A Selected Chronological Bibliography of Biology and Medicine

 

Part 6A

 

1964 — 1970

 

 

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: James S. Steen, Ph.D., Professor Emeritus, jsteen08@bellsouth.net

 

1964

“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 (826).

           

“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 (701).

 

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 W. Menzel (US) and Ralph F. Vaccaro (US) reported that organic carbon in aqueous solution may be measured with a precision of ± 0.1 mg C/l using persulfate as an oxidant. Oxidation is accomplished in sealed ampules. The evolved CO2 is quantified with an infrared detector (1144).

 

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 (1862).

 

Patrick Andrews (GB) developed a way to determine the molecular weights of proteins using Sephadex gel-filtration (38).

 

Leonard Ornstein (US) and Baruch J. Davis (US) introduced the use of synthetic polyacrylamide gels in disc (discontinuous) electrophoresis (395; 1287).

 

Alfred Zettner (US) and David Seligson (US) were the first to use atomic absorption spectrophotometry to measure serum calcium (1870).

David L. Trudeau (US) and Esther F. Freier (US) first described the use of lanthanum in the measurement of calcium in biological fluids (1697).

 

Henry N. Wagner, Jr. (US), David C. Sabiston, Jr. (US), Masahiro Iio (US), John G. McAfee (US), Jon K. Meyer (US), and James K. Langan (US) developed an isotope tracer technique whih allowed them to determine regional pulmonary blood flow in man (750).

 

Beverly E. Pearson Murphy (CA) and Chauncey J. Patee (CA) described a simple, rapid method for the determination of serum thyroxine, which is based on the specific binding properties of thyroxine-binding globulin (TBG). One-half ml of the test sample is deproteinized and the thyroxine thus freed is measured according to its competition with a fixed amount of thyroxine-I131 for a fixed amount of TBG (1212).

 

Arne Dahlqvist (SE) described a simple method for testing disaccharidase activity. It has now been used for numerous clinical investigations, especially for peroral biopsies of the small intestinal mucosa (380; 381).

 

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 (939).

 

Wilfrid G. Duncombe (GB) devised a method useful in a variety of applications in which the concentration of long-chain fatty acids extracted from biological materials was required. Long-chain fatty acids dissolved in chloroform will form chloroform-soluble copper soaps. The reaction of these with a chromogenic reagent for copper is the basis for the determination described (471).

 

Henry N. Wagner, Jr. (US), David C. Sabiston, Jr. (US), John G. McAfee (US), Donald Tow (US), and Howard S. Stern (US) developed a way to use radioiodine labeled macroaggregates of albumin in the rapid diagnosis of acute pulmonary embolism (1738).

 

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 (1020-1023).

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 (891).

 

Malcolm Daniel Lane (US), Karl L. Rominger (DE), David L. Young (US), and Feodor Felix Konrad Lynen (DE), using Propionibacterium shermanii, showed that the synthetase catalyzed a two-step reaction. The first step involved the ATP-dependent formation of biotinyl-5'-AMP and pyrophosphate after which the biotinyl group was transferred from the AMP derivative to the appropriate lysyl epsilon-amino group of the apotranscarboxylase (993). Synthetase had been shown to catalyze biotin loading onto the apoenzyme.

Carlo Gregolin (IT), Elena Ryder (VE), Robert C. Warner (US), Albrecht K. Kleinschmidt (US), Huei-Che Chang (US), and Malcolm Daniel Lane (US) described the molecular characteristics of chicken acetyl coenzyme A carboxylase, including its reversible inter-conversion between protomeric and polymeric forms. They determined that the carboxylase has a binding site for citrate and another for acetyl-CoA and that citrate binding might be involved in regulating the enzyme (672).

Ras B. Guchhait (US), S. Efthimios Polakis (US), Donald Hollis (US), Catherine Fenselau (US), and Malcolm Daniel Lane (US) used the acetyl coenzyme A carboxylase system from Escherichia coli to provide definitive evidence that the ureido-N of biotin is the site of carboxylation (681).

S. Efthimios Polakis (US), Ras B. Guchhait (US), Eberhard E. Zwergel (US), Malcolm Daniel Lane (US), and Terrance G. Cooper (US) gave a thorough analysis of the acetyl coenzyme A carboxylase system from Escherichia coli. They define the requirements and properties of isotopic exchange and stoichiometric reactions representative of the two half- reactions in acetyl-CoA carboxylation and describe studies using prosthetic group and intermediate model derivatives as substrates to elucidate the mechanisms of the partial reactions (1350).

 

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

 

W. Robert Jenkins (US) presented a simple, rapid, and inexpensive method for the extraction of nematodes from soil (850).

 

Clinton Edward Edgerton Ballou (US) and Yuan Chuan Lee (TW-US-TW) determined the structures of the family of mannosyl phosphoinositides in the mycobacteria (76; 1015).

 

Karl Sune Detlof Bergström (SE), Henry Danielsson (SE), and Bengt Samuelson (SE) demonstrated the enzymatic conversion of arachidonic acid to prostaglandin E2 (127). Because arachidonic acid is synthesized from linoleic acid in humans, this discovery helped establish prostaglandins as products of the metabolism of essential fatty acids.

 

Vladimir P. Skipski (US), Robert F. Peterson (US), and Marion Barclay (US) described the conversion of their previously-developed procedure for qualitative separation of phospholipids by thin-layer chromatography to a quantitative analysis which permitted the determination of the main known phospholipids in animal tissues (1549).

 

Choh Hao Li (CN-US) and Yehudith Burk (US) isolated and purified beta-lipotropin (beta-LPH) (1034).

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 (1033).

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 (298).

 

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 (1359). This was a major clue to unraveling the acetyl-CoA pathway.

 

Martin Rodbell (US) isolated individual fat cells then showed that insulin bounds directly to receptors on these cells and stimulates glucose metabolism (1419).

 

Merton Franklin Utter (US), D. Bruce Keech (US), and Michael C. Scrutton (US) demonstrated that acetyl-CoA regulates the activity of pyruvate carboxylase (combines CO₂ with pyruvate in glucogenesis), thus providing one of the first examples of allosteric control of enzymes (1498; 1720).

 

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 (119).

 

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 (1640).

 

Kendrick W. Dungan (US) and Paul M. Lish (US) were the first to describe sotalol (472). 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 (1540).

 

Sipra Guha (IN) and Satish C. Maheshwari (IN) obtained haploid plants of Datura innoxia Mill (Angel's trumpet) from anther cultures (683; 684).

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) (1515).

 

Henry M. Cathey (US) explained that chemical growth retardants (8 families) block cell elongation of stems without affecting leaf formation, resulting in compact, stress-resistant plants. With many woody plants the treated plants initiate flowers earlier than typical for the species. Chemical growth retardants are one of the reasons for the house plant boom in America. They have permitted the sizing of plants to fit any space (279).

 

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 (111).

 

Abraham Marcus (US) and John Feeley (US) analyzed the mechanism for protein synthesis in intact seeds and isolated seed embryos. They found that the protein synthesis apparatus is functional in the ungerminated seed, yet imbibition is necessary if sufficient messenger RNA for germination is to be made (1108).

 

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 (870).

 

Traian Losef Stopler (RO), Victoria Camuescu (RO), Mihaela Voiculescu (RO), J. Donald Coonrod (US), Peter J. Leadley (US), and Theodore C. Eickhoff (US) successfully isolated Bacillus cereus as the etiological agent from cases of bronchial pneumonia. It was cultured from the blood and pleural fluid (341; 1611). Bacillus cereus is an opportunistic human pathogen and is occasionally associated with infections, causing periodontal diseases and other more serious infections.

Bacillus cereus can spread easily to many types of foods such as plants, eggs, meat, and dairy products, and is known for causing 25% of food-borne intoxications due to its secretion of emetic toxins and enterotoxins (1645).

Lucas M. Wijnands (NL), J.B. Dufrenne (NL), Marcel H. Zwietering (NL), and Frans M. van Leusden (NL) reported that immunocompromised patients are susceptible to bacteremia, endocarditis, meningitis, pneumonia, and endophthalmitis caused by Bacillus cereus (1809). Its potential to cause systemic infections is of current public health and biomedical concerns.

 

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 (1337).

 

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 (293; 1137; 1614). 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 (430; 743; 1154; 1712).

 

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 (236).

 

Robert Tod Schimke (US) was the first to report protein degradation as a regulatory process and thereby established a new field of biochemistry (1481).

 

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 (327).

 

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" (650).

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 (392-394; 649; 651; 1583).

 

Malcolm Andrew Ferguson-Smith (GB) discovered that the pattern of multiple associations suggests that three long and two short chromosomal bivalents are capable of forming terminal nucleoli during pachytene. The evidence suggests that these five bivalents are the five pairs of satellited chromosomes in the human mitotic ideogram (533).

 

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 (1762).

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 (604).

 

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 (45; 511; 1073; 1389).

 

Te-Wen Chang (US) and Louis Weinstein (US) report that the antibiotic cephalothin inhibits cell wall peptidoglycan synthesis (290).

 

Gordon Leslie Ada (AU), Gustav Joseph Victor Nossal (AU), John Pye (AU), and Andrew Abbot (AU) described the preparation and physical and chemical properties of the monomeric protein flagellin and of the formation in vitro of polymerized forms which appear similar in appearance to the parent flagella particles from Salmonella adelaide (4).

 

Max Bernard Lurie (LT-US) discovered that macrophages must be activated to digest cells of Mycobacterium tuberculosis (1079).

 

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 (1429).

 

Cyril Moore (US) and Berton Charles Pressman (US) presented evidence that the antibiotic valinomycin acts as an ionophore that transports potassium ions down its electrochemical gradient and across the cell membrane. It is an energy dependent accumulation of potassium ions in mitochondria (1192).

 

Daniel Nathans (US) demonstrated that puromycin inhibits protein synthesis by being incorporated into the growing polypeptide chain, resulting in premature termination of translation (1218).

 

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) (324; 627; 642-644; 797; 1303; 1709).

 

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) (534).

 

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 (299; 300; 1728).

 

Myron C. Ledbetter (US), Keith R. Porter (US), David M. Phillips (US), Lewis G. Tilney (US), Joseph Bryan (US), Doris J. Bush (US), Keigi Fujiwara (US), Mark S. Mooseker (US), Douglas B. Murphy (US), and Daniel H. Snyder (US) described the 13-protofilament structure of microtubules which they found to be widespread among many organisms (1007; 1339; 1674).

 

Fritz Miller (DE) and George Emil Palade (RO-US) carried out one of the first examples of combined cytochemistry and electron microscopy. They found that enzymes and substrates colocalize in lysosomes (1161).

 

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 lymphoid site tend to return, or home back to the same site when reinjected, suggesting that they possess homing receptors (660; 1105).

 

Gerhard Malnic (US), Ruth M. Klose (US), Gerhard Giebisch (US), Cristobal G. Duarte (US), Francoise Chomety (US), Margarida de Mello Aires (BR), Fred S. Wright (US), Nikolaus Strieder (US), and Nicole B. Fowler (US) perfected the method of performing micropuncture and microperfusion studies on the distal tubule of the nephron. They unequivocally demonstrated that potassium is reabsorbed by the proximal tubule and the loop of Henle, that potassium reabsorption by these nephron segments is constant in a variety of experimental and metabolic conditions, and that it is the distal tubule that primarily determines the amount of potassium excreted in the urine by either continuing potassium reabsorption, or by secreting potassium into the tubular fluid. Furthermore, they provided the first insight into the cellular mechanisms of potassium transport by the distal tubule (464; 1097-1100; 1843).

 

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 (1834).

 

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 (487).

 

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 (446; 728; 1008; 1239; 1240; 1332).

 

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 (1057; 1242; 1767).

 

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 to start transcribing from DNA into RNA. They named this element the promoter (841).

 

Patricia Farnes (US), Barbara E. Barker (US), L.E. Brownhill (US), and Herbert Fanger (US) discovered that the extract of pokeweed is mitogenic to lymphocytes of peripheral blood (528).

 

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 could be stabilized (338-340).

 

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, could 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 (1452).

 

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 (1396).

 

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 response (502; 1541).

 

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 (104; 108-110).

 

Philip Jacobus Hoedemaeker (NL), Jules J. Abels (NL), J.J. Wachters (NL), Albertus Arends (NL), and Hendrik Omgo 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 (778; 779).

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 (664; 665).

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 (874).

 

Kurt J. Isselbacher (US) and Norton J. Greenberger (US) reported that alcohol has many effects on hepatic, carbohydrate, protein, and lipid metabolism. Many of the actions of alcohol on the liver cell are of a direct or toxic nature. Other effects are indirect and the result of changes in the redox state of the hepatocyte secondary to ethanol oxidation. Their knowledge of the metabolic actions of alcohol has provided insight into the mechanism of alcohol-induced hyperlipidemia, hyperuricemia, and hypoglycemia (836).

 

Nasrollah T. Shahidi (US), David G. Nathan (US), and Louis K. Diamond (US) during examination of two sibling patients discovered an error in iron metabolism characterized by massive hepatic iron deposition and absent stainable bone marrow iron stores. The association of this discrepancy with the chronic hypochromic anemia present in these two siblings is unique (1508).

 

John E. Phillips (CA) demonstrated that active ion transport occurs in the locust rectum. The coupling of metabolic energy to the movement of compounds across the epithelium is vital for osmoregulation and for the retention of ions, water and nutrients. Microelectrode measurements showed that chloride transport set up an electrical gradient that facilitated the movement of sodium and potassium from the lumen into the hemolymph. The most startling and significant finding was that water could be transported from the rectum to the hemolymph when the rectum was filled with a solution of 800-mOsm xylose, even though the hemolymph remained at a lower concentration of about 400-mOsm. He demonstrated that rectal capacity for ion and water transport exceeds the rate at which ions and water enter the rectum in the urine. His results provided a mechanistic explanation for the observation that the fecal pellets of Schistocerca are in equilibrium with a very concentrated solution, but essentially devoid of sodium, potassium and chloride ions. Phillips had simultaneously shown how ions and water were retained in the locust under desiccating conditions and clarified the mechanisms by which highly concentrated feces were produced (1340-1342).

 

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 (1367).

 

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 (1072).

 

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 this work was done in muscle fibers of the giant barnacle (493; 698-700).

Graham Hoyle (US) and Thomas Smyth, Jr. (US) had discovered the giant muscle fibers in the North Pacific barnacle (807).

 

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 (1089).

 

William F.H. Jarrett (GB), William B. Martin (GB), George W. Crighton (GB), Roger G. Dalton (GB), Mary F. Stewart (US-GB), Elizabeth M. Crawford (GB), and F. Davie (GB) showed feline leukemia to be transmissible experimentally in cats using cell-free extracts of lymphosarcoma tissue from a spontaneous field case. Type C virus particles were demonstrated in the experimentally induced tumor and in cells cultured from it. This was the first transmission of a spontaneous mammalian leukemia (847; 848).

 

John W. Littlefield (US) introduced HAT medium (hypoxanthine, aminopterin, and thymidine) for the selective growth of somatic cell hybrids (1059). 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 (1106).

 

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 (276).

 

Edmund Brisco Ford (GB) coined ecological genetics to refer to the study of evolution in action by a mixture of laboratory and fieldwork (565).

 

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 (1148; 1149).

 

Fred B. Abeles (US) and Bernard Rubinstein (US) found that auxin stimulated ethylene production, and that it was the gas which promoted abscission after the ability of auxin to delay aging was lost. This paper provided experimental proof for the principle that ethylene could act as a second messenger in some of the effects of auxin on plant growth and development (3).

 

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 (363). 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 (984).

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 (1644; 1732).

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 (1467; 1468).

 

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 to be incorporated into the head protein of the virus. This strongly suggested that nonsense codons act as termination signals during polypeptide synthesis (1470).

 

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 (795).

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 (823). Gene conversion represents the nonreciprocal transfer of information between two homologous sequences where one allele is duplicated while another is lost.

Jack William Szostak (CA-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 (1638).

Alain Nicolas (FR), Douglas Treco (US), Neil P. Schultes (US), Liang Cao (US), Eric Alani (US), Nancy Kleckner (US), and Jack William Szostak (CA-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 (258; 1236).

 

Hunt Potter (US) and David Dressler (US-GB) demonstrated the validity of the Holliday model of recombination (1360).

 

Paul Ichiro Terasaki (US) and John D. McClelland (US) developed the microcytotoxicity test, critical for further development and practical use of HLA typing (1661).

 

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 (59; 68).

 

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 (723).

 

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 (1085).

Roger L. Lundblad (US) and Earl Warren 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 (1078).

Earl Warren Davie (US) and Oscar D. Ratnoff (US) presented a blood coagulation scheme based on the concept that clotting factors were present in blood in an inactive or precursor form and were converted to active enzymes in a step-by- step manner most likely via limited proteolysis they called a "waterfall sequence for intrinsic blood clotting" (390). Later the extrinsic (now called the tissue factor pathway) was added.

 

Rose Payne (US) Millie Tripp (US), Joan Weigle (CH-US), Walter Fred Bodmer (GB), and Julia Bodmer (GB) defined the allelic system now known as HLA-A 1, 2, and 3 (1315).

 

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 (48; 1398).

 

Gustav Joseph Victor Nossal (AU), Aleksander Szenberg (AU), Gordon Leslie Ada (AU), and Caroline M. Austin (AU) observed that individual B cells can switch immunoglobulin (Ig) class upon activation (1256).

Tohru Kataoka (JP), Toshiaki Kawakami (JP), Naoki Takahashi (JP), Tasuku Honjo (JP), and Akira Shimizu (JP) elucidated the mechanism of immunoglobulin class switching (class-switch recombination), whereby B cells switch their antibody production from one antibody type to another depending on the type of antigen with which they are presented (906; 1519).

 Masamichi Muramatsu (JP), Kazuo Kinoshita (JP), Sidonia Fagarasan (JP), Shuichi Yamada (JP), Yoichi Shinkai (JP), and Tasuku Honjo (JP) presented results suggesting that activation-induced cytidine deaminase (AID) may be involved in regulation or catalysis of the DNA modification step of both class switching and somatic hypermutation in immunoglobulins (1210).

 

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 (773).

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) (1440).

Masanobu Karakami (JP), Anthony Cerami (US), Phillip H. Pekala (US), and Malcolm Daniel Lane (US) found that macrophages secrete cachectin, which suppresses lipoprotein lipase activity (919; 920).

 

Edward Claus Franklin (DE-US), Jerome Lowenstein (US), Bradley Bigelow (US) and Martin Meltzer (US) were the first to report a case with gamma heavy chain disease. The patient presented with an unexplained lymphadenopathy, fever, and a spike in the gamma fraction of serum (572).

Elliott F. Osserman (US) and Kiyoshi Takatsuki (JP) coined the phrase gamma heavy chain disease (1289).

 

Wolfgang Rapp (FR), Samuel B. Aronson (US), Pierre Burtin (FR), Pierre Grabar (RU-DE-FR), Paul A. Crabbé (BE), Joseph Felix Heremans (BE), Raymond Havez (FR), Francoise 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 immunoglobulins—IgA, IgG, IgM, and IgD—into the gastric fluid (360; 361; 708; 732; 1387).

 

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 (330).

Jerome W. Conn (US), Edwin L. Cohen (US), David R. Rovner (US), and Reed M. Nesbit (US) showed that hypokalemia (deficiency of potassium in the bloodstream) is likely a late manifestation of aldosterone excess, if it occurs at all (331).

 

John Rouben David (US), Salah Al-Askari (US), H. Sherwood Lawrence (US), Lewis Thomas (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 (150; 387; 388). They named this substance migration inhibitory factor (MIF). Note: This was the third cytokine discovered. Stanley Cohen (US) coined the neologism cytokine (320).

 

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 several 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 (1797).

 

Roger Boucher (CA), Robert Veyrat (CA), Jacques de Champlain (CA) and Jacques Genest (CA) described an improved procedure for angiotensin isolation and determination and also a new method for the measurement of plasma renin activity (167).

Leonard Skeggs, Jr. (US),Walton H. Marsh (US), Joseph R. Kahn (US), and Norman P. Shumway (US) found that angiotensin existed in two forms: angiotensin I and angiotensin II. Angiotensin I was a biologically inactive decapeptide which was converted to a highly active octapeptide by an enzyme in the plasma (1542).

Kevin K.F. Ng (SG) and John Robert Vane (GB) discovered angiotensin converting enzyme (ACE) in the lung of dogs (1233; 1234). Note: This work led to the development and clinical use of angiotensin converting enzyme (ACE) inhibitors in medicine. The discovery of the pulmonary converting enzyme and its inhibition by Bradykinin Potentiating Factor (BPF) led to the synthesis of captopril (Capoten).

A. Brew Atkinson (GB), J. Ian S. Robertson (GB), Martin J. Kendall (US), Steven R. Smith (US), M.H. Thompson (US), Alessandra Sturani (IT), Carla Chiarini (IT), Ezio Degli Esposti (IT), Antonio Santoro (IT), Alessandro Zuccalà, Pietro Zucchelli (IT), and Larry Neil Gever (US) reported on Captopril, the first ACE inhibitor used clinically in the treatment of hypertension and cardiac failure (52; 613; 933; 1615). Note: There are now ten ACE inhibitors available in the United States for the treatment of hypertension, congestive heart failure, and diabetic kidney disease: captopril, enalapril, fosinopril, lisinopril, benazepril, moexipril, perindopril, quinapril, ramipril and trandolapril.

 

Seymour M. Glick (US-IL), Jesse Roth (US), Rosalyn Sussman Yalow (US), and Solomon Aaron Berson (US) determined that plasma radioimmunoassayable human growth hormone (HGH) levels fluctuate widely and rapidly in response to stimuli that have in common a shortage of carbohydrate energy substrate, and to stress. Glucose lowers plasma HGH in normals but not in acromegalics. The HGH response to insulin hypoglycemia distinguishes normals from hypopituitary subjects (630).

 

Allan Kliman (US) and Mark E. Lesses (US) introduced plasmapheresis as a means of collecting plasma for fractionation (956).

 

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 (1757).

 

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 be 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 (442).

 

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 (1504).

 

Joseph T. Doyle (US), Thomas R. Dawber (US),William B. Kannel (US), Sandra H. Kinch (US), and Harold A. Kahn (US) reported the relationship of smoking habit to total mortality and to the incidence of new manifestations of coronary heart disease (CHD) from an examination in 2,282 middle-aged men under medical surveillance for ten years in Framingham, Mass, and 1,838 middle-aged men followed for eight years in Albany, NY. It was found that in men who report habitual consumption of 20 or more cigarettes per day the risk of myocardial infarction was about three times greater than in nonsmokers, former cigarette smokers, or pipe and cigar smokers (461).

 

Ernst J. Drenick (US), Marion E. Swendseid (US), William H. Blahd (US), and Stewart G. Tuttle (US) selected eleven obese, ambulatory patients that were then starved for periods of 12 to 117 days. Only water and vitamins were consumed. Weight losses averaged 0.91 pounds (0.41 kg) daily. Hunger was virtually absent. Complications which developed during starvation were severe orthostatic hypotension in three cases; severe normocytic, normochromic anemia in one case; and gouty arthritis in two cases. With refeeding all ill effects were promptly reversed. Serum electrolytes, lipids, proteins, and amino acids remained unchanged during starvation. Serum uric acid increased; blood glucose levels fell in some cases. Considerable amounts of body protein and potassium were lost. Prolonged starvation is not advised for obese patients with a history of ischemic cardiovascular or cerebral disease, with history of gout, or with hepatic diseahypole (462).

 

Edmund L. Dubois (US) and Denny L. Tuffanelli (US) reported that diagnosis of systemic lupus erythematosus (SLE) was confirmed by the presence of lupus erythematosus cells in 75.7% of the patients, findings of skin biopsies in 6.0% and of renal biopsies in 1.2%, and by the clinical picture alone in 17.1%. Negroes comprised 34% of the subjects. Spontaneous remissions occurred in 35% of the patients. Proven familial SLE occurred in 2%. Myalgia was present in 48.2%. No history of cutaneous involvement at any time was found in 28%. Classic skin lesions of chronic discoid lupus at the onset of their illness were present in 10.8%. Urinary abnormalities were noted in only 46.1%. Uremia caused 34% of the 135 deaths and progressive central nervous system involvement caused 18.4%. The prognosis has markedly improved. The mean duration is now 94.8 months for the entire series versus 38.5 months in an untreated control group (466).

 

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 (1027; 1261). This metabolic disease was later named The Lesch-Nyhan Syndrome.

Werner Catel (DE) and Johann-Anton Schmidt (DE) were probably the first to describe this syndrome (278).

Jarvis Edwin Seegmiller (US), Arthur I. Grayzel (US), Leonard Laster (US), and Lois Liddle (US) found that an increased rate of purine biosynthesis de novo contributes to the hyperuricemia in most gouty patients (1500).

Jarvis Edwin Seegmiller (US), R. Rodney Howell (US), and Stephen E. Malawista (US) reported that microcrystals of uric acid interact with all of the major synovial cell types, including neutrophils, fibroblasts, and monocytes/macrophages to produce a variety of inflammatory mediators (1501).

 Jarvis Edwin Seegmiller (US), Frederick M. Rosenbloom (US), and William N. Kelley (US) discovered that the rare genetic disease, Lesch–Nyhan syndrome, was due to a profound deficiency of an enzyme known as hypoxanthine guanine phosphoribosyltransferase (HGPRT). Deficiency that causes high levels of uric acid in the blood and leads to the development of gouty arthritis and the formation of uric acid stones in the urinary tract, i.e, Kelley-Seegmiller syndrome (1502).

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 (926).

 

D.A.L. Davies (US), Edward Arthur Boyse (GB-US), Elisabeth Stockert (US), Silvi Luell (US), and Lloyd John Old (US) discovered TL (the thymus-leukemia antigen in mice), which represented the first link between the major histocompatibility complex and a disease state: mouse leukemia (176; 177; 391). Note: This knowledge helped pave the way for the recognition of the importance of the major histocompatibility complex in the immune response.

Edward Arthur Boyse (GB-US, Masaaki Miyazawa (US), Tadao Aoki (US), and Lloyd John Old (US) identified the Ly-A and Ly-B series of mouse cell surface isoantigens (175). Note: These discoveries led directly to the wide use of cell-surface markers to distinguish and classify normal and malignant cells and directly to the CD (cluster of differentiation) classification. This research laid the groundwork for the identification of the molecular markers on the surfaces of cells that allowed them to be experimentally and diagnostically separated and distinguished, which revolutionized immunology and medicine as it is practiced today.

Edward Arthur Boyse (GB-US) and Harvey I. Cantor (US) determined that Ly-A (later Lyt-1) and Ly-B (Lyt-2/3) hallmarked functionally distinct subclasses of lymphocytes, the former denoted ‘helper’ and the latter ‘killer-suppressor’ (255; 256). Note: This turned out to hold true in all mammalian species. In humans these subsets are now known as CD4 and CD8.

 

Ernst H. Beutner (US) and Robert E. Jordan (US) demonstrated the skin antibodies in sera of pemphigus vulgaris and bullous pemphigoid patients by indirect immunofluorescent staining (134).

Ernst H. Beutner (US), Walter F. Lever (US), Ernest Witebsky (US), Robert Jordon (US), and Burton Chertock (US) found antibodies to an intercellular substance of stratified squamous epithelium using indirect immunofluorescent (IF) staining in the sera of eight out of 16 patients with pemphigus vulgaris. The autoantibody nature of these antibodies could be demonstrated by testing the patient's skin with the patient's own serum (136).

Robert E. Jordon (US), Ernest H. Beutner (US), Ernest Witebsky (US), George Blumental (US), William L. Hale (US), and Walter F. Lever (US) observed that indirect immunofluorescent (IF) staining in 14 of 16 patients with active lesions of bullous pemphigoid the sera contained antibodies specific for the basement zone beneath stratified squamous epithelium while the sera from six patients in remission contained no demonstrable antibodies. The sera of 18 patients with dermatitis herpetiformis and 94 patients with various bullous and nonbullous dermatoses yielded negative reactions to the basement zone by indirect IF staining. In four of five skin biopsy specimens from patients with bullous pemphigoid direct IF staining indicated that γ-globulin had been bound in vivo to the basement zone (876).

Ernst H. Beutner (US), Robert E. Jordan (US) and Tadeusz P. Chorzelski (PL) found in pemphigus that these antibodies react with a surface protein on epithelial cells, and in bullous pemphigoid they fix to the basement membrane, as seen by indirect immunofluorescence (IF) tests of sera on normal epithelia. Direct IF tests of patients’ biopsies show that these antibodies react in vivo with normal skin and oral mucosa (135).

 

Ernest Pillsbury Walker (US), et al., completed a two- volume Mammals of the World. It is a great reference work in which each genus is illustrated, and its characteristics and habits tersely stated (1747).

 

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 (1590).

