful animal anticoagulant(4341).

Venkatesan Sundaresan (US), Patricia Springer (US), Thomas Volpe (US), Samuel Haward (GB), Jonathan D.G. Jones (GB), Caroline Dean (GB), Hong Ma (US), and Robert Martienssen (US) demonstrated that "enhancer trap" and "gene trap" transposable elements could be realized on a genome-wide scale in Arabidopsis to detet and clone genes in any plant process(4342). 

Acaimo Gonzalez-Reyes (GB), Heather Elliott (GB), and Daniel St. Johnston (GB) found that in Drosophila the gurken gene (grk) produces a protein which sets up the anterior-posterior (AP) polarization of the microtubule cytoskeleton that directs the correct transport of bicoid and oskar mRNAs to opposite ends of the oocyte. As well as being crucial for setting up the anterior-posterior (AP) body axis, microtubule polarization is also essential for the dorso-ventral (DV) body axis polarity. The localized secretion of gurken that initiates dorsal follicle-cell fate depends on the movement of the oocyte nucleus along microtubules to the anterior–dorsal corner of the oocyte, leading to the accumulation of gurken mRNA close to the dorsal surface. The fact that this occurs after the posterior follicle cells have been specified indicates that the gurken-dependent microtubule polarization that initiates AP polarity might also be responsible for determining the position of the DV axis. This was confirmed when it was shown that the oocyte nucleus does not migrate to its correct position in gurken mutants. In addition, gurken mRNA fails to localize to the correct position at the anterior–dorsal corner of the oocyte when the gurken receptor in the follicle cells is absent(4343).

Nathalie Auphan (FR), Joseph A. DiDonato (US), Caridad Rosette (US), Arno Helmberg (AT), and Michael Karin (US) show that glucocorticoids are potent inhibitors of nuclear factor kappa B (NF-kB) activation in mice and cultured cells. This inhibition is mediated by induction of the IkB alpha inhibitory protein, which traps activated NF-kB in inactive cytoplasmic complexes. Because NF-kB activates many immunoregulatoy genes in response to pro-inflammatory stimuli, the inhibition of its activity can be a major component of the anti-inflammatory activity of glucocorticoids(4344).

Tetsuya Nosaka (US), Jan M. van Deursen (US), Ralph A. Tripp (US), William E. Thierfelder (US), Bruce A. Witthuhn (US), Anthony P. McMickle (US), Peter C. Doherty (US), Gerard C. Grosveld (US), and James N. Ihle (US) found that the Janus tyrosine kinase Jak 3 plays a critical role in gamma signaling and lymphoid development(4345).

Calman Prussin (US) and Dean D. Metcalfe (US) detected intracytoplasmic cytokine using flow cytometry and directly conjugated anti-cytokine antibodies(4346).

Peter Openshaw (GB), Erin E. Murphy (US), Nancy A. Hosken (US), Vernon Maino (US), Kenneth Davis (US), Kenneth Murphy (US), and Anne O'Garra (US) determined that 4 + T helper (Th) cells can be classified into different types based on their cytokine profile. Cells with these polarized patterns of cytokine production have been termed Thl and Th2, and can be distinguished functionally by the production of lFN-gamma and IL-4, respectively. Using immunofluorescent detection of intracellular IFN-gamma/and IL-4, they studied the emergence of Thl and Th2 cells in response to antigen exposure and the patterns of cytokine synthesis in established T cell clones. IFN-gamma production by Thl clones was detectable in almost all cells by 4 h, and it continued in most cells for >24 h. IL-4 production in Th2 cells peaked at 4 h, then declined rapidly. In Th0 cells containing both cytokines, fewer cells produced IFN-gamma which did not appear until IL-4 synthesis declined(4347).

Louis J. Picker (US), Manoj K. Singh (US), Zoran Zdraveski (US), John R. Treer (US), Sharr L. Waldrop (US), Paul R. Bergstresser (US), and