A Selected Chronological Bibliography of Biology and Medicine


Part 4B


1937 — 1947



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



"Now my own suspicion is that the Universe is not only queerer than we suppose, but queerer than we CAN suppose." John Burdon Sanderson Haldane (665).


"What does it matter to Science if her passionate servants are rich or poor, happy or unhappy, healthy or ill? She knows that they have been created to seek and to discover, and that they will seek and find until their strength dries up at its source. It is not in a scientist's power to struggle against his vocation: even on his days of disgust or rebellion his steps lead him inevitably back to his laboratory apparatus." Eve Curie Labouisse (FR) in her biography of Madame Curie (907).


Clinton Joseph Davisson (US) and George Paget Thomson (GB) were awarded the Nobel Prize in Physics for their experimental discovery of the diffraction of electrons by crystals.


Walter Norman Haworth (GB) for his investigations on carbohydrates and vitamin C and Paul Karrer (RU-CH) for his investigations on carotenoids, flavins, and vitamins A and B2 were awarded the Nobel Prize in Chemistry.


Albert Imre Szent-Györgyi (HU-US) was awarded the Nobel Prize in Physiology or Medicine for his discoveries in connection with the biological combustion processes, with special reference to vitamin C and the catalysis of fumaric acid.


William S. Koffman (US) developed a rapid photoelectric method for the determination of glucose in blood and urine (755).


Arthur James Ewins (GB) and Montague Alexander Phillips (GB), in 1937, synthesized sulfapyridine, which was the first sulfonamide used with great success in the treatment of pneumonia (528; 529).

Ralph Campbell Lindsay Batchelor (GB), Robert G. Lees (GB), Marjorie Murrell (GB), and George Ian Hector Braine (GB) discovered that gonorrhea can be successfully treated using sulfapyridine (79).


Yasushige Ohmori (JP) reported a method for the determination of alkaline phosphatase in the blood (1154).


Tadeus Reichstein (PL-CH) discovered a steroid hormone from the adrenal cortex which he named substance M (cortisol) (1275).


Hermann Karl Felix Blaschko (DE-GB), Derek Richter (DE), and Hans Schlossmann (DE) discovered an adrenaline-degrading enzyme, initially called adrenaline oxidase, today monoaminooxidase (132; 133).


Esmond Emerson Snell (US), Frank Morgan Strong (US), William Harold Peterson (US), and M. Swaminathan (IN) introduced microbial assays to estimate the concentration of growth factors, including vitamins (1475; 1549).


Hans Molisch (DE) coined the word allelopathy to describe both the beneficial and the deleterious chemical interactions of plants and microorganisms (1099). Note: in recent years the term has been used more often to signify a negative impact of one plant on another through their production and release of chemical compounds.


Vilém Laufberger (CZ) isolated a crystallizable protein from horse spleen, which contained over 20 per cent by dry weight of iron. He named it ferritine (ferritin) and speculated that it served as a depot for iron in the body (932).

Arthur L. Schade (US) and Leona Caroline (US) identified transferrin as an abundant plasma iron transport protein (1383). Both ferritin and transferrin sequester iron to keep it nonreactive.

M. Edward Kaighn (US), Alfred M. Prince (US), Michael K. Skinner (US), Michael D. Griswold (US), Kathleen R. Zahs (US), Violeta Bigornia (US), and Christian F. Deschepper (US) reported that transferrin is actively secreted by hepatocytes, Sertoli cells of the testes, and distinct cells at the blood/brain barrier (827; 1451; 1757).

Kevin M. Shannon (US), James W. Larrick (US), Samuel A. Fulcher (US), Kathy B. Burck (US), John Pacely (US), Jack C. Davis (US), and David B. Ring (US) determined that transferrin receptor, TFR1, is found on rapidly dividing cells, on activated lymphocytes, and on erythroid precursors. TFR1 binds diferric transferrin to internalize it (1424).

