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, DSU Box 3262, Cleveland, MS 38733. 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 (887).

 

“Discovery consists of seeing what everybody has seen and thinking what nobody has thought.” Albert Szent-Györgyi (1500).

 

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 (190).

 

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 buoyancy in solution (1045).

 

Marvin Lee Minsky (US) patented the principle of confocal imaging (1054).

 

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 lipids from animal tissues (454)

 

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 (1112).

 

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 (478). 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 (1429).

 

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).

 

Hal Oscar Anger (US) invented a type of gamma camera that is a scintillation camera, which permits visualization of radiotracer distribution in biological systems and makes possible dynamic studies (33).

 

Russell L. Steere (US) invented freeze-fracture specimen preparation for electron microscopy (1468).

Hans Moor (CH), Kurt Mühlethaler (CH), Heinz Waldner (CH), and Albert Frey-Wyssling (CH) perfected the freeze fracture technique (1091; 1092).

 

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 (454).

 

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 (607). 

 

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 (1586).

 

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 (1666).

 

Arthur J. Kornberg (US) reported that all four of the deoxynucleotide triphosphates must be present for DNA synthesis to take place (830).

 

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 (1053).

 

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 (477).

 

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 (1512).

 

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 (812; 813). 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 (1497).

David Lipkin (US), William H. Cook (US), and Roy Markham (US) determined the structure and molecular weight of adenosine-3', 5'-phosphate (cyclic AMP) (924).

 

Gary Felsenfeld (US), David R. Davies (US), and Alexander Rich (US) discovered that RNA molecules can form triple helices (431).

 

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 (791).

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 (792).

Seymour Kaufman (US) found that the cofactor is a double bond tautomer of the inactive 7,8-dihydropteridine (793). 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 (32; 592; 1390).

 

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 (107; 165; 226; 514; 834; 835; 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 (840).

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 (837).

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 (838; 839).

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" (833).

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 (703).

 

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 (461; 902; 903).

 

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 (847).

 

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 (1150).

 

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 (659).

Hugh John Forster Cairns (GB-US-GB) calculated the mass of T2 bacteriophage DNA to be 110 X 106 daltons (207).

 

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 (271).

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 (999). 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; 1304; 1523).

 

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 (406). 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 (1356; 1670-1672).

 

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 (118-122).

 

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 (524).

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) (682).

 

John Clark Sheehan (US) and Kenneth R. Henery-Logan (US) synthesized Penicillin V (1399; 1400). 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 (754; 1432-1435).

 

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 (116; 676; 677; 1380).

 

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 (1702).

 

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 (379; 380; 640).

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 (286).

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 (816).

 

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 (715). This method has found widespread use in clinical medicine.

 

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 (94).

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 (1007)

 

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” (949).

 

John E. Vogel (US), Alexis Shelokov (US), and Lotta Chi (US) developed the hemagglutination-adsorption (hemadsorption) technique for detecting myxoviruses (1403; 1595).

 

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 (346).

 

Jordi Casals (ES-US) grew the yellow fever virus in suckling mice (238).

 

 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 (1577). 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 (354).  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 (1681). 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 (22; 374; 1389). 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; 1367; 1411; 1707).

 

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 (701). 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) (1521).

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 (154).

 

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 (731).

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 (449; 450; 832).

 

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 (1359).

 

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 (102; 103).

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.) (104).

 

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) (85).

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 (1549; 1550).

 

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 (1055).

 

Joshua Lederberg (US) and Thomas Foxen Anderson (US) demonstrated that following bacterial conjugation the female generates a mixed clone, including recombinants, among the offspring (28; 886).

 

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 (86; 948).

 

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 (259).

 

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 (522).

 

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 (471). 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 (421; 567-569; 1410).

Helge Sigurd Sjövall (SE) had earlier proposed this but thought the lymphocytes recycled mainly through the tissue spaces of the body generally (1428).

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 (571).

Douglas D. McGregor (GB) and James Learmonth Gowans (GB) made the link between lymphocytes and antibody formation (1029).

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 (421).

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 (1305).

 

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 (14; 290).

 

Robert Paul Hanson (US) and Carl A. Brandly (US) worked out the epizootiology of vesicular stomatitis virus (609).

