A Selected Chronological Bibliography of Biology and Medicine

 

Part 5B

 

1957 — 1963

 

 

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










 

1957

“Humility and perspective are necessary ingredients of scientific craftsmanship; here they concur in stressing the far reaches of our ignorance.” Joshua Lederberg (889).

 

“Discovery consists of seeing what everybody has seen and thinking what nobody has thought.” Albert Szent-Györgyi (1504).

 

"It is necessary to postulate genes that have opposite effects on fitness at different ages, or, more accurately, in different somatic environments." George Christopher Williams (US) (1661). See, Staub 2016. Note: This theory is now widely accepted in aging research and elsewhere, and it is called antagonistic pleiotropy theory.

 

Alexander Robertus Todd (GB) was awarded the Nobel Prize in Chemistry for his work on nucleotides and nucleotide co-enzymes.

 

Daniel Bovet (CH-FR-IT) was awarded the Nobel Prize in Physiology or Medicine for his discoveries relating to synthetic compounds that inhibit the action of certain body substances, and especially their action on the vascular system and the skeletal muscles.

 

E. Margaret Burbidge (US), Geoffrey R. Burbidge (US), William A. Fowler (US), and Fred Hoyle (US) suggested that the heavy elements originated in the furnaces of supernovas (191).

 

Matthew Stanley Meselson (US), Franklin William Stahl (US), and Jerome R. Vinograd (US) invented density gradient centrifugation. This technique separates large molecules based on their different buoyancys in solution (1047).

 

Marvin Lee Minsky (US) patented the principle of confocal imaging (1053).

 

Jordi Folch (ES-US), Marjorie Berman Lees (US), and Gerald H. Sloane-Stanley (US) devised a simple method for the isolation and purification of total lipides from animal tissues (456).

 

Marvin M. Nachlas (US), Kwan-Chung Tsou (US), Eustace De Souza (US), Chao-Shing Cheng (US), and Arnold M. Selingman (US) introduced the use of 2,2'-di(-p-nitrophenyl) -5,5'-diphenyl-3,3'-(3,3'-dimethoxy-4,4'-diphenylene)-di(tetrazolium chloride) (Nitro BT, or NBT) as the ideal substrate for the cytochemical demonstration of DPN and TPN diaphorase systems, as well as the succinic dehydrogenase system. The ‘NBT’ method has since become the most popular method for the demonstration of dehydrogenases in histochemistry (1111).

 

Alfred H. Free (US), Chauncey O. Rupe (US), and Ingrid Metzler (US) formulated two simple colorimetric tests for protein in urine; one is a tablet test, consisting of a salicylate buffer and bromphenol blue, and the other is a strip test, consisting of a paper strip impregnated with a citrate buffer and tetrabromphenol blue. The basic principle in both tests is that of "protein error of indicators." Experiments with approximately 5000 urines, taken from both hospital patients and normal subjects, revealed that these tests are simple, rapid, accurate, sensitive, specific, and capable of being used with turbid urines (480). See, George Oliver and Fritz Feigl, 1883

 

Leonard T. Skeggs, Jr. (US) described the first completely automatic method for colorimetric analysis. It employed a new analytical technique that was performed in a continuously flowing stream. The determination of urea nitrogen in whole blood was described as one application of a generally applicable method (1431).

 

Gerald O. Aspinall (GB-CA) and Robin J. Ferrier (GB-NZ) developed a convenient micro-method is described for following the oxidation of carbohydrates by periodate. The spectrophotometric procedure is based on changes in the ultraviolet light absorption of periodate at its maximum at 223 nm, and corrections are made for absorption by iodate formed (66).

 

Russell L. Steere (US) invented freeze-fracture specimen preparation for electron microscopy (1471).

Hans Moor (CH), Kurt Mühlethaler (CH), Heinz Waldner (CH), and Albert Frey-Wyssling (CH) perfected the freeze fracture technique (1090; 1091).

 

Jordi Folch (ES-US) Marjorie B. Lees (US), and Gerald H. Sloane-Stanley (US) developed a simple method to do a total lipid extraction from animal tissues. This method quickly became the standard for lipid extraction (456).

 

Milton W. Hamolsk (US), Myron Stein (US), and A. Stone Freedberg (US) presented a new in vitro method, based on the ‘uptake’ of I-131 T-3 by red blood cells from whole blood. The simple test accurately differentiates hyper-, hypo-, and euthyroidism, is unaffected by iodine exposure, avoids administration of radioactivity to patients, and indicates several epiphenomena of wide biologic and clinical interest. Their studies were based on a) the fact that thyroxin (T-4) and triiodothyronine (T-3) molecules are both hydrophilic and lipophilic, and b) the notion that their hormonal action might therefore involve alignment at, and alteration of, the aqueous plasma-lipid membrane interface (612).

 

Emile Van Handel (US) and Don B. Zilversmit (US) presented a microprocedure for the direct determination of triglyceride concentrations in biologic specimens. The method depends on the quantitative removal of phosphatides from the sample and the subsequent determination of esterified glycerol (1590).

 

Donald E. Wolf (US), Carl H. Hoffman (US), Paul E. Aldrich (US), Helen R. Skeggs (US), Lemuel D. Wright (US), and Karl August Folkers (US) determined the structure of beta, delta-dihydroxy-beta-methylvaleric acid (the acetate-replacing factor for Lactobacillus acidophilus) which was christened mevalonic acid. In subsequent studies, mevalonic acid was shown to be a key intermediate in the synthesis of isoprenoid compounds arising from acetate, including cholesterol, ubiquinones, menoquinones, dolichol, and other isoprene derivatives (1670).

 

Arthur J. Kornberg (US) reported that all four of the deoxynucleotide triphosphates must be present for DNA synthesis to take place (832).

 

Julian E. Philip (US), Jay R. Schenck (US), and Martha P. Hargie (US) isolated the antibiotic ristocetin from Nocardia lurida (1216).

 

Gordon C. Mills (US) determined that glutathione peroxidase is an erythrocyte enzyme, which protects hemoglobin from oxidative breakdown in the intact erythrocyte (1052).

 

Alfred H. Free (US), Ernest C. Adams (US), Mary Lou Kercher (US), Helen M. Free (US), and Marion H. Cook (US) developed a simple, specific, sensitive, and speedy test for glucose in urine. Data are presented to show that the test has a high accuracy with both positive and negative specimens (479).

 

Tomio Takeuchi (JP), Tokuro Hikiji (JP), Kazuo Nitta (JP), Seiro Yamazaki (JP), Sadao Abe (JP), Hisaro Takayama (JP), and Hamao Umezawa (JP) isolated the antibiotic kanamycin from Streptomyces kanamyceticus (1516).

 

Shuko Kinoshita (JP), Katsunobu Tanaka (JP), Shigezo Udaka (JP), Sadao Akita (JP), and Masakazu Shimono (JP) discovered that bacteria can be used to produce monosodium glutamate and amino acids (811; 812). This led to a new industry; the microbial production of amino acids for human and animal consumption.

 

Theodore W. Rall (US), Earl Wilbur Sutherland, Jr. (US), and Jacques Berthet (BE) reported the isolation of a small, heat stable molecule, with a UV light absorption spectrum reminiscent of that of ATP. Careful chemical analysis revealed that this substance is a cyclic derivative of ATP, i.e., cyclic AMP (1255).

Earl Wilbur Sutherland, Jr. (US), Theodore W. Rall (US), and Tara Menon (US) discovered adenyl cyclase, the enzyme that converts ATP into 3’, 5’-cyclic AMP (1501).

David Lipkin (US), William H. Cook (US), and Roy Markham (US) determined the structure and molecular weight of adenosine-3', 5'-phosphate (cyclic AMP) (927).

 

Gary Felsenfeld (US), David R. Davies (US), and Alexander Rich (US) discovered that RNA molecules can form triple helices (433).

 

Seymour Kaufman (US) partially purified two enzymes that participate in the conversion of phenylalanine to tyrosine. He discovered that the reaction also requires the presence of triphosphopyridine nucleotide (TPNH; now known as NADPH) and oxygen (790).

Seymour Kaufman (US) determined that a co-factor different from any other known vitamin or coenzyme was necessary for the above reactions. Preliminary studies suggested that the cofactor interacted directly with TPNH (791).

Seymour Kaufman (US) found that the cofactor is a double bond tautomer of the inactive 7,8-dihydropteridine (792). The new cofactor was eventually identified as a tetrahydropteridine.

 

Michael Sela (IL), Frederick H. White, Jr. (US), Christian Boehmer Anfinsen, Jr. (US), and Edgar Haber (US) helped explain the connection between the amino acid sequence and the biologically active conformation in proteins (33; 597; 1392).

 

Harry Beevers (GB-US), Hans Leo Kornberg (GB-US), David T. Canvin (US), Ann Oaks (US), R. William Breidenbach (US), and Bernt P. Gerhardt (DE) discovered the glyoxylate cycle in seedlings of plants that store fat in their seed and utilize this fat as a source of energy and for the production of glucose during early seedling growth. These studies demonstrated that the glyoxylate cycle of fat-storing seeds is in a specific metabolic/cytoplasmic compartment, the glyoxysome (108; 166; 227; 520; 836; 837; 1164).

Hans Leo Kornberg (GB-US) and Jack R. Sadler (US) were able to show that the provision of energy from glycolate could occur via a dicarboxylic acid cycle, in which an isoform of malate synthetase catalyzed the condensation of glyoxylate and acetyl coenzyme A as the first step in a sequence of reactions that led from malate via oxaloacetate and pyruvate to the loss of two carbons as CO2 and to the reformation of the acetyl coenzyme A acceptor (842).

Hans Leo Kornberg (GB-US) and Tony Gotto (US) described the ancillary route, which operates to replenish the intermediates of the tricarboxylic acid (TCA) and dicarboxylic acid cycles, as they are withdrawn during biosyntheses (839).

Hans Leo Kornberg (GB-US) and J. Gareth Morris (GB) uncovered another novel route for growth on glycolate. In this pathway (apparently unique to Micrococcus denitrificans), the utilization of glyoxylate proceeds by a sequence involving an initial condensation of this C2 compound with glycine to form erythro-beta-hydroxyaspartate, which undergoes transamination with a second molecule of glyoxylate to reform glycine and to yield oxaloacetate (840; 841).

Hans Leo Kornberg (GB-US) presented the concept of anaplerotic pathways as those various pathways, which serve to maintain the central metabolic routes during the growth of microorganisms on C2 compounds. The term anaplerotic was suggested by Abraham Wasserstein (GB) to mean "filling up again" (835).

Anthony H.C. Huang (US) and Harry Beevers (GB-US) noted that the glyoxysome turned out to be the first of a new class of plant organelles called microbodies (709).

 

Leonard S. Lerman (US), Leonard J. Tolmach (US), and Maurice S. Fox (US) succeeded in labeling transforming DNA with 32P and demonstrated that the radioactivity was incorporated into a genetically transformed strain of Pneumococcus (Streptococcus). These results provided quantitative information on the stoichiometry of the transformation event, showing that incorporation of the tracer into recipient cells was concomitant with genetic modification (463; 904; 905).

 

Hans Adolf Krebs (DE-GB) and Hans Leo Kornberg (GB-US) proposed that a single enzyme in a biochemical pathway might act as a pacemaker that controls the supply of substrate for subsequent reactions (849).

 

Aaron Novick (US) and Milton Weiner (US) concluded that the induced synthesis of beta-galactosidase at low concentrations of inducer bears close resemblance to the phenomenon of mutation (in the sense of a chromosomal change). In the case of mutation, a cell is either mutant or wild type; in the case of enzyme induction a bacterium is either fully induced and makes beta-galactosidase at maximum rate or is uninduced and makes no beta-galactosidase (1149).

 

Alfred Day Hershey (US), Elizabeth Burgi (US), Joseph D. Mandell (US), and Jun-ichi Tomizawa (US) concluded that the chromosome of bacteriophage is a naked DNA molecule (664).

Hugh John Forster Cairns (GB-US-GB) calculated the mass of T2 bacteriophage DNA to be 110 X 106 daltons (208).

 

Joseph A. Cifonelli (US) and Albert Dorfman (US) established that the group A streptococci contain the uridine nucleotide sugars, UDP-N-acetylglucosamine and UDP-glucuronic acid, requisite for the synthesis of hyaluronic acid (272).

Alvin Markovitz (US) and Albert Dorfman (US) concluded that the enzyme responsible for glycosyl transfer among group A streptococci is localized on the protoplast membrane (1002). This is one of the first observations relating a macromolecular synthesis—glycosyl transfer—to membrane-associated enzymes.

Robert L. Perlman (US), Alvin Telser (US), Albert Dorfman (US), and Howard C. Robinson (US) developed cell-free preparations of embryonic chick cartilage that synthesized chondroitin sulfate using glycosyl transfer from UDP-N-acetylgalactosamine and UDP-glucuronic acid to small acceptor oligosaccharides. They also characterized a xylosylserine linkage within these proteoglycans (1213; 1306; 1527).

 

Robert Emerson (US), Ruth V. Chalmers (US), and Carl N. Cederstrand (US) discovered the enhancement effect, which occurs during photosynthetic oxygen evolution when two beams of light, with different wavelengths, are given simultaneously. The yield of oxygen is greater than the sum of the yields with each beam alone. Chlorella pyrenoidosa was their experimental organism (408). After the same effect was found in red algae, diatoms, and a cyanobacterium there evolved the concept of two pigment systems and two light reactions within the photosynthetic mechanism.

 

Harland Goff Wood (US), Per Schambye (DK), Max Kleiber (CH-US), Georges J. Peeters (BE), Patrick M.L. Siu (US), Seymour Joffe (US), R. Gillespie (US), Roger G. Hansen (US), and Harry Hardenbrook (US) found that in cows lactose is synthesized when free glucose reacts with UDP-galactose (1358; 1674-1676).

 

Karl Sune Detlof Bergström (SE), Jan Sjövall (SE), Ragnar Ryhage (SE), and Bengt Ingemar Samuelsson (SE) obtained crystals of two prostaglandins, alprostadil (PGE1) and PGF1a. They worked out the structures of the first family of prostaglandins all of which contain the C-20 carbon framework of prostanoic acid (119-123).

 

Irving I. Geschwind (US), Choh Hao Li (CN-US), and Livio Barnafi (CL) isolated, characterized and determined the amino-acid sequence of a melanocyte-stimulating hormone from bovine pituitary glands (530).

Klaus Hofmann (CH-US), Miriam E. Wollner (US), Haruaki Yajima (JP), Gertrude Spühler (US), Thomas A. Thompson (US), and Eleanore T. Schwartz (US) synthesized a physiologically active blocked tridecapeptide amide possessing the amino acid sequence of alpha-melanocyte-stimulating hormone (MSH) (688).

 

John Clark Sheehan (US) and Kenneth R. Henery-Logan (US) synthesized Penicillin V (1401; 1402). This was the first penicillin produced synthetically.

 

Jens Christian Skou (DK), Carsten Hilberg (DK), and Peter L. Jorgensen (DK) discovered the sodium, potassium-stimulated adenosine triphosphatase (Na+, K+-ATPase). This enzyme breaks down ATP and uses the liberated energy to transport sodium and potassium ions across cellular membranes, maintaining a proper balance inside the cell. Skou was the first to identify an enzyme that controls the movement of ions across the cellular membrane (758; 1434-1437).

 

Mahlon Bush Hoagland (US), Paul Charles Zamecnik (US), Mary Louise Stephenson (US), Jesse Friend Scott (US), Liselotte I. Hecht (US), Paul Berg (US), E. James Ofengand (US), Richard S. Schweet (US), Freeman P. Bovard (US), Esther Allen (US), and Edward Glassman (US) performed experiments suggesting that each sRNA (tRNA) is specific for only one amino acid (117; 682; 683; 1382).

 

George Yerganian (US) described the morphologic components of nine isolated human pachytene bivalents. Each bivalent is characterized by a distinct and recognizable form assumed after being released from the nuclear membrane. In the absence of chromosomal lampbrushing, large chromatic knobs, diffuse segments of chromatin, and in some cases, attached nucleoli, make up the general features for identifying these particular bivalents (1706).

 

Charles Heidelberger (US), Nabendu K. Chaudhuri (US), Peter B. Danneberg (US), Dorothy Mooren (US), Lois Griesbach (US), Robert Duschinsky (US), Robert J. Schnitzer (US), Edward Pleven (US), James I. Scheiner (US), and Willi E. Oberhänsli (CH) synthesized 5-flurouracil (FU) and 5-fluoro-2’-deoxyuridine (FUdR) as antimetabolites to treat tumors (380; 381; 645).

Seymour Stanley Cohen (US), Joel G. Flaks (US), Hazel D. Barner (US), Marilyn R. Loeb, and Janet Lichtenstein (US) showed that the antitumor agent 5-fluorouracil and its deoxyribosyl derivative are converted to the deoxyribonucleotide in E. coli and provoke thymine deficiency and ‘thymineless death.’ Fluorodeoxyuridylate, isolated from the bacteria or synthesized enzymatically in vitro, is an irreversible inhibitor of the thymidylate synthetase isolated from phage-infected bacteria (287).

Edmund Klein (US) developed a protocol for the application of a highly effective topical anticancer agent, 5-fluorouracil (5-FU), to superficial basal cell carcinoma (815).

 

Arthur St. George Joseph McCarthy Huggett (GB) and D.A. Nixon (GB) described a method for determination of glucose levels in blood and urine using a fungal oxidase preparation (721). This method has found widespread use in clinical medicine.

 

Hugo Wilhelm Knipping (DE), Wilhelm Bolt (DE), Helmut Venrath (DE), Helmut Valentin (DE), Hans Ludes (DE), and Paul Endler (DE) used xenon-133 to measure lung ventilation (826-828).

 

George W. Bartelmez (US) showed that there is continuity between prepregnant and pregnant states from the standpoint of circulation, this is most apparent in the persistence of an intrinsic contractile potential in the spiral arteries. This is manifested during the menstrual cycle by isolated contractions at the myoendometrial junction which produce ischemia leading to foci of endometrial necrosis and slough (95).

Chester B. Martin, Jr. (US), Harry S. McCaughey, Jr. (US), Irwin H. Kaiser (US), Martin W. Donner (US), and Elizabeth Mapelsden Ramsey (US) found that during pregnancy the intermittency of flow through individual spiral arteries into the intervillous space is sufficent to maintain the myometrium (1010).

 

André Michel Lwoff (FR) articulated major differences between viruses and bacteria, based on molecular structure and physiology. The virus contained either RNA or DNA enclosed in a coat of protein, and it possessed few if any enzymes except those concerned with attachment to and penetration into the host cell. The virus was not a cell and did not reproduce by division like a cell. Its replication occurred only within a susceptible cell, which always contains both DNA and RNA and an array of different proteins endowed with enzymatic functions mainly concerned with the generation of ATP and the synthesis of varied organic constituents of the cell from chemical compounds in the environment. “Viruses should be treated as viruses” (952).

 

John E. Vogel (US), Alexis Shelokov (US), and Lotta Chi (US) developed the hemagglutination-adsorption (hemadsorption) technique for detecting myxoviruses (1405; 1599).

 

Harold F. Deutsch (US), Jane I. Morton (US) reported that when gamma globulins with molecular weights of about 1,000,000 are treated with mercaptans at neutral pH they are readily converted into subunits of about one-fifth the size of the parent molecules. Removal of the mercaptan leads to some reformation of the original protein and this reaggregation is blocked by alkylating agents. This demonstrated that the macromolecular type of antibody molecule contains subunits linked by disulfide bonds (347).

 

Jordi Casals (ES-US) grew the yellow fever virus in suckling mice (239).

 

 Norman R. Underdahl (US), Oliver D. Grace (US), and Alvin B. Hoerlein (US) cultivated a cytopathogenic agent in tissue culture from a case of bovine mucosal disease (1581). Note: This virus would later be called bovine virus diarrhea virus (BVDV).

 

Elvis R. Doll (US), John T. Bryans (US), William H. McCollum (US), and M.E. Ward Crowe (US) isolated a filterable agent causing arteritis of horses and abortion by mares (355). Note: This agent would become known as equine arteritis virus (EAV).

 

Telford H. Work (US), F.R. Roderiguez (US), and Pravin N. Bhatt (IN-US) discovered the Kyasanur Forest disease virus (1685). Note: This is a tick-born viral hemorrhagic fever

 

J. H. Seddon (NZ), in 1957, submitted a report to the Research Committee of the New Zealand Council, College of General Practitioners, describing eight cases, in children, of a new clinical illness that has come to be known as hand-foot-and-mouth disease. His report was not published until 1961 (23; 375; 1391). Hand, foot, and mouth disease (HFMD), first reported in New Zealand in 1957 is caused by Coxsackievirus A16 (CVA16) and human enterovirus 71 (HEV71) and occasionally by Coxsackievirus A4-A7, A9, A10, B1-B3, and B5.

 

Huang Zhi-Shang (RU), Anatonina Konstantinova Shubladze (RU), C.S. Huang (RU), Karl Edward Schneweis (DE), and Gordon Plummer (US) serologically differentiated herpes simplex virus type 1 (labial) from herpes simplex type 2 (genital) (1223; 1369; 1413; 1711).

 

Gueh-Djen Hsiung (CN-US) and Joseph Louis Melnick (US) led the way in using selective cell cultures and the recognition of distinctive enterovirus plaque morphology to identify viral pathogens (707). Note: This was a crucial step in developing rapid methods for differential identification of viruses .

 

James Herbert Taylor (US), Philip Sargent Woods (US), and Walter L. Hughes (US) were the first to apply 3H-labelled thymidine to the study of biological phenomena. Their work in Vicia (the broad bean) confirmed the semiconservative mode of DNA replication in eukaryotes (Eucarya) (1525).

Victor P. Bond (US), Theodore M. Fliedner (US), Eugene P. Cronkite (US), Joseph R. Rubini (US), George Brecher (US), and P.K. Schork (US) showed that in vitro incubation with tritiated thymidine of blood from normal individuals and patients with infection and infectious mononucleosis, demonstrated the presence of small numbers of labeled large mononuclear cells of different morphological types indicating that the cells are capable of DNA synthesis and division (155).

 

Francois Jacob (FR), Clarence R. Fuerst (US), and Élie L. Wollman (FR) discovered that viral proteins of the T-even bacteriophages appear to be synthesized either as early or late. Early proteins are associated with phage multiplication and late proteins constitute the phage coat (735).

Joel G. Flaks (US), Seymour Stanley Cohen (US), Arthur J. Kornberg (US), Steven B. Zimmerman (US), Sylvy R. Kornberg (US), and John Josse (US) subsequently showed that, at the outset of intracellular phage growth, the T-even phage DNA induces formation of an ensemble of early enzymes whose presence is required before replication of the phage DNA can begin. This ensemble, which is wholly foreign to the uninfected Escherichia coli, includes enzymes that catalyze the synthesis and glucosylation of 5-hydroxymethylcytosine, the synthesis of thymine by a new metabolic pathway, and the polymerization of the phage DNA from its nucleoside triphosphate building blocks. Synthesis of these early enzymes ceases near the end of the eclipse phase (451; 452; 834).

 

Carl A. Scheel (US), Stanley D. Beck (US), and John T. Medler (US) were the first to develop an artificial diet for a phytophagous piercing-sucking insect (1361).

 

Stanley D. Beck (US) and Edward E. Smissman (US) were the first to perform a systematic study of the chemical basis of plant resistance to insects (103; 104).

Stanley D. Beck (US) and John F. Stauffer (US) isolated three compounds (A, B, and C) from first-generation European corn borer resistant corn varieties. These factors were shown to be deleterious to European corn-borer larvae (Pyrausta nubilalis (Hbn.) (105).

 

David W.H. Barnes (GB) and John Freeman Loutit (GB) made the first attempt to treat leukemia in mice by bone marrow transplantation after lethal total body irradiation (TBI) (86).

Edward Donnall Thomas (US), Harry L. Lochte, Jr. (US), Wan Ching Lu (US), Joseph W. Ferrebee (US), Joe H. Cannon (US), and Otto D. Sahler (US) made the first attempts to treat leukemia in humans using high dose chemotherapy or total body irradiation or a combination of both followed by bone marrow transplantation (1553; 1554).

 

Theodore W. Rall (US), Earl Wilbur Sutherland, Jr. (US), and Jacques Berthet (US) established the concept of transmembrane signaling and the receptor-regulated production of intracellular second messengers (1254; 1255).

 

Beatrice Mintz (US) and Elizabeth Buckley Shull Russell (US) provided the first proof of the extra-gonadal origin of germ cells in the mammalian embryo (1054).

 

Joshua Lederberg (US) and Thomas Foxen Anderson (US) demonstrated that following bacterial conjugation the female generates a mixed clone, including recombinants, among the offspring (29; 888).

 

Salvador Edward Luria (IT-US), Jeanne W. Burrous (US), Louis S. Baron (US), Warren F. Carey (US), and Walter M. Spilman (US) demonstrated bacterial conjugation across species boundaries, Escherichia coli K-12 to Shigella and Escherichia coli to Salmonella typhimurium (87; 951).

 

Fu-Chuan Chao (US) described the microsome/ribosome of yeast as composed of two unequal pieces, which will separate from one another unless a trace of magnesium is present (260).

 

Frederick G. Germuth, Jr. (US) and George Edward McKinnon (US) demonstrated that purified soluble antigen-antibody complexes can, by themselves, induce systemic anaphylaxis and that these soluble complexes form in moderate antigen excess, diffuse throughout the interstitial fluids, and can react with complement (528).

 

Edward C. Franklin (US), Halsted R. Holman (US), Hans J. Muller-Eberhard (US), and Henry G. Kunkel (US) found an unusual protein component of high molecular weight (22S) in the serum of certain patients with rheumatoid arthritis (473). Note: This was the first recognition that rheumatoid arthritis sera contain autoantibodies specific for determinants on native IgG molecules.

 

James Learmonth Gowans (GB), Roy G. Shorter (US), Jesse L. Bollman (US), Newton B. Everett (US), Ruth W. Caffrey (US), William O. Rieke (US), and E. Julie Knight (GB) confirmed that the turnover of lymphocytes is more apparent than real, since the same lymphocytes continuously recycle from blood to lymph; but they recycle by way of the lymph nodes (423; 572-574; 1412).

Helge Sigurd Sjövall (SE) had earlier proposed this but thought the lymphocytes recycled mainly through the tissue spaces of the body generally (1430).

James Learmonth Gowans (GB), Douglas D. McGregor (GB), Diana M. Cowen (GB), and Charles Edmund Ford (GB) showed the involvement of lymphocytes in immune tolerance (576).

Douglas D. McGregor (GB) and James Learmonth Gowans (GB) made the link between lymphocytes and antibody formation (1032).

Newton B. Everett (US), Ruth W. Caffrey (US), and William O. Rieke (US) found that one population of small lymphocyte lives less than two weeks (423).

Stephen H. Robinson (US), George Brecher (US), Ira S. Lourie (US), and James E. Haley (US) determined that another population of small lymphocyte lives at least 10 months (1307).

 

John S. Colter (US), Harris H. Bird (US), Arden W. Moyer (US), Raymond A. Brown (US), Hattie E. Alexander (US), Gebhard Koch (US), Isabel Morgan Mountain (US), and Olga Van Damme (US) discovered that poliovirus genomic RNA is infectious and functions as messenger RNA (15; 291).

 

Robert Paul Hanson (US) and Carl A. Brandly (US) worked out the epizootiology of vesicular stomatitis virus (614).

 

James P. Duguid (GB) and Robert Reid Gillies (GB) discovered that Shigella flexneri adheres to epithelial surfaces using fimbriae (pili) (376).

 

Daniel Israel Arnon (PL-US), Frederick Robert Whatley (GB), and Mary Belle Allen (US) determined that triphosphopyridine nucleotide (TPN or NADP) acts as a catalyst in photosynthetic phosphorylation (61).

Daniel Israel Arnon (PL-US), Frederick Robert Whatley (GB), Mary Belle Allen (US), Manuel Losada (ES), Achim V. Trebst (DE), Shoitsu Ogata (JP), Harry Y. Tsujimoto (US), David O. Hall (US), and Alan A. Horton (US) confirmed that the light and dark phases of photosynthesis could be separated temporally. First, they illuminated chloroplasts in the absence of carbon dioxide, which resulted in trapping some of the light energy in a chemical form. They then disrupted the chloroplasts and removed the grana, in which the light trapping reaction takes place, and added radioactive carbon dioxide to the remaining stroma. They found that the carbon dioxide is converted in the dark into radioactive hexoses at the expense of the chemical energy generated in the preceding light period. These experiments also showed that chloroplasts are capable of the entire photosynthetic process leading to hexose formation; i.e., they are complete photosynthetic units, just as the mitochondria are complete respiratory units.

Arnon’s group theorized that light energy drives electrons off chlorophyll and into a redox series where oxidized NADP ultimately accepts them. While passing through the redox series energy is made available to drive the synthesis of ATP. If the electrons return to chlorophyll the process represents cyclic photophosphorylation. If photophosphorylation is cyclical, then reduced coenzyme (PNH2) must be generated by a dark reaction of some sort. Some sources of reducing power are sufficiently energetic (e.g., hydrogen) to donate their electrons directly to coenzyme thereby reducing it. Other sources of reducing power such as thiosulfate and succinate do not possess the reducing capacity to convert oxidized coenzyme to reduced coenzyme, therefore additional energy is required. Arnon’s group proposed (incorrectly) that electrons donated by thiosulfate, succinate, or other sources are transferred via cytochromes to chlorophyll and then raised at the expense of light energy to a reducing potential sufficient to produce reduced coenzyme. If the electrons do not pass to coenzyme they may be picked up by external acceptors such as nitrogen, or protons generating ammonia and hydrogen (52-54; 57; 58; 62). Note-Current evidence indicates that organisms using cyclic photophosphorylation generate reducing power by using ATP to reverse electron flow through a redox series to produce NADPred. Some electron sources, such as hydrogen, possess sufficient reducing potential to donate electrons directly to NADPox.

In higher plants low energy electrons are split from water and passed to chlorophyll where they are energized at the expense of light. From the chlorophyll they pass through a redox series, to chlorophyll again, then through another redox series eventually to be accepted by NADPox. to form NADPred. While passing through the redox series the electrons drive the synthesis of ATP.

 

Anton Lang (RU-US) and Amos E. Richmond (IL) discovered that cytokinin delays senescence of detached Xanthium (cocklebur) leaves (873). This indicated that cytokinins are likely produced in the root then transported to the shoot where they prevent processes associated with senescence, e.g., breakdown of protein and chlorophyll.

 

Folke Karl Skoog (SE-US) and Carlos O. Miller (US) put forth the concept of hormonal control of organ formation in plants. They showed that the differentiation of roots and shoots in tobacco (Nicotiana tabacum) pith tissue cultures is a function of the auxin/cytokinin ratio, and that organ differentiation can be regulated by changing the relative concentrations of the two substances in the medium; high concentrations of auxin promote rooting, whereas high levels of cytokinin support shoot formation. At equal concentrations of auxin and cytokinin the tissue tends to grow in an unorganized fashion. This concept of hormonal regulation of organogenesis in plants is now applicable to most plant species (1433).

 

Kenneth David Roeder (GB-US) and Asher E. Treat (US) established that the tympanal organs of noctuid moths are specifically tuned to the ultrasonic signals used by bats (1311).

 

Edwin J. Furshpan (GB-US) and Davis D. Potter (GB-US) examined the mechanism of nerve impulse transmission at the giant motor synapses of the crayfish, by inserting one or two microelectrodes into both pre- and post-synaptic axons. These fibers could be readily recognized by their distinctive physiological characteristics. The distance of the pre- fiber electrodes from the synapse was usually 10-20% of the characteristic length of that fiber. At least one of the post-fiber electrodes was usually in the immediate region of the junction.

From the results they hypothesized that electrotonic current readily flows across the junction, but the ‘synaptic membrane’ is a rectifier allowing positive current to cross only in the direction from pre-to post-fiber.

This evidence supported the idea that neurons were communicating through sparks -- electrical synapses. Thus, crayfish provided the first conclusive evidence for the existence of a different way that neurons could communicate (496; 497).

 

Karl Patterson Schmidt (US) was one of the most important herpetologists in the 20th century. Though he made only a few important discoveries by himself, he named more than 200 species and was a leading expert on coral snakes (330). Note: Schmidt died in 1957 after being bitten by a juvenile boomslang snake (Dispholidus typus). He wrongly believed that it could not produce a fatal dose.

 

Edgar Gustav Franz Sauer (DE) and Eleanore M. Sauer (DE) used a planetarium to subject Old-World warblers to various synthetic night skies of star settings. They found these birds capable of stellar navigation (1353; 1354).

 

Klaus Schwarz (US) and Calvin M. Foltz (US) were the first to recognize that selenium (Se) is important to normal human metabolism (1380).

 

Joseph S. Wall (US), Robert Steele (US), Richard C. de Bodo (US), Norman Altszuler (US), Ralph A. DeFronzo (US), Jordan D. Tobin (US), and Reubin Andres (US) made it possible for the first time to measure, accurately and outside of steady-state conditions, 1) the rate of hepatic glucose production and glucose utilization using a radio-tracer infusion method, and 2) insulin sensitivity and the effect of insulin by the glucose clamp method (342; 1613).

 

Vernon Benjamin Mountcastle (US) discovered and characterized the columnar organization of the cerebral cortex (1104).

 

Sam L. Clark, Jr. (US) first spotted autophagy in differentiating kidney cells as they redirected their metabolic energies (273). Autophagy is the destructive process in which a double membrane envelops cytoplasm and organelles before targeting them to lysosomes for destruction.

Thomas P. Ashford (US) and Keith R. Porter (US) suggested that the lysosomes represent portions of the cytoplasm (mitochondria included) set aside for hydrolysis with the general purpose of providing the protoplast with breakdown products for use in a reoriented physiology. The lysosomal membrane shields the rest of the cell from the general spread of the degradative process (64). At this time, they did not know whether microbodies were supplying hydrolytic enzymes to the lysosome.

Pierre Baudhuin (BE), Russell L. Deter (US), and Christian Rene de Duve (GB-BE-US) discovered that autophagy is a process for the bulk degradation of proteins, in which cytoplasmic components of the cell are enclosed by double-membrane structures known as autophagosomes for delivery to lysosomes or vacuoles for degradation (99; 345; 346). The term autophagy was introduced in the 1960s.

 

Anton Jervell (NO) and Fred Lange-Nielsen (NO) reported on a case of hereditary, functional syncopal arrhythmia in combination with profound congenital deafness in a family with six children. Four of the children were deaf and suffered from episodes of loss of consciousness and exhibited a long QT interval on the electrocardiograph (751). This is called the Jervell and Lange-Nielsen syndrome.

Ciro Romano (IT), Gianluca Gemme (IT), R. Pongiglione (IT), and Owen Conor Ward (IE) described an inherited functional syncopal heart disorder with prolonged QT interval (long QT syndrome type 2) (1313; 1622). This is called the Romano-Ward syndrome.

 

Ole Z. Dalgaard (DK) clarified that adult polycystic kidney disease ADPKD was familial and transmitted in a dominant manner (317).

Stephen T. Reeders (GB), Martijn H. Breuning (NL), Kay Elizabeth Davies (GB), Robert D. Nicholls (GB), Andrew Paul Jarman (GB), Douglas R. Higgs (GB), Peter L. Pearson (NL), David J. Weatherall (GB) gave the original description of the genetic linkage of ADPKD to chromosome 16 (1272).

 

Henri Jean Pascal Gastaut (FR), Micheline Vigouroux (FR), Carlo Trevisan (US), Henri Régis (FR), Frederic Andrews Gibbs (US), Erna Leonhardt Gibbs (DE-US), and William G. Lennox (US) were among the first to describe myoclonic and akinetic seizures in children with a petit mal type of EEG (Lennox–Gastaut syndrome) (507; 537).

 

William Beecher Scoville (US) and Brenda Milner (CA), in 1954, preformed a "bilateral medial temporal lobe resection combined with orbital undercutting." This work revealed that humans with hippocampal lesions are severely impaired in their ability to acquire new long-term memories of people, places, and events (1384).

 

Roland Kuhn (CH) observed that imipramine, a tricyclic compound, could relieve depression in patients (856).

Jacques Glowinski (FR) and Julius Axelrod (US) found that tricyclic antidepressant drugs block the uptake of 3H labelled-norepinephrine in brain neurons (547).

Susan G. Amara (US) and Michael J. Kuhar (US) reported that cocaine, amphetamines, and antidepressants also block the uptake of dopamine (prolactin-inhibiting hormone) and serotonin (24). Prozac (fluoxetine), a specific serotonin uptake inhibitor is the best-known antidepressant, which works in this manner.

Lionel Gordon Whitby (GB), Georg Hertting (AT), and Julius Axelrod (US) found that cocaine blocks the uptake of norepinephrine in sympathetic nerves. This allows greater amounts of the neurotransmitter to remain in the synaptic cleft after cocaine and act on the post-synaptic receptors more intensely and for longer periods of time (1656).

Julius Axelrod (US) found that amphetamine blocks the uptake as well as the release of 3H-labelled-norepinephrine in the brain (74).

 

Heinz Berendes (DE-US), Robert A. Bridges (US), and Robert Alan Good (US) described a fatal syndrome in children consisting of chronic suppurative lymphadenitis, hepatosplenomegaly, pulmonary infiltrations, and eczematoid dermatitis about the eyes, nose, and mouth (116).

 

William Benjamin Schwartz (US), Warren Bennett (US), Sidney Curelop (US), and Frederic Crosby Bartter (US) described a syndrome of renal sodium loss and hyponatremia probably resulting from inappropriate secretion of antidiuretic hormone (ADH or vasopressin) (1379).

 

Stanley Reitman (US) and Sam Frankel (US) devised a colorimetric method to detect acute myocardial infarction that is sufficiently simple to be used in any laboratory (1278). Note: It is called the Reitman-Frankel procedure or test.

 

Orvan W. Hess (US) and Edward Hon (US), in 1957, became the first in the world to continuously monitor electrical cardiac signals from a fetus. They were using a fetal heart monitor invented by Hess (666).

 

Michael Ellis DeBakey (US), E. Stanley Crawford (US), Denton A. Cooley (US), and George C. Morris, Jr. (US) performed the first successful resection with graft replacement of a fusiform aneurysm of the entire aortic arch in humans (339).

 

George W. Comstock (US) found that Afro-Americans have higher blood pressures at all ages and in both sexes than do Caucasians (294).

 

The Asian flu started in southwest China in February 1957, possibly having originated in 1956 in Vladivostok. Globally it affected 10-35% of the population but overall mortality was much lower than in the 1918 epidemic, about 0.25%. The flu spread to Hong Kong and Singapore in April 1957, Japan in May, elsewhere in Pacific in June, the middle east and Africa in July, Europe in August-October, and the U.S. in October of 1957 (830).

Burke A. Cunha (US) reports that this pandemic of influenza A was the first to be studied using modern scientific techniques (315). 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 (1642).

 

Leslie Foulds (GB) proposed that the development of cancer is a multistep process (461).

 

Ernest Beutler (US) developed the 'Glutathione stability test', the first reliable means for in vitro detection of primaquine-sensitivity. It quickly led to the discovery that the defect was sex-linked and that its basis was a deficiency in the enzyme glucose-6-phosphate dehydrogenase. This work stimulated awareness that the metabolism of red blood cells might be important in the origin of hemolytic disease (134). Note: At this time primaquine was a newly introduced antimalarial drug. It occasionally induced hemolytic anemia.

 

Harry P. Loomer (US), John C. Saunders (US), and Nathan S. Kline (US) reported the beneficial effects of iproniazid, a monoamine oxidase inhibitor, in the treatment of severe depression (825; 935). Note: Iproniazid was withdrawn from the market because of its hepatotoxicity.

 

Noam Chomsky (US), in his book Syntactis Structures, argued that human language, the most blatantly cultural of all our behaviors, owes as much to instinct as it does to culture (267).

 

George Evelyn Hutchinson (US) developed the formal notion of the ecological niche as a geometric hypervolume with both biotic and abiotic dimensions, a concept that led to a revolution in niche theory (727; 728)}.

 

Donald E. Broadbent (GB) was the first person to bring together the work on information processing with the problem of attention. He developed a mechanical model, which successfully illustrated his hypothesis that the human perceptual system has a limited capacity, that in consequence a selective operation is performed upon all inputs to the system, and that this operation takes the form of selecting all inputs having some characteristic in common. Broadbent suggested that "our mind can be conceived as a radio receiving many channels at once." The brain separates incoming sound into channels based on physical characteristics (such as location) (175).

 

Theodosius Grigorievich Dobzhansky (RU-US), and Olga Pavlovsky (RU-US) concluded from their experiments with Drosophila pseudoobscura that it may be reasonably inferred that evolutionary changes involving interactions of natural selection and random drift of the kind observed in their experiments are not infrequent in nature (353).

 

Larry Sandler (US) and Edward Novitski (US) described meiotic drive as an evolutionary force (1345).

James F. Crow (US) coined the phrase ultra-selfish genes to describe genes which spread despite, or rather because of the damage they cause to their host (314). Note: Meiotic drive chromosomes, B-chromosomes, and Medea genes all exhibit ultra-selfish behaviour. See, Sandler, 1927.

 

John Burdon Sanderson Haldane (GB) writes that it is difficult for breeders to simultaneously select all the desired qualities, partly because the required genes may not be found together in the stock. Especially in slowly breeding animals such as cattle, one cannot cull even half the females, even though only one in a hundred of them combine the various qualities desired. The problem for the cattle breeder is that keeping only the specimens with the desired qualities will lower the reproductive capability too much to keep a useful breeding stock. Haldane states that this same problem arises with respect to natural selection. Characters that are positively correlated at one time may be negatively correlated later, so simultaneous optimization of more than one character is a problem also in nature (601).

 

George Christopher Williams (US) concludes that any factor that decreases the rate of decline in reproductive probability intensifies selection against senescence. Any factor that increases the rate of this decline causes a relaxed selection against senescence and a greater advantage in increasing youthful vigor at the price of vigor later on. These considerations explain much of what is known of phylogenetic variation in rates of senescence (1661).

 

J. Roger Bray (US) and John Thomas Curtis (US) developed the method of polar ordination (now known as Bray-Curtis ordination) with its inherent distance measure, the Bray-Curtis dissimilarity (165).

John Thomas Curtis (US) wrote The Vegetation of Wisconsin: An Ordination of Plant Communities. This definitive survey established the geographical limits, species compositions, and as much as possible of the environmental relations of the communities composing the vegetation of Wisconsin (316).

 

Roger Mason (GB) Tina Negus (GB), in 1957, along with other school children discovered in Charnwood Forest, England the Precambrian fossil remains of what may very well be the oldest known multicellular animal (later named Charnia). Trevor D. Ford (GB) reported this discovery (460). The position of the clade for this organism in the tree of life remains uncertain.

Jonathan B. Antcliffe (GB) and Martin D. Brasier (GB) note that Charnia is both temporally and geographically the most widespread Ediacaran fossil (35).

Guy M. Narbonne (CA) and James G. Gehling (AU) report that the greatest abundance of Charnia fossils, which are also the oldest reliably dated Ediacaran fossils, are found along the southeast coast of Newfoundland (1113).

 

Ralph Stefan Solecki (US) and coworkers, from 1951-1960, examined the Shanidar cave in North Central Iraq for fossil remains. Nine partial Homo sapiens neanderthalensis; Homo neanderthalensis skeletons were removed (1442; 1443). The specimens have been dated between 23-52 K B.C.E.

Thomas Dale Stewart (US), discovered Shanidar I at Shanidar cave in Iraq. This Neanderthal male, 30-45 years of age, had an underdeveloped right shoulder blade, collar bone, and upper right arm bone. He believes that Shanidar I was crippled, with a useless right arm, which had been amputated in life just above the elbow (1486). This is surely one of the earliest known examples of surgery.

 

1958

“A gifted man cannot handle bacteria or equations without taking fire from what he does and having his emotions engaged.” Jacob Bronowski (178).

 

"Protein synthesis is a central problem for the whole of biology, and… it is in all probability closely related to gene action." Francis Harry Compton Crick (308).

 

Frederick Sanger (GB) was awarded the Nobel Prize in Chemistry for his work on the structure of proteins, especially that of insulin.

 

George Wells Beadle (US) and Edward Lawrie Tatum (US) for their discovery that genes act by regulating definite chemical events and Joshua Lederberg (US) for his discoveries concerning genetic recombination and the organization of the genetic material of bacteria shared the Nobel Prize in physiology and medicine.

 

Egon Stahl (DE) described production and use of thin layers of standard silica gel G for chromatography. Substances are made visible with the help of aggressive spray reagents and by heating on these ‘open columns,’ and consequently, adsorption chromatographic separations and detection of numerous chemical substance mixtures in the microgram range are possible (1460).