Hiromi Gunshin (US), Bryan Mackenzie (US), Urs V. Berger (US), Yoshimi Gunshin (US), Michael F. Romero (US), Walter F. Boron (US), Stephan Nussberger (US), John L. Gollan (US), and Matthias A. Hediger (US) determined that most iron enters the body by way of the duodenum where it is pumped through enterocytes by a proton-coupled metal-ion transporter (648).

Alexander Krause (DE), Susanne Neitz (DE), Hans-Jürgen Mägert (DE), Axel Schulz (DE), Wolf-Georg Forssmann (DE), Peter Schulz-Knappe (DE), Knut Adermann (DE), Christina H. Park (US), Erika V. Valore (US), Alan J. Waring (US), Thomas Ganz (US), Christelle Pigeon (FR), Gennady Ilyin (FR), Brice Courselaud (FR), Patricia Leroyer (FR), Bruno Turlin (FR), Pierre Brissot (FR), and Olivier Loréal (FR) discovered hepcidin, a peptide hormone produced in the liver, that has primary responsibility for modulating iron availability to meet iron needs (885; 1175; 1210).

Cindy N. Roy (US), David A. Weinstein (US), and Nancy C. Andrews (US) proposed a central role for hepcidin in anemia of chronic disease, linking the inflammatory process with iron recycling and erythropoiesis (1341).

Elizabeta Nemeth (US), Marie S. Tuttle (US), Julie Powelson (US), Michael B. Vaughn (US), Adriana Donovan (US), Diane McVey Ward (US), Tomas Ganz (US), Jerry Kaplan (US), Ivana de Domenico (US), Charles Langelier (US), Wesley L. Sundquist (US), and Giovanni Musci (IT) found that hepcidin binds to cell-surface ferroportin, triggering its tyrosine phosphorylation, internalization, and ubiquitin-mediated degradation in lysosomes. By removing ferroportin from the plasma membrane, hepcidin shuts off cellular iron export. This is particularly important in the intestine, where inactivation of basolateral ferroportin leads to retention of iron in the intestinal epithelium, and in iron-recycling macrophages of the reticuloendothelial system, where inactivation of ferroportin interrupts release of iron recovered from senescent erythrocytes (385; 1136).

George C. Shaw (US), John J. Cope (US), Liangtao Li (US), Kenneth Corson (US), Candace Hersey (US), Gabriele E. Ackermann (US), Babette Gwynn (US), Amy J. Lambert (US), Rebecca A. Wingert (US), David Traver (US), Nikolaus S. Trede (US), Bruce A. Barut (US), Yi Zhou (US), Emmanuel Minet (US), Adriana Donovan (US), Alison Brownie (US), Rena Balzan (MT), Mitchell J. Weiss (US), Luanna L. Peters (US), Jerry Kaplan (US), Leonard I. Zon (US), and Barry H. Paw (US) found that precise regulation of iron transport in mitochondria is essential for heme biosynthesis, hemoglobin production, and Fe-S cluster protein assembly during red cell development. Mitoferrin functions as the principal mitochondrial iron importer essential for heme biosynthesis in vertebrate erythroblasts (1425).

Tomas Ganz (US) found that induction of hepcidin in inflammation and consequent iron sequestration augments innate immune defenses against invading pathogens. The resulting decrease in plasma iron levels eventually limits iron availability to erythropoiesis and contributes to the anemia associated with infection and inflammation (590).

Thomas T. Chen (US), Li Li (US), Dong-Hui Chung (US), Christopher D.C. Allen (US), Suzy V. Torti (US), Frank M. Torti (US), Jason G. Cyster (US), Chih-Ying Chen (US), Frances M. Brodsky (US), Eréne C. Niemi (US), Mary C. Nalamura (US), William E. Seaman (US), and Michael R. Daws (US) reported that ferritin receptors are present on lymphocytes and other cell types but their physiologic function has not been fully defined (287).


Alwin Max Pappenheimer, Jr. (US) isolated, crystallized, and characterized diphtheria toxin (1174). This was the first bacterial toxin to be obtained in pure crystalline form.