Thomas Earl Starzl (US) established rules to prevent ABO-incompatibility in renal transplantation surgery (1588).

 

Robert Austrian (US) and Jerome Gold (US) reported on examined cases of pneumococcal bacteremia treated at the Boston City Hospital in Massachusetts, between 1929 and 1935. Clinical manifestations; biology of infections caused by several pneumococcal types; results of diagnostic examinations; disease overview; treatment regimen; mortality in untreated and treated infections (56).

Robert Austrian (US), Robert M. Douglas (US), Gerald Schiffman (US), A. Maureen Coetzee (ZA), Hendrik J. Koornhof (ZA), Stanley Hayden-Smith (ZA), and Robert 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 (54; 55). Austrian also played a major role in the successful clinical trials, which resulted in the vaccine's licensure.

 

Alfred J. Luessenhop (US) and Alfredo C. Velasquez (US) introduced endovascular surgery for arteriovenous malformations (AVMs) and aneurysms (1077).

 

Howard Earle Skipper (US), Frank M. Schabel, Jr. (US), William S. Wilcox (US), L. Bruce Mellett (US), John A. Montgomery (US), Lee J. Wilkoff (US), Harris H. Lloyd (US), and R. Wallace Brockman (US) proposed a model for tumor growth which was formulated and popularized by investigators at the Southern Research Institute. Called the log-kill model, it was the original, and is still the preeminent, model of tumor growth and therapeutic regression. They determined that a given dosage of a chemotherapy drug killed a relatively consistent fraction of cells in a malignant-cell population, as opposed to an absolute number. All that was needed was for a single leukemic cell to survive, and the doubling would start anew, and the disease would return with a vengeance. One survivor: That was all it took.

They demonstrated the curability of cancer in several animal tumor model systems, and first introduced the concepts of total cell kill. Their experimental work elucidated the logic of chemotherapy as an adjunct to surgery and has delineated the idea of prompt eradication of all evidence of disease (1544-1548).

 

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 (705; 755; 756; 1039-1041).

 

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 (529; 1075; 1822).

 

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 (458). 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 (678).

 

H. Vernon Ingram (DE-GB-US) introduced the use of the laser for eye surgery (831).

 

Rolla B. Hill (US), David T. Rowlands, Jr. (US), and David Rifkind (US) reported that pulmonary infections were present terminally in 26 of 32 patients dying one to two hundred and seven days after receiving an organ transplant. The responsible organisms included many unusual agents not commonly producing clinical disease. Candida, Aspergillus, Nocardia, Pneumocystis and Cytomegalovirus were identified in 28 cases, and various bacteria, notably Pseudomonas, in 17 cases. Multiple infections were common (766).

 

C. Andrew L. Bassett (US), Robert J. Pawluk (US), Robert O. Becker (US), and Arthur A. Pilla (US) reported that electromagnetic fields promote bone fracture repair (95; 96).

 

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 (703).

Victor H. Denenberg (US) following his work with hemispheric laterality in rats presented his theory that the brain possesses innate functional asymmetry (424).

 

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; tool making; 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 tool making 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 (409; 637-639; 1657).

 

William Donald Hamilton (GB) proposed a theoretically robust explanation of altruism, kin selection, and inclusive fitness based on genetics. 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) (704). These ideas have since been extended to social behaviors of many species—vertebrate as well as invertebrate.

 

Dmitry Konstantinovich Belyayev (RU), in the 1950's, conceived and initiated his attempt to domesticate the silver fox and test whether its biochemistry was altered as domestication occurred. He selected for low flight distance, that is, the distance one can approach the animal before it runs away. By selecting this behavior he mimicked what happened through natural selection in the ancestral past of dogs. Unexpectedly during the experiment pleiotropy occurred. The gene for tameness (i.e. low flight distance) also keys for other "dog-like" traits such as raised tail and coming into heat every six months rather than annually. Indeed it is now accepted that dogs look as they do more because of this pleiotrophic behavior of coding rather than the human intervention thousands of years ago(114-116; 641).

Lyudmila N. Trut (RU) domesticated the silver fox, a color variation of the red fox (Vulpes vulpes), in a controlled experiment at the Institute of Cytology and Genetics in Novosibirsk, Russia. Starting in 1959, and selected solely on behavioral criteria for more than 40 generations, a strain of foxes with behavior extremely similar to domestic dogs was produced (1700; 1701).

 

Austin Bradford Hill (GB) made a landmark presentation of criteria for inferring causality from observational data dealing with environment and disease (764). Austin Bradford Hill

 

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 (496).

 

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 (c.a 130,000) (405).

 

1965

“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) (237).

 

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 Michel Lwoff (FR) shared the Nobel Prize in Physiology or Medicine for their discoveries concerning genetic control of enzyme and virus synthesis.

 

Dr. Benjamin Rubin (US) patented the bifurcated needle for delivery of smallpox vaccine (1443).

 

Cambridge Instruments produced the first commercial scanning electron microscope. ref

 

Robert Burns Woodward (US) accomplished the total synthesis of colchicine (1836).

 

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 (441).

 

Albert M. Kligman (US) reported that the unequivocally demonstrated spectrum of biologic activities of dimethyl sulfoxide includes enhancement of penetration through plant and animal membranes and preservation of living cells and tissues during freezing. It is exceptionally nontoxic. The acute median lethal dose values for mice are, for example, (a) 21,400 mg/kg (oral administration), and (b) 3,820 mg/ kg (intravenous administration) (955).

 

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 (1650).

 

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 (1111).

 

Ivan Stanley De la Lande (AU) and Michael J. Rand (AU) described the pharmacology of an isolated, perfused nerve-blood vessel preparation which responded rapidly and reproducibly to sympathetic nerve stimulation. As a result, the preparation has come into widespread use for the study of adrenergic transmission in arteries and of the modification of transmission by drugs, particularly drugs acting via pre-synaptic receptors (403).

 

Jenifer J. Jowsey (US), Patrick J. Kelly (US), B. Lawrence Riggs (US), Anthony J. Bianco, Jr. (US), Donald A. Scholz (US), and Jacob Gershon-Cohen (US) found that quantitative microadiography permits comparison of stained sections of bone with a microradiograph depicting mineral distribution. Also, that bone formation, resorption, abnormalities of mineralization, and differences in remodeling can be quantitated in metabolic bone diseases, and the early effects of therapy in bone disease can be evaluated (877).

 

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 (1101).

 

Frederick Clark (GB) and D.B. Horn (GB) compared the diagnostic accuracy of the PBI (plasma bound iodine), the resin uptake of 131l-T3, and their mathematical product: the free thyroxine index. The latter was shown to give the better diagnostic discrimination in patients with thyroid disease and corrected for variations in protein binding of thyroid hormones seen in certain conditions, e.g., pregnancy [Clark, 1965 #24052}.

 

Titus H.J. Huisman (US) and Andree M. Dozy (US) presented a modified procedure for the separation of various hemoglobin types by anion exchange chromatography. DEAE-Sephadex, A-50 medium, was preferred over DEAE-cellulose as chromatographic medium. Complete separations of many hemoglobin fractions were obtained by applying a single pH gradient to the columns using TRIS-HCl buffers of reasonably high concentrations (0.05 M). The method was applicable both for analytical and preparative purposes (818).

 

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 (1722).

 

David T. Dennis (US), Christian D. Upper (US), and Charles A. West (US) show that several plant growth retardants, which were thought to act by inhibiting gibberellin biosynthesis in vivo, specifically inhibit cyclization of trans-geranylgeranyl pyrophosphate to form kaurene in the first step unique to gibberellin biosynthesis (425).

 

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 (1416).

Reginald William Butcher (US), Ren-Jye Ho (US), Raymond H.C. Meng (CN-CA-US), and Earl Wilbur Sutherland, Jr. (US) showed that elevated cellular cyclic AMP stimulates lipolysis (239).

 

Robert Tod Schimke (US), E.W. Sweeney (US), and Cheston M. Berlin, Jr. (US) from their studies of the rat liver, concluded, “rates of enzyme synthesis are mediated by hormonal action, whereas substrates or cofactors act by altering the rate of enzyme degradation" (1484).

 

Herbert Weissbach (US), Betty G. Redfield (US), Herbert Dickerman (US), and Nathan Brot (US) investigated the effects of cobamide derivatives on the formation of the holoenzyme that catalyzes the terminal reaction of the pathway in which a methyl group from a folate derivative is added to homocysteine to generate methionine. It was known that the holoenzyme is formed in the presence of the vitamin and that the vitamin or a derivative of B12 needed to be added to the apoenzyme to fulfill the cobamide requirement for the enzymatic reaction. They showed that certain alkylcobamides react with the apoenzyme forming an inactive enzyme, which is readily converted to active holoenzyme by exposure to visible light. From these experiments, they deduced that a methyl B12 intermediate is likely involved in the mechanism (1794).

Robert T. Taylor (US) and Herbert Weissbach (US) studied the role of S-adenosyl-L- methionine, a cofactor that is necessary for the conversion of homocysteine to methionine. From the cofactor activities of various related compounds, they suggested that S-adenosyl-L- methionine activates the vitamin B12 enzyme by methylation (1655).

 

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 (1731).

 

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; using two of the “energy-rich” bonds of adenosine triphosphate surmounts the energy barrier. This essentially allows the reversal of glycolysis (342-345).

 

John Leslie Fahey (US) and Eugene M. McKelvey (US) performed a quantitative determination of serum immunoglobulins in antibody-agar plates (526).

 

William D. Odell (US), John F. Wilber (US), and William E. Paul (US) developed a radioimmunoassay capable of quantifying human thyrotropin (hTSH) in serum. Very scarce, highly purified hTSH was used to immunize two rabbits; each developed high titer antisera. Separation of bound from free hormone was by differential alcohol/saline solubility —antibody bound hTSH was precipitated; free hTSH remained in solution. Data on 101 patients with varied thyroid function were reported (euthyroid, pregnant, hypopituitary, hyperthyroid, and myxedematous). Several patients had repeated measurements of serum TSH during treatment with antithyroid drugs or thyroxine (1270).

 

E. Frederick Wheelock (US) found that phytohemagglutinin (PHA) from the kidney bean induces in human leukocyte cultures an inhibitor of the cytopathic effects of Sindbis virus. The physicochemical and biological properties of this virus-inhibitor are like those of interferon induced by Newcastle disease virus (1798). Note: This is interferon-gamma, the sole member of the interferon type II class, and was the first identified lymphocyte-derived mediator.

 

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 (1009; 1666).

 

David J. Weatherall (GB), John B. Clegg (GB), and Michael Naughton (GB) figured out how to separate the α and β chains of hemoglobin (1771).

David J. Weatherall (GB) and John B. Clegg (GB) developed a way to accurately measure rates of α- and β-globin synthesis. Applying their scheme to blood from thalassemic patients they generated the first clear evidence that thalassemias spring from imbalanced globin-chain production. Note: Many groups subsequently adapted the method to define defects that underlie different forms of thalassemias.

Sergio Ottolenghi (IT), W. George Lanyon (US), John H. Paul (US), Robert Williamson (US), David J. Weatherall (GB), John B. Clegg (GB), Jon Pritchard (GB), Sa-nga Pootrakul (TH), and Wong Hock Boon (SG) showed that babies who were stillborn because of a particularly severe form of α thalassemia did not make any α chains (1292).

David J. Weatherall (GB), and Paul F. Milner (GB) suggested that the messenger RNA blueprint for the α chain may encode an amino acid at the spot where it normally would instruct the protein-making machinery to stop. Consequently, the cell continues adding amino acids until it fortuitously hits another "stop" signal. This genetic glitch somehow results in diminished amounts of α hemoglobin (312).

William G. Wood (GB) and David J. Weatherall (GB) demonstrated that fetal blood cells start manufacturing small amounts of β hemoglobin chains at eight weeks' gestation (1833).

John M. Old (GB), Ryk H. Ward (GB), Mary Petrou (GB), F. Karagözlu (GB), Bernadette Modell (GB), David J. Weatherall (GB) published the first series of first-trimester diagnoses of β thalassemia (1280).

Bernadette Modell (GB), Elizabeth A. Letsky (GB), Darren M. Flynn (GB), Réka Petö (GB), and David J. Weatherall (GB) significantly advanced "chelation" therapy, to remove excess iron from the body. In particular, they modified a constant-infusion procedure devised by David Nathan (Children's Hospital Medical Center, Boston) (1183).

David J. Weatherall (GB), Douglas R. Higgs (GB), Cody Bunch (GB), John M. Old (GB), David M. Hunt (US), L.C. Pressley (), John B. Clegg (GB), Nicholas C. Bethlenfalvay (US), Soren Sjolin (GB), Robert D. Koler (US), Ellen Magenis (US), Jennifer L. Francis (US) and David Bebbington (GB) identified forms of the hemoglobin H blood disorder associated with mental retardation (1772).

 

David M. Gates (US), Harry J. Keegan (US), John C. Schleter (US), and Victor R. Weidner (US) reported the spectral reflectance, transmittance, and absorptance of plant leaves in the ultraviolet, visible, and infrared frequencies. Mechanisms for the interaction of radiation with a leaf are described. The amount of sunlight absorbed by a leaf through clear or overcast sky is given and seasonal changes in leaf properties (601).

 

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 (1835).

 

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 (828).

 

Igor Bert Dawid (US) found that an egg of the frog Xenopus laevis contains orders of magnitude higher molecular DNA than the amount expected of a single cell (400).

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 (401). These discoveries led to the realization that an individual's mitochondria are maternally inherited.

Eleftherios Zouros (GR-CA), Kenneth R. Freeman (CA), Amy Oberhauser Ball (CA), Grant H. Pogson (CA-GB), Carlos Saavedra (ES), David Owen Francis Skibinski (GB), Catherine Gallagher (GB), and Christine M. Beynon (GB) presented some rare exceptions where mitochondrial DNA is inherited through paternal transmission (1543; 1871; 1872).

 

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 by Streptomyces cacaoi (1635).

 

C. Fred Fox (US) and Eugene Patrick Kennedy (US) partially purified a surface protein (permease) of Escherichia coli that specifically recognizes beta-galactosides (569). 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 (1678; 1679; 1826).

 

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 cloverleaf like secondary structure (794).

 

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 (186; 1093).

 

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 (1169).

 

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 (1338).

 

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 could synthesize infectious viral RNA from precursor nucleotides (1295; 1575). 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 (1119).

 

Robert Hill (GB) discovered that illuminated chloroplasts can affect chemical reductions (767).

 

Margarita Salas (ES), Marvin A. Smith (US), Wendell M. Stanley, Jr. (US), Albert J. Wahba (US), and Severo Ochoa (ES-US-ES) used a cell-free system consisting of Lactobacillus arabinosus supernatant with low nuclease activity combined with Escherichia coli ribosomes to successfully determine the direction of the genetic message. Azotobacter polynucleotide phosphorylase was used to prepare short polyadenylic acid messengers with one cytidine residue at the 3'-end. These polynucleotide messengers produced water-soluble lysine polypeptides with COOH- terminal asparagines, thus confirming that the polynucleotide message is read from the 5'- to 3'-end. These results also unequivocally established that AAC is the nucleotide sequence for one of the asparagine-coding triplets (1458). Ochoa and Grunberg-Manago had earlier isolated polynucleotide phosphorylase. See, Grunberg-Mango, 1955a.

 

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) (44; 224; 225; 537; 538; 771; 886-889; 959; 1371-1373; 1379; 1479; 1480; 1865; 1866).

 

Kurt Mühlethaler (CH), Hans Moor (CH) and Jan Wlodzimierz Szarkowski (CH) postulated a model of the thylakoid membrane, consisting of a lipid bilayer in which globular protein complexes were embedded. For their geometry, these particles appeared able to bridge the lipid layer contacting proteins on the opposite side of the membrane. The possible formation of protein bridges seemed potentially important for a better understanding of transport processes (1204).

Daniel Branton (US) used freeze-etching, a new method of preparing specimens for electron microscopic examination, to split membranes in the frozen specimen to expose inner membrane faces. Examination of these suggests that the organization of biological membranes is an extended bilayer interrupted by globular subunits (182).

 

Britton Chance (US) did work critical in assigning carriers to a sequence in mitochondrial electron transport (289).

 

Floyd C. Rector, Jr. (US), Norman W. Carter (US), and Donald W. Seldin (US), using rats, concluded that HCO3- reabsorption in the proximal tubule was mediated by H+ secretion, but that carbonic anhydrase located in the luminal membrane of the cell prevented H2CO3 from accumulating in the tubular fluid. It was also concluded that HCO3- reabsorption in the distal segment was accomplished by H+ secretion (1391).

 

William S. Bullough (GB) put forward a new concept of the control of tissue growth by mitotic inhibitors, called chalones. Slowly this concept has become generally accepted, and it has also proved to have a significant bearing on the understanding of cancer (223).

 

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 (78).

 

J. Claude Bennett (US), Leroy E. Hood (US), William J. Dreyer (US), and Michael Potter (US) examined immunoglobulin structural variation through analysis of L-chain type proteins produced by a variety of distinct plasma cell tumors of the mouse. It appeared from these studies that these proteins all contained a common amino acid sequence throughout a large portion of the molecule. Nevertheless, each of the proteins contained a unique region of amino acid sequence which allowed it to be distinguished from any other on the basis of certain variable peptides. This suggested the possibility of a second chain, loosely linked by non-covalent bonding or joined through disulfide bonding. It became apparent from the peptide map data that variation must occur in some type of “specialized area”. Although the role of the various chains of immune globulins is not yet clear, they suggested that this remarkable type of amino acid sequence variation reflects in part the mechanism by which specificity is conferred (122).

 

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 (317; 434; 435).

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 (317; 861; 1520; 1761).

 

Johan A. Hellebust (CA) reported the release of organic substances synthesized from photoassimilated 14CO2 by a large variety of cultured marine microalgae. Similar investigations were also made with natural marine phytoplankton populations to evaluate the importance of excretion in relation to primary productivity (741).

 

Shinpei Kasakura (CA), Louis Lowenstein (CA), Julius Gordon (CA), and Lloyd D. MacLean (CA) found that the medium from human leukocytes cultured in vitro with homologous leukocytes or heterologous leukocytes contains a mitogenic substance produced by the leukocytes (645; 905).

 

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 (305).

 

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 (51). 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 (787).

Robin C. Valentine (GB) and Helio Gelli Pereira (BR-GB-BR) reported the first analysis of the structure of adenovirus (1721).

 

Ned H. Wiebenga (US), Patricia A. Webb (US), Karl M. Johnson (US), Ronald B. MacKenzie (US), Merle L. Kuns (US), Johng S. Rhim (US), and Bunsiti Simizu (US) discovered Machupo virus to be the etiological agent of Bolivian hemorrhagic fever (BHF), also known as black typhus or Ordog Fever, a hemorrhagic fever and zoonotic infectious disease originating in Bolivia after infection by Machupo mammarenavirus. Calomys callosus, the field mouse, is the reservoir of the virus (1406; 1773; 1807).

 

Wayne H. Thompson (US), Bernard Kalfayan (US), and Ralph O. Anslow (US) discovered La Crosse encephalitis in 1965, after the virus was isolated from stored brain and spinal tissue of a child who died of an unknown infection in La Crosse, Wisconsin in 1960 (1671). Note: The mosquito Aedes albopictus is an efficient vector of La Crosse virus.

 

Yoshihisa Suyama (JP) and John R. Preer, Jr. (US) discovered that the mitochondrial DNA of Tetrahymena is linear (most known mtDNA is circular) (1632).

 

Clarence C. Bowen (US) and Thomas Edgar 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 (170).

 

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 (168). This result indicated that recognition of the operator and inducer is linked to the structure of the protein produced by the i gene (168).

 

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 (974).

 

Renato Baserga (US) expressed the advantages of studying tumor growth in terms of cell cycle kinetics and opened the possibility of a new field of endeavor in biochemistry and cell proliferation (93).

 

Paul H. Black (US) and George Joseph Todaro (US) found that a virus that is a hybrid between the simian virus 40 and adenovirus 7 could induce transformation in both human and hamster tissue in vitro (147).

 

Paul H. Black (US) and Wallace Prescott Rowe (US) performed experiments demonstrating that there is not an association between morphological transformation and tumorigenicity (146).

 

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 (714).

 

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 (1827).

 

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 class of nucleic acid, either RNA or DNA, is fused with one that did, synthesis is initiated in the nucleus of the inactive partner (712).

 

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 (1628; 1629).

 

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 (287; 288; 455; 456; 1382).

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) (1423). 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) (922).

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 (1421; 1422; 1550).

 

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 (128).

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 (DE-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 (266; 308; 446; 728; 927; 1239; 1332; 1569; 1571-1573).

 

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 (372).

 

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 that 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 (179; 875; 1094; 1095; 1511). 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 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 (1587).

 

Andrew Wright (US), Marcelo A. Dankert (AR), and Phillips W. Robbins (US) discovered and elucidated the role of carrier lipids in polysaccharide synthesis (1841).

 

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 (1331).

 

Albertus Burgerjon (FR), and Pierre-Francis Galichet (FR) discovered that Bacillus thuringiensis endospores contain a protein crystal (Bt toxin) which kills certain insect larvae (228). In more recent times the Bt gene has been transferred to plants such as tomatoes making them resistant to certain insects (784).

 

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 (1205).

 

Brian S. Cox (US) discovered a non-Mendelian determinant, [PSI⁺] that affects the level of expression of nonsense suppressors (356).

Francois Lacroute (FR) discovered another non-Mendelian element, [URE3] that affects the level of expression of nonsense suppressors (986).

Reed B. Wickner (US) proposed that these cytoplasmically inherited elements are prions (1806).

 

Emanuel Margoliash (IL), Jay R. Schenck (US), Martha P. Hargie (US), S. Burokas (US), Ward R. Richter (US), Grant 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 (1049; 1109).

 

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 (1143).

 

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 (871).

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 (1412; 1413).

 

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 (509; 668). 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 (16).

 

John Langridge (AU) described three mutants of Arabidopsis requiring specific vitamins for growth at certain temperatures. These mutants comprise naturally occurring ecotypes in Spain and Austria. Experiments indicate that an inability to make biotin at high temperatures may be adaptively advantageous. The consequent cessation in growth is a balanced one, readily reversible by a lowering of temperature, which allows the plant to escape the irreversible sterilizing effect of heat (994).

 

Ola Nilsson (SE), Luciano Barajas (US), Jacqueline Müller (US), Svatopluk Dolezel (SE), Lars Edvinsson (SE), Christer Owman (SE), and Titti Owman (SE) established the intimate relationship between the renin producing cells of the juxtaglomerular apparatus in the kidney and sympathetic nerve terminals (79; 454; 1238).

 

Jane Swanson (GB), Herbert F. Polesky (GB), Patricia Tippett (GB), and Ruth Sanger (GB) discovered a 'new' human blood group antigen named Do^a (1637).

 

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 (1684).

Joseph Felix Heremans (BE), M.T. Heremans (BE), and Hermann Edward Schultze (BE) first described IgA in serum in 1959 (751).

 

Stewart S. 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 (1505).

 

Raymond D.A. Peterson (US), Max D. Cooper (US), and Robert Alan Good (US), based on clinical observations and experimental laboratory studies, categorized immunodeficiency diseases of man based on their underlying cellular deficiency. This paper outlined the rationale for this classification (1333).

 

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 (1850).

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 (989; 1530; 1860).

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 (1696; 1715).

 

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 (1298; 1765; 1766).

 

Brian S. Bull (US), Marvin A. Schneiderman (US), and George Brecher (US) described a method for the machine counting of platelets in human blood utilizing small samples of platelet-rich plasma. The method includes correction factors by which the resultant count determined on platelet-rich plasma can be transformed into a whole blood platelet count (222).

 

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’ (1328; 1781).

 

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 (663; 706).

 

Donald Kennedy (US) and Kimihisa Takeda (US), in their work on crustacean motor systems, established a general principle of motor control: there is a division of labor among available motor neurons and muscle fibers. The investigators recognized two types of muscle in the crayfish abdomen, which they categorized as slowly contracting or 'tonic' (capable of sustained, fatigue-resistant, graded contractions), and rapidly contracting or 'phasic' (producing very rapid, twitch-like, non-sustained contractions). The two types of muscle are anatomically separated and supplied by two sets of motor neurons with very different physiological properties. The motor neurons of the tonic musculature exhibit a lot of spontaneous impulse activity and are responsible for postural adjustments and everyday locomotion. In contrast, the motor neurons of the phasic musculature are silent most of the time, but when recruited for vigorous escape activity they fire a few impulses at a time in intermittent bursts, producing relatively brief episodes of intense movement. Many variations on this theme have since been found throughout the animal kingdom, but in selecting the musculature of the crayfish abdomen, Kennedy and Takeda presented an extremely clear-cut case of complete separation of phasic and tonic motor systems, with anatomically distinct sets of muscles innervated by separate groups of specialized motor axons (now often referred to as 'phasic' and 'tonic' motor axons) (934; 935).

Robert E. Burke (US) found that the principle of differential recruitment of 'phasic' and 'tonic' motor systems for specific acts applies in mammals as well. For example, in the medial gastrocnemius muscle of the cat, only about 25% of the motor unit pool innervating slow-twitch muscle fibers is used for posture and walking; about 60% of the motor unit pool innervating 'fast fatigable' muscle fibers is used only for demanding efforts such as jumping (233).

 

Michel Bouteille (FR), C. Fontaine (FR), C.L. Vedredd (FR), Jacques 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 (80; 169; 334; 917; 1659).

 

William E. Hathaway (US), Loretta P. Belhasen (US) and Helen S. Hathaway (US) discovered the human blood coagulation factor called Fletcher factor (729). This factor was later to be identified as plasma prekallikrein.

 

Eric Richard Kandel (US) and Ladislav Tauc (FR) introduced a 'simplified' brain (the Aplysia nervous system) to study the cellular and molecular basis of organized neuronal interactions. They presented neurophysiological evidence that strength of many synapses between pairs of neurons change when the neurons on both sides of the synapse are repeatedly electrically active at the same time (894; 895).

Pramod K. Dash (US), Binyamin Hochner (US), and Eric Richard Kandel (US) showed that extracts of the Aplysia central nervous system and extracts of sensory neurons contain a set of proteins, including one with properties like mammalian cAMP-responsive-element-binding proteins, that specifically bind the mammalian cAMP-responsive-element (CRE) sequence. Microinjection of the CRE sequence into the nucleus of a sensory neuron selectively blocks the serotonin-induced long-term increase in synaptic strength, without affecting short-term facilitation. Taken together, these observations suggest that one or more CRE-like transcriptional activators are required for long-term facilitation (385).

 

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 (495).

 

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 (702).

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 (898).

 

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 (607).

Richard K. Sibley (US), David E.R. Sutherland (US), Frederick C. Goetz (US), and Alfred F. Michael (US) proved that Gepts’ suggestion was correct (1527).

 

John D. Utley (SE) and Arvid Carlsson (SE) discovered that dopamine (prolactin-inhibiting hormone) is a neurotransmitter in the brain (1719).

 

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 (970-972).

Hanns Möhler (CH) and Toshikazu Okada (JP) showed that the tranquilizer, benzodiazeprine, acted on the neurotransmitter, GABA (1185; 1186).

 

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 (770).

 

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 (1347).

Eugene B. Buynak (US), Maurice Ralph Hilleman (US), Robert E. Weibel (US), and Joseph Stokes, Jr. (US) described the development and clinical testing of their attenuated rubella virus vaccine prepared in duck embryo cell culture (245).

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 (1687).

 

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” (747-749; 1136; 1846).

 

Bayard H. Brattstrom (US) confirmed that reptiles are not “cold- blooded” and that they can maintain their body emperature at high levels by behavior. Yet it also showed that temperate, tropical, alpine, desert, shade-dwelling, and burrowing reptiles have a diversity of thermal requirements and abilities to regulate body temperature. It introduced the notion of physiological control of temperature regulation in some species (183).

 

Horace B. Barlow (GB) and William R. Levick (AU) discovered motion selectivity in the rabbit retina (85).

 

Malcolm Fowler (AU) and Rod F. Carter (AU) first described the potential for free-living amebae to cause disease when they described a case of acute pyogenic meningitis probably due to Acanthamoeba sp. (568).

Cecil G. Butt (US) reported several cases in Florida, coining the term primary amebic meningoencephalitis (PAM) (243).

 This is very dangerous infection. Naegleria fowleri usually infects people when contaminated water enters the body through the nose. Once the ameba enters the nose, it travels to the brain where it causes PAM, with an in-hospital case fatality rate of ~97% (3% patient survival rate).

The etiological agent was named Naegleria fowleri to honor Mathieu Naegler (FR) and Malcolm Fowler (AU) above.