 

Lawrence K. Coachman (US), Edvard A. Hemmingsen (NO-US), and Per Fredrik Thorkelsson Scholander (SE-NO-US) first proposed that clues about past atmospheric air composition could be obtained from gas bubbles trapped in glacier ice centuries or millennia ago (284).

 

John L. Riggs (US), Robert J. Seiwald (US), Joseph H. Burkhalter (US), Cora M. Downs (US), and Theodore G. Metcalf (US) were the first to develop isothiocyanate compounds as fluorescent labeling agents for immune serum (1290).

 

Åke Bertler (SE), Arvid Carlsson (SE), and Evald Rosengren (SE) described the first chemical method for the analysis of adrenaline and noradrenaline that proved sufficiently sensitive and specific for permitting accurate quantitative analyses of extracts of animal tissues in general (127).

 

Morris John Karnovsky (ZA-US) and Richard C. Graham, Jr. (US) extended the horseradish peroxidase (HRP) tracer method of Werner Straus (US) to both the light and electron microscopic level, by introducing diaminobenzidine (DAB) as an electron donor. HRP oxidizes DAB in the presence of H2O2 and converts it to an insoluble primer, which causes the reduction of added osmium tetroxide. The reduced osmium forms an insoluble electron opaque precipitate, localized to the site of the HRP (782; 1492).

Richard C. Graham, Jr. (US), Ulla Lundholm (US), and Morris John Karnovsky (US) reported the cytochemical staining of peroxidase activity (577).

Ludwig A. Sternberger (US), Paul H. Hardy, Jr. (US), John J. Cuculis (US), and Howard G. Meyer (US) developed the cytochemical staining of peroxidase activity into an immunochemical technique (1480).

 

Paul A.J. Janseen (BE), Corn. Van de Westeringh (BE), Anton H.M. Jageneau (BE), Paul J.A. Demoen (BE), Bert K.F. Hermans (BE), Georges H.P. Van Daele (BE), Karel H.L. Schellekens (BE), Cyriel A.M. Van der Eycken (BE), and Carlos J.E. Niemegeers (BE) reported on the synthesis of haloperidol and its screening in mice (746).

Paul Divry (BE), Jean Bobon (BE), Jackie Collard (BE), André Pinchard (BE) and Emile Nols (BE) performed the clinical trials of haloperidol, which became a treatment for schizophrenia (351).

 

Vernon Martin Ingram (DE-GB-US) developed the peptide fingerprinting technique (732).

 

Herbert E. Carter (US), Donald B. Smith (GB), and D.N. Jones (US), using egg yolk, were the first to isolate an ether phospholipid (238).

 

Geigy Chemical Company introduced the herbicide atrazine, a symmetrical triazine, which is useful in corn (Zea mays), orchards, pineapple (Ananas comosus), sorghum (Sorghum cereale), and sugar cane (Saccharum officinarum). ref

 

Amchem Chemical Company introduced the herbicide chloramben, a benzoic acid derivative, useful in soybeans (Glycine max), corn (Zea mays), and peanuts (Arachis hypogaea). ref

 

Robert A. Goldwasser (US), Robert E. Kissling (US), Theodore R. Carski (US), and Thomas S. Hosty (US) developed rabies immunofluorescence diagnostics (556; 557).

 

Setsuo Takeuchi (JP), Kosei Hirayama (JP), Kazaburo Ueda (JP), Heiichi Sakai (JP), and Hiroshi Yonehara (JP) discovered the antibiotic blasticidin S as an isolate from Streptomyces griseochromogenes (1515).

Tomomasa Misato (JP), Itaru Ishii (JP), Masaru Asakawa (JP), Yoichiro Okimoto (JP), Kazuo Fukunaga (JP), and Kensuke Hashimoto (JP) discovered that the antibiotic blasticidin S can be used to successfully treat rice blast (1055-1058).

 

Robert Laing Noble (CA), Charles Thomas Beer (CA) and James H. Cutts (CA) discovered the effects of extracts of the Madagascar periwinkle (Vinca rosea) on the body’s blood-forming system then isolated and purified the active substance, vinblastine, from the leaves (1145). This work is considered a milestone in the history of cancer drug development. Vinblastine, which blocks the polymerization of tubulin monomers to form microtubules, is used to treat many cancers, particularly Hodgkin’s disease, testicular cancer, and breast cancer.

Marion E. Hodes (US), Robert J. Rohn (US), and William H. Bond (US) reported the effect of vincaleukoblastine, isolated from Vinca rosea, in human beings…. Complete hematologic remission was achieved in acute lymphocytic and monocytic leukemia. In those situations where hematologic remission was not achieved, tumor cell infiltrates have decreased in size (684; 685).

 

Anthony San Pietro (US) and Helga M. Lang (US) discovered ferredoxin and its role in photosynthesis (1344).

 

Anthony San Pietro (US) and Helga M. Lang (US) discovered that the reduction of NADP+ and the evolution of oxygen by illuminated spinach-chloroplast suspensions can be greatly accelerated by addition of a soluble protein isolated from spinach. They showed this factor to be an enzyme that promotes the transfer of electrons to NADP+. Highly purified versions were found to contain iron and sulfur in a labile form (1344).

Leonard Earl Mortenson (US), Raymond C. Valentine (US), and James E. Carnahan (US) isolated a protein from extracts of Clostridium pasteurianum, which they showed to be essential for nitrogen fixation by serving as the electron carrier to nitrogenase. The purified factor was found to have a molecular weight of 6,000 and to contain seven atoms of iron and seven atoms of acid-labile sulfur. No heme was present. They called this protein ferrodoxin; it was the first of many iron-sulfur proteins to be isolated from natural sources (1099; 1100). Various ferredoxins were quickly recognized as important redox catalysts in photosynthesis and other metabolic processes.

Kunio Tagawa (JP), Daniel Israel Arnon (PL-US), Masateru Shin (JP), Harry Y. Tsujimoto (US), Reinhard Bachofen (CH), and Bob B. Buchanan (US) showed that a red iron-sulfur protein (ferrodoxin) is a universal part of the photosynthetic apparatus. They found that ferrodoxin, reduced by light, provides the electrons for generating the NADPH required for carbon assimilation. They also found that the reduction of NADP is light independent. This observation suggested that an iron-sulfur protein resembling bacterial ferrodoxin is one of the components carrying electrons from photosystem 1 to NADP+ (55; 56; 59; 60; 1511).

 

Joel Mandelstam (GB) showed that the breakdown as well as the synthesis of proteins occurs in intact bacteria (991).

 

Shigetoshi Wakaki (JP), Hakudai Marumo (JP), Keitaro Tomioka (JP), G. Shimizu (JP), E. Kato (JP), Hideo Kamada (JP), Shiro Kudo (JP), and Yasuo Fujimoto (JP) isolated the antibiotic mitomycin C from Streptomyces caespitosus (1607; 1608).

 Shugo Shiba (JP), Asaharu Terawaki (JP), Takeo Taguchi (JP), and Junya Kawamata (JP) showed that mitomycin C acts by specific damage to DNA (1409).

 

Henry A. Lardy (US), Diane Johnson (US) and William C. McMurray (US) tested antibiotics toxic to animals. They were found to have specific inhibitory effects on mitochondrial metabolism —some as inhibitors of respiratory enzymes, others as inhibitors of phosphorylation (oligomycin), some as uncouplers or inhibitors of respiration specific for certain substrates. Subsequent work in many laboratories confirmed the prediction that ‘toxic antibiotics might prove to be generally useful tools for investigating metabolic systems’ (877).

 

Herbert Tabor (US), Sanford M. Rosenthal (US), and Celia White Tabor (US) synthesized doubly labeled [15N, 14C] putrescine and showed that it is incorporated into spermine and spermidine in Escherichia coli and Aspergillus nidulans. Both 15N and 14C were incorporated to the same extent, indicating that putrescine was incorporated as a unit. They also showed that the biosynthesis of spermidine in E. coli requires putrescine, L-methionine, ATP, and Mg2+ and that S-adenosylmethionine was an intermediate in the reaction (1510). Eventually, the Tabors determined that S-adenosylmethionine synthase, S-adenosylmethionine decarboxylase, and putrescine aminotransferase were involved in the reaction.

 

John Cowdery Kendrew (GB), Gerhard Bodo (GB), Howard Marvin Dantzis (GB), Robert Guy Parrish (GB), Harold Winfield Wyckoff (GB), Richard Earl Dickerson (GB), Bror Erik Strandberg (SE), Robert George Hart (GB), David R. Davies (US), David Chilton Phillips (GB), and Violet Catherine Sinclair Shore (GB) were the first to report the entire three dimensional tertiary structural for a protein, sperm whale myoglobin. This model provided the first direct evidence for the occurrence of the alpha helix in a globular protein (797-799). Note: myoglobin's function is to store oxygen (originally supplied by hemoglobin) in the tissues. This is particularly important to diving animals, such as whales, seals, and penguins, thus the choice of sperm whale tissue as a source.

 

Kau van Asperen (NL) discovered that resistance to organophosphate insecticide is due to a phosphatase-type hydrolysis resulting from the gene-controlled conversion of an aliesterase for which the organophosphate compounds are inhibitors, to an A-esterase for which these organophosphates are substrates (1585; 1586).

 

Frederic Middlebrook Richards (US) was the first to demonstrate that a protein, RNase-S, can spontaneously undergo reversible denaturation, including disulfide bond rupture and reformation (1286).

Frederic Middlebrook Richards (US) and Paul J. Vithayathil (IN) purified and characterized RNase S, separated it into S-peptide and S-protein, showed that almost all enzymatic activity is recovered when the two components are recombined, and also reported that the only observed change in covalent structure during the conversion of RNase A to RNase S is the hydrolysis of the peptide bond between residues 20 and 21 (1287). The demonstration that two separate, inactive fragments of the enzyme RNase A can be reconstituted to form an active enzyme provided the first experimental evidence that the ability of a protein to form a three-dimensional structure is an intrinsic property of its amino acid sequence.

Harold W. Wyckoff (US), Demetrius Tsernoglou (US), Albert W. Hanson (CA), James R. Knox (US), Byungkook Lee (US), and Frederic Middlebrook Richards (US) determined the complete three-dimensional structure of RNase S to 2 Å. This structure tied with three others for the third protein structure ever solved to atomic resolution. They also showed that RNase S is enzymatically active in crystal form, putting to rest the widely held view at that time that protein crystal structures were irrelevant to the conformation and behavior of enzymes in solution (1697).

 

Ruth Hubbard (US) and Allen Kropf (US) showed that the only action of light in vision is to isomerize the chromophore of a visual pigment from the 11-cis to the all-trans configuration (712; 855).

 

Daniel Edward Koshland, Jr. (US), Stephen C. Mockrin (US), and Larry D. Byers (US) described their concept of an induced fit between the enzyme and its substrate. It holds that for many enzymes flexibility is a prerequisite for activity. This represented a significant advance over Hermann Emil Fischer’s lock-and-key theory (843; 1082).

 

Israel Robert Lehman (US), Maurice J. Bessman (US), Ernest S. Simms (US), Julius Adler (US) and Arthur J. Kornberg (US) synthesized small polynucleotides in a cell-free environment (9; 133; 893).

 

Feodor Felix Konrad Lynen (DE), Ulf Henning (DE), Clark Bublitz (US), Bo Sörbo (SE) and Luistraud Kröplin-Rueff (DE) discovered the chemical mechanism producing acetoacetic acid in the liver of a person exhibiting ketosis because of diabetes mellitus and/or starvation. The mechanism is a metabolic cycle they called the HMG-CoA (hydroxymethylglutaryl-CoA) cycle (957).

Otto H. Wieland (DE), Ludwig Weiss (DE), and I. Eger-Neufeldt (DE) successfully explained how this represented a deficiency in the citric acid cycle’s ability to handle excess acetyl-CoA (1658).

 

Jack Leonard Strominger (US), and Eiji Ito (US) determined that the first phase of the synthesis of bacterial cell wall material occurs in the soluble cytoplasmic fraction and leads to the production of UDP-acetylmuramyl-pentapeptide (733; 1496; 1497). The antibiotics D-cycloserine and O-carbamyl-D-serine inhibit this phase.

 

Julius Axelrod (US), Robert Tomchick (US), and Marie-Jeanne LaRoche (US) discovered that catecholamines are metabolized by deamination, O-methylation, glycol formation, oxidation, and conjugation to glucuronides and sulfates. In the process they discovered catechol-O-methyltransferase (75; 76).

 

William E.M. Lands (US) discovered phospholipid retailoring or the “Lands” pathway. His work suggested, “the diglyceride unit of the phospholipids is metabolically different in some respect from that of the triglycerides" (872). This initial finding led to a series of papers describing the selective placement of acyl chains by phospholipid acyltransferases.

 

Paul Talalay (US), H. Guy Williams-Ashman (US), and Barbara Hurlock (US) demonstrated that oxidoreductions of steroid hormones by hydroxysteroid dehydrogenases (HSDs) could promote reversible transfer of hydride groups between NAD (H) and NADP (H) (1518; 1519).

 

Matthew Stanley Meselson (US), and Franklin William Stahl (US) in an elegant experiment using density gradient centrifugation and heavy nitrogen proved that the DNA of Escherichia coli is replicated in a semiconservative manner (1046).

 

Francis Harry Compton Crick (GB) proposed the sequence hypothesis, which states that DNA base sequence and protein sequence are collinear. Genetic information must therefore be arrayed in a strictly linear fashion along the length of a DNA molecule. Crick also proposed the central dogma which holds that genetic information stored in DNA flows through RNA to proteins. RNA is the intermediate translator of the genetic code (308; 309). Horace Freeland Judson says the 1958 paper by Crick “permanently altered the logic of biology” (761).

 

Francis Harry Compton Crick (GB) and James Dewey Watson (US) had, as early as 1953, from knowledge, intuition, and luck brilliantly deduced that the genetic code would need to specify only twenty different amino acids. They correctly specified which twenty (308).

 

Israel Robert Lehman (US), Steven B. Zimmerman (US), Julius Adler (US), Maurice J. Bessman (US), Ernest S. Simms (US), and Arthur J. Kornberg (US) demonstrated that newly synthesized DNA is made of a single stranded DNA template with the base content of the template determining the composition of the product (894). This work was the first laboratory confirmation of the Watson and Crick hypothesis that DNA serves as a template during its replication.

 

Gunther Siegmund Stent (US) reasoned that it would be logical for RNA base sequence information to be transferred to DNA base sequence information (1474).

 

Francis Harry Compton Crick (GB) proposed that amino acids had to first be attached to some form of adapter molecules before they could chemically bind to an RNA template (308).

 

Arthur Beck Pardee (US), Francois Jacob (FR), and Jacques Lucien Monod (FR) reported the results of what became known as the PaJaMo experiment. In Escherichia coli, they manipulated genes of what was later called the lactose operon, and concluded that the cytoplasm contained a substance, which carried amino acid sequence information between DNA and the ribosomes, i.e., a messenger. The experiment also strongly suggested that cells produce repressors, which turn genes off unless there is an inducer substance to block the repressor, i.e., negative control (736; 1201; 1202). The 1959 article by Jacob and Monod introduced the word operator as the target of the repressor.

Georges Cohen (FR) shortly thereafter demonstrated that in the case of tryptophan synthesis there is an inactive form of repressor, which will not suppress the pathway unless it interacts with the end product of the pathway (tryptophan), thereby being converted to the active form, which shuts down the genes of the pathway (286).

 

Liselotte I. Hecht (US), Mary Louise Stephenson (US), Paul Charles Zamecnik (US), Hans Georg Zachau (DE), George Acs (US), and Fritz Albert Lipmann (DE-US) discovered that all sRNA (tRNA) molecules have the same three terminal bases, CCA, on the free 3’ end, which binds to the amino acid. Consequently, all amino acids are transported while attached to the adenosine moiety (643; 644; 1709).

 

Nathaniel B. Kurnick (US), Barbara W. Massey (US), and Georgianna Sandeen (US) suggested that the nuclear damage observed after large doses of radiation might be mediated through an enzyme system rather than by direct effect on the chromosomal desoxyribonucleic acid, as was generally thought. Specifically, they suggested that radiation might inactivate an inhibitor of the enzyme desoxyribonuclease (DNase) thus permitting autolysis to occur (862).

 

John R. McLean (US), George L. Cohn (US), Ira K. Brandt (US), Melvin V. Simpson (US), Donald B. Roodyn (GB), Patricia J.M. Reis (AU), and Thomas Spence Work (GB) presented evidence that mitochondria are capable of independent protein synthesis (1035; 1315).

 

Guido Pontecorvo (IT-GB) observed that the rule that genes controlling metabolically sequential enzymes constitute genetic clusters does not apply, in general, to organisms other than bacteria (1227).

 

Richard Brooke Roberts (US) proposed that the name ribosome (ribonucleoprotein particles of the microsomal fraction) be used in place of what had heretofore been called microsomes (1305).

 

Alfred Tissières (CH), James Dewey Watson (US), David Schlessinger (US), and Barbara R. Hollingsworth (US) carried out the first physical characterization of ribosomes when they isolated four kinds of ribonucleoprotein particles from Escherichia coli cells. They were observed to have sedimentation coefficients of 30S, 50S, 70S, and 100S (1563; 1564).

 

John Spizizen (US) demonstrated DNA mediated genetic transformation in Bacillus subtilis. As this organism could grow in simple minimal media, it was possible to utilize a variety of auxotrophic markers (1454). This made it possible to investigate the genetic controls of biosynthetic pathways as was being done in Escherichia coli using other gene transfer systems found to be highly transformable. Refinements to achieve optimal conditions for transformation were later introduced.

 

Jakob Reinert (DE), Frederick C. Steward (US), Marion O. Mapes (US), Joan Smith (US) and Kathryn Mears (US) accomplished the formation of pro-embryonic tissue in callus clumps and cell suspensions of plant tissue (1275; 1276; 1483; 1484).

 

Peter C. Nowell (US), David A. Hungerford (US), and Carter D. Brooks (US) discovered that phytohemagglutinin (PHA) is mitogenic for peripheral lymphocytes of the blood. In this same work they were the first to see Giemsa banding of chromosomes (1156). This banding is now called G banding of chromosomes.

 

Gerald Maurice Edelman (US), Henry George Kunkel (US), and Edward C. Franklin (US) provided evidence for interaction of the rheumatoid factor with antigen-antibody complexes and aggregated gamma globulin. This interaction appears to occur in the circulation of patients with rheumatoid arthritis.

The question of whether the rheumatoid factor represents an antibody to gamma globulin was discussed (387). Note: This is identification of the first autoantibody and first recognition of autoimmune disease.

 

Nathan Kaliss (GB) discovered a special form of immunological unresponsiveness—immune enhancement—defined by the depression of cell-mediated immunity by circulating antibody (768).

 

Emanuel Riklis (IL) and Juda Hirsch Quastel (GB-CA) showed that the process of active transport of sugars (glucose, galactose, and fructose) by the isolated surviving guinea pig intestine is markedly affected by the cation concentrations present in the salt solutions bathing the intestine (1291).

 

Moselio Schaechter (US), Ole Maaløe (DK), and Niels Ole Kjeldgaard (DK) discovered that bacteria can grow in a continuum of physiological states determined by the growth rate (1356). This is a seminal paper in bacterial growth physiology.

 

Jacques C. Senez (FR) and Francis Pichinoty (FR) discovered a group of bacteria, which are nutritionally halfway between autotrophs and heterotrophs when characterized metabolically. Desulfovibrio is a typical organism in this group. This organism can oxidize hydrogen with sulfate forming water and sulfide. The energy released can be coupled to the assimilation of organic materials (1398).

 

Marvin P. Bryant (US), Milton J. Allison (US), and Raymond N. Doetsch (US) were the first to show that many rumen bacteria, other heterotrophic bacteria, and most methanogenic anaerobic bacteria have a very limited ability to utilize organic nitrogen sources such as amino acids or peptides. Instead, they utilize ammonia as their essential and major nitrogen source and utilize carbon dioxide and various volatile fatty acids, such as acetate, as a source of carbon (186).

 

Gustav Joseph Victor Nossal (AU) and Joshua Lederberg (US) discovered that a single lymphocyte can produce only one specific type of antibody (1148). Note: This became known as the "one cell-one antibody" rule.

Martin C. Raff (CA-GB), Marc Feldmann (GB), and Stefanello de Petris (GB) offered an elegant proof of this by showing that incubation of lymphocytes with antigen can aggregate (cap) all the surface immunoglobulin on antigen-binding cells; this indicated that the only immunoglobulin on the surface of these cells is antibody of a single specificity (1252).

 

Peter Brian Medawar (GB) coined the phrase immunologically competent cell to define a cell that is fully qualified to undertake an immunological response (1039).

 

John D. Marshall, Jr. (US), Warren C. Eveland (US), and Chauncey W. Smith (US) compared three methods for preparing fluorescein conjugated globulins by using two derivatives of fluorescein amine, and recommended fluorescein isothiocyanate for fluorescent antibody staining (1009).

 

Robert E. Kissling (US) grew the rabies virus in non-nervous tissue culture (hamster kidney) (814).

 

Howard Martin Temin (US) and Harry Rubin (US) developed he first quantitative assay for viral transformation. In the mid 1950s Rous sarcoma virus, an avian retrovirus was found to induce morphological changes and extend the life of chick embryo fibroblast cells in culture. Transformation was detected as foci of dense morphologically altered cells in monolayers of chick embryo fibroblasts. It depends on the loss of contact inhibition following transformation (1543). Note: This work led to the genetic era of cancer investigation.

Harry Rubin (US) found that the addition of newly transformed cells to a confluent, contact-inhibited culture of chicken fibroblasts would result in the morphologic normalization of the Rous sarcoma virus transformed cells and inhibition of their proliferation. Transformed focus formation of RSV-infected cells was suppressed by substituting fetal bovine serum (FBS) for calf serum (CS) in the medium, or raising the concentration of the latter, but suppression was effective only when the infected cells were surrounded by normal cells (1331; 1332).

Michael George Parke Stoker (GB), Moira Sheare (GB), and Charles O’Neill (GB) reported that mammalian fibroblasts transformed by polyoma virus were also inhibited by contact with a quiescent layer of mouse fibroblasts. Thus, the transformed cells seem to obey the regulation state present in the normal culture (1488).

 

Emilio Weiss (US), Harry R. Dressler (US), William F. Myers (US), Charles L. Wisseman, Jr. (US), Anna D. Waddell (US), and David J. Silverman (US) determined that Rickettsia prowazekii microorganisms are truly bacteria and not life forms halfway between bacteria and viruses, and rickettsial membranes are not leaky. Relative to Escherichia coli, Rickettsia are about half the size, have a genome one-third as large, and grow twenty times slower (1110; 1648; 1649; 1666; 1667).

 

P.R. Fry (NZ), Raymond G. Grogan (US), Frank W. Zink (US), William Boright Hewitt (US), and Kenneth A. Kimble (US) discovered that the soil fungus Olpidium brassicae serves as a host and vector of the lettuce big-vein virus (494; 583).

 

A 4,850-year-old Great Basin bristlecone pine (Pinus aristata var. longaeva) tree growing high in the White Mountains of Inyo County in eastern California was for many years thought to be the world's oldest known living non-clonal organism, until it was superseded in 2012 by the discovery of another bristlecone pine in the same area with an age of 5,068 years (germination in 3050 BC) (1; 4). This age, now in excess of 5,068 years, is yet to be confirmed.

 

Masasuke Okamoto (JP) and Ernest Robert Sears (US) discovered that chromosome pairing in wheat is genetically controlled. Consequently, the chromosomes of many other species, not ordinarily able to pair and recombine with those of wheat, could be induced to do so by removing chromosome 5B from commercially grown hybrids (1176; 1389).

Ralph Riley (GB) and Victor Chapman (GB) described the genetic systems by which pairing of wheat chromosomes at meiosis is limited to those which are fully homologous, and by which pairing between distantly related chromosomes is precluded. This basic knowledge allowed them to pair and recombine chromosomes in a way that is normally illegitimate (1293-1295).

 

Theodore Thomas Puck (US), Steven J. Cieciura (US), and Arthur Robinson (US) established that diploid human cells can be maintained in vitro for a maximum of one year (50 to 60 passages) before they degenerate and progress to aneuploid (1244-1246). This allowed persons with genetic defects to provide stocks with known markers, the underlying biochemistry of which can be studied in vitro.

 

Yoshio Okada (JP) and Jun Tadokoro (JP) showed that high concentrations of the HVJ (Sendai) virus (alive or dead) cause Ehrlich ascites cells to rapidly fuse (1172-1175).

 

Erwin Bünning (DE) proposed that the environment forms a plant’s natural internal rhythm into 24-hour cycles, each consisting of a 12-hour light-loving or photophile phase, in which light promotes flowering, followed by a 12-hour dark-loving or scotophile phase, in which light inhibits flowering (189).

 

William Boright Hewitt (US), Dewey J. Raski (US), and Austin C. Goheen (US) discovered that the ectoparasitic nematode, Xiphinema index, serves as a vector for soil-borne fanleaf virus of grapevines (669).

 

Preben Christian Alexander von Magnus (DK), Else Krag Andersen (DK), Knud Birkum Petersen (DK), and Aksel Birch-Andersen (DK) first identified monkeypox virus in 1958 as a pathogen of crab-eating macaque monkeys (Macaca fascicularis) being used as laboratory animals (1605).

Ivan Danilovich Ladnyj (RU), Peter Ziegler (), and A. Kima () were the first to identify monkeypox in man. This occurred in the Basankusu district, Equateur Region, Zaire, in 1970, 2 years after the last case of smallpox had occurred in the area (864).

 

Trevor Walworth Goodwin (GB) and Hartmut K. Lichtenthaler (DE) showed that the different leaf colors in autumn deciduous trees arise from the preferential degradation of chlorophylls over carotenoids and the synthesis of red-colored pigments like anthocyanins (566; 915).

Edward Himelblau (US) Richard M. Amasino (US) found that senescence has adaptive value among plants because of the associated remobilization of nutrients, especially nitrogen, and, to a lesser extent, phosphorus, sulfur, and other elements (674).

 

Gottfried Samuel Fraenkel (DE-US) discovered the reason for secondary plant compounds, “as only…to repel and attract insects” (468-470).

Miriam Rothschild (GB), Joseph von Euw (PL-CH), Lev Fishelson (IL), John A. Parsons (GB), and Tadeus Reichstein (PL-CH) offered the first proof of the sequestration and storage by brightly colored, aposematic, insect herbivores of toxic secondary plant substances and toxic, self-secretions (1320; 1603; 1604).

 

Leonard Muscatine (US) provided direct evidence for the transfer of materials from symbiotic algae to the tissues of a coelenterate (1109).

Robert K. Trench (US), Richard W. Greene (US), and Barbara G. Bystrom (US) confirmed the above by showing the assimilation of photosynthetic products of zooxanthellae by two marine coelenterates (1572; 1573). Note: This symbiosis promotes the growth and survival of reef corals in nutrient-poor tropical waters; indeed, coral reefs could not exist without this symbiosis.

Robert K. Trench (US), Merriley E. Trench (US) and Leonard Muscatine (US) showed that symbiotic chloroplasts provide photosynthetic products that contribute to mucus synthesis in two marine slugs (1574).

 H.H. West (US), D.A. Graves (US), M.A. Gibson (US), and J.S. Bleakney (US) observed that the ascoglossan sea slug Elysia chlorotica feeds on the intertidal alga Vaucheria litorea. It punctures the algal cell wall with its radula, then holds the algal strand firmly in its mouth and sucks out the contents as from a straw (578; 1653).

Huimin Cai (CN), Qiye Li (CN), Xiaodong Fang (CN), Ji Li (CN), Nicholas E. Curtis (US), Andreas Altenburger (DK), Tomoko Shibata (JP), Mingji Feng (CN), Taro Maeda (JP), Julie A. Schwartz (US), Shuji Shigenobu (JP), Nina Lundholm (DK), Tomoaki Nishiyama (JP), Huanming Yang (CN), Mitsuyasu Hasebe (JP), Shuaicheng Li (CN), Sidney K. Pierce (US), and Jian Wang (CN) confirmed that one of several algal genes needed to repair damage to chloroplasts, and keep them functioning, is present on the slug chromosome (205).

Anna Petherick (GB) reported that Ryan Kerney of Dalhousie University in Halifax, Nova Scotia, Canada, while looking at a clutch of emerald-green balls—embryos of the spotted salamander (Ambystoma maculatum) noticed that their bright green colour comes from within the embryos themselves, as well as from the jelly capsule that encases them.This viridescence
is caused by the single-celled alga Oophila amblystomatis. Kerney reported that these algae are, in fact, commonly located inside cells all over the spotted salamander's body. Moreover, there are signs that intracellular algae may be directly providing the products of photosynthesis

(1215).

 

 Richard Bainbridge (GB) showed that the major factor controlling swimming speed of fish was modulation of tail-beat frequency, with a small effect of amplitude at lower speeds, results that have been confirmed for many additional species by other researchers using several different methods. For much of the swimming range, speed proves to be a linear function of tail-beat frequency, and the distance travelled per beat, or stride length, is essentially constant. Bainbridge further showed that size effects of tail-beat frequency and amplitude could be expressed in a common form by normalizing speed with body length, describing speed in body-lengths s–1, or L s–1. Remarkably, most of the variation in tail-beat patterns with speed, for all three species (dace Leuciscus leuciscus, goldfish Carassius auratus, and trout Salmo irideus=Oncorhynchus mykiss) could be expressed in a single equation, sometimes called Bainbridge's Equation: U/L= 0.25[L (3F-4)], where U=swimming speed (cm s–1), L=total length (cm), and F=tail beat frequency (Hz). Expressing speed in body-lengths s–1 is still used in most studies on swimming to collapse size-related data (78).

 

Robert Helmer MacArthur (CA-US) made the first definitive study of community resource partitioning. He studied five species of warblers (MacArthur’s warblers) that breed in boreal forests of North America. He and Eric R. Pianka (US) concluded that feeding in different places and in different manners allowed these species to coexist in the same community (966; 968; 969).

 

Knut Schmidt-Nielsen (DK-US) and Ragnär Fange (SE) found that marine turtles possess a salt-secreting gland to eliminate excess salt, which collects in their tissues (1368).

Knut Schmidt-Nielsen (DK-US) discovered that marine birds eliminate the salts taken in with food and water by a gland in the head, which can be called the salt-excreting gland or simply the salt gland (1366).

 

Denis Parsons Burkitt (GB) postulated that a mosquito-transmitted infectious agent causes a lymphoma common among African children. This lymphoma became known as Burkitt’s lymphoma (197).

Herbert F. Oettgen (DE-US) Denis Parsons Burkitt (GB) and Joseph H. Burchenal (US) used methotrexate to treat malignant lymphoma involving the jaw in African children (1166).

Michael Anthony Epstein (GB), Bert Geoffrey Achong (TT-GB), and Yvonne M. Barr (GB) cultured human lymphocytes from Burkitt’s lymphoma and in the process demonstrated the presence of a Herpes virus (418). These human herpes virus 4 particles (HHV-4) have since been called Epstein-Barr virus. Note: This was the first time a virus was shown to cause cancer in humans.

Michael Anthony Epstein (GB) and Yvonne M. Barr (GB) were the first to grow human lymphocytes in continuous culture (419).

Victor Anomah Ngu (CM), John L. Ziegler (US), Avrum Z. Bluming (US), Richard H. Morrow, Jr. (US), Leroy Fass (US), Sebastian K. Kyalwazi (US), and Paul P. Carbone (US) made outstanding contributions toward increasing the cure rate of Burkitt's tumor by chemotherapy (1132; 1133; 1712-1714).

Joseph H. Burchenal (US) promoted the use of Burkitt's tumor as a model for understanding leukemia (192-194).

George Klein (SE), Gary R. Pearson (US), Gertrude Henle (US), Werner Henle (US), Volker Diehl (US), and James C. Niederman (US) reported that infectious mononucleosis is not only caused by a herpetovirus but is also caused by an agent that cannot be distinguished from the Epstein-Barr virus (652; 816). See, Nil Feodorovich Filatov, 1887.

James C. Niederman (US), Robert W. McCollum (US), Gertrude Henle (US), and Werner Henle (US) found that tested sera from 50 randomly selected college freshmen revealed Epstein-Barr virus antibodies in 12, two of whom had positive histories of infectious mononucleosis. Of 38 without demonstrable antibodies none had had IM, but the illness developed in three in the next two years. These and other observations strongly indicate that Epstein-Barr virus, or a closely related one, is the etiologic agent of infectious mononucleosis (1134).

George T. O’Connor (US) noted that current evidence suggested that the etiology of African Burkitts Lymphoma was related to Epstein Barr virus infection in a host whose immunologic state had been severely affected by constant and severe malarial infections (1163). Note: Epstein Barr virus infection is later shown to cause several other cancers, including nasopharyngeal carcinoma, Hodgkin lymphoma, and some gastric (stomach) cancers.

 

Min Chueh Chang (CN-US) and Thorsteinn Thorsteinsson (US) found that rabbit sperm are not affected by being placed in Ringer’s solution from 0.5X to 2X in concentration. Furthermore, at isotonicity these sperm can tolerate a pH range from 5.57 to 10.94 (254).

 

William Barry Wood, Jr. (US) and M. Kenton King (US) discovered the leucocytic origin of endogenous pyrogen in acute inflammatory exudates and investigated its role in the inflammatory process (1678-1681).

 

William F. Jarrett (GB), Frank W. Jennings (GB), W. Ian McIntyre (GB), William Mulligan (GB), Beatrice A.C. Thomas (GB) and George MacDonald Urquhart (GB) developed an irradiation-attenuated vaccine against lungworm (Dictyocaulus viviparus) of sheep and cattle (747; 748). Its commercial name is Dictol.

 

Börje Larsson (SE), Lars Leksell (SE), Bror Rexed (SE), Patrick Sourander (SE), William George Parker Mair (SE), and Bengt Andersson (SE) developed the concept of radiosurgery. They first employed proton beams coming from several directions into a small area in the brain, in experiments in animals and in the first treatments of human patients (878).

Lars Leksell (SE) later developed a special apparatus known as the Gamma Knife. It is a stereotactic device, which contains multiple radioactive cobalt sources and is dedicated solely to radiosurgery (897). Gamma Knife surgery is recognized worldwide as the preferred treatment for brain tumors, arteriovenous malformations and brain dysfunctions like trigeminal neuralgia.

 

Basil Isaac Hirschowitz (ZA-US), Larry E. Curtiss (US), C. Wilbur Peters (US), and H. Marvin Pollard (US) applied fiber optics in the development and construction of a completely flexible optical instrument, which allowed direct visualization of the cavity of the duodenum, the esophagus, and stomach (680).

 

Ian Donald (GB), John MacVicar (GB), and Tom Graham Brown (GB) produced what is considered the most important paper on obstetrical and gynecological sonography ever written. The paper deals with 100 patients. It contained B-mode sonograms of the gravid uterus, ovarian cysts, fibroids and ascites and various normal and pathological conditions. Other papers are included which emphasize the use of this technique to guide the amniocentesis needle, exclude twins, and avoid the anterior placenta (356-359).

 

Maurice Ralph Hilleman (US), Frederick J. Flatley (US), Sally A. Anderson (US), Mary L. Luecking (US), and Doris J. Levinson (US) introduced a vaccine to the Asian influenza (673).

 

Alfred Gottschalk (DE-AU) found that as the influenza virus attaches to red cells or cells of the upper respiratory tract it cuts N-acetyl neuraminic acid, or sialic acid on the surface of the host cell. When the progeny viruses are escaping from the infected cell they must cut off this anchoring molecule to make their getaway. The viral protein that dues the cutting is called neuraminidase (568; 569).

Richard T. Huang (DE), Rudolf Rott (DE), K. Wahn (DE), Hans Dieter Klenk (DE), and Takafumi Kohama (DE) worked out the function of the neuraminidase in membrane fusion induced by myxoviruses. It was found that the presence of neuraminidase is essential for fusion between the liposomes and cells (711).

 

Karl Erik Aström (SE-US), Elliott Lee Mancall (US), and Edward Peirson Richardson, Jr. (US) were the first to describe progressive multifocal leukoencephalopathy (PML) (67). This is a disease of the white matter of the brain, caused by a virus infection that targets cells that make myelin--the material that insulates nerve cells (neurons). Polyomavirus JC (often called JC virus) is carried by most people and is harmless except among those with lowered immune defenses. The disease is rare and occurs in patients undergoing chronic corticosteroid or immunosuppressive therapy.

Billie L. Padgett (US), Gabriel M. ZuRhein (US), Duard L. Walker (US), Robert J. Eckroade (US), and Bert H. Dessel (US) isolated the polyomavirus JC responsible for progressive multifocal leukoencephalopathy (PML) (1195).

 

Herman Moritz Kalckar (DK-US) proposed that fallout following atmospheric tests of nuclear weapons could be measured by analysis of the content of strontium-90 in the milk teeth of young children (767).

 

Endre Kelemen (HU), István Cserhati (HU), and Belá Tanos (HU) coined the term thrombopoietin when they described the humoral substance responsible for the rebound thrombocytosis that follows states of thrombocytopenia (795). Thrombopoietin (TPO) stimulates the development of megakaryocyte precursors of platelets, leading to an increase in the number of circulating platelets in a manner that is analogous to the erythropoietin (EPO) stimulation of erythroid precursors.

 

Bertha A. Bouroncle (US), Bruce K. Wiseman (US), and Charles A. Doan (US) gave a detailed description of twenty-six cases of leukemic reticuloendotheliosis (hairy cell leukemia) which identified it as an independent hematologic and pathologic entity (160).

 

Rudolf Rabl (DE) discovered the first example of gender dimorphism in the human brain, conferring to women greater thalamic connectivity in the region massa intermedia (1250).

 

Alice M. Stewart (GB), Josefine Webb (GB), and David Hewitt (GB) carried out an epidemiological study to see if there was a relationship between X rays during pregnancy and leukemia in children (1485). This paper is significant because it prompted two important discoveries—that all childhood cancers have fetal origins and that cancers of the immune system can affect reactions to other diseases before they are themselves recognizable clinically.å

 

Elizabeth Stern (CA-US), Alan B. Forsythe (US), Lee Youkeles (US), and J. Dixon Wilifrid (US) identified 250 stages of a cervical cell's progression from normal to cancerous, making early cancer detection and treatment possible (1477; 1479).

Elizabeth Stern (CA-US), Virginia A. Clark (US), and Carl F. Coffeit (US) discovered a link between oral contraceptives and cervical cancer (1478).

 

Ernest W. Walton (GB) provided the definitive description of Wegener’s granulomatosis (1618).

 

Theodore Brown Rasmussen (CA), Jerzy Olszewski (PL-CA), and Donald Lloyd-Smith (CA) described the features of a chronic neurological syndrome characterized by brain dysfunction, encephalitis, and intractable epilepsy, i.e., Rasmussen’s encephalitis (1267).

Scott W. Rogers (US), P. Ian Andrews (US), Lorise C. Gahring (US), Teri Whisenand (US), Keith Cauley (US), Barbara Crain (US), Thomas E. Hughes (US), Stephen F. Heinemann (US), and James O. McNamara (US) suggested that autoantibodies to glutamate receptor GluR3 might be the cause of Rasmussen's encephalitis (1312).

 

Carl Axel Gemzell (SE), Egon Diczfalusy (SE), and Karl Gunnar Tillinger (SE) used extracts of human pituitary gonadotropins (hPG), containing both follicle-stimulating hormone (FSH) and luteinizing hormone (LH) to successfully induce ovulation in humans (517).

 

Joshua Harold Burn (GB) and Michael John Rand (GB) established that reserpine depletes the stores of norepinephrine in arterial walls. They used reserpine-treated animals to demonstrate that some sympathomimetic amines (e.g. tyramine and other noncatechol phenylethylamine derivatives) only act when the tissue catecholamine stores are intact, and therefore presumably owe their own actions to the release of catecholamines (198).

 

Robert H. Silber (US), Robert D. Busch (US), and Raymond Oslapas (US) introduced a simplified fluorometric procedure for estimating the quantity of corticosterone or hydrocortisone. It has practical applications for the estimation of these steroids in samples that are small in volume or low in concentration, or in studies that are designed primarily to demonstrate increases or decreases in adrenocortical hormones in plasma or adrenals without requiring absolute specificity (1416).

 

Joaquin Barraquer (ES) and Joaquin Rutllan (ES) discovered that alpha-chymotrypsin can be used to enzymatically dissolve the zonules of the eye for removal of a lens with cataract (90; 91).

 

Manucher Javid (US) introduced osmotic diuretics for reduction of intracranial pressure (749).

 

Malcolm Andrew Ferguson-Smith (GB) and Ian B. Munro (GB) reported a case of Klinefelter’s syndrome whose nuclear sex is female, but who shows clearly in a routine unilateral testicular biopsy active, but scanty, spermatogenesis with the production of mature spermatozoa (437).

 

Charles E. Ford (GB), Patricia A. Jacobs (GB), and Lazlo G. Lajtha (GB) introduced chromosome analysis using fresh bone marrow (458).

Paul S. Moorehead (US), Peter C. Nowell (US), William J. Mellman (US), D.M.A. Battips (US), and David A. Hungerford (US) developed a method for chromosome preparations of leukocytes cultured from human peripheral blood. The key ingredient was phytohaemagglutinin, added to remove red cells from plasma, which coincidently caused lymphocyte transformation (1094). This method largely replaced the bone marrow method.

G.K. Chrustschoff (RU) and E.A. Berlin (RU) had much earlier observed that autolysis of red cells induces cell division in lymphocytes (269).

 

John H. Laragh (US), Henry O. Heinemann (US), and Felix E. Demartini (US) reported on the effect of chlorothiazide on electrolyte transport in man; its use in the treatment of edema of congestive heart failure, nephrosis, and cirrhosis (876).

 

James H. Austin (US) described cases of probable chronic inflammatory demyelinating polyneuropathy by recognizing a fluctuating motor-predominant neuropathy that produced severe weakness that would either improve spontaneously or in response to corticosteroids. He noted that some of the cases presented with weakness without muscle atrophy and hypothesized that focal areas of segmental demyelination rather than axonal degeneration were likely the pathological cause because of the lack of atrophy (70).

Peter James Dyck (US), Alfred C. Lais (US), Michiya Ohta (US), James A. Bastron (US), Haruo Okazaki (US), and Robert V. Groover (US) studied 57 patients and subsequently introduced the name chronic inflammatory polyradiculoneuropathy (to which the term demyelinating was subsequently added) and thus defined CIDP as a separate disease entity (383).

 

Anne McLaren; Anne Laura Dorinthea McLaren (GB) and John Dennis Biggers (GB) successfully grew mouse embryos in vitro. The embryos were then transferred into the wombs of female mice, where they developed into a healthy litter (1033). Note: This experiment was a vital proof of principle. It showed that it was possible to mix sperm and eggs outside the mother’s body and create a healthy embryo, which could then grow to term in the womb of a recipient mother. Louise Joy Brown (GB) the world’s first test tube baby (in vitro fertilization) was born in Oldham, Northern England, on July 25, 1978. Patrick Christopher Steptoe (GB) and Robert G. Edwards (GB) performed the operation (1476).

 

Aubrey Leatham (GB) provided a new classification for heart murmur analysis. Prior to this work, systolic murmurs were seldom differentiated by their configuration or timing. Leatham's new classification of mid-systolic ejection murmurs versus pansystolic regurgitant murmurs, based on his graphic analysis, changed the way clinicians approached the bedside diagnosis of valvular disease and contributed to decision making for cardiac surgery (886).

 

Charles Theodore Dotter (US) and Louis H. Frische (US) developed a new method to reliably and safely visualize the coronary vessels. The method employed a soft, double-lumen balloon catheter. Prior to this time, there had been no reliable way to visualize the coronary vessels (362).

 

Hannibal Hamlin (US), William H. Sweet (US), and William M. Lougheed (US) performed one of the first successful carotid bifurcation reconstructions (608).

 

G. Rainey Williams, Jr. (US) and Frank C. Spencer (US) used hypothermia to treat patients who sustained neurological damage following cardiac arrest (1662).

 

Oscar Creech, Jr. (US), Edward T. Krementz (US), Robert F. Ryan (US), and James N. Winblad (US) developed a technique of regional perfusion found to be useful with cases of malignant melanoma, soft tissue sarcomas in the limbs, and some pelvic cancers (306).

 

Emil Frei, 3rd. (US), James F. Holland (US), Marvin A. Schneiderman (US), Donald Pinkel (US), George Selkirk (US), Emil J. Freireich (US), Richard T. Silver (US), G. Lennard Gold (US), William Regelson (US), demonstrated that combination chemotherapy with the drugs 6-mercaptopurine and methotrexate can induce partial and complete remissions and prolong survival in children and adults with acute leukemia (484-488).

 

Donald Heath (GB) and Jesse E. Edwards (US) recognized six grades of progressive histological changes which occur in the small pulmonary blood vessels in association with the chronic pulmonary hypertension complicating many congenital cardiac septal defects (640).