William Charlton (GB), Walter Norman Haworth (GB), Stanley Peat (GB), Edmund Langley Hirst (GB), Frederick A. Isherwood (GB), Fred Smith (GB), William Zev Hazzid (GB), and Israel Lyon Chaikoff (GB-US) settled the basic structural features of the starch, and glycogen molecules (283; 696; 699; 700).


Otto Fritz Meyerhof (DE-US) proposed that the splitting of ATP might supply energy to initiate the succession of events in muscular activity (1076).


Otto Fritz Meyerhof (DE-US), Walter Schulz (DE), Philipp Schuster (DE), Paul Ohlmeyer (DE-US), and Walter Möhle (DE) found that the oxidation of D-3-phosphoglyceraldehyde to D-3-phosphoglyceric acid requires phosphate, diphosphopyridine nucleotide (DPN), and adenosine diphosphate (ADP). It yields adenosine triphosphate (ATP), and reduced diphosphopyridine nucleotide (DPNH) (1081-1083).


Alexander Logie du Toit (ZA) championed continental drift and was the first to realize that the southern continents had at one time formed the super continent Gondwanaland (455).


Eugene I. Rabinowitch (US) and Joseph Weiss (US) provided evidence that chlorophyll a can be oxidized by light and ferric compounds (1245).


Michael Heidelberger (US), Kai O. Pedersen (SE), and Elvin Abraham Kabat (US) determined the molecular weight of antibodies (706; 822). They were measuring mostly immunoglobulin gamma.


Rudolf Schoenheimer (DE-US) and David Rittenberg (US) found that the degradation and synthesis of saturated fatty acids proceeds two carbon atoms at a time and saturated fatty acids can be converted to mono-unsaturated fatty acids and vice versa. When mice were fed fatty acids labeled with deuterium, most of the deuterium was recovered in the fat tissues rather than being immediately utilized, i.e., newly ingested fat is stored whereas older fat is used. When water labeled with deuterium was administered to mice, it was found that 50 percent of the hydrogen atoms of cholesterol were derived from the hydrogen atoms of the water. Body fat is not static, as was previously thought, but rather in a dynamic turnover state even when adequate fat is supplied in the diet (1299; 1395).

Rudolf Schoenheimer (DE-US), David Rittenberg (US), Marvin Fox (US), Albert S. Keston (US), and Sarah Ratner (US) used heavy nitrogen (N15) labeled amino acids to trace the fate of amino nitrogen and found that there was rapid changing and shifting, even though the overall movement might be small. In their words, “It is scarcely possible to reconcile our findings with any theory which requires a distinction between these two types of nitrogen. It has been shown that nitrogenous groupings of tissue proteins are constantly involved in chemical reactions; peptide linkages open, the amino acids liberated mix with others of the same species of whatever source, diet, or tissue. This mixture of amino acid molecules, while in the free state, takes part in a variety of chemical reactions: some re-enter directly into vacant positions left open by the rupture of peptide linkages; others transfer their nitrogen to deaminated molecules to form new amino acids. These in turn continuously enter the same chemical cycles, which render the source of the nitrogen indistinguishable. Some body constituents like glutamic acid and aspartic acid and some proteins like those of the liver, serum, and other organs are more actively involved than others in this general metabolic pool originating from interactions of dietary nitrogen with the relatively larger quantities of reactive tissue nitrogen” (1394; 1396-1398).

This work on fats and proteins led to a biochemical generalization concerning the biochemical constituents of the body: The large, complex macromolecules are constantly involved in rapid chemical reactions with their smaller component units, a continuing and constant process of degradation and resynthesis. This generalization overthrew the prevailing opinion that the dietary constituents are used only for repair and for energetic purposes.


Ernest Francois Auguste Fourneau (FR), Jacques Gustave Marie Tréfouël (FR), Frederico Nitti (FR), Daniel Bovet (CH-FR-IT), and Thérèse Tréfouël, née Boyer (FR) discovered the antibacterial activity of diasone (Diamidin), 4-4’ diaminodiphenyl sulfone, dihydrostreptomycin (DDS). It is also called dapsone (565).