 

Thomas A. Stamey (US), Duncan E. Govan (US), and John M. Palmer (US) presented methodology for accurately localizing the specific site of urinary tract infections, especially the separation of bladder from renal infection and the identification of the urethra or prostate as the tissue site of bacterial persistence in the male. Additional data demonstrate that the cure of kidney infections is dependent upon the urinary concentrations of antimicrobial agents and not the serum levels (1584).

 

Phil Gold (CA) and Samuel O. Freedman (CA) discovered a carcinoembryonic antigen (CEA) produced during growth of cancer cells of the digestive system (633). 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 (2). 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 (1660).

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) (952).

 

Charles E. Reed (US), Abe Sosman (US), and Robert A. Barbee (US) described pigeon-breeders' lung. A newly observed interstitial pulmonary disease (1392).

 

Roscoe O. Brady (US), Julian N. Kanfer (US), and David Shapiro (US) discovered the precise metabolic defect—a 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 (180; 181).

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 (1324).

 

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 (1354).

 

Forrest M. Bird (US) developed the first highly reliable, low-cost, mass-produced medical respirator in the world, the Bird Mark 7 (143). In 1970, he introduced the first infant ventilators, the BABYbird, which reduced infant mortality by 60% for infants with Infant Respiratory Distress Syndromes (IRDS) (142).

 

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 (39). 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 (265).

 

Giacomo Meschia (US), Donald Henry Barron (US), Julian R. Cotter (US), and Caoimhghin S. Breathnach (GB) presented a method for the introduction of plastic catheters into the umbilical vessels of fetal goats and lambs whereby samples of blood may be obtained over a period of days and weeks in conditions in which the mother is free from obvious stress. The results of the analyses of samples so obtained, indicate that (1) the oxygen capacity of the fetal blood does not increase after 100 days and (2) that the oxygen saturation does not fall systematically in the last month of gestation. Data on the day to day variations in the blood levels of oxygen, carbon dioxide and pH are reported (1150).

 

Stephen E. Epstein (US), Brian F. Robinson (GB), Richard L. Kahler (US), and Eugene Braunwald (US) determined the sympathetic contribution to the cardiac response to exercise in man using propranolol, a beta-adrenergic blocking agent. Blocking sympathetic stimulation reduced heart rate, cardiac output, and mean arterial pressure during submaximal and maximal exercise, and diminished both maximum VO2 and capacity for strenuous exertion (510).

 

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 (1607). The syndrome is thought to arise from a mutation of several collagen genes during fetal development.

 

Gaston Cordier (FR), Henri Garnier (FR), Jean-Pierre Clot (FR), M. Bertrand (FR), P. Camplez (FR), J.P. Gorin (FR), Philippe H. Clot (FR), Jean-Paul Rassinier (FR), M. Nizza (FR), and Richard N. Lévy (FR) observed that liver allografts in untreated pigs frequently were not rejected (348; 599).

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 (1589).

 

Evan M. Hersh (US) and Joost J. Oppenheim (US) investigated whether the impaired in vivo immunocompetence in Hodgkin's disease was related to an intrinsic lymphocyte defect expressed by impaired in vitro blastogenic response. They found impaired blastogenesis and mitoses in the lymphocytes of Hodgkin patients compared to controls. These responses correlated with skin test anergy, the stage of disease, and the prognosis. This paper is one of the first to relate impaired lymphocyte competence to stage of disease and prognosis in malignancy (754).

 

Evan M. Hersh (US), Gerald P. Bodey (US), Boyd A. Nies (US), and Emil Jay Freireich (US) studied the causes of death in acute leukemia: a ten-year study of 414 patients from 1954-1963. This was one of the first clinical studies specifically to evaluate the causes of death in malignant disease and served as a prototype for subsequent similar studies. It proved that supportive care can have a major effect on the course of malignant disease. Most important was the observation that leukemia patients often do not die of the direct effects of the disease. These implications have influenced developments in supportive care, antibiotic therapy, chemotherapy, and immunotherapy. Today most patients with leukemia enter complete remission and 50% of children and 20% of adults are apparently cured (752).

 

Lee W. Wattenberg (US) reported that a variety of chemicals are shown to prevent cancer induced by chemicals by activating the detoxification system, competitively inhibiting the carcinogen, preventing initiation of carcinogenesis and other unknown mechanisms (1768; 1769). Note: The term chemoprevention was later coined as a new area of focus in cancer research.

 

Vincent T. DeVita, Jr. (US), Mary Anne Hahn (US), and Vincent T. Olivorio (US) reported the first chemotherapy-induced cure of adults with advanced Hodgkin lymphoma. They found that a combination of four drugs – mechlorethamine, vincristine (Oncovin), procarbazine and prednisone, a regimen named MOPP – induced long-term remissions in more than 50 percent of adults with the disease in a clinical trial (431).

 

Henry Jay Heimlich (US) invented the flutter valve (Heimlich valve) which greatly facilitated the surgical removal of fluid and air from a collapsed lung (734; 735).

 

William Beetham (US), Lloyd M. Aiello (US), Marios C. Balodimos (US), and Lajos Koncz (US), beginning in 1965, pioneered pan-retinal coagulation, a treatment that uses lasers to halt the sight-stealing proliferation of blood vessels in people with diabetes (113).

 

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 (149; 413; 414; 600; 1044).

 

Jose Maria Gil-Vernet (ES) introduced extended pyelolithotomy, a technique applicable for removal of most staghorn, and large pelvic and caliceal calculi (620).

 

Jean Dennis Aicardi (FR), Jacques Lefebvre (FR), A. Lerique-Koechin (FR), Jean-Jacques Chevrie (FR), and Francoise Rousselie (FR) described the combination of infantile spasms, agenesis of the corpus callosum, chorioretinal lacunae and psychomotor deterioration later called Aicardi syndrome (13; 14).

 

Louis J. Poirier (CA) and Theodor L. Sourkes (CA) presented evidence that a well-identified group of neurons (originating in the substantia nigra) exert through their efferent fibers a direct role in the elaboration of a specific substance (dopamine) in a distant structure (the striatum) contributes to a better understanding of brain circuitry. Moreover, this intracerebral 'dopaminergic' pathway is directly involved in Parkinson's and related diseases (1349).

 

Charles Miller Fisher (CA-US) and Hiram B. Curry (US) contributed greatly to the understanding of stroke, more specifically carotid artery disease and lacunar infarcts and their syndromes. With regard to the lacunar syndromes he described the concept, the "pure motor stroke", the "pure sensory stroke", and the mechanism underlying the different stroke syndromes (544-548; 550; 553).

Fred H. Hochberg (US), Charles Miller Fisher (CA-US), and Glenn H. Roberson (US) contributed to the understanding of subarachnoid hemorrhage due to cerebral aneurysms (776).

Fred H. Hochberg (US), Charles S. Bean (US), Charles Miller Fisher (CA-US), and Robert G. Ojemann (US) made a number of contributions to the understanding of cervical artery dissection (carotid artery dissection and vertebral artery dissection) (549; 554; 775).

Fisher proved, by a series of pathological studies, the relationship between stroke and the formation of blood clots in the heart in patients with atrial fibrillation. He also showed the relationship between stroke and carotid artery stenosis, which made preventive surgery possible and greatly reduced the incidence of subsequent strokes (551). He contributed greatly towards the current use of anticoagulants for stroke prevention in atrial fibrillation.

Charles Miller Fisher (CA-US) took careful histories from stroke patients within the course of one week to reveal the passing mention of a transient monocular blindness contralateral to the hemiplegic side. He avoided the possible pitfall of misinterpreting this symptom as a hemianopic phenomenon, and it was this careful detail that contributed to the discovery of the transient ischemic attack (TIA) as a warning sign of stroke. He realized that ischaemic stroke often followed transient neurological symptoms in the same arterial territory (552).

 

Vincent Paul Dole (US), Marie E. Nyswander (US), and Mary Jeanne Kreek (US) developed methadone treatment for heroin addiction (450-453).

 

Dame Cicely Mary Strode Saunders (GB) founded the modern hospice movement (St. Christopher’s hospice) during the early 1960s (1475).

 

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 (203).

 

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 being selected for (154).

 

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 (1800).

 

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 (1064).

 

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 (1493). 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 (82; 1492).

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 (938).

 

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 (969). The remains are dated at c.a 185,000 BP

 

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 a part of the hominid line, the line that eventually led to Homo sapiens (1535).

 

1966

Reflecting on his study of salamanders blinded 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 descendants.” Victor Chandler Twitty (1705).

 

“Only the genius or unsung hero can make an intellectual judgment when his feelings, emotions and beliefs are engaged.” William Bennett Bean (103).

 

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 Grenville Turner (US) presented the first 40Ar/39Ar dating results (1146).

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 (473; 1175). 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) (798). 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: Archer John Porter Martin (GB) predicted HPLC in 1941, in his famous paper with Richard Laurence Millington Synge (GB) (1113).

 

Norman Gulack Anderson (US) invented the rate-zonal ultracentrifugation process (33).

 

David T. Denhardt (CA) developed a membrane-filter technique for the detection of complementary DNA (423).

 

Carl-Bertil Hugo Laurell (SE) described a method for rapid quantitative analysis of proteins with a charge differing from that of the bulk of the immunoglobulins. The method utilizes the difference between the rate of electrophoretic migration of proteins and of their antibody complexes in agarose gel (999; 1000).

 

Thomas J. Vecchio (US) observed that when a new test for a disease is being evaluated it is customary to perform the test in two selected groups of subjects: those with an indisputable diagnosis of the disease by other criteria; and those from the normal population who have no evidence of the disease and in whom all the factors known to result in a higher than normal risk of the disease can be excluded. The test results may be expressed dichotomously as "positive" or "negative," or by some numerical units along a scale, usually with the bulk of values on either side of an arbitrary dividing line (1729).

 

W. David Loomis (US) and Julian Battaile (US) found that inability to isolate active enzymes from certain plants was found to be due to plant phenolic compounds. These bind to proteins more strongly than biochemists had realized. Polymeric adsorbents, adapted from brewing chemistry, released the plant enzymes from these complexes (1065).

 

Mary Ellen Jones (US) and Sally E. Hager (US) isolated the glutamine-dependent carbamyl-phosphate synthetase from the rat liver. They were the first to demonstrate the existence of carbamyl-phosphate synthetase II (697; 873).

 

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 (1840).

 

Søren Jensen (SE) discovered polychlorinated biphenyls (PCBs) in the environment (863).

Robert W. Risebrough (US), P. Reiche (US), David B. Peakall (US), Steven G. Herman (US), and Monte N. Kirven (US) showed that polychlorinated biphenyls (PCBs) are widely dispersed in the global ecosystem and are powerful inducers of hepatic enzymes which degrade oestradiol. Together with other chlorinated biocides, such as DDT, they could account for a large part of the aberration in calcium metabolism which has been observed in many species of birds since the Second World War (1410).

 

Morris Lieberman (US), Alice Kunishi (US), L.W. Mapson (GB), and D.A. Wardale (GB) demonstrated that methionine is a precursor of ethylene and they were the first to show that ethylene carbons are derived from carbons 3 and 4 of methionine (1046).

Douglas O. Adams (US) and Shang Fa Yang (US) identified 1-aminocyclopropane-1-carboxylic acid as an intermediate that proved to be the missing link between methionine and ethylene, establishing the following biosynthesis sequence for ethylene: methionine / S-adenosylmethionine / 1-aminocyclopropane-1-carboxylic acid / ethylene (5).

 

Toshio Ando (JP) and Koichi Suzuki (JP) determined the amino acid sequence of clupeine, a protamine of salmon (36; 37; 1633; 1634). 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.

 

Alvin Rees Midgley, Jr. (US) developed a radioimmunoassay for human luteinizing hormone (LH) (1157).

Gordon D. Niswender (US), Alvin Rees Midgley, Jr. (US), Scott E. Monroe (US), and Leo E. Reichert, Jr. (US) developed a radioimmunoassay procedure for quantification of luteinizing hormone (LH) in the blood of rats utilizing an immunological cross-reaction between rat LH and a unique antiserum produced in a rabbit against ovine LH. The assay was characterized carefully to demonstrate that other pituitary hormones or components of serum did not interfere with the measurement of LH. The extreme sensitivity of the assay (5 pg NIH-LH-S1) allowed quantification of the hormone in as little as 0.02 to 0.2 ml serum (1243).

 

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 (504; 505).

 

Robert L. Letsinger (US) and Viswanath Mahadevan (IN) were among the first to accomplish the in vitro synthesis of oligodeoxyribonucleotides (1028).

 

Ira Harry Pastan (US), 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 (1016; 1017; 1311).

 

Michael B. Kemp (GB) and John Rodney Quayle (GB) confirmed the presence in crude cell extracts of Pseudomonas metnanica (now Methanomonas methanica) of a novel formaldehyde-condensing enzyme indicating the presence of a pentose phosphate cycle for formaldehyde assimilation, analogous to the RuBP pathway for carbon dioxide assimilation. This was confirmed by a thorough examination of the labelling patterns and by characterizing the novel enzyme responsible for condensing formaldehyde with ribulose monophosphate to give a sugar phosphate (932).

Mchael B. Kemp (GB) identified this sugar phosphate as a novel hexulose phosphate, d-arabino-3-hexulose phosphate (931).

John Rodney Quayle (GB) eventually completed the pathway, now known as the ribulose monophosphate pathway (RuMP pathway) by purifying and characterizing a second novel enzyme, hexulose phosphate isomerase, and by demonstrating the presence of essential cleavage and rearrangement enzymes (1370).

 

 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 (758; 1652).

 

John L. Hess (US) and Nathan Edward Tolbert (US) detected glycolate, glycine, serine, and glycerate formation during photosynthesis by tobacco leaves (759).

John L. Hess (US), Nathan Edward Tolbert (US), William J. Bruin (US), and Edward B. Nelson (US) established that the glycolate pathway of metabolism is present in unicellular green algae (213; 760).

Arun Goyal (IN-US) and Nathan Edward Tolbert (US) associated glycolate oxidation with photosynthetic electron transport in plant and algal chloroplasts (661).

 

Marlene L. Forrester (CA), Gleb Krotkov (CA), and Charles D. Nelson (CA) helped establish the interrelationship between O2, CO2, photosynthesis, and photorespiration in C3 plants (567).

 

Rodney Robert Porter (GB), Ronald C. Weir (GB), Gerald Maurice Edelman (US) and Joseph A. Gally (US) described the structure and nature of antibodies (481; 483; 1356; 1357).

 

Hugh R. Wallace (GB) and Max Luciano Birnstiel (CH) were the first to purify a eukaryotic chromosomal gene. It was amphibian ribosomal DNA (1749).

 

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 (624).

Mark Steven Ptashne (US) isolated the lambda phage repressor shortly thereafter (1365).

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 (625; 1366). Note: This was the first genetic control protein to be isolated.

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 (834).

Larry Eron (US) and Ricardo Block (US) elegantly confirmed the promoter using an in vitro transcription system (513).

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 (623).

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 P_R and P_L promoters, but also activates transcription at the lambda P_RM promoter. They proposed that activation required a protein–protein interaction between the lambda repressor and RNA polymerase (680; 777).

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 (1038).

 

Arthur Beck Pardee (US) crystallized and characterized a protein that appears to be the recognition part of the sulfate transport system of Salmonella typhimurium (1304).

 

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 (72).

 

Julien Marcot-Queiroz (FR) and Roger Monier (FR) isolated 18S ribosomal RNA (18SrRNA) from the ribosomes of Escherichia coli (1107).

 

Radoslav J. Bachvaroff (RU-US) and Veniamin S. Tongur (RU) isolated 5S ribosomal RNA (5SrRNA) from mammalian tissue (61).

 

Jerry M. Adams (US) and Mario Renato Capecchi (US) determined that N-formylmethionyl transfer RNA is the initiator of protein synthesis in Escherichia coli (6).

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 (1555).

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 (1445).

 

Douglas M. Fambrough (US) and James Frederick Bonner (US) discovered that there are only five different species of histones (each with its subspecies) (527).

 

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 (194; 358; 615-617; 1032; 1207; 1334; 1614; 1677).

 

David Freifelder (US) determined that x-ray inactivation of bacteriophage T7 results primarily from double strand breakage in DNA (578).

Henry Seymour Kaplan (US) found that in Escherichia coli single-strand scissions caused by x-irradiation are usually repaired during reincubation (901).

Robert A. McGrath (US) and Robert W. Williams (US) demonstrated that Escherichia coli possesses a mechanism, probably enzymatic, to repair DNA damaged by x-rays (1132).

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 (579).

 

Hideo Okeda (JP) and Jun-ichi Tomizawa (JP) showed that prophage P1, unlike lambda, is a plasmid and not part of the host chromosome (827).

 

Bernard S. Strauss (US), Tetsuo Searashi (JP), and Mary Louise Robbins (US) showed that an extract of Micrococcus lysodeikticus acts like an endonuclease specific for DNA that contains radiation-induced lesions, most probably pyrimidine dimers (1613). 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 (1641).

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 (587).

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 (112). 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 (DE-US), David 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 (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 (1112; 1569; 1570; 1572; 1573).

 

William Meredith Stanley, Jr. (US), Margarita Salas (US), Albert J. Wahba (US), and Severo Ochoa (ES-US-ES) 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 (1586).

Kentaro Iwasaki (US), Steven Sabol (US), Albert J. Wahba (US), and Severo Ochoa (ES-US-ES) determined that a third factor (F₃) is also necessary for initiation of the translation of mRNA in Escherichia coli (838).

Severo Ochoa (ES-US-ES) 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 (1267).

 

Hans Georg Zachau (DE), Dieter Dütting (DE), Horst Feldmann (DE), Fritz Melchers (DE), and Wolfgang Karau (DE) proposed that all tRNAs have a cloverleaf type secondary structure (1864).

 

John P. Richardson (US), using T7 bacteriophage, found that RNA polymerase has approximately 50 specific binding sites on a single T7 DNA molecule (1408).

 

Peter Traub (US), Kei-ichi Hosokawa (JP), Masayasu Nomura (JP-US), and Dieter Söll (DE-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 subsequently identified the specific protein and designated it P10 (1688-1692).

 

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) (308; 927).

 

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 (800).

William A. Held (US), Shoji Mizushima (JP), and Masayasu Nomura (JP-US) separated and purified each of the proteins in the 30 S subunit and then reconstituted functionally active 30 S subunits from these purified components and 16 S RNA. This reconstitution proved that the necessary information for the assembly of active ribosomes is contained in their molecular components rather than in some extraneous factor (739).

William A. Held (US), Byron Ballou (US), Shoji Mizushima (JP), and Masayasu Nomura (JP-US) generated a revised "assembly map” showing the cooperative effects among the various 30 S ribosomal proteins in the assembly reaction of the 30S subunit (738).

William A. Held (US) and Masayasu Nomura (JP-US) showed that the S16 and S18 ribosomal proteins from E. coli play roles in the assembly process of the 30S ribosomal subunit but do not have a functional role in the polypeptide chain elongation (740).

 

Margit M.K. Nass (US) was the first to demonstrate the circularity of mitochondrial DNA (1217).

 

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 (1670).

 

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 (975; 1639).

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 (1639; 1654).

 

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 (1431).

 

Donald L. Schneider (US), Yasuo Kagawa (US), Larry 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. Complexes 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 (885; 886; 889; 1491).

 

Richard G. Jensen (US) and James Al Bassham (US) demonstrated that isolated chloroplasts could carry out complete photosynthesis (862).

 

André Tridon Jagendorf (US) and Ernest G. Uribe (US) demonstrated that ATP could be generated in isolated chloroplasts by imposing an artificial pH gradient across the thylakoid membrane of the chloroplast (844). 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) (218; 520).

 

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 (66; 214; 669; 727; 889; 1320).

 

Charles R. Hackenbrock (US) determined that mitochondria from rat livers alter their shape as their metabolic activity varies (692).

 

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 (488; 1831). Along with Jonathan Alan King (US), Ilga Lielausis (US), and M. Henninger (US) they went on to formulate a pathway for intracellular assembly of bacteriophage T4 (946; 1832).

 

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 represents the arrangement of genes on the phage DNA molecule (788).

 

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 (1407).

 

Bill R. Brinkley (US) and T. Elton Stubblefield (US) first described the kinetochore. They saw, by electron microscopy, a trilaminar, proteinaceous disc structure that flanked the centromere (196).

 

Ludwig Guttmann (DE-GB) and Hans L. Frankel (GB) established clean intermittent self-catheterization (689).

 

Carmia Borek (US) and Leo Sachs (US-IL) showed that x-irradiation could induce cell transformation (160).

 

Dorothea Zucker-Franklin (US), Zanvil Alexander 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 (321; 1873).

 

Jane Mink Rossen (DK) and Majken Westergaard (DK) demonstrated conclusively that recombination takes place during prophase I of meiosis (1436).

 

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 (1299; 1585).

 

Sarit Kumar Shome (IN) and Usha Shome (IN) found a fungus capable of trapping nematodes (1521).

 

Sean P. Flanagan (GB) described a homozygous recessive nude (nu) mutation on chromosome 11 in mice (556).

Evagoras Michael Pantelouris (GR-GB) would later report that nude mice are congenitally athymic, leading to their widespread use in biomedical research (1301).

 

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 like those made in pseudomonas infections (1060). 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 (1739-1743).

 

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 (713; 1031).

Jack L. Hubby (US) and Richard Charles Lewontin (US) introduced the use of electrophoresis as a tool for studying polymorphisms (811).

 

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 (1).

 

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 likely 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 (845; 1665). 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 (97). The theoretical and practical studies of Hans Ericsson (SE) and Gunvor Svartz-Malmberg (SE) helped prepare the way for this advance (512).

 

George M. Hughes (US) founded the modern age of gill biophysics, by measuring various gill tissue dimensions in fish ranging from 12 g mackerel (Trachurus trachurus) to 1.5 kg angler fish (Lophius piscatorius), to analyze gill resistance to water flow. This is the first study to apply engineering principles to gills. Hughes came to two conclusions: 1) the gill surface area correlates with lifestyle in marine fishes, as Gray had already stated (666), as well as for hemoglobin-free icefish (Chaenocephalus sp.) and two fresh-water species; the sea trout (Salmo trutta) and the tench (Tinca tinca) and 2) not only was the mesh of the gill sieve formed by the interlamellar spaces calculated to be large enough to allow direct ventilation, but also the maximum calculated ventilatory rate based on the morphometric data was an order of magnitude greater than that measured physiologically (817).

 

Marian R. Neutra (US) and Charles Philippe Leblond (CA) examined the goblet cells of the rat intestine, which had the twin virtues of secreting lots of carbohydrate-loaded mucin glycoprotein and having a large, distinctive U-shaped Golgi complex. They found that radioactive sugars concentrate exclusively in the Golgi early and then move out to the mucigen granules later. The results were confirmed with other sugars and other cell types. They concluded that the Golgi is the site where simple sugars become immobilized on larger molecules (1229; 1230).

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 (1804).

 

Robert Smith (US) and Marilyn Gist Farquhar (US) working with prolactin secreting pituitary cells found that excess secretory granules are not stored but fuse with multivesicular bodies (MVBs) that then mature and fuse with lysosomes. They also noted that excess endoplasmic reticulum and ribosomes, ramped up for prolactin production, were down-regulated by autophagic structures that also converged on the lysosomal pathway (1563).

 

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 (303; 304).

 

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 could 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 (588-590; 1313; 1437).

 

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 (477; 1104; 1172; 1173; 1415).

 

E. Richard Stiehm (US) and H. Hugh Fudenberg (US) determined serum levels of IgG, IgM, and IgA immunoglobulins on 296 normal infants and children at various ages and in 30 adults. The technique employed radial immunodiffusion in agar, using monospecific antisera. The marked alterations of immunoglobulins with age, particularly in the first year of life, necessitate comparison of the immunoglobulins obtained on any pediatric patient with appropriate age-matched controls (1608).

 

Sydney Brenner (ZA-GB) and Cesar Milstein (AR-GB) discussed how molecular diversity is produced among antibodies (190).

 

Julia Bodmer (GB), Walter Fred Bodmer (GB), Rose Payne (US), Paul Ichiro Terasaki (US), and Donna L. Vredevoe (US) were among the pioneers in human leukocyte antigen (HLA) cell typing (156).

 

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 (325; 1086; 1180; 1181).

 

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 (813).

 

Andrzej Krzysztof Tarkowski (PL) developed a technique which enabled observing chromosomes in oocytes, which has been widely used in early studies of the embryo (1648).

 

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 (27-30; 1123; 1124; 1559).

 

Theodore M. Bayless (US) and Norton S. Rosensweig (S) surveyed the incidence of milk intolerance and lactase deficiency in 40 healthy nonpatient volunteers. There were 20 blacks and 20 whites. Nineteen of the 20 black subjects and two of the 20 white subjects gave a history of milk intolerance. The majority had noted the onset during or after adolescence. Lactose intolerance occurred in 20 of the 21 milk-intolerant subjects; 18 of the 20 were blacks. There was also a prominent racial difference in the incidence of low levels of intestinal lactase activity. Deficient levels were observed in 70% of the 20 blacks in contrast to only one of 20 whites. These data strongly favor a genetic etiology for the isolated lactase deficiencies seen so commonly in adults (101).

 

Elizabeth Mapelsden Ramsey (US), Chester B. Martin, Jr. (US), Harry S. McGaughey, Jr. (US), Irwin H. Kaiser (US), and Martin W. Donner (US) concluded that maternal blood pressure is the the propulsive force which drives blood into the placental intervillous spaces in discreet, fountain-like “spurts.” The incoming blood wafts aside the villi surrounding the orifices of entry, but once the propulsive force is reduced, in part by the, baffle action of the villi, the blood disperses laterally crowding the existing content of blood through the venous orifices in the basal plate into the uterine drainage channels (Fig. 8). During uterine contractions both inflow and outflow cease, in whole or in part, depending upon the strength of the contraction (1381).

 

Daniel S. Bernstein (US), Norman Sadowsky (US), D. Mark Hegsted (US), Charles D. Guri (US), and Frederic J. Stare (US) summoned evidence that osteoporosis, reduced bone density, and collapsed vertebrae was substantially higher in the low-fluoride area, especially in women. Visible calcification of the aorta was significantly higher in the lowfluoride area, particularly in men. Limited information on milk and cheese consumption does not indicate that differences in calcium consumption are a significant factor. Fluoride consumption is important in the prevention of osteoporosis and may also play a significant role in preventing calcification of the aorta (130).

 

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 (631).

 

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

Francoise Grumbach (FR) and Noel Rist (FR) found rifampicin to be a potent antituberculous drug in both animal and human studies,comparable with isoniazid in its activity (677).

P.J. Coletsos (), V. Nitti (), E. Catena (), A. Ninni (), A. Di Filippo (), Adam Vojtech Havel (CZ), Jaromir Tousek (CZ), Ludek Trnka (CZ), Adalbert Liener (AT), O. Jahn (AT), Michele Lucchesi (IT), Pietro Mancini (IT), and Martino Zubiani (IT) introduced rifampin—a lipophilic ansamycin—into tuberculosis therapy (323; 731; 1047; 1074; 1248).

Robert H. Gelber (GB), Michael F.R. Waters (GB), James M.H. Pearson (GB), Roland J.W. Rees (GB), and A. Colin McDougall (GB) demonstrated that rifampicin is an excellent anti-leprosy drug (605).

 

Harry M. Meyer, Jr. (US), Paul Douglas Parkman (US), and Theodore Constantine Panos (US) developed a vaccine against rubella virus (1153).

 

Eugene B. Buynak (US) and Maurice Ralph Hilleman (US) described their live attenuated mumps virus vaccine (244). Note: Hilleman had obtained, then isolated, the virus from his daughter in 1963.

 

Seiichi Matsumoto (JP) and Kaneatsu Miyamoto (JP) presented their electron-microsopic studies on rabies virus multiplication and the nature of the Negri body (1118).

 

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 (1780).

 

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 (1485).

 

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 (1662).

 

Deborah Doniach (GB), Ivan M. Roitt (GB), Geoffrey J. Walker (GB) and Sheila Sherlock (GB) reported the finding of mitochondrial antibodies in the serum of almost all cases of primary biliary cirrhosis and in very few patients having other clinically similar disorders. This made it possible to avoid unnecessary and harmful laparotomies by a correct preoperative diagnosis of the ‘autoimmune’ cases (457).

 

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 (564).

 

Myron Winick (US) and Andadele Noble (US), by measuring DNA content and RNA/DNA and protein/DNA ratios of various rat organs, showed that neonatal malnutrition retarded the rate of cell division, permanently reducing cell number. By contrast, later malnutrition prevented the increase in cell size, a change that was reversible on refeeding (1823).

 

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 (375).

 

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 (248).

George Francis Cahill, Jr. (US) and Oliver E. Owen (US) noted that quantitatively, amino acids are the major source of carbon for gluconeogenesis and can be oxidized to CO₂ and H₂O during starvation. When the carbon skeletons of the amino acids are converted to glucose in the liver, the amino nitrogen is used for the synthesis of urea via the urea cycle and is excreted in the urine (249).