 

James P. Duguid (GB) and Robert Reid Gillies (GB) discovered that Shigella flexneri adheres to epithelial surfaces using fimbriae (pili) (375).

 

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 (871). 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 (1431).

 

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 (1309).

 

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 (490; 491).

 

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 (329). 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 (1351; 1352).

 

Klaus Schwarz (US) and Calvin M. Foltz (US) were the first to recognize that selenium (Se) is important to normal human metabolism (1378).

 

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 (341; 1609).

 

Vernon Benjamin Mountcastle (US) discovered and characterized the columnar organization of the cerebral cortex (1105).

 

Sam L. Clark, Jr. (US) first spotted autophagy in differentiating kidney cells as they redirected their metabolic energies (272). 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 (98; 344; 345). 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 (747). 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) (1311; 1618). 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 (316).

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 (1271).

 

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) (501; 531).

 

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 (1382).

 

Roland Kuhn (CH) observed that imipramine, a tricyclic compound, could relieve depression in patients (854).

Jacques Glowinski (FR) and Julius Axelrod (US) found that tricyclic antidepressant drugs block the uptake of 3H labelled-norepinephrine in brain neurons (541).

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 (23). 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 (1652).

Julius Axelrod (US) found that amphetamine blocks the uptake as well as the release of 3H-labelled-norepinephrine in the brain (73).

 

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 (115).

 

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) (1377).

 

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 (1277). 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 (661).

 

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 (338).

 

George W. Comstock (US) found that Afro-Americans have higher blood pressures at all ages and in both sexes than do Caucasians (293).

 

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 (828).

Burke A. Cunha (US) reports that this pandemic of influenza A was the first to be studied using modern scientific techniques (314). 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 (1638).

 

Leslie Foulds (GB) proposed that the development of cancer is a multistep process (459).

 

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 (133). 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 (826; 932). 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 (266).

 

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 (721; 722)}.

 

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) (174).

 

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 (352).

 

Larry Sandler (US) and Edward Novitski (US) described meiotic drive as an evolutionary force (1343).

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 (313). 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 (596).

 

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 (1657).

 

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 (164).

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 (315).

 

Roger Mason (GB) Tina Negus (GB) and 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 (458). 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 (1114).

 

1958

“A gifted man cannot handle bacteria or equations without taking fire from what he does and having his emotions engaged.” Jacob Bronowski (177).

 

"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 (307).

 

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 (1457).

 

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 (283).

 

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 (1288).

 

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 (126).

 

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 (783; 1488).

Richard C. Graham, Jr. (US), Ulla Lundholm (US), and Morris John Karnovsky (US) reported the cytochemical staining of peroxidase activity (572).

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 (1477).

 

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 (742).

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 (350).

 

Vernon Martin Ingram (DE-GB-US) developed the peptide fingerprinting technique (726).

 

Herbert E. Carter (US), Donald B. Smith (GB), and D.N. Jones (US), using egg yolk, were the first to isolate an ether phospholipid (237).

 

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 (550; 551).

 

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 (1511).

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 (1056-1059).

 

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 (1146). 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 (678; 679).

 

Anthony San Pietro (US) and Helga M. Lang (US) discovered ferredoxin and its role in photosynthesis (1342).

 

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 (1342).

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 (1100; 1101). 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; 1507).

 

Joel Mandelstam (GB) showed that the breakdown as well as the synthesis of proteins occurs in intact bacteria (988).

 

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 (1603; 1604).

 Shugo Shiba (JP), Asaharu Terawaki (JP), Takeo Taguchi (JP), and Junya Kawamata (JP) showed that mitomycin C acts by specific damage to DNA (1407).

 

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’ (875).

 

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 (1506). 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 (798-800). 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 (1581; 1582).

 

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 (1285).

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 (1286). 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 (1693).

 

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 (706; 853).

 

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 (841; 1083).

 

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 (8; 132; 891).

 

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 (954).

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 (1654).

 

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 (729; 1492; 1493). 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 (74; 75).

 

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" (870). 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) (1514; 1515).

 

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 (1044).

 

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 (307; 308). Horace Freeland Judson says the 1958 paper by Crick “permanently altered the logic of biology” (757).

 

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 (307).

 

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 (892). 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 (1471).

 

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 (307).

 

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