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, DSU Box 3262, Cleveland, MS 38733. jsteen08@bellsouth.net



“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 (815).


“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 (690).


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 (1133).


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 (1851).


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 (386; 1277).


Alfred Zettner (US) and David Seligson (US) were the first to use atomic absorption spectrophotometry to measure serum calcium (1859).

David L. Trudeau (US) and Esther F. Freier (US) first described the use of lanthanum in the measurement of calcium in biological fluids (1687).


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 (739).


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 (1202).


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 (372; 373).


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 (928).


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 (462).


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 (1728). 


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 (1009-1012).

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 (880).


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 (982). 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 (661).

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 (670).

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 (1340).


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 (839).


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; 1004).


Karl Sune Detlof Bergström (SE), Henry Danielsson (SE), and Bengt Samuelson (SE) demonstrated the enzymatic conversion of arachidonic acid to prostaglandin E2 (125). 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 (1539).


Choh Hao Li (CN-US) and Yehudith Burk (US) isolated and purified beta-lipotropin (beta-LPH) (1023).

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 (1022).

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 (291).


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 (1349). 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 (1409).


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 (1488; 1710).


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 (117).


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 (1630).


Kendrick W. Dungan (US) and Paul M. Lish (US) were the first to describe sotalol (463). 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 (1530).


Sipra Guha (IN) and Satish C. Maheshwari (IN) obtained haploid plants of Datura innoxia Mill (Angel's trumpet) from anther cultures (672; 673).

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) (1505).


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 (272).


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 (112).


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 (1097).


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 (859).


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 (333; 1601). 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 (1635).

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 (1799). 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 (1327).


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 (286; 1126; 1604). 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 (421; 732; 1143; 1702).


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 (231).


Robert Tod Schimke (US) was the first to report protein degradation as a regulatory process and thereby established a new field of biochemistry (1471).


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 (319).


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" (639).

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 (383-385; 638; 640; 1573).


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 (524).


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 (1752).

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 (595).


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; 502; 1062; 1379).


Te-Wen Chang (US) and Louis Weinstein (US) report that the antibiotic cephalothin inhibits cell wall peptidoglycan synthesis (283).


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 (1068).


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 (1419).


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 (1182).


Daniel Nathans (US) demonstrated that puromycin inhibits protein synthesis by being incorporated into the growing polypeptide chain, resulting in premature termination of translation (1208).


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) (316; 618; 631-633; 786; 1293; 1699).


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) (525).


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 (292; 293; 1718).


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 (996; 1329; 1664).


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 (1151).


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 (649; 1094).


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 (455; 1086-1089; 1832).


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 (1823).


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 (478).


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 (437; 717; 997; 1229; 1230; 1322).


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 (1046; 1232; 1757).


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 (830).


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 (519).


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 (330-332).


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 (1442).


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 (1386).


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 (493; 1531).


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 (105; 109-111).


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 (767; 768).

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 (653; 654).

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 (863).


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 (825).


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 (1498).


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 (1330-1332).


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 (1357).


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 (1061).


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 (484; 687-689).

Graham Hoyle (US) and Thomas Smyth, Jr. (US) had discovered the giant muscle fibers in the North Pacific barnacle (796).


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 (1078).


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 (836; 837).


John W. Littlefield (US) introduced HAT medium (hypoxanthine, aminopterin, and thymidine) for the selective growth of somatic cell hybrids (1048). 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 (1095).


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 (269).


Edmund Brisco Ford (GB) coined ecological genetics to refer to the study of evolution in action by a mixture of laboratory and fieldwork (556).


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 (1137; 1138).


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 (355). 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 (973).

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 (1634; 1722).

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 (1457; 1458).


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 (1460).


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 (784).

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 (812). 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 (1628).

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 (251; 1226).


Hunt Potter (US) and David Dressler (US-GB) demonstrated the validity of the Holliday model of recombination (1350).


Paul Ichiro Terasaki (US) and John D. McClelland (US) developed the microcytotoxicity test, critical for further development and practical use of HLA typing (1651).


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 (712).


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 (1074).

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 (1067).

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" (382). 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 (1305).


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; 1388).


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 (1246).

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 (895; 1509).

 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 (1200).


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 (762).

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) (1430).

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 (908; 909).


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 (563).

Elliott F. Osserman (US) and Kiyoshi Takatsuki (JP) coined the phrase gamma heavy chain disease (1279).


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 (352; 353; 697; 721; 1377).


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 (322).

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 (323)


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 (148; 379; 380). They named this substance migration inhibitory factor (MIF). Note: This was the third cytokine discovered. Stanley Cohen (US) coined the neologism cytokine (312).


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 (1787).


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 (165).

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 (1532).

Kevin K.F. Ng (SG) and John Robert Vane (GB) discovered angiotensin converting enzyme (ACE) in the lung of dogs (1223; 1224). 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 Zuccalŕ, 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; 604; 922; 1605). 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 (621).


Allan Kliman (US) and Mark E. Lesses (US) introduced plasmapheresis as a means of collecting plasma for fractionation (945).


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 (1747).


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 (433).


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 (1494).


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 (452).


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 (453).


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 (457).


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 (1016; 1251). 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 (271).

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 (1490).

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 (1491).

 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 (1492).

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 (915).


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 (132).

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 (134).

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 (865).

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 (133).


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 (1737).


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 (1580).

Thomas Earl Starzl (US) established rules to prevent ABO-incompatibility in renal transplantation surgery (1578).


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 (1066).


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 (1534-1538).


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 (694; 744; 745; 1028-1030).


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 (520; 1064; 1811).


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 (449). 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 (667).


H. Vernon Ingram (DE-GB-US) introduced the use of the laser for eye surgery (820).


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 (755).


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 (96; 97).


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 (692).

Victor H. Denenberg (US) following his work with hemispheric laterality in rats presented his theory that the brain possesses innate functional asymmetry (415).


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 (400; 627-629; 1647).


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) (693). These ideas have since been extended to social behaviors of many species—vertebrate as well as invertebrate.


Austin Bradford Hill (GB) made a landmark presentation of criteria for inferring causality from observational data dealing with environment and disease (753). 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 (487).


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) (396).



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) (232).


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 (1433).


Cambridge Instruments produced the first commercial scanning electron microscope. ref


Robert Burns Woodward (US) accomplished the total synthesis of colchicine (1825).


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 (432).


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) (944).


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 (1640).


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 (1100).


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 (394).