Guy Henry Faget (US), Frederick A. Johansen (US), Sister Hilary Ross (US), R.C. Pogge (US), J.F. Dinan (US), Bernard M. Prejean (US), and C.G. Eccles (US) of the National Leprosarium, United States Marine Hospital #66, pioneered sulfone drug therapy. Dr. Faget and his staff demonstrated the efficacy of sulfone drugs, including Promin, Diasone, and Promizole in the treatment of Hansen's disease (leprosy) (531-534).

James A. Doull (US) carried out clinical trials on the efficacy of using diasone (Diamidin), 4-4’ diaminodiphenyl sulfone, and dihydrostreptomycin for the treatment of leprosy. It is also called DDS or dapsone. The trials were successful and even today it is still used in combination with antibiotics for treatment of Hansen’s disease (leprosy) (451).


André Pirson (DE) discovered that manganese is essential for oxygenic photosynthesis (1212; 1213).


Albert Francis Blakeslee (US), Amos G. Avery (US), and Albert Levan (SE) discovered that the plant alkaloid colchicine—isolated from autumn crocus and other members of the genus Colchicum—can induce mutations in cells by interfering with cell division. It prevented chromosomes, once doubled, from being partitioned into daughter cells (129; 955).


James Frederick Bonner (US) and James English, Jr. (US) discovered a plant wound hormone, which stimulates cell division. They called it traumatin. Chemically it is 1-decene-1, 10-dicarboxylic acid (160).

Don C. Zimmerman (US) and Carol A. Coudron (US) determined that the wound hormone results from a non-enzymatic oxidation of 12-oxo-trans-10-dodecenoic acid, the first compound in the jasmonic acid pathway (1764).


Charles E. Clifton (US) reported that both sodium azide and 2,4-dinitrophenol inhibit oxidative assimilation, therefore, suggesting an inhibition of energy transfer to the energy-requiring assimilatory reactions (304).

Henry Arnold Lardy (US) and Paul H. Phillips (US) gave the first clear evidence that 2,4-dinitrophenol interferes with the energy-coupling mechanism with the result that oxidation and glycolysis run rampant, while the energy is lost as heat rather than being conserved for work (927).

Jacques Lucien Monod (FR) proved that agents, which uncouple oxidative phosphorylation, such as 2,4-dinitrophenol, completely blocked the shift from one substrate to the other. This suggested that the shift required synthesis of another enzyme thus requiring considerable energy (1100).


M.I. Nakhimovskaia (RU) was the first to survey the soil for the presence of actinomycetes antagonistic to bacteria. Of 80 isolates studied, 47 could suppress bacterial growth, but only 27 released antagonistic substances into the medium (1130).


Selig Hecht (PL-US) explained that when the eyes are exposed to light visual purple (rhodopsin) is converted into a nerve stimulator and retinene (retinal) (yellow). New visual purple is synthesized from vitamin A (retinol) obtained from the blood stream (703).


Harry N. Holmes (US) and Ruth E. Corbet (US) crystallized vitamin A (retinol) from liver oil of mackerel and other fishes (759).


Thaddeus Robert Rudolph Mann (PL-GB) found that in plant tissues the highest concentration of hematin (iron protoporphyrin) occurred in the meristematic tissues and concluded that these higher concentrations correlated with higher metabolic activity (1022; 1023).


Aleksandr Evseyevich Braunstein (RU) and Maria Grigorievna Kritzmann (RU) reported that in minced pigeon-breast muscle, the alpha-amino group of glutamic acid is transferred reversibly to pyruvic acid (to form alanine) or to oxaloacetate (to form aspartic acid) thus effecting a transamination reaction. This discovery provided a metabolic linkage between the ornithine cycle and the citric acid cycle (187).

Philip Pacy Cohen (US) pointed out problems of earlier papers on transamination then refined and made precise the study of transamination. Cohen originated the term transaminase for the enzyme catalyzing transamination (308; 309).