Daniel G. Sapir (US), Oliver E. Owen (US), J. T. Cheng (US), Richard Ginsberg (US), Guenther Boden (US) , and William G. Walker (US) demonstrated the exquisite sensitivity of urinary nitrogen excretion rates to ingestion of small quantities of carbohydrate (1469).

 

Ian P. Howard (GB) and William Brian Templeton (GB) presented a review about how people perceive the direction and orientation of things. Early chapters review the relevant physiology of vision, eye movements, kinesthesis, the vestibular system, and auditory localization. Middle chapters review behavioral studies on gravitational, geographical, and egocentric orientation. End chapters review the behavioral consequences of distorting sensory inputs, with a chapter on the behavioral effects of weightlessness (801).

 

Phillip I. Lerner (US) and Louis Weinstein (US) reviewed one hundred patients with infectious endocarditis over an eight-year period and concluded that we yet do not know the correct dose, duration, or combination of antibiotics necessary to treat most cases, and, indeed, we probably over-treat most patients because we lack this knowledge. Even more discouragingly they found that early diagnosis remains an elusive goal, thereby delaying the initiation of appropriate therapy, which unfortunately still determines the ultimate outcome in most patients with infective endocarditis (1026).

 

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 leukemia (1288).

 

Reuben Matalon (US) and Albert Dorfman (US) determined that elevated dermatan sulfate is characteristic of fibroblasts from Hurler’s syndrome patients (1116).

Elizabeth Fondal Neufeld (US), Joseph C. Fratantoni (US), Clara W. Hall (US), Ulrich N. Wiesmann (US), Scot Hickman (US), Gideon Bach (IL), 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 excess mucopolysaccharides accumulate within lysosomes—the minute cellular organelles in which large molecules are broken down—thus, also defining these conditions as lysosomal storage disorders. Additionally, they discovered the specific enzyme deficiencies involved in several diseases of this group (60; 575; 576; 761; 1228; 1808).

Robert W. Barton (US), Elizabeth Fondal Neufeld (US), Michael Cantz (DE), Andreas Chrambach (US), and Gideon Bach (IL) found that Hurler syndrome could be corrected by a macromolecular factor derived from fibroblasts or urine from donors who did not have Hurler syndrome. They purified and characterized the factor (92; 257).

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 (1117). This was the first enzyme defect established in the mucopolysaccharidoses. Both Hurler Syndrome and Scheie Syndrome are due to a deficiency of alpha-L-iduronidase.

Timple W. Lim (US), Irwin G. Leder (US), Gideon Bach (IL), 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 (1045; 1055; 1227).

 

Olga Suhren (NL-DE), 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 (1619).

 

Zvi Laron (RO-IL), Athalia Pertzelan (IL), and Shoshana Mannheimer (IL) described a new kind of genetic dwarfism with high serum levels of human growth hormone. The original paper hypothesized a defective growth hormone molecule, but the problem is a defective growth hormone receptor gene (997).

 

Francois Dessertenne (FR) was the first to describe torsade de pointes heart waves. This is a specific form of dangerous ventricular tachycardia in which an undulating series of ventricular beats appear on the QRS axis (427).

 

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) (1081-1084). 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 (793; 1810-1814).

 

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 (1591).

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 (1214).

 

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 (227). This paper ranks as one of the greatest advances in 20^th century renal physiology.

 

Gerald P. Bodey (US), Monica Buckley (US), Y.S. Sathe (US), and Emil J. Freireich (US) presented a study, which examined the quantitative relationships between the presence of infection and the degree and duration of leukemia in patients with acute leukemia. Methods; Leukocyte distribution; Cranulocytes and infection (155).

 

Eng Meng Tan (US) and Henry G. Kunkel (US) demonstrated that sera of patients with systemic lupus erythematosus contain precipitating antibodies to soluble tissue components other than DNA. One dominant reaction was observed which was provisionally termed the Sm system. The antigen involved was identified in nuclei of a wide variety of cells from different species. It was associated with protein fractions but was a non-histone substance quite sensitive to periodate treatment. Antibodies to the Sm antigen could also be detected by complement fixation. They showed a high incidence in systemic lupus erythematosus with considerable specificity for the disease (1646).

 

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. Electroshock and drugs can produce amnesia even if the animals are given the treatment long after they have demonstrated "learning" of the task (1131).

 

Catherine Tchobroutsky (FR), Monique Clauvel (FR) and Daniel N. Laurent (FR) provided long-term support of puppies and fetal lambs in a controlled environment using extracorporeal circulation (1656).

 

Robert B. Salter (CA) introduced the classic innominate osteotomy in the treatment of congenital dislocation and subluxation of the hip in the older child (1459).

 

Oscar Creech, Jr. (US) combined the endoaneurysmorrhaphy technique of Matas with graft replacement that left the aneurysmal sac in place (371).

 

Richard H. Dyer, Jr. (US) pioneered a renewed interest in intraoperative autotransfusion leading to the development of the first commercial auto-transfusion apparatus (478).

 

Ilyia Iosifovich Gokhman (RU) examined a skeleton (No. 6285-9) from the Vasilyevka II cemeteries in the Dnieper Rapids region, Ukraine, with evidence that trephination— surgical removal of bone from the cranial vault— had been performed during the Mesolithic period. The cemetery, excavated in 1953 by Abram Davydovich Stolyar (RU), has been dated to between 7.3-6.2 K BCE, making this trephined cranium the oldest known example of a healed trephination 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 rate of the patient, a man who was more than 50 years old at his death (632; 1053).

Kurt W. Alt (DE) and his colleagues discovered a 5,000 BCE burial at Ensisheim, in the French region of Alsace, which yielded unequivocal evidence for trepanation (1745).

 

Elso Sterrenberg Barghoorn (US) and J. William Schopf (US) discovered fossilized cyanobacteria approximately 3.1 billion years old in Warrawoona Group rocks in Africa (83).

 

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 (336; 1199; 1802; 1803). 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 (217).

 

Henry de Lumley (FR), at Terra Amata, in the south of France, found red, purple, yellow, and brown ochre associated with Acheulian tools (c.a 300,000 BCE) with lumps of the ochre showing signs of wear (404; 1444). 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 occurring 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” (506).

 

Joaquin Cravioto (MX), Elsa R. DeLicardie (MX), and Herbert G. Birch (US) presented the results of an ecologic study documenting that malnutrition in children influences the development of effective interrelations among the separate sense systems as it influences the child’s physical size. With the exception of mother’s education, none of the demographic factors present in the malnourished environment influenced neurointegrative development (369).

 

Richard Charles Lewontin (US) and Louis Charles Birch (AU) noted that hybridization is a major source of genetic variation for adapting species to new environments (1030).

 

John Maynard-Smith (GB) initiated the development of mathematical models aiming to identify the conditions for sympatric speciation (1122).

 

Robert Treat 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 sea star Pisaster ochraceus is the top carnivore. The viewpoint was supported by a controlled field experiment involving sea star removal leading to a decline in community species richness. He would later refer to a species impacting an ecosystem in this manner as a keystone species (1296; 1297).

Anthony R.E. Sinclair (TZ), Holly T. Dublin (US), and Markus Borner (CH), used the Wildebeest (Connochaetes taurinus (Burchell) population time series—monitored by Sinclair from 1977 until a few years ago and supplemented by earlier observations—a classic in population ecology, to show the population’s recovery from the rinderpest virus throughout the 1960s and 1970s and then a levelling off punctuated with drought-related declines. The elephant time series, collected by both aerial and ground methods, showed that the stress of poachers resulted in a zero birth rate between 1977 and 1987. A breakthrough discovery came when they observed a huge population surge of wildebeest in the Serengeti leading to the realization that wildebeest were the key to keeping the ecosystem balanced by acting as a keystone species while serving as both prey and predator (1536-1539).

Mary Eleanor Power (US), David Tilman (US), James A. Estes (US), Bruce A. Menge (US), William J. Bond (ZA), L. Scott Mills (US), Gretchen Daily (US), Juan Carlos Castilla (CL), Jane Lubchenko (US), and Robert Treat Paine (US) redefined keystone species as one whose impact on its community or ecosystem is large, and disproportionatcly large relative to its abundance. They stressed that identifying keystone species is difficult but worth the effort (1362).

John Terborgh (US), Lawrence Lopez (US), Percy Nuñez (PE), Madhu Rao (US-GB), Ghazala Shahabuddin (IN), Gabriela Orihuela (PU), Mailen Riveros (VE), Rafael Ascanio (ES), Greg H. Adler (US, Thomas D. Lambert (CA), and Luis Balbas (VE) reported that on small islands impounded by water, following dam construction, predators of vertebrates are absent and densities of rodents, howler monkeys, iguanas, and leaf-cutter ants are 10 to 100 times greater than on the nearby mainland, suggesting that predators normally limit their populations. The densities of seedlings and saplings of canopy trees are severely reduced on herbivore-affected islands, providing evidence of a trophic cascade unleashed in the absence of top-down regulation (1663). Note: typically jaguars, which are predators of small vertebrates, and army ants, the major predator of leaf cutter ants, were absent from these small islands.

James A. Estes (US), Alexander Burdin (US), and Daniel F. Burdin (US) used recent and historical information on sea otters and kelp forests to show that the extinction of Steller's sea cow from the Commander Islands in the mid-1700s would have been a nearly inevitable consequence of the overhunting of sea otters, which occurred a decade earlier (519). Note: the sea otter is seen as the keystone species.

Anthony R.E. Sinclair (TZ) and L. Francisco Henao-Diaz (CA) used bird surveys to shown that parks are effective in doubling bird diversity as compared to adjacent agricultural fields (746).

 

George Christopher Williams (US) offers an excellent explanation for adaptation and a convincing defense of natural selection (1816).

 

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.

 

1967

“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 (1733).

 

“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.

 

“To use a metaphor, we might say that the organism is constantly playing a game with its environment, a game where the rules are not defined, and the moves planned by the opponent are not known.” Nikolai Aleksandrovich Bernstein (RU) (131).

 

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.

 

Nathan Radin (US) reviewed the definition and the use of standards and the standards available for clinical chemists and discussed the limitations of various so-called standards (1374).

 

Peter Albersheim (US), Donald J. Nevins (US), Patricia D. English (US), and Arthur Karr (US) designed a methodology to allow those working on complex carbohydrates to determine accurately and easily the neutral sugar compositions of their preparations (18).

 

Stuart J. Edelstein (US) and Howard Kapnek Schachman (US) developed a method for the simultaneous measurement of partial specific volumes and molecular weights of proteins and other substances by sedimentation equilibrium experiments in H₂O and D₂O (or D₂18O) solutions. Using their method, they were able to determine the partial specific volumes and molecular weights of several proteins including ferredoxin, ribonuclease, myoglobin, alpha-chymotrypsinogen, and bovine plasma albumin, as well as the small molecule adenosine (484).

 

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 (1510).

 

Jean-Paul Thiéry (FR) developed a way to demonstrate polysaccharides in thin sections by electron microscopy (1667).

 

Edward P. Marbach (US) and Max Harry Weil (US) presented a simplified assay for lactate and pyruvate in blood (1103).

 

Jacobo Ghitis (US-IL) and Cristina Lora (US) showed that the free-folic acid activity of milk appears to be bound to a protein. The binding seems to be highly specific, as it is not broken by autoclaving. Synthetic PGA, but not 4-amino-10-methyl PGA, is able to bind to milk. This binding seems to be semi-specific only, the bond being broken by autoclaving (614).

 

Irwin A. Rose (US) and Jessie V.B. Warms (US) gave perhaps the first really clear demonstration of an association of hexokinase with mitochondria (1428).

Ernesto Bustamante (PE), Harold P. Morris (US), and Peter L. Pedersen (US) demonstrated that the mitochondrial hexokinase is the enzyme responsible for driving the high rates of glycolysis that occur under aerobic conditions characteristic of rapidly growing malignant tumor cells (238). Note: Aerobic glycolysis by malignant tumors is utilized clinically to diagnose and monitor treatment responses of cancers by imaging uptake of 2-18F-2-deoxyglucose (a radioactive modified hexokinase substrate) with positron emission tomography (PET).

 

Beverly E. Pearson Murphy (US) described a simple and highly sensitive assay for the steroid hormone, cortisol, based on the ‘competition’ between radioactive and non-radioactive cortisol for binding to a plasma protein, corticosteroid binding globulin (CBG or transcortin) (1211).

 

Eijiro Ozawa (JP) and Setsuro Ebashi (JP) discovered the regulation of phosphorylase b kinase activity by calcium ions (1294).

 

Patrick Brennan (US) and Clinton Edward Edgerton Ballou (US) proposed that in Mycobacterium phlei guanosine diphosphate mannose acts as the sugar donor in the conversion of phosphatidylmyoinositol to phosphatidylmyoinositol dimannoside (dimannophosphoinositide C), which is then acylated in a two-step process to first yield dimannophosphoinositide B and then dimannophosphoinositide A (187; 188).

 

Donald R. Mills (US), Ronald L. Peterson (US), and Solomon Spiegelman (US), using RNA from the coliphage Qβ, performed the first extracellular Darwinian experiments. Short RNAs that later became known as “Spiegelman's Monsters” or simply “minimonsters” quickly took over the population. Being replicated but not replicases, they exhaust supplies of resources such as nucleotides, running the molecular ecosystem into the ground unless the resources are constantly replenished. And even if they are, in a serial dilution experimental format, these parasites will out-compete replicator species simply by having a higher reproductive rate (1168).

Benoit Dubertret (US), Shumo Liu (US), Qi Ouyang (US), and Albert Libchaber (US) reported the first experimental study of the dynamics of in vitro evolution of DNA. Starting from a random pool of DNA sequences, they used cycles of selection (binding to the lac repressor protein), amplification, and mutations to evolve to a unique DNA sequence, the lac operator. Statistical analysis of the DNA sequences obtained during the cycles of evolution shows that the DNA bases are selected at different rates. The rates of selection provide a quantitative measure of the interaction of the DNA bases with the protein during the complex formation (465).

 

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 (1375).

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 (102).

 

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 (410-412).

 

E. Stephen Garnett (GB), Victor Parsons (GB), and Norman Veall (GB) found the renal clearance of ⁵¹Cr-E.D.T.A., as measured by the continuous-infusion technique, to be the same as that of inulin. Its quilibration with interstitial fluid in non-edematous patients takes less than 2 hours and there is no detectable extrarenal uptake so that the " slope " method based on 2-4-hour plasma-activity measurements can be used as a simple routine procedure. Results obtained in this way accord well with 24-hour endogenous creatinine-clearance data, but the technique is not applicable to edematous patients where equilibration is delayed. They suggested that ⁵¹Cr-E.D.T.A. seems to be eminently suitable for clinical use (598).

 

Jean-Paul Revel (AT-US) and Morris John Karnovsky (ZA-US) introduced the use of colloidal lanthanum as an electron opaque tracer. Using this tracer, they were the first to reveal the fine structure of gap junctions, the structural correlate of electrophysiologically defined electrical synapses that were known to occur in cells of excitable tissues (1404).

Luca Turin (GB), Anne E. Warner (GB), David C. Spray (US), Andrew L. Harris (US), and Michael V.L. Bennett (US) demonstrated that cytoplasmic pH and junctional voltage could dynamically regulate cellular connexin (gap junction) channels in vertebrates (1580; 1703).

David L. Paul (US), Nalin M. Kumar (US), and Norton B. Gilula (US) cloned the 1.5 Kb cDNA of a 32-kD gap junction protein from the rat (978; 1314). It is now known as connexin 32 (Cx32). Later studies turned up the sequence-unrelated innexins (invertebrate connexins), the mammalian pannexins (a group more ancient than mammalian connexins), and the insect virus vinnexins.

JoAnn Bergoffen (US), Steven S. Scherer (US), Suping F. Wang (US), M. Oronzi-Scott (US), Linda Jo Bone (US), David L. Paul (US), Ke-Lian Chen (US), Mathew W. Lensch (US), Phillip F. Chance (US), and Kenneth H. Fischbeck (US) found that Cx32 mutations are a common cause of the peripheral nerve disorder Charcot-Marie-Tooth disease (126).

Connexin26 mutations account for about half of all cases of genetic deafness, Connexin46 and Connexin50 mutations cause familial cataracts.

 

George G. Brownlee (GB), Frederick Sanger (GB), and Barclay George Barrell (GB) determined the complete nucleotide sequence for 5S ribosomal RNA from Escherichia coli (211).

 

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 (389).

 

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 (11). 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) (1426).

 

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 (558-560).

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 (561). Verapamil is an alkaloid found in raw opium from the Papaver somniferum plant.

 

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 (359; 603; 606; 1281; 1793).

 

Ruth Sager (US) and Mary G. Hamilton (US) discovered ribosomes in the chloroplast of Chlamydomonas (1455).

 

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 (1269).

 

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 (1096).

 

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 (839).

 

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 (195).

 

Christopher Reid (CA), Leslie Eleazer Orgel (GB-US), and Cyril Ponnamperuma (Ceylonese-US) found that random processes alone could form nucleotides and dinucleotides. They have also demonstrated the formation of ATP through the ultimate agency of solar energy (1395).

 

Christopher Reid (CA), Leslie Eleazer Orgel (GB-US) synthesized sugars in potentially prebiotic conditions (1394).

 

Lionel V. Crawford (GB) and Michael J. Waring (GB) described supercoiling of polyoma virus DNA measured by its interaction with ethidium bromide (370).

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 (315).

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 (252).

William R. Bauer (US) reported that the DNA in all organisms is negatively supercoiled, and to about the same degree (98). 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 (1276-1279; 1617; 1618).

 

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 (1622; 1623).

 

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 (659).

 

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 (364; 977; 1043; 1318; 1763).

 

Giovanni B. Rossi (IT) and Charlotte Friend (US) showed that cancer cells could be induced to differentiate by an exogenous agent, such as a virus (1437).

 

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 (907; 1208).

 

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) (937).

 

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 (1272). They found that simultaneous breaks in both strands are also repaired but at a much lower efficiency (1686).

 

Mario Renato Capecchi (US) found that the release of newly synthesized polypeptides from ribosomes depends on a release factor and a terminator codon (259).

 

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 (830).

 

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 (1190).

 

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 (240; 996; 1417).

 

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 (1614; 1677).

 

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) and that the pathway proceeds via a symmetrical 4-carbon intermediate. Furthermore, they found that the conversion of pyruvate to glyceride-glycerol via this pathway increases when the animal is fasted, due in part to the induction of PEPCK-C activity that occurs in adipose tissue. They proposed that this pathway, later termed glyceroneogenesis (i.e. the de novo synthesis of glyceride-glycerol from precursors other than glycerol or glucose) is involved in the re-esterification of fatty acid to triglyceride in adipose tissue during fasting (74).

Erela Gorin (IL), Z. Tal-Or (IL), and Eleazar Shafrir (IL) coined the term glyceroneogenesis to name the pathway described above (648).

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 (1402; 1403). Later it became apparent that glyceroneogenesis is involved in the triglyceride-fatty acid cycle. This cycle is a critical factor in regulating the amount of fatty acid that is re-esterified back to triglyceride during fasting in all mammals (and probably all vertebrates) and thus has a potential role in type 2 diabetes.

 

Lawrence I. Gilbert (US) reviewed the field of insect lipids up to 1966 and may be in part responsible for the logarithmic increase in the number of studies on insect lipid metabolism and natural products chemistry over the ensuing decade (621).

 

Håkan Björndal (SE), Bingt Lindberg (SE), and Sigfrid Svensson (SE) investigated the mass spectrometry of partially methylated alditol acetates. They demonstrated that these substances are readily identified from their mass spectra. Analysis of mixtures of such derivatives by gas chromatography-mass spectrometry has become a standard method in structural studies of complex carbohydrates (145).

 

John H. Exton (NZ) and Charles Rawlinson Park (US) studied the basic process of gluconeogenesis (i.e. the conversion of lactate, pyruvate, glycerol, alanine, and a mixture of amino acids to glucose) and demonstrated that physiological increases in these substrates alone led to increased glucose production by the liver, indicating the importance of substrate supply in the regulation of gluconeogenesis. Comparison of the rates of gluconeogenesis from lactate, pyruvate, fructose, and dihydroxyacetone suggested that the rate-limiting step for lactate gluconeogenesis was located between pyruvate and triose phosphate in the gluconeogenic pathway. Measurements of the conversion of [14C] pyruvate to glucose and CO2 were used in a mathematical analysis to determine the flow of isotope from this substrate into the gluconeogenic pathway and the Krebs cycle (524).

John H. Exton (NZ) and Charles Rawlinson Park (US) found that physiological concentrations of glucagon were effective in stimulating gluconeogenesis. Exogenous cyclic AMP stimulated gluconeogenesis, consistent with this being the mediator of the effect of glucagon. Studies of gluconeogenesis from fructose indicated that glucagon/cyclic AMP stimulated the pathway somewhere between pyruvate and phosphoenolpyruvate in the gluconeogenic pathway (525).

 

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 (1447).

 

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 (618).

 

Andrew M. Wright (GB), Marcelo Alberto Dankert (AR), Paul V. Fennessey (US) and Phillips W. Robbins (US) found that lipid intermediates derived from a polyprenol, undecaprenol, are involved in the biosynthesis of Salmonella lipopolysaccharide (1842).

Yasushi Higashi (JP), Jack Leonard Strominger (US), and Charles C. Sweeley (US) found the same undecaprenol lipid intermediate mechanism in the synthesis of bacterial peptidoglycan (763). Note: Dolichol, a related intermediate, is involved in the glycosylation of some animal proteins.

 

Thomas S. Reese (US) and Morris John Karnovsky (US) determined that the endothelial cells in the brain vasculature, and more precisely the junctions between these cells, form the cellular correlate for the so-called blood–brain barrier. Unlike cell junctions found in other endothelia, the cell junctions of endothelial cells in the brain appeared to be extensive and were surmised to form an unbroken belt between cells (903; 1393).

 

George E. Moore (US, Robert E. Gerner (US), and H. Addison Franklin (US) established continuous permanent normal lymphocyte cell lines derived from the peripheral blood which many ‘basic’ scientists said couldn’t be done and was a malignant transformation (1193).

 

Gary Guy Borisy (US-GB) and Edwin W. Taylor (US) isolated a colchicine-binding activity from extracts of tissue culture cells (164).

Gary G. Boisy (US-GB) and Edwin W. Taylor (US) found that when the colchicine-binding activity was extracted under low salt conditions that led to the disappearance of microtubules. They concluded that the binding site of colchicine is the subunit protein of microtubules (165).

Hideo Mohri (JP) named this subunit protein of microtubules tubulin (1187).

Fernando L. Renaud (US), Arthur J. Rowe (GB), and Ian Robert Gibbons (US) discovered that the microtubules consist of two closely related proteins (1399).

 

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 (1325).

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 (1001; 1002; 1775).

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 (1477; 1776). 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 (772).

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 (1524).

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 (1526).

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 (671). Note: Viruses carrying the H1N1, H2N2 and H3N2 antigen combinations were responsible for the Spanish flu of 1918, the Asian flu in 1957 and Hong Kong flu in 1968, respectively (1777).

 

Jack L. Pate (US) and Erling J. Ordal (US) discovered the mechanism of gliding motility in Cytophaga (1312).

 

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 (1676).

Lewis G. Tilney (US) and John R. Gibbins (US) found evidence that microtubule polymerization is important for the development and maintenance of cell shape (1675).

 

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 (199-201). These papers stimulated renewed interest in extremophiles. Thermus aquaticus produces a heat stable DNA polymerase that 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 inhibits the first organism (216). 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 (726).

 

Roger M. Spanswick (GB-US) and John W. Costerton (GB) demonstrated that many plant cells are directly connected by way of their cytoplasm (1574).

 

David Koffler (US), Peter H. Schur (US), and Henry George 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 (961).

 

George Bellamy Mackaness (US), and Robert Vincent Blanden (AU) discovered that macrophages must be activated before they could digest the bacteria causing brucellosis (1086).

 

Phil Filner (US) and Joe E. Varner (US) were the first in plant biology to employ density labelling technology in protein synthesis studies and secondly, they provided the first evidence of complete synthesis of hormone-induced enzymes in plant tissues (540).

John V. Jacobsen (AU) and Joe E. Varner (US) reported that isolated aleurone layers of barley secreted protease in response to gibberellic acid. Density labelling studies showed that the protease arose by new synthesis (842).

 

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 (439). This represents the discovery and naming of viroids.

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 (437-439; 1466; 1610).

Theodor Otto Diener (US) and Roger H. Lawson (US) found that the etiologic agent of chrysanthemum stunt is a viroid (438).

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 (1385).

 

William H. Northway, Jr. (US), Robert C. Rosan (US), and David Y. Porter (US) were the first to describe a new syndrome of acute, subacute, and chronic lung disease in the newborn infant with severe respiratory distress syndrome (RDS). This syndrome was rapidly recognized as occurring throughout the world when newborn infants with respiratory difficulty were artificially ventilated with supplemental oxygen. It was named bronchopulmonary dysplasia (BPD) (1254).

 

Akio Takeuchi (US) used the electron microscope to demonstrate that salmonellae invade epithelial cells of the guinea pig intestine by an endocytic process (1643).

 

Theo M. Konijn (NL), J.G.C. van de Meene (NL), John Tyler Bonner (US), David S. Barkley (US), and Ying Ying Chang (US) discovered that bacterial 3´, 5´ cyclic AMP causes cellular slime molds to aggregate (965; 966).

 

Shinya Inoué (US) and Hidemi Sato (JP) demonstrated that microtubules of the spindle apparatus are in dynamic equilibrium with a subunit pool (833).

 

Ian K. Buckley (AU) and Keith R. Porter (US), using electron microscopy of cultured rat embryo fibroblasts showed that cytoplasmic filaments and microtubules are intimately associated with components known to be highly motile in the living cells. Seemingly immobile cortical filament bundles appear to be involved in the stabilization of cellular attachment sites (219).

 

Charles Allen Thomas, Jr. (US) proved that the DNA of T-even phages exists in a circular form (1668).

 

Moshe Shilo (US) discovered myxobacteria, which are specific in their ability to lyse cyanobacteria) (1517).

 

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 (1355).

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 (396).

 

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 (1368).

 

James H. Renwick (GB) and David Bolling (US) introduced a computer program for encoding, analyzing, and storing human genetic linkage data (1400).

 

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 (1471).

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 (436; 555; 879; 880; 947; 1216; 1275; 1471; 1819). This is often referred to as non-Darwinian evolution or the molecular clock. Emile Zuckerkandl (US) introduced the phrase molecular evolutionary clock (1874).

 

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 (1790).

 

Yoji Doi (JP), Michiaki Teranaka (JP), Kiyoshi Yora (JP), and Hidefumi Asuyama (JP) found mycoplasma- or phytoplasma-like microorganisms in the phloem elements of plants infected with mulberry dwarf, potato witches' broom, aster yellows, or Paulownia witches' broom. They observed pleomorphic bodies susceptible to tetracyclines leading them to a phytoplasma hypothesis in the cause of disease (448). These are Mollicutes, a class of bacteria distinguished by the absence of a cell wall.

Robert E. Davis (US), Joseph F. Worley (US), Robert F. Whitcomb (US), Takashi Ishijima (JP), and Russell L. Steere (US) discovered spiroplasma while exploring the cause of corn stunt disease. These are helical Mollicutes exhibiting a twisting motion (398; 399).

 

Olive S. Pettengill (US) and George D. Sorenson (US) succeeded in growing myeloma cells in suspension culture (1336).

 

Henry Bennet-Clark (GB), Eric C.A. Lucey (GB), R.H.J. Brown (GB), Miriam Rothschild (GB), Yosef Schlein (IL), Kim Parker (GB), A. Carolyn Neville (GB), Steve Sternberg (IL), and William James Heitler (GB) showed that insects jump with a three-step process: first, insects lock their joints; second, they contract their muscles slowly to store energy in cuticular ‘springs’; and third, insects unlock their joints, causing the recoil of the spring to catapult the insect into the air (121; 209; 737; 1439).

Henry Bennet-Clark (GB) solved the problem of energy storage in the jump of the locust. Some of the energy is stored in the cuticular springs and some in the apodemes (tendon-like structures). Bennet-Clark's careful calculation of energy budgets followed by a synthetic kinetic model provided an excellent example of how biomechanical hypotheses should be tested (120). Many arthropods would be found to use similar structures whenever a behavior required large amounts of power.

Gregory P. Sutton (GB) and Malcolm Burrows (GB) found that mathematical models using the whole leg as a lever arm system to transmit the forces through the tarsus (Bennet-Clark’s hypothesis) did produce movements that were consistent with the high-speed movies of the action. Thus, Henry Bennet-Clark’s hypothesis was correct (1631). No one knows how fleas lock their springs in place and then release them, and no one knows how fleas snap their two rear hindmost legs at the same time.