 

Konrad Zacharias Lorenz (AT) defined ethology as, “the application of orthodox biological methods to the problems of behavior” and credited Charles Robert Darwin with being its scientific father. His comparative studies showed that man and simpler animals have many behavioral patterns in common (936; 937).

 

Carl B. Huffaker (US) performed predator/prey experiments, which suggested that in a sufficiently natural environment (of reasonable size for meaningful interaction), continuity is possible without stipulation of prey immigration or specific prey refuges (720).

 

Robert Ashley Couper (NZ) presented fossil evidence for the earliest undisputed angiosperm pollen. It is from the Barremian stage (late early Cretaceous), c.120 mya (303).

 

Roland E. Beschel (AT) developed the method of using lichen growth to date rocks and other objects covered by lichens (lichenometry) (130-132). Note: This method is most accurate within 100 to 9,000 years ago.

 

1959

“Pythagoras discovered the simple numerical relations of what we call musical intervals…It has been suggested that the three intervals of the tuned string were compared with the three ways of life. While this must remain speculation, it is certainly true that the tuned string henceforth plays a central part in Greek philosophical thought. The notion of harmony, in the sense of balance, the adjustment and combination of opposites like high and low, through proper tuning, the conception of the mean or middle path in ethics, and the doctrine of the four temperaments all of these go back in the end to Pythagoras’ discovery…It is very likely that the discoveries in music led to the notion that all things are numbers. Thus, to understand the world around us, we must find the number in things.” Bertrand Russell (1335).

 

"When playing around in the ocean, dolphins are pleasing to the eye no end, but let it only add to your thrill that these rascals are a graveyard to our wits. For is not finding out infinitely more exciting than knowing the answer?" Per Fredrik Thorkelsson Scholander (1370).

 

Severo Ochoa (ES-US-ES) and Arthur J. Kornberg (US) were awarded the Nobel Prize in Physiology or Medicine for their discovery of the mechanisms in the biological synthesis of ribonucleic acid and deoxyribonucleic acid.

 

E. Graham Bligh (CA) and William J. Dyer (CA) developed a rapid method of total lipid extraction and purification from biological materials (149).

 

Rudolf Thalacker (DE) and Martin Behrens (DE) devised a non-aqueous method for isolation of chloroplasts (1548).

Clifford Ralph Stocking (US) and Susan A. Larson (US) first demonstrated the significance of shuttle transfer across chloroplast membranes in energy metabolism (1487).

Hans W. Heldt (DE), Ulrich Heber (DE), Gotthard Heinrich Krause (DE), and Kurt A. Santarius (US) identified specific translocators in the chloroplast envelope and published on their role in transport (641; 642; 648).

David A. Walker (GB) wrote an excellent review of the movement of certain key substances, etc. across the chloroplast envelope (1612).

 

Leonard Warren (US) developed a colorimetric assay for the measurement of sialic acids in which the products of periodate oxidation are coupled with thiobarbituric acid to form a red chromophore. Since only free sialic acids are measured the reaction could be used for the detection and measurement of neuraminidase (sialidase) which hydrolytically releases sialic acids from their bound form (1625).

 

Stanford Moore (US), Darrel H. Spackman (US), and William H. Stein (US) described a procedure for the chromatographic fractionation of mixtures of amino acids by elution analysis on columns of Dowex-50, a sulfonated polystyrene resin. Compared to starch the resin columns possess higher resolving power, are more convenient to operate, are faster, and the separation is not adversely affected by the presence of inorganic salts in the material chromatographed (1093).

 

Arnold Martin Katz (US), William J. Dreyer (US), and Christian Boehmer Anfinsen, Jr. (US) described a modified method for the separation of peptides on filter paper that utilizes chromatography followed by high voltage electrophoresis cooled by a non-explosive organic solvent (786).

 

Albrecht K. Kleinschmidt (DE), H. Rüter (DE), Wilhelmine Hellmann (DE), Rudolf K. Zahn (DE), Annesuse Docter (DE), E. Zimmermann (DE), H. Rübner (DE), A.M. Al Ajwady (DE) Dimitri Lang (DE) and Diether Jacherts (DE) developed a method, which allowed the visualization of DNA molecules as smooth, flexible filaments (819; 820).

 

Hazel D. Barner (US) and Seymour Cohen (US) presented evidence that phage infection also stimulates the formation of a new form of thymidylate synthase, even though this enzyme was already known to exist in uninfected bacteria. This work suggested that the virus needed not only novel enzymes to produce the unique base but also needed to augment the activities of pre-existing enzymes to promote the big metabolic shift toward DNA synthesis (85).

 

Adolf Friedrich Johann Butenandt (DE), Roland Beckmann (DE), Dankwart Stamm (DE), and Erich Hecker (DE) identified and determined the structure of the sex attractant (bombykol) of the silkworm, Bombyx mori, as (E, Z)-10,12-hexadecadien-1-ol. This was the first insect pheromone to be identified (203; 204).

 

Jakob Schreiber (CH), Willy Leimgruber (US), Mario Pesaro (CH), Peter Schudel (CH), Terry L. Threlfall (GB) and Albert Eschenmoser (CH) carried out the total synthesis of colchicine (1374; 1375).

 

Grant R. Bartlett (US) developed a method for assaying phosphorus using column chromatography (96).

 

Louis Frederick Fieser (US) and Mary Fieser (US) coined the term steroid to denote any structure like cholesterol (493).

 

Jon Bremer (NO) and David M. Greenberg (US), using in vivo labeled methionine, discovered that phosphatidylethanolamine may generate phosphatidylcholine via three successive methylation steps (168).

 

Sydney Brenner (ZA-GB) and Robert W. Horne (GB) developed the negative staining technique, invented four years previously by Hall, into a generally useful technique for visualizing viruses, bacteria, and protein filaments (171).

 

Joan Oró (US) Aubrey P. Kimball (US), Richard Reed Fritz (US), and Fenil Master (US) synthesized amino acids from formaldehyde and hydroxylamine under primitive Earth conditions (1192).

 

David F. Elliott (GB), Eric William Horton (GB), and Geoffrey P. Lewis (GB) isolated, purified, and determined the amino-acid composition of bradykinin (402-405). They later determined that it is a nonapeptide (401).

 

Rodney Robert Porter (GB), Gerald Maurice Edelman (US), and Miroslav Dave Poulik (CZ-CA-US) discovered that antibody molecules are composed of four protein molecules called chains. Each antibody molecule possesses two identical heavy chains and two identical light chains (389; 1230).

Alfred Nisonoff (US), Marvin H. Winkler (US), and David Pressman (US) demonstrated that the antibody molecule has two combining sites with the same specificity for an antigenic determinant (1143).

Alfred Nisonoff (US), Franklyn C. Wissler (US), and L.N. Lipman (US) determined the properties of the major component of a peptic digest of rabbit antibody as the F(ab’)2 fragment of the antibody molecule, which is the single bivalent fragment that is produced after pepsin cleavage(1144). Note: Later, it was found that this F(ab')2 fragment is responsible for antigen interaction and agglutination and precipitation reactions.

An-Chuang Wang (US), Stephen K. Wilson (US), John E. Hopper (US), Hugh H. Fudenberg (US), and Alfred Nisonoff (US) provided evidence for control of synthesis of the variable regions of the heavy chains of immunoglobulins gamma and immunoglobulin macroglobulin M by the same gene (1619).

Klaus Eichmann (US), Amar S. Tung (US), and Alfred Nisonoff (US) discovered the linkage and rearrangement of genes encoding mouse immunoglobulin heavy chains (394).

Alfred Nisonoff (US), J.A. Laskin (US), Alfred Gray (US), Norman R. Klinman (US), and Paul G. Gottlieb (US) discovered how segregation at a locus determining an immunoglobulin genetic marker for the light chain variable region affects inheritance of expression of an idiotype (1142).

 

Mortimer M. Elkind (US), Harriet Sutton (US) and Willie B. Moses (US) showed that following exposure of eukaryotic cells to radiation the surviving cells rapidly repaired the damage caused by radiation, and by the time they had divided once after initial exposure they had already eliminated its sublethal or recessive lethal damage (398-400). Note: This finding confirmed the presence of DNA repair mechanisms, later shown to be defective in some cancers.

 

Lloyd John Old (US), Donald A. Clarke (US), and Baruj Benacerraf (VE-US) introduced Bacille Calmette-Guérin (BCG), the tuberculosis vaccine, as a way to stimulate nonspecific resistance to tumor growth (1180). Note: Today, BCG is widely used as a first-line treatment for superficial bladder cancer.

 

 Baruj Benacerraf (VE-US) and Philip G.H. Gell (GB) found that immunization with conjugates (protein carriers linked to a hapten) is followed by the appearance of delayed hypersensitivity to the protein “carrier” in the absence of detectable antibodies against it, although antibodies are produced at that time against the haptenic group itself. Delayed hypersensitivity to the haptenic group has not been detected at any time; blocking it with specific antibody does not lead to the appearance of delayed hypersensitivity, but merely suppresses antibody formation against that group (112).

Bernard B. Levine (US), Antonio Ojeda (US), and Baruj Benacerraf (VE-US) developed the concept of Ir (immune response) genes. Individuals with this gene would be able to recognize certain carriers and thereby synthesize antibodies or manifest delayed-type hypersensitivity to the target hapten (909).

Ira Green (US), William E. Paul (US), and Baruj Benacerraf (US) found that hapten-poly-L-lysine conjugates behaved as complete antigens in genetic responder and as haptens in nonresponder guinea pigs (582).

 

Sidney Walter Fox (US), Kaoru Harada (JP), Kenneth R. Woods (US), Charles Ray Windsor (US), and Allen Vegotsky (US) showed how amino acids can be heated under Earth conditions to form proteinoids or "thermal proteins," which when placed in water self-organize into microspheres or protocells, possible precursors of the contemporary living cell (464-467).

 

Siro Senoh (US), John Daly (US), Julius Axelrod (US), and Bernhard Witkop (US) discovered catechol-O-methyltransferase (CMOT) and determined that it can catalyze the methylation of a wide variety of natural catechols. They proposed a metabolic pathway for the metabolism of noradrenaline and adrenaline (1399).

 

Antonio Lima-de-Faria (SE) showed that heterochromatin replicated later than euchromatin (923).

 

O. Arunlakshana (US) and Heinz Otto Schild (GB) demonstrated that drugs and drug antagonists compete for receptors according to the law of mass action (63).

 

William H. Prusoff (US) reported on 5-iodo-2’-deoxyuridine (IDU), one of the first compounds tested and shown to be active against DNA viruses (1243). It was soon shown to be effective against Herpes simplex virus in a rabbit eye model.

 

Feodor Felix Konrad Lynen (DE), Joachim Knappe (DE), Ekkehard Lorch (DE), Gerd Jütting (DE), Erika Ringelmann (DE), and Jean-Paul Lachance () discovered that biotin is a coenzyme acting along with enzymes such as carboxylase in the transfer of activated carbon dioxide (956; 958; 959).

 

Howard Rasmussen (US), Lyman Creighton Craig (US) and Gerty Hochster (US) isolated and characterized the main hormone produced by the parathyroid glands, parathyroid hormone (PTH) (1265; 1266).

 

Frank Ralph Batchelor (GB), Frank Peter Doyle (GB), John Herbert Charles Nayler (GB), and George Newbolt Rolinson (GB) discovered 6-aminopenicillanic acid (6-APA), the penicillin nucleus. It provided the ideal starting point for the preparation of new penicillins because different side chains could be attached to the nucleus, through the free amino group, by chemical means (98).

 

Federico Maria Arcamone (IT), Cesare Bertazzoli (IT), Mario Ghione (IT), and Tullio Scotti (IT) isolated the antibiotics melanosporin and elaiophylin from Streptomyces melanosporus (46).

 

Federico Maria Arcamone (IT), Cesare Bertazzoli (IT), Mario Ghione (IT), and Tullio Scotti (IT) isolated the antibiotic gabbromycin or aminosidine sulfate from Streptomyces crestomyceticus (47; 48).

 

Theodore H. Haskell (US), James C. French (US), and Quentin R. Bartz (US) isolated the antibiotic paromomycin from Streptomyces rimosus (625).

 

Christine O. Dawson (GB) and James C. Gentles (GB) discovered the teleomorphs (perfect or sexual state) of Trichophyton (Keratinomyces) ajelloi (331).

 

Alvin Markovitz (US), Joseph A. Cifonelli (US), and Albert Dorfman (US) synthesized hyaluronic acid in a cell-free preparation of streptococci (1001). This was the first cell-free synthesis of a heterologous polysaccharide.

 

Jerker Olof Porath (SE) and Per Flodin (SE) introduced gel filtration using cross-linked dextran gels. This produced a so-called molecular sieving (1228; 1229).

 

Samuel Raymond (US) and Lewis S. Weintraub (US) introduced the polyacrylamide gel electrophoresis (PAGE) technique. It is superior to starch gels for separating proteins by electrophoresis (1270).

Baruch Joel Davis (US) and Leonard Ornstein (US) described the use of polyacrylamide gel for disc electrophoresis (1187; 1188).

 

Stauffer Chemical Company introduced the herbicide EPTC, a thiocarbamate, for use in crops such as alfalfa (Medicago sativa), certain beans, potatoes (Solanum tuberosum), and sweet potatoes (Ipomea batatas). ref

 

An Italian company, Lepetit, isolated and tested the antibiotic rifampicin (rifampin, rifamycin, or rifaldazine). It was isolated from Streptomyces mediterranei (Amycolatopsis mediterrani) found in a wooded area of Northern Italy. The antibiotic was named for a movie, Rififi, being filmed in the area at the time (562). Rifamycin blocks initiation of RNA chains by binding to RNA polymerase (prevents RNA synthesis) in prokaryotes only.

 

Peter Karlson (DE) and Adolf Friedrich Johann Butenandt (DE) proposed the name pheromone to designate substances secreted by an animal to the outside and causing a specific reaction in a receiving individual of the same species. This term is synthesized from the Greek pherein (to carry) and horman (to excite) (779). See, Fabre, 1879; Bethe, 1932; Butenandt, 1961; Corpéchot, 1985; and Cutler,1986.

 

Samuel B. Weiss (US) and Leonard Gladstone (US) were the first to describe the RNA-synthetic activity of a RNA polymerase. They used rat liver as experimental material (1650).

Audrey Stevens (US), using E. coli, almost simultaneously discovered RNA polymerase (1481).

Ru-Chih C. Huang (US), Nirmala Maheshwari (IN), and James Frederick Bonner (US) discovered the synthesis of RNA from DNA in peas (158; 710).

Jerard Hurwitz (US), John J. Furth (US), Monika Anders (US), Priscilla J. Ortiz (US), and J. Thomas August (US) presented their studies with the E. coli RNA polymerase, which provided an enzymatic mechanism by which DNA supported RNA synthesis (726).

 

Bention Nisman (FR), Hiroshi Fukuhara (FR), Tadanori Kameyama (JP), G. David Novelli (US), Alfred Tissieres (US), David Schlessinger (US), and Francoise Gros (FR) observed that DNAase inhibits in vitro incorporation of amino acids into proteins thus suggesting that protein synthesis depends on DNA templates (769; 1141; 1562).

 

Francois Jacob (FR) and Jacques Lucien Monod (FR) isolated and genetically analyzed many mutants in the lactose utilization pathway. Their studies of these mutants led to the conclusion that induction and repression are under the control of specific proteins, which are coded for by regulatory genes. They proposed that regulator genes are closely associated with the structural genes coding for specific enzyme proteins but are distinct from them. They visualized regulator substance interacting with a genetic element, an operator, which controlled expression of the structural genes (736; 739). The term operon was coined in the 1960 paper.

 

Milislav L. Demerec (Yugoslavian -US) and Philip E. Hartman (US) noted that in bacteria the genes controlling enzymes of the same biochemical pathway tend to remain clustered because they are all controlled by the same operator gene (343).

 

Alice L. Tuttle (US) and Howard Gest (US) discovered that the photosynthetic apparatus of the photosynthetic bacteria is associated with the cytoplasmic membrane and/or membranous extensions into the cytoplasm (1578).

 

Micheline M. Mathews (US) and William R. Sistrom (US) determined that the function of carotenoid pigments in non-photosynthetic bacteria is to diminish the harmful effects of light radiation (1019).

 

P. Gaastra (NL) performed experiments designed to analyse the photosynthetic activity of crop plants. The following features are successively discussed: technical requirements and details of the experimental set-up, the influence of light intensity, carbon dioxide concentration, and leaf temperature on photosynthesis of cucumber, tomato, spinach, turnip, and sugar beet, the effect of light intensity and carbon dioxide concentration on the stomatal diffusion resistance, and the stomatal control of photosynthesis (500; 501).

 

R. Clinton Fuller (US) and Martin Gibbs (US) found that purple bacteria contain the Calvin-Benson cycle of carbon fixation (495).

 

Choh Hao Li (CN-US) and Phil G. Squire (US) purified and determined the properties of interstitial cell-stimulating hormone from sheep pituitary glands (912).

 

Clement L. Markert (US) and Freddy Møller (US) proposed the term isozyme or isoenzyme to denote different enzymes which share functional specificity, but which vary slightly reflecting their tissue of origin, their ontogeny, or their species of origin (1000).

Louis Barkhouse Flexner (US), Josefa B. Flexner (ES-US), Richard B. Roberts (US), and Gabriel L. de la Haba (US) independently discovered isoenzymes (455).

 

Jennie Ciak (US) and Fred E. Hahn (US) showed that the antibiotic D-cycloserine, an analog of D-alanine, inhibits cell wall synthesis (271).

 

Jack Leonard Strominger (US) and Robert H. Threnn (US) reported that the antibiotic novobiocin inhibits cell wall synthesis (1498).

 

Shimon Gatt (US), Ray Wu (US) and Efraim Racker (PL-AT-US) showed that glycolysis is dependent on the continuous regeneration of ADP and inorganic phosphate by an ATPase. This was the first indication that an ATPase is in the family of glycolytic enzymes (509; 510; 1691; 1692).

 

Joshua Lederberg (US) theorized that lymphocytes pass through an obligatory paralyzable state early in their ontogeny during which an encounter with an antigen will silence or kill them. If they pass this point without antigenic stimulation they become inducible, i.e., capable of being activated (890).

 

Ernst Freese (US) hypothesized about the molecular basis of mutations caused by base analogues, such as bromouracil and nitrous acid. He proposed two distinct classes of base substitutions in DNA. The first was a simple copying error whereby one purine was switched to another (A for G or the reverse) or one pyrimidine for another (T for C or the reverse). Such errors he called transitions. Base analogues and nitrous acid caused transitions. Transitions revert to the wild type easily.

Most spontaneous mutations and those induced by dye such as proflavine rarely reverted to the wild type. He suggested that in these a purine was replaced by one of two pyrimidines or a pyrimidine by one of the two purines. He called this type of substitution a transversion (481-483).

 

Benjamin D. Hall (US), Paul Mead Doty (US), Uriel Z. Littauer (IL), Heini Eisenberg (IL), Serge N. Timasheff (US), Raymond A. Brown (US), John S. Colter (US), and Maurice C. Davies (US) reported that ribosomal RNA from higher organisms sedimented as two distinct components, 18S and 28S (603; 928; 1559).

 

Joseph-Felix Heremans (BE), M.T. Heremans (BE), and Hermann Edward Schultze (BE) described IgA and laid one of the foundations for our understanding of intestinal immunity (656).

 

Stewart S. Sell (US) and William O. Weigle (US) found that sensitization by injection of immune precipitates in adjuvant induces not only delayed hypersensitivity but also the steps leading to immune antigen elimination—i.e., the production of circulating antibody. It appears that during the course of immunization the delayed hypersensitive state develops first, then gives way to the Arthus type of sensitivity as antibody production is manifest (1393).

 

Kenneth McQuillen (US), Richard Brooke Roberts (US), and Roy John Britten (US) proved that in Escherichia coli protein synthesis occurs on ribosomes (1037).

 

Tracy Morton Sonneborn (US) established that the “kappa” particles of Paramecium aurelia represent the first known case of cytoplasmic inheritance in animals. He hypothesized that intracellular symbiotes and cell organelles have become inextricably combined during evolution (1446).

Lemuel Ruscoe Cleveland (US) and Albert Victor Grimstone (GB) described Mixotricha paradoxa, a protozoan symbiotic to Darwin’s termite (Mastotermes darwiniensis), as a very unusual protozoan that is a composite of a eukaryotic protozoan with three independent prokaryotic symbionts: spirochetes, bacteria associated with the spirochetes, and endosymbiotic bacteria (279).

Lynn Margulis (US) proposed that the eukaryotic cell is an evolutionary chimera, put together from at least three quite different, previously prokaryotic, lineages (999; 1341).

Tom Cavalier-Smith (US) coined the collective term Archezoa to include amitochondrial protists (the diplomonads, mastigamoebae and retortamonads) and microsporidians. He explained the origin of mitochondria and chloroplasts within eukaryotic cells by proposing what became known as the endosymbiotic or endosymbiont theory (245; 246). See Mereschkowsky, 1905.

 

Gordon Alastair Maclachlan (CA) and Helen K. Porter (CA) discovered that higher plants can also continue to produce ATP by photophosphorylation in the absence of CO2 for assimilation (975).

 

Richard L. Wood (US) discovered septate junctions. They are found in invertebrate tissues where they participate in adhesion, sealing, and communication (1677).

 

Harry Eagle (US) introduced his minimum essential medium (MEM) for the cultivation of eukaryotic cells. Except for a small amount of dialyzed serum this medium is defined and can support cell multiplication (385).

 

S. Jon Singer (US) used antibodies coupled to ferritin to detect cellular molecules in the electron microscope (1425).

 

Takashi Hayashi (JP) found that application of gamma-aminobutyric acid (GABA) strongly suppressed electrical activity in the mammalian nervous system (636).

Edward A. Kravitz (US), Stephen William Kuffler (US), David D. Potter (US), and Masanori Otsuka (JP) proved that γ-aminobutyric acid, or GABA, is the inhibitory neurotransmitter at the lobster neuromuscular junction (847; 1194).

 

David W. Krogmann (US), André Tridon Jagendorf (US), and Mordhay Avron (IL) presented evidence for the coupling of ATP synthesis to electron transport in illuminated chloroplasts (854).

 

Peter Dennis Mitchell (GB) and Jennifer Moyle (GB) proposed that energy-yielding and energy-requiring reactions of oxidative phosphorylation are linked by a high-energy state, rather than by a compound. They theorized that an electrochemical gradient of protons across the mitochondrial inner membrane serves as the means of coupling the energy flow from electron transport to the formation of ATP. The membrane is an integral part of the coupling mechanism and must be intact in the form of a continuous closed vesicle for oxidative phosphorylation to take place. They postulated that it is the function of the electron carriers of the respiratory chain to serve as an active-transport system or pump to transport protons from the mitochondrial matrix across the inner membrane, thus generating a gradient of protons across the membrane, which they postulated to be impermeable to protons. The electrochemical gradient thus generated is then postulated to drive the synthesis of ATP by causing dehydration of ADP and Pi. They determined that mitochondria translocate approximately two protons across the mitochondrial membrane for each ATP generated by oxidative phosphorylation and demonstrated that in mitochondria ATP can be artificially generated by making the medium outside the inner mitochondrial membrane moderately acidic vis-à-vis the mitochondrial matrix. They were the first to realize that the buildup of protons in the thylakoid sac of chloroplasts might serve as a source of energy to drive phosphorylation of ADP to ATP and predicted that the thylakoid membrane should be asymmetrical (1034; 1059-1079; 1105; 1106). The four parts of the chemiosmotic coupling theory are stated in the 1966 article

 

Roger Yate Stanier (CA), Michael Doudoroff (RU-US), Riyo Kunisawa (US), and Rebecca Contopoulou (US) found that when photosynthetic bacteria oxidize organic substrates they use only a small portion of the reducing power gained to reduce carbon dioxide. Most of these substrates were found to be assimilated directly as poly-beta-hydroxybutyric acid (PHB) or as polysaccharide (1461).

 

Michael Doudoroff (RU-US) and Roger Yates Stanier (CA) used Pseudomonas saccharophilia and Rhodospirillum rubrum to show that excess substrate carbon accumulates within the cell as poly-beta-hydroxybutyric acid (PHB). When the external substrate is removed, the stored PHB is degraded intracellularly. PHB is therefore an important carbon and energy reserve for these bacteria (364).

 

Albert Bruce Sabin (PL-US) grew the reovirus in monkey kidney tissue culture and coined the name reovirus to reflect the fact that viruses of this group had been isolated from the respiratory and enteric tracts and were orphan viruses without known associated disease (reo) (1339).

 

Philippe Vigier (FR) and Alice Golde (FR) showed that chick embryo cells infected with Rous sarcoma virus continued to grow in culture and produce more virus. The infected cells underwent a change in morphology and exhibited rapid, disordered growth characteristic of cancer cells (1598).

 

Bolivian Health Officials first isolated the Machupo virus from 1959-1962. It is a New World arenavirus from the Arenaviridae family (151). Machupo virus is the etiological agent of viral hemorrhagic fever (Bolivian hemorrhagic fever, South American hemorrhagic fever, arenavirus, black typhus, Ordog Fever).

 

Armando S.Parodi (AR), Héctor R. Rugiero (AR), Daniel J. Greenway (AR), Norma E. Mettler (AR), A. Martinez (AR), Martha C. Boxaca (AR), and J.M. De La Barrera (AR) isolated Junin virus, the causative agent of Argentine haemorrhagic fever, which has been known since 1943 (1203).

 

Lynne Kilham (US) and Louis J. Olivier (US) isolated a latent virus from rats using tissue culture (807). Note: This is a parvovirus known as Kilham rat virus.

 

Frank Macfarlane Burnet (AU) and George Keble Hirst (US) suggested that the genome of the influenza virus might be segmented because of its unexpectedly high frequency of recombination (199; 681).

Peter H. Duesberg (US), Marcel W. Pons (US), and George Keble Hirst (US) found that the influenza virus appeared to consist of about six segments (374; 1226).

Peter Palese (US), Jerome L. Schulman (US), Duncan McGeoch (GB), Peter Fellner (GB), and Clive Newton (GB) showed that influenza A viruses (IAVs) and type B viruses (IBVs) contain 8, negative-sense, single-stranded viral RNA (vRNA) gene segments, which encode transcripts for 10 essential viral proteins (1031; 1198).

Robert G. Webster (US), William J. Bean (US), Owen T. Gorman (), Thomas M. Chambers (US), and Yoshihiro Kawaoka (US) report that two partly overlapping reservoirs of influenza A viruses exist in migrating waterfowl and shorebirds throughout the world. These species harbor influenza viruses of all the known HA and NA subtypes (1641).

Steven J. Gamblin (GB) and John J. Skehel (GB) reported that the classification of influenza A viruses (IAVs) into subtypes is based on the genetic and antigenic properties of the surface antigens hemagglutinin antigen (HA) and neuraminidase antigen (NA), which mediate viral entry and release, respectively (505).

 

Björn A. Afzelius (SE-US) used 40% osmium tetroxide to treat preparations for the electron microscope and found that in the 9+2 pattern of the axoneme he could spot arms that reached from one outer doublet toward another. He suggested that the beating movements of eukaryotic flagella are produced by active microtubular sliding powered by arms extended from the microtubular doublets toward one another (10).

Ian R. Gibbons (US) correlated the presence of the crossing arms with the ATPase activity of the cilia (533).

Ian R. Gibbons (US) and Arthur J. Rowe (GB) subsequently named these connecting arms dynein (dynein, force protein) (536).

Ian R. Gibbons (US) and Barbara H. Gibbons (US) discovered an ATPase activity in eukaryotic flagella (532; 534).

Ian R. Gibbons (US) stated that dynein arms are ATPases responsible for generating the sliding movements between microtubules that undergo ciliary and flagellar motility with the microtubules being arranged in 9 doublets surrounding two central tubules, the so-called 9+2 arrangement (535). Dynein was the first microtubule force-producing protein motor to be described and has since been shown to be involved in intracellular trafficking as well as locomotion, including translocation of membrane-bounded vesicles in neurons, Golgi vesicles, kinetochores, and mitotic spindle astral microtubules.

Ian R. Gibbons (US), Peter Satir (US), Linda A. Amos (US), Aaron Klug (US), Carol Allen (US), Gary Guy Borisy (US), Bruce R. Telzer (US), Montrose J. Moses (US), Joel L. Rosenbaum (US), Roy R. Gould (US), Lawrence G. Bergen (US), Ryoko Kuriyama (US), Steven R. Heidemann (US), J. Richard McIntosh (US), Ursula Euteneuer (US), J. Richard McIntosh (US), Leah T. Haimo (US), Timothy J. Mitchison (US), Marc W. Kirschner (US), Conly L. Reider (US), and Stephen P. Alexander (US) built on one another’s work to discover that dynein cross-bridges linked microtubules (MTs) together and that MT polymers have polarity (534); microtubules slide past each other to give cilia their movement (1351); that polarity is reflected by both the orientation of asymmetric subunits (26) and the different rates at which the MT “plus” and “minus” ends add subunits (18); several in vitro studies revealed that MTs can be initiated from both kinetochores and centrosomes (570; 1529) and also that both kinetochore and centrosome MTs polymerize with their plus ends distal to the organizing center (118); predicted that in late anaphase, when chromatin moved to the poles, only minus ends of the centrosome MTs should be left at the midplate (646); observed that in anaphase cells, 90–95% of the MTs in a half-spindle were oriented with their plus ends toward the middle (421); found that in late anaphase, when chromatin moved to the poles, only minus ends of the centrosome MTs should be left at the midplate and showed that the majority of MTs in a meiotic half-spindle are oriented with their plus ends distal to the poles (1528). The idea that half-spindles contain parallel MTs was sealed. Later good evidence was presented that kinetochores do indeed capture and stabilize the dynamically unstable MTs growing from the asters (1081), a process that was documented in vivo (1274).

 

Annemarie Weber (DE-US), Ruth Herz (DE), Ingrid Reiss (DE), Wilhelm Hasselbach (DE), Madoka Makinose (JP), Shinpei Yamada (JP), Taibo Yamamoto (JP), and Yiji Tonomura (JP), showed that the sarcoplasmic reticulum is a vesicular membrane possessing a calcium ion, magnesium ion dependent ATPase system capable of reducing external calcium to micromolar concentrations and that, following the addition of permeate anions such as oxalate or phosphate, calcium ion precipitates can be detected within the sarcoplasmic reticulum vesicles. These observations clearly showed that calcium ion is being transported by the vesicular sarcoplasmic reticulum. Simultaneous measurements of ATP concentrations revealed that the hydrolysis of one mole of ATP results in the uptake of two moles of calcium ion. This intercellular calcium ion pump is the first known example of a cellular energy-driven counter transport mechanism. ATPase activity and the state of contraction of natural actomyosin and myofibrils are unique functions of free calcium ion concentration (626-628; 1630-1638; 1640; 1699).

 

Richard H. Kessler (US), Klaus Hierholzer (US), Ruth S. Gurd (US), Robert Franklin Pitts (US), Lawrence P. Sullivan (US), Walter S. Wilde (US), Richard L. Marvin (US), John R. Jaenike (US), and Robert William Berliner (US) demonstrated that potassium accumulates in the more distal parts of the nephron, leaving little question that this is the site of potassium secretion (744; 803; 1500).

 

Wilfrid Rall (US) created a theoretical framework for modeling electrical current flows in dendritic trees (1256; 1257).

Wilfrid Rall (US), Robert E. Burke (US), Tom G. Smith (US), Phil G. Nelson (US), Karl Frank (US), and John Rinzel (US) analyzed theoretically how synaptic potentials (and currents) spread in the dendritic tree, and how they are expected to influence the voltage response at the neuron's soma and axon attached to it. They showed that, in contrast to the accepted notion at the time, distal excitatory synapses do contribute to the depolarizing charge that reaches the cell body and that, due to filtering of high frequencies by the distributed capacitance along the dendritic membrane, the time course of the somatic excitatory postsynaptic potential (EPSP) changes as a function of input location. The more distal the synapse is, the slower the EPSP rises and the broader it is at the soma (1258; 1259; 1299).

Wilfrid Rall (US) and Gordon M. Shepherd (US) predicted that mitral and granule cells interact with each other via dendro-dendritic synapses. They also raised the possibility that dendrites may be decorated by nonlinear (excitable) ion channels (1260). This model has been tested many times and is fundamental for current concepts of processing in several neural systems, including the olfactory bulb, the retina, the olivary nucleus, etc. It is now widely known that most synaptic inputs are made on dendrites and that it is there where important plastic changes (which probably underlie learning and memory processes in the brain) take place.

 

Lewis Thomas (US) and Frank MacFarlane Burnet (AU) proposed the immunosurveillance theory, which holds that eliminating precancerous cells is one of the primary duties of patrolling lymphocytes (200; 1555; 1556). See, Paul Ehrlich, 1909.

 

Susumu Ohno (JP-US), William D. Kaplan (US), Riojun Kinosita (JP-US), and Sajiro Makino (JP) discovered that the chromatin body in cells of female mammals is a condensed heterochromatic X chromosome (1170; 1171). This suggested that the condensed X chromosome is inactive.

Mary Frances Lyon (GB) postulated that in nearly every cell of a woman’s body one or the other of her two X chromosomes is inactive. The tissues of the adult female are thus a mosaic in which about half of the cells contain an active paternal X and half contain an active maternal X. This phenomenon termed dosage compensation by X-inactivation is also called Lyonization (963-965).

Ronald G. Davidson (US), Harold M. Nitowsky (US), and Barton Childs (US) confirmed, by using gel electrophoresis, that some females had two forms of the enzyme glucose-6-phosphate dehydrogenase (G6PD), encoded by alleles on the two X chromosomes. However, when individual cells were cloned and tested, each clone now only expressed one form or the other, not both. Therefore, females clearly expressed only one G6PD gene in each cell, and the other appeared to be silenced (329).

Carolyn J. Brown (US), Andrea Ballabio (US), James L. Rupert (US), Ronald G. Lafreniere (US), Markus Grompe (US), Rossana Tonlorenzi (US), and Huntington F. Willard (US) discovered that the Xist gene is only expressed from the inactive human X chromosome, so it presumably acts in cis on the chromosome that produces the Xist RNA (179).

Neil Brockdorff (GB), Alan Ashworth (GB), Graham F. Kay (AU), Penny J. Cooper (GB), Sandy Smith (GB), Veronica M. McCabe (GB), Dominic P. Norris (GB), Graeme D. Penny (GB), Dipika Patel (GB), Sohaila Rastan (AU), Sally Swift (GB), and Steven A. Sheardown (GB) found the same for Xist in the mouse, and went on to identify the 15 kb untranslated nuclear transcript that is conserved in sequence and structure between mice and humans. The targeted knockout of Xist in XX mouse embryonic stem (ES) cells showed conclusively that the gene is essential for X-inactivation (176; 177; 793; 1211).

In eutherian mammals, X-inactivation is random, but in marsupials, imprinting ensures that the paternal X is preferentially inactivated. The same also happens in extra-embryonic tissues of eutherian mammals, and probably in pre-implantation mouse embryos too. A chromosome-counting mechanism seems to allow inactivation of all but one X chromosome during development.

Jeannie T. Lee (US) studied transgenic embryonic stem (ES) cells and embryos harboring deletions of sequences in the antisense strand of the DNA. She found that Xist is regulated by its 40 kb antisense partner, Tsix, which codes for another cis-acting untranslated RNA. It now seems that both the imprinting and counting mechanisms control Xist through Tsix, thereby ensuring that only one X chromosome will remain active in the cells (891).

 

Sydney Brenner (ZA-GB), George Streisinger (HU-US), Robert W. Horne (GB), Sewell P. Champe (US), Leslie Barnett (GB), Seymour Benzer (US), and M.W. Rees (GB) studied the structure of the T2 bacteriophage and found that the tail consists of a sheath surrounding a core at the base of which are attached tail fibers. The sheath appears to be built of helically arranged subunits, which form a hollow cylinder. The sheath can contract in length. The core of the tail is hollow with a 25-angstrom opening. The sheath is composed of about 200 repeated subunits each of approximately 50,000 molecular weight. The head covering is composed of many repeated subunits each with a molecular weight of 80,000. The tail fibers appear to have a subunit with a molecular weight not less than 100,000. The head, sheath, and tail fibers are all composed of proteins, which have different primary structures (173).

 

Robert Louis Sinsheimer (US) and Walter Charles Cornelius Fiers (BE)) were able to show that phi-X174, a bacteriophage of Escherichia coli, is a small tailless polyhedron only 250 Å in diameter, and hence of a volume about 1/40 that of the T-even phage head. It contains a single DNA molecule made up of 5000 nucleotides. But most importantly Sinsheimer discovered that the DNA is single stranded and circular. The single stranded viral DNA uses one of the host’s enzymes to convert itself into a double stranded replicative form (438; 1427).

 

Renato Dulbecco (IT-US), Gustave Freeman (US), and Marguerite Vogt (DE-US) described the morphological features of cells infected by polyoma virus in vitro. They noted that the virus can induce a cancer-like state in some cell lines (non-permissive) even though it does not replicate, while in other cell lines it can replicate causing no cancer-like condition (permissive) (377; 1600-1602).

 

John J. Holland (US), Leroy C. McLaren (US), and Jerome T. Syverton (US) found that the restriction of poliovirus to primates and the insusceptibility of non-primates to this infection are due to the presence of specific poliovirus receptors on the host cells. They also observed that poliovirus RNA alone is infectious over a much broader host range (692; 693).

 

Anne Gemmell (GB) and Hugh John Forster Cairns (GB-US-GB) were the first to demonstrate gene linkage in an animal virus (516).

 

Irwin Tessman (US) demonstrated that some naturally occurring viral genomes are composed of single stranded DNA (1547).

 

Samuel L. Katz (US), John Franklin Enders (US), Sidney Kilbrick (US), Milan V. Milovanovic (CS), and Ann Hollowqy (US) produced a live attenuated measles (rubeola) vaccine (411; 787; 788). Note: In the decade before 1963 when a vaccine became available, nearly all children got measles by the time they were 15 years of age. It is estimated 3 to 4 million people in the United States were infected each year. Also, each year an estimated 400 to 500 people died, 48,000 were hospitalized, and 4,000 suffered encephalitis (swelling of the brain) from measles.

 

Carl Lamanna (US) reported that Clostridium botulinum produces the most poisonous toxins known (865).

 

Nirmal Kumar Dutta (IN), Madhusudan V. Panse (IN-US), D.R. Kulkarni (IN), and Sambhu Nath De (IN) implicated a toxin in the etiology of cholera (337; 382).

 

Norman Strauss (US) and Edelmira D. Hendee (US) demonstrated that diphtheria toxin completely blocks amino acid incorporation by cultured human cells. It was found that the toxin inhibits polypeptide chain elongation (1493).

 

Zanvil Alexander Cohn (US), F. Marilyn Bozeman (US), Janis M. Campbell (US), James W. Humphries (US), and Thomas K. Sawyer (US) concluded that the penetration of host cells by Rickettsia tsutsugamuchi requires the active participation of both the bacterium and its host cell (288).

 

Richard L. Riley (US), Cretyl C. Mills (US), Walenty Nyka (US), N. Weinstock (US), Patrick B. Storey (US), Louise U. Sultan (US), Mary Catesby Riley (US), and William F. Wells (US) proved that even small numbers of tubercle bacilli can account for the spread of human tuberculosis by aerosol and that patients with the highest counts of tubercle bacilli in their sputa are the most infectious ones (1296; 1297).

 

Hisakichi Matsubayashi (JP), Tamotsu Kioke (JP), Ittaku Mikata (JP), Hiroshi Takei (JP), Setsuo Hagiwara (JP) reported the first authenticated record of a microsporidian infection in humans—an Encephalitozoon sp. in a boy with convulsions (1020).

The microsporidia constitute a phylum (Microspora) of spore-forming unicellular parasites. They were once thought to be protists but are now known to be fungi. Microsporidian infections of humans sometimes cause a disease called microsporidiosis. At least 14 microsporidian species, spread across eight genera, have been recognized as human pathogens. These include Trachipleistophora hominis. The rise in microsporidiosis is associated with the arrival and spread of HIV; microsporidiasis is primarily found in patients with AIDS or are otherwise immuno-compromised (like organ transplant patients). However, at least three species of Nosema and one of Brachiola have been documented in immuno-competent patients. Microsporidia are considered casual, accidental or opportunistic agents in humans. The transmission of microsporidia is still unclear, but the most common way is thought to involve inhaling, ingesting or otherwise contracting spores (for example ocular or sexually transmitted).

 

Harry Eagle (US) announced two generalizations about the requirements of mammalian cell lines propagated in vitro. With few exceptions both normal and malignant cells have the same nutritional requirements and differentiation disappears quickly (384). Read article to verify

 

Waclaw Szybalski (PL-US), M. Joan Smith (US), Elizabeth H. Szybalski (US), R. Wallace Brockman (US), and Giorgio Ragni (IT) were the first to mount a systematic search for mutants among cell lines propagated in vitro (1505-1508).

 

David A. Hungerford (US), Andrew J. Donnelly (US), Peter C. Nowell (US) and Sidney Beck (US) described a human individual of outwardly male appearance, clinically diagnosed a ‘true hermaphrodite.’ This intersex was found to have an XX sex chromosome complement. The first full description appears here of their adaptation to cytogenetic use of a method for culturing human leukocytes (723).

 

Harold B. Hewitt (GB) and Charles W. Wilson (GB) were the first to obtain survival curves for mammalian cells irradiated in vivo (667; 668).

 

Howard Green (US), R.A. Fleischer (US), Paul Barrow (US), and Burton Goldberg (US) supplied the first clear evidence that serum complement produces functional holes in cell membranes rather than membrane ruptures (581).

 

Anthony G. Searle (GB) reported a dominant mutant on chromosome 1 of mice, Dominant hemimelia (Dh) which causes the animals to be congenitally asplenic (1386).

 

Henry Quastler (US) and Frederick G. Sherman (US) analyzed data obtained from autoradiographs of mouse intestinal epithelial cells labeled with tritiated thymidine. This led to a description of the kinetics of cell proliferation. The precise localization of the exposed emulsion allows cells synthesizing DNA to be identified, estimates to be made of the average time cells remain in the various compartments, the number of cells per compartment, and the number of cells per unit time in transit from one compartment to another. Additionally, it was found that for the transition from a proliferative to a 'functional' cell to occur, the cell must not only be in a certain neighborhood, but it must also be in a certain phase of its generative cycle (1248).

 

Georges Schaltenbrand (DE) and Percival Bailey (US) produced a stereotactic atlas of the human brain that became an instant classic because of the caliber and accuracy of the photographs of the brain (1357).

 

Brian F. Hoffman (US), Paul F. Cranefield (US), Jackson H. Stuckey (US), Norman S. Amer (US), Richard R. Cappelletti (US), and Rodolfo T. Domingo (US) made the first recordings of electrical activity of the atrioventricular bundle in humans (686; 1499). Dr. Hoffman and his colleagues identified the cellular electrophysiologic basis for the actions of digitalis, catecholamine, and antiarrhythmic drugs.

 

David Hunter Hubel (CA-US) and Torsten Niels Wiesel (SE-US) made recordings from single cells in the striate cortex of lightly anaesthetized cats. The retinas were stimulated separately or simultaneously with light spots of various sizes and shapes. Effective driving of a unit required a stimulus specific in form, size, position and orientation, based on the arrangement of excitatory and inhibitory regions within receptive fields. Restricted retinal areas that on illumination influenced the firing of single cortical units were called receptive fields (714).

Robert H. Wurtz (US) described the technique of recording the activity of single neurons in the visual system of the conscious monkey, and this study replicated Hubel and Wiesel's finding in the anesthetized monkey of cells with motion selectivity and orientation selectivity. The second paper showed that this system could be used to answer a cognitive question: could neurons in the striate cortex distinguish, as do normal humans, between the motion across the retina of stimulus moving in the world and the motion across the retina induced by the eye's moving across a stimulus stable in the world. The answer was no (1695; 1696).

David Hunter Hubel (CA-US) and Torsten Niels Wiesel (SE-US) provided the first clue to how the brain circuits represent the shape of a given object, by demonstrating that neurons in the primary visual cortex are selectively tuned to respond to the edges oriented in various angles (716; 718).

David Hunter Hubel (CA-US) and Torsten Niels Wiesel (SE-US) concluded that the long narrow stripes of alternating left-eye and right- eye input to layer IV are an anatomical counterpart of the physiologically observed ocular dominance columns. Because of this segregation of inputs, cells of layer IV are almost invariably influenced by one eye only. A cell above or below layer IV will be dominated by the eye supplying the nearest IVth layer stripe, but will generally, though not always, receive a subsidiary input from the other eye, presumably by diagonal connections from the nearest stripes supplied by that eye (717).