Herman Moritz Kalckar (DK-US), Vladimir Aleksandrovich Belitzer; Vladimir Aleksandrovich Belitser (RU), and Elena T. Tsibakova; Elena T. Tsibakowa (RU) independently supplied evidence that phosphorylation is coupled to respiration. They showed that when various intermediates in the tricarboxylic acid cycle were oxidized by buffered suspensions of freshly minced liver, kidney, or muscle tissue, inorganic phosphate present in the medium disappeared. Concomitantly, there was an increase in the concentration of organic phosphate compounds, such as glucose 6-phosphate and fructose 6-phosphate, whose phosphate groups are derived from ATP. When the tissue suspensions were deprived of oxygen or poisoned with cyanide, uptake of inorganic phosphate did not take place. It was therefore concluded that phosphorylation of ADP is coupled to aerobic respiration as a mechanism for energy recovery.

Belitzer and Tsibakova reported that the phosphorylation of creatine in pigeon heart muscle is coupled to the oxidation of any one of a number of metabolites (e.g., citrate, alpha-ketoglutarate, succinate, pyruvate, lactate, malate, fumarate) and that approximately two molecules of creatine phosphate are synthesized per atom of oxygen consumed (103; 828; 830; 834).


Erwin Paul Negelein (DE) and Hans Joachim Wulff (DE) crystallized alcohol dehydrogenase from yeast (1134).


Mortimer Louis Anson (US) crystallized carboxypeptidase (34).


Robert A. Fulton (US) and Horatio C. Mason (US) produced the first evidence for the absorption and translocation of a bulky insecticidal molecule foreign to the plant, when they found that derris applied to the first two leaves of bean plants reduced the attack by the Mexican bean beetle (Chrysomelidae) on leaves subsequently produced (586). This was evidence that the insecticide had spread to become systemic.


Conrad Arnold Elvehjem (US), Robert James Madden (US), Frank Morgan Strong (US), and Dilworth Wayne Woolley (CA-US) demonstrated that lack of sufficient nicotinic acid (vitamin B3 or nicotinamide) in a dog’s diet leads to a disease called black-tongue (510; 511). Pellagra is the human equivalent of black-tongue.


Joseph Gilbert Hamilton (US) used radioactive sodium to perform the first medical physiology studies of the dynamics of sodium transport in the human. Both test subjects were leukemia patients (671).


Homer William Smith (US) discovered that since inulin is completely filterable at the glomerulus and not reabsorbed, excreted, or synthesized by the renal tubules it can be used to measure glomerular filtration (1458).


Kenneth Vivian Thimann (GB-US) and Frits Warmolt Went (NL-US) suggested that depending on its concentration auxin might produce inhibitory effects in one tissue and stimulation in another, different tissues being characterized by a series of overlapping optimal concentration curves (1570; 1677).


George S. Avery, Jr. (US), Paul R. Burkholder (US) and Harriet B. Creighton (US) found that methyl 3-indole acetate, potassium 3-indole acetate, gamma-3-indole butyric acid, methyl gamma-3-indole butyrate, potassium gamma-3-indole butyrate, alpha-naphthalene acetic acid, potassium alpha-naphthyl acetate, methyl alpha-naphthyl acetate, ethyl alpha-naphthyl acetate, beta-3-indole propionic acid, and potassium beta-3-indole propionate are effective in promoting growth curvatures of the Avena coleoptile (Went method) (50).


Edward Calvin Kendall (US) and Dwight Joyce Ingle (US) characterized the relation between the adrenal gland and salt and water metabolism, a phenomenon that subsequently became the basis for a bioassay system that led to the recognition that the adrenal cortex secretes a mineralocorticoid hormone (aldosterone) (850).


Dwight Joyce Ingle (US) and Edward Calvin Kendall (US) found that administration of adrenalcortical extracts or purified glucocorticoids to intact rats causes atrophy of the adrenal glands. Adrenal atrophy could be avoided by simultaneous administration of pituitary extracts (798; 801).