 

Adolf Friedrich Johann Butenandt (DE), Peter Karlson (DE), Helmut Hofmeister (DE), Hans Hummel (DE), Peter Hocks (DE), and Gerhard Spiteller (DE) isolated and crystallized the insect prothoracic gland hormone, which Karlson named ecdysone, from the butterfly Bombyx (241; 242; 902).

Jules Alphonse Hoffmann (LU-FR), Pierre Joly (FR), and Aimé Porte (FR), by using a combination of experimental biology (namely severe bleeding) and histology/ultrastructural studies, eventually identified a well-organised hemopoietic tissue in the vicinity of the dorsal blood vessel in the abdomens of both larval and adult grasshoppers. Ultrastructural analysis of the grasshopper hemopoietic tissue revealed some unexpected similarities with hemopoiesis in mammals (781-783). Note: Grasshoppers which had their hemopoietic tissue selectively subjected to X-ray treatment rapidly succumbed to septicemia by opportunistic microbes; sham irradiated grasshoppers did not show a similar phenotype. This result underlined the crucial role of hemopoiesis in antimicrobial defences, namely through the massive production of phagocytes. X-ray treatment also upset the endocrine control of moulting. In short, grasshopper larvae undergo five cycles of moulting: it was understood that these cycles were dependent on a gland, referred to as prothoracic gland, and that this gland released the moulting hormone ecdysone (ecdysis meaning moult in Greek) at a precise moment within each larval instar (referred to as a “critical period”).

Hans G. Boman (SE), Ingrid Nilsson (SE), and Bertil Rasmuson (SE) discovered an inducible and highly potent antimicrobial immune response in Drosophila (173).

Dan Hultmark (SE), Hakan Steiner (SE), Torgny Rasmuson (SE), and Hans G. Boman (SE) purified three inducible bacteriolytic proteins, designated P7, P9A and P9B, from the hemolymph of immunized pupae of the giant silk moth Hyalophora cecropia. P7 is a lysozyme while both forms of protein P9 clearly differ from the lysozyme class of enzymes and may represent a new type of bacteriolytic protein (820).

Ingrid Faye (SE) and Gerard R. Wyatt (CA) demonstrated in vitro expression of immune proteins in the Hyalophora cecropia fat body, today considered the main antimicrobial producing organ (531).

Hakan Steiner (SE), Dan Hultmark (SE), Ake Engström (SE), Hans Bennich (SE), and Hans Boman (SE) identified the inducible antimicrobial peptides cecropin A and cecropin B from challenged pupae of the moth Hyalophora cecropia (1593).

Jaehag Lee (SE), Thomas Edlund (SE), Tor Ny (SE), Ingrid Faye (SE), and Hans G. Boman (SE) identified attacin (P5) and P4 as the most strongly induced proteins upon bacterial challenge (1010).

Jean-Luc Dimarcq (FR), Elisabeth Keppi (FR), Bryan Dunbar (GB), Jean Lambert (FR), Jean-Marc Reichhart (FR), Danièle Hoffmann (FR), Susan M. Rankine (GB), John E. Fothergill (GB), and Jules Alphonse Hoffmann (LU-FR) purified and characterized a family of novel inducible antibacterial proteins from immunized larvae of the dipteran Phormia terranovae and the complete amino-acid sequence of a predominant member, diptericin A (440).

Anette Carlsson (SE), Ake Engström (SE), Erkki Tapio Palva (SE), and Hans Bennich (SE) showed that attacin-induced alteration in the structure and the permeability of the outer membrane of Escherichia coli is associated with a specific inhibition of the synthesis of several outer membrane proteins, including OmpC, OmpF, OmpA, and LamB. The inhibition is expressed as a reduction in the steady-state mRNA levels and is at least in part the results of a block in transcription of the corresponding genes (261). Note: Attacin was a name given to antimicrobial proteins.

Sophia K. Ekengren (SE) and Dan Hultmark (SE) found that the P9 antimicrobial polypeptides (AMPs), now called cecropins, were antifungal in Drosophila (503).

Michael Zasloff (US) isolated and characterized one of the first vertebrate AMPs from the African clawed frog, Xenopus levis. It was designated magainin (meaning ‘shield’ in Hebrew), and was expressed in tandem in one transcript then cleaved after translation (1867).

Jong-Youn Lee (SE), Anita Boman (SE), C.X. Sun (SE), Mats Andersson (SE), Hans Jörnvall (SE), Victor Mutt (SE), and Hans G. Boman (SE) isolated hormonal peptides from pig intestine. Upon sequencing, the first hormonal peptide turned out to be a type of antimicrobial polypeptides (AMP) called a cecropin, later named cecropin P1 (1011).

Shao Cong Sun (SE), Ingrid Lindström (SE), Hans G. Boman (SE), Ingrid Faye (SE), and Otto Schmidt (SE), upon sequencing of the P4 cDNA, revealed the first immunoglobulin superfamily protein that was part of an immune response in insects and was designated hemolin (1626). Note: Ascaris suum, a parasitic nematode that resides in the pig intestine, was later discovered to be the source of the pig's cecropin (35).

Birgitta Agerberth (SE), Hans Gunne (SE), Jacob Odeberg (SE), Per Kogner (SE), Hans G. Boman (SE), Jack B. Cowland (SE), Anders H. Johnsen (SE), Niels Borregaard (SE), James W. Larrick (US), Michimasa Hirata (US), Robert F. Balint (US), Jaehag Lee (US), Jian Zhong (US), and Susan C. Wright (US) discovered LL-37, the first human antimicrobial polypeptide (AMP), cathelicidin (10; 355; 998). Note: Peptides that in their preform are bound to cathelin were classified as cathelicidins.

Katrin Pütsep (SE), Göran Carlsson (SE), Hans G. Boman (SE), and Mats Andersson (SE) found that morbus Kostmann patients are deficient of LL37 in saliva and plasma, confirming the vital importance of this antimicrobial polypeptide (AMP) in humans (1369).

Bruno Lemaitre (FR), Emmanuelle Nicolas (FR), Lydia Michaut (FR), Jean-Marc Reichhart (FR), and Jules Alphonse Hoffmann (FR) combined genetic, biochemical, and molecular approaches to reveal that the Toll signaling pathway, originally recognized to regulate dorsoventral patterning in Drosophila embryos by activating an NF-κB–like Rel protein, was also responsible for transcriptional activation of the gene that encodes Drosomysin, an antifungal peptide (1024).

Ruslan Medzhitov (RU-US), Paula Preston-Hurlburt (US), and Charles Alderson Janeway, Jr. (US) showed that a human homologue of the Drosophila Toll protein signals activation of adaptive immunity (1141). Note: Toll-like receptors (TLRs) are a class of proteins that play a key role in the innate immune system. They are single, membrane-spanning, non-catalytic receptors usually expressed on sentinel cells such as macrophages and dendritic cells, that recognize structurally conserved molecules derived from microbes. Once these microbes have reached physical barriers such as the skin or intestinal tract mucosa, they are recognized by TLRs, which activate immune cell responses.

Alexander Poltorak (US), Xiaolong He (US), Irina Smirnova (US), Mu-Ya Liu (US), Christophe Van Huffel (US), Xin Du (US), Dale Birdwell (US), Erica Alejos (US), Maria Silva (US), Chris Galanos (DE), Marina Freudenberg (DE), Paola Ricciardi-Castagnoli (IT), Betsy Layton (US), and Bruce Alan Beutler (US) found that the mammalian Tlr4 protein has been adapted primarily to subserve the recognition of lipopolysaccharide (LPS) and presumably transduces the LPS signal across the plasma membrane. Destructive mutations of Tlr4 predispose to the development of gram-negative sepsis, leaving most aspects of immune function intact (1353).

Peck Y. Ong (US),Takaaki Ohtake (US), Corinne Brandt (US), Ian Strickland (US), Mark Boguniewicz (US), Tomas Ganz (US), Richard L. Gallo (US), and Donald Y.M. Leung (US) discovered that a deficiency in the expression of antimicrobial peptides may account for the susceptibility of patients with atopic dermatitis to skin infection with S. aureus (1283).

 

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 (1476).

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 (963).

 

Klaus Thurau (DE), Jürgen Schnermann (DE), Wolfram Nagel (DE), Michael Horster (DE), and Michael Wahl (DE) demonstrated the operation of a sodium-sensitive feedback mechanism at the level of the juxtaglomerular apparatus in each single nephron unit (1672). They hypothesized that the physiological meaning of this mechanism may be to adjust glomerular filtration rate, and thereby tubular sodium load, to the reabsorptive capacity of the nephrons for sodium chloride; it may therefore be an intrarenal sodium-conserving mechanism.

 

Adrian I. Katz (US) and Franklin H. Epstein (US) observed selective and concordant changes in sodium-potassium-adenosine triphosphatase (Na-K-ATPase) activity of renal microsomes when tubular sodium reabsorption was chronically increased or diminished by various experimental maneuvers. These adaptive responses supported the concept that the enzyme plays a physiologic role in active sodium transport by the kidney (908).

 

Irving L. Weisman (US) demonstrated that thymocytes emigrate from the thymus to the "T cell domains" within peripheral lymphoid organs (1786).

 

Nicholas Avrion Mitchison (GB) was among the first to suggest that a normal immune response requires co-operation of various types of lymphocytes (1176).

Donald Mosier (US) was the first to show that lymphocytes must interact with nonlymphoid cells to be able to generate an antibody response (1202).

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 (1177).

 

Beatrice Mintz (US) and Willys K. Silvers (US) found that mice experimentally derived from pairs of conjoined, undifferentiated, cleavage-stage embryos of different histocompatibility genotypes can retain cells of each strain, which still produce their characteristic antigenic products. The animals are permanently tolerant of cells of both original types, remain free of runt disease, and display a normal and specific immune response to introduction of a foreign antigen. Absence of autoimmunity in development of ordinary animals is explainable by the "intrinsic" kind of tolerance found here (1171).

 

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 (500; 501).

 

Michael G. Davey (CA) and Ernst F. Lüscher (CH) found that thrombin is the most potent stimulator of platelet aggregation (386).

 

John Allen Clements (US), Don F. Tierney (US), Harold J. Trahan (US), and Jean Nellenbogen (US) defined and described the role of pulmonary surfactant (313; 314; 1673).

 

Elwood Vernon Jensen (US), Eugene R. de Sombre (US), Daniel J. Hurst (US), Takugi Kawashima (JP), Peter Wilhelm Jungblut (DE), Taiga Suzuki (JP), Walter Erich 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. They noticed that most tissues — skeletal muscle, kidneys and liver, for example — started expelling the labelled hormone within 15 minutes. In contrast, tissues known to respond to the hormone — those of the reproductive tract — held onto it tightly. Furthermore, the hormone showed up in the nuclei of cells, where genes reside. Something there was apparently grabbing the estradiol (406-408; 852-860).

David Toft (US) and Jack Gorski (US) reported the discovery of the key induced protein (E2-IP) for estrogen stimulation (1682).

Nachum A. Reiss (IL) and Alvin M. Kaye (IL) purified and identified E2-IP as an isozyme of creatine kinase. E2-IP was to become the standard biochemical marker of “early” rat endometrial responses to estrogen (1397).

Jeffrey C. Hansen (US) and Jack Gorski (US) noted that the dna-associated receptor underwent fundamental changes in conformation when it bound estrogen and anti-estrogens, such as tamoxifen (707).

Michael Fritsch (US), Cynthia M. Leary (US), J. David Furlow (US), Helga Ahrens (US), Timothy J. Schuh (US), Gerald C. Mueller (US), and Jack Gorski (US) showed this change, characterized by the loss of hydrophobic surface of the steroid-binding domain led to “tighter” binding to chromatin and the interactions with the transcriptional machinery (591). See, Elwood Vernon Jensen in Part 3b

 

 Jimmy D. Neill (US), Elof D.B. Johansson (SE), and Ernst Knobil (US) were the first to describe the time course of progesterone during the ovarian cycle of any species (the rhesus monkey, Macaca mulatta) (1223; 1224).

Jimmy D. Neill (US), Elof D.B. Johansson (SE), J.K. Datta (US), and Ernst Knobil (US) established unequivocally and for the first time the relationship between the secretion of progesterone and luteotrophic hormone (LH). At that time, progesterone was believed to be the ovarian stimulus for the increased LH secretion that results in ovulation. They showed that progesterone secretion increased only after the increase in plasma LH and hence was not the ovarian signal. They also established that the regression of the corpus luteum —as signified by a decrease in plasma progesterone levels —was not associated with changes in the secretion of its LH (1222).

 

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 (909-916; 1159).

 

Vincent Paul Dole (US) and Marie E. Nyswander (US) postulated the physiological basis of narcotic addiction (449; 452).

 

David J. Randall (CA), Lynwood S. Smith (CA), J. Roland Brett (CA), George F. Holeton (CA-GB), E. Don Stevens (CA), and Gordon R. Bell (CA) performed the first mechanistic studies of gas exchange in intact, unanesthetized, unrestrained but confined fish; paving the way for direct physiological measurements in fish in vivo (193; 789; 790; 1383; 1384; 1562; 1604; 1605).

 

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 (20).

 

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 (1432; 1433).

 

Clarence Merskey (US), Alan J. Johnson (US), George J. Kleiner (US), and Herbert Wohl (US) demonstrated that nearly all cases of defibrination syndrome are associated with evidence of intravascular coagulation. Fibrinolysis is probably a secondary phenomenon as it cannot be shown by circulating plasmin or activator in the great majority of cases. Heparin therapy is occasionally beneficial (1147).

 

Joseph M. Hill (US), Joseph Roberts (US), Ellen Loeb (US), Amanullah Khan (US), Ayten MacLellan (US), and Robert W. Hill (US) reported that enzyme therapy directed at depletion of an amino acid, asparagine, indispensable for tumor cell growth but not required by normal tissues, offers a new and promising approach to the problem of treatment of leukemia and disseminated cancer. Therapy with the enzyme L-asparaginase in three cases of acute lymphatic leukemia resulted in measurable improvement in two advanced cases. Furthermore, a variety of human malignant diseases including acute lymphatic leukemia and acute and chronic granulocytic leukemia have been shown to be asparagine-dependent by this test (765).

 

Dame Cicely Saunders (GB) and her colleagues, in 1967, 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 (1474).

 

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 (1420).

 

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) (1726; 1744).

 

Johannes Joseph van Rood (NL) proposed the creation of the first international organ exchange organization (1725).

 

Charles David Kelman (US) transformed cataract surgery by devising a relatively noninvasive procedure for removing a flawed lens; he called it phaco-emulsification and aspiration. Kelman replaced a high-risk operation that required a lengthy hospital stay with a 10-minute outpatient procedure. This procedure is now the most frequently performed surgery in many countries of the western world. It aids about three million people annually in the United States and approximately the same number in Western Europe — figures that are increasing as the population ages. Kelman's innovation of removing a relatively large piece of tissue through a tiny incision paved the way toward similar 'keyhole' surgeries on many other parts of the body (929; 930). See: Harold Ridley, 1951.

 

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 (117; 118).

 

John E. Craighead (US), James B. Hanshaw (US), and Charles B. Carpenter (US) presented data strongly suggesting that active cytomegalovirus infection in renal graft recipients can result either from the activation of "latent" virus or from exposure to the virus after transplantation. The occurrence of the infection did not correlate with a well-defined clinical syndrome even though generalized cytomegalic inclusion disease was found in some patients at autopsy (365).

 

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 (941).

 

Bernard Lown (LT-US) reported on sinus node dysfunction. He referred to it as “sick sinus syndrome” (1071).

 

Edward Osborne Wilson (US) and Robert Helmer MacArthur (CA-US) authored The Theory of Island Biogeography, a study of islands that 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 (1820).

Daniel Solomon Simberloff (US) and Edward Osborne Wilson (US) tested the equilibrium theory in the Florida Keys and found it to be valid (1533; 1534).

Edward F. Connor (US) and Earl D. McCoy (US) showed that the number of species found on an island, in a wooded lot, on an individual plant, on a harbor piling, in a county, or in virtually any circumscribed region increases as a function of the area or size of that region. They implicated three mechanisms, habitat diversity, area per Se, and passive sampling, as possibly causing any given species-area relationship, and suggested that the three were not mutually excluive. The statistical description of this pattern yields parameters that are of biological significance only when comparing the species richness of regions of different areas or sizes (333).

 

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 (373; 1286; 1828).

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 (498; 1625).

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) (22; 23; 280-286; 682; 973; 1868).

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 (19; 622; 1006; 1799). This is commonly referred to as the RNA world hypothesis.

Gerry A. Prody (US), John T. Bakos (US), Jamal M. Buzayan (US), Irving R. Schneider (US), and George Bruening (US) discovered a dimeric plant virus satellite RNA which was autolytic (1364).

Jennifer A. Doudna (US) and Jack William Szostak (CA-US) found that the Tetrahymena ribozyme could splice together multiple oligonucleotides aligned on a template strand to yield a fully complementary product strand. This reaction demonstrates the feasibility of RNA-catalyzed RNA replications and supports the RNA world hypothesis (459).

Heinz W. Pley (US), Kevin M. Flaherty (US), and David B. McKay (US) published the structure of a 'hammerhead RNA-DNA ribozyme-inhibitor complex' at 2.6 Ångstrom resolution, in which the autocatalytic activity of the ribozyme was disrupted via binding to a DNA substrate (1346).

Jamie H.D. Cate (US), Anne R. Gooding (US), Elaine Podell (US), Kaihong Zhou (US), Barbara L. Golden (US), Craig E. Kundrot (US), Thomas Robert Cech (US), and Jennifer A. Doudna (US) described the crystal structure of a group I ribozyme domain and principles of RNA packing (277).

 

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 (1695).

 

Nikolai Aleksandrovich Bernstein (RU) was one of the pioneers in the field of motor control and motor learning. The field of motor control studies how the Central Nervous System (CNS) controls posture and movement. He was the first to address the question of how the CNS is capable of adequately controlling the many degrees of freedom of the musculoskeletal system. Bernstein suggested that the CNS is capable of "functionally freezing degrees of freedom." As an analogy, controlling the four wheels of a car independently is very difficult. Yet, by functionally freezing degrees of freedom (the two rear wheels are only allowed to rotate around one shared horizontal axis, and the two front wheels are also allowed to rotate in parallel around a longitudinal axis, controlled by the steering wheel) a car becomes much easier to control. The question of how the CNS is capable of adequately controlling the many degrees of freedom of the musculoskeletal system was first addressed by Bernstein (131). Note: Bernstein’s work was begun in the 1920s but because it took place during the “Cold War” era it was not appreciated until translation in 1967.

 

John H. Laragh (US), Jean E. Sealey (US), John G. G. Ledingham (US), and Michael A. Newton (US) established a relationship between the institution of oral contraceptive therapy and the development or enhancement of high blood pressure in eight of 11 patients (995).

 

Bernard Lown (US), Ali M. Fakhro (US), William B. Hood Jr. (US), and George W. Thorn (US)

 

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 (711).

 

Robert A. Rescoria (US) and Richard L. Solomon (US) presented a review of the emergence of the distinction between Pavlovian conditioning and instrumental learning and evaluated some of the evidence supporting it. They further presented a theory of how these two kinds of learning might interact in producing learned behavior (1401).

 

Alec Coppen (GB) reviewed various investigations into the role of neurotransmitters, endocrine factors, and electrolytes in the etiology and treatment of depressive and manic illness (347).

 

 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 (41; 42).

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 (1746).

 

1968

“... 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 (1140).

 

"The energy that flows through a system acts to organize that system." Harold Joseph Morowitz (1195).

 

“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) (202).

 

“Life is very strange,” said Jeremy. “Compared to what?” replied the spider. Norman Moss (1203).

 

“When resources are scarce, free access to common property —meadows, ocean fisheries, or pollution-sinks like the atmosphere—is ruinous. Those who restrain their demands because of long- term bad effects lose out in competition with short-term maximizers. This perverse logic makes ruin inevitable.” Garrett Hardin (710).

 

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.

 

Kurt Wuethrich (CH) developed nuclear magnetic resonance spectroscopy for determining the three-dimensional structures of biological molecules (1847-1849).

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

 

 

Charles Tanford (US) Kazuo Kawahara (JP), Savo Lapanje (SI), Annette G. Kirschner (US), Thomas M. Hooker, Jr. (US), Mario H. Zarlengo (US), Ahmau Salahuddin (US), Kirk C. Aune (US), Toshio Takagi (JP), and Jacqueline Reynolds (US) proved the sequence/structure/function hypothesis; denatured proteins did in fact behave as truly structureless polymer chains (‘random coils’). Proteins, alive and functioning, carry within their structure the secret of virtually all life processes. But when they are denatured, they are dead (1647).

 

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 (883).

 

Jerry L. Hedrick (US) and Alan J. Smith (US) devised a simple method for relating the electrophoretic mobility of a protein determined by disc gel electrophoresis to its size and charge characteristics. The method is applicable to a single protein or to mixtures of proteins, provided a specific detection test is available. Knowing the relative size and charge of proteins is not only useful for their differential characterization but also as a predictive aid in their purification (733).

 

Arne Bøyum (NO) presented methodology for isolation of mononuclear cells and granulocytes from human blood as follows: isolation of mononuclear cells by one centrifugation, and of granulocytes by combining centrifugation and sedimentation at one gravity (178).

 

Ken Shortman (AU) found that lymphocytes were separated according to their buoyant density, by centrifugation to equilibrium in continuous gradients of albumin. The procedure gave good resolution, high reproducibility, and good recovery of biologically active cells. Lymphocytes were separable into a series of discrete density sub- populations (1523).

 

Robert Burns Woodward (US), Albert Eschenmoser (CH), and Claude E. Wintner (US) synthesized cyanocobalamin (vitamin B12) (514; 1837-1839).

 

David M. Blow (GB) and Paul Sigler (GB) solved the tertiary structure of chymotrypsin (151; 152; 1531).

 

Carl Gustaf Hellerqvist (SE-US), Bengt Lindberg (SE), Sigfrid Svensson (SE), Tord Holme (SE), and Alf A. Lindberg (SE) described the application of a new methodology to structural analysis of complex carbohydrates, in this case a bacterial antigenic polysaccharide, utilizing gas chromatography for the separation and tentative identification and mass spectroscopy for positive identification of partially methylated alditol acetates obtained from the original and partially degraded polysaccharide (742).

 

Margaret J. Fletcher (US) devised a method for estimating the level of serum triglycerides. The glycerol released by saponification of the serum glycerides is oxidized to formaldehyde, which reacts with acetylacetone to form a yellow dihydrolutidine derivative absorbing at 405 mμ (562).

 

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 (814).

 

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) (197; 198).

 

Nancy G. Nossal (US) and Maxine Frank Singer (US) found that enzymatic degradation by Escherichia coli ribonuclease II starts at the 3'-hydroxyl end. Furthermore, they demonstrated that the enzyme hydrolyzes a given polyribonucleotide chain to completion before releasing a small oliogonucleotide and initiating hydrolysis of a new chain. Singer termed this “processive degradation” (1257).

Claude B. Klee (US) and Maxine Frank Singer (US) used PNPase from Micrococcus lysodeikticus and showed that this enzyme also degrades polyribonucleotide chains to completion before releasing the end product and starting degradation of another chain. They present several ways in which an enzyme might hang on to a growing polymer, such as threading the polymer through a hole or depression in the enzyme. These two papers were the first demonstrations of processive reactions (954).

 

Bernard Weiss (US), Theodore R. Live (US), and Charles C. Richardson (US) prepared duplex DNA molecules containing either internal 32P-phosphomonoesters, external 32P-phosphomonoesters, or both (1788).

Bernard Weiss (US), Alain Jacquemin-Sablon (FR), Theodore R. Live (US), George C. Fareed (US), and Charles C. Richardson (US) used polynucleotide kinase-labeled DNAs as substrates for characterization of the reaction catalyzed by T4 polynucleotide ligase, an enzyme that repairs DNA single strand breaks. They described a refinement of the isolation procedure for T4 ligase, as well as a rapid assay for partially purified ligase that is based on its ability to catalyze ATP-PPi exchange (1787).

Bernard Weiss (US), Ann Thompson (US), and Charles C. Richardson (US) described the properties of an intermediate in the ligase reaction. They directly isolated and characterized a radioactively labeled ligase-AMP complex thus providing direct evidence for its participation in the reaction (1789).

 

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 (686).

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 (511; 1073; 1551).

Brian F.C. Clark (GB-DK), Bhupendra P. Doctor (US), Kenneth C. Holmes (GB), Aaron Klug (ZA-GB), Kjeld Adrian Marcker (DK), Shirley J. Morris (GB), and Heinrich H. Paradies (DE) crystallized a transfer RNA molecule. The specific type was n-formyl-methionyltransfer RNA (306).

 

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 (884).

 

Friedrich Cramer (DE), Helmut Doepner (DE), Friedrich von der Haar (DE), Eckhard Schlimme (DE), and Hans-Peter Seidel (DE) proposed a general tertiary structure for tRNA molecules (367).

 

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 (307).

 

Peter Traub (US) and Masayasu Nomura (JP-US) completely reconstituted the 30S ribosomal subunit of Escherichia coli from 16S RNA and proteins (1690).

 

Robert Palese Perry (US) and Dawn E. Kelley (US) were among the first to isolate 28S ribosomal RNA (28SrRNA) (1330).

 

Shahla Riyasaty (IE) and John F. Atkins (IE-US) showed that messenger RNA (mRNA) molecules are not always translated in a triplet manner (1411).

 

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 (1857).

 

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 (463).

 

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 (768).

 

W.S.L. Roberts (IE), Jack Leonard Strominger (US), and Dieter Söll (DE-US) isolated two threonyl-tRNAs from M. roseus R27 that catalyzed the incorporation of L-threonine onto the -amino group of lysine in the bacteria’s interpeptide bridge. The threnyl-tRNAs were also able to catalyze protein biosynthesis (1414).

Jean-Francois Petit (FR), Jack Leonard Strominger (US), and Dieter Söll (DE-US) isolated four seryl-tRNAs involved in the transfer of serine to a lipid intermediate of peptidoglycan synthesis. However, only three of the tRNAs could be shown to participate in protein synthesis (1335). It was later discovered that the tRNA which apparently did not participate in protein synthesis is the bacterial selenocysteine tRNA.

Robert M. Bumsted (US), June L. Dahl (US), Dieter Söll (DE-US), and Jack Leonard Strominger (US) reported on their isolation of three glycine acceptor tRNAs from S. aureus. All three tRNAs are active in peptidoglycan synthesis, but only two can produce polypeptides (226).

Thomas S. Stewart (AU), Richard J. Roberts (US), and Jack Leonard Strominger (US) found a species of tRNA^Gly from Staphylococcus epidermidis, which participates in peptidoglycan synthesis but not in protein synthesis. They purified it to homogeneity. It contains only a single modified base, 4-thiouridine (1606).

 

Aaron Jeffrey Shatkin (US) and Jean D. Sipe (US), working with reovirus, were the first to find a virion-bound RNA-dependent RNA polymerase (1516).

 

Donald F. Summers (US), Jacob V. Maizel, Jr. (US), Michael F. Jacobson (US), and David Baltimore (US) demonstrated with poliovirus that the proteolytic processing of RNA virus proteins could be mediated by a virus-encoded rather than cellular proteinase (843; 1620).

 

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 (1568; 1750).

 

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 (1582).

 

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 (1487).

 

Yasuchiro Anraku (US) isolated galactose-binding and leucine-binding proteins from the surface material of Escherichia coli K12 cells (40).

 

Howard Michael Goodman (US), John Norman 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 a mutated tRNA, which carries a single base change in its anticodon, causes this. This allows it to read the chain-terminating codon as an amino acid (640).

 

B. van der Westhuizen (ZA), Yuji Inaba (JP), Yoshio Tanaka (JP), Kunihiko Sato (JP), Hiroshi Ito (JP), Tuneyoshi Omori (JP), and Minoru Matumoto (JP) discovered the Aedes albopictus transmitted virus responsible for bovine ephemeral fever (bovine epizootic fever) characterized by fever, running eyes and nose, respiratory distress, stiffness, leukopenia and low fatality (829; 1723).

 

Stephen Cooper (US), Charles Helmstetter (US), Olga Pierucci (US), and Eras Revelas (US) established the rules for replication in the Escherichia coli life cycle (346; 744).

 

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 (1273).

 

Richard C. Weisenberg (US) and Edwin W. Taylor (US) were the first to describe the presence of non-axonemal dynein within cells (1784).

 

Richard C. Weisenberg (US), Gary Guy Borisy (US), and Edwin William Taylor (US) identified tubulin as the protein subunit of microtubules (1783).

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 named 'dynamic instability' (1178). They also found that growth of microtubules from centrosomes is governed by dynamic instability (1179).

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 (1266).