David Hunter Hubel (CA-US), Torsten Niels Wiesel (SE-US), and Simon LeVay (US) identified in neonatal animals a critical period during which deprivation of visual stimulation may induce permanent blindness. The length and timing of critical periods differ among species, which suggests that throughout the brain each functional unit has a unique program of development. This type of blindness is associated with changes in the functional architecture in layer IVc of the brain’s striate cortex (713; 719).

David Hunter Hubel (CA-US) and Margaret S. Livingstone (US) showed that some neurons in the brain’s primary visual cortex respond selectively to color but not shape (930).

 

Ashton Graybiel (US), Robert H. Holmes (US), Dietrich E. Beischer (US), Gerald E. Champlin (US), George P. Pedigo (US), W. Carroll Hixon (US), Thomas R.A. Davis (US), Norman L. Barr (US), Wallace G. Kistler (US), Jorma I. Niven (US), Edward Wilbarger (US), Donald E. Stullken (US), William S. Augerson (US), Robert Clark (US), and James H. Berrian (US) gave an account of experiments in which two monkeys were recovered unharmed after ballistic space flight (579).

 

Crawford Stanley Holling (CA) distinguished two levels of predation: (1) the behavioral acts performed by an individual predator searching for and consuming prey; and (2) the population processes of mortality and fecundity influencing the growth of predator and prey populations. He quantified both the behavioral and population components in terms of the number of individual prey killed as a function of prey density (698).

 

William Henry Hildemann (US), William D. Linscott (US), M.J. Morlino (), James Learmonth Gowans (GB), Douglas D. McGregor (US), and Paul Ichiro Terasaki (US) discovered that in both mammals and birds normal peripheral blood contains immunologically competent cells in its leukocyte moiety and from among them it is the small lymphocyte which initiates the graft versus host reaction (575; 671; 1544).

 

Eugene Raymond Hall (US) and Keith R. Kelson (US) issued their big systematic Mammals of North America with keys for identification, descriptions, measurements, and 500 distributional maps (605).

 

Charles Edmund Ford (GB), Ken W. Jones (GB), Paul Emanuel Polani (GB), J. Carlos de Almeida (GB), Joseph H. Briggs (GB), Patricia Ann Jacobs (GB), John A. Strong (GB), William L. Russell (US), Liane Brauch Russell (AT-US), Josephine S. Gower (US), and Bruce M. Cattanach (US) deduced the existence of male determinants on the Y chromosome in both mice and humans (244; 459; 743; 1337).

 

Kendall Brooks Corbin (US) introduced artane, or benzhexol, for treatment of Parkinson disease (297).

 

Robert Schwartz (US) and William Dameshek (US) prevented rabbits from producing antibody against human serum albumin by treating them for two weeks with the antimetabolite, 6-mercaptopurine. This "drug-induced tolerance" remained after drug treatment was stopped, even though the animals could react normally against another protein antigen, bovine gamma globulin. Thus, the tolerance seemed to be specific for an antigen introduced at the time of drug administration (1377).

William R. Meeker, Jr. (US), Richard M. Condie (US), Daniel Weiner (US), Richard L. Varco (US), Robert Alan Good (US), Robert Schwartz (US), and William Dameshek (US) demonstrated a 6-mercaptopurine dose-related prolongation of rabbit skin allograft survival rate (1041; 1378).

Roy Y. Calne (GB), Charles F. Zukoski (US), Hyung M. Lee (GB), and David M. Hume (US) obtained very similar results with canine renal homografts (216; 1719).

Gertrude Belle Elion (US). Sandra W. Callahan (US), George Herbert Hitchings (US), and R. Wayne Rundles (US) synthesized azatioprine, an analog of 6-mercaptopurine, to use in chemotherapy (397).

Roy Y. Calne (GB) carried out extensive preclinical studies in dogs on the efficacy of using 6-mercaptopurine and its analogue azathioprine as immunosuppressive agents in transplantation surgery. He successfully delayed kidney rejection in dogs from the usual ten days to forty-four days (217).

 

Roger Michael Hardisty (GB) and Joel Margolis (PL-AU) suggested activation of plasma thromboplastin antecedent (PTA) by activated Hageman factor (617).

Oscar Davis Ratnoff (US), Earl Warren Davie (US), and David L. Mallett (US) provided clear evidence for the activation of plasma thromboplastin antecedent (PTA) by activated Hageman factor (1269).

Jean-Pierre Soulier (FR), Odette Prou-Wartelle (FR), and Doris Menache (FR) suggested that activated plasma thromboplastin antecedent (PTA) activates Christmas factor (1449).

Oscar Davis Ratnoff (US) and Earl Warren Davie (US) proved the activation of Christmas factor by activated plasma thromboplastin antecedent (PTA) (1268).

 

Hilda Margaret Bruce (GB) found that if she housed newly mated pregnant females with male mice that were not the father of the carried embryo the rate of miscarriages increased, these females subsequently returning to estrus and mating with the new male. No increased rate of miscarriages occurred when pregnant mice were paired with juvenile or castrated mice (183; 184). This is referred to as the Bruce effect.

 

Andrzej Krzysztof Tarkowski (PL) showed that a single blastomere isolated from a 2-cell stage mouse embryo is fully able to develop and the result is a healthy and fertile mouse

 

Oliver Murray Wrong (GB) and Howard E.F. Davies (GB) described the urinary response to an acid load, taken as a single oral dose of ammonium chloride. Study of normal subjects and patients with different forms of kidney disease distinguished the factors influencing urinary acidification and ammonium excretion (1687).

 

Charles S. Lieber (US), Leonora M. DeCarli (US) and Rudi Schmid (US) documented two new fundamental concepts: (1) Ethanol exerts direct effects on the liver which might play a role in the development of liver disease. (2) Some of these effects on the liver could be traced to the metabolism of ethanol (918; 920).

Charles S. Lieber (US), Don P. Jones (US), and Leonora M. Carli (US) established in vivo: with the development of a new alcohol feeding technique as part of a nutritionally adequate, totally liquid diet, rats were shown to develop a fatty liver—the first stage of alcoholic liver disease—in the absence of dietary deficiencies. This was later confirmed in man (919).

Charles S. Lieber (US), Leonora M. DeCarli (US), and Emanuel Rubin (US) noted, the final and irreversible stage of liver disease, namely cirrhosis, was produced in the baboon despite adequate diets (917).

Charles S. Lieber (US) showed the link between ethanol effects and its metabolism, led to the demonstration that alcoholic hyperuricemia, ketosis, hypoglycemia, and various other metabolic complications can be ultimately attributed to such a mechanism. Extension of this concept prompted studies concerning the hepatotoxicity of acetaldehyde. Further investigation of the metabolism of ethanol resulted in the discovery of an alternate pathway in the microsomes associated with activation and inactivation of drugs, hepatotoxic agents, carcinogens, and endogenous steroids (916).

 

Alan J. Johnson (US) and W. Ross McCarty (US) were the first to report that artificially induced thrombi in human volunteers could be lysed by infusion of purified streptokinase (SK) preparation (752).

Inga Marie Nilsson (SE) and Bertil Olow (SE) administered various doses of streptokinase (SK), SK plus plasminogen, and SK plus E-amino caproic acid (EACA) in a series of 67 surgical patients. SK produced a high fibrinolytic activity but had a significant effect on the coagulation factors. It proved possible to counteract the coagulation defect by SK combined with EACA without affecting the lysis of the clot (1135; 1184).

 

Henri-Géry Hers (BE) first identified hepatic phosphorylase deficiency (Hers disease) when he saw three patients presenting with hepatomegaly and glycogen storage in the liver (658).

 

Paul E. Teschan (US), Thomas F. O’Brien (US), and Charles R. Baxter (US) introduced “prophylactic daily dialysis” for the treatment of acute renal failure. Blood cloting was very common (1546).

Wayne Quinton (US), David Dillard (US), Belding Hibbard Scribner (US), Rachit Buri (US), John E.Z. Caner (US), Robert M. Hegstrom (US), and James M. Burnell (US) developed dialysis arterioveneous cannulas using teflon tubing. For the first time, blood flow could be keep open for days allowing continuous dialysis (1249; 1385). Note: Improvements to the technique came rapidly and by 1962 the world’s first freestanding dialysis center was opened in Seattle, Washington.

S.T. Boen (NL), Adyr Soares Mulinari (BR), David H. Dillard (US) and Belding Hibbard Scribner (US) published on Boen’s concept for peritoneal dialysis (150).

 

M. Henry Cass (GB) and Russell C. Brock (GB) described the standard current practice of combining the multiple pulmonary venous and venacaval anastomoses into two large atrial anastomoses during the replacement of the heart in dogs. No dogs survived this operation (243).

Richard R. Lower (US) and Norman E. Shumway (US) independently developed the same procedure but preserved allografts with immersion hypothermia. The dogs survived (940).

Norman E. Schumway (US), Richard R. Lower (US), Raymond C. Stofer (US), Edward J. Hurley (US), and Eugene Dong, Jr. (US) begin a long series of experiments in animal heart transplantation (940-943; 1414).

Richard R. Lower (US), Raymond C. Stofer (US), and Norman E. Shumway (US) conceptualized and refined the atrial cuff technique of orthotopic heart transplantation in dogs. This innovation enabled the transplanted heart to adequately support the circulation and allowed the recipient dogs to survive and exercise normally for up to three weeks (943). Tissue rejection was a serious problem at this time.

Richard R. Lower (US), Raymond C. Stofer (US), Edward J. Hurley (US), and Norman E. Shumway (US) completed technically successful canine heart-lung transplantation in nonimmunosuppressed dogs with 5-day survival (942). With long survival the same operation was done under cyclosporine two decades later, first in monkeys then in man.

Richard R. Lower (US), Raymond C. Stofer (US), Edward J. Hurley (US), Eugene Dong, Jr. (US), Roy B. Cohn (US), and Norman E. Shumway (US) discovered that dog hearts intended as allografts can be preserved for 7 hours by immersion at 2°to 4C° (939; 941).

Bruce A. Reitz (US), John L. Pennock (US), and Norman E. Shumway (US) reported successful heart-lung transplantation in humans (1279).

 

Basil M. Wright (GB) and Colin B. McKerrow (GB) introduced the peak flow meter to measure maximum forced expiratory flow rate (1686). This is especially helpful in diagnosis of pneumoconiosis, i.e., lung damage due to inhalation of minute particles.

 

Henry L. Price (US), Harry W. Linde (US), Richard E. Jones (US), Gerald W. Black (US), and Mary L. Price (US), following the development of a sensitive, highly specific method for detecting catecholamines determined, for the first time, whether certain general anesthetics caused sympathetic nervous excitation in man. They found that diethyl ether and cyclopropane did so, thus explaining the great safety of these anesthetic agents, since their directly depressant actions on myocardium are partially antagonized by sympathetic stimulation (1240).

 

Norman Orentreich (US) performed autograft hair transplant surgery to remedy hair loss (alopecias) (1185).

 

Francis Daniels Moore (US), Louis L. Smith (US), Thomas K. Burnap (US), Frederick D. Dallenbach (DE), Gustave J. Dammin (US), Ulrich F. Gruber (CH), William C. Shoemaker (US), Richard W. Steenburg (US), Margaret R. Ball (US), and John S. Belko (US) developed the surgical technique for orthotopic canine liver transplantation (1092).

Thomas Earl Starzl (US), Carl G. Groth (US), Lawrence Larry Brettschneider (US), Israel Penn (US), Vincent A. Fulginiti (US), John B. Moon (US), Herve Blanchard (US), Alfred J. Martin, Jr. (US), Ernest K. Cotton (US), and Kendrick Arthur Porter (US) gave the first report of prolonged survival rates of children after orthotopic liver transplantation (1464; 1465).

 

Orrie A. Couch, Jr. (US) reported the first successful surgical treatment of ventricular tachycardia, when he resected a ventricular aneurysm in a male patient with anterior wall/apex aneurysm (302).

 

Colonel R. Montgomery (GB), Robin D. Powell (US), George J. Brewer (US), Alf S. Alving (US), Joseph S. Lunn (US), G. Robert Coatney (US), Don Edgar Eyles (US), C.C. Hoo (MY), McWilson Warren (US), Arthur Anamthara Sandosham (MY), Martin D. Young (US), Peter G. Contacos (US), Joseph E. Stitcher (US), Jack W. Millar (US), Edith D. Box (US), Quellin T. Box (US), and David Payne (CH) reported chloroquine resistance in Plasmodium falciparum and Plasmodium vivax, the 2 parasite species responsible for most human malaria cases. Foci of resistant P. falciparum were detected in Malaya, Colombia, the Cambodia-Thailand border, and Porto Velho, Brazil during the late 1950s (161; 295; 424; 1088; 1089; 1208; 1235; 1346; 1708).

 

Victor Bruce Darlington Skerman (AU) composed keys for the identification of bacteria and wrote A Guide to the Identification of the Genera of Bacteria (1432).

 

Bengt E. Gustafsson (SE) found that germ-free rats fed a diet without vitamin K rapidly become hemorrhagic and required their diet to be supplemented with vitamin B to survive. Germ-free rats require a higher intake of exogenous sources of vitamins K, B12 and B6 compared to their conventional counterparts. Microbial communities are in direct and continuous contact with their host from birth, contributing to host nutrition and metabolism through vitamin production (594).

Denise Kelly (GB), Timothy King (GB), Rustam Aminov (GB), Silvia C. Resta (US), Dan R. Littman (US), and Eric G. Pamer (US) showed that gut bacteria play a pivotal role in immune modulation and development of the nervous system and are the main source of vitamin K, and to a lesser extent the vitamin B complex (796; 929; 1280).

 

Meyer Friedman (US) and Ray H. Rosenman (US) used three groups of men, selected solely according to the behavior pattern which they habitually manifested in their work, were compared with respect to their serum cholesterol levels, clotting times, presence of clinical coronary disease, and presence of arcus senilis. A group (A) of 83 men were chosen as manifesting an intense, sustained drive for achievement and as being continually involved in competition and deadlines, both at work and in their avocations. In this group the serum cholesterol level, the frequency of arcus senilis, and the incidence of coronary artery disease were much higher than in a group (B) of 83 men who manifested the opposite sort of behavior pattern and a group (C) of 46 unemployed blind men selected as manifesting a chronic state of insecurity and anxiety. Clinical coronary artery disease was seven times more frequent in group A than in group B or group C. Analysis of factors other than the overt behavior pattern described indicated that this pattern per se was largely responsible for the striking differences found (491).

 

Morton H. Maxwell (US), Robert E. Rockney (US), Charles R. Kleeman (US), and Mary R. Twiss (US), reported that complications of earlier methods of peritoneal dialysis are eliminated by a new technique of intermittent dialysis utilizing commercially prepared electrolyte solutions, special catheters, and a "closed system" of infusion and drainage. This was mechanically successful in 76 instances. Conditions treated satisfactorily included acute renal failure, barbiturate poisoning, intractable edema, hepatic coma, hypercalcemia, and chronic uremia. Although less efficient than the artificial kidney on an hourly basis, peritoneal lavage is easier to use over extended periods of time (1027).

 

Eugene F. Poutasse (US) developed renal arteriography. He discovered that in many patients with renal hypertension the condition can be corrected by removing the obstruction, grafting a new vessel, or removing the part of the kidney supplied by the diseased artery (1234).

 

Seymour Solomon Kety (US) used adoption as a means of separating environmental and genetic factors in the transmission of schizophrenia among family members. He concluded that about 50% of schizophrenia is of genetic origin, and the mode of inheritance polygenic (804).

 

Maxwell Finland (US), Wilfred F. Jones, Jr. (US), and Mildred W. Barnes (US) highlighted that the introduction and widespread use of chemotherapeutic and antibiotic agents has resulted in profound changes in the number and character of infections that are being encountered. Emphasis has been placed most recently on the number and seriousness of staphylococcic infections, particularly those occurring within hospitals. This has been brought strikingly into our consciousness because of the large number of outbreaks in nurseries and maternity wards and by the high incidence of infections in originally clean surgical wounds and as complications of debilitating diseases, events which have resulted in considerable morbidity and appreciable mortality within hospitals. There is also some evidence of extension of these infections into the communities. The problem has been recognized as being world-wide and extending to all areas where antibiotics have been extensively used (439).

 

Samuel Noah Kramer (US) reported that Sumerian cuneiform tablets list various drugs to be used in the treatment of common ailments, c. 5,500 BCE (846).

 

Mary Douglas Nicol Leakey (GB-KE) found a hominid skull belonging to the ultra-robust Australopithecus boisei: Paranthropus boisei: Zinjanthropus boisei at Olduvai Gorge, Tanzania (881). Australopithecus boisei: Paranthropus boisei: Zinjanthropus boisei existed between 2.1 and 1.1 million years ago. It is like robustus, but the face and cheek teeth are even more massive, some molars being up to 2 cm across. The brain size is very similar to robustus, about 530 cc. A few experts consider boisei and robustus to be variants of the same species.

 

The journal Biochemical and Biophysical Research Communications was founded.

 

1960

"By their diseases ye shall know them - the endocrines." James H. Means (1038).

 

"Gamble did more than anyone to bring the various ideas of the behavior of body water and electrolytes into a coherent picture. He was responsible for many of the fundamental concepts. His way of looking at extracellular fluids was his great contribution and provides the basis for modern fluid therapy." Daniel C. Darrow (US) commenting on the work of James L. Gamble (US) (326).

 

Willard Frank Libby (US) was awarded the Nobel Prize in Chemistry for his method to use carbon-14 for age determination in archaeology, geology, geophysics, and other branches of science.

 

Frank Macfarlane Burnet (AU) and Peter Brian Medawar (GB) were awarded the Nobel Prize in Physiology or Medicine for discovery of acquired immunological tolerance.

 

Theodore H. Maiman (US) built the first practical laser, a device that produces monochromatic coherent light, or light in which the rays are all of the same wavelength and phase (981). His invention relied on theoretical work by Charles Hard Townes (US) and Arthur Leonard Schawlow (US) (1360). The term laser (Light Amplification by Stimulated Emission of Radiation) was coined for the device.

 

Irving Friedman (US) and Robert L. Smith (US) described obsidian hydration as a new method for dating obsidian artifacts (490). The relative and occasionally absolute dates ascribed to obsidian artifacts are possible because obsidian "sorbs" moisture from the atmosphere. This method is most accurate for objects between 500 and 200,000 years old.

 

Alan B. Cameron (US), and Raymond J. Thabet (US) introduced the sigmoidoscope as part of routine cancer clinic examinations. This permitted early identification of colorectal cancer as well as precancerous polyps, leading to increased survival rates (218).

Iris Lansdrop-Vogelaar (NL), Marjolein van Ballegooijen (NL), Deborah Schrag (NL), Rob Boer (NL), Sidney J. Winawer (NL), J. Dik F. Habbema (NL), and Ann G. Zauber (NL) noted that today, it is estimated that screening, by sigmoidoscopy, colonoscopy, barium enema, or fecal occult blood testing, may result in a 20% decrease in colorectal cancer mortality (874).

 

George A. Bray (US) offered a modification of the naphthalene-dioxane system for counting radioactive compounds in aqueous solutions using a liquid scintillation counter that has a relatively high efficiency for both carbon-14 and tritium. The modification of the naphthalene-dioxane procedure has been used to count glycolytic intermediates on paper chromatograms. It has also been used to determine radioactive glucose incorporation into glycogen by counting the acid hydrolyzate of the isolated glycogen (164).

 

John Oró (US), E. Stephen-Sherwood (US), and Aubrey P. Kimball (US) synthesized adenine, thymine, amino acids, and other biochemical compounds from HCN in a primitive Earth environment (1189; 1191; 1475).

 

Emil Palecek (CZ) discovered the electroactivity of nucleic acids (1196).

 

Karl A. Piez (US) and Louise Morris (US) modified the Sparkman, Moore, and Stein procedure for amino acid analysis by using a continuous salt and pH gradient for elution and separation on a single column of all the amino acids in protein hydrolysates, including hydroxyproline and hydroxylysine (1218).

 

W. Gordon Whaley (US), Hilton H. Mollenhauer (US), and James H. Leech (US) gave the first demonstration of a substantial number of organelles in the plant cell and thus a closer equation of the plant cell and the animal cell. They depicted plant systems in which progressive stages of differentiation could be followed (1654).

 

David M. Neville, Jr. (US) described a procedure for isolating cell membranes from rat liver homogenates (1129).

 

Leslie G. Paleg (AU) established the basis of a new understanding of the relationship between the cereal embryo and endosperm. It gave the first indication of a hormonal effect on enzyme activity in plants, and suggested a very sensitive, short, and reliable hormonal bioassay (1197).

 

David L. Trout (US), E. Harvey Estes, Jr. (US), and Samuel J. Friedberg (US) identified substances that interfere with Dole’s titrimetric method for measuring plasma free fatty acids and added a step to remove them from the fatty acid extract (1576).

 

Jules Hirsch (US) described a simple method for the analysis of the fatty acid composition of stored fat in man. The composition is a close reflection of mean dietary fat composition over years, and changes slowly in relation to dietary changes (675).

 

Beginning in the 1960's the National Aeronautics and Space Administration (NASA) has directly or indirectly provided numerous contributions to medicine. Examples are digital imaging breast biopsy system, breast cancer detection using solar cells, laser angioplasty, ultrasound skin damage assessment, human tissue stimulator, cool suit, programmable pacemaker, ocular screening, automated urinalysis, medical gas analyzer, voice-controlled wheelchair, arteriosclerosis detection, ultrasound scanners, automatic insulin pump, portable x-ray device, invisible braces, dental arch wire, palate surgery technology, clean room apparel, implantable heart aid, magnetic resonance imaging (MRI), bone analyzer, and cataract surgery tools.

 

Joseph D. Mandell (US) and Alfred Day Hershey (US) developed a fractionating column which could separate closely similar nucleic acids, e.g. those derived from T2 and T4 bacteriophages of E. coli; deoxyribonucleic acid broken by hydrodynamic shear from its starting material (990).

 

Mary Ellen Jones (US) and Leonard Spector (US) established that carbon dioxide or bicarbonate is the source for the initial activation step leading to carbamyl phosphate formation by carbamyl-phosphate synthetase in animal tissues. They showed that oxygen was added to the orthophosphate residue of carbamyl phosphate via equilibration of water with bicarbonate (757).

 

Maria A. Rongine DeFekete (AR), Luis Federico Leloir (AR), and Carlos Eugenio Cardini (AR) discovered the role of sugar nucleotides in the synthesis of starch (341).

 

Robert Burns Woodward (US), William A. Ayer (US), John M. Beaton (US), Friedrich Bickelhaupt (NL), Raymond Bonnet (GB), Paul Buchschacher (US), Gerhard L. Closs (DE-US), Hans Dutler (CH), John Hannah (US), Fred P. Hauck (US), Sho Ito (JP), Albert Langemann (US), Eugene LeGoff (US), Willy Leimgruber (US), Walter Lwowski (DE-US), Jürgen Sauer (DE), Zdenek Valenta (CZ) and Heinrich Volz (DE) reported the total in vitro synthesis of chlorophyll a. In the process the authors discovered the remarkable susceptibility of chlorophyll to electrophilic attack (1684).

Martin Strell (DE), Anton Kalojanoff (DE), and Hugo Koller (DE) independently carried out the total synthesis of chlorophyll a (1495).

 

Sakae Katoh (JP) discovered plastocyanin, a small copper containing protein which functions as an electron transfer agent between cytochrome f of the cytochrome b6f complex of photosystem 2 and P700+ from photosystem 1 (784). He and Atusi Takamiya (JP) worked on the photo-reduction (Hill reaction) of this substance and its effect on the photo-reduction of other known Hill reagents (785).

Peter M. Colman (AU), Hans C. Freeman (AU), J. Mitchell Guss (AU), Mitsuo Murata (), Valerie A. Norris (AU), John A.M. Ramshaw (AU), Madhugiri P. Venkatappa (IN) used x-ray crystal analysis at 2.7 angstrom resolution to determine the 3-dimensional structure of oxidized [Cu (II)] plastocyanin from poplar leaves (290).

 

Earl B. Herr, Jr. (US), Michael E. Haney, Jr. (US), Gail E. Pittenger (US), and Calvin E. Higgins (US) isolated the antibiotic capreomycin from Streptomyces capreolus (657).

 

Maynard E. Pullman (US), Harvey S. Penefsky (US), Anima Datta (IN), and Efraim Racker (PL-AT-US) were the first to identify an enzyme of oxidative phosphorylation, the Factor 1 or F1 portion of the ATP synthase unit from mitochondria (1210; 1247).

 

Helmut Beinert (DE-US) and Richard H. Sands (US) used paramagnetic resonance spectrometry (EPR) to discover the class of cellular electron carriers called iron-sulfur centers (110). These centers are involved in the transfer of reducing equivalents from the flavin to ubiquinone.

 

Maxine Frank Singer (US), Russell J. Hilmoe (US), and Leon A. Heppel (US) showed that short oligonucleotides could serve as primers for polynucleotide phosphorylase (PNPase). Specifically, they found that oligoribonucleotides with an unesterified, terminal, C-3' hydroxyl group served as primers for the polymerization of adenosine 5'- diphosphate, uridine 5'-diphosphate, and thymine ribonucleoside pyrophosphate catalyzed by polynucleotide phosphorylase. The oligonucleotides were starting points for chain proliferation but were not incorporated into the finished polymer (1423).

Maxine Frank Singer (US), Russell J. Hilmoe (US), and Leon A. Heppel (US) discuss the polymerization of guanosine diphosphate by PNPase. They showed that GDP, when present alone, is not polymerized by enzyme fractions from Agrobacterium agile or Escherichia coli. However, polymerization of GDP did take place in the presence of oligonucleotide primers with an unsubstituted hydroxyl group at carbon 3' of the terminal nucleoside residue. Unlike polymerization reactions with adenosine 5'-diphosphate, uridine 5' diphosphate, and thymine ribonucleoside pyrophosphate, the primers were incorporated into the polymer (1424).

 

George R. Stark (US), William Howard Stein (US), and Stanford Moore (US) discovered that cyanate, formed from urea, can carbamylate the amino groups of proteins (1462).

 

Kimiko Sato-Asano (JP) and Fujio Egami (JP) discovered takadiastase ribonuclease T1, an enzyme that cleaves RNA chains at guanylic acid (G-) residues (1352).

 

Torkel Weis-Fogh (DK-GB) describes resilin. He explains its roles in the thorax of flying insects: as elastic tendons in dragonflies and as elastic wing hinges in locusts. He also shows that these structures could be strained for weeks without plastic deformation and, by simple tests, that the elasticity was rubber-like. This contrasted with commercial rubbers, which are polymeric unsaturated hydrocarbons: resilin is a cuticular protein that, typically, is deposited after ecdysis. Weis-Fogh notes the ability of resilin structures to snap back after deformation but shows that their rubbery nature is affected by their hydration and pH. He describes a simple test to identify resilin: with very dilute solutions of methylene Blue or toluidine Blue, the protein stains a deep sapphire blue (1646).

 

John Bishop (US), John Leahy (US), Richard S. Schweet (US), and Howard M. Dintzes (US) demonstrated that proteins grow by stepwise addition of individual amino acids beginning at the amino terminal end and growing toward the carboxyl end (140; 350).

 

Esther A. Allen (US), Edward Glassman (US), Eugene Cordes (US) and Richard S. Schweet (US) were the first to refer to soluble RNA (sRNA) as transfer RNA (tRNA) (19).

 

Alexander Rich (US) showed that RNA and DNA can accommodate one another to form a hybrid helix containing one strand of poly dT and one strand of poly rA. This was the first experimental demonstration of a hybrid helix (1284). This immediately provided experimental support for a model of how DNA could “make” RNA.

John J. Furth (US), Jerard Hurwitz (US), and Monika Goldmann (US) demonstrated that the formation of a DNA-RNA hybrid is critical to the transfer of information from DNA to RNA (499).

 

Charles Yanofsky (US) and Patricia St. Lawrence (US) suggested that certain mutations might lead to the formation of either altered tRNA or altered AA-tRNA synthetases which could modify the translation process (1703).

 

Francis Harry Compton Crick (GB), Sydney Brenner (ZA-GB), and Francois Jacob (FR) were at Cambridge University on Good Friday brainstorming about how the genetic code might work when they conceived the notion of the messenger—a molecule, which delivered the gene’s instructions to the location where proteins are, assembled (761).

 

Britton Chance (US) and Gunnar Hollungar (US) found experimental evidence that the reduction of mitochondrial NAD can be accomplished by oxidation-reduction couples having potentials several hundred millivolts higher than that of the NAD couple. These results indicated that the respiratory chain could utilize energy conserved at some sites to drive energy-requiring reactions at others (252).

 

Akira Tsugita (US), Duane Tolbert Gish (US), Janis D. Young (US), Heinz Ludwig Fraenkel-Conrat (DE-US), C. Arthur Knight (US), and Wendell Meredith Stanley (US) worked out the entire 158 amino acid sequences of the capsomere protein subunits in tobacco mosaic virus (1577).

 

Cedric Inglis Davern (US) and Matthew Stanley Meselson (US) discovered that the ribosomal RNA of bacteria is extremely stable (327).

 

Charles G. Kurland (SE) showed that the 18S RNA molecule is part of the 40S ribosomal subunit while the 28S RNA is part of the 60S ribosomal subunit (861).

 

Julius Marmur (US), Paul Mead Doty (US), Dorothy Lane (US), Carl L. Schildkraut (US), Joseph Eigner (US), and Robert Rownd (US) discovered that double stranded DNA can be converted to single-stranded units by heat treatment. Such treatment is a type of denaturation and is called melting. They showed that the complementary single strands of DNA recombine to form native double helices when they are kept for several hours at sub-denaturing conditions (approximately 65° C). This is called annealing or renaturation. The degree and efficiency of annealing is believed to be related to base sequence homology and therefore a reflection of phylogeny (363; 1004; 1006-1008; 1364).

 

Arthur J. Kornberg (US), Samuel Bernard Weiss (US), Charles Clifton Richardson (US), Baldomero M. Olivera (US), Israel Robert Lehman (US), Steven B. Zimmerman (US), John W. Little (US), Carol K. Oshinsky (US), and Martin Frank Gellert (US) made major contributions to discovering those proteins associated with DNA replication (833; 1183; 1652; 1715).

Richard H. Epstein (CH), Antoinette Bolle (CH), Charles M. Steinberg (US), Eduard Kellenberger (US), Robert S. Edgar (US), Millard Susman (US), Getta Harmr Denhardt (US), and Ilga Lielausis (US) determined that at least seven viral gene products are required for the T4 bacteriophage to replicate its DNA (420). These results strongly suggested that the replication of DNA requires not one but a group of enzymes.

 

Masayasu Nomura (JP-US), Benjamin D. Hall (US), and Solomon Spiegelman (US) found that viral RNA produced immediately following infection of Escherichia coli by T2 bacteriophage is not soluble viral RNA nor is it ribosomal viral RNA. It appears to associate itself with the 30S ribosomal particles (1146).

 

Ulrich Clever (DE) and Peter Karlson (DE) discovered that the molting hormone, ecdysone, induces puffs in the giant salivary chromosomes of Chironomus tentans (282).

Peter Karlson (DE) proposed that hormones, such as ecdysone, control gene activity by stimulating transcription and translation (778).

Peter Karlson (DE), Hans Hoffmeister (DE), Walter Hoppe (DE), and Robert Huber (DE) were the first to identify ecdysone, a molting hormone found in arthropods. They extracted it from 1,000 pounds of silkworm pupae (780).

 

Wolfgang Haupt (DE) presented evidence that the photoreversible pigment (phytochrome) is associated with the cell membrane in Mougeotia, a green alga (632; 633).

 

Mohammad Iqbal Hussain Aleem (PK-US) and Alvin Nason (US), while studying Nitrobacter, gave the first conclusive evidence that oxidative phosphorylation occurs in chemolithotrophic bacteria (14).

 

Robert Emerson (US) and Eugene I. Rabinowitch (US) demonstrated the importance of auxiliary pigments to the efficiency of photosynthesis (409).

 

Richard H. Hageman (US) and Donna Flesher (US) found that both light and substrate, nitrate, are required for the formation (induction) of nitrate reductase in leaves of young maize seedlings. Light was also required for maintenance of nitrate reductase in seedlings well supplied with endogenous nitrate. Correlations between activity and changes in protein content indicated that the in vitro activities reflected in situ activities (599).

Richard H. Hageman (US), Christopher F. Cresswell (ZA), and Eric J. Hewitt (GB) demonstrated the enzymatic conversion of nitrate to ammonia in the presence of the non-physiological electron donor reduced benzyl vologen in higher plants (598). Note: This work stimulated a search for the endogenous reductant which was characterized as ferredoxin providing support for the close association of photosynthesis and nitrite assimilation. It was recognized that nitrate availability influenced the tissue levels of nitrate reductase and it was suspected that the enzyme was substrate induced.

Leonard Beevers (US) and Richard H. Hageman (US) provided a review of nitrate metabolism in higher plants. In addition to reviewing the properties of enzymes involved in nitrate and nitrite assimilation, the review discussed the factors regulating activity and level of the enzymes and the physiological consequences of an altered nitrate metabolism (109).

 

Hans Joachim Müller-Eberhard (DE-US-DE) and Ulf R. Nilsson (SE) isolated the beta 1C-globulin (C3c) component of complement (1107).

 

Benjamin H. Sweet (US) and Maurice Ralph Hilleman (US) discovered simian virus 40 (SV40) as a vacuolating agent in African green monkey cell cultures (1503).

 

John D. Smith (US), Gustave Freeman (US), Marguerite Vogt (US), and Renato Dulbecco (IT-US) demonstrated that simian virus 40 (SV40), and polyoma virus are both DNA viruses in which the DNA occurs in a cyclic, or circular, shape as well as a linear form; both forms giving rise to new virus and to cancer when they enter receptive cells, but the ring form is more active (378; 1440).

 

 Vernon Riley (US) K.E.K. Rowson (GB), Myer H. Salaman (GB), and D.H. Adams (GB) found that lactate dehydrogenase-elevating virus (LDV), a.k.a. Riley's virus, when coupled with a transplantable tumors of many types caused a five- to ten-fold increase in plasma lactate dehydrogenase (LDH) activity within 3 days of transplantation and before the tumors were clinically obvious. To produce this dramatic increase in plasma enzyme level it was not necessary to transplant cells; cell-free plasma from tumor-bearing mice was equally effective. The raised enzyme level could be serially transmitted from mouse to mouse and proved to be caused by a virus which replicated rapidly in mouse macrophages (1298; 1327; 1328).

 

David Arthur John Tyrrell (GB), Griselda Hitchcock (KE-GB), M.L."Will" Bynoe (BR), Helio Gelli Pereira (BR), and Christopher Howard Andrewes (GB) grew the rhinovirus (common cold) in primary human fetal and monkey kidney tissue culture (1579).

Christopher Howard Andrewes (GB) named them rhinoviruses (31).

Michael George Rossmann (US), Edward Arnold (US), John W. Erickson (US), Elizabeth A. Frankenberger (US), James P. Griffith (US), Hans-Jürgen Hecht (DE), John E. Johnson (US), Greg Kamer (US), Ming Luo (US), Anne G. Mosser (US), Roland R. Rueckert (US), Barbara Sherry (US), and Gerrit Vriend (NL) worked out the three dimensional structures of human rhinovirus (HRV) by x-ray crystallography (1319).

Donald E. Staunton (US), Vincent J. Merluzzi (US), Robert Rothlein (US), Richard Barton (US), Steven D. Marlin (US), and Timothy Alan Springer (US) discovered that I-CAM-1 is the major surface receptor for the rhinoviruses (CAM=cell adhesion molecules) (1470).

Steven D. Marlin (US), Donald E. Staunton (US), Timothy Alan Springer (US), Christian Stratowa (AT), Wolfgang Sommergruber (AT), and Vincent J. Merluzzi (US) solubilized the I-CAM-1 receptor and found that it would block the normal rhinovirus receptor site. This could have promise as a prophylactic for the common cold (1003).

 

Walter Plowright (GB), R.D. Ferris (GB), and Gordon R. Scott (GB) discovered the bovine malignant catarrhal fever virus (1222).

 

Daniel S. Rowe (US), Richard H. Michaels (US), Robert Merritt Chanock (US), Hyun Wha Kim (US), Andrew J. Vargosko (US), Ann Deleva (US), Karl M. Johnson (US), Christine Cumming (US), Robert H. Parrott (US), Horace C. Turner (US), Robert Joseph Huebner (US), Albert Zaven Kapikian (US), Joseph A. Bell (US), and Francis M. Mastrota (US) first described viral pneumonia caused by respiratory syncytial virus (RSV) in older adults (259; 775; 1204; 1321). RSV was not appreciated as a significant pathogen until outbreaks of infection in nursing homes were reported in the 1980s.

William H. Barker (US) and John P. Mullooly (US) noted that influenza vaccination of elderly persons led to a reduction in pneumonia and influenza hospitalizations and deaths (82).

 

Marvin R. Lamborg (US) and Paul Charles Zamecnik (US) developed the first bacterial cell-free system, which proved to be reliable for metabolic experiments (867).

Alfred Tissières (CH), David Schlessinger (US), and Francoise Gros (FR) improved this system and reached the conclusion that in Escherichia coli the active ribosomes are 70S units, which contain a functional component. The 30S or 50S units are not active (1562).

 

Francois Jacob (FR), David Perrin (FR), Carmen Sanchez (FR), and Jacques Lucien Monod (FR) worked with the Lac segment of Escherichia coli and defined the operon as the genetic unit of co-ordinate expression, i.e., composed of a combination of structural and regulator genes used to control the production of enzymes necessary for the utilization of lactose (739).

 

Monica Riley (US), and Arthur Beck Pardee (US), Francois Jacob (FR), and Jacques Lucien Monod (FR) performed an experiment with Escherichia coli which indicated that for a protein to be produced a gene must continually express itself through the production of an intermediate molecule which is not ribosomal RNA (1292).

Alain Bussard (FR), Shiro Naono (FR), Francoise Gros (FR), and Jacques Lucien Monod (FR) performed an experiment where Escherichia coli was grown in the presence of a base analog of uracil (beta-fluorouracil). The results implicated an RNA molecule as an intermediate between DNA and protein synthesis (202).

Martynas Ycas (US) and Walter S. Vincent (US) found a transient RNA in yeast cells with base ratios matching those of the yeast’s DNA (1705).

Francois Jacob (FR), Jacques Lucien Monod (FR), Sydney Brenner (ZA-GB), Matthew Stanley Meselson (US), Francois Gros (FR), Howard H. Hiatt (US), Walter Gilbert (US), Charles G. Kurland (SE), Robert W. Risebrough (US), and James Dewey Watson (US) reported their classic experiments proving the existence of messenger RNA (172; 584; 737; 738).

“The molecular structure of proteins is determined by specific elements, the structural genes. These act by forming a cytoplasmic transcript of themselves, the structural messenger, which in turn synthesizes the protein. The synthesis of the messenger by the structural gene is a sequential replicative process, which can be initiated only at certain points on the DNA strand, and the cytoplasmic transcription of several, linked, structural genes may depend upon a single initiating point or operator. The genes whose activity is thus coordinated form an operon.

The operator tends to combine (by possessing a base sequence) specifically with a certain (RNA) [now known to be proteinaceous] fraction possessing the proper (complementary) sequence. This combination blocks the initiation of cytoplasmic transcription and therefore the formation of the messenger by the structural genes in the whole operon. The specific repressor (RNA?), acting with a given operator, is synthesized by a regulator gene.

The repressor in certain systems (inducible enzyme systems) tends to combine specifically with certain specific small molecules. The combined repressor has no affinity for the operator, and the combination therefore results in activation of the operon.

In other systems (repressible enzyme systems) the repressor by itself is inactive (i.e., it has no affinity for the operator) and is activated only by combining with certain specific small molecules. The combination therefore leads to inhibition of the operon.

The structural messenger is an unstable molecule, which is destroyed in the process of information transfer. The rate of messenger synthesis, therefore, in turn controls the rate of protein synthesis…

The property attributed to the structural messenger of being an unstable intermediate is one of the most specific and novel implications of this scheme…This leads to a new concept of the mechanism of information transfer, where the protein synthesizing centers, (ribosomes) play the role of non-specific constituents which can synthesize different proteins, according to specific instructions which they receive from the genes through M-RNA” (737).

 

Charles C. Shepard (US) was the first to grow Mycobacterium leprae in an experimental animal. He injected the microorganism into the footpads of mice (1407).

 

Robert Day Allen (US), John W. Cooledge (US) and Prudence J. Hall (US) showed that the cytoplasm of amoeba retains the ability to move by cytoplasmic streaming when extracted from cells (21).

 

Peter C. Nowell (US) found that the mucoprotein plant extract, phytohemagglutinin (PHA) is a specific initiator of mitotic activity: in its presence, cell division occurs; on its absence, no mitosis appears. The data suggested that the mitogenic action of PHA does not involve mitosis per se but rather the stage preceding mitosis—the alteration of circulating monocytes and large lymphocytes to a state wherein they are capable of division (1151).

Peter C. Nowell (US) found that the glucocorticoid prednisolone 21-phosphate has almost precisely the opposite effect in its role as an inhibitor of mitosis in leukocytes (1152).

Daniel B. Fisher (US) and Gerald C. Mueller (US) were the first to report the relationship between inositol lipids and cell proliferation (lymphocytes stimulated with phytohemagglutinin) (446).

 

Robert Lee Hill (GB) and Fay Bendall (GB) used herbicide inhibitors to block steps in the electron transport system of photosynthesis. These techniques revealed what they called the Z pathway. The first leg of the Z is the flow of electrons from water through photosystem 2. The electrons then flow through a series of carriers that connect photosystems 2 and 1; this series forms the diagonal of the Z. As they pass through this series, electrons lose energy; some of the released energy is used to pump protons across the membrane housing the carriers. The electrons then pass through photosystem 1 and are transferred to a short transport chain leading to the final acceptor of the chloroplast system, NADP+ (672).

 

Mordhay Avron (IL) presented a detailed study for optimizing the conditions for preparation of chloroplasts from leaves of higher plants and of the reaction conditions for measuring photophosphorylation. Under the conditions specified, the world record rate (which still holds) of light-induced ATP formation, approaching 2500 μ moles X mg chl-1 X hr-1, was attained. A simple assay system for following the incorporation of radioactive inorganic phosphate into ATP is described and is used to evaluate several mechanistic aspects of the process (71).

 

James M. Shewan (GB), Geoffrey Hobbs (GB), and William Hodgkiss (GB) defined the methods and determinative criteria appropriate to the identification of psychrophilic bacteria. Broad groups are outlined based on a small number of preliminary tests. The further differentiation of motile gram-negative organisms of the genera Pseudomonas, Aeromonas, and Vibrio is described (1408).

 

Hoechst Chemical Company introduced the herbicide linuron, a substituted urea, useful in soybeans (Glycine max), corn (Zea mays), sorghum (Sorghum cereale), wheat (Triticum spp.), and potatoes (Solanum tuberosum). ref

 

Samuel McDonald McCann (US), Samuel Taleisnik (AR), and H.M. Friedman (US) obtained crude aqueous extracts from hypothalamic tissues, which stimulated the secretion of luteinizing hormone. A polypeptide seemed to be the likely candidate as stimulant. The active substance was named LH-releasing factor (LRF) (1030).

 

Peter J. Nowell (US) discovered that given the proper chemical stimulus lymphocytes will proliferate (1441).

 

J. Herbert Taylor (US) showed that in the Chinese hamster chromosomes do not replicate in synchrony but rather there is an orderly temporal sequence in the replication of individual chromosomes. The pattern is maintained from one generation to the next (1522).

 

André Govaerts (BE) found that lymphocytes from the thoracic duct of dogs that had been given a kidney graft are cytotoxic for kidney epithelial cells of the donor dog but not for those from non-donor dogs (571).

 

Stephen V. Boyden (GB-AU) and Ernst Sorkin (CH) were the first to describe cytophilic antibodies in terms of their intermediary role between effector cell and antigen. They were detected as specific antibodies, which would passively sensitize macrophages for subsequent attachment of radiolabeled or cellular antigens (162; 163).

 

Edward C. Cocking (GB) developed the enzymatic isolation and culture of protoplasts. The method involves removing the cell wall with purified preparations of cellulase and pectinase, while regulating protoplast expansion with an external osmoticum. The cultured protoplasts regenerate new cell walls, form cell colonies, and ultimately form plantlets (285).

 

David L. Dewey (GB) was the first to demonstrate that anoxia (reduced oxygen) makes cells more resistant to radiation (348).

 

Georges Barski (FR), Serge Sorieul (FR), Francine Cornefert (FR), and Boris Ephrussi (RU-FR) made the first observations indicating that the somatic cells of animals can hybridize in vitro. It was Serge Sorieul (FR) who did the cytogenetic monitoring and made the discovery (93; 94; 416).