Dwight Joyce Ingle (US), Choh Hao Li (CN-US), and Herbert McLean Evans (US) established that the changes in adrenal size and activity are mediated by the pituitary hormone adrenocorticotropin (800; 802; 803). Note: The elucidation of the feedback mechanism between the adrenal cortex and the pituitary became the model for similar studies.


Alan Lloyd Hodgkin (GB) demonstrated the dependence of nerve conduction on the electronic spread of depolarization induced by local current from the region of the action potential to that ahead of it to cause enhanced excitability and excitation (748; 749).


Edward Holbrook Derrick (AU), Frank Macfarlane Burnet (AU), and Mavis Freeman (AU), worked on an outbreak of febrile disease among abattoir workers, described Q fever (Nine-Mile Fever) and Derrick designated Rickettsia burnetii (Coxiella burnetii) as the etiological agent (225-228; 423; 424). The Q stands for query and not Queensland as some writers have reported.

Gordon E. Davis (US) and Herald Rea Cox (US) identified a new rickettsial disease, which they called Nine Mile Fever (named for Nine Mile Creek where the ticks were collected). It is synonymous with Q fever (381).


Fred R. Beaudette (US) and Charles B. Hudson (US) were the first to isolate a coronavirus. The source was chickens with infectious bronchitis (90).

David Arthur John Tyrrell (GB) and M.L. Bynoe (GB) used cultures of human ciliated embryonal trachea to propagate the first human coronavirus in vitro (1595).

Jane Parry (GB) reported that severe acute respiratory syndrome (SARS) is likely caused by a strain of coronavirus (1178). It was later called SARS-Associated Coronavirus (SARS-CoV).

Victor M. Corman (DE), Isabelle Eckerle (DE), Tobias Bleicker (DE), Ali Muhammad Zaki (SA), Olfert Landt (DE), Monika Eschbach-Bludau (DE), Sander van Boheemen (NL), Robin Gopal (GB), Tobias M. Ballhause (DE), Theo M. Bestebroer (NL), Doreen Muth (DE), Marcel A. Müller (DE), Jan Felix Drexler (DE), Maria Zambon (GB), Albert D. Osterhaus (NL), Ron A.M. Fouchier (NL), and Christian Drosten (DE) first reported a novel coronavirus called “Middle East Respiratory Syndrome Coronavirus” (MERS-CoV) in 2012 in Saudi Arabia (351).


Gilbert Julias Dalldorf (US), Margaret Douglass (US), and Horace Eddy Robinson (US) demonstrated the ability of one virus to modify the course of infection by another (infection with lymphocytic choriomeningitis virus protected monkeys from infection by poliomyelitis) (370-373).


Charles Armstrong (US) announced successful passage of a fresh human strain of poliomyelitis virus (Lansing strain) from the monkey to Eastern cotton rats (Sigmodon hispidus hispidus) (35).

Charles Armstrong (US) successfully transfered the Lansing strain of poliomyelitis virus from the Eastern cotton rat to the white mouse (36).


Eugene Wollman (FR) and Elisabeth Wollman (RU-FR) noted that immediately after being infected bacteriophages pass through a noninfectious stage (1728).

August H. Doermann (US), for the first time, methodically investigated the complete life cycle of a bacteriophage and rediscovered the virus eclipse phase, the time elapsed between successful infection of the host cell and the start of new virus production. During this phase no infectious particles were present within the host cell (441).


Thomas Milton Rivers (US) devised a set of postulates, like Koch’s, which were very useful in establishing the causal role of a virus in disease. River’s postulates, applicable to both animal and plant viruses, can be stated as follows:

1) The viral agent must be found either in the host’s body fluids at the time of the disease or in the cells showing specific lesions.

2) The viral agent obtained from the infected host must produce the specific disease in a suitable healthy animal or plant or provide evidence of infection in the form of antibodies (substances produced by vertebrates in response to a virus) against the viral agent. It is important to note that all host material used for inoculation must be free of any bacteria or other microorganisms.

3) Similar material from such newly infected animals or plants must in turn be capable of transmitting the disease in question to other hosts (1300).