Berl R. Oakley (US), C. Elizabeth Oakley (US), Yisang Yoon (US), and M. Katherine Jung (US) noted that gamma-tubulin has microtubule-nucleating properties (1265).

 

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 (1019).

 

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 (570).

 

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 (1525).

 

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 r^-. The discovery of an antibiotic-resistant marker residing on the r 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 (1669).

 

William L. Brown, Jr. (US) describes an interspecific chemical signal as an allomone (210). If the benefit is to the recipient the substance is referred to as a kairomone, if both organisms benefit then it is a synomone.

 

John T.O. Kirk (GB-AU) argues that the dependence of chlorophyll pigment synthesis on protein synthesis is not due to the lability of the enzyme used to make the chlorophyll precursor, d-aminolae- vulinic acid, but to inhibition of formation of chlorophyll-carrier protein (950).

 

Ralph D. Amen (US) considered seed dormancy as a specific developmental pathway that can be subdivided into a sequence of stages. He recognized four stages: induction, maintenance, triggering, and germination. Consideration of schemes such as these suggest that each stage will be subject to its own regulatory controls, and that these will be ultimately gene controlled. Thus, dormancy can now be seen not simply as a phase of arrested growth, but as a genetically determined sequence of developmental events (26).

 

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 (566).

 

Kamal K. Mittal (US), Max R. Mickey (US), Dharam P. Singal (US), and Paul IchiroTerasaki (US) devised a microtest method for human leukocyte antigen (HLA) typing and tissue matching of human donors and recipients of organ or tissue transplants. The method was made simple and highly reproducible through critical evaluation of each step of the test procedure (1182).

 

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 (864; 865; 1251; 1255).

 

Evan M. Hersh (US) and Jules E. Harris (US) presented experimental results consistent with the view that macrophage uptake of antigen and macrophage-lymphocyte interaction are necessary for the blastogenic response of lymphocytes to antigen in vitro (753).

 

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)-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 (1129).

 

Emil R. Unanue (CU-US) and Brigette A. Askonas (GB) found that when peritoneal macrophages were cultured for several hours after uptake of iodine-131-labeled hemocyanin. The cells degraded most of the iodine-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 (1713).

 

Motoo Kimura (JP) proposed that genetic variability is maintained in a finite population due to mutational production of neutral and nearly neutral isoalleles (944; 945). 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 1000-fold excess in oocyte GVs, a phenomenon that they named specific gene amplification (205; 594).

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 (21; 1482; 1483). Gene amplification can result in cellular resistance to cancer chemotherapy drugs.

 

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 (206; 207).

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 (1166).

 

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 usefulness of the parasexual fusion-segregation approach to human gene mapping (1158).

 

Jacques Francis Albert Pierre Miller (FR-AT-AU) and Graham F. Mitchell (Australia) demonstrated experimentally that antibody-producing cells originate in the bone marrow (1164; 1165).

 

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 (374).

 

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 (447).

 

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 (335).

 

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 (1451).

 

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 (693).

 

William N. Lipscomb (US) solved the structure of carboxypeptidase (1058).

 

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 (799).

 

Samuel Rahbar (IR) discovered three rare human hemoglobins, two of the patients also showed an abnormal fast-moving hemoglobin fraction: both were suffering from diabetes mellitus. He also discovered HbA1c which he called the "diabetes protein" (1380).

Ronald J. Koenig (US), Charles M. Peterson (US), Robert L. Jones (US), Christopher Saudek (US), Mark Lehrman (US) and Anthony Cerami (US) discovered a correlation of glucose regulation and hemoglobin A1C blood level in diabetes mellitus (960).

The Diabetes Control and Complications Trial Research (DCCT) Group, D.M. Nathan (GB), S. Genuth (GB), J. Lachin (GB), P. Cleary (GB), O. Crofford (GB), M. Davis (GB), L. Rand (GB), and C.Siebert (GB) established HbA1c as a valuable clinical marker in people with type 1 diabetes (433).

The United Kingdom Prospective Diabetes Study (UKPDS) Group established HbA1c as a valuable clinical marker in people with type 2 diabetes (676).

Note: HbA1c became arguably the most important indicator of blood glucose control, enabling doctor and patient to, for the first time, critically assess the impact of lifestyle changes and medication on long-term health.

 

 

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 (1824; 1825).

 

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 (215). 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 (1704).

 

David Arthur John Tyrrell (GB), June Dalziel Almeida (GB), Daniel M. Berry (GB), Charles H. Cunningham (US), Dorothy Hamre (GB), Melvin S. Hofstad (US), Livio Mallucci (GB), Ken McIntosh (US), Walter R. Dowdle (GB), M. Tajima (GB), L.Y. Zakstelskaya (GB), Bernard C. Easterday (GB), Albert Zaven 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 (1706-1708).

 

Robert Paul Hanson (US) and Richard F. Marsh (US) reported the physical and chemical properties of the transmissible mink encephalopathy agent (709).

 

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 (1352).

 

Murray A. Matthews (US) found that there is a critical diameter for the initiation of myelin production ranging from 1-2 µm (1120).

 

Torbjörn Oskar Caspersson (SE), Sidney Farber (SE), Jan Kudynowski (SE), Lore Zech (SE), Claes Johansson (SE), Edward J. Modest (US), George E. Foley (US), Ulhas V. Wagh (SE), Eva 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 (267-275; 1499; 1624).

Tao C. Hsu (US) and Frances E. Arrighi (US) were the first to present a centromeric or C-banding technique. C-banding preferentially stains consecutive heterochromatin based on satellite DNA (809).

Bernard Dutrillaux (FR) developed telomeric banding which is the staining of the telomeric (end) regions of chromosomes (475).

Bernard Dutrillaux (FR) and Jérome Jean Louis Marie Lejeune (FR) developed reverse or R-banding which shows as the reverse of Giemsa or G-bands (476).

 

Harunori Ishikawa (US), Richard Bischoff (US), and Howard Holtzer (US) identified intermediate filaments as a completely new kind of cellular filament (835).

 

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 (105-107).

 

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 (322).

Georg Wick (AT) characterized this avian model as the closest counterpart to human Hishimoto’s disease (1805).

 

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 (153; 420).

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), Vince 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 (421; 574; 792; 1005; 1252; 1253).

Michael F. Holick (US), Anke Kleiner-Bossaller (US), Heinrich K. Schones (US), Patricia M. Kasten (US), Iain T. Boyle (US), and Hector F. DeLuca (US) found 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 (791).

Richard E. Gray (US), John L. Omdahl (US), Jacob G. Ghazarian (US), and Hector F. DeLuca (US) found the subcellular location of the enzyme responsible for the hydroxylation of 25-hydroxyvitamin D3 to 1,25-dihydroxyvitamin D3 in the chicken kidney. Some of the properties of the hydroxylase, which DeLuca determined was in the mitochondria, are also described (667).

Tai C. Chen (US), and Hector F. DeLuca (US) were able to show that most of the vitamin derivative was in a crude nuclear debris fraction. It was subsequently confirmed that the active vitamin D metabolite binds to a transcription factor in the nucleus of cells in the intestine. The transcription factor then regulates gene expression of transport proteins that are involved in calcium absorption in the intestine (294).

Michael F. Holick (US), Anke Kleiner-Bossaller (US), Heinrich K. Schones (US), Patricia M. Kasten (US), Iain T. Boyle (US), and Hector F. DeLuca (US) reported on the isolation and characterization of the vitamin D metabolite, 1,24,25-trihydroxyvitamin D3. It had been found that under normal calcemia, hypercalcemia, and hyperphosphatemia conditions, the kidney limited the production of 1,25-dihydroxyvitamin D3 and instead synthesized 24,25-dihydroxyvitamin D3. Evidence had also indicated that this metabolite was further metabolized to a more polar compound responsible for biological responses. This suggested that there might be an alternate pathway for vitamin D3 metabolism and that the metabolite of 24,25-dihydroxyvitamin D3 might be a tissue-specific hormone that would stimulate only intestinal calcium transport. They isolated the metabolite in pure form from chicken kidney homogenates and identified it as 1,24,25-trihydroxyvitamin D3 (791).

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 (422). See Brumbaugh, 1975.

 

Nicholas Bruchovsky (US) and Jean D. Wilson (US) showed that within 1min following its administration testosterone is taken up by the prostate, and at least 90% is converted to three products, androstandiol, dihydrotestosterone, and androsterone. From prostatic nuclei, however, only testosterone-3H and dihydrotestosterone-3H were recovered for as long as 2 hours following testosterone injection (212).

 

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 (1135).

 

Yoko Takahashi (US), David M. Kipnis (US), and William H. Daughaday (US) discovered that in young adults a remarkable peak of growth hormone (GH) secretion occurs about one hour after the onset of deep sleep. This GH secretion is clearly entrained with the onset of deeper levels of sleep and not with discernible metabolic stimuli (1642).

 

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) (467).

 

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 (1463).

Kinichiro Oda (JP) and Renato Dulbecco (IT-US) found that if 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 (1268).

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 (1056).

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), Sarah Jane 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 (563; 674; 1293; 1460-1462; 1514). 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 (382; 1319).

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 infant’s body (43).

 

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 (1528; 1529). Ebola, the second filovirus to be identified caused its first known outbreak of hemorrhagic fever in the Sudan of Africa during 1976 (185; 1285). All filoviruses are classified as biosafety level 4 (BSL 4) agents based on their high mortality rate.

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 (867). This virus would later be called Ebola.

Zhi-Yong Yang (US), Henricus J. Duckers (US), Nancy J. Sullivan (US), Anthony Sanchez (US), Elizabeth G. Nabel (US), and Gary J. Nabel (US) identified a glycoprotein of the Ebola virus as the main viral determinant of vascular cell cytotoxicity and injury (1858)

 

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 (1612).

 

Elwood Vernon Jensen (US) identified estrogen receptor a (ERa) (851). 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) (976). 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. It was in a child with otherwise uniformly lethal X-SCID [X-linked agammaglobulinemia, thymic alymphoplasia, and severe combined immunodeficiency disease] (602). Note: The patient lived to become a healthy adult. They subsequently performed a successful bone marrow transplant for correction of immunological deficit in lymphopenic agammaglobulinemia and treatment of immunologically induced pancytopenia (636).

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 (58).

 

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 several cell types including neutrophils, macrophages, and lymphocytes (362; 1556).

C. Wayne Smith (US), Armond S. Goldman (US), and Robert D. Yates (US) found that many milk leukocytes are living, motile, and interactive (1556-1558).

 

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 (1174).

 

Vance Tucker (US) was the first to measure an identifiable relationship between flight speed and the metabolic power required. He obtained these results by training two budgerigars (Melopsittacus undulates) to fly at different speeds, while wearing a light weight acetate mask designed to capture the birds expired gases. Tucker found that his birds required high rates of energy release at both fast and slow flight speeds but at intermediate speeds flight costs were more economical (1702).

Colin James Pennycuick (GB-KE) obtained similar results using the pigeon Columba livia (1321).

Subsequent studies of flight metabolism in other species generated essentially flat metabolic power curves, suggesting that some birds require little change in metabolic power to fly across a wide range of speeds.

 

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 (1683).

 

David R. Nalin (US), Richard A. Cash (US) Rafigul Islam (BD), Majid Molla (BD), and Robert Allan Phillips (US) introduced an oral solution containing glucose, sodium chloride, sodium bicarbonate, and potassium chloride or citrate as maintenance therapy for acute cholera. In comparison with control patients who received only intravenous replacement of their stool losses, the patients who received the oral solution required 80% less intravenous fluids for cure (1215). The English medical journal, The Lancet calls oral replacement therapy (ORT) “potentially the most important medical advance of this century."

 

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 (619).

 

Yuet Wai Kan (CN-US) and David Gordon Nathan (US) developed a way to detect beta-thalassemia trait at birth (893).

 

 

David Negus (GB), Donald J.P. Pinto (US), Leslie Philip Le Quesne (GB), Nathaniel F. Brown (US), and Mark Jonathan Chapman (US) reported that ninety-three post-operative patients were investigated by intravenous 125I-labelled fibrinogen and leg scanning. A 93% correlation with phlebography was observed in 26 legs with deep-vein thrombosis, and 100% correlation in normal veins. Most thrombi were detected within 48 hours of operation, and physical signs were present in only a few (1221).

 

Robert L. Baehner (US) and David G. Nathan (US) first described the Nitroblue Tetrazolium Test to determine the oxidation capacities of blood polymorphonuclear leukocytes from children and adults in a wide assortment of disease states. Several slide tests were adapted to assess NBT reduction by individual cells and to establish the diagnosis of chronic granulomatous disease prenatally (62). The test is now standard in many clinical and research laboratories throughout the world.

Brigette Royer-Pokora (US), Louis M. Kunkel (US), Anthony P. Monaco (US), Sabra C. Goff (US), Peter E. Newburger (US), Robert L. Baehner (US), F. Sessions Cole (US), John T. Curnutte (US), and Stuart H. Orkin (US) used “reverse genetics” to identify the defect in chronic granulomatous disease (1441; 1442). Note: “Reverse genetics” is an approach to discover the function of a gene by analyzing the phenotypic effects of specific engineered gene sequences. This investigative process proceeds in the opposite direction of so-called forward genetic screens of classical genetics.

 

Etienne-Emile Baulieu (FR), Ilse Lasnitzki (FR), and Paul Robel (FR) found that rat prostate explants in organ culture were able to metabolize tritiated-testosterone to dihydrotestosterone (DHT) and other 5 alpha-reduced metabolites. DHT, not testosterone (T), accumulated in cell nuclei. DHT stimulated cell proliferation to a greater extent than (T). Hence, (T) was a prohormone converted in situ to active metabolite(s) (99; 100).

 

Alton I. Sutnick (US), W. Thomas London (US), Betty Jane S. Gerstley (US), Malcolm M. Cronlund (US), and Baruch S. Blumberg (US) searched for a reason that the frequency of anicteric hepatitis associated with Australia antigen is high in patients with Down's syndrome in large institutions (27.7%) and is low in patients without this syndrome in the same institutions (3.2%). It is rare in patients with Down's syndrome in small institutions (1.5%) and absent in newborn patients and those who are not institutionalized. They concluded that findings are best explained by the operation of an environmental factor, probably infectious, present in the large institutions, and a host susceptibility factor present in association with Down's syndrome (1630).

 

 Gail Lorenz Miller (US) and Jean E. Wilson (US) developed tumor-specific cytotoxic heterologous antiserum against human cancer cells (1162).

 

James Edward Cleaver (GB-US) observed that xeroderma pigmentosum cells are defective in unscheduled DNA synthesis and in repair synthesis of UV-irradiated DNA (311).

 

Tomisaku Kawasaki (JP) saw his first case of Kawasaki disease in January 1961 and published his first report in Japanese in 1967 (921). Note: Kawasaki disease is a condition that causes inflammation in the walls of medium-sized arteries throughout the body, including the coronary arteries, which supply blood to the heart muscle. Kawasaki disease is also called mucocutaneous lymph node syndrome because it also affects lymph nodes, skin, and the mucous membranes inside the mouth, nose and throat. It is an autoimmune disease suspiciously like infantile polyarteritis of which the specific cause is unknown.

 

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 (125). It is often called Berger’s disease.

 

Robert Ho Man Kwok (CN-US) described dizziness and the sensation of burning in the face and chest due to monosodium glutamate used in food (Chinese restaurant syndrome) (981).

 

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 (1464).

 

Douglas W. Wilmore (US) and Stanley J. Dudrick (US) oversaw the feeding of all nutrients to an infant exclusively by vein for 44 days; normal growth and development occurred (1818).

 

A modern technique of using an open skull flap in prefrontal leucotomy was used on patients at the combined neurosurgical unit of King’s College, Guy’s Hospital, and Maudsley Hospital in London.

John Logothetis (GR) reported on the long-term evaluation of convulsive seizures following prefrontal lobotomy (1062).

 

Henn Kutt (US) and Fletcher McDowell (US) explained management of epilepsy with diphenylhydantoin sodium along with dosage regulation for problem patients (980).

 

Bruce Sherman 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 higher uptake and longer retention of the corticosterone by the septum and hippocampus regions of the brain (1130).

 

Donald G. Lawrence (CA-NL-CA) and Henricus G.J.M. Kuypers (NL-US-NL-GB) showed that the capacity for independent movements of the digits was permanently lost after a complete, bilateral lesion of the corticospinal system. These studies also revealed that the brainstem pathways contribute to fundamentally different aspects of motor control, with one set of pathways (the ventromedial system) involved in the control of head, trunk and girdle movements, while the other, lateral set of fibers control movements of the extremity such as reach and grasp (1003; 1004).

 

John Charnley (GB) and Joseph A. Dupont (GB) developed the technique for total hip replacement and pioneered arthrodeses (fusing joint surfaces) for the knee and hip (292; 474).

 

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 (316; 357).

 

James C. Hogg (CA), Peter T. Macklem (CA), and William M. Thurlbeck (CA) determined the site and nature of airway obstruction in chronic obstructive pulmonary disease (COPD). When the resistance within the human lung's small airways (<2 mm in diameter) was tested at post mortem, lungs with COPD exhibited a resistance 4- to 40-fold higher than that of normal lungs. Bronchographic and histologic studies showed that the resistance was increased because of mucus plugging, narrowing, and obliteration of the small airways. They noted that most of the small airways could be damaged or destroyed before symptoms occur and before any of the conventional tests of lung function—measurements of airway resistance—show loss of function (786).

 

William Howard Wallace Inman (GB) and Martin P. Vessey (GB) performed a study in which women who died from various types of thromboembolism in the United Kingdom during 1966 were practice-matched with healthy women. It revealed a significant excess of oral contraceptive use among those dying from cerebral thrombosis or pulmonary embolism (832).

Philip E. Sartwell (US), AlfonseT. Masi (US), Federico G. Arthes (US), Gerald R. Greene (US), and Helen E. Smith (US) made a case-control study of 175 women aged 15-44, hospitalized with idiopathic thromboembolism, and 175 matched hospital patients as controls. By interview, the relative risk of thrombosis for users of oral contraceptives within the month preceding onset was found to be 4.4 (1472).

 

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 (US), Dov Jaron (US), and Jacques L. Sherman, Jr. (US) pioneered the clinical use of intra-aortic balloon pumping (899; 900).

 

William K. Hass (US), William S. Fields (US), Richard R. North (US), Irvin I. Kricheff (US), Norman E. Chase (US), and Raymond B. Bauer (US) made complete four-vessel examinations of 80% of their 4,748 patients with cerebrovascular insufficiency. Although the primary purpose was localization of surgically accessible extracranial lesions, intracranial studies were also obtained in a high percentage of cases. The overall grave complication rate was 1.2%. A test of interinstitutional comparability of x-ray interpretation revealed greatest agreement when lesions compromised more than 50% of the arterial lumen (724).

 

Theodor Kolobow (US), Warren Myron Zapol (US), Jean Elizabeth Shaw Pierce (US), Ambrose F. Keeley (US), Robert L. Replogle (US), and April 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 (964). This has been called "artificial placentation."

 

James Maxwell Glover Wilson (GB) and Gunner Jungner (SE) descrbed the principles of a screening program that formed the basis of many medical diagnoses (1821).

 

M.Irene Ferrer (US) found that certain clinical states can be grouped into a syndrome resulting from a failing sinoatrial (SA) node. One or more of the following symptoms appears: persistent, severe, and unexpected sinus bradycardia; cessation of sinus rhythm for short intervals with other rhythms supervening; long periods of sinus arrest without rescue rhythm, which produces cardiac arrest; untreated chronic atrial fibrillation with slow ventricular rate; no sinus rhythm after cardioversion; SA exit block. Symptoms spring from hypoperfusion of vital organs (536).

 

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 (124).

 

John Brereton Barlow (ZA), Paul Marchand (ZA), Wendy A. Pocock (ZA), Michael G.S. Denny (ZA), Chris K. Bosman (ZA), and J.W. Craig Cochrane (ZA) reaffirmed that late systolic murmurs and mid-systolic clicks are intracardiac in origin (86-90).

 

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 (612).

 

Charles Flanc (GB), Vijay Vir Kakkar (GB) and Martin B.T. Clarke (GB) investigated the use of 125-iodine labeled 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 (557).

 

Martin L. Cody (US) showed that in grassland bird communities, ecological segregation occurs by dint of species using different habitats, feeding at different heights, or foraging in different ways with ± dissimilar morphologies. Although the relative importance of one or another means of segregation differs with vegetation structure, the species at different sites show comparable limiting similarity in resource use. Since these patterns apply to bird communities over a variety of habitats both within and between continents, they provide evidence for convergent evolution and parallel selection, via resource competition, for similar levels of ecological divergence within communities (318).

 

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 (1274).

 

1969

“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 (234).

 

"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 (1760).

 

"You can't always get what you want. But if you try, sometimes you find, you get what you need." lyrics by Keith Richards (GB) and Mick Jagger (GB)

 

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 (1774).

Ulrich K. Laemmli (CH) improved this technique, which has now become a very popular method for polypeptide analysis and characterization (987).

 

H. Russel Hulett (US), William A. Bonner (US), Janet Barrett (US), and Leonard A. Herzenberg (US) developed a system for high-speed sorting of fluorescent cells with which they were able to sort mouse spleen cells from Chinese hamster ovarian cells after development of fluorochromasia. Highly fluorescent fractions separated after similar treatment from mouse spleen cells immunized to sheep erythrocytes were enriched in antibody-producing cells by factors of 4 to 10 (819).

Michael H. Julius (US), Tohru Masuda (US), and Leonard A. Herzenberg (US) obtained viable and functional populations of antigen-binding cells enriched up to 500-fold from primed spleen-cell suspensions by fluorescent labeling and by a new electronic cell sorter that sorts viable cells according to fluorescence. Concomitantly, populations largely depleted of antigen-binding cells were obtained. While neither population alone is capable of a full adoptive secondary response when injected into irradiated recipients, a reconstituted mixture restores the full response of the unfractionated spleen cells (881).

 

Edgar Haber (US), Theresa Koerner (US), Lot B. Page (US), Bernard Kliman (US), and André Purnode (BE) applied radioimmunoassay, with a highly specific antiserum to angiotensin I, to the determination of the plasma enzyme renin. Plasma renin activity was shown to vary in normal individuals with sodium intake, posture, and the administration of diuretics. The values of renin activity obtained by immunoassay of angiotensin I correspond closely to those observed by bioassay in similar metabolic studies but provide an advantage of relative simplicity, specificity, and reproducibility (691).

 

Mark R. Haussler (US) and Anthony W. Norman (US) provided evidence for the existence of an acidic protein(s) or protein portion of a more complex molecule which has a high affinity for binding non-covalently a biologically active metabolite of vitamin D. Characterization of the crude receptor fraction showed that it contains significant amounts of RNA and that it may exist in multiple forms, i.e., a 50,000-70,000 and a >200,000 molecular weight species. The binding capacity of the receptor fraction for the metabolite is saturated after administration of a physiological dose of the parent vitamin D (730).

 

Norman G. Anderson (US) presented a new microanalytical system that employs a rotor containing 15 cuvets spinning past a beam of light. The signal is displayed on an oscilloscope, and a peak is observed continuously for each cuvet. Standards, samples, and reagents are placed in a central loading disc, and all solutions moved out into the cuvets by centrifugal force. Minimum volume to fill the cuvets is 200 λ. By using the Weichselbaum biuret reagent for proteins, 15 analyses may be completed in as little as 30 secs after the rotor is started. The data are obtained photographically (34).

 

Stan Sajdera (US) and Vincent C. Hascall, Jr. (US) developed a method for the extraction and purification of proteoglycans from cartilage. They showed that cartilage proteoglycans in the dissociative extracts reformed aggregates (722; 1457). They did not know that hyaluronan was present and necessary for reformation.

Dick K. Heinegard (SE) and Vincent C. Hascall, Jr. (US) defined the role of hyaluronan and the link protein in forming the cartilage proteoglycan (aggrecan) aggregates. They showed that two proteins were bound to hyaluronan. One protein was the link protein, and the other was derived from a domain of the core protein of aggrecan, now referred to as the G1 domain. These results led to a model for the proteoglycan aggregates in which the link protein and the G1 domain were bound to each other as well as to hyaluronan (736).

 

Thomas H. Jukes (US) and Charles R. Cantor (US) discovered a way to examine molecular evolution by comparing the polypeptide chains of homologous proteins. Cantor devised a computer program to calculate the mean number of nucleotide substitutions that has occurred in a nucleotide sequence over time. The mathematical equation upon which the program relies assumes that all single base changes (nucleotide substitutions) are equally probable and that the frequencies of all four bases in DNA are the same.

The two genes containing the sequences to produce alpha hemoglobin and beta hemaglobin diverged from a common ancestor at least 400 million years ago. Humans carry in every red blood cell the evidence that we are in a line of descent from an ancestor who lived 400 million years ago (878).

 

Meir Lahav (IL), Ted H. Chiu (US), Charles J. Waechter (US), John J. Lucas (US), and William Joseph Lennarz (US), based on their investigations, reasoned that in eukaryotic systems, as in bacterial systems, activated lipid-linked sugars mediate the synthesis of glycose-containing macromolecules that are associated with the membranous components of the cell (990; 1737).

 

Bernd Gutte (US), and Robert Bruce 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 (687; 688; 774).

 

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) (349-353).

 

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 (15; 896).

Weici Wang (US), and Gerhard Eisenbrand (DE) reported that paeoniflorin exhibits sedative, anticoagulant, and anti-inflammatory activity (1759).

 

Takuro Kisaki (JP) and Nathan Edward Tolbert (US) contributed to the discovery of photorespiration by tracing the pathway into peroxisomes. They found that glycolate is converted to glyoxylate in peroxisomes by the action of glycolate oxidase, which consumes oxygen and releases hydrogen peroxide. Catalase recycles the hydrogen peroxide (951).

 

Joe M. McCord (US) and Irwin Fridovich (US) isolated superoxide dismutase (SOD) from bovine erythrocytes (1125).

Bernard B. Keele, Jr. (US), Joe M. McCord (US), and Irwin Fridovich (US) isolated superoxide dismutase (SOD) from Escherichia coli (923).

All the eukaryotic SODs contained copper and zinc whereas the prokaryotic SODs contained manganese.

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 might have evolved to prevent unwanted oxidations within the cell (1126).

Richard A. Weisiger (US) and Irwin Fridovich (US) isolated superoxide dismutase from mitochondria. While looking at the SOD of chicken liver, they noticed that it contained two types of SOD, one localized to the mitochondria and the other to the cytosol. Surprisingly, the mitochondrial SOD contained manganese. The differences between the two dismutases and their purification are discussed (1785). The similarity between mitochondrial and bacterial SODs suggested that mitochondria evolved from aerobic prokaryotes, which entered an endocellular symbiotic relationship with a prokaryote.

Fred J. Yost, Jr. (US) and Irwin Fridovich (US) isolated an iron containing SOD from Escherichia coli (1861).

Howard M. Steinman (US) and Robert L. Hill (US) determined the amino acid sequence of the first 29 residues from the amino terminus of the mitochondrial manganese dismutase, the bacterial manganese dismutase, and the bacterial iron dismutase (1594). The high degree of sequence identity among the bacterial and mitochondrial dismutases served as further support for the endosymbiotic origin of mitochondria.

Howard M. Steinman (US), Vishweshwar R. Naik (US), John L. Abernathy (US), and Robert L. Hill (US) determined the complete amino acid sequence of the CuZn dismutase (1595).

Hosni M. Hassan (EG-US) and Irwin Fridovich (US) showed that the herbicide paraquat (methyl viologen) caused a marked increase in the rate of biosynthesis of Mn-SOD. The cells that had augmented levels of Mn-SOD also showed an increase in resistance to the toxicities of oxygen and the quinone streptonigrin (725).

Thomas W. Kirby (US), Jack R. Lancaster (US), and Irwin Fridovich (US) isolated and characterized the iron-containing superoxide dismutase of Methanobacterium bryantii (949).

 

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 (1036).

 

John W. Olney (US) showed that glutamate, when administered subcutaneously to infant mice, destroys neurons in certain regions of the brain, including the endocrine hypothalamus, and that this caused animals to grow up with obesity and multiple endocrine abnormalities (1282).

 

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 (337).

 

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 (417; 418).

 

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 (482).

 

Donald Metcalf (AU) discovered colony-stimulating factors (CSFs) (1151).

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 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 (229).

Antony W. Burgess (AU) and Donald Metcalf (AU) and identified granulocyte-macrophage colony stimulating factor (GM-CSF) (230).

They identified granulocyte colony stimulating factor (G-CSF) and macrophage colony stimulating factor (231).

Donald Metcalf (AU) and Nicos A. Nicola (AU) discovered multi-colony stimulating factor (Multi-CSF) (1152). 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), Thomas R. Watson (AU), and L.A. Wilson (AU) determined the structure of carpanone, a lignin found in the carpano tree (204).