Boris Ephrussi (RU-FR) and Serge Sorieul (FR) observed that following the in vitro hybridization of different cell types there is a slow progressive reduction in chromosome number (416).

Henry Harris (GB) induced hybridization of cells on a large scale, with cells of widely different species as well as cells of widely differing types in the same species (621).

 

Kenneth David Roeder (GB-US), Lillian S. Tozian (US), Nancy Milburn (US), and Elizabeth A. Weiant (US) determined conclusively that coordinated patterns of motor spikes destined for the phallic apparatus of mantids and cockroaches are generated endogenously in the last abdominal ganglion and are suppressed most of the time by descending signals from the brain (1051; 1310).

 

Robert J. Fitzgerald (US) and Paul H. Keyes (US) found that dental caries was induced in ‘caries-inactive’ albino hamsters by oral inoculation of pure cultures of a Streptococcus isolated from a caries lesion of a caries active hamster. A streptomycin-resistant mutant of this organism was used to demonstrate its presence in caries lesions and to trace the transmission of the labeled’ organisms between animals (450).

 

Issac Harary (US) and Barbara Farley (US) discovered that rat heart cells, separated by trypsin treatment, and grown attached to glass in a liquid medium, exhibit periodic contractions like a whole beating heart. The rate of beating, which is up to 150 beats per minute, is affected by cardiac drugs and by metabolic substrates and inhibitors (615).

 

Arthur L. Hall (US) and Richard J. Martin (US) reported the results when a naval aviator-flight surgeon wore a Mark III Mod II Navy full pressure suit (3.5 psi) in an altitude chamber for 76 h at altitude equivalents up to 170,000 ft. More than 72 h were spent above 30,000 ft. and 47 h above 80,000 ft. Fluid balance, caloric intake, O2 consumption, and leak rates were measured. The suit was well tolerated, with the biggest problem being the effects of the low-humidity O2 on the oro-nasal pharynx (602).

 

Jan Gosta Waldenström (SE) presented his concept of monoclonal versus polyclonal gammopathies. He described patients with a narrow band of hypergammaglobulinemia as having monoclonal protein. Although many of these patients had multiple myeloma, others had no evidence of malignancy and were described as having essential hypergammaglobulinemia or benign monoclonal gammopathy (1610). Most physicians now use the term monoclonal gammopathy of undetermined significance (MGUS) because some of these patients will eventually develop multiple myeloma, macroglobulinemia, or a related disorder.

 

David G. Harnden (GB) accomplished the culture of fibroblastic cells from tiny pieces of skin that could be taken from patients or volunteers. He used these cells for studying the chromosomes of patients with a variety of developmental abnormalities (620).

 

John Hilton Edwards (GB), David G. Harnden (GB), A. Hugh Cameron (GB), V. Mary Crosse (GB), and Otto H. Wolff (GB) were the first to describe the trisomy-18 syndrome in man (392). The affected infants exhibit: mental retardation, a peculiar skull with a small mandible and prominent occiput, low-set and malformed ears, a receding chin and stubby fingers, tightly flexed, with the index commonly overlapping the medius. The feet are of rocker-bottom type. Ventricular septal defect is often present.

 

Klaus Patau (DE), David W. Smith (US), Eeva Therman (FI), Stanley L. Inhorn (US), and Hans P. Wagner (CH) were the first to confirm the human trisomy-13 syndrome by cytogenetic analysis (1207; 1439). The infants are mentally retarded and have multiple abnormalities. Such eye defects as colobomata or anophthalmia are common and there are neurological features such as fits and hypotonia. Cleft palate and harelip are often present. Sometimes capillary hemangiomata are present. Congenital heart disease is characteristic. The constellation of findings in this condition was described as far back as the 1600's.

 

Malcolm Andrew Ferguson-Smith (GB), Alan W. Johnston (GB), and Stanley D. Handmaker (GB) reported two patients with primary amentia and micro-orchidism associated with an XXXY sex-chromosome constitution (436).

 

Peter C. Nowell (US) and David A. Hungerford (US) discovered that a marker chromosome, the Philadelphia chromosome (Ph+), is consistently associated with chronic myelogenous leukemia (CML). They speculated that it was caused by a translocation (1154; 1155). Note: this was the first chromosomal abnormality associated with cancer using cytogenetics. See, Janet Davison Rowley, 1977.

Janet Davison Rowley (US) using chromosome banding techniques found that the Philadelphia chromosome is a reciprocal translocation between chromosome 22 and another chromosome, usually chromosome 9, rather than a deletion of chromosome 22 as had previously been thought (1324). This was the first time that a specific human disease was linked to a chromosomal rearrangement.

Janet Davison Rowley (US) reported another translocation between chromosomes 8 and 21 in acute myeloblastic leukemia cells (1325).

Peter C. Nowell (US) encouraged the use of chromosome studies to diagnose various cancers (1153).

Janet Davison Rowley (US), Harvey M. Golomb (US), and Charlotte Dougherty (US) reported that a 15/17 translocation is a consistent chromosomal change associated with acute promyelocytic leukemia in man (1326).

Annelies de Klein (NL), Ad Geurts van Kessel (NL), Gerard Grosveld (NL), Claus R. Bartram (NL), Anne Hagemeijer (NL), Dirk Bootsma (NL), Nigel K. Spurr (NL), Nora Heisterkamp (NL), John Groffen (NL), and John R. Stephenson (NL) showed that when the Philadelphia chromosome is formed (a reciprocal translocation between chromosomes 22 and 9) in cells resulting in human chronic myeloid leukemia that an oncogene on chromosome 9 is translocated to chromosome 22 near the immunoglobulin locus (336).

Riccardo Dalla-Favera (US), Marco Bregni (US), Jan Erikson (US), David Patterson (US), Robert Charles Gallo (US), and Carlo M. Croce (US) discovered that the (8;14) translocation characteristic of Burkitt’s lymphoma involves the transposition of the cellular homologue of the myc viral oncogene, normally located on chromosome 8, to the immunoglobulin locus on chromosome 14 (318). This was the first indication that translocations can lead to in-frame fusion and the formation of chimeric genes that encode a fusion mRNA and protein.

Nora C. Heisterkamp (US), Kees Stam (US), John Groffen (US), Annelies de Klein (US), and Gerard Grosveld (US) figured out that the Philadelphia chromosome translocation resulted in the fusion of two genes that created a new gene known as BCR-ABL (647).

Tracy Gross Lugo (US), Ann Marie Pendergast (US), Alfred J. Muller (US), and Owen N. Witte (US) discovered that this fusion gene causes the body to produce an abnormally active form of an enzyme called a tyrosine kinase that stimulates uncontrolled cell growth in white blood cells (950). Chronic myelogenous leukemia (CML) is not the result of a series of gene mutations, but rather is caused by one translocation resulting in a singular mutatiion, the BCR-ABL fusion gene.

Brian J. Druker (US), Shu Tamura (US), Elisabeth Buchdunger (CH), Sayuri Ohno (US), Gerald M. Segal (US), Shane Fanning (US), Jürg Zimmermann (CH) and Nicholas B. Lydon (GB) proved that Bcr-Abl protein tyrosine kinase could be targeted in leukemia cells, a crucial finding that led to the development of Gleevec (369). Note: The BCR-ABL oncogene is present in 95% of patients with chronic myelogenous leukemia.

 Michael J. Mauro (US), Michael E. O’Dwyer (US) and Brian J. Druker (US) developed imatinib (ST1571 or Gleevac) to target the abnormal protein produced by this genetic translocation (1025; 1026).

Brian J. Druker (US), Moshe Talpaz (US), Debra J. Resta (US), Bin Peng (US), Elisabeth Buchdunger (DE-CH), John M. Ford (US), Nicholas B. Lydon (GB), Hagop Kantarjian (LB-US), Sayuri Ohno-Jones (US), and Charles L. Sawyers (US) established the efficacy and safety of imatinib (Gleevec), a specific inhibitor of the Bcr-Abl protein tyrosine kinase, in treatment of chronic myeloid leukemia (368).

A. Thomas Look (US), Tim Veldman (US), Christina Vignon (US), Evelin Schrock (US), Janet Davison Rowley (US), and Thomas Ried (US) found that most translocations in acute leukemia and in sarcomas lead to in-frame fusion genes that along with their protein products represent unique tumor markers of considerable diagnostic importance (934; 1594).

 

Aaron Bunsen Lerner (US), James D. Case (US), Seithikurippu R. Pandi -Perumal (IN), Nava Zisapel (IL), Venkataramanujan Srinivasan (IN), and Daniel P. Cardinali (AR) provided research that led to the incidental discovery of the sleep-promoting effects of melatonin (907; 1200).

Richard Wurtman (US), Amnon Brzezinski (IL), Mark G. Vangel (US), Gillian Norrie (GB), Abraham Ben-Shushan (IL), Ian Ford (GB), and Irina Zhdanova (US) reported that melatonin treatment significantly reduced sleep onset latency, increased sleep efficiency and increased sleep duration (187; 1694).

Venkatramanujam Srinivasan (IN), Daniel P. Cardinali (AR), Uddanapalli S. Srinivasan (IN), Charanjit Kaur (IN), Gregory M. Brown (CA), D. Warren Spence (CA), Rüdiger Hardeland (DE), Seithikurippu R. Pandi-Perumal (IN) Seithikurippu R. Pandi-Perumal (IN) , Ahmed S. BaHammam (IN), Vijay K. Bharti (IN), and Burkhard Poeggeler (DE) showed that melatonin exhibits protective effects against certain neurodegenerative disorders such as Alzheimer's disease and Parkinson's disease (1199; 1457; 1458).

Annemarieke de Jonghe (NL), Joke C. Korevaar (NL), Barbara C. van Munster (NL), Sophia E. de Rooij (NL), Tracy A. Bedrosian (US), and Randy J. Nelson (US) reported that melatonin relieves the symptoms of Sundowning syndrome (107; 335).

Ze-Ping Hu (CN), Xiao-Ling Fang (CN), Nan Fang (CN), Xiao-Bian Wang (CN), Hai-Yan Qian (CN), Zhong Cao (CN), Yuan Cheng (CN), Bang-Ning Wang (CN), Yuan Wang (CN), Flavia Radogna (IT), Marc Diederich (IT), Lina Ghibelli (IT), Luigi Fabrizio Rodella (IT), Gaia Favero (IT), Eleonora Foglio (IT), Claudia Rossini (IT), Stefania Castrezzati (IT), Claudio Lonati (IT), Rita Rezzani (IT), Petra H. Wirtz (CH), Maria Spillmann (CH), Carmen Bärtschi (CH), Ulrike Ehlert (CH), and Roland von Känel (CH) credited melatonin with anti-inflammatory, antioxidant, anticoagulopathic as well as endothelial-protective properties (708; 1251; 1309; 1665). See, McCord, 1917.

 

John Rock (US), Celso-Ramon Garcia (US), Gregory Goodwin Pincus (US), Min Chuch Chang (US), and Carl Djerassi (US) contributed to the discovery of a method of so altering a female’s physiology by means of synthetic hormones as to keep her infertile without altering her capacity for sexual enjoyment. This is a situation, which takes place naturally during pregnancy, and the synthetic hormone duplicates that condition. They helped produce the first oral contraceptive pill after being persuaded to do so by Margaret Sanger, a leader in the American birth-control movement, and Katherine Dexter McCormick, an heir to the International Harvester fortune. Pincus received a grant from the Planned Parenthood Federation in 1951. Pincus and Chiang began to look for a progestin or a synthetic progestin that could be used as a birth control agent. After much experimentation with more than 200 substances, the two derived the steroid compounds from the roots of the wild Mexican yam. The steroids were found to be successful in inhibiting ovulation in laboratory animals and appeared to be harmless. Pincus started conducting field tests for the steroids in pill form with hundreds of women in Brookline, Massachusetts; Puerto Rico; and Haiti in 1955. They proved to be effective. The only side effects were brief feelings of nausea (1308). The United States Food and Drug Administration (FDA) authorized the marketing of these steroids for limited use in 1957. Three years later the FDA licensed Enovid, a birth-control pill produced by G.D. Searle Company.

 

Arhur J. Buller (GB), John Carew Eccles (AU-GB-AU), and Rosamund M. Eccles (AU) demonstrated the reversal of contractile characteristics in fast- and slow-twitch muscles after cross-innervation in the cat (188).

John O. Holloszy (US) demonstrated adaptation of the energy metabolism system in rat skeletal muscle to chronic exercise training (700).

Philip D. Gollnick (US), Robert B. Armstrong (US), Carl W. Saubert, IV (US), Karin Piehl (US), Bengt Saltin (SE), Walter L. Sembrowich (US), and Raymond E. Shepherd (US) addressed the question of whether a stimulus such as exercise training could produce not only metabolic adaptations, but also transform fiber types in human skeletal muscle. In the 1972 paper they reported that skeletal muscle from trained endurance athletes is predominantly slow-twitch fibers with a relatively high oxidative capacity. The 1973 paper concluded that chronic exercise training does not significantly alter the distribution of fast- and slow-twitch fibers in human skeletal muscle (558; 559). It is now generally recognized that skeletal muscle fibers do not exist in three discrete forms at the subcellular level, but rather in a continuum based on the multitude of combinations of myosin heavy and light chain isoforms, polymorphic expression of protein isoforms, metabolic potential, and calcium ion handling characteristics. Moreover, all these cellular characteristics exhibit some degree of plasticity in response to exercise training.

 

Leif Wide (SE) and Carl A. Gemzell (US) described an immunological method for the assay of chorionic gonadotrophin (HCG) in human urine. The method is useful as a simple and rapid pregnancy test and can be applied for quantitative determinations of HCG in urine (1657).

 

Lawson Wilkins (US) found that masculinization of the female fetus frequently resulted from administration of progestins to mothers in treating habitual or threatened abortion. In 25 cases the mothers were given estrogens with the progestins in order that the estrogen might offset the virilizing effect of the progestin, but the evidence showed that the estrogens did not prevent fetal masculinization (1659).

 

Harold Theodore Hammel (US), James Daniel Hardy (US), Madeline M. Fusco (US), and Bjørn Hellstrøm (NO) found that moderate local cooling of the hypothalamus elicits vasoconstriction and shivering without thermal drives from the periphery and in the presence of possible inhibitory drives due to elevated skin and visceral temperature (609; 649).

Harold Theodore Hammel (US), Don C. Jackson (US), Jan A.J. Stolwijk (NL-US), James Daniel Hardy (US), and Sigmund B. Strømme (NO) found that for the dog and rhesus monkey, 1) a resting animal shivers in a cold environment with the same or higher hypothalamic temperature as the same animal in a neutral environment; 2) a resting animal pants in a hot environment with the same or lower hypothalamic temperature as the same animal in a neutral environment; 3) the hypothalamus is nonetheless strongly responsive to an increase or decrease of 1 C; 4) the rate of heat loss increases at the onset of sleep while the hypothalamic temperature is falling; 5) the hypothalamic temperature is 1–2 C lower during sleep even though thermoregulatory responses are the same as when awake; 6) the rate of heat loss decreases upon awakening while the hypothalamic temperature is rising (610).

 

William L. Nastuk (US), Otto J. Plescia (US), Kermit E. Osserman (US), and John A. Simpson (GB) proposed that myasthenia gravis is an autoimmune disorder involving an immunologic response to a protein in the neuromuscular junction (1118; 1420).

 

Ockert Stephanus Heyns (ZA), W.A.B. Roberts (ZA), and H.G. Smulian (ZA) introduced abdominal decompression as a method of pain relief in labor. He applied negative pressure via a shell (Heyns bag) that could be controlled by the patient (670).

 

George Milton Shy (US) and Glenn A. Drager (US) described a progressive neurological disorder accompanied by postural hypotension, rigidity and tremor (Shy–Drager syndrome) (1415).

 

Jacques Genest (CA), Wojciech Nowaczynski (CA), Erich Koiw (CA), Tamás Sandor (HU), Pierre Biron (CA), John Henry Laragh (US), Marielene Angers (US), William G. Kelly (US), and Seymour Lieberman (US) showed that angiotensin II infused intravenously caused increased aldosterone production (518; 875). Note: This established a connection between kidney function and hormone production by the adrenal gland.

 

Georges Klein (SE), Hans Olof Sjögren (SE), Eva Klein (SE), Karl E. Hellström (SE), Lloyd J. Old (US), Edward A. Boyse (US), Donald A. Clarke (US), Elizabeth A. Carswell (US), Amiela Globerson (IL), and Michael Feldman (IL) were the first to prove the existence of specific antigenic differences in animal tumors (546; 817; 1179).

 

Charles S. Kennedy (US), Elmer B. Miller (US), Donald C. McLean (US), Marvin S. Perlis (US), Raymond M. Dion (US) and Victor S. Horvitz (US) were the first to put into practice an operation referred to as a hemicorporectomy. The procedure involves removal of the bony pelvis, both lower limbs, the external genitalia, the bladder, rectum and anus. The operation was completed in a single stage in a 74-year-old man with locally invasive rectal cancer. The patient died of pulmonary edema 10 days post-operatively (800).

J. Bradley Aust (US) and Karel B. Absolon (US) performed the first successful hemicorporectomy (at the level between the lowest lumbar vertebra and the sacrum) on a 29-year-old paraplegic with malignancy arising in a decubitus ulcer in 1961. The procedure was performed in two stages and the patient survived for 19 years, before finally succumbing to pulmonary edema (68).

 

John J. Shea, Jr. (US), Harold G. Tabb (US), and David F. Austin (US) performed the first transcanal, under-surface tympanoplasties using connective tissue from veins (69; 1400; 1509).

 

Albert Wollenberger (DE), Otto Ristau (DE), and Georg Schoffa (DE) described how tissue and organs can be frozen in situ in a fraction of a second by being compressed to a thin layer between two aluminum blocks that are precooled in liquid nitrogen and for convenient handling form part of a clamp (1672).

 

Thomas Earl Starzl (US) and Harry A. Kaupp, Jr. (US) performed transplantation in dogs of multiple abdominal viscera, including liver and intestine, nearly identical to human procedures done three decades later (1466).

 

Cyrus E. Rubin (US), Lloyd Brandborg (US), Patricia C. Phelps (US), and Hawley C. Taylor, Jr. (US) upon examination of patients from infancy to old age with celiac disease or idiopathic sprue found abnormalities of villous architecture in duodenojejunal biopsies from all. Such abnormalities were not seen in normals or in patients with a wide variety of other types of malabsorption. Heal mucosal morphology was normal in two celiac sprue patients with abnormal duodenojejunal mucosa (1330).

 

Nathan Oram Kaplan (US), Margaret M. Ciotti (US), Milton W. Hamolsky (US), Robert E. Beiber (US), and Don Dennis (US) were among the first to recognize the potential of using isoenzyme analysis in clinical diagnosis and for this reason developed methods for detecting lactic acid dehydrogenase isoenzymes in human serum (344; 611; 776). Tissue breakdown releases LDH, and therefore LDH can be measured as a surrogate for tissue breakdown, e.g. hemolysis. Other disorders indicated by elevated LDH include cancer, meningitis, encephalitis, acute pancreatitis, and HIV. It can also be used as a marker of myocardial infarction. Following a myocardial infarction, levels of LDH peak at 3–4 days and remain elevated for up to 10 days.

 

David A. Price Evans (US), Keith A. Manley (US), and Victor Almon McKusick (US) investigated the large person to person variations in the metabolism of isoniazid, which was in general use to treat tuberculosis. They concluded that the variation is due to a genetic polymorphism (422).

 

Sidney Farber (US), Giulio D'Angio (US), Audrey Evans (US), and Anna Mitus (US), at what is now Dana-Farber Cancer Institute, achieved the first remissions in Wilms tumor of the kidney, a common form of childhood cancer. By prescribing the antibiotic actinomycin D in addition to surgery and radiation therapy, they boosted cure rates from 40 to 85 percents (426).

 

Myron Prinzmetal (US), Ali Ekmekci (US), Rexford Kennamer (US), Jan K. Kwoczynski (US), Herbert Shubin (US), and Hideo Toyoshima (US) observed a variant form of angina pectoris in 23 patients. Electrocardiograms, recorded during this type of anginal pain, showed an elevation of the S-T segment which disappeared when the pain stopped. The electrocardiogram may, therefore, show findings opposite to those of ordinary angina pectoris. Sufficient diagnostic features are pointed out to allow for clinical diagnosis of typical cases (1242).

 

Henry A. Schroeder (US) examined the relation between mortality from cardiovascular disease and treated municipal water supplies. In all cases correlations were negative, i.e., softer water was associated with higher death rates. Some factor either present in hard water or missing or entering in soft water appears to affect death rates from degenerative cardiovascular disease (1376).

 

John Christopher Wagner (AU), Chris A. Sleggs (AU), and Paul Marchand (AU), wrote a seminal paper in establishing mesothelioma as a disease arising from exposure to asbestos. Primary malignant tumors of the pleura are uncommon. Thirty-three cases of diffuse pleural mesothelioma were described; all but one has a probable exposure to crocidolite asbestos (Cape blue) (1606).

James C. McNulty (AU) reported the first diagnosed case of malignant mesothelioma. It was in an Australian asbestos worker (1036).

 

Min C. Li (US), Willet F. Whitmore Jr. (US), Robert Golbey (US), and Harry Grabstald (US) reported striking improvement obtained when some cases of patients with advanced metastatic testicular cancer were treated using a combined drug therapy (913).

 

Francis F. Foldes (US), Robert Molloy (US), Pearl G. McNall (US), and Ludwig R. Koukal (US) performed a clinical comparison of toxicity of intravenously given local anesthetic agents in man (457).

 

Nikolaas Tinbergen (NL) explained that during predation the cognitive process appears to consist of a transitory increase in a predator's ability to detect cryptic prey when items of a similar appearance are encountered in rapid succession, a phenomenon termed "hunting by searching image". Because of the shift in detectability, visual predators tend to search for only a limited number of prey types at any moment in time, focusing on the most common prey available and effectively overlooking the others (1560).

 

Nelson Hairston (US), Frederick E. Smith (US) and Lawrence B. Slobodkin (US) are generally credited with originating the concept of a trophic cascade, although they did not use the term. Hairston, Smith and Slobodkin argued that predators reduce the abundance of herbivores, allowing plants to flourish. Often referred to as the green world hypothesis (600).

 

Robert Helmer MacArthur (US) presented three mechanistic niche apportionment models for species. He believed that ecological niches within a resource pool could be broken up like a stick, with each piece of the stick representing niches occupied in the community (967).

 

Elwyn LaVerne Simons (US), from 1960-1968, conducted the most extensive excavations ever undertaken on the Oligocine formation of the Fayum in Egypt, contributing enormously to our knowledge of the early development of the higher primates (1419).

 

Petros Kokkoros (GR) and Antonis Kanellis (GR) reported on the fossil remains of a Homo erectus; Homo erectus petraloniensis from near Petralona in eastern Greece (831). It is dated at 350,000-400,000 BP

 

The journal Analytical Biochemistry was first published.

 

c. 1961

Beecham Labs: Ampicillin

 

1961

“We report genetic experiments which…suggest that the genetic code is of the following general type: (a) A group of three bases…codes one amino-acid. (b) The code is not of the overlapping type… (c) The sequence of the bases is read from a fixed starting point…. If the starting point is displaced by one base, then the reading into triplets is displaced and thus becomes incorrect.” Francis Harry Compton Crick, C. Leslie Barnett, Sydney Brenner, and Richard J. Watts-Tobin (310). This is the monumental paper explaining that the genetic code is triplet in nature.

 

Researchers at Ames Diagnostics created the first blood sugar monitor. This monitor was called Ames Reflectance Meter. ref

 

“[The] system of regulation [of the rate of protein synthesis] appears to operate directly at the level of synthesis by the gene of a short-lived intermediary, or messenger, which becomes associated with the ribosomes where protein synthesis takes place.” François Jacob and Jacques Lucien Monod (737).

 

Francois Jacob (FR) and Jacques Lucien Monod (FR) comment, “the discovery of units of coordinated genetic activity and of regulator genes which control the activity of structural genes, via cytoplasmic repressors, able in turn to interact electively with exogenous or endogenous chemical agents, appears to offer precisely the type of elements needed to build the complex and precise chemical networks of information transfer upon which the development and physiological functioning of organisms must rest.” François Jacob and Jacques Lucien Monod (737).

 

Melvin Calvin (US) was awarded the Nobel Prize in Chemistry for his research on carbon dioxide assimilation in plants.

 

Georg von Békésy (HU-US) was awarded the Nobel Prize in Physiology or Medicine for his discoveries of the physical mechanism of stimulation within the cochlea.

 

Lawrence Hugh Aller (US) stated that nucleosynthesis within stellar interiors generates carbon, nitrogen, oxygen, phosphorus, and other biogenic elements (22).

 

William Henry Oldendorf (US) described the results of experiments in X-ray scanning an object from many angles along its perimeter. These experiments showed that cross-sectional images might be obtained from the detection and recording of slight density variations in the composition of structures within the head. He used a collimated beam and arranged the source and a sensitive crystal detector, so that they spun at opposite poles around the object to be visualized. This data could then be assembled into coherent images of the object under scan (1181). Note: This work directly anticipated and demonstrated the feasibility of computerized axial tomography. A device, the CT scanner, using similar principles, was introduced in April 1972 by EMI, Ltd.

Allan MacLeod Cormack (ZA-US) developed mathematical theory and built machines to achieve two-dimensional x-ray image reconstruction, i.e., axial tomagraphy (298; 299).

Godfrey Newbold Hounsfield (GB) devised a system whereby the brain can be scanned from its perimeter by a collimated beam. The transmitted beam is measured, and its variations recorded at frequent intervals by a sensitive crystal detector, as the beam and the detector scan across the brain from many different directions. Very small differences in the tissue absorption of a collimate beam are measured and recorded, and these data are subsequently reconstructed by a computer giving a cross-sectional image of the anatomy of the brain in detail, i.e. computerized axial tomography (CAT scan) (704). See, Vallebona, 1930.

 

Sydney M. Friedman (CA) and Miyoshi Nakashima (CA) demonstrated that a cannula-type metal-connected electrode is a practical device for the measurement of sodium in single aliquots of biological materials such as blood or urine. They presented evidence suggesting significant sodium binding in plasma (492).

 

Helmut K. Mangold (DE-US) described the technique of thin- layer chromatography (TLC) and its applicability in the lipid field, stressing the simplicity, sensitivity, capacity, versatility, and efficiency of the method (992).

 

Joan Oró (ES) found that concentrated solutions of ammonium cyanide in water can produce the nucleotide adenine, a discovery that contributed to theories on the origin of life. He also described a mechanism for the synthesis of adenine from hydrogen cyanide under possible primitive Earth conditions (1189; 1190).

 

 Walter B. Dandliker (US) and George A. Feigen (US) used polarized fluorescence to give the first description of a true homogeneous assay in which the antigen-antibody event was measured directly in real time (319).

 

Morris John Karnovsky (US) presented a simple method for staining with lead at high pH in electronmicroscopy (781).

John H. Venable (US) and Richard A. Coggeshall (US) developed a simplified lead citrate stain for use in electron microscopy (1595).

 

David Aminoff (US) developed the thiobarbituric acid assay to follow the chemical and enzymatic release of sialic acid from many biologically important compounds. This assay is extremely sensitive, specific, and reproducible (25).

 

Robert G. Martin (US) and Bruce Nathan Ames (US) studied enzymes using sedimentation rates in sucrose (1013).

 

George L. Ellman (US), K. Diane Courtney (US), Valentino Andres (US), and Robert M. Featherstone (US), developed a spectrophotometric method for determining acetylcholinesterase activity of tissue extracts, homogenates, cell suspensions, etc. The activity is measured by following the increase of yellow color produced when the thio anion produced by the enzymatic hydrolysis of the substrate (acetylthiocholine) reacts with dithiobisnitrobenzoate. The method was used to study the activity of human erythrocytes and homogenates of rat brain, kidney, lungs, liver, and muscle tissue (406).

 

Harry P.C. Hogenkamp (US), Horace Albert Barker (US), and Jeffrey N. Ladd (US) determined that the entity used as an enzymatic cofactor in living systems, including mammals, is not vitamin B12, but what is now called coenzyme B12. This coenzyme possesses an adenosyl residue and lacks the cyanide ion of vitamin B12 (690; 691).

P. Galen Lenhert (US) and Dorothy Mary Crowfoot-Hodgkin (GB) used x-ray analysis to reveal the structure of coenzyme B12 along with the surprise that it contains a cobalt-carbon bond, the first true organometallic system (as distinct from a single cyanide ligand) to be discovered in living systems (900).

 

Choh Hao Li (CN-US), Johannes Meienhofer (US), Eugen Schnabel (DE), David Chung (US), Tung-Bin Lo (US) and Janakiraman Ramachandran (US) synthesized a biologically active nonadecapeptide corresponding to the first nineteen amino-acid residues of adrenocorticotropins (ACTH). In addition to adrenal-stimulating activity the nonadecapeptide also has melanocyte-stimulating activity, as does the complete ACTH hormone with 39 residues (911).

Klaus Hofmann (CH-US), Haruaki Yajima (JP), Noboru Yanaihara (JP), Teh-Yung Liu (US), and Saul Lande (US) synthesized a tricosapeptide possessing essentially the full biological activity of natural ACTH (689).

 

Allen B. Edmundson (US) and Christophe Henri Werner Hirs (GB-US) reported the entire 153 amino acid primary structure of sperm whale myoglobin (390).

 

William Howard Stein (US), Arthur M. Crestfield (US), and Stanford Moore (US) began an investigation that led to the understanding of the connection between chemical structure and catalytic activity of the active center in the bovine pancreatic ribonuclease A molecule (307; 1472).

 

Eraldo Antonini (IT), Jeffries Wyman (US), Romano Zito (IT), Alessandro Rossi-Fanelli (IT), and Antonio Caputo (IT) used carboxypeptidase A to digest the C-terminal tyrosine and histidine from the human hemoglobin beta chain and carboxypeptidase B to remove the C-terminal lysine, tyrosine, and arginine on the human hemoglobin alpha chain. The resulting protein appeared intact but had an increased oxygen affinity, lowered cooperativity, and dramatically reduced Bohr effect (37).

Romano Zito (IT), Eraldo Antonini (IT), and Jeffries Wyman (US) used carboxypeptidases A and B, to show that the rate of digestion is different for the oxy- and deoxy-forms of the hemoglobin molecule, indicating a differential accessibility of the C-terminal residues to these enzymes (1716).

 

Georg Hertting (AT), Julius Axelrod (US), Irwin J. Kopin (US), and Lionel Gordon Whitby (GB) found that sympathetic nerve endings take up and retain circulating norepinephrine when it is released into the bloodstream. They also found that norepinephrine released from sympathetic nerve endings has one of three fates: 1) uptake by the nerve ending, 2) uptake by effector cells, and 3) entering the bloodstream (665).

David E. Wolfe (US), Lincoln T. Potter (US), Keith C. Richardson (US), and Julius Axelrod (US) found that norepinephrine is stored within granulated (microsomal) vesicles of non-myelinated axons in the sympathetic system (1671).

Beth J. Hoffman (US), Eva Mezey (US), Michael J. Brownstein (US), Mary C. Ritz (US), Richard J. Lamb (US), Steven R. Goldberg (US), and Michael J. Kuhar (US) found that the monoamine neurotransmitters serotonin and dopamine (prolactin-inhibiting hormone) are also inactivated by uptake into nerves (687; 1303).

Leslie Iversen (GB) reported that the amino acid neurotransmitters gamma-aminobutyric acid (GABA), glycine, proline, and L-glutamate are taken up by neurons and thus inactivated (734).

Maarten E.A. Reith (US) reported that the neurotransmitter uptake sites are sodium/chloride-dependent transporters (1277).

 

Boris Magasanik (AT-US) coined the phrase catabolic repression to describe a phenomenon discovered in bacteria and given the name glucose effect (979; 980). See, Dienert, 1900.

Ellis Englesberg (US), Joseph Irr (US), Joseph Power (US), and Nancy Lee (US) accumulated evidence in Escherichia coli for a mode of gene regulation called positive control. They deduced the existence of an activator protein required for the expression of the genes determining arabinose metabolism in Escherichia coli (412; 413).

Richard S. Makman (US) and Earl Wilbur Sutherland, Jr. (US) found that the level of cyclic AMP (cAMP) increases strongly in glucose starved E. coli cells (987).

Benoit de Crombrugghe (US), Robert L. Perlman (US), Harold Elliot Varmus (US), and Ira Harry Pastan (US) found that cyclic AMP overcomes the glucose repression of the synthesis of several inducible enzymes including beta-galactosidase, galactokinase, glycerokinase, and thymidine phosphorylase. From these results, Pastan concluded, “Since glucose lowers the intracellular concentration of cyclic AMP in E. coli, we propose that the intracellular level of cyclic AMP regulates the rate of synthesis of many inducible enzymes in E. coli and other microorganisms and that glucose lowers the rate of synthesis of these enzymes by decreasing the intracellular level of cyclic AMP” (334).

Ira Harry Pastan (US), Robert L. Perlman (US), Agnes Ullmann (FR), and Jacques Lucien Monod (FR) discovered that cyclic AMP in Escherichia coli can overcome glucose’s catabolic repression of the lactose operon (1206).

Geoffrey Zubay (US), Daniele Schwartz (US), Jonathan Roger Beckwith (US), Michael Emmer (US), Benoit de Crombrugghe (US), Ira Pastan (US), and Robert Perlman (US) characterized an activator of the lac operon. (Expression of the lac operon is inhibited in the presence of glucose and its catabolites, and increased levels of cyclic AMP (cAMP) had shortly before been shown to reverse the inhibitory effect of glucose and its catabolites.) They proposed that cAMP binds to a protein factor, the catabolite gene-activator protein (CAP), causing it to bind to a DNA site in the lac promoter thus stimulating the initiation of transcription. Using the first cell-free system for transcription and translation, they showed directly that CAP plus cAMP stimulated the expression of the lac operon. They isolated and characterized the same factor based on assays of cAMP binding activity and named it cAMP receptor (CR) protein (later revised to CRP) (410; 1717).

Ira Harry Pastan (US), Robert L. Perlman (US), Harold Elliot Varmus (US), Max E. Gottesman (US), Wayne B. Anderson (US), Beatrice Chen (US), and Benoit de Crombrugghe (US) found that cyclic AMP has a major role in controlling gene expression in E. coli and subsequently showed it did this by producing an allosteric change in a specific cyclic AMP-receptor protein (CRP). This change increased the affinity of CRP for DNA sequences in the promoter of many genes. Therefore, transcription was initiated, and gene activity increased (333; 1206; 1593). This was the first example of positive control of gene expression.

Wayne B. Anderson (US), Arthur B. Schneider (US), Michael Emmer (US), Robert L. Perlman (US), and Ira Harry Pastan (US) described the purification and properties of cyclic AMP receptor protein (CRP) (30).

 

Charles D. Salmon (FR), D. Salmon (FR), Geneviève Liberge (FR), Robert G. Andre (FR), Patricia Tippett (GB), and Ruth Sanger (GB) discovered a new erythrocytic blood group antigen present in 80 per cent of subjects of the white race. It is called Auberger's (1343).

 

Hoffmann-LaRoche Laboratories (CH) introduced the drug valium. ref

 

Hans Leo Kornberg (GB-US) and Antonio M. Gotto, Jr. (US) discovered the glycerate pathway by which phosphoenolpyruvate is formed from glyoxylate. This pathway allows an organism to grow when its sole organic carbon source is glycine, glycollate, or oxalate (838).

 

Feodor Felix Konrad Lynen (DE), Dieter Oesterhelt (DE), Eckhart Schweizer (DE), and Klaus Willecke (DE) discovered fatty acid synthetase, the enzyme system which catalyzes the synthesis of saturated long-chain fatty acids from malonyl-CoA (954-956; 961; 962).

 

Howard Marvin Dintzis (US), and Mike A. Naughton (US) showed that polypeptide chains grow by stepwise addition of single amino acids, starting with the amino-terminal amino acid and finishing with the carboxyl-terminal amino acid (350; 1121).

 

Emanuel Margoliash (IL), Emil L. Smith (US), Gunther Kreil (AT), and Hans Tuppy (AT) determined the primary structure of horse heart cytochrome c (998).

 

David Elson (IL), Francis Galibert (FR), Christopher J. Larsen (FR), Jean Claude Lelong (FR), Michel Boiron (FR), Roland Rosset (FR), and Roger Monier (FR) discovered the 5S ribosomal RNA (5S rRNA) (407; 504; 1318).

Jacques J. Pene (FR), Ernest J. Knight, Jr. (US) and James Edwin Darnell, Jr. (US) discovered the 5.8S ribosomal RNA (5.8S rRNA) (1209).

 

Ying Ying Chang (US), Eugene Patrick Kennedy (US), Julian Kanfer (US) and Alvin R. Tarlov (US) worked out most of the steps in the metabolic pathway for phospholipid synthesis (255; 770; 771; 801; 802; 1521). This became known as the Kennedy pathway.

 

Daniel Nathans (US) and Fritz Albert Lipmann (DE-US) developed a bacterial cell-free system that supported protein synthesis. They found that during protein synthesis amino acids are transferred from aminoacyl-sRNA to polypeptide on ribosomes of E. coli (1119).

 

Richard Schweet (US), Hildegarde Lamfrom (DE-US), Esther Allen (US), Ellen R. Glowacki (US), and Paul M. Knopf (US) developed one of the first in-vitro translation systems, using rabbit reticulocyte lysate to study protein synthesis (a process called translation) in a cell-free context. This allowed them to make a number of contributions to the field. By mixing components of different animal cells, and showing that sheep ribosomes (protein-making complexes) could make rabbit hemoglobin and vice versa, they provided some of the first direct experimental evidence for the existence of messenger RNA and its role in determining what protein ribosomes make (868-871; 1381).

 

Jacques Lucien Monod (FR), Jeffries Wyman (FR), Jean-Pierre Changeux (FR), Arthur Beck Pardee (US), John C. Gerhart (US), and Harold Edwin Umbarger (US) presented evidence that enzymes involved in feedback controls have two separate sites, one for the substrate and another for the feedback molecule (256; 521; 522; 1086; 1580). Monod was to name this phenomenon allostery, from the Greek allo, other, and stere, solid. The enzymes are said to be allosteric (1085; 1087).

 

Robert Kellogg Crane (US), David Miller (US), and Ivan Bihler (US) presented for the first time their discovery of the sodium-glucose cotransport as the mechanism for intestinal glucose absorption (304; 305). Note: Their discovery of cotransport led directly to the development of oral rehydration therapy; a treatment that counterbalances the loss of water and electrolytes caused by cholera via a glucose containing salt solution that accelerates water and electrolyte absorption. This is possible because cholera does not interfere with sodium-glucose cotransport (223; 595).

 

Robert William Holley (US), Bhupendra P. Doctor (US), Jean Apgar (US), Susan H. Merrill (US), Paul L. Zubkoff (US), James T. Madison (US), John Robert Penswick (US), George A. Everett (US), Mark Marquisee (US), Ada Zamir (US), Merton R. Bernfield (US), Marshall Warren Nirenberg (US), Jacques R. Fresco (US), Bruce Michael Alberts (US), Paul Mead Doty (US), Hans Georg Zachau (DE), Dieter Dütting (DE), Horst Feldmann (US), Huei-Kuen Kung (US), Uttam L. RajBhandary (US), Simon H. Chang (US), Alexander Stuart (US), Robert D. Faulkner (US), Ronald M. Hoskinson (US), Har Gobind Khorana (IN-US), Alexander Aleksandrovich Bayev (RU), T.V. Vekstern (RU), Andrei Darievich Mirzabekov (RU), L. Li (RU), Vladimir D. Axelrod (RU), Antomina I. Krutilina (RU), I. Fodor (RU), L.Ya Kazarinova (RU), Howard Michael Goodman (US), John Norman Abelson (US), Arthur Landy (GB), Sydney Brenner (ZA-GB), J.D. Smith (GB), Shyam K. Dube (US), Kjeld Adrian Marcker (DK), Brian F.C. Clark (GB-DK), Suzanne Cory (GB), Shosuke Takemura (JP), Takaharu Mizutani (JP), Masazumi Miyazaki (JP), Matthys Staehelin (CH), Harald Rogg (CH), Bruce C. Baguley (CH), Theodore Ginsberg (CH), Walter Wehrli (CH), Jeanne A. Nelson (US), and Susan Clark Ristow (US) purified then worked out the primary nucleotide sequences for the yeast and some bacterial tRNA molecules then postulated that they have a cloverleaf like structure with unpaired bases in some regions and paired bases in others (39-41; 101; 126; 354; 370; 489; 563; 694-696; 977; 978; 1125; 1212; 1253; 1459; 1514; 1710).

 

Benjamin D. Hall (US) and Solomon Spiegelman (US) showed that single stranded T2 phage DNA can form a hybrid with RNA from T2 infected Escherichia coli, thus, for the first time demonstrating the potential of DNA-RNA hybridization experiments (604).

Agnar P. Nygaard (US) and Benjamin D. Hall (US) reported a technique for detecting RNA-DNA hybrids by their retention on nitrocellulose membrane filters (1158).

David Gillespie (US) and Solomon Spiegelman (US) perfected this procedure for detecting RNA/DNA hybrids by annealing sheared, single-stranded RNA with high molecular weight DNA immobilized on nitrocellulose membrane filters. This technique was useful in determining the degree of homology or complementarity between a fragment of RNA and a fragment of DNA (540).

 

Murray G. Williams (GB), Allan F. Howatson (CA) and June Dalziel Almeida (CA) performed a morphological characterization of papillomavirus of the human common wart (verruca vulgaris) using the electron microscope (1663). This virus is also known as human papova virus.

 

John Josse (US), Armin Dale Kaiser (US), and Arthur J. Kornberg (US) were the first to produce good experimental evidence that the two backbones of DNA run in opposite directions (antiparallel) (759).

Francis Harry Compton Crick (GB) and James Dewey Watson (US) had suggested this antiparallel structure (311; 1626-1628).

Samuel Bernard Weiss (US) and Tokumasa Nakamoto (US) reported that the antiparallel arrangement occurs between the messenger RNA and its complimentary DNA template during transcription (1651).

 

Francis Harry Compton Crick (GB), C. Leslie Barnett (GB), Sydney Brenner (ZA-GB), and Richard J. Watts-Tobin (GB) proposed that “A group of three bases (or, less likely, a multiple of three bases codes one amino-acid. The code is not of the overlapping type… The sequence of bases is read from a fixed starting point. This determines how the long sequences of bases are correctly read off as triplets. There are no special commas to show how to select the right triplets. If the starting point is displaced by one base, then the reading into triplets is displaced, and thus becomes incorrect. The code is probably degenerate; that is, in general, one amino-acid can be coded by one of several triplets of bases” (310).

Sydney Brenner (ZA-GB), C. Leslie Barnett (GB), Francis Harry Compton Crick (GB), and Alice Orgel (GB) predicted that adding or subtracting a base pair from DNA was “likely to cause not the substitution of just one amino acid for another, but a much more substantial alteration, such as…a considerable alteration of the amino acid sequence, or the production of no protein at all” (170).

 

Marshall Warren Nirenberg (US), and Johann Heinrich Matthaei (DE) used synthetic mRNA polynucleotides such as poly U (UUUUUUU…) and poly A (AAAAAAA…) to see how they influenced the polypeptides synthesized. They found that poly U yielded polyphenylalanine, poly A yielded polylysine, poly C yielded polyproline. They further demonstrated that it was single-stranded versions of these polynucleotides and not double- or triple-stranded versions, which were active as templates for protein synthesis (1022; 1138).

Peter Lengyel (US), Joseph F. Speyer (US), and Severo Ochoa (ES-US-ES) also made synthetic polynucleotides and carried out very similar experiments (899).

 

Francois Jacob (FR) and Jacques Lucien Monod (FR) postulated that in Escherichia coli a specific repressor molecule exists that binds near the beginning of the ß-galactosidase gene at a specific site called the operator and that, by binding to the operator site on the DNA, sterically prevents RNA polymerase from commencing synthesis of ß-gal mRNA; and that lactose acts as an inducer which, by binding to the repressor, prevents the repressor from binding to the operator. In the presence of lactose, the repressor is inactivated and the mRNA is made. Upon removal of the lactose, the repressor regains its ability to bind to the operator DNA and switch off the lactose gene (738).

Francois Jacob (FR), Raquel Sussman (FR), and Jacques Lucien Monod (FR) provided evidence that the lambda CI repressor is a protein (740).

Konrad Beyreuther (DE), Klaus Adler (DE), Norbert Geisler (DE), and Alex Klemm (DE) determined the amino acid sequence of the Lac repressor in E. coli (136). Note: Philip J. Farabaugh (US) and Konrad Beyreuther (DE) corrected the primary structure (135; 425).

David VanNorman Goeddel (US), Daniel G. Yansura (US), and Marvin H. Caruthers (US) reached the conclusion that Lac repressor binds to two major grooves on one side of the DNA (549; 550).

Francois Jacob (FR) and Élie L. Wollman (FR) were able to estimate the efficiency of the integration process in bacteria. They found that once a donor gene has been transferred from Hfr cell to F minus cell, its chance of being integrated into a recombinant genome is about 0.5 (741).

Francois Jacob (FR) and Élie L. Wollman (FR) found it possible to relate genetic linkage inferred from recombinant analysis to the temporal distances established based on transfer kinetics. They found that the two loci lac and pur are separated, on the one hand, by a crossover probability of 22% and, on the other hand, by one minute of transfer time. Hence 22% linkage is equivalent to one minute of transfer. Since transfer of the entire chromosome requires about 100 minutes, and since the Escherichia coli genome is represented by a circular DNA molecule of 4000 kb pairs, we can calculate that the probability of crossover per nucleotide base pair is (22% x 100)/(1 x 4 x 106) = 0.0006% (741).

 

Leonard S. Lerman (US), Vittorio Luzzati (FR), and F. Masson (US) demonstrated that acridines bind to DNA by inserting between adjacent stacked base pairs—a process Lerman called “intercalation”—which results in the partial unwinding of the DNA double helix and an increase in viscosity (901-903). Note: Intercalation is relevant to the action mechanisms of certain antibiotics, antiparasitics (including antimalarials), anticancer agents, and carcinogens and mutagens.

Eric Terzaghi (US), Yoshimi Okada (US), Joyce Emerich (US), Masayori Inouye (US), Akira Tsugita (US), and George Streisinger (Hungarian-US) produced biochemical evidence that acridines lead to additions or deletions within DNA (1545).

 

Charles R. Spotts (US) and Roger Yate Stanier (CA) proposed that the expression of streptomycin-sensitivity, resistance and dependence, are concerned with a single intracellular site, specifically the ribosome. Subsequent studies confirmed their proposal (1455; 1456).

 

Morris Goodman (US), John Barnabas (US), Genji Maysuda (JP), G. Wiliam Moore (US), Didier Casane (FR), Stephanie Boissinot (US), Benny H.J. Chang (US), Lawrence C. Shimmin (US), and Wen-Hsiung Li (CN-US) found that computer programs applied to data from phylogenetic trees and protein polymorphism can be used to find the rate of molecular evolution of different species. It can be shown that this is slower for higher primates than for other mammals (242; 564; 565). See, Sarich, 1967 and Margoliash, 1963

Wen-Hsiung Li (CN-US) and Masako Tanimura (US) suggested that the variation in rate among mammals is primarily due to differences in generation time, rather than changes in DNA repair mechanisms. They also proposed a method for estimating the divergence times between species when the rate constancy assumption is violated (914).

 

Jean-Pierre Waller (FR), J. Ieuan Harris (GB), and Pierre-Francois Spahr (CH) performed experiments suggesting that ribosomes of Escherichia coli contain at least 20 different types of proteins; most of which carry a net negative charge (1450; 1616).

 

Peter E. Reynolds (GB) reported that vancomycin inhibits incorporation of cell-wall amino acids into cell-wall material (peptidoglycan) of bacteria (1283).

 

Joseph Polkinghorne Martin (AU), Ernest Victor Abbott (AU), and Cecil Graham Hughes (AU) were the first to report chlorotic streak of sugar cane (Saccharum officinarum) as a disease (1011).

 

Göran Möller (SE) used the fluorescent antibody technique to demonstrate mouse isoantigens at the cellular level (1083).

 

Hans G. Schlegel (DE) and Norbert Pfennig (DE) showed that Thiorhodaceae are much easier to isolate if a mud extract is added to the medium and that many Thiorhodaceae require vitamin B12 as a growth factor (1365).

 

Zoltán Klement (HU), Lászió Lovrekovich (HU) and Gyula L. Farkas (HU) were the first to report the defensive hypersensitive reaction (HR) of plants to a bacterial pathogen. In the HR the plant responds to the pathogen by generating a hypersensitive necrosis, which prevents the spread of the pathogen (821-823).

 

Heather J. Shelley (GB), John M. Bassett (GB), and Robert David George Milner (GB) described the changes in tissue glycogen concentration which occur during fetal life and the first few days after birth. Large amounts accumulate in the liver and skeletal muscles of many species as a store for use after birth. The high concentration in the heart enables the fetus to survive for long periods without oxygen (1403).

Robert Boyle (GB) had remarked on the ability of fetal and newborn animals to survive for long periods without oxygen, an ability which was lost with increasing maturity, however, the mechanism was obscure (1403; 1404).

 

Ronald Finn (GB), Cyril Astley Clarke (GB), William Thomas Atkin Donohoe (GB), Dermot Lehane (GB), Richard Bonar McConnell (GB), Philip Macdonald Sheppard (GB), William Kulke (GB), John C. Woodrow (GB), Julius R. Krevans (US), and Catherine M. Durkin (GB) revealed how the unborn child is protected from the immune system of the mother then documented the sequence of events leading to Rh disease in the child. In 1959, they began the first prospective study of the relation between ABO blood type and Rh antigen incompatibilities. By monitoring the blood of Rh-negative mothers during pregnancy and after delivery, they established that fetal erythrocytes enter the mother's blood stream usually at delivery and that, when the fetus and the mother are ABO-incompatible, the mother's immune system destroys the cells before she can become sensitized to Rh antigen.

Finn postulated that if an Rh-negative mother were given anti-Rh antibody soon enough, any fetal erythrocytes in her circulation would be inactivated before her immune system could become sensitized to the Rh antigen. At a scientific meeting in 1960, he became the first Rh investigator to suggest this. Using crude semen from sensitized Rh-negative donors, he showed that sensitization could be prevented in Rh-negative male volunteers. Experiments with pure anti-Rh antibody, given by American investigators who were independently pursuing similar research, confirmed these findings. In 1964, Finn and Clarke proved their point in a carefully-designed clinical trial, among high-risk Rh-negative women (274-276; 440-445; 1682).

Vincent J. Freda (US), John G. Gorman (US), William Pollack (US), John G. Robertson (US), Elmer R. Jennings (US), and John F. Sullivan (US) also demonstrated that anti-Rh antibody given at the time of delivery, will block sensitization and prevent Rh disease in the woman's next Rh-positive child (474-477).

 

Manfred Martin Mayer (DE-US) proposed the one-hit theory of immune hemolysis. He postulated that a single membrane lesion is sufficient to cause lysis of an erythrocyte and that a single complement molecule at least at some stage of reaction suffices for production of this lesion (1028).

Fred A. Rommel (US) and Manfred Martin Mayer (DE-US) qualified the theory slightly (1314).

 

Annemarie Weber (DE-US) and Sandra Winicur (DE) showed that contraction and relaxation of muscles is dependent upon the concentration of free calcium ion (1639).

 

Francois Henri Duckert (CH), Ernst G. Jung (CH) and David H. Shmerling (CH) discovered blood coagulation Factor XIII, also called fibrin stabilizing factor (FSF), Laki-Lorand factor (LLF), or fibrinase (373).

 

Jacques Roskam (BE), Jean Hugues (BE), and Yves Bounameaux (BE) showed that the collagen component of connective tissue leads to platelet adhesion and aggregation culminating in viscus metamorphosis (1317).

 

Erich E. Windhager (US) and Gerhard Hans Giebisch (AT-US) found that active transport of sodium occurs in the proximal convolution of the renal tubule (1664).

 

Marilyn Gist Farquhar (US), Steven L. Wissig (US), and George Emil Palade (RO-US) observed that in both the normal and the nephrotic glomerulus the basement membrane functions as the main filtration barrier; however, in nephrosis, the basement membrane is defective and allows leakage of increased quantities of ferritin and presumably plasma proteins. The basement membrane defect appears to be fine and widespread, occurring at or near the molecular level of organization of the filter. The accumulation of unfiltered ferritin in axial regions together with the demonstration of its subsequent phagocytosis by the "deep" endothelial cells suggest that the latter may function in the removal of filtration residues. Finally, the findings indicate that in the nephrotic, as in the normal animal, the epithelium acts as a monitor that recovers, at least in part, the protein which leaks through the filter, and that in nephrosis, the recovering activities of the epithelium are greatly enhanced because of the increased permeability of the basement membrane (427; 431).

 

Howard E. Morgan (US), Margaret J. Henderson (US), David M. Regen (US), Robert L. Post (US), Tomi Kim Sawyer (US), and Charles Rawlinson Park (US) studied the regulation of glucose uptake in muscle by insulin and other hormones. They showed that the limiting step for glucose uptake is the transport of the sugar across the cell membrane and that this is accelerated by insulin and anoxia. Diabetes was shown to decrease this transport and reduce its sensitivity to insulin. Hypophysectomy reduced basal glucose transport but made it more sensitive to insulin, whereas growth hormone treatment in vivo had the opposite effect. Diabetes was also shown to decrease glucose phosphorylation, which was relieved by hypophysectomy or adrenalectomy and restored by treatment with growth hormone or cortisol (650; 651; 1096; 1097; 1232).

 

Guido Majno (RO-US), George Emil Palade (RO-US), and Gutta Ingeborg Schoefl (US) found that endogenous chemical inflammatory mediators, of which histamine is the prototype, increase the permeability of blood vessels by causing gaps to appear between endothelial cells. The leaking vessels always belonged to the venous side of the circulation. The heaviest deposits were found in venules 20 to 30 microns in diameter (984; 985).

Guido Majno (RO-US-CH), Stephen M. Shea (US), and Monika Leventhal (US) used morphologic and statistical evidence to suggest that endothelial cells contract under the influence of inflammatory mediators, and that this contraction causes the formation of intercellular gaps (986).

 

Francois Jacob (FR) and Élie L. Wollman (FR) proposed that the chromosome of the Escherichia coli F+ bacterium is circular. They envisaged that the mutation from F+ to Hfr represents the spontaneous breakage of the circular chromosome and the assignment of an origin O to one of the two chromosome ends created by that breakage. This now rectilinear Hfr chromosome was then supposed to be capable of being transferred to the F- cell, beginning with the O locus, a process that the circular F+ (and presumably, also circular F-) chromosome was imagined to be incapable of performing.

The F plasmid carried by an F+ bacterium can be inserted into the host-cell chromosome in either clockwise or counterclockwise orientation at many different sites, to generate a diversity of Hfr strains with different points of origin and either direction of transfer. Second, the aberrant excision of the plasmid from the chromosome of an Hfr bacterium can give rise to a variety of different F´ plasmids, with individual plasmids carrying different amounts of host-cell chromosome contiguous to the inserted fertility factor (741).

 

Irwin Rubenstein (US), Charles A. Thomas, Jr. (US), and Alfred Day Hershey (US) determined the molecular weight of T2 bacteriophage DNA to be 130 million by using radiographic determination of the phosphorus content (1329).

 

Matthew Stanley Meselson (US) and Jean-Jacques Weigle (CH-US) provided the first conclusive proof that bacteriophage recombinants do contain part of the DNA of the parental genomes that entered the cross, and hence that genetic exchange occurs because of breakage and reunion rather than copy choice (1048).

 

Seymour Benzer (US) used deletion mutants for establishing the detailed map of the rII region in a way that made it unnecessary to cross every mutant of the collection to every other mutant. He divides the rII region of the T4 phage genome into segments, each segment being defined by the length of the map covered by one deletion but not by another. It was then a simple task to make a preliminary placement of each rII mutant to be mapped into its appropriate segment, by establishing the deletions with which the mutant does and does not produce wild-type recombinants in crosses. He proceeded to assign each of the rII mutants to one of 47 segments of the rII region (113). Note: This is the origin of the cis-trans test.

 

Marvin Fishman (US) found that RNA extracted from macrophages exposed to T2 phages in vitro could when incubated, in vitro; with normal, nonimmune rat lymph node cells stimulate them to make anti-T2 antibodies (447).

 

In 1961, a cholera pandemic originated in Indonesia. It ravaged populations across Asia and the Middle East, eventually reaching Africa by 1971. By 1973, the pandemic had spread to Italy. There were also small outbreaks of the same strain — El Tor — in Japan and the South Pacific late in the same decade (639).

 

Tim Loeb (US) and Norton David Zinder (US) discovered the RNA bacteriophage f-2 (931).

 

Heinz Stolp (DE) and Mortimer P. Starr (US) described and named Bdellovibrio bacteriovorus which Stolp and Hartmut Petzold (DE) had isolated in 1962 (Bdello (=leech). They determined it to be an ectoparasite, which invades and lyses gram-negative bacteria (1489; 1490).

Jeffrey C. Burnham (US), Tadayo Hishimoto (US), and Samuel F. Conti (US) provided electron microscopic observations on the penetration of Bdellovibrio bacteriovorus into gram-negative hosts (201).

 

Louis Stanley Diamond (US) prepared axenic cultures of Entamoeba histolytica (349).

 

L. Jonathan Tolmach (US), Thomas Terasima (US), Warren K. Sinclair (US), and Richard A. Morton (US) noted that a cell’s sensitivity to radiation fluctuates during the mitotic cell cycle (1421; 1422; 1568).

 

Malcolm Andrew Ferguson-Smith (GB) and Stanley D. Handmaker (US) presented evidence that five pairs of chromosomes in man are satellited (435).

Malcolm Andrew Ferguson-Smith (GB), Marie E. Ferguson-Smith (GB), Patricia M. Ellis (GB), and Marion Dickson (GB) confirmed that the chromosomes showing secondary constrictions most frequently in this human somatic material are chromosomes 13, 14, 15, 21 and 22. In these five pairs, a secondary constriction in the short arm separates a terminal mass, the satellite, from the rest of the chromosome arm. Secondary constrictions were also observed at specific sites in other chromosomes, although less frequently. In chromosomes 1, 6, 9 and 17 the constriction peculiar to each appeared in over 20% of the available chromosomes of the respective chromosome pair (434).

 

Leonard Hayflick (US) and Paul S. Moorhead (US) discovered that human cells (fibroblasts) derived from embryonic tissues can only divide a finite number of times in culture. They noted that cultures stopped dividing after an average of fifty cumulative population doublings (CPDs) (637; 638). This phenomenon is known as Hayflick's limit, Phase III phenomenon, or replicative senescence (RS).

 

Ian A. Macpherson (GB) and Michael George Parke Stoker (GB) devised the baby hamster kidney (BHK) cell line. Baby Hamster Kidney fibroblasts (BHK cells) are an adherent cell line used in molecular biology to study transfections and viral infections (976).

 

Alexander Mauro (US) discovered what he called "satellite cells" associated with striated muscle fiber. He suggested that they might be pertinent to the vexing problem of skeletal muscle regeneration.

 

James Edgar Till (CA) and Ernest Armstrong McCulloch (CA) discovered the clonal nature of hematopoietic stem cells (HSCs) (1558).

 

Werner Rosenau (US) and Henry D. Moon (US) demonstrated that lymphocytes from one inbred-mouse strain, previously sensitized to cells from another strain with a background of different histocompatibility, would destroy the latter type of cells in tissue culture. The lymphocytes aggregated about the (homologous, allogeneic) target-cells, resulting in marked, progressive cytopathogenic changes, with extensive lysis of the targets. These events occurred without the demonstrable involvement of serum complement or antibody and permitted the direct study of cytolytic cellular immune reactions (1316).

 

Roy L. Swank (US) observed that the microviscosity of stored blood is significantly greater than that of fresh blood leading to the discovery and filtration theory of microaggregates (1444; 1502).

 

James W. Apple (US) and Stanley D. Beck (US) published a landmark paper on voltinism in the European corn borer in which they tested the hypothesis that the adaptation of the borer to local conditions involves changes in the frequencies of genetic factors controlling its photoperiodic responses (42).

 

Susumu Ohno (JP-US) found that the chicken (Gallus domesticus) genome consists of approximately 39 chromosome pairs, including the sex chromosomes Z and W (1169).

 

James Edgar Till (CA) and Ernest Armstrong McCulloch (CA) demonstrated in mice that bone marrow from genetically identical animals contains stem cells, which can restore their immune system following its destruction by irradiation. They observed that irradiated animals given graded doses of bone marrow cells intravenously at doses insufficient to prevent death had bumps on their spleens. Andy J. Becker (CA), Ernest Armstrong McCulloch (CA), and James Edgar Till (CA) concluded that each bump is a colony of myeloerythroid cells derived from a single bone marrow precursor cell. These are called colony-forming units for the spleen (CFUs) (106; 553; 1558).

Louis Siminovitch (CA), Ernest Armstrong McCulloch (CA), and James Edgar Till (CA) provided convincing evidence that splenic colonies truly represented the proliferation of primitive hematopoietic stem cells (1417; 1418).

Alan M. Wu (CA), James Edgar Till (CA), Louis Siminovitch (CA), and Ernest Armstrong McCulloch (CA) reported that B and T cells develop from multipotent hematopoietic stem cells through restrictions during lineage progression (1688).

 

Andrzej Krzysztof Tarkowski (PL) reported the birth of the first chimaeric mice produced experimentally by injecting blastomeres from one embryo into a genetically different embryo (1520).

 

Ananda S. Prasad (US), James A. Halsted (US) and Manucher Nadimi (IR) reported a syndrome of iron deficiency anemia, stunting, hypogonadism, and hepatosplenomegaly in Iranian farmers. They speculated that zinc deficiency was the cause of the stunting and delayed development (1236).

Ananda S. Prasad (US), August Miale, Jr. (US), Zoheir Farid (EG), Harold H. Sandstead (US), Samir Bassilly (EG), William J. Darby (US), and Arthur R. Schulert (US) confirmed the hypothesis concerning zinc deficiency mentioned above (1237; 1347).

 

Edward Peirson Richardson, Jr. (US) provided the original description of progressive multifocal leukoencephalopathy, a neurological disorder characterized by destruction of cells that produce myelin, an oily substance that helps protect nerve cells in the brain and spinal cord, also known as central nervous system (CNS) white matter. It is caused by a virus called JC virus (JCV), named after the initials of the patient in whom it was first discovered, John Cunningham. The virus is widespread, found in up to 85% of the general adult population. It remains inactive in healthy individuals and causes disease only when the immune system has been severely weakened (1288). Note: John Cunningham virus (JCV) constitutes a family of polyoma viruses, which plays important roles in the progressive multifocal leukoencephalopathy (PML) and tumorigenesis.

 

Frank James Dixon (US), Joseph D. Feldman (US), and Jacinto J. Vazquez (US) found that in experimental animals making antibody responses too small to cause elimination of antigen but sufficient to result in the formation of circulating complexes chronic progressive disease develops. A chronic disease like glomerulonephritis can be turned on or off by changing the dose of antigen (352). This behavior of the immune system appears to be the underlying agent of chronic diseases such as rheumatic fever, rheumatoid arthritis, chronic glomerulonephritis, lupus erythematosus, and polyarteritis nodosa. Individuals who are poor antibody formers would appear to be predisposed to develop these chronic diseases.

 

Charles R. Anderson (US), Leslie Spence (US), Wilbur G. Downs (US), and Thomas H. Aitken (US) first isolated oropouche virus (a bunyavirus) from a patient with an acute febrile illness on the island of Trinidad off the coast of Brazil (28).

 

Fred Brown (GB), James L. Bittle (US), Richard A. Houghten (US), Hannah Alexander (US), Thomas M. Shinnick (US), J. Gregory Sutcliffe (US), Richard A. Lerner (US), David J. Rowlands (GB), C.B. Bolwell (GB), Alan L. Brown (GB), Paul V. Barnett (GB), Richard O. Campbell (GB), Berwyn E. Clarke (GB), Nigel R. Parry (GB), Elizabeth J. Ouldridge (GB), Johnny D. Callahan (US), Fernando A. Osorio (US), Jung H. Sur (US), Ed Kramer (US), Gary W. Long (US), Juan Lubroth (US), Stefanie J. Ellis (US), Katina S. Shoulars (US), Kristin L. Gaffney (US), Daniel L. Rock (US), William M. Nelson (US), David Cavanagh (GB), David V. Sangar (GB), Marie Chow (US), John F.E. Newman (ZA), David J. Filman (US), James M. Hogle (US), Graham Fox (GB), Nigel R. Parry (GB), Paul V. Barnett (GB), Brian McGinn (GB), Michael James Francis (GB), Gillian Z. Hastings (GB), John McDermed (GB), Yi-An Lu (GB), James P. Tam (GB), Peter A. Lowe (GB), Juan Lubroth (US), Marvin J. Grubman (US), Tom G. Burrage (US), Peter W. Mason (US), Barry Baxt (US), James Harber (US), Andrew Murdin (US), Eckard Wimmer (US), Richard F. Meyer (US), Gwen D. Babcock (US), Kathy Toohey (US), Frances E. Nargia (US), J. Mezencio (BR-US), J. Zamparoa (US), Cecelia Whetstone (US), Marc H.V. Van Regenmortel (FR), Jean Paul Briand (FR), Sylviane Muller (FR), B. Cartwright (GB), Timothy R. Doel (GB), Elizabeth Rieder (US), Thomas Bunch (US), Donald N. Black (GB), Timothy J.R. Harris (GB), Fan Shen (US), Pei De Chen (US), Alan M. Walfield (US), John Ye (US), James A. House (US), Chang Yi Wang (US), Ravindra Acharya (GB), Elizabeth Fry (GB), and David Stuart (GB) performed seminal studies on the chemical structure, replication, diagnosis, and vaccinology of foot-and-mouth disease viruses (5; 142; 153; 154; 182; 215; 247; 248; 268; 462; 471; 622; 938; 946; 947; 1016; 1050; 1114; 1131; 1289; 1322; 1323; 1349; 1406).

 

Theodoras Krawicz (PL) introduced cryosurgery to remove lens from the eye with a tiny probe that could attach by freezing a small area on the surface of the cataract (848).

 

Lowell O. Randall (US), George A. Heise (US), William Schallek (US), Robert E. Bagdon (US), Ralph F. Banziger (US), A. lu. Boris (US), Robert A. Moe (US), and William B. Abrams (US) first described the pharmacological properties of Valium. It was qualitatively like Librium but more potent in many pharmacological tests for taming, muscle relaxant, anticonvulsant, and sedative effects. It was well tolerated in rats, dogs, monkeys, and man (1261).

 

Thomas A. Waldmann (US), Jesse L. Steinfeld (US), Thomas F. Dutcher (US), Jack D. Davidson (US), and Robert S. Gordon, Jr. (US) described a new syndrome they named intestinal lymphangiectasia in patients previously diagnosed as having idiopathic hypoproteinemia. Intestinal lymphangiectasia is characterized by a generalized disorder of lymphatic channels including dilated small intestinal lymphatics that leads to excessive gastrointestinal protein loss and to hypoproteinemia and edema (1611).

 

Gordon Allen (US), Clemens E. Benda (US), Jan A. Böök (SE), Cedric O. Carter (GB), Charles E. Ford (GB), E. H. Y. Chu (US), Ernst Hanhart (CH), George Jervis (US), W. Langdon-Down (GB), Paul Jérome Lejeune (FR), Hideo Nishimura (JP), J. Oster (DK), Lionel S. Penrose (GB), Paul E. Polani (GB), Edith L. Potter (US), Curt Stern (US), Raymond Alexander Turpin (FR), Josef Warkany (US), and Herman Yannet (US) campaigned for human trisomy 21 (mongolism) to have its name changed to a designition such as "Langdon-Down anomaly" or "Down's syndrome or anomaly" (20).

 

Edward H. Lambert (US), E. Douglas Rooke (US), Lealdes McKendree Eaton (US), and Corrin H. Hodgson (US) described a disease, which was later called Lambert-Eaton Syndrome (LES). Its symptoms are very similar to those of myasthenia gravis but it is caused by defective release of acetylcholine from the presynaptic membrane (866).

 

Resistance to chloroquine by the malarial parasite was reported in South America and Asia. ref

 

Franz Gabl (DE) and Helmut Wachter (DE) reported that the three major human immunoglobulins, IgG, IgA, and IgM occur in whole mixed saliva (502).

 

J. Richard Crout (US), John J. Pisano (US), and Albert Sjoerdsma (US) elucidated the biochemical pathways of catecholamines and developed diagnosis of pheochromocytoma prior to exploration (313).

 

Hugh Edward de Wardener (GB), Ivor H. Mills (GB), W.F. Clapham (GB), and Clive James Hayter (GB) showed that when glomerular filtration rate and the steroid hormone aldosterone are controlled, the dog kidney is still able to increase sodium excretion in response to a salt load. Several lines of evidence argued for a small-molecule signal as a definitive modulator of sodium excretion by the kidney (338).

Christopher D. Cain (US), Frank C. Schroeder (US), Stewart W. Shankel (US), Mark Mitchnick (US), Michael Schmertzier (US), Neal S. Bricker (US) reported the identification and natriuretic activity of two closely related small molecules isolated from human urine, xanthurenic acid 8-O-beta-d-glucoside and xanthurenic acid 8-O-sulfate. Both compounds caused substantial and sustained (1- to 2-h) natriuresis in rats and no or minimal concomitant potassium excretion. They surmised that these compounds constitute a class of kidney hormones that also could influence sodium transport in nonkidney tissues given that these tryptophan metabolites presumably represent evolutionarily old structures (206).

 

Kurt Brück (DE) showed that, in the neonate, the actions of the thermoregulatory control elements are adjusted to the heat loss conditions which are determined by factors related to body size. It disproved the widespread concept of a grossly undeveloped thermoregulatory system. It is not the unresponsiveness but the very sensitive thermoregulatory reactions which require the observation of special environmental conditions for the well-being of the neonate (185).

 

Doreen Kimura (CA) found that in left-hemisphere dominant patients, speech is comprehended more accurately in the right ear and music in the left (808).

 

Ralph Waldo Gerard (US) was probably the first to suggest that endogenous stress hormones can “hasten the fixation process” of new memories thus leading to a vivid experience (519).

 

David H. Carr (CA), Murray Llewellyn Barr (CA), and Earl R. Plunkett (CA) described the Carr-Barr-Plunkett syndrome characterized by four X chromosomes (48 XXXX). The symptoms include mental deficiency (IQ average 55) and variable abnormalities, including mid-facial hypoplasia, hypertelorism, micrognathia, epicanthic folds, clinodactyly of the fifth finger, radioulnar synostosis, narrow shoulder girdle, webbed neck, amenorrhea, and irregular menstrual cycles. Behavioral disorders may be associated (236).

 

James Edgar Till (CA) and Ernest Armstrong McCulloch (CA) described a technique for the measurement of the number of cells in a bone marrow suspension capable of continued proliferation. It involves 'the formation of colonies of proliferating cells' which, in irradiated mice, appear as gross nodules in the spleen (1558).

 

Jacob Gershon-Cohen (US), Mortimer B. Hermel (US), and Simon M. Berger (US) reported the results of a five-year survey for detection of breast cancer by periodic x-ray examinations. Their results suggested that routine mammography is useful for early detection of breast cancer (529).

 

Albert William Liley (NZ) found a correlation between the spectrophotometrically estimated bilirubinoid pigment concentration in amniotic fluid and the severity of fetal anemia in Rh hemolytic disease. The paper presents a method by which this correlation could be used with precision in selecting the optimal time for delivery of each baby (921).

Albert William Liley (NZ) reported the first successful intrauterine blood transfusion. It was to save the life of a severely anemic Rh-positive fetus (922).

 

Byron H. Waksman (US), Simone Arbouys (US), and Barry G. Arnason (US) demonstrated the efficacy of using anti-lymphocyte serum to enhance skin allograft survival rates in rats (1609).

Michael Francis Addison Woodruff (GB) and N.A. Anderson (GB) showed that thoracic duct drainage along with anti-lymphocyte serum further enhanced survival rates of skin allografts in rats (1683).

Anthony P. Monaco (US), William M. Abbott (US), H. Biemann Othersen (US), Richard Lawrence Simmons (US), Mary L. Wood (US), Martin H. Flax (US), and Paul Snowden Russell (US) demonstrated the therapeutic value of anti-lymphocyte serum for improving canine kidney transplant survival (1084).

Thomas Earl Starzl (US), Thomas L. Marchioro (US), Kendrick Arthur Porter (US), Yoji Iwasaki (US), and G. James Cerilli (US) carried out the first clinical trial of anti-lymphocyte globulin as an adjunct to azathioprine and prednisone for enhancing human kidney transplant survival (1467). With the later advent of monoclonal antibodies these anti-lymphocytic sera became much more specific.

A. Benedicta Cosimi (US), Robert B. Colvin (US), Robert C. Burton (US), Robert H. Rubin (US), Gideon Goldstein (US), Patrick C. Kung (US), W. Peter Hansen (US), Francis L. Delmonico (US), and Paul S. Russell (US) introduced monoclonal anti-CD3 antibody to clinically enhance survival of renal allografts (301).

 

John C. Callaghan (CA) and Jose Delos Angeles (US) developed an artificial placenta for extracorporeal support of newborns with respiratory distress syndrome (RDS) (214).

 

Abraham M. Rudolph (US), James E. Drorbaugh (US), Peter A.M. Auld (US), Arnold J. Rudolph (US), Alexander S. Nadas (US), Clement A. Smith (US), and John P. Hubbell (US) performed cardiac catheterization studies in newborn infants which demonstrated that the ductus arteriosus is usually closed functionally in normal gestationally mature babies within 15-20 hours. Premature infants with respiratory distress had a widely patent ductus arteriosus with a large shunt, predominantly left-to-right, within the first 20 hours after birth (1333).

 

Geoffrey M. Berlyne (US) was the first to report of renal ultrasound in which the focus was mainly on the value of ultrasound in aiding renal biopsy (124).

 

Harold R. Novotny (US) and David L. Alvis (US) were the first to demonstrate the technique of fluorescein angiography in the human eye. This enabled excellent contrast studies of ocular circulation and the diagnosis of vascular disease (1150).

 

Frank J. Ayd, Jr. (US) found among 3,775 patients treated with tranquilizers of the phenothiazine group, 1,472 developed extrapyramidal reactions; 21.2% had akathisia, 15.4% parkinsonism, and 2.3% dyskinesia. There was correlation between the absolute frequency of these reactions and the chemical structure and milligram potency of the phenothiazine derivative used. Akathisia and parkinsonism occurred twice as often in women as in men, but dyskinesia happened twice as often in men. Dyskinesia was most prevalent between ages 5 and 45, akathisia between 12 and 65, and parkinsonism between 15 and 80. Dyskinesia occurred the earliest, akathisia next, and parkinsonism last in the course of treatment. These reactions appeared only in neurologically susceptible patients. A close parallel was found between drug-induced and naturally occurring extrapyramidal reactions. Drug-induced striopallidal symptoms can be adequately treated with antiparkinsonian drugs (77).

 

James R. Jude (US), William Bennett Kouwenhoven (US) and G. Guy Knickerbocker (US) performed the first external cardiac massage to restart a heart (760).

 

John F. Burke (US) found that there is a definite short period when the developing staphylococcal dermal or incisional infection may be suppressed by antibiotics. This effective period beginning the moment bacteria gain access to the tissue and is over in 3 hours. Systemic antibiotics have no effect on primary staphylococcal infections if the bacteria creating the infection have been in the tissue longer than 3 hours before the antibiotics are given. Antibiotics cause maximum suppression of infection if given before bacteria gain access to tissue (196).

 

Desmond G. Julian (GB) presented the first description of the coronary care unit (CCU) to the British Thoracic Society in July 1961 (764).

 

Kesava Mukund Lele (IN) and John Walton (GB) reported that the earliest plant stomata appeared in Zosterophyllum myretonianum. These were more like stomata found in modern moss sporophytes. The type found in vascular plants appeared 4 to 5 million years later (898).

 

William Homan Thorpe (GB) "showed that even where a programmatic element in behavior is unmistakeably large, environmental clues and cues are necessary for its complete realization. Even so, the programmatic element in behaviour is large enough and distinct enough to unseat the fundamental axiom of empericism that nothing enters the mind except by way of the senses." (1040; 1557).

 

Keller Breland (US) and Marian Breland (US) after 14 years of continuous conditioning and observation of thousands of animals, concluded that the behavior of any species cannot be adequately understood, predicted, or controlled without knowledge of its instinctive patterns, evolutionary history, and ecological niche (167).

 

J. McVicker Hunt (US) assembled the evidence against the beliefs that intelligence is essentially fixed, and that development is predetermined by each individual’s heredity. The evidence supported plasticity in development and suggested that, once the adaptive interaction between young individuals and their environmental circumstances are better understood, it should be possible to increase the average level of intelligence within the population substantially, as then and now measured, by something like 30 points of IQ (724).

 

Vero Copner Wynne-Edwards (GB) expounds a general theory that animals can limit their own numbers by social mechanisms. In so doing they avoid depleting their food resources, in the way man has so often done by overexploiting whales, fish, and game; or by overgrazing with livestock (1698).

 

Brian W. Logan (AU), Richard Rezak (US), and Robert N. Ginsburg (US) discovered living cryptozoon and associate stromatolites at Shark Bay, Western Australia (932; 933).

 

The Tokyo University Scientific Expedition to Western Asia (Director: Hisashi Suzuki) discovered fossil remains of Homo sapiens neanderthalensis; Homo neanderthalensis in a cave in Wadi Amud, north of Tiberias, Israel (1584). The remains are c. 25K-40K BP

 

Jonathan Leakey (KE-GB), Phillip V. Tobias (ZA), and John R. Napier (GB) found several fossilized bone fragments of a Homo habilis skull at Olduvai Gorge in Kenya. Leakey’s wife Meave carefully assembled the fragments to make a nearly complete skull minus the lower jaw. The skull was named KNMER 1470 for its registration at the Kenya National Museum in East Rudolf. Potassium argon dating placed it at 2.61 Ma old (882; 885).

Louis Seymour Bazett Leakey (KE), Phillip V. Tobias (ZA), and John R. Napier (GB) proposed that KNMER 1470 be designated as a new species, Homo habilis (884).

Valerii P. Alexeev (RU) described KNMER 1470 as Pithecanthropus rudolfensis (16). The name was subsequently changed to Homo rudolfensis.

 

Louis Seymour Bazett Leakey (KE), in 1961, discovered the upper jawbone of Kenyapithecus wickeri; Rangwapithecus wickeri in 14 Ma deposits in Kenya (883).

 

Brian W. Logan (AU), Richard Rezak (US), and Robert N. Ginsburg (US) discovered living cryptozoon and associate stromatolites at Shark Bay, Western Australia (932; 933; 1219; 1220).

Stanley M. Awramik (US), J. William Schopf (US), Malcolm R. Walter (US), and Bonnie M. Packer (US) found rock bearing 3.5 Ga. microfossils within early Archean (Gk. archaios=ancient) stromatolites (73; 1371; 1373). The microfossils were interpreted to be prokaryotes and to represent the oldest fossils known (1372).

 

Publication of the first issue of CDC's Morbidity and Mortality Weekly Report (then U.S. Communicable Disease Center)

 

c. 1962

The methylbenzimidazole carbamates (MBCs) were introduced as systemic plant fungicides. These include benomyl, carbendazin, thiophanate, and thiophanate-methyl. See, C.J. Delp, 1987. Benzimidazole and related fungicides. In Modern Selective Fungicides—properties, applications, mechanisms of action. H. Lyr, Ed. Longman Group, London. These fungicides inhibit the formation of normal microtubules.

 

1962

“A living system is constantly fighting against, rather than relying upon, thermodynamic equilibrium. The thermodynamic significance of specific cellular control systems precisely is that they successfully circumvent thermodynamic equilibration (until the organism dies, at least…. Still, the arbitrariness, chemically speaking, of certain allosteric effects appears almost shocking at first sight, but it is this very arbitrariness which confers upon them a unique physiological significance, and the biological interpretation of the apparent paradox is obvious. The specific structure of any enzyme-protein is of course a pure product of selection, necessarily limited, however, by the structure and chemical properties of the actual reactants. No selective pressure, however strong, could build an enzyme able to activate a chemically impossible reaction. In the construction of an allosteric protein this limitation is abolished, since the effector does not react or interact directly with the substrates or products of the reaction but only with the protein itself…. By using certain proteins not only as catalysts or transporters but as molecular receivers and transducers of chemical signals, freedom is gained from otherwise insuperable chemical constraints, allowing selection to develop and interconnect the immensely complex circuitry of living organisms.” Jacques Lucien Monod (761).

 

"Let us never forget that Nature is the most original of all experimenters and that it is the patient’s physician who is privileged to learn most directly from her sometimes cruel, but never meaningless, clinical presentations." William Bosworth Castle. From his speech accepting the Kober Medal of the Association of American Physicians, in 1962.

 

Max Ferdinand Perutz (AT-GB) and John Cowdery Kendrew (GB) were awarded the Nobel Prize in Chemistry for their studies of the structures of globular proteins.

 

Francis Harry Compton Crick (GB), James Dewey Watson (US) and Maurice Hugh Frederick Wilkins (GB) were awarded the Nobel Prize in Physiology or Medicine for their discoveries concerning the molecular structure of nuclear acids and its significance for information transfer in living material.

 

Tibor Barka (US) and Paul J. Anderson (US) analyzed problems inherent in the histochemical demonstration of acid phosphatase activity and described methods which provide reliable, accurate localizations (81).

 

Osamu Shimomura (JP-US), Frank H. Johnson (US), and Yo Saiga (US) extracted, purified and noted the properties of aequorin, a bioluminescent protein from the luminous hydromedusan, Aequorea. Green fluorscent protein (GFP) was also isolated at this time (1411).

James G. Morin (US) and J. Woodland Hastings (US) detected an intermolecular energy transfer between aequorin and GFP in jellyfish (1098).

Osamu Shimomura (JP-US) characterized the structure of the chromophore of Aequorea green fluorescent protein (1410).

Douglas C. Prasher (US), Richard O. McCann (US), and Milton J. Cormier (US) cloned and expressed the Cdna coding for aequorin, a bioluminescent calcium-binding protein (1239).

Douglas C. Prasher (US), Virginia K. Eckenrode (US), William W. Ward (US), Franklyn G. Pendergast (US), and Milton J. Cormier (US) determined the primary structure of the Aequorea victorea green fluorescent protein (1238).

Chris W. Cody (US), Douglas C. Prasher (US), William M. Westler (US), Frank G. Pendergast (US), and William W. Ward (US) determined the chemical structure of the hexapeptide chromophore of the Aequorea green fluorescent protein .

Martin Chalfie (US), Yuan Tu (US), Ghia Euskirchen (US), William W. Ward (US), and Douglas C. Prasher (US) discovered how to use green fluorescent protein as a marker for gene expression (249).

Mats Ormö (US), Andrew B. Cubitt (US), Karen Kallio (US), Larry A. Gross (US), Roger Yonchien Tsien (US), S. James Remington (US), Fan Yang (US), Larry G. Moss (US), and George N. Phillips, Jr. (US) produced the first crystal structures of wild-type and enhanced GFP. Tsien designed T203Y mutant based on crystal structure of S65T GFP. It is yellow fluorescent (1186; 1700).

Mikhail V. Matz (RU), Arkady F. Fradkov (RU), Yulii A. Labas (RU), Aleksandr P. Savitisky (RU), Andrey G. Zaraisky (RU), Mikhail L. Markelov (RU), and Sergey A. Lukyanov (RU) cloned six fluorescent proteins homologous to the green fluorescent protein (GFP) from Aequorea victoria. Two of these have spectral characteristics dramatically different from GFP, emitting at yellow and red wavelengths. Many new fluorescent proteins and chromoproteins were discovered. GFP was found to tolerate insertion of entire proteins in certain locations and can be circularly permuted (1024). Note: DsRed, a red fluorescent protein from coral, was discovered.

Robert E. Campbell (US), Oded Tour (US), Amy E. Palmer (US), Paul A.. Steinbach (US), Geoffrey S. Baird (US), David A. Zacharias (US), and Roger Yonchien Tsien (US) produced a monomeric form of red fluorescent protein (mRFP1) which proved to be much more useful than DsRed as a genetically encoded fusion tag (222).

Malte C. Gather (US) and Seok Hyun Yun (KR-US) showed that fluorescent proteins in cells are a viable gain medium for optical amplification, and report the first successful realization of biological cell lasers based on green fluorescent protein (GFP) (508).

 

Klaus Scherrer (CH) and James E. Darneil, Jr. (US) described how techniques developed for extraction of infectious viral nucleic acid were used to extract cell RNA, resulting in the recognition, for the first time, of high molecular weight nuclear RNA from mammalian cells. The dominant rapidly labeled peaks, ‘45S’ and ‘35S,’were subsequently found to be ribosomal precursor RNA, and the polydisperse material was characterized as the so-called ‘heterogeneous nuclear RNA,’ the hnRNA (1362).

 

Wendell Caraway, Jr. (US) deals with a survey and discussion of variables and potential sources of error in the individual specimen that affect the chemical specificity of clinical laboratory tests. Special attention is directed to factors less subject to correction by means of the usual technics of quality control. These include consideration of chemical specificity, anticoagulants, stability of specimens, hemolysis, lipemia, control of temperature and pH, contamination, effect of medications, and normal physiologic variations in persons (228).

 

William Wallace Cleland (US), from his analysis of many enzymatic reactions, described a general method for predicting initial velocity, dead end, and product inhibition patterns by inspection of the mechanism (278).

 

Thomas Samuel Kuhn (US) argued that science is not a steady, cumulative acquisition of knowledge but instead a series of peaceful interludes punctuated by intellectually violent revolutions. He described science in terms of paradigms—pervasive frameworks of scientific thoughts (857).

 

Lucien G. Caro (CH) and Robert P. van Tubergen (CH) described methods used in obtaining high resolution in autoradiography, with special emphasis on the technique of electron microscopic autoradiography, together with control experiments designed to establish the optimum conditions or procedures. These methods give a good localization of the label, at the subcellular level, and good reproducibility in relative grain counts (235).

 

Aaron H. Anton (US) and David F. Sayre (US) presented a reliable, quantitative, highly sensitive, adaptable method for the estimation of catechol-amines in diverse biological material from various vertebrate species. This method involves the selective adsorption of the catecholamines onto a constant amount of aluminum oxide, elution with constant volume of perchloric acid (0.05 N), and their measurement by the formation of a fluorescent trihydroxyindole derivative in the presence of potassium ferricyanide and alkaline (10 N alkali) ascorbate (36).

 

Dianne Mattingly (GB) greatly improved and simplified a fluorimetric method for the estimation of free 11-hydroxycorticoids in human plasma. Their plasma concentration is a valuable measure of adrenocortical activity, provided that the normal circadian rhythm is considered (1023).

 

Arthur S. Barclay (US), in 1962, collected the bark of the Pacific Yew tree, Taxus brevifoli Nutt. as part of a joint effort by the United States Department of Agriculture and the National Cancer Institute to discover new anticancer agents (810). Circa 1963 its extract was found it be anticancerous in an animal study. ref

Scientists at the Research Triangle Institute (RTI) in North Carolina extracted from the Pacific Yew an anticancer agent they named taxol.

Mansukh C. Wani (US), Harold L. Taylor (US), Monroe E. Wall (US), Philip Coggon (US), and Andrew T. McPhail (US) reported the molecular structure of taxol based on x-ray crystallographic studies (1621). Taxol is an antileukemic and antitumor agent isolated from Taxus brevifolia Nutt.

Peter B. Schiff (US), Jane Fant (US), and Susan Band Horwitz (US) discovered that taxol interferes with cell division by binding to the protein tubulin, which is a key factor in mitosis. Unlike some other cancer drugs, which prevent tubulin from assembling into microtubules, taxol binds to assembled microtubules and blocks them from disassembling (1363).

 

Colin C.F. Blake (GB), Ruth H. Fenn (GB), Roberto J. Poljak (FR), Don F. Koenig (US), Gareth A. Mair (GB), A.C. Tony North (GB), David Chilton Phillips (GB), V. Raghu Sarma (GB), and Louise N. Johnson (GB) used x-ray analysis to solve the structure of lysozyme, the first enzyme to be so analyzed. They also got the first detailed molecular view of an enzyme’s active site. The analysis was carried out on crystalline lysozyme from egg white at a resolution of two angstroms (145-148; 754; 1217). The Johnson paper is the first in which x-ray crystallographic studies gave direct information about the active site.

 

Christian Boehmer Anfinsen, Jr. (US) demonstrated that the information required to fold the polypeptide chain of ribonuclease into the specific three-dimensional form of the active enzyme resides in the sequence of amino acids (32).

 

Gustav V.R. Born (GB) introduced a photometric method with which platelet aggregation and its inhibition by adenosine diphosphate and related compounds respectively are investigated quantitatively (159).

 

James L. German, 3rd (US), using human blood cells, found that experiments using pulse-labeling with tritiated-thymidine provide information concerning the location of synthesis of DNA at various times, and the pattern has been found to be complex. The different chromosomes follow no consistent pattern such as replication beginning at the centromeres and continuing to the telomeres. However, during the final 150 to 180 minutes of the S period, one chromosomal region after another becomes fully replicated although the pattern at this time also is complex and different in each chromosome.