 

Koiti Titani (JP), Tomotaka Shinoda (JP), and Frank William Putnam (US) determined the amino acid sequence and location of the disulfide bridges in human kappa Bence-Jones protein Ag. They determined the 214-amino acid sequence by analyzing the sequences of tryptic and chymotryptic peptides from the carboxymethylated protein, the aminoethylated protein, and the disulfide bridge peptides. Comparing this sequence to those of other known human kappa Bence-Jones proteins, they discovered that, “these proteins differ in many positions in the amino-terminal or variable half of the molecule but appear to have an identical sequence in the carboxy-terminal or constant half except for a substitution at position 191 that is correlated with the Inv genetic factor" (1680).

Koiti Titani (JP), Maurice Wikler (US), Tomotaka Shinoda (JP), and Frank William Putnam (US) determined the sequence and location of the disulfide bridges in the human lambda Bence-Jones protein Sh. They then compared this sequence to the sequences of other human lambda Bence-Jones proteins and confirmed their earlier observations with the kappa proteins. Namely, that the amino-terminal half of the protein has great variation in sequence while the carboxyl-terminal portion of the molecule has a constant sequence. They also noted that Sh is homologous to both the human and mouse kappa chains, indicating a common ancestral gene (1681).

 

Susan E. Lowey (US), Henry S. Slater (US), Alan G. Weeds (GB), Herman M. Baker (US), Gerhard Frank (CH), Harry Baker (GB), and Dennis Risby (US) characterized the myosin molecule (1069; 1070; 1778).

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 (1390).

 

Mark R. Adelman (US) and Edwin William Taylor (US) isolated actin and myosin from a non-muscle source, the slime mold Physarum (7; 8).

 

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. 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. 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, during the normal procedures for extracting DNA from Escherichia coli, the smaller circular plasmid DNA remains circular, whereas the larger circular bacterial chromosome is sheared into several linear fragments (815).

 

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 (1235).

 

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 (1061).

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 (685).

 

Richard A. Finkelstein (US) and Joseph J. LoSpalluto (US) isolated, purified, tested and named choleragen, the exotoxin of Vibrio cholerae (541).

 

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) a synthesis of RNA molecules is terminated, and RNA polymerase molecules are liberated at the site of ultraviolet 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 ultraviolet the rate of RNA chain initiation is reduced. (5) Most fragments and some complete molecules of ribosomal RNA synthesized after ultraviolet irradiation are broken down within 45 minutes after synthesis (1156).

 

Roman B. Khesin (RU), Zhosefine M. Gorlenko (RU), Michael F. Shemyakin (RU), Sergey L. Stvolinsky (RU), Sophia Z. Mindlin (RU), and Tamilla 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 (940).

 

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, 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 (232; 1621).

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 (1694).

Andrew A. Travers (US) showed that some of the products of viral early genes helped endow RNA polymerase with specificity for viral genes (1693).

Joan Weliky 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 (328; 329).

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 (479).

Young-Joon Kim (US), Stefan Bjorklund (US), Yang Li (US), Michael H. Sayre (US), and Roger David 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 (942).

 

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 (1067).

 

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 (189). 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 (1133).

 

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 gene—the lacZ gene (1512).

 

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 (904).

 

Joan Elaine Argetsinger Steitz (US), Karen S. Jakes (US), and Deborah A. Steege (US) showed how during polypeptide synthesis the ribosomal RNA is used to initiate translation at the start site of mRNA (1596-1598).

 

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 (1853).

 

John B. Sprague (CA) recommends the advantageous methods for toxicity tests with fish, following a review. Fisheries biologists should adopt a combination of existing techniques including pharmacological ones. Investigators should use thresholds of effect, probit analysis, confidence limits, and tests for significant differences (1579).

 

Gerald M. 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 a human gamma G1 immunoglobulin (Eu) and the arrangement of all of the disulfide bonds has been established (482).

 

J. Michael Kehoe (US) and Michel Fougereau (US) suggested that the constant heavy 2 (CH2) region of the antibody molecule could bind complement (925).

 

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 (157).

 

Jack A. Lucy (GB), Quet Fah Ahkong (CA), F.C. Cramp (GB), Derek Fisher (GB), and J. Isobel Howell (GB) pioneered in methods to induce cell fusion and the formation of hybrid cells (12; 368; 806; 1076).

 

Peter Perlmann (SE), Hedvig Perlmann (SE), Hans Joachim Müller-Eberhard (DE-US-DE), and Jorge A. Manni (AR) noted that cytotoxic effects of leukocytes could be triggered by complement bound to target cells (1327).

 

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 (1424).

 

Kevin John Lafferty (AU) and Michael A. Jones (AU) in their studies of the graft versus host reaction concluded that the ability of an animal to distinguish between "self" and "not-self" components may operate at two distinct levels; one involves the recognition of foreign antigens, and the other the recognition of cells derived from genetically related but not identical animals (988).

 

Martin C. Raff (CA-GB) determined that theta isoantigen can be used as a marker of thymus-derived lymphocytes in mice. To establish that theta is such a marker in man, it is necessary to demonstrate that there is a discrete population of peripheral lymphocytes which carry the antigen and that these cells are thymus-dependent (1376).

 

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 (166; 1237).

Jonathan M. W. Slack (GB), Barry G. Darlington (GB), Joan K. Heath (AU), and Susan F. Godsave (NL) published the results of testing various 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 (1553).

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 (943).

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 (1561).

 

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 (84; 849).

 

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 (1844).

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 (892).

 

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 (184; 1088; 1609).

 

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 (571; 1241).

 

Ruth Arnon (IL) and Michael Sela (IL) demonstrated that conformation of a molecule could be important to its antigenicity (46; 47).

 

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 (837).

 

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 leukocytes (63-65; 530).

 

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 (662; 872). This layer is now referred to as the glycocalyx.

 

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 (595; 1307). The Giemsa banding technique also stained the regions to which the DNA probes annealed selectively. See, above.

Mary Lou Pardue (US), Larry H. Kedes (US), Eric S. Weinberg (US), and Max Luciano Birnstiel (CH), using Drosophila melanogaster polytene chromosomes, visualized the location of histone genes on individual chromosomes (1308).

 

ElizabethB. Robson (GB), Paul Emanuel Polani (IT-AT-GB), S.J. Dart (GB), Pete A. Jacobs (GB), and James H. Renwick (GB) provided evidence for the probable assignment of the alpha locus of haptoglobin to chromome 16 in man (1418).

 

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 (469; 470).

 

J. Isobel Howell (GB) and Jack A. Lucy (GB) were the first to fuse plant protoplasts using a chemical, lysolecithin, to promote the union (806).

 

Robin A. Weiss (US) suggested the existence of an integrated retrovirus in normal chick embryo cells (1791; 1792).

Robert Joseph Huebner (US) and George Joseph Todaro (US) presented their hypothesis on latent retroviruses and coined the term 'oncogene' (816).

Susan M. Astrin (US), Harriet L. Robinson (US), Lyman B. Crittenden (US), Edward G. Buss (US), Jim Wyban (US), and William S. Hayward (US) determined that numerous separately integrated endogenous proviruses are present in the chicken genome (50).

Catherine D. O'Connell (US) and Maurice Cohen (US) discovered that the human genome contains endogenous retrovirus genes (1263).

Masao Ono (US) determined that the haploid human genome contains approximately 50 copies of the human endogenous retrovirus genes (HERV-K) (1284).

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 (573).

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 (1110).

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 (1068).

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 (673; 1730).

 

Charles A. Mebus (US), Norman R. Underdahl (US), Marvin B. Rhodes (US), and Marvin J. Twiehaus (US) discovered bovine rotavirus, the most common cause of neonatal diarrhoea in calves (scours) (1138).

 

Eugene B. Buynak (US), Robert E. Weibel (US), James E. Whitman (US), Joseph Stokes, Jr. (US), and Maurice Ralph Hilleman (US) presented their combined live measles, mumps, and rubella virus vaccines (246).

 

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 a new pilus has been generated, he proposed that the F pilus serves as a conjugation bridge (1258).

 

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 (1167).

 

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 (53).

 

S. Ronald Smithers (GB), Roland J. Terry (GB), and David J. Hockley (GB) demonstrated that schistosomes absorb host antigens and, thus disguised, protect themselves against immune attack (1567).

 

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 (1244-1247).

 

Simon H.P. Maddrell (US) helped to establish the field of insect osmoregulation with his elegant studies on the Malpighian tubules of Rhodnius prolixus (Hemiptera) (1090).

 

Scott Murphy (US) and Frank H. Gardner (US) demonstrated the feasibility of storing blood platelets at room temperature, revolutionizing platelet transfusion therapy (1213).

 

David G. Ashbaugh (US), Thomas L. Petty (US), D. Boyd Bigelow (US) and Timothy M. Harris (US) defined the clinical syndrome of acute respiratory distress in the adult both physiologically and pathologically. The use of continuous positive-pressure breathing in treatment of these patients resulted in a dramatic improvement in morbidity and mortality (49).

The Nocturnal Oxygen Therapy Trial Group (US) used continuous or nocturnal oxygen therapy in hypoxemic chronic obstructive lung disease: a clinical trial. They concluded that in hypoxemic chronic obstructive lung disease, continuous oxygen therapy is associated with a lower mortality than is nocturnal oxygen therapy (675).

 

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 (1163).

 

Priscilla J. Piper (GB) and John Robert Vane (GB) demonstrated the first association between prostaglandin production and the actions of aspirin-like drugs (1345).

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 (1727).

William L. Smith, Jr. (US) and William E.M. Lands (US) found that aspirin and indomethacin blocks arachidonic acid-induced O₂ uptake and concluded that these drugs were blocking oxygenase activity. They also observed that the two drugs act in a time-dependent manner, suggesting that they cause a chemical modification of their target (1566).

Gerald J. Roth (US), Nancy Stanford (US), and Philip W. Majerus (US) showed that the acetyl group of aspirin is incorporated into a protein (1438).

Martin Hemler (US), William E.M. Lands (US), and William L. Smith, Jr. (US) purified the protein now known as prostaglandin endoperoxide H synthase-1 (PGHS-1) or cyclooxygenase-1 (COX-1) (745).

David L. DeWitt (US), El-Harith A. El-Harith (SA), Stacey A. Kraemer (US), Martha J. Andrews (US), Eveline F. Yao (US), Robert L. Armstrong (US), and William L. Smith, Jr. (US) showed that substitution of Ser-530 with alanine rendered the protein refractory toward aspirin but had relatively little effect on the kinetic properties of the cyclooxygenase. They concluded that the Ser-O-acetyl protrudes into the cyclooxygenase active site thereby interfering with arachidonic acid binding (432). There is now general acceptance of the concept that these drugs work by inhibition of the enzyme cyclooxygenase (COX) or prostaglandin H2 synthase, now known 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 (515-518; 1716-1718; 1734-1736).

 

Emil C. Gotschlich (US), Irving Goldschneider (US), Teh Y. Liu (US), and Malcolm S. Artenstein (US) developed a vaccine against Neisseria meningitidi (635; 655; 656).

 

Maurice Ralph Hilleman (US) and his colleagues rushed to manufacture a vaccine from the new flu strain Type A2, Hong Kong. In four months, Merck had manufactured more than nine million doses of vaccine (769).

 

David V. Reynolds (US) described the analgesic effect produced by electrical stimulation of the periaqueductal gray area (1405).

 

Gabor Szasz (DE) developed a clinical method for determining the serum level of gamma-glutamyl transpeptidase. The method is clinically valuable because some kidney and liver diseases cause abnormal serum levels of this enzyme (57).

 

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 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 (816).

 

Jay M. Goldberg (US), Paul B. Brown (US), Tom C.T. Yin (US), and Joseph Chan (KR) provided important information on the binaural functioning of the medial superior olive (634; 1859).

 

Paul Bessou (FR) and Edward R. Perl (US) described two populations of unmyelinated primary afferents that respond to noxious stimulation: polymodal nociceptors and high-threshold mechanoreceptors. The polymodal nociceptors were named such because they respond to mechanical, thermal (both hot and cold) and chemical (weak acids) stimuli, but only in the noxious range. Bessou and Perl further showed that polymodal nociceptors are sensitized by heat applied to the receptive field (132).

Burgess N. Christensen (US) and Edward R. Perl (US) examined dorsal horn units receiving input from slowly conducting afferents. They demonstrate that cells in the superficial dorsal horn, principally in lamina I, respond to unmyelinated and lightly myelinated primary afferents. They described cells that respond only to noxious mechanical stimulation, those that respond to noxious mechanical and thermal stimuli and those that respond to innocuous thermal changes, principally in the cooling direction (301).

 

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 (1829; 1830). 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 (953).

 

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 (1128).

 

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 (250).

 

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 (1029).

 

Theodore Pincus (US), Peter H. Schur (US), James A. Rose (US), John L. Decker (US), and Norman Talal (US) applied the Farr, ammonium sulfate technique to measure antibodies to double-stranded DNA found in patients with systemic lupus erythematosus (SLE). This method provides an easily performed specific clinical test for diagnosis and management of SLE (1344).

 

Thomas W. Smith (US), Vincent P. Butler, Jr. (US), and Edgar Haber (US) presented a rapid, sensitive, and specific radioimmunoassay for the cardiac glycoside digoxin. Concepts arising from this work were the recognition that antibody populations of sufficient specificity and affinity allow the measurement of minute concentrations of drugs and endogenous substances in biological fluids without prior separation procedures. Also, of importance has been the recognition that antibody populations directed against a non-antigenic drug molecule coupled as a hapten to a carrier macromolecule frequently achieve affinity constants of 1010 M-1 or greater (1565).

 

Geoffrey M. Collins (US), Maria Bravo-Sugarman (US), and Paul I. Terasaki (US) described a method for kidney preservation by which the organ could be stored in ice for up to 30 hours with minimal damage. The main departure from previously used methods was in the composition of the flush solution, which was formulated to resemble the intracellular rather than the extracellular ionic content (326).

 

Frederick P. Li (US) and Joseph F. Fraumeni, Jr. (US) studied children with rhabdomyosarcoma who had relatives who developed other organ-site cancers at an early age. This led to the identification of a familial cancer syndrome later shown to be primarily influenced by inherited mutations in p53 (1037).

 

Jørgen Rygaard (DK) and Carl O. Povlsen (DK) achieved heterotransplantation of a human malignant tumor to athymic "nude" mice (1450).

 

Howard A. Pearson (US), Richard P. Spencer (US), and Eugene A. Cornelius (US) designated decreased splenic reticuloendothelial uptake of radiocolloid (99mTc) in young children with sickle cell anemia who had clinical splertomegaly as “functional asplenia.” This defect is the probable basis for the high mortality from pneumococcal sepsis that these children experience in the first years of life (1316).

 

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 (824).

 

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 (580-586).

 

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 (1427).

 

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 (1050-1052).

 

William H. Harris (US) described treatment of traumatic arthritis of the hip after dislocation and acetabular fractures by mold arthroplasty. He included an end-result study using a new method of result evaluation—Harris Hip Score (715).

 

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 (1322; 1323).

 

Eugene Pleasants Odum (US) stated that ecological succession is regarded as orderly and directional, and therefore predictable, because of modifications of the physical environment by the community itself (1271).

 

Warren P. Porter (US) and David M. Gates (US) emphasized that animals must be in a thermodynamic equilibrium with their environment (1358).

 

Michael F. Land (GB) discovered in jumping spiders (Salticids) that the principal-eye retina is organized into four tiers of receptors, with light passing first through Layer 4 and then successively through Layer 3 and 2 before finally reaching Layer 1. In fact, what Land gave us, derived from serial 10μ m thick wax sections along the anterior–posterior and dorsal–ventral axes, was a remarkably detailed 3-dimensional understanding of the internal structure of the principal eye and he also showed that primary neural fibers from the receptors of each layer of the retina terminated in layer-specific areas in the part of the brain to which the optic nerve is attached.

Land hypothesized that the tiered retina functions in color vision. Land's other hypothesis was that, owing to each layer receiving in-focus images from objects at different distances in front of the eye, layering might function to expand the eye's depth of focus (991).

Land discovered that the principle eyes engage in four types of eye movement: 1) spontaneous, 2) saccades, 3) tracking, and 4) scanning. Scanning consists of a regular pattern of periodic horizontal movement simultaneous with slower rotational movement and may be unique (992).

David S. Williams (AU) and Peter McIntyre (AU) demonstrated that a pit at the rear of the principal-eye tube functions as a lens, turning the salticid principal eye into a Galilean telescope (1815).

 

Robert S. Schwab (US), Albert C. England Jr. (US), David C. Poskanzer (US), and Robert R. Young (US) reported that sixty-six percent of a group of 163 patients with Parkinson's disease exhibited subjective or objective improvement of their akinesia, rigidity, and tremor while receiving amantadine hydrochloride (1496).

 

Eddy D. Palmer (US) found that diagnostic management of 1,400 patients with severe, active upper-gastrointestinal tract hemorrhage by immediate esophagogastroscopy and contrast roentgenography provided confident identification of the bleeding lesion in 93%. Preexamination ice-water lavage of the stomach by Ewald tube and syringe proved remarkably effective for control of active hemorrhage (1300).

 

Wallace H. Clark, Jr. (US), Lynn From (US), Evelina A. Bernardino (US), and Martin C. Mihm (US) developed a five-part scale, based on the depth of penetration of the lesion from the epidermis into the dermis and down to the subcutaneous tissue, which can be used to predict the likely progression of malignant melanomas and the prognosis for the patient (310). Note: Clark and his colleagues also made seminal observations on the importance of mitotic rate and tumor infiltrating lymphocytes in primary melanomas as important prognostic variables.

 

Benton J. Underwood (US) proposed that a memory is a collection of attributes. These serve to discriminate one memory from another and to act as retrieval mechanisms. The attributes identified are temporal frequency, modality, orthographic, associative nonverbal, and associative verbal (1714).

Fergus I.M. Craik (GB-CA) and Robert S. Lockhart (AU-CA) postulated that human memory be viewed as the record of mental operations carried out primarily for the purposes of perception and comprehension. The operations are performed at various levels of processing, where ‘deeper’ levels involve greater semantic analysis and are associated with longer-lasting memory traces (366).

John Robert Anderson (US) and Gordon H. Bower (US) described an associative theory of human memory, embodied in a computer simulation that made a wide range of predictions about sentence memory and other verbal learning phenomena. The theory dealt successfully with organizational phenomena thought to disconfirm associative theories (32).

 

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 disruptive 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 (497).

 

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 (696).

 

Margaret B. Davis (US), by identifying and counting pollen grains at Rogers Lake in Connecticut, was able to construct a plant history of this area from 8,000 to 14,000 years ago (397).

 

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 BCE (652-654; 1473).

 

John Harold Ostrom (US) described the carnivorous dinosaur Deinonychus as an agile, active warm-blooded theropod who may have hunted in packs (1291).

Robert T. Bakker (US) strongly argues that dinosaurs were warm-blooded and that many were very agile runners (69-71).

 

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 (802-805).

 

Michael H. Day (GB) discovered fossil Homo sapiens in the lower basin of the Omo River, Southwest Ethiopia (402). It was dated at c.a 130K BP

 

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), i.e., Whittaker's five kingdoms taxonomic scheme (1801).

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 (785).

Ernst Heinrich Philipp August Haeckel (Häckel) (Heckel) (DE) suggested that bacteria deserved to be placed in a separate kingdom, which he named Monera (694; 695).

 

1970

“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.” Frank Macfarlane Burnet (235).

 

“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 (1189).

 

"We live in a world where unfortunately the distinction between true and false appears to become increasingly blurred by manipulation of facts, by exploitation of uncritical minds, and by the pollution of the language." Arne Vilhelm Kaurin Tiselius. Note: As attributed in prepared statement by David I. Haberman to Tiselius (1970 Nobel Prize Ceremony) in United States Congress, Senate Committee on Foreign Relations, Subcommittee on Multinational Corporations, Multinational Corporations and United States Foreign Policy (1974), 41

 

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.

 

Bernard Katz (DE-GB), Ulf Svante Hansson von Euler-Chelpin (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.

 

Susan N. Meloan (US), Linda S. Valentine (US), and Holde Puchtler (US) established the structure of carmine and its Ca⁺⁺ and Al⁺⁺⁺ lakes (1142).

 

Paul J. Crutzen (NL) wrote an article explaining that nitrogen oxides can promote decomposition of atmospheric ozone (378).

 

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 (597; 1139). 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 (460).

 

Jean-Pierre Changeux (FR), Michiki Kasai (FR), Monique Huchel (FR), and Jean-Claude Meunier (FR) isolated the nicotinic acetylcholine receptor of the eel electric organ, the first ever isolated membrane pharmacological receptor (291).

Ricardo Miledi (GB), Perry Molinoff (GB), and Lincoln T. Potter (GB) also reported the isolation of the cholinergic receptor (1160).

Anne Devillers-Thiéry (FR), Jerome Giraudet (FR), Martine Bentaboulet (FR), Jean-Pierre Changeux (FR), Masaharu Noda (JP), Hideo Takahashi (JP), Tsutomu Tanabe (JP), Mitsuyoshi Toyosato (JP), Yasuji Furutani (JP), Tadaaki Hirose (JP), Michiko Asai (JP), Seiichi Inayama (JP), Takashi Miyata (JP), Shosaku Numa (JP), Marc Ballivet (US), James Patrick (US), James Lee (US), and Stephen F. Heinemann (US) elucidated the primary structure of the subunits of the cholinergic receptor (75; 428; 429; 1249).

 

Mohammed Salah El Din Balegh (US) and Orlin Biddulph (US) showed that leaves do absorb and use much green light in photosynthesis, despite the common misconception that they reflect all green light (73).

 

Saul B. Needleman (US) and Christian D. Wunsch (US) provided a computer adaptable method for finding similarities in the amino acid sequences of two proteins (1220).

Temple Smith (US) and Michael Waterman (US) extended this dynamic programming approach to solve the local alignment problem. These exact solutions placed sequence comparisons on a firm mathematical grounding and formed the basis for the early alignment search algorithms (1564).

William R. Pearson (US) and David J. Lipman (US) devised a successful heuristic algorithm to enable efficient searching of large databases, FASTA. This simplified the problem by searching for short regions of exact match and then extending them (1317).

Stephen Altschul (US), Warren Gish (US), Webb Miller (US), Eugene W. Myers (US), and David J. Lipman (US) presented the basic local alignment search tool (BLAST), which instead searched for all short matches above a given scoring threshold and showed that this improved speed. In addition, Altschul developed a statistical framework for sequence alignment that provided a conceptual basis for understanding similarity measures, and a method for assessing the statistical significance of a given alignment. BLAST indexes the query sequence and scans against a database (24; 25).

W. James Kent (US) showed how the reverse could increase speed (at tolerably reduced sensitivity), with the BLAST-like alignment tool (BLAT) (936).

Arthur L. Delcher (US), Simon Kasif (US), Robert D. Fleischmann (US), Jeremy Peterson (US), Owen White (US), and Steven L. Salzberg (US) invented a new system for aligning whole genome sequences. Using an efficient data structure called a suffix tree, the system is able to rapidly align sequences containing millions of nucleotides (419).

Scott Schwartz (US), W. James Kent (US), Arian Smit (US), Zheng Zhang (US), Robert Baertsch (US), Ross C. Hardison (US), David Haussler (US), and Webb Miller (US) followed with 'BLASTZ' (an independent implementation of the Gapped BLAST algorithm) which is useful for cross-species comparisons, allowing alignment and searching of mammalian chromosome-length sequences. BLASTZ was subsequently modified, both to attain efficiency adequate for aligning entire mammalian genomes and to increase its sensitivity (1497).

 

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 (137-139).

 

San-pin Wang (CN-US) and J. Thomas Grayston (US) developed the Micro-Immunofluorescence (micro-IF) Test (1758).

 

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 (158; 1506; 1507).

 

David H. MacLennan (CA) purified ATPase from sarcoplasmic reticulum via fractionation. Based on several observations, including the fact that the enzyme has sites for both Mg2 and Ca2, the enzyme carries out partial reactions of Ca2 transport, and the enzyme contains phospholipid and can form in membranes, MacLennan concluded that the ATPase is also the calcium transporter (1087).

 

Peter H. Duesberg (US) and Peter K. Vogt (US) noted that the 60–70S RNAs of several transforming and nontransforming avian tumor viruses have different electrophoretic mobilities. The RNA of transforming viruses contains two electrophoretically separable subunit classes: a and b. The relative concentrations of these subunits vary with the virus strain. Avian leukosis viruses and nontransforming derivatives of a sarcoma virus lack subunits of class a. It is suggested that the presence of the class asubunit is related to the transforming ability for fibroblasts of the virus (468). Note: This is one of the firt articles in molecular cancer research.

 

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 (CN-US) was examining the necessity of a calcium binding activator for cyclic 3', 5'-nucleotide phosphodiesterase when they discovered calmodulin (295; 890).

Wai Yiu Cheung (CN-US), Thomas J. Lynch (US), and Robert W. Wallace (US) named it calmodulin (296; 297).

Rajendra K. Sharma (CA), Rekha Desai (CA), David M. Waisman (CA), and Jerry H.C. Wang (TW-CA) isolated calmodulin and was able to show that its function is calcium- dependent. He also isolated calcineurin as the major calmodulin-binding protein of the central nervous system and several isoforms of cyclonucleotide phosphodiesterases (1513).

D. Martin Watterson (US), Farida Sharief (US), and Thomas C. Vanaman (US) determined the primary amino acid structure of calmodulin (1770).

 

June L. Biedler (US) and Hansjørg Riehm (DE) performed investigations which support the hypothesis that the development of resistance to Actinomycin D in Chinese hamster cells is due to qualitative difference in cell membrane, resulting in decreased permeability to Actinomycin D and other compounds. Actinomycin D-resistant cells were cross-resistant, in decreasing order, to mithramycin, vinblastine, vincristine, puromycin, daunomycin, demecolcine, and mitomycin C (141). Note: Identifying drug transporters in the cell membranes that control entry of drugs in and out of the cell is very important for the pharmacokinetics of drug action.

 

Michael B. Jackson (GB) and Daphne J. Osborne (GB) showed that “natural” leaf fall is triggered by increased ethylene production in senescing cells close to abscission zones (840).

Irene Ridge (GB) and Daphne J. Osborne (GB) found that towards the end of cell elongation in Pisum sativum there is a large rise in peroxidases and hydroxyproline-rich protein components and thereafter a continuing slow rise which is associated with increasing age of tissue. Ethylene at concentrations of 0.1 ppm or more increases both peroxidase activity and hydroxyproline levels in the walls, the greatest response occurring in immature tissue including the apical hook. Growth of these tissues is highly sensitive to ethylene which causes an inhibition of elongation in extending cells and an enhanced lateral cell expansion. They suggested that the effects of ethylene on wall-bound peroxidase and hydroxyproline are implicated in the ethylene regulation of cell growth (1409).

 

Tai Te Wu (CN-US) and Elvin Abraham Kabat (US) found that the three hypervariable segments of the variable regions of light and of the heavy chains of human and mouse immunoglobulins have been delineated from a statistical examination of sequences aligned for maximum homology and postulated to be the complementarity determining residues of antibody combining sites (882; 1845).

 

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 (140). Later, CRL cells became known a B-lymphocytes and non-CRL cells as T lymphocytes.

 

Martin C. Raff (CA-GB) described how to identify murine B-lymphocytes by the presence of immunoglobulin (Ig) in their surface membrane. It was apparent that this simple method could be directly applied to human cells (1377; 1378).

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 (1329).

Alan C. Aisenberg (US) and Kurt J. Bloch (US) found that the neoplastic lymphocytes of nearly all of 25 patients with chronic lymphocytic leukemia (CLL) carried surface immunoglobulin (Ig) molecules of a single heavy (mu) and light chain (either kappa or lambda) type. B-lymphocytes show a similar restriction of their surface Ig to a single heavy and light chain type. Thus, the observations in CLL provided evidence for the clonal origin of the neoplastic cells and established their B-cell lineage (17).

 

John D. Crossland (GB), M.D. Pepper (GB), Carolyn M. Giles (GB), and Elizabeth W. Ikin (GB) discovered the MV blood antigen (376).

 

Carolyn M. Giles (GB), J. Darnborough (GB), Peter Aspinall (GB), and M.W. Fletton (GB) identified the Cob blood antigen (626).

 

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 (9).

 

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 (415; 416).

Takashi Murachi (JP) demonstrated that trypsin exhibits similar behavior (1209).

 

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 (957; 967; 1200; 1201).

 

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 (499).

 

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 (77; 1092).

 

Masayasu Nomura (JP-US) and Volker A. Erdmann (DE) were the first to reconstitute the 50S ribosomal subunit. Their material was from Bacillus stearothermophilus (1250).

 

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 (1198).

 

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 (144; 1748).

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 (1764).

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 (628; 1752; 1754).

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) (1753).