One striking finding strongly suggested that the pattern of DNA replication may be of functional significance.

These experiments gave the best confirmation of the single-X origin of sex chromatin (527).

 

Hans Ris (CH-US) and Walter Plaut (US) found DNA in the chloroplast of Chlamydomonas moewusii. They speculated that this may represent the genetic system of the chloroplast and hypothesized that the chloroplast represents an evolved endosymbiont (1300).

Edward H.L. Chun (US), Maurice Vaughn, Jr. (US), Alexander Rich (US) Ruth Sager (GB), M.R. Ishida (US) and John T.O. Kirk performed the first unambiguous isolations of DNA from chloroplasts of spinach, beet, Chlamydomonas, and ChlorelIa reported by Edward H. L. Chun, Maurice H. Vaughan, Jr., and Alexander Rich; from Chlamydomonas by Ruth Sager (US) and M. R. Ishida (US); and from broad bean by John T. O. Kirk (GB) (270; 813; 1342).

 

Daphne J. Osborne (GB) noted that as leaves age and yellow, changes take place within the cells which include degradation of proteins and nucleic acids. She discovered that senescence and loss of integrity of these macromolecules could be arrested by simply applying the requisite plant hormone to the leaves opening a new and exciting era in studies of cellular senescence. The incorporation of radioactive precursors indicated that the hormone-maintained synthesis of nucleic acids and proteins deferred senescent change and retained cellular homeostasis (1193).

Kathryn S.E. Cheah (GB) and Daphne J. Osborne (GB) found that in dry seeds, fragmentation of nuclear DNA and activation of DNases occur in vivo during embryo senescence. This loss of DNA integrity could be the source of chromosomal aberrations and impaired transcription observed when seeds of low viability germinate (264).

 

Peter Reichard (AT-SE), using Escherichia coli, managed to purify two enzyme fractions, A and B (later called R) that participated in the formation of deoxycytidine phosphates from CMP. He found that Fraction A catalyzed the phosphorylation of cytidine 5-phosphate (CMP) to cytidine 5-diphosphate (CDP) whereas Fraction B (later called R) carried out the reduction of the cytidine diphosphate to deoxycytidine diphosphate (dCDP). The reaction catalyzed by Fraction B required ATP, Mg2 ions (1273).

Anders Ehrenberg (SE) and Peter Reichard (AT-SE) discovered that R2 contains a signal characteristic of a free radical. The presence of this signal is also linked to the enzymatic activity of R2, suggesting that ribonucleotide reduction proceeds by radical chemistry. They also found that it contains two atoms of iron (393).

Jens Harder (SE), Rolf Eliasson (SE), Elisabet Pontis (SE), Marcus D. Ballinger (US), and Peter Reichard (AT-SE) showed that the overall reduction of CTP occurred in two steps. The first step is the activation of the reductase (dA3) by dA1 and RT. During this step AdoMet (S-adenosyl-L-methionine) is reductively cleaved into methionine and 5-deoxyadenosine. The second step involves the actual reduction of CTP with dithiothreitol as the hydrogen donor (616).

 

James Whyte Black (GB), John S. Stephenson (GB), Anne C. Dornhorst (GB), and Brian F. Robinson (GB) discovered the first clinically useful beta-blocker, called pronethalol. The doses at which it is useful are carcinogenic in mice (144; 361).

James Whyte Black (GB), Albert Frederick Crowther (GB), Robin G. Shanks (GB), Lloyd Hollingsworth Smith, Jr. (GB), and Anne C. Dornhorst (GB) produced propanolol, a much safer and more efficient beta blocker (143).

Beta-blockers are so called because they block the absorption of hormones by beta-receptors in the nervous system. Blocking these receptors causes the heart to slow down so it uses less oxygen. It also lowers the blood pressure.

 

R. Charlier (BE), G. Deltour (BE), Rene Tondeur (BE), and Fernand Binon (BE) discovered amiodarone (262). This drug is used to treat angina pectoris and cardiac arrhythmias.

 

Donald J. Mason (US), Alma Dietz (US), and Clarence DeBoer (US) isolated the antibiotic lincomycin from Streptomyces lincolnensis found in soil near Lincoln, Nebraska (1015).

 

Wagn O. Godtfredsen (DK), Sverre Jahnsen (DK), Henning O.B. Lorck (DK), Knud Roholt (DK), and Leif Tybring (DK) isolated the antibiotic fusidic acid (fucidin) from Fusidium coccineum (548).

 

B.B. Gokhale (IN), Arvind A. Padhye (IN-US), M.V. Joglekar (IN), and R. Anjaneyuln (IN) isolated the antifungal antibiotic hamycin from Streptomyces pimprina (551).

 

Albert L. Chaney (US) and Edward P. Marbach (US) described a simplified indophenol reaction for the measurement of ammonia in biological fluids (253).

 

Kurt M. Dubowski (US) described a single-reagent manual method for measurement of glucose in biological fluids (372).

 

Gilbert N. Ling (CN-US) presented the principles of his new theory and developed the Association-Induction (A-I) Hypothesis. This theory incorporates the ideas that (a) cell water is structured—by “structured” it is meant that the water molecules are not free or random but exhibit an orderly arrangement as in ice crystals—although cellular structured water is much less solid than ice (b) cell cations are associated mostly with macromolecules and (c) cation pumps do not exist (925).

 

George Yohe Lesher (US), Ernest J. Froelich (US), Monte D. Gruett (US), John H. Bailey (US), and R. Pauline Brundage (US) prepared and identified nalidixic acid as an antibacterial agent worthy of clinical development. It is the prototype of the highly potent class of antibacterial agents called quinolones (908).

Martin Frank Gellert (US), Kiyoshi Mizuuchi (US), Mary H. O'Dea (US), Tateo Itoh (JP), and Jun-Ichi Tomizawa (JP) identified DNA gyrase of bacteria as the target of nalidixic acid and oxolinic acid (515).

Hitoshi Koga (JP), Akira Itoh (JP), Satoshi Murayama (JP), Seigo Suzue (JP), and Tsutomu Irikura (JP) discovered the fluorinated quinolone norfloxacin, which possesses considerable broad-spectrum antibacterial activity (829).

 

Gerald Maurice Edelman (US) and Joseph A. Gally (US) found that the light chains of myeloma proteins and Bence Jones proteins are identical (386).

 

Calvin M. Kunin (US) discovered an antigen common to all Enterobacteriaceae and designated it as enterobacterial common antigen (CA or ECA) (858; 859). It has also been called the Kunin-antigen. Through the efforts of many its composition was ultimately determined to be an amino sugar polymer built of N-acetyl-D-glucosamine and N-acetyl-D-mannosaminuronic acid partially esterified by acetic and palmitic acids.

 

Joseph D. Mann (US), Amos Cahan (US), Allen G. Gelb (US), Nathalie Fisher (US), Jean Hamper (GB), Patricia Tippett (GB), Ruth Sanger (GB), and Robert Russell Race (GB) discovered the Xg blood group antigen (993).

 

Roger Wolcott Sperry (US) provided the direct histological evidence and proposed the chemoaffinity hypothesis for axon guidance, i.e., growing axons are guided principally by molecular determinants, rather than mechanical determinants such as cells, extracellular material and other neurons. The growing axons take a path by responding to specific guidance molecules that either attract or repel the growth cone (1451).

 

Ferruccio M. Ritossa (IT) described a new puffing pattern in salivary gland chromosomes of Drosophila following heat shock (1301). This was the first description of a heat shock response.

Alfred Tissières (CH), Herschel K. Mitchell (US) and Ursula M. Tracy (US) were the first to identify the relevant gene products—the heat shock proteins (1561).

 

Michael J. Chamberlin (US), Paul Berg (US), John J. Furth (US), Jerard Hurwitz (US), and Monika Anders (US) described the purification and characterization of a RNA polymerase from Escherichia coli. This enzyme catalyzes the synthesis of RNA from the four ribonucleoside triphosphates, and is completely dependent on DNA (250; 498).

 

Johann Heinrich Matthaei (US), Oliver W. Jones (US), Robert G. Martin (US), and Marshall Warren Nirenberg (US) created a cell-free protein synthesizing system in which they could test the effect of template RNA (mRNA) on amino acid sequence. They found: (1) that longer polynucleotide chains are more effective than shorter ones at directing the synthesis of polyphenylalanine from polyuridylic acid, 2) One molecule of polyuridylic acid may direct the synthesis of a number of molecules of polyphenylalanine, 3) randomly mixed polynucleotides as well as homopolynucleotides can be used to direct cell-free amino acid incorporation, 4) two coding units corresponding to leucine were found; thus, part of the code was shown to be degenerate, 5) certain nucleotide sequences in a polynucleotide did not code for any amino acid: therefore, the presence of nonsense coding units was suggested, 6) the minimum number of nucleotides per coding unit appeared to be three, and 7) comparison between the composition of RNA coding units in E. coli and amino acid replacement data in tobacco mosaic virus suggested that at least a part of the code may be universal (1021).

 

Bernard Weisblum (US), Seymour Benzer (US), and Robert William Holley (US) found that Escherichia coli contains two different sRNAs (tRNAs) acting as acceptor-carriers for leucine. One reacts with poly UC, while the other reacts with poly UG. This provides an explanation for the degeneracy observed in coding experiments with leucine. The experiments also confirm that the coding specificity is carried by the sRNA (tRNA) (1647).

 

Dario Giacomoni (US) and Solomon Spiegelman (US), using RNA-DNA hybridization techniques, concluded that the genome contains tRNA complementary sequences for more than twenty amino acids. This evidence they concluded supports the idea that the code is degenerate. They found that tRNA molecules specific for a given amino acid did differ in some of their nucleotide sequence if taken from different species (531).

 

Sewell P. Champe (US) and Seymour Benzer (US) found that 5-fluorouracil is incorporated into messenger RNA in place of uracil, there acting partially like cystine. This allows 5FU to partially reverse defective phenotypes of certain rII mutants of phage T4. The results are consistent with the idea that only one strand of the DNA duplex is copied into useful messenger RNA (251).

Julius Marmur (US), Carol M. Greenspan (US), Emil Palecek (CZ), Frederick M. Kahan (US), James Levine (US), and Manley Mandel (US), using Bacillus subtilis and the bacteriophage SP8, also presented experimental evidence that only one of the two complementary strands of DNA acts as a template for messenger RNA (1005).

 

Raymond Valentine Tomlinson (CA-US), Gordon Malcolm Tener (CA), Robert William Holley (US), James T. Madison (US), and Ada Zamir (US) developed methodologies by which they could determine the nucleotide base sequence in small oligonucleotides (697; 1570; 1571).

 

Seymour Benzer (US) and Sewell P. Champe (US), Alan Garen (US), and Obaid Siddiqi (IN) discovered, using the T4 bacteriophage of Escherichia coli, that nonsense mutations can produce codons which behave as nonsense codons, meaning they do not code for an amino acid (115; 506).

 

Seymour Benzer (US), Sewell P. Champe (US), Sydney Brenner (ZA-GB), Anthony O.W. Stretton (US), Samuel Kaplan (US), Leslie Barnet (GB), Eugene R. Katz (US), Francis Harry Compton Crick (GB), Martin G. Weigert (US), Erich Lanka (DE), and Alan Garen (US) provided evidence that there are three nonsense codons, UAA (ochre), UAG (amber), and UGA which do not specify an amino acid. Brenner, Stretton, and Kaplan suggested that the nonsense codons should be more properly considered to be the codons for polypeptide chain termination (115; 169; 174; 1643; 1644).

Giuseppe Macino (IT), Gloria Coruzzi (US), Francisco G. Nobrega (US), May Li (US), and Alexander Tzagoloff (US) performed a sequence analysis of yeast mitochondrial DNA regions coding for structural genes of cytochrome b, cytochrome oxidase, and the ATPase. They concluded that the classic UGA terminator regularly occurs as a tryptophan codon in yeast mitochondrial DNA (970).

Susan G. Bonitz (US), Roberta Berlani (US), Gloria Coruzzi (US), May Li (US), Giuseppe Macino (IT), Francisco G. Nobrega (US), Marina P. Nobrega (US), Barbara E. Thalenfeld (US), and Alexander Tzagoloff (US) established the codon recognition rules in yeast mitochondria as follows: The four codons of unmixed families are recognized by single tRNAs that always have a U in the wobble position of the anticodon. Two different tRNAs read the codons of the mixed families. Codons terminating in a C or U are recognized by tRNAs with a G and codons terminating in a G or A are recognized by tRNAs with a U in the corresponding positions of the anticodons. There are two exceptions to these rules. In the AUN family for isoleucine and methionine, the isoleucine tRNA has a G and the methionine tRNA has a C in the wobble position. The tRNA for the arginine CGN family also has an A in the wobble position of the anticodon. It is of interest that the CGN codons have not been found in the mitochondrial genes sequenced to date. The simplified decoding system of yeast mitochondria allows all the codons to be recognized by only 24 tRNAs (157).

 

Dennis Francis Cain (US) and Robert E. Davies (US) poisoned muscles with 1-fluoro-2, 4-dinitrobenzene (DFNB), thus preventing phosphocreatine from reconverting ADP to ATP. The amount of ATP lost with each muscle twitch was determined and was found to account for the energy needed to cause the muscles to shorten. Finally, ATP had been shown to be the direct source of energy for muscle contraction (207).

 

Ellis T. Bolton (US) and Brian John McCarthy (US) reported a DNA-agar technique for determining the degree of complementarity between two fragments of DNA (152).

 

Maurice Hugh Frederick Wilkins (GB) demonstrated that the B form of DNA was present in all the organisms he tested, from viruses to mammals (1660).

 

Francois Chapeville (US), Fritz Albert Lipmann (DE-US), Günter von Ehrenstein (US), Bernard Weisblum (GB), William J. Ray (US), and Seymour Benzer (US) developed a method to demonstrate directly that only the sRNA (tRNA) molecule, and not its attached amino acid, found the place on the template (mRNA) calling for that amino acid (261).

 

Marshall Warren Nirenberg (US) and Johann Heinrich Matthaei (DE), and Oliver W. Jones (US) performed an experiment demonstrating that when poly-uracil directs the synthesis of poly-phenylalanine a transfer RNA specific to phenylalanine is an obligate intermediate in the process (1139).

 

Sydney Brenner (ZA-GB) invented the term codon as it applies to an RNA sequence, which specifies a specific amino acid (761).

 

Cyrus Levinthal (US), Alexander Keynan (IL), and Akiko Higa (US) used Bacillus subtilis to demonstrate that messenger RNA is used on average 10-20 times with a half-life of 20 minutes (910).

 

Daniel Nathans (US), Gursuran Notani (US), James H. Schwartz (US), and Norton David Zinder (US) used a cell-free system from E. coli with bacteriophage f2 RNA to produce viral coat protein identical in amino acid sequence to that isolated directly from the virus. This was the first example of purified mRNA directing the synthesis of a specific protein (1120).

 

Jonathan R. Warner (US), Alexander Rich (US), Cecil E. Hall (US), and Paul M. Knopf (US) found that the predominant species of ribosome synthesizing hemoglobin consisted of a cluster of five ribosomes acting on the same messenger RNA strand (1623; 1624). These findings were interpreted to mean that the ribosomal particles begin protein synthesis by attaching at one end of the messenger RNA strand then move along it as the polypeptide chain elongates. This represents the discovery of polyribosomes (polysomes).

Alexander Rich (US) and Walter Gilbert (US) independently discovered that a single messenger RNA molecule can be read simultaneously by several ribosomes. These complexes of mRNA with ribosomes are called polyribosomes (polysomes) (538; 539; 1285).

 

Lloyd Barr (US) and Maynard M. Dewey (US) described intercellular connections (gap junctions) between smooth muscle cells in canine gut tissue (88).

 

Tracy Morton Sonneborn (US) and Janine Beisson (US), in studies of the cortex of Paramecium aurelia, showed that the form and arrangement of the pre-existing structures determine the form and arrangement of new structures (111; 1447; 1448).

 

Mary Agnes Chase (US) and Cornelia D. Niles (US) produced their Index to Grass Species. This is a verified card index, some 80,00 cards, for all (worldwide) published names of grasses (263). The collection accessions of Chase, mostly grasses, ran to about 12,000 numbers.

 

Knut Schmidt-Nielsen (DK-US) reported that desert reptiles maintain their osmotic regulation by avoiding excessive heat exposure, eating prey with high water content, and excreting uric acid (1367).

 

 Michael Hollings (GB) was the first to clearly implicate a virus infection as the cause of die-back disease of cultivated mushrooms (699).

 

Aron Arthur Moscona (US) and Robert E. Hausman (US) proposed that cells recognize each other using very specific surface molecules (634; 1101).

 

Youssef Hatefi (IR-US), Arne G. Haavik (US), L.R. Fowler (US), and David E. Griffiths (GB) reconstituted a functional electron transport system from fragmented beef heart mitochondria and identified its components (630).

 

Walter Plowright (GB) developed a rinderpest vaccine which is so effective that it has almost eradicated the disease (1221).

 

William C. Russell (GB) demonstrated plaques in tissue culture caused by Herpes virus type 1 (1336).

 

James S. Porterfield (GB), Jordi Casals (ES-US), Charles H. Calisher (US), and Nick Karabatsos (US) participated in the development of the arbovirus serological classification scheme (213; 240; 241; 1231).

 

Julio G. Barrera-Oro (AR-US), Kendall O. Smith (US), and Joseph Louis Melnick (US) discussed the quantitation of papova virus particles in human warts (92).

 

George Bellamy Mackaness (AU-US) while studying the phagocytosis of Staphylococcus aureus, showed that this bacterium was relatively resistant to phagocytosis by macrophages, unless a specific immune serum was provided. The greater efficiency observed with polymorphonuclear phagocytes led him to suggest that the antibacterial mechanisms of the two cell types were fundamentally different (971).

George Bellamy Mackaness (AU-US) discovered that successful infection by Listeria monocytogenes depends upon its ability to multiply within macrophages and monocytes. He also showed that inactivation of Listeria monocytogenes is better achieved in convalescent mice, thanks to the presence of resistant macrophages, because of immunological activation occurring during the primary infection (972; 974). Note: This work led him to introduce the concept of macrophage activation.

Robert J. North (GB) and George Bellamy Mackaness (AU-US) used electron microscopic observations of peritoneal macrophages from mice immunized with L. monocytogenes to reveal structural differences with macrophages from normal mice (1147).

George Bellamy Mackaness (AU-US) while studying Brucella abortus or M. tuberculosis infection, in addition to Listeria, showed that the acquired resistance was dependent on the immunological reactivity of the host and specific antibodies against microbial antigens (973).

George Bellamy Mackaness (AU-US) discovered cellular cooperation. He demonstrated that the acquired resistance was dependent on the activation of macrophages through a product resulting from specific interaction between sensitized lymphoid cells and the microorganism (974).

James Gerald Hirsch (US) characterized a bactericidal substance isolated from polymorphonuclear cells he called, “phagocytin”. Phagocytin, identified in rabbit neutrophils, was bactericidal on gram-negative and -positive bacteria but was not bacteriolytic. Extracts from human and guinea pig neutrophils were less efficient, and the activity was absent from mouse and rat cells (676).

James Gerald Hirsch (US) and Alice B. Church (US) also reported that group A streptococci exert an antiphagocytic effect through the action of the hyaluronic acid capsule and M protein. Factors present in human plasma but absent in rabbit plasma can counteract this antiphagocytic effect (678).

James Gerald Hirsch (US) and Zanvil Alexander Cohn (US) used microscopic and “cinemicrophotographic” studies to provide details of the fusion between the granule membrane and the invaginated cell membrane overlying the ingested particle with discharge of granule contents directed into the phagocytic vacuole (677; 679).

Gordon T. Archer (US) and James Gerald Hirsch (US) identified a similar mechanism within eosinophils (49).

Zanvil Alexander Cohn (US), and Edith Wiener (US) discovered that specific phagocyte granules, the lysosomes, discharge their contents into the phagosome containing the ingested microorganism, leading to the digestion of the microbes (289).

Ralph van Furth (NL) and Zanvil Alexander Cohn (US) identified blood monocytes as the precursors for tissue macrophages and bone marrow as the source of monocytes (1589).

Ralph van Furth (NL) published an elaborate figure depicting the origin and kinetics of mononuclear phagocytes and the nature of the involved hematopoietic factors (1588).

 

Janet V. Passonneau (US) and Oliver H. Lowry (US) observed that during glycolysis high levels of inorganic phosphate counteracted the ATP inhibition of 6-phosphofructokinase (1205).

 

Allan McCulloch Campbell (US) proposed a model for the attachment of the prophage to the bacterial chromosome. According to this model, the phage genome is capable at some stage during its life cycle of circularizing—i.e., its ends become physically associated with each other. Lysogenization results from a reciprocal crossover between a specific region of the circularized phage genome and its homolog in the bacterial chromosome. The result is the prophage is inserted into the bacterial chromosome. The vegetative phage and the prophage are both linear structures, derived by cutting the same circle at different points. The gene order on one is a circular permutation of that on the other (219-221). Note: Enrico Calef (IT), Giuseppe Licciardello (IT), Alfred Day Hershey (US), Elizabeth Burgi (US), Laura Ingraham (US), Martin Frank Gellert (US), Ray Wu (CN-US), and Armin Dale Kaiser (US) made significant contributions which led to the understanding of lambda prophage insertion (212; 514; 663; 1689).

 

Werner Arber (CH) and Daisy Dussoix (CH) found that lambda bacteriophages carry a host specificity determined by the bacterial strains on which they were produced. Upon infection of a different bacterial host (1) the phage DNA may be either accepted or rejected based on this specificity, (2) if accepted, the phage multiplies, and progeny phage are produced carrying the same specificity of the original infecting phage. Working with Escherichia coli K-12 Arber discovered that lambda virus will not grow in cells infected with P1 virus. His results suggested that P1 is methylated and thus protected from cellular nucleases (43; 44).

Werner Arber (CH), Urs Kuhnlein (CA), Stuart M. Linn (US), Matthew Meselson (US) and Robert Yuan (US), working with extracts of Escherichia coli strain B, discovered a specific enzyme capable of methylating DNA and another specific enzyme capable of breaking down unmethylated DNA (43; 45; 926; 1049). These extracts contained the first known restriction endonucleases, which represent a cellular defense mechanism, preventing hydrolysis of the parental DNA by nucleases in the cell. The nucleases protect against the introduction of foreign DNA.

 

Robert Louis Sinsheimer (US), Barbara Starman (US), Carolyn Nagler (US), and Shirley Guthrie (US) studied the intracellular replication of single stranded DNA from øX174 and found that the circular infectious plus strand serves as template for the synthesis of a complementary minus strand, yielding the double-stranded replicative form, or RF. At early stages of infection, RF replicates semiconservatively to yield daughter RF molecules. At late stages of infection, when phage-capsid protein molecules are already present, a new, asymmetric mode of replication sets in. Now only the minus strands of the RF serve as template for the synthesis of a daughter plus strand, thereby expelling the old plus strand from the RF molecule. The expelled plus strand is then encapsulated into a progeny phage capsid (1428; 1429).

 

Seymour Benzer’s (US) second, and probably most important use of the rII mutants provided an experimental definition of the gene. In order to examine whether two different rII mutants belong to the same functional unit, he adapted to phages the cis-trans or complementation test, which had been developed previously with higher organisms for the very purpose of probing the nature of the functional unit of the gene. Benzer’s complementation test is based upon the finding that, in a strain K bacterium infected jointly with rII mutant and r+ wild-type phages, both types can grow normally. The normal rII+ gene of the wild-type parent is, therefore, able to supply the function necessary for growth in the strain K bacterium, not only for itself but also for the defective rII mutant. Or, in genetic parlance, in mixed infection the r+ wild-type gene is dominant over its rII mutant allele. Based on this test, Benzer found that rII point mutations fall into two functional groups, A and B; all mutants belonging to one group complement any member of the other group in the production of infectious progeny in joint growth in strain K, but do not complement in this way any members of their own group. It turned out, furthermore, that the two groups A and B could be assigned definite positions on the genetic fine structure map of the T4 phage (114). It was Seymour Benzer (US) who introduced the concept of the cistron: the smallest unit of function of the gene.

 

John J. Trentin (US), Yoshiro Yabe (US), and Grant Taylor (US) demonstrated that a human virus, adenovirus type 12, possesses oncogenic properties upon intrapulmonary injection into newborn hamsters (1575).

 

James Learmonth Gowans (GB), Douglas D. McGregor (US), Diana M. Cowen (GB), and Charles Edmund Ford (GB) found that the small lymphocyte can mount both cellular and humoral immune responses to specific antigens (576).

 

Audrey N. Roberts (US) and Felix Haurowitz (CZ-US) showed that when a cell takes in antigen it is deposited in the cytoplasm and not the nucleus (1304).

 

David W. Dresser (US) was the first to perform an experiment, which showed that T cells of the immune system require a minimum of two signals to become activated. They must be exposed to both antigen and to a molecular signal from the antigen-presenting cell (367).

 

Stanislaw Dubiski (PL), Jan Rapacz (PL), Anna Dubiska (PL), Julian B. Fleishman (GB), Roger H. Pain (GB), Rodney Robert Porter (GB), and Gerald W. Stemke (CA) demonstrated that immunoglobulins are composed of two polypeptide chains encoded by unlinked genes (371; 453; 1473).

 

Vincenzo Buonassisi (US), Gordon Hisashi Sato (US), and Arthur I. Cohen (US) developed a reliable method for producing and maintaining highly differentiated tumor cell lines in vitro (190).

 

Ernest Robert Sears (US) used telocentric chromosomes in wheat to determine the frequency of crossing over between a genetic locus and the centromere (1387; 1388).

 

John Bertrand Gurdon (GB), Tom R. Elsdale (GB), Donald D. Fischberg (GB), Donald D. Brown (GB), Vreni Uehlinger (GB), Charles D Lane (GB), Hugh R. Woodland (GB), Gerard Marbaix (GB), Ronald A. Laskey (GB), O. Raymond Reeves (GB), transferred nuclei from adult cells into eggs and showed that the resulting cells took on embryonic characteristics. This advance established that cells retain all of their genes as they specialize and that fully developed cells can be re-set to an embryonic state — controversial discoveries at the time (180; 181; 586-593).

Kazutoshi Takahashi (JP), Shinya Yamanaka (JP), Keisuke Okita (JP), Koji Tanabe (JP), Mari Ohnuki (JP), Merumi Narita (JP), Tomoko Ichisaka (JP), Kiichiro Tomoda (JP), Masato Nakagawa (JP), Michiyo Koyanagi (JP), Takashi Aoi (JP), Yuji Mochiduki (JP), and Nanako Takizawa (JP) unlocked a new realm of practical possibilities for nuclear reprogramming when they made adult cells behave like embryonic cells by adding only a few factors. This revelation has offered scientists novel ways to harness and study the powers of embryonic development (38; 1112; 1177; 1178; 1512; 1513).

 

Robert Palese Perry (US), Jan-Erik Edström (SE), Joseph Grafton Gall (US), Max Luciano Birnstiel (CH), Margaret I.H. Chipchase (US), Beal B. Hyde (US), J. Jacob (GB), Julio L. Sirlin (GB), Donald D. Brown (US), John Bertrand Gurdon (GB), Mikhail I. Lerman (RU), V.L. Mantieva (RU), Georgii Pavlovich Georgiev (RU), Ferruccio M. Ritossa (IT), and Solomon Spiegelman (US) established the nucleolus as the site of ribosomal RNA synthesis (138; 139; 180; 391; 906; 1214; 1302).

 

John M. Thoday (GB) and John B. Gibson (GB) established a population of Drosophila melanogaster from four gravid females. They applied selection on this population for flies with the highest and lowest numbers of sternoplural chaetae (hairs). In each generation, eight flies with high numbers of chaetae were allowed to interbreed and eight flies with low numbers of chaetae were allowed to interbreed. Periodically they performed mate choice experiments on the two lines. They found that they had produced a high degree of positive assortative mating between the two groups. In the decade or so following this, eighteen labs attempted unsuccessfully to reproduce these results. This is an example of isolation by disruptive selection (1549).

 

Basil Kassanis (GB) discovered satellite virus in some cultures of tobacco necrosis virus (783). Satellite RNAs are virus associated RNAs which depend on a helper virus for replication. They do not share any significant nucleotide sequence identity with the genome of the virus with which they associate.

Jacobus M. Kaper (US), Marylou Tousignant (US), Hervé Lot (FR), and Howard E. Waterworth (US) associated satellite RNA with cucumber mosaic virus (CMV) and showed that CMV containing this satellite RNA induced a lethal necrosis in the tomato (773; 774).

 

Beverly Wolf (US) and Rollin Douglas Hotchkiss (US) discovered that some bacteria become resistant to sulfonamides by producing a target enzyme (tetrahydropteroic acid) which has a reduced affinity for the drug (1669).

 

Thomas W. Whitaker (US) and Glen Norton Davis (US) authored the leading world text on cucurbits (1655).

 

Oliver Evans Nelson, Jr. (US), using the waxy locus (wx) in maize (Zea mays L.), demonstrated that genes of higher organisms, like those of lower ones, could mutate at several different sites (1126; 1127).

Oliver Evans Nelson, Jr. (US) and Howard W. Rines (US) showed that the product of the waxy gene is a starch-bound ADP-glucose glucosyl transferase (1128). This was one of the earliest identifications of an enzyme underlying a phenotype in a higher plant. Nelson later extended these observations to show that transposable elements can produce mutations themselves by inserting themselves at any of many different positions within the gene.

 

Frank M. Hull (US) completed his monograph on robber flies of the world. Robber flies (Diptera: Asilidae) comprise one of the largest groups of extant flies (722).

 

E. Donnall Thomas (US), John A. Collins (US), Emery C. Herman, Jr. (US), Joseph W. Ferrebee (US), Ronert B. Epstein (US) Jeanl Bryant (US), C. Dean Buckner (US), Reginald A. Clift (US), Alexander Fefer (US), F. Leonard Johnson (US), Paul Neiman (US), Robert E. Ramberg (US), and Rainer Storb (US) used bone marrow transplants to replace blood-cell-generating hematopoetic cells in patients with leukemia who had radiation therapy. Initially, transplants were from twin donors and later from donors matched by cell surface antigens. More recently, culturing stem cells extracted from the patient’s blood before treatment has been the method (1550-1552).

 

André Michel Lwoff (FR), Robert Horne (FR), and Paul Tournier (FR) were the first to develop a means of virus classification, based on the Linnaean hierarchical system. This system bases classification on phylum, class, order, family, genus, and species. They used size and shape as distinctive criteria (953).

 

Albert S. Cosgrove (US) was the first to describe infectious bursal disease of chickens (300). It has been called Gumboro disease after the geographic location of these outbreaks (Gumboro, Delaware).

Y. Cho (US) and Samuel Allen Edgar (US) identified the causative agent as a picornavirus (265).

 

Lisbeth M. Kraft (US) and W. Robert Adams (US) discovered a lethal mouse hepatitis virus, strain MHV-LIVIM (6; 845).

 

Toshio Murashige (US) and Folke Karl Skoog (SE-US) devised an improvised nutrient medium which enabled substantially greater growth of tobacco tissue cultures—Murashige and Skoog medium or (MSO or MS0 (MS-zero). The new formulation was conspicuously high in all macronutrient salts, also included all micronutrients, and provided iron in the slowly but more readily available chelated form. Among organic substances, sucrose was increased from 2 to 3% and myo- inositol was made a standard addendum. When suplemented with suitable additions of auxin and cytokinin, the medium enhanced the monthly yield of tobacco callus from 5 g to 125 g/culture (1108). Note: This is the most commonly used medium in plant tissue culture experiments.

 

Victor Herbert (US) identified the stages of the development of folate deficiency, events he demonstrated by placing himself on a folate deficiency diet. Evidence of biochemical deficiency was progressively followed by the development of classic anemia characteristics: insomnia, irritability, fatigue, memory impairment and in this case the appearance of abnormal red cell precursors called megaloblasts in the bone marrow. He nearly died of heart failure from the potassium depletion induced as a side effect (655).

 

James van Gundia Neel (US) proposed that diabetes today may be the result of a “thrifty” genotype made disadvantageous by environmental changes (1123; 1124).

 

Carl R. Morgan (US) and Arnold Lazarow (US) presented a detailed account of a two-step procedure for radio-immunoassay of insulin. In the first reaction, insulin forms a soluble complex with its specific antibody obtained from immunized guinea pigs. In the second reaction, this soluble complex is precipitated by an antibody to guinea pig serum obtained from immunized rabbits. Using a radioactive insulin tracer, the amount of radioactivity in the precipitate is dependent upon the concentration of insulin in the reaction mixture; i.e., with increasing concentrations of unlabeled insulin, the amount of radioactive insulin in the precipitate is decreased correspondingly (1095).

 

John Hans Menkes (US), Milton Alter (US), Gerd K. Steigleder (DE), David R. Weakley (US), and Joo Ho Sung (US) described an X-linked recessive disorder characterized by early retardation in growth, peculiar hair, and focal cerebral and cerebellar degeneration in a family of English-Irish descent living in New York (1042).

David Miles Danks (AU), Peter E. Campbell (AU), J. Walker-Smith (AU), Brian J. Stevens (AU), J. Morton Gillespie (AU), J. Blomfield (AU), Brian Turner (AU), Valerie Mayne (AU), Elizabeth Cartwright (AU), and Rudge R.W. Townley (AU) announced that Menkes syndrome (congenital hypocuremia) is a disease of copper transport (322-325).

Julian F. Mercer (US), Janie Livingston (US), Bryan Hall (US), Jenny A. Paynter (AU), Catherine Begy (US), Settara Chandrasekharappa (US), Paul J. Lockhart (AU), Andrew Grimes (AU), Mrinal Bhave (AU), David Siemieniak (US), and Thomas W. Glover (US) succeeded in identifying and cloning the Menkes gene (1043).

 

S. Ikuta (JP) and S. Murakami (JP) discovered the Sid.Cad blood group antigen. A rare erythrocyte blood group antigen expressed on both sialoglycoprotein and ganglioside structures (730).

 

From 1962 to 1965 there was pandemic of rubella in Europe which later spread to the United States (830).

 

Marc Armand Ruffer (GB) demonstrated the presence of Schistosoma haematobium ova in the kidneys of mummies belonging to the 20th dynasty (1220-1000 BCE) of Egypt (1334).

 

J. Jansen, Jr. (NL) and Hans J. Over (NL) revealed the presence of the parasitic worm Trichuris trichiura (whipworm) in a 2100 to 2500-year-old human refuge mound in Northwest Germany (745).

 

Michael Potter (US) and Charlotte Robertson Boyce (US) found that adjuvants containing mineral oil could cause plasma cell malignancies (plasmacytomas), or plasmacytomas, in mice (1233).

 

David J. Weatherall (GB) and Corrado Baglioni (IT-US) used hemoglobin fingerprinting to prove that the alpha chains of fetal and adult hemoglobin are derived from the same genetic loci (1629). Weatherall and Baglioni then added further evidence that the fetal-to-adult hemoglobin switch involves a change in the expression of non-alpha chains during development.

 

Jean Hamburger (FR), Jean Vaysse (FR), Jean Crosnier (FR), Jean Auvert (FR), Claude M. Lalanne (FR), and James Hopper, Jr. (US) performed a successful renal transplantation between two living related but non-twin humans. The recipient was preconditioned with total body irradiation and post-surgically treated with steroids (606).

 

René Küss (FR), Marcel Legrain (FR), Georges Mathé (FR), Raymond Nedey (FR), and Maurice Camey (FR) performed a renal tansplantation between two nonrelated humans. The recipient was preconditioned with total body irradiation and post-surgically treated with steroid and 6-mercaptopurine. The graft survived for eighteen months (863).

 

Sylvester J. Sanfilippo (US) and Robert A. Good (US) were the first to describe what became known as Sanfilippo syndrome, a rare inherited dementia transmitted as an autosomal recessive (1348).

Hans Kresse (AT) and Elizabeth Fondal Neufeld (US) purified Sanfilippo A Corrective Factor from normal human urine. They found that incubation of stored mucopolysaccharide with the purified factor resulted in release of inorganic sulfate, suggesting that the Sanfilippo A Factor is a heparan sulfate sulfatase (851).

Bruce A. Gordon (CA), Vera Feleki (CA), Cathryne H. Budreau (CA), and Louise Tyler (CA) demonstrated that in cases of Sanfilippo Syndrome heparan sulfate polymer is inadequately desulphated because of a significantly low amount of heparan sulfate sulfatase. Large amounts of heparan sulfate are excreted in the urine (567).

Masu Masayuki (JP) and Masu Kazuko (JP) found that this reaction occurs within the Golgi apparatus (1014).

Hans Kresse (AT) described Sanfilippo Syndrome Type A (mucopolysaccharidosis IIIA) as an autosomal recessive lysosomal storage disease caused by a deficiency of heparin sulfamidase required for heparan sulfate degradation (850).

Hans Kresse (AT) and Kurt von Figura (DE) demonstrated that Sanfilippo Syndrome Type B is the result of a deficiency of the enzyme known as N-acetyl-alpha-D-glucosaminidase (NAG) required for heparan sulfate degradation (853).

Udo Klein (DE), Hans Kresse (AT), Kurt von Figura (DE) determined that Sanfilippo Syndrome Type C is caused by a deficiency in acetyl-CoA: a-glucosamine N acetyl transferase required for heparan sulfate degradation (818).

Hans Kresse (AT), Eduard Paschke (AT), Kurt von Figura (DE), Walter Gilberg (DE), and Walburga Fuchs (DE) proposed that Sanfilippo Disease Type D results from a deficiency of N-acetylglucosamine-6-sulfate sulfatase required for heparan sulfate degradation (852).

 

Frederic Crosby Bartter (US), Pacita Pronove (US), John R. Gill, Jr. (US), and Ross C. MacCardle (US) described hyperplasia of the juxtaglomerular complex with hyperaldosteronism and hypokalemic alkalosis coexisting with normal blood pressure: now called Bartter’s Syndrome (97).

 

Richard C. Reba (US), John McAfee (US), and Henry Wagner (US) used measurement of Hg-203 chlormerodrin accumulation by the kidneys for detection of unilateral renal disease (1271).

 

Rolf Luft (SE), Dennis Ikkos (SE), Genaro Palmieri (US), Lars Ernster (SE) and Björn A. Afzelius (SE), upon examination of a young woman with severe hypermetabolism, mild weakness, and normal thyroid function, discovered Luft disease, the first mitochondrial disease and the first example of organellar medicine (949).

Rolf Luft (SE) introduced the phrase mitochondrial medicine (948).

Ian J. Holt (GB), Alexander E. Harding (GB), John A. Morgan-Hughes (GB), Douglas C. Wallace (US), Gurparkash Singh (US), Marie T. Lott (US), Judy A. Hodge (US), Theodore G. Schurr (US), Angela Lezza (IT), Louis J. Elsas (US), and Eeva K. Nikoskelainen (FI) were the first to associate mutations in mitochondrial DNA with human disease (701; 1614).

 

John Brereton Barlow (ZA) and Wendy A. Pocock (ZA) were the first to interpret a form of congenital heart disease in which one or both leaflets of the mitral valve protrude into the left atrium during the systolic phase of ventricular contraction as an expression of a mitral valve prolapse (Barlow’s syndrome) (83; 84). It may be associated with valve infection, arrhythmias and atypical chest pain. Inheritance is autosomal dominant.

 

Spyros D. Moulopoulos (US), Robert Stephen (US), Stephen R. Topaz (US), Willem Johan Kolff (NL-US) invented the use of a single chambered intra-aortic balloon, positioned in the descending thoracic aorta, to accomplish the same hemodynamics as did arterial counterpulsation (1102; 1103). The primary goals of intra-aortic balloon treatment are to increase myocardial oxygen supply and decrease myocardial oxygen demand: secondarily to improve cardiac output (CO), ejection fraction (EF), increase coronary perfusion pressure, increase systemic perfusion, decrease heart rate, decrease pulmonary capillary wedge pressure, and decrease systemic vascular resistance.

 

Bernard Lown (US), Raghavan Amarasingham (US), and Jose Neuman (US) developed a new method for terminating cardiac arrhythmias transthoracically. They used a synchronized capacitor discharge (944; 945).

 

Michael Ellis DeBakey (US), E. Stanley Crawford (US), George C. Morris, Jr. (US), and Denton A. Cooley (US), to counteract narrowing of an artery caused by an endarterectomy, performed the first successful patch-graft angioplasty. This procedure involved patching of the slit in the artery from an endarterectomy with a Dacron or vein graft. The patch widens the artery so that when it is closed, the channel of the artery returns to normal size (340).

 

David H. Hubel (US) and Torsten N. Wiesel (US) studied the visual cortex in anaesthetized cats by recording extracellularly from single cells. Light-adapted eyes were stimulated with spots of white light of various shapes, stationary or moving. Receptive fields of cells in the visual cortex varied widely in their organization. They tended to fall into two categories, termed' simple' and 'complex'. There were several types of simple receptive fields, differing in the spatial distribution of excitatory and inhibitory ('on' and 'of’) regions. For maximum response the shape, position and orientation of these stimuli were critical. Receptive fields were termed complex when the response to light could not be predicted from the arrangements of excitatory and inhibitory regions. The stimuli that were most effective in activating cells with simple fields- slits, edges, and dark bars-were also the most effective for cells with complex fields. Four fifths of all cells were influenced independently by the two eyes. In a binocularly influenced cell the two receptive fields had the same organization and axis orientation and were situated in corresponding parts of the two retinas. It is suggested that columns containing cells with common receptive- field axis orientations are functional units, in which cells with simple fields represent an early stage in organization, possibly receiving their afferents directly from lateral geniculate cells, and cells with complex fields are of higher order, receiving projections from several cells with simple fields within the same column (715).

 

János Hugo Bruno “Hans” Selye (AT-HU-CA) discovered calciphylaxis, anaphylactoid edema, new roles of mast cells, new models of experimental cardiovascular diseases, and the anesthetic properties of steroids that are certainly associated with the “stress syndrome” (1394-1397).

 

Michael S. Gazzangia (US), Joseph E. Bogen (US), and Roger Wolcott Sperry (US) found that the general picture of collosal functions based on the animal studies tends to be supported in current early testing of a 48-year-old male war veteran with recent complete section of the corpus callosum, anterior and hippocampal commissures (511).

 

In 1962-1965 a rubella (German measles or three-day measles) pandemic started in Europe and spread to the United States

Leslie Alexander Geddes (GB-CA-US), Hebbel E. Hoff (US), David M. Hickman (US), Andrew G. Moore (US), Carlos Vallobana (US), and Joseph Canzoneri (US) developed the method of obtaining the electrocardiogram and respiration from chest electrodes for NASA, which is routinely used in patient monitoring today (512; 513).

 

Fred J. Ansfield (US), John M. Schroeder (US), and Anthony R. Curreri (US) found that of 428 patients with measurable lesions treated with 5-fluorouracil (5-FU), 91 met all their criteria of improvement for an average duration of 9 months before reactivation of the disease occurred. The lesions found most responsive to the drug were cancer of the breast, colon or rectum, stomach, cervix, ovary, and malignant hepatoma. Squamous-cell carcinoma of the head and neck, carcinoma of the lung, hypernephroma, and malignant melanoma were unresponsive (34).

 

Ronald A. Malt (US), in 1962, led a team of surgeons who accomplished the first successful replantation of a completely severed human limb (989).

 

Stanley Schachter (US) and Jerome Singer (US) hypothesized that "an emotional state may be considered a function of a state of physiological arousal and of a cognition appropriate to this state of arousal". They were interested in what happens if you covertly induce a physiological change in a subject, will they cognitively assign an emotional state to their bodies' heightened arousal when they have no apparent causal reason for their bodily changes? That people will assign an emotion to a physiological change based on the available emotions in the social situation. They found that people will assign an emotion to a physiological change based on the available emotions in the social situation, i.e., people search the immediate environment for emotionally relevant cues to label and interpret unexplained physiological arousal (1355).

 

Irving Bieber (US), Harvey J. Dain (US), Paul R. Dince (US), Marvin G. Drellich (US), Henry G. Grand (US), Ralph H. Gundlach (US), Malvina W. Kremer (US), Alfred H. Rifkin (US), Cornelia B. Wilbur (US), and Toby B. Bieber (US) demonstrated the influence of specific types of disordered parent-child relationships in the genesis of male homosexuality, particularly the salience of defective father-son inter-relatedness, and it identified a continuity of disturbed relations with other males in childhood and preadolescence (137).

 

Rachel Carson (US) wrote Silent Spring, which awakened people to the danger to life posed by the indiscriminate use of pesticides and herbicides (237).

 

John M. Teal (US) did a relatively detailed study of the energy flow in a salt-marsh ecosystem of Georgia (1526).

 

Martin Fritz Glaessner (CZ-AU) and Mary Wade (AU) determined fossils in the Ediacara Hills of South Australia (Ediacaran fauna) to be late Precambrian in age, making them the oldest-known multicelled organisms (542-545).