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 (1755). “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” (1751).

Davis T.W. Ng (US), Jeremy D. Brown (GB), and Peter Walter (US) discovered an SRP-independent targeting to the ER membrane (1232).

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 (690; 1290).

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 (1756).

 

Virginia M. Tennyson (US) noted the presence of ribosomes in the early embryonic axons suggesting that protein synthesis may continue in these segments at a considerable distance from the perikaryon (1658).

Douglas S. Campbell (GB) and Christine E. Holt (GB) have documented ribosomes, mRNA, translational initiation proteins, and protein synthesis in axons and growth cones (253).

 

Prafullachandra Vishnu Sane (IN), David J. Goodchild (US), and Roderic B. Park (US) proposed a model for chloroplast membrane structure. One large membrane is folded into stacked and unstacked interconnecting regions. While photosystem I and small freeze fracture particles exist in both regions, photosystem II and large particles are restricted to the stacked regions (1309; 1465).

 

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 (262-264).

 

Ruth Sager (US) and Zenta Ramanis (US) produced a genetic map of non-Mendelian (chloroplast) genes in Chlamydomonas (1456).

 

Andrzej Krzysztof Tarkowski (PL), Anna Witkowska (PL), and Jolanta Nowicka (PL) showed for the first time in history that parthenogenetically activated mouse oocytes are able of developing until mid-gestation (1649).

 

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 (1386). 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 (379; 716-721). Note: This work laid the groundwork for the discovery of checkpoint proteins and how cancer cells derail checkpoints.

 

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 (1115). MPF was later identified as cyclin B-CDC2. See below.

Paul Maxime 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 characterization 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” (1260).

Paul Maxime 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 (1259).

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 (609).

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 (1231). 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 (869).

Tom Evans (GB), Eric T. Rosenthal (US), James Youngblom (US), Dan Distel (US), and Tim Hunt; Richard Timothy Hunt (GB) discovered and named cyclin from sea urchin eggs. It is identical to the larger polypeptide (523).

Robert T. Johnson (US) and Potu N. Rao (US) identified a soluble factor, which promotes condensation of chromosomes (868). 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 (1063).

Jean-Claude Labbé (FR), Melanie G. Lee (GB), Paul Maxime 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 (982; 983).

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 (1454).

Arthur Beck Pardee (US) proposed that cells go into a Gap 0 (G0) state, and that this is an equivalent state irrespective of how 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 (1305; 1306).

Anders Zetterberg (SE) and Olle Larsson (SE) showed that a variable growth-factor-dependent phase preceded a growth-factor-independent phase (1869).

Viesturs Simanis (CH) and Paul Maxime Nurse (GB) found that the cell cycle control gene cdc2+ of fission yeast encodes a protein kinase potentially regulated by phosphorylation (1532).

Paul Russell (GB) and Paul Maxime 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 (1448).

Paul Russell (GB) and Paul Maxime Nurse (GB) found that wee1+ functions as a dose-dependent inhibitor of mitosis, the first such element to be specifically identified and cloned (1449).

Melanie G. Lee (GB) and Paul Maxime 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 (1013).

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 (1782).

Melanie G. Lee (GB), Christopher J. Norbury (GB), Nigel K. Spurr (GB), and Paul Maxime 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 (1012).

Jean-Claude Labbé (FR), Melanie G. Lee (GB), Paul Maxime 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+ (983).

Kathleen L. Gould (GB) and Paul Maxime 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 (658). 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 (485; 486). 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 (808; 1042).

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" (796).

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 (948).

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 (1616). 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), Tim Hunt; 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 (593).

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 (67; 532; 1552).

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 (302).

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 (679; 1066; 1155; 1710). C. Michaelis and his colleagues coined the term cohesins.

Leland Harrison Hartwell (US), Tim Hunt; Richard Timothy Hunt (GB), and Paul Maxime 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), 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 can occur in the absence of an antigen-antibody reaction (657; 985).

 

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 (1627; 1711).

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 (958; 1711).

Matthew Daniel Scharff (US) and Reuven Laskov (IL) discovered that the genes for the heavy and light chains of the immunoglobulin molecule are not linked and are translated onto separate messengers (1478).

 

Peter B. Moore (GB), Hugh Esmor Huxley (GB-US), and David J. DeRosier (GB-US) showed how myosin cross-bridges could interact with actin filaments. They suggested that myosin cross bridging supplied the power source for muscle contraction (825; 1194).

Birdwell Finlayson (US), Richard W. Lymn (US), Edwin William Taylor (US) and George Moll (US), among others, worked out many of the biochemical details (542; 543; 1080; 1653).

 

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 (508).

 

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 (489-491; 592).

 

Alan Bernheimer (US) proposed the terms cytotoxin or cytolytic toxin to describe the range of biological activity exhibited by the membrane-damaging toxins (129).

 

Johann Stenflo (SE) showed that administration of the vitamin K antagonist dicumarol leads to the biosynthesis of an abnormal prothrombin that is chemically like prothrombin but is biologically inactive (1599). See, Harold A. Campbell, 1941, for the discovery of dicumarol.

Johann Stenflo (SE), Per-Olov Garnot (SE), Gary L. Nelsestuen (US), and John W. Suttie (US) showed that the two forms of prothrombin are similar in carbohydrate and amino acid composition, molecular weight, and antibody-antigen reactions, but the inactive prothrombin does not bind calcium to the same degree as the active protein (1225; 1600; 1603).

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 (1091; 1226; 1601).

Johan Stenflo (SE) showed that the differences in the two forms of prothrombin are confined to two peptides, residues 4–10 and residues 12–44 (1601).

Johann Stenflo (SE), Per Fernlund (SE), William Egan (SE), and Peter Roepstorff (DK) discovered that the smaller peptide from normal prothrombin contains 2 residues of glutamic acid modified to gamma-carboxyglutamic acid, a previously unknown amino acid (1602).

Per Fernlund (SE), Johan Stenflo (SE), Peter Roepstorff (DK), and Johannes Thomsen (DK) determined the structure of the second peptide and identified the residues containing modified glutamic acid. They found that the first 10 glutamic acid residues in prothrombin are carboxylated to form gamma-carboxyglutamic acid and that these gamma-carboxyglutamic acid residues constitute the entire vitamin K-dependent modification of prothrombin (535). Stenflo’s work on prothrombin and vitamin K was a major contribution to understanding the role of calcium and the mechanism of prothrombin activation in blood clotting.

 

Peter S. Carlson (US) developed in vitro methods to select biochemical mutants in tobacco (260).

 

David A. Hungerford (US), William J. Mellman (US), Gloria B. Balaban (US), Gundula U. LaBadie (US), Linda R. Messatzzia (US), and Gail Haller (US) described how the trisomy mutation associated with Down syndrome developed in meiosis (822).

David A. Hungerford (US) reported that a prolonged hypotonic treatment (60 minutes) spreads the pachytene bivalents enough for an analysis of the chromomere pattern (821).

 

James W. Truman (US) and Lynn Riddiford (US), using two species of silk moths which eclose at different times of day showed that eclosion gating is governed by the brain. By exchanging brains between the two species they `transplanted' the timing of eclosion. These experiments provided compelling evidence that the moth brain contains a photoreceptor mechanism, a clock and a neuroendocrine output that are necessary and sufficient for the synchronization of eclosion behavior with the environmental photoperiod (1699). Eclosion is the emergence of the adult from its pupal cuticle.

Once it was clear that ecdysis into the adult is controlled by the circadian clock, Truman asked whether the same holds true for larval ecdyses. He reported on the circadian organization of the endocrine events underlying the larval moulting cycle. Using the tobacco hornworm, Manduca sexta, Truman showed in this study that larval ecdyses in Manduca occur at a specific time of day and that release of a major insect developmental neurohormone is gated by the circadian clock. The insect moulting cycle starts with the release of the prothoracicotropic hormone (PTTH), which stimulates the production of ecdysone by the prothoracic glands. Ecdysone initiates secretion of a new cuticle and digestion of the old one, followed by the ecdysis behavior. He showed that in contrast to adult eclosion, the synchrony of larval ecdysis does not arise from circadian gating of the ecdysis behavior itself (1698). That the circadian clock gates PTTH has been confirmed even in distantly related insect species.

 

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 (1361).

 

Patricia A. Black-Cleworth (US) discovered that weakly electric fish use their electric organs for social communication such as aggressiveness, submission, and probably courtship (148).

 

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 (1518).

 

Workers in Switzerland at Sandoz Ltd. while looking for new antifungal agents discovered the cyclosporins. 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.

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 that is produced by Trichoderma polysporum (1446).

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 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 (161-163; 1145).

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 (251; 1363). Cyclosporine was the first immunosuppressive medication powerful enough to allow transplants to become life-saving treatments, rather than experimental research.

Ronald M. Wenger (CH) worked out the complete structural analysis and synthesis of cyclosporin A and cyclosporin H (1795; 1796).

Elizabeth A. Emmel (US), Cornelis L. Verweij (US), David B. Durand (US), Kay M. Higgins (US), Elizabeth Lacy (US), and Gerald R. Crabtree (US) showed that cyclosporin A either directly inhibits the function of nuclear proteins critical to T lymphocyte activation or inhibits the action of a more proximal member of the signal transmission cascade leading from the antigen receptor to the nucleus (507).

 

Peter A. Bretscher (CA) and Melvin Cohn (US) proposed the two-signal theory of lymphocyte activation. This theory states that for an effector lymphocyte to become stimulated it must receive two signals, one from an antigen the other from a helper T cell (192). This had already been demonstrated by Henry Neumann Claman (US), Edward A. Chaperon (US), and R. Fraser Triplett (US) (303; 304).

 

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) (610).

 

Peter J. McCullagh (AU), Richard K. Gershon (GB), and Kazunari Kondo (JP) discovered suppressor T lymphocytes (611; 1127).

 

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 (254).

 

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 (319).

Beatrice Mintz (US), Karl Illmensee (US), Virginia E. Papaioannou (US), Michael W. McBurney (CA), Richard L. Gardner (GB), and Martin John 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 (1170; 1302). 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 (810).

 

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 (1351).

 

David J. DeRosier (GB-US), Peter B. Moore (US), 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 (377; 426; 1194).

 

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 (123; 608; 1434; 1435; 1817).

 

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 (1560).

Thomas J. Kelly, Jr. (US), Hamilton Othanol Smith (US), and Kent W. Wilcox (US) determined the base sequence recognized by the restriction endonuclease, Hind II (928; 1560).

 

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 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 (354; 521; 522; 1134; 1206; 1264; 1592; 1854-1856).

 

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 (1453).

 

Morton Mandel (US) and Akiko High (JP) 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 could be rendered more competent than can cells in other stages of growth (762; 1102).

 

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 (1219).

Anatol Eberhard (US) found that the autoinducer does exist (480).

 

Choh Hao Li (CN-US), David Chung (US), Waleed Danho (DE-US), Kalman Kovacs (HU), and Yolande Kovacs-Petres (US) synthesized the pituitary human growth hormone (HGH) or somatatropin, the largest protein molecule yet put together in the laboratory (383; 384; 968; 1035).

 

Robert Huber (DE) determined the atomic structure of insect hemoglobin (812).

 

Phillip Periman (US) was the first to demonstrate that antibody production persisted when a lymphoid cell was fused with an established cell line (1326).

 

Louis Lim (GB), Evangelos S. Canellakis (GR-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 (492; 1014; 1054).

 

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 (924; 1196; 1197; 1262; 1863).

 

Paul Greengard (US), Jacqueline F. Kuo (US), and Howard Schulman (US) identified cGMP- and Ca2 -calmodulin-dependent kinases, which established that second messengers other than cAMP were also involved in brain signaling mechanisms (670; 979; 1494; 1495).

 

 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 (1425).

 

Geoffrey A. Parker (GB) proposed that when a female mates with several partners rather than with a single male, the potential exists for sperm competition to occur, between the gametes of rival males, for access to her ova (1310).

 

Saimon Gordon (US), Zanvil Alexander Cohn (US), and Carolyn S. Ripps (US) produced high yields of mouse macrophage-melanocyte heterokaryons and macrophage-macrophage homokaryons through the virus-induced fusion of cells spread on a glass surface. These observations indicate that typical macrophage properties cease to be expressed in heterokaryons, and melanocyte functions presumably predominate in heterokaryons and hybrids (646; 647).

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 (1184).

 

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) (220). Lassa fever is an acute viral illness that occurs in West Africa.

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 (1188).

 

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 (962).

 

Leendert C. van Loon (NL) and Albert van Kammen (NL) discovered that additional proteins associated with systemic acquired resistance (SAR) are induced in tobacco (Nicotiana tabacum) plants that react hypersensitively to tobacco mosaic virus (1724). These are now well known as pathogenesis-related proteins (PRs), novel proteins that are induced in pathological or related situations.

Angela Schlumbaum (CH), Felix Mauch (CH), Urs Vögeli (CH), and Thomas Boller (CH) found that fungal attack, as well as ethylene, induced a chitinase in bean (Phaseolus vulgaris) leaves that could act as a potent inhibitor of fungal growth (1486).

Marianne B. Sela-Buurlage (NL), Anne S. Ponstein (NL), Sandra A. Bres-Vloemans (NL), Leo S. Melchers (NL), Peter J.M. van den Elzen (NL), and Ben J.C. Cornelissen (NL) reported evidence that the pathogen-inducible, apoplastic PRs do not contribute much to resistance against the inducer (but may still play a role in SAR against subsequent attack), whereas the constitutive, vacuolar counterparts may readily attack invading pathogens upon rupture of the tonoplast (1503).

Michel Legrand (FR), Serge Kauffmann (FR), Pierrette Geoffroy (FR), and Bernard Fritig (FR) found that some of the virus-induced tobacco PRs possess endochitinase activity (1018).

Serge Kauffmann (FR), Michel Legrand (FR), Pierrette Geoffroy (FR), and Bernard Fritig (FR) found that some of the virus-induced tobacco PRs possess endo-b-1,3-glucanase activity (918). Note: These results provided a first explanation for why SAR was effective not only against viruses but also against other types of pathogens.

Felix Mauch (CH), Brigette Mauch-Mani (CH), and Thomas Boller (CH) reported that the nonhost pathogen Fusarium solani f. sp. phaseolicola induced both chitinase and glucanase activities in pea (Pisum sativum) pods and that combinations of the purified chitinases and glucanases could fully explain the inhibitory action of protein extracts from the pods on the in vitro growth of various pathogenic and saprophytic fungi (1121). Note: These data clearly indicated that pathogen-inducible hydrolytic enzymes contribute to the inhibition of potential fungal pathogens and the reduction of disease.

 

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 (1779).

 

Delia B. Budzko (AR-US) 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 (221).

 

Eleanor H. Slifer (US) reviewed evidence for minute pores or openings that penetrate the otherwise impermeable cuticle that covers insect chemoreceptors. It is through these pores that odors pass to stimulate the sensory neurons (1554).

 

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 (1685).

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 (1488-1490).

 

Kenneth M. Yamada (US), Brian S. Spooner (US), and Norman K. Wessells (US) studied the 50 angstrom thin filament of the cell and provided the necessary correlative link: only when there was 50 angstrom filament structure was there also motile function (1578; 1851; 1852).

James A. Spudich (US) and Shin Lin (US) showed that cytochalasin B (an alkaloid) specifically binds to purified muscle actin, supporting the conclusion that the thin filaments required for cell movement are indeed actin-like proteins (1581).

Brian S. Spooner (US), John F. Ash (US), Joan T. Wrenn (US), Robin B. Frater (US), Norman K. Wessells (US), and Carter R. Holladay (US) confirmed the work of Spudich and Lin (1576; 1577).

 

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 (914).

 

Donald R. Hoff (US), Michael H. Fisher (US), Richard J. Bochis (US), Aino Lusi (US), Frank S. Waksmunski (US), John R. Egerton (US), Jerome J. Yakstis (US), Ashton C. Cuckler (US), and William Cecil Campbell (IE-US) described a new broad-spectrum anthelmintic: 2-(4-thiazolyl)-5-isopropoxycarbonylamino-benzimidazole (780).

 

Albert Herz (DE), Klaus Albus (US), Jan Metys (DE), Peter Muenchen Schubert (DE) and Hansjörg Teschemacher (DE) found that microinjection of opioids into various brain areas and application of opioids into separated parts of the cerebroventricular system in rabbits revealed that complete antinociception can be obtained from caudal parts of the periaqueductal grey and adjacent areas of the floor of the fourth ventricle (757).

 

Aubrey E. Boyd III (US), Harold E. Lebovitz (US), and John B. Pfeiffer (US) showed clearly that the administration of L-dopa, a precursor of central nervous system catecholamines, stimulated the release of growth hormone in man. The data indicated that a dopaminergic mechanism in the median eminence or norepinepheine sensitive site in the hypothalamus was involved in human growth hormone regulation (174).

 

Derek A. Radcliffe (GB) discovered changes attributable to pesticides in egg breakage frequency and eggshell thickness in some British birds (1388).

 

Walter Plowright (GB), C.T. Perry (GB), and Mike A. Peirce (GB) confirmed transovarial infection with African Swine Fever virus in the argasid tick, Ornithodoros moubata porcinus, Walton (1348).

Leon Rosen (US), Robert B. Tesh (US), Jih Ching Lien (US), and John H. Cross (US) described transovarial transmission of Japanese encephalitis virus by mosquitoes (1430).

Robert B. Tesh (US) and Donald A. Shroyer (US) described the mechanism of arbovirus transovarial transmission in mosquitoes: San Angelo virus in Aedes albopictùs (1664).

 

Paul G. Lendvay (AU) and Earl R. Owen (AU) pioneered microsurgery techniques when they rejoined an amputated index finger (1025).

 

Robert Ellis Shope (US), Frederick A. Murphy (US), Alyne Keiran Harrison (US), Ottis R. Causey (US), Graham E. Kemp (US), D. I. H. Simpson (IE), and Dorothy L. Moore (CA) reported that Lagos bat virus and an isolate from shrews (IbAn 27377), both from Nigeria, were found to be bullet-shaped and to mature intracytoplasmically in association with a distinct matrix. They were related to, but readily distinguishable from, rabies virus and each other by complement fixation and neutralization tests. The three viruses, including rabies, form a subgrouping within the rhabdoviruses (1522).

 

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 (prolactin-inhibiting hormone) receptors but not noradrenaline receptors (31).

 

Isaac Djerassi (US), Jung Sun Kim (US), Chulee Mitrakul (US), Udom Suvansri (US), and W. Ciesielka (US) invented leukocyte filtration (leukopheresis) and popularized leukocyte transfusions (444; 445).

Isaac Djerassi (US) and Jung Sun Kim (US) invented gravity leukopheresis (443).

 

Chester B. Martin, Jr. (US) and Elizabeth Mapelsden Ramsey (US) reported that propelled by the force of fetal blood pressure, fetal blood courses through the umbilical arteries into the subdivisions which run laterally through the chorionic plate. Finally, the vessels dip into the substance of the placenta and travel through the arborizations of the fetal villous tree. They proceed in comparable subdivisions to the terminal villi. There the fetal capillary bed, coming into its closest proximity to maternal blood in the intervillous space, forms the ultimate area of matemalfetal exchange. Oxygenated blood returns via vessels running through the same villous stems to the umbilical vein and thence to the fetal body (1114).

 

Thomas Martin Barratt (GB), Peter N. McLaine (GB-CA), and James F. Soothill (GB) developed a method by which a single voided urine sample could be used to estimate quantitative proteinuria (91).

Jay M. Ginsberg (US), Bruce S. Chang (US), Richard A. Matarese (US), and Serafino Garella (US) also developed a technique for use of single voided urine samples to estimate quantitative proteinuria (629).

 

Millard Bass (US) investigated an epidemic of 110 sudden sniffing deaths without plastic bag suffocation which occurred in American youths during the 1960's. Volatile hydrocarbons most frequently involved were trichloroethane and fluorinated refrigerants. Sudden sniffing death occurred in all socioeconomic groups, with a preponderance in the suburban middle-income white family. Severe cardiac arrhythmia, resulting from light plane anesthesia, and intensified by hypercapnia or stress or activity or a combination of these, is the most likely explanation for sniffing death (94).

 

Donald R. Taves (US), Bill W. Fry (US), Richard B. Freeman (US), and Alastair J. Gillies (US) measured the concentrations of inorganic fluoride and nonvolatile organic fluoride in a patient with nephrotoxic effects following methoxyflurane anesthesia. Concentrations of both were markedly elevated compared to two patients who received methoxyflurane without subsequent nephrotoxic effects. Indirect evidence suggests that the inorganic fluoride concentration was sufficient to account for the nephrotoxic effects. The prolonged elevation of inorganic fluoride observed can be explained on the basis of the breakdown of the nonvolatile organic fluoride to inorganic fluoride and the poor renal clearance of both types (1651).

 

Raymond J. Shamberger (US) reported that in 5 of 6 nondietary tumor-promotion experiments, sodium selenide significantly reduced the number of tumors in mice. In 2 of these 6 experiments, vitamin E also significantly reduced the number of animals with tumors. In all 6 experiments, both selenium and vitamin E decreased the total number of papillomas. Another antioxidant and 2 lysosomal stabilizers were ineffective. After 19 weeks of administration, sodium selenide did not significantly lower the number of mice with 3-methylchol-anthrene-induced papillomas nor after 30 weeks of administration did it reduce the number of cancers. Nonetheless, the total number of papillomas and cancers were greatly decreased. Torula yeast diets containing 1.0 part per million (ppm) sodium selenite given to mice markedly decreased the number of skin tumors induced by 7,12-dimethylbenz[a]anthracene plus croton oil and benzo[a]pyrene. Torula diets containing 0.1 ppm sodium selenite and a commercial diet (Rockland) did not decrease tumor incidence (1509).

 

C. Lowell Edwards (US) and Raymond L. Hayes (US) reported that gallium has an affinity for some human as well as animal neoplasms. Carrier-free gallium citrate Ga 67 administered intravenously is localized in a variety of malignant tumors that can then be detected on scintiscans. Nonosseous as well as skeletal lesions can be seen, including some that are not otherwise detectable. Gallium localization is greatest in viable tumor, less in fibrotic or necrotic tumor, and diminished by irradiation and effective chemotherapy (494).

 

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 (191).

 

William S. Fields (US), Valentina Maslenikov (UY), John Stirling Meyer (US), William K. Hass (US), Richard D. Remington (US), and Mary Macdonald (US) provided a progress report of prognosis following surgery or nonsurgical treatment for transient cerebral ischemic attacks and cervical carotid artery lesions (539).

 

William B. Kannel (US), Philip A. Wolf (US), Joel Verter (US), and Patricia M. McNamara (US) found that control of hypertension, labile or fixed, systolic or diastolic, at any age, in either sex appears to be central to prevention of atherothrombotic brain infarction (ABI). Prospectively, hypertension proved the most common and potent precursor of ABI's. Its contribution was direct and could not be attributed to factors related both to stroke and hypertension. Asymptomatic, causal "hypertension" was associated with a risk of ABI about four times that of normotensives. The probability of occurrence of an ABI was predicted no better with both blood pressure measurements or the mean arterial pressure than with systolic alone. Since there was no diminishing impact of systolic pressure with advancing age, the concept that systolic elevations are, even in the aged, innocuous is premature. Comparing normotensives and hypertensives in each sex, women did not tolerate hypertension better than men (897).

 

Harold James Charles Swan (US), William Ganz (US), James Forrester (US), Harold Marcus (US), George Diamond (US), and David Chonette (US) developed a self-guiding flow-directed catheter, which permitted catheterization of the right side of the heart and pulmonary artery without the use of fluoroscopy and with minimal complications. The addition of multiple sensors has allowed for the quantitative measurement of cardiac function. This development has permitted the application of quantitative cardiac catheterization procedures to the management of the critically ill (1636).

 

Alex S. Gallus (AU), John F. Cade (AU), John K. Clareborough (AU), Jack Hirsh (AU-CA), John Hugh Nicholas Bett (AU), Peter A. Castaldi (AU), G.S. Hale (AU), James P. Isbister (AU), K.H. McLean (AU), Edward F. O'Sullivan (AU), James C. Biggs (AU), Colin N. Chesterman (AU), Jack Hirsh (AU), Iryna G. McDonald (AU), John J. Morgan (AU), and Murray 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 (133; 247; 596).

 

Hershel Jick (US), Olli S. Miettinen (US), Samuel Shapiro (US), George P. Lewis (US), Victor Siskind (US), and Dennis Slone (US)satisfied the urgent need for information about clinical drug effects by utilizing a large-scale comprehensive drug surveillance program designed to permit the detection of unsuspected side effects and drug interactions, the quantitation of known effects, and the evaluation of the role of influencing factors. Such a program, the Boston Collaborative Drug Surveillance Program, now involving eight hospitals, is described (866).

 

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 (1048).

 

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 occasionally, 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 (577).

 

Daniel H. Janzen () and Joseph H. Connell (US) independently proposed that the maintenance of tree species biodiversity in tropical rainforest 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 (332; 846). 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.

 

Eric R. Pianka (US) stated that natural selection in saturated environments (where demand for resources approximates supply) is density dependent, favoring competitive ability at the expense of slow growth and delayed reproduction. In contrast, in competitive vacuums (resource supplies greatly exceed demand), selection is independent of population density and favors rapid growth, early reproduction, and short life spans. Concepts of r and K selection are clarified, and their correlates listed (1343).

 

Robert C. Bolles (US) starts with the assumption that animals have innate defensive behaviors, such as freezing, fleeing and fighting. He proposes that if an avoidance response is rapidly learned, then that response must necessarily be one of the animal's species-specific defense reactions, or part of such a reaction. Some reinforcement-produced learning does occur with more slowly learned avoidance responses, but it is slow, uncertain, and not based on the conventional mechanism (159).

 

Scott E. Monroe (US), Linda E. Atkinson (US), and Ernst Knobil (US) performed a systematic investigation of control of the menstrual cycle, with the rhesus monkey, Macaca mulatta, as an experimental animal (1191).

 

Jerram L. Brown (US) and Gordon H. Orians (US) predicted “cost-benefit models for the evolution of space-related aggression point to the importance of measuring the temporal and spatial distribution of resources, the costs of exclusion, and the rates of predation on clumped and spaced individuals. Future studies will concern themselves primarily with measuring differences in fitness of individuals of the same species under different conditions and with analyzing changes in spacing patterns in species which exploit a variety of environments. Thus, the study of spacing may rapidly develop into a theoretically rigorous and more experimentally oriented science” (208).

 

James M. Bowler (AU), Rhys Jones (AU), Harry Allen (AU), Alan G. Thorne (AU), and Mike Barbetti (AU) reported Lake Mungo 1 (Mungo Lady) which was discovered in 1969 and is one of the world's oldest known cremations (81; 171; 172). Note: Lake Mungo is in New South Wales, Australia.

 

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” (309).

 

English country names and code elements taken from the International Organization for Standardization:

DZ = Algerian; US = American; AR = Argentinian; AU = Australian; AT = Austrian; AT/HU = Austro/Hungarian; BA = Bosnian-Herzegovinian; BE = Belgian; BR = Brazilian; GB = British; BG = Bulgarian; CM = Cameroonian; CA = Canadian; TD = Chadian; CL = Chilean; CN = Chinese; CO = Colombian; CR = Costa Rican; HR = Croatian; CU = Cuban; CY = Cypriot; CZ = Czechoslovakian; DK = Danish; NL = Dutch; EC = Ecuadorian; EG = Egyptian; EE = Estonian; ET = Ethiopian; FI = Finnish; FR = French; DE = German; GR = Greek; GT = Guatemalan; GU = Guamanian; HU = Hungarian; IS = Icelander; IN = Indian; ID = Indonesian; IR = Iranian; IQ = Iraqi; IL = Israeli; IE = Irish; IT = Italian; JP = Japanese; KE = Kenyan; KR = South Korean; KW = Kuwaiti ; LV = Latvian; LB = Lebanese; LT = Lithuanian; LU = Luxembourgian; MK= Macedonian; MG = Malagasy; MT = Maltese; MY = Malaysian; MX = Mexican; NA = Namibian; NZ = New Zealander; NG = Nigerian; NO = Norwegian; PK = Pakistani; PA = Panamanian; PE = Peruvian; PH = Filipino; PL = Polish; PT = Portuguese; PR = Puerto Rican; RO = Romanian; RU = Russian; SA = Saudi Arabian; SN = Senegalese; CS = Serbian-Montenegrin; SG = Singaporean; SK = Slovakian; Slovenian = SI; ZA = South African; ES = Spanish; LK = Sri Lankan; SE = Swedish; CH = Swiss; SY = Syrian; TW = Taiwanese; TZ = Tanzanian; TH = Thai; TN = Tunisian; TR = Turkish; UG = Ugandan; UA = Ukrainian; UY = Uruguayan; VE = Venezuelan; ZW = Zimbabwean

 

 

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