 

Reidar Nydal (NO) radiocarbon dated a total of six wooly mammoths yielding an average age of 31,400 BP (1157).

 

Émile Ennouchi (FR) reported the discovery of fossil remains of archaic Homo sapiens sapiens at Jebel Ighoud southeast of Safi, Morocco (414; 415). The fragments have been dated to c. 300K BP

 

The journal Biochemistry was founded.

 

1963

“The one mark of maturity, especially in a physician, and perhaps it is even rarer in a scientist, is the capacity to deal with uncertainty.” William Bennett Bean (102).

 

John Carew Eccles (AU), Alan Lloyd Hodgkin (GB) and Andrew Fielding Huxley (GB) were awarded the Nobel Prize in Physiology or Medicine for their discoveries concerning the ionic mechanisms involved in excitation and inhibition in the peripheral and central portions of the nerve cell membrane.

 

Manfred Eigen (DE), Leo DeMaeyer (DE), Joseph Schoen (DE), Gerhard Schwarz (DE), Georg Czerlinski (DE), Hartmut Diebler (DE), Walter Kruse (DE), Günter Maass (DE), and Georg Ilgenfritz (DE) developmented relaxation techniques that made possible a quantitative study of fast elementary reactions and a dissection of complex reaction mechanisms, which could be explained in terms of elementary steps. Application to biological reactions led to the conclusion that enzymes are optimal catalysts (395; 396).

 

David Domingo Sabatini (US), Klaus George Bensch (US), and Russell J. Barrnett (US) introduced gluteraldehyde (usually followed by osmium tetraoxide) as a fixative for electron microscopy (1338).

 

Edward S. Reynolds (US) introduced a method for staining ultrathin sections for electron microscopy with solutions of lead citrate at high pH. Lead citrate solutions are stable for long periods of time and do not significantly contaminate the sections with unwanted precipitate (1282).

 

Lars A. Carlson (SE) described the final version of his method for determination of serum triglycerides with major emphasis on practicality. Water-soluble interfering substances are removed; the method is specific for triglycerides, and it can easily be used for tissues (229).

 

Robert S. Lees (US), Frederick T. Hatch (US), Donald S. Frederickson (US), Robert I. Levy (US), Ronald A. Wong (US), Paul G. Banchero (US), Lin C. Jensen (US), Suzanne S. Pan (US), Gerald A. Adamson (US), and Frank T. Lindgren (US) drew attention to an important group of diseases that are common and often potentially fatal. They introduced a new system of classifying blood lipid disorders, which is a useful and practicable system for the classification, investigation, and treatment of hyperlipoproteinemic patients. They developed a suite of relatively simple methods that would enable quantitative or semiquantitative measurements of lipoprotein patterns from sera of animals and humans when performed in biophysically unsophisticated laboratories (478; 629; 892; 1673).

 

Frantz A. Vandenheuvel (CA) obtained a plausible tri-dimension arrangement of molecules in the lipid bilayer of myelin. Data on myelin was obtained from analytical, X-ray, and other studies then integrated by using exact molecular parameters and force calculations (1592).

 

Robert Bruce Merrifield (US) described the development of solid-phase peptide synthesis (1044; 1045).

Robert Schwyzer (CH) and Paul Sieber (CH) synthesized the 39-residue porcine adrenocorticotropic hormone by solution-phase segment condensation methods (1383).

 

Severo Ochoa (ES-US-ES), Susumu Nishimura (JP), David S. Jones (GB), and Har Gobind Khorana (IN-US) developed a non-enzymatic in vitro technique for synthesizing long strands of RNA with known, simple repeating units. Using these they determined the base sequence for many codons (805; 806; 1140; 1165; 1445).

 

Du Pont Chemical Company introduced the herbicide bromacil, a derivative of uracil, for the control of a wide variety of weeds in citrus and pineapple crops.

 

Dow Chemical Company introduced the herbicide picloram, a picolinic acid derivative, for the control of most perennial broadleaf and woody species. ref

 

Eli Lilly Chemical Company introduced the herbicide trifluralin, a dinitroaniline, useful in cotton (Gossypium spp.) and soybeans (Glycine max). ref

 

Donald F. Ashman (US), Richard M. Lipton (US), Meyer M. Melicow (US), Tracy D. Price (US), Thomas R. Price (US) found cyclic guanylic acid (cyclic GMP) in urine (65; 1241).

 

Alfred W. Alberts (US), Peter Goldman (US), Pindaros Roy Vagelos (US), Philip Warren Majerus (US), and Barbara Talamo (US) discovered the role of the acyl carrier protein in fatty acid synthesis (12; 13; 554; 555; 982; 983).

 

Kazuhiko Ohkuma (JP), Frederick T. Addicott (US), Jessye Lorene Lyon (US), Orrin E. Smith (US), Wilfred E. Thiessen (US), Harry R. Carns (US), J.L. McMeans (US), O.E. Smith (US), John W. Cornforth (AU-GB), B.V. Milborrow (GB), G. Ryback (GB), and P.F. Wareing (GB) isolated, determined the structure of, and named abscisic acid during their studies of leaf adscission. They first named this plant hormone abscisin II then later changed it to abscisic acid (7; 8; 1167; 1168).

Andrew C. Allan (GB), Mark D. Fricker (GB), Jane L. Ward (GB), Michael H. Beale (GB), and Anthony J. Trewavas (GB) showed that abscisic acid is also involved in plant response to water stress and to function in the gain and loss of solutes during changes in stomatal guard cell turgor (17).

 

Charles J. Epstein (US), Robert F. Goldberger (US), and Christian Boehmer Anfinsen, Jr. (US) articulated what they called the thermodynamic hypothesis to explain the three dimensional structure of a native protein in its normal physiological milieu (solvent, pH, ionic strength, presence of other components such as metal ions or prosthetic groups, temperature, etc.) as the one in which the Gibbs free energy of the whole system is lowest; that is, that the native conformation is determined by the totality of interatomic interactions and hence by the amino acid sequence, in a given environment (417).

 

David Ezra Green (US) and Sidney Fleischer (US) were the first to emphazize the importance of lipid-protein interactions within membranes with structure and function of membranes being largely determined by lipid-protein interactions (580).

 

Robert F. Goldberger (US), Charles J. Epstein (US), Christian Boehmer Anfinsen, Jr. (US), Pál Venetianer (HU), and Ferenc Brunó Straub (HU) discovered that the endoplasmic reticulum in cells that are actively secreting proteins with disulfide bridges contains an enzyme system which catalyzes the rapid formation of the correct native disulfide pairing (552; 1596).

 

Merton Franklin Utter (US) and D. Bruce Keech (US) discovered pyruvate carboxylase and noted that this enzyme works in concert with phosphoenolpyruvate carboxykinase to convert pyruvate to phosphoenolpyruvate by a sequence, which differs from a reversal of the glycolytic pathway (794; 1582; 1583).

 

Shu-Fang Wang (US), Frank S. Kawahara (US), and Paul Talalay (DE-US) discovered the mechanism of delta 5-3-ketosteroid isomerase (KSI), which catalyzes the migration of the double bond from delta 5 to the delta 4 position of 3-ketosteroids. They found that the isomerization proceeds without exchanging protons with the medium, suggesting that there is a direct transfer of a proton from position 4 to 6 on the enzyme surface. Talalay and his colleagues were able to gain insight into the mechanism of KSI from absorption and fluorescence spectra of enzyme-steroid complexes. They concluded that the reaction involves an enolic intermediate (1620). KSI occurs in animal tissues concerned with steroid hormone biosynthesis such as the adrenal, testis, and ovary.

 

Zdenek Hruban (US), Benjamin Spargo (US), Hewson Swift (US), Robert W. Wissler (US), and Ruth G. Kleinfeld (US) using ultrastructural studies established an intracellular process consisting of the sequestration of cytoplasmic components followed by the formation of complex dense bodies, which correspond to the lysosomes of biochemists. This natural process is enhanced by cellular injury. The noxious agent codetermines the structure of the bodies (706).

 

Philip J. Randle (GB), Peter B. Garland (GB), C. Nick Hales (GB), and Eric A. Newsholme (GB) performed a series of experiments that were designed to test the supposition that cardiac and skeletal muscle possess mechanisms that allow them to shift readily back and forth between carbohydrate and fat as oxidative energy sources, depending primarily on the availability of free fatty acids (FFAs). These experiments eventually focused on the biochemical mechanisms that are involved in the switch from carbohydrate to fat metabolism. The main features of the model that was developed were that increased fat oxidation in muscle would inhibit both pyruvate dehydrogenase (PDH) and phosphofructokinase by accumulation of acetyl-CoA and citrate, respectively. These roadblocks placed in the glycolytic pathway would lead to increased glucose 6-phosphate concentration, inhibiting hexokinase and resulting in reduced glucose uptake and oxidation. This homeostatic mechanism became known as the glucose fatty acid cycle or the Randle cycle (1262-1264).

 

John Walter Drake (US) published the first spectrum for UV-induced mutagenesis. His experimental system was the r II region of bacteriophage T4 (366).

 

Thomas H. Plummer, Jr. (US) and Christophe Henri Werner Hirs (US) isolated ribonuclease B in pure form from pancreatic juice and showed it to be the same as A but with the addition of a carbohydrate side-chain attached to one asparagine residue (1224; 1225).

 

Robert E. Canfield (US), Jacqueline Jollès (FR), Pierre Jollès (FR), Sandra Kammerman (US), Joan H. Sobel (US), and Francis J. Morgan (US) determined that lysozyme is a single polypeptide chain of 129 amino acid subunits of 20 different kinds (224; 225; 755; 756).

 

Robert G. Martin (US) discovered that the enzyme responsible for carrying out the first step in histidine biosynthesis in Salmonella typhimurium exhibits the phenomenon of feedback inhibition. He presented evidence that the enzyme’s conformation changes because of binding L-histidine (1012).

 

John C. Gerhart (US), Arthur Beck Pardee (US), Howard K. Schachman (US), Jean-Pierre Changeux (FR), and Merry M. Rubin (US) presented evidence that aspartate transcarbamylase from Escherichia coli mediates indirect, i.e., allosteric, interactions among substrate and/or inhibitor molecules which bind at topographically distinct sites on the enzyme surface. This allosteric binding led to changes in enzyme conformation (257; 258; 523-525).

 

Feodor Felix Konrad Lynen (DE), Michio Matsuhashi (JP), Shosaku Numa (JP), and Eckhart Schweizer (DE) discovered that long-chain acyl-CoA derivatives exhibit a typical end-product inhibition of lipogenesis at the level where acetyl-CoA carboxylase is active (960).

 

Solomon Spiegelman (US) and Miyuki Hayashi (JP-US) found an enzyme capable of specifically recognizing and replicating viral RNA. This is the discovery of nucleic acid polymerases (replicases) (1453).

Ichiro Haruna (JP) and Solomon Spiegelman (US) coined the term template specificity to describe the affinity of these polymerases (623).

 

Miyuki Hayashi (JP-US), Marie N. Hayashi (JP-US) and Solomon Spiegelman (US) discovered that only one strand of a DNA’s double helix transmits the genetic information to the cell’s protein making machinery (635).

 

Ichiro Haruna (JP) and Solomon Spiegelman (US) performed the first in vitro synthesis of infectious viral RNA (Qß) (624).

 

Marvin J. Weinstein (US), George M. Luedemann (US), Edwin M. Oden (US), Gerald H. Wagman (US), Jean-Pierre Rosselet (US), Joseph A. Marquez (US), Carmine T. Coniglio (US), William Charney (US), Hershel L. Herzog (US), and Jack Black (US) isolated the antibiotic gentamycin (gentamicin) from Micromonospora purpurea, an actinomycete (1645).

 

Charles H. Wallas (US) and Jack Leonard Strominger (US) reported that the antibiotics restocetin A and B inhibit bacterial cell wall synthesis (1615).

 

Peter J. Gomatos (US) and Igor Tamm (US) found that reovirus has double-stranded RNA as its genome (560; 561).

 

Hiroshi Yoshikawa (JP) and Noboru Sueoka (JP) determined elative frequencies of various genetic markers in the DNA of B. subtilis, strain W23, in exponential and stationary growth phases using a transformation system. If the chromosome replication has a polarity, the frequency of each marker in the exponential phase should be a function of its location on the chromosome. The results indicate that such polarity exists in B. subtilis. Based on the results, a genetic map has been constructed in which the adenine marker is located near the point of origin, from which the chromosome starts replicating, and methionine and isoleucine near the terminus. The results also indicate that chromosomes in the stationary phase are in completed form (1707).

 

Michael Cannon (US), Robert Krug (US), and Walter Gilbert (US), using Escherichia coli, determined that sRNA (tRNA) has a high affinity for ribosomes (226).

 

Marshall Warren Nirenberg (US), Oliver W. Jones, Jr. (US), Philip Leder (US), Brian F.C. Clark (GB-DK), William S. Sly (US), Sidney Pestka (US), Joseph F. Speyer (US), Peter Lengyel (US), Carlos Basilio (US), Albert J. Wahba (US), Robert S. Gardner (US), and Severo Ochoa (ES-US-ES) determined the most likely base compositions, not order, of approximately 50 codons by analyzing proteins synthesized using randomly-ordered RNA templates containing different combinations of the four nitrogenous bases. These results also showed that multiple codons can correspond to the same amino acid, therefore the code was characterized as being degenerate (1136; 1137; 1452).

 

Heinz Guenter Wittmann (DE), and Brigitte Wittmann-Leibold (DE) used the synthesis of coat protein in tobacco mosaic virus to provide experimental evidence that codons are translated in a linear non-overlapping fashion (1668).

 

Y. Yasumura (JP) and M. Kawakita (JP) established the 'Vero' lineage cell line in cell culture. These kidney epithelial cells, extracted from an African green monkey (Chlorocebus sp.), are continuous and aneuploid. A continuous cell lineage can be replicated through many cycles of division and not become senescent (1704). Note: This cell line is important for cancer research in vitro.

 

Ralph B. Arlinghaus (US), Gabriel Favelukes (AR), Richard S. Schweet (US), Akira Kaji (US), and Hideko Kaji (US) discovered that when poly-U mRNA is used Phe-tRNA attaches to ribosomes prior to the formation of the peptide bond (51; 766).

 

Violet Daniel (IL) and Uriel Z. Littauer (IL) purified and characterized tRNA nucleotidyltransferase from rat liver. The enzyme was found to have an important role in the proofreading and repair of the universal 3'-CCA end of tRNA (320; 321).

Jacov Tal (IL), Murray P. Deutscher (IL), and Uriel Z. Littauer (IL) showed that tRNA nucleotidyltransferase adds CMP to tRNA... N by a nonprocessive mechanism (1517).

 

Elizabeth Burgi (US), and Alfred Day Hershey (US) worked out a method for determining the molecular weight of DNA using sedimentation rates in a sucrose solution (195).

 

Ruth Sager (US) and Masahiro R. Ishida (JP) were the first to isolate DNA from chloroplasts. The material was Chlamydomonas (1342).

 

Mordhay Avron (IL) discovered the chloroplast-coupling factor, CF1, for photophosphorylation, later known as ATP synthase (72).

 

Frantisek Franek (CZ), Roald S. Nezlin (CZ), Gerald Maurice Edelman (US), Donald E. Olins (US), Joseph A. Gally (US), Norton David Zinder (US), Seymour Jonathan Singer (US), Russell F. Doolittle (US), Edgar Haber (US), Dan Inbar (IL), Jacob Hochman (IL), and David Givol (IL) determined that both the variable heavy regions (VH) and the variable light regions (VL) of the antibody molecule contribute to the antigen-binding function. The effector functions being carried out by constant regions (388; 472; 596; 731; 1182; 1426).

 

Hugh Esmor Huxley (GB) was the first to suggest a likely mode of aggregation of myosin molecules to form cylindrical myosin filaments. He discovered myosin decoration, an important technique in muscle chemistry. The reaction of microfilaments with heavy meromyosin subfragment (HMMS-1) reveals, upon microscopic examination, an unmistakable characteristic arrowhead pattern (729).

 

Jean Hanson (GB) and Jack Lowy (GB) demonstrated that F-actin filaments consist of a helical array of G-actin molecules and proposed that tropomyosin molecules lie end-to-end along each groove of the F-actin helix (613).

 

Dorothy Mary Moyle Needham (GB) and James M. Williams (GB) demonstrated the presence of myosin molecules in vertebrate smooth muscle cells (1122).

 

Haim Ginsberg (US) and Leo Sachs (US-IL) were the first to report the in vitro growth of cells of hemopoietic origin and documented the generation of mast cells from cultures of thymic cells (541).

 

Murray Llewellyn Barr (CA), Evelyn L. Shaver (CA), and David H. Carr (CA) described the Barr-Shaver-Carr syndrome. These patients have 48 chromosomes (XXXY karotype). XXXY syndrome resembles Klinefelter's syndrome: tall slim build, flat nasal bridge, epichantal folds, mild prognathism, delayed puberty, testes small or undescended, small penis, gynaecomastia (excessive breast development in the male), and mental retardation (89).

 

George Joseph Todaro (US) and Howard Green (US) showed that with mouse embryo cells, transformed cell lines that were capable of indefinite propagation grew out of the cultures regularly. Compared to untransformed cells the transformed cells were able to grow from much smaller inocula, reach higher saturation density, and form multilayers (no contact inhibition). One of their established cell lines (3T3) is nontransformed and exbibits contact inhibition. They concluded that, “the malignant properties of many established lines may be the result of the selective processes usually operating in cell culture and not related to the process of establishment per se.” (1565).

George Joseph Todaro (US), Howard Green (US), and Burton D. Goldberg (US) developed an aneuploid mouse fibroblast line 3T3 that appears very sensitive to contact inhibition of cell division. Two different oncogenic viruses, SV40 and polyoma, rapidly transform this line (1566).

 

Yoheved Berwald (IL) and Leo Sachs (US-IL) showed that known chemical carcinogens can transform normal hamster cells in vitro (128; 129).

 

Ulrich Clever (DE) and Carole G. Romball (US) gave the first evidence that steroid hormones can affect gene activity (280; 281; 283).

 

Charles Yanofsky (US), Bruce C. Carlton (US), John R. Guest (GB), Donald Raymond Helinski (US), and Ulf Henning (DE) studied mutations associated with the synthesis of tryptophan synthetase alpha subunit in Escherichia coli and found that the relative position of each amino acid replacement matched the relative position of its respective mutation along the genetic map (1701; 1702). This was proof of the sequence hypothesis (colinearity) proposed in 1957 by Francis Harry Compton Crick (GB), which held that DNA sequence and protein sequence are colinear. Genetic information must therefore be arrayed in a strictly linear fashion along the length of a DNA molecule. See, Crick, 1958.

Anand S. Sarabhai (IN), Anthony O.W. Stretton (US) Sydney Brenner (ZA-GB), and Antoinette Bolle (CH) reached the same conclusion almost simultaneously (1350).

 

George Streisinger (HU-US) Robert S. Edgar (US), and Georgetta Harrar Denhardt (US) proposed that the linear T-even phage DNA molecule is terminally redundant, so that its sequence of genes can be represented as: abcdef…wxyzabc. When such a terminally redundant phage DNA molecule replicates in the infected cell, genetic recombination can proceed within the region of terminal redundancy of two daughter molecules, giving rise to concatenates of the type: abcdef…wxyzabc x abcdef…wxyzabc abcdef…wxyzabcdef…wxyzabc.

These concatenates would then have to be cut into phage-genome-sized pieces before incorporation into the heads of infective progeny particles. If this cutting process were to be of such a nature that it started to take its measure of phage-genome length always at the same genetic site, say at a, then there would arise only one kind of terminally redundant phage genome—namely, that redundant for the abc sector. Hence terminal-redundancy heterozygotes could arise only for genes residing in that sector. But if the cutting process were to start taking its measure of genome length at any randomly chosen genetic site, then there would arise a collection of phage genomes whose terminal redundancy would be circularly permutated, such as ghijkl…cdefghi and mnopqr…ijklmno . It is in this paper that the circular nature of the T4 genome was proposed (1494).

 

Alfred Day Hershey (US) and Elizabeth Burgi (US), and Laura Ingraham (US) demonstrated that the DNA of the lambda bacteriophage of Escherichia coli could exist as a linear molecule or as a circular molecule. The circularity is possible because each end has a single chain overhang, which is complementary to a single chain overhang on the other end of the molecule. These overhangs produce ends, which behave as though they are sticky and are called cohesive sites (COS) (662; 663).

Ray Wu (US) Armin Dale Kaiser (US) later determined the structure and base sequence of these cohesive ends (1690).

Ray Wu (US) and Ellen Taylor (US) completed sequencing the cohesive ends of lambda phage and showed that they were only 12 nucleotides long out of the 50,000 nucleotides of the complete molecule (1693).

 

Hubert Henri Malherbe (ZA), Robert Harwin (ZA), and M. Ulrich (ZA) were the first to describe simian rotavirus particles (988).

Ruth F. Bishop (AU), Geoffrey P. Davidson (AU), Ian H. Holmes (AU), Brian J. Ruck (AU), Thomas H. Flewett (GB), A.S. Bryden (GB), and Heather A. Davies (GB) gave the first descriptions of Rotavirus in association with a human disease—diarrhea in infants and young children (141; 454).

Geoffrey P. Davidson (AU), Ruth F. Bishop (AU), R. Rugely W. Townley (AU), and Ian H. Holmes (AU) demonstrated Rotavirus, the cause of acute sporadic enteritis in children, using electron microscopy (328).

 

Wilbur George Downs (US), Charles R. Anderson (US), Leslie Spence (US), Thomas H.G. Aitken (US), and Arthur H. Greenhall (US) discovered Tacaribe virus: the first known western hemisphere arenavirus (365).

 

Stanley Hattman (US) and Toshio Fukasawa (US) provided the first clue to explain how foreign viral DNA is protected from attack by host cell nucleases. T-even bacteriophage DNA is glucosylated as it is replicated in Escherichia coli strain B host cells rendering it immune to enzyme degradation (631).

 

Hugh John Forster Cairns (GB-US-GB) demonstrated the circular nature of the bacterial chromosome using autoradiography. In the 1963a paper he discovered the replication fork (209-211).

 

Friedrich Bonhoeffer (DE) and Alfred Gierer (DE) proved that at most a few replicating forks of Escherichia coli DNA are active at any given time (156).

 

James Herbert Taylor (US) performed the experiment, which established to the satisfaction of most scientists that physical breakage and exchange of DNA molecules occur during eukaryotic recombination. He used the grasshopper, Romalea (1523; 1524).

 

Margit M.K. Nass (SE) and Sylvan Nass (SE) reported intramitochondrial fibers with DNA characteristics (1115; 1117). Some consider this to be the discovery of mitochondrial DNA (mtDNA). Others consider the following article by Schatz, et al., to represent the discovery.

Gottfried Schatz (AT-CH), Ellen Haslbrunner (AT), and Hans Tuppy (AT) presented evidence that preparations of mitochondria from baker’s yeast contain a significant quantity of DNA (1359).

Margit M.K. Nass (SE), Sylvan Nass (SE), and Björn A. Afzelius (SE) presented evidence that preparations of mitochondria from many other sources contain a significant quantity of DNA (1116).

 

David B. Slautterback (US), Myron C. Ledbetter (US) and Keith R. Porter (US) gave intracellular "microtubules" their name, fully described them, and recognized their ubiquity (887; 1438).

Peter K. Helper (US) and Eldon H. Newcomb (US) presented a study of the relationship of microtubules to cell plate formation in dividing cells (653).

Eldon H. Newcomb (US) examined in detail the evidence correlating the orientation of plant cortical microtubules with that of newly deposited wall microfibrils. Considerable evidence suggests that cortical microtubules may control the orientation of cellulose microfibrils as the latter are being deposited in the cell wall (1130).

 

Madeleine Sebald (FR) and Michel Véron (FR) established the taxonomic legitimacy of the genus Campylobacter (Greek, curved rod) (1390).

 

Albert A. Stonehill (US), Stephen Krop (US), and Paul M. Borick (US) introduced glutaraldehyde as a germicide (1491).

 

Emanuel Margoliash (IL), Walter Monroe Fitch (US), Gillian M. Air (AU), Edward Owen Paul Thompson (AU), Abel Schejter (IL), Barry J. Richardson (AU), Geoffrey B. Sharman (AU), Thomas H. Jukes (US), Richard Holmquist (US), and Emil L. Smith (US) presented data on the amino acid sequences of hemoglobin and cytochrome c from many species. This data was sufficient to permit construction of elaborate family trees (11; 448; 449; 762; 763; 994-997).

Bill Henriksen Hoyer (US), Brian John McCarthy (US), and Ellis Truesdale Bolton (US) pointed out that similarities in polynucleotide sequences in DNA from different species could be used as a measure of phylogenetic proximity. They also recognized that some such sequences might represent genes that have been retained with little change throughout vertebrate history. Possibly representing features held in common such as bilateral symmetry, notochord, hemoglobin, and others (705).

Emile Zuckerkandl (US) and Linus Carl Pauling (US) predicted that comparing gene and protein sequences directly and indirectly would allow phylogeny to be reconstructed. They pointed out that the sequence of a nucleic acid or protein is much more evolutionarily informative than is knowledge about whether its activity is present or absent (usually inferred from the presence of a corresponding metabolic product). The identification of specific macromolecular sequences in natural biomass therefore provides a more precise and powerful characterization of a population than do inventories of lipids or chromatophores. Sequences allow a quantitative definition of both the genetic diversity and the organismal relationship within a niche (1718).

 

Marilyn Gist Farquhar (US) and George Emil Palade (RO-US), using frogs and toads, discovered the tight junction, or occluding junction (zonula occludens) between cells. They deduced that the diffusion of water, ions, and small, water-soluble molecules is impeded along the intercellular spaces of the epidermis by zonulae occludentes while it is facilitated from cell to cell within the epidermis by zonulae and maculae occludentes. (428-430).

Phillippa Claude (US) and Daniel A. Goodenough (US) determined that the depth (number of occluding strands) in a tight junction correlates with the leakiness or tightness of a tight junction (277).

Bruce R. Stevenson (US), Janet D. Siliciano (US), Mark S. Mooseker (US), and Daniel A. Goodenough (US) isolated a polypeptide of approximately 225,000 D that is the first protein known to be specific to tight junctures and potentially a ubiquitous component of all mammalian tight junctions (1482).

 

Howard Martin Temin (US) proposed the provirus hypothesis to explain how RNA viruses might cause human cancer. According to the provirus concept, after infection of a cell by an RNA tumor virus, the cell makes a DNA copy from the viral RNA and incorporates the genetic information into its own DNA. This gives the cell the capacity to produce oncogenic viruses and transforms it from a normal cell to a neoplastic one (1530-1532; 1534; 1537; 1538).

Howard Martin Temin (US), Satoshi Mizutani (US) and David Baltimore (US) discovered that Rous Sarcoma virus contains reverse transcriptase, an enzyme capable of synthesizing DNA from RNA (79; 80; 1533; 1535; 1536; 1539; 1541; 1542).

Inder M. Verma (US), Gary F. Temple (US), Hung Fan (US), and David Baltimore (US) demonstrated that the reverse transcriptase could be used in vitro to synthesize cDNA from mammalian mRNAs (1597).

Daniel L. Kacian (US), Sol Spiegelman (US), Arthur Bank (US), Masaaki Terada (US), Salvatore Metafora (US), Lois W. Dow (US), and Paul A. Marks (US) used avian myeloblastosis virus reverse transcriptase to synthesize DNA complementary to human globin mRNA in vitro (765).

Howard Martin Temin (US) presented what he called the protovirus hypothesis to explain the origin of RNA tumor viruses. He suggested that the relationships between avian ribodeoxyviruses and reticuloendotheliosis viruses are a relic of the origin of these viruses; that these ribodeoxyviruses are representatives of a part of the avian genome, which evolved by a process of DNA to RNA to DNA information, transfer and escaped to become viruses. He speculated that the process is widespread in vertebrates (1540).

Piero Carninci (JP), Catrine Kvam (IT-NO), Akiko Kitamura (JP), Tomoya Ohsumi (JP), Yasushi Okazaki (JP), Mitsuteru Itoh (JP), Mamoru Kamiya (JP), Kazuhiro Shibata (JP), Nobuya Sasaki (JP), Masaki Izawa (JP), Masami Muramatsu (JP), Yoshihide Hayashizaki (JP), Claudio Schneider (IT), Yoko Nishiyama (JP), Arthur Westover (JP), Masayoshi Itoh (JP), Sumiharu Nagaoka (JP), Yuko Shibata (JP), Norihito Hayatsu (JP), Yuichi Sugahara (JP), and Hideaki Konno (JP) improved the synthesis of full length cDNA molecules by biotin capping of the mRNAs to ensure that only full-length cDNAs were selected. After first-strand cDNA synthesis, RNAse I was used to destroy any part of any mRNA that was not bound to cDNA. This caused the removal of the 5' biotin cap from the mRNAs of all non-complete cDNAs. Magnetic beads were used to select only the full-length cDNAs for second-strand synthesis and cloning (232-234).

 

Ralph Mitchell (US) and Martin Alexander (US) discovered soil bacteria, which can lyse fungi (1080).

 

James Edward van der Plank (ZA) wrote, Plant Diseases: Epidemics and Control in which he taught plant pathologists how to interpret the logistic progress of an epidemic in terms of compound and simple interest, infection rates and latent periods, and horizontal and vertical resistance (1587).

 

George Henry Hepting (US) wrote Climate and forest diseases, a paper considered the authoritative treatise on climatology and plant pathology (654).

 

Resistance to the insecticide, carbaryl, appeared between 1963 and 1966 in the Orchard leafroller in New Zealand, in cotton leafworm, Spodoptera, in Egypt, and in the tobacco budworm, Heliothis virescens, on American cotton (Gossypium spp.). refs

 

Eugene J. Van Scott (US) and Thomas N. Ekel (US) reported that epidermal hyperplasis is found to be primarily due to expansion of the germinative cell population, less so to increased mitotic rates. Expansion of the germinative cell population may be initiated by proliferation of supporting connective tissue (1591). Note: Psoriasis is a notable example. See, other references under Eugene J. Van Scott.

 

Henry George Kunkel (US), Mart Mannik (US), and Ralph C. Williams (US) found that human antibodies against three different antigens were themselves antigenically unique in rabbits. Furthermore, the rabbit anti-antibodies were active only against the antibodies of a particular person. They would not couple with antibodies against the same immunogen isolated from different people. Thus, idiotypes were found to be clone-specific (860).

 

Fred S. Kantor (US), Antonio Ojeda (US), and Baruj Benacerraf (VE-US) presented evidence, which established that conjugation of the immunogenically silent polylysine molecule with dinitrophenyl groups results in a synthetic antigen capable of inducing anti-DNP antibodies in guinea pigs (772).

 

Nils Kaj Jerne (GB-DK) and Albert A. Nordin (US) developed the hemolytic plaque technique for demonstrating which cells within a mixture produce antibody (750).

 

Charles W. Todd (US), Arnold Feinstein (GB), Thomas J. Kindt (US), Marion E. Koshland (US), Judith J. Davis (US), and N. Joan Fujita (US) discovered a group a allotype on several different immunoglobulin isotypes in the rabbit. This finding challenged a basic paradigm of genetics, the one-gene-one-polypeptide chain theory and suggested multiple gene control of a single polypeptide chain (432; 809; 844; 1567).

 

Olga K. Archer (US), David E.R. Sutherland (US), and Robert Alan Good (US) proposed that rabbit gut associated lymphoid tissue (GALT) might be the functional equivalent of the bursa in the chicken (50).

 

Thomas B. Tomasi, Jr. (US), Sheldon D. Zigelbaum (US), and William B. Chodirker (US) showed that immunoglobulin gamma (IgG) is almost absent in lacrimal fluid (tears), and that virtually all lacrimal immunoglobulin is immunoglobulin alpha (IgA) (266; 1569).

 

The Centers for Disease Control (CDC) reported one of the few smallpox epidemics in Western nations in recent years not evidencing a predominant spread among hospital contacts. The outbreak emphasizes the sinister role of mild or vaccine-modified cases of smallpox in initiating and propagating outbreaks of severe disease (2). Note: Sweden was the first major country to eliminate indigenous smallpox, a distinction it achieved in 1895 (702).

 

Georges Mathé (FR), Jean Louis Amiel (FR), Leon Schwarzenberg (FR), Albert Cattan (FR), Maurice Schneider (FR) Marco J. de Vries (NL), Maurice Tubiana (FR), Claude M. Lalanne (FR), Jacques-Louis Binet (FR), Martine Papiernik (FR), Gabriel Seman (FR), Michio Matsukura (JP), Annabelle M. Mery (FR), V. Schwarzmann (FR), and Albert Flaisler (FR) accomplished the first prolonged engraftment of human allogeneic bone marrow. The adult recipient with leukemia conditioned with total body irradiation died without disease reoccurrence after 20 months, probably from complications of graft-versus-host disease (1017; 1018). Note: Soon after they identified what was then called secondary disease, the debilitating and wasting condition that follows transplantation, they deduced that this must be due to an immune reaction of the cells in the donor marrow against the cells in the patient.” Mathé and colleagues thus became the first to define what is now known as graft versus host disease, and to study it in man.

 

Ernst Klenk (DE) and Winfried Kahlke (DE) showed that the Refsum disease in humans is associated with accumulation of phytanic acid in blood and tissues (824). The cardinal clinical features of Refsum disease are retinitis pigmentosa, chronic polyneuropathy, and cerebellar signs.

 

Jérôme Jean Louis Marie Lejeune (FR), Jacques Lafourcade (FR), Roland Berger (FR), Jacques Vialette (FR), Marc Boeswillwald (FR), Philippe Seringe (FR), and Raymond Alexandre Turpin (FR) characterized and named the Cri du Chat Syndrome ("cry of the cat" in French) as a genetic disorder caused by the loss or misplacement of genetic material from the fifth chromosome. They described the syndrome after the sound that many of the babies and young children make when crying (895).

 

Robert Royston Amos Coombs (GB) and Philip George Houthem Gell (GB) proposed a classification scheme, which defined 4 types of hypersensitivity reactions. The first 3 are mediated by antibody, the fourth by T cells (296). The Gell and Coombs classification now contains six categories: Type 1: Immediate Hypersensitivity; Type 2: Cytotoxic Antibody; Type 3: Immune Complex; Type 4: Delayed Hypersensitivity; Type 5: Stimulating Antibody; Type 6: Antibody Dependant Cell Mediated Cytotoxicity (ADCC).

 

Henri-Géry Hers (BE), Nicole Lejeune (FR), Denise Thinès-Sempoux (FR), Pierre Baudhuin (FR), and Helmuth Loeb (BE) discovered that the absence of a lysosomal enzyme, acid maltase, is the cause of a fatal genetic glycogen storage disorder, glycogenesis II or Pompe’s disease (100; 659; 896).

Henri Géry Hers (BE) proposed the concept of inborn lysosomal diseases (660).

Henri-Géry Hers (BE) and Francois Van Hoof (BE) noted that this concept applies to most polysaccharidoses, lipidoses, and other storage diseases (661).

 

Vaughn Critchlow (US), Robert A. Liebelt (US), Mildred Elwers Bar-Sela (US), W. Mountcastle (US), and Harry S. Lipscomb (US) performed a rigorous series of experiments directed at resolving a controversy of whether there were differences in pituitary-adrenal function between male and female animals under resting conditions. Their experiments provided validation that the pituitary-adrenal axis is sexually dimorphic under resting (control) conditions and can be modulated both by hormonal status and by neurological processes inhibited by barbiturates (312).

 

Thelma B. Dunn (US) and Arleigh W. Green (US) found that newborn mice receiving estrogen injections developed tissue pathologies such as cysts, cancers, and lesions. Results indicate that exposure to naturally occurring hormones early in life can produce harmful health effects and point to possible early life causes of cancer in adult human populations (379).

 

Robert M. Berne (US), Eckehardt Gerlach (DE), B. Deuticke (DE), and Robert H. Dreisbach (US) proposed that adenosine mediates local metabolic control of coronary blood flow. The balance between oxygen supply and myocardial oxygen consumption is reflected in the intracellular myocardial oxygen tension (PO2). If myocardial oxygen consumption increases (as during exercise), then there will be a fall in cardiac myocyte PO2 that will lead to the breakdown of adenine nucleotides (ATP, ADP, AMP) and to the generation of adenosine that diffuses out of the cardiac cell. The adenosine crosses the interstitial space to act on adenosine receptors on coronary arteriolar smooth muscle to cause vasodilation. The ensuing increase in coronary blood flow delivers more oxygen to the myocardium and thus returns myocardial PO2 back toward the normal operating range (125; 526).

 

Arvid Carlsson (SE) and Margit Lindqvist (SE) described for the first time a specific action of major neuroleptic (antipsychotic) drugs upon the metabolic processes in the brain, and a mode of action was proposed. Chlorpromazine and haloperidol enhanced the turnover of dopamine (prolactin-inhibiting hormone) and noradrenaline in the brain (230).

 

Emanuel Grunberg (US), Edith H. Titsworth (US), and Michael Bennett (US) reported the antifungal activity of 5-fluorocytosine (585).

 

Oleh Hornykiewicz (AT) reported the clinical effectiveness of L-dopa in patients with post-encephalitic Parkinsonism, a current mainline drug for the treatment of Parkinson disease (703).

Oliver W. Sacks (GB) revealed the clinical effectiveness of L-dopa in patients with post- encephalitic Parkinsonism (1340).

Nils-Erik Birger Andén (SE), Arvid Carlsson (SE), Jüri Kerstell (SE), Tor Magnusson (SE), Rolf Olsson (SE), Björn-Erik Roos (SE), Bertil Steen (SE), Göran Steg (SE), Alvar Svanborg (SE), Georg Thieme (SE), and Bengt Werdinius (SE) carried out clinical trials for the treatment of Parkinsonism with L-dopa (27).

 

Samuel Lawrence Katz (US), John Franklin Enders (US), Sidney Kibrick (US), Ann Holloway (US), C. Henry Kempe (US), Francis L. Black (US), Martha L. Lepow (US), Saul Krugman (US), and Robert J. Haggerty (US) transformed their Edmonston-B strain of measles (rubeola) virus into a vaccine and, in 1963, licensed it in the United States (787-789). In 1968, an improved and even weaker measles (rubeola) vaccine, developed by Maurice Hilleman and colleagues, began to be distributed. This vaccine, called the Edmonston-Enders (formerly “Moraten”) strain has been the only measles vaccine used in the United States since 1968 (503).

 

John H. Karam (US), Gerold M. Grodsky (US), Peter H. Forsham (US) and Nancy B. McWilliams (US) showed that obese, non-diabetic subjects had levels of serum immunoreactive insulin three to four times higher than those of non-obese, normal subjects after identical rapid intravenous glucose loads. These findings established the relevance of obesity in interpreting the excessive insulin responses to glucose in early maturity-onset diabetics (777).

 

William Griffith McBride (AU) discovered the link between thalidomide and child deformities (1029).

James W. Lash (US) and Lauri Saxén (FI) suggested how thalidomide might cause limb defects in human embryos (879; 880).

 

John Lindenbaum (US) and Edgar Leifer (US) found varying degrees of hepatic injury, usually mild, and with fatty degeneration as the most commonly reported change noted after prolonged administration of halothane or 2-bromo, 2-chloro-1,1,1-trifluoroethane (Fluothane) to animals (924).

 

Philip Jacobs (GB) gave a good clinical description of ankylosing spondylitis (742).

 

Ralph Douglas Kenneth Reye (AU), Graeme Morgan (AU), Jim Baral (AU-US), George Magnus Johnson (US), Theodore D. Scurletis (US), and Norma B. Carroll (US) described an encephalopathy (Reye’s syndrome) which is more common in childhood (3; 753; 1281).

Eugene S. Hurwitz (US), Michael J. Barrett (US), Dennis Bergman (US), Walter J. Gunn (US), Paul Pinsky (US), Lawrence B. Schonberger (US), Joseph S. Drage (US), Richard A. Kaslow (US), D. Bruce Burlington (US), Gerald V. Quinnan (US), John R. LaMontagne (US), William R. Fairweather (US), Delbert Dayton (US), Walter R. Dowdle (US) in a Public Health Service study confirmed that the syndrome is associated with aspirin consumption by children with viral diseases such as chicken pox. Caution when administering salicylates to treat children with viral illnesses, particularly chickenpox and influenza-like illnesses is prudent (725).

 

John Richard O’Brien (GB) concluded that aspirin might be protective in several thrombotic conditions. He was one of the first to call for a trial of aspirin after a thrombotic event such as a heart attack, and to show that low doses of the drug were likely to be effective (1159-1162).

 

Hughes W. Day (US) reported that the first coronary care unit had reduced patient mortality by 60%, leading to the rapid proliferation of such units (332).

 

Thomas Earl Starzl (US), Thomas L. Marchioro (US), and William R. Waddell (US) reported evidence that human kidney allografts performed under azathioprine/prednisone induced variable donor specific nonreactivity. This represents the first systematic use of azathioprine and prednisone with long survival of most kidney allografts (1463; 1469).

 

Thomas Earl Starzl (US), Thomas L. Marchioro (US), Kurt N. von Kaulla (US), Gilbert Hermann (US), Robert S. Brittain (US), and William R. Waddell (US) performed the first successful orthotopic liver transplantation in humans. Immunosuppression was used in all three attempts with the best survival time course being 21 days (1468).

 

James D. Hardy (US), Sadan Eraslan (TR), Martin L. Dalton, Jr. (US), Fikri Alican (US), M. Don Turner (US), Watts R. Webb (US), and George R. Walker, Jr. (US) performed the first successful lung transplant in humans. A pneumonectomy for carcinoma with pleural adhesions had to be performed first. The patient died on the 17th post-operative day (618; 619).

 

Joseph Louis Melnick (US) was among the first researchers to demonstrate that the poliovirus belongs to a group known as enteroviruses and that they only rarely invade the central nervous system.

In 1955 the Committee on the ECHO viruses issued its first report in which 13 antigenically distinct members of the ECHO group were listed (293). Since then the name of the committee has been changed to indicate that it deals with poliomyelitis, Coxsackie, and ECHO viruses, which are now regarded as members of a single family of human enteroviruses (292).

Craig Wallis (US) and Joseph Louis Melnick (US) led a team that developed thermostabilized live polio vaccines, making possible the immunization of millions of people in countries without deep-freeze storage facilities. His team showed that the poliovirus was transmitted among people chiefly by fecal contamination (1617).

Most of the human enterovirus serotypes were discovered and described between 1948 and 1963 because of the application of cell culture and suckling mouse inoculation to investigations of cases of infantile paralysis (paralytic poliomyelitis) and other central nervous system diseases (Committee on Enteroviruses, 1962; Panel for Picornaviruses, 1963).

The history of the enteroviruses is described, and how poliovirus came to be recognized as the prototype species of the genus, a subdivision of the family Picornaviridae. Albert Sabin was one of the main contributors. He isolated several enterovirus types and established them as causative agents of human disease. The enteroviruses were discovered only after new methods were introduced for working with viruses. They are now recognized as constituting one of the genera of the picornavirus family. Pico-rna-virus stands for viruses, which are small (pico), and have an RNA genome. The enterovirus genus includes the polioviruses, the coxsackieviruses and the echoviruses of humans, plus a number of enteroviruses of lower animals (e.g., monkeys, cattle, pigs, mice). Over 100 serotypes are now recognized, the first having been the polioviruses.

 

Peter L. Carlton (US) suggested that brain-acetylcholine acts to inhibit nonrewarded behaviors. This activity thereby provides a kind of ‘guidance system’ by which irrelevant behaviors are eliminated from the animal’s goal-directed repertoire of responses (231).

 

John L. Hamerton (GB) and Harold P. Klinger (CH) speculated that man might have rapidly evolved from chimpanzee/gorilla type ancestors (both of which have 48 chromosomes) via chromosomal rearrangements. On examining the chromosomes of primates generally it is seen that a decrease in the total number of chromosomes is related to an increase in the number of metacentric at the expense of acrocentric chromosomes. This could be brought about if two acrocentric chromosomes broke in the middle (in one case losing the centric region) and the two long portions joined together to make a single new long metacentric chromosome (607).

 

Martin W. Donner (US), Elizabeth M. Ramsey (US), and George W. Corner, Jr. (US) explained the mechanism of circulation within the placenta of the rhesus monkey, first hypothesized upon the basis of anatomical data, then established by radioangiographic studies (360).

 

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; SK = Slovakian; ZA = South African; ES = Spanish; LK = Sri Lankan; SE = Swedish; CH = Swiss; SY = Syrian; TW = Taiwanese; TH = Thai; TN = Tunisian; TR = Turkish; UG = Ugandan; UA = Ukrainian; UY = Uruguayan; VE = Venezuelan; ZW = Zimbabwean

 

 

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