Thomas Francis, Jr. (US), Thomas P. Magill (US), Jonas E. Salk (US), Monroe D. Eaton (US), Gordon Meiklejohn (US), Frederick M. DavenPort (US), C. Henry Kempe (US), William G. Thalman (US), Edwin H. Lennette (US), George Keble Hirst (US), Elsmere R. Rickard (US), William F. Friedewald (US), Theodore C. Eickhoff (US), Jerome L. Schulman (US), and Edwin D. Kilbourne (US) were major participants in the development of influenza vaccines (379; 483; 503; 570; 571; 745; 746; 1062; 1063; 1412).


Arthur Quinton Wells (GB) discovered and characterized the acid-fast bacillus Mycobacterium microti as the cause of an epizootic, chronic infection of the field vole, i.e., vole tuberculosis (1672).


Robert Lee Hill (GB), Fay Bendall (GB), and Ronald Scarisbrick (GB) discovered that light-induced oxygen evolution can be observed in cell-free granular preparations extracted from green leaves. Illumination of such preparations in the presence of artificial electron acceptors, such as ferricyanide or reducible dyes, caused evolution of oxygen and simultaneous reduction of the electron acceptor —this later became known as the Hill reaction. Carbon dioxide was apparently not required, nor was it reduced to a stable form that accumulated, suggesting that the photoreduction of carbon dioxide to hexose is a later step in photosynthesis. Electrons are being induced to flow away from water molecules to an acceptor, thus yielding molecular oxygen from the water. Yet in animal tissues electrons arising from organic substrates flow toward molecular oxygen, which is reduced to water. Clearly, the direction of electron flow is opposite to that in respiration. The energy of this reversed electron flow, which takes place only on illumination, comes from the absorbed light (730-735). The 1960 paper was the first to describe a ‘Z’-scheme for the two light reactions of photosynthesis.


H. Close Hesseltine (US) presented evidence indicating that pregnancy and diabetes mellitus are predisposing conditions for mycotic vulvovaginitis (723).


John Burdon Sanderson Haldane (GB-IN) introduced the concept of genetic load which was defined as the proportion of the population that die each generation because of the action of selection on a genetic system (664).


Tracy Morton Sonneborn (US) demonstrated the mechanism for inheritance of mating type in Paramecium aurelia. He determined that a single gene controlled mating type. This was the first gene to be demonstrated in the ciliates (1482-1485).


Gladwyn Kingsley Noble (US) and Adolf H. Schmidt (US) discovered that two groups of snakes, the pit vipers (Crotalidae) and the boas (Boidae) use thermal radiation from a warm-blooded animal such as a mouse to guide their striking motion (1145).

Theodore Holmes Bullock (US) and Friedrich P.J. Diecke (US) showed that pit vipers could detect long-wavelength infrared radiation (221).


Frank Fraser Darling (GB) did a classic field study of red deer and wrote A Herd of Red Deer. This research would be instructive reading for any aspiring field biologist (378).


Theodosius Grigorievich Dobzhansky (Ukrainian-US) authored Genetics and the Origin of Species in which he concluded that genetic mutations generate numerous variations thus providing the raw material for natural selection. This book also made a deep impression on naturalists by relating systematics to genetics (437).


Walter Michel (DE) was the first to produce artificial heterokaryons. He fused plant protoplasts from different species and genera (1084).


William Jacob Robbins (US), Mary A. Bartley (US) and Frederick Kavanagh (US) showed that vitamin B1 (thiamine) promotes the growth of tomato root tips and fungi in culture (1304; 1305). This was the first time that a vitamin was shown to be necessary for plant or fungal growth.

William Jacob Robbins (US) and Mary Stebbins (US), had by 1949, kept tomato roots through 131 consecutive passes in a solution of mineral salts, cane sugar, and thiamine or thiazole. A period of over twenty years!


Charles Drechsler (US) discovered that the fungus Arthrobotrys dactyloides throttles its nematode prey with nooses of three cells held out on a short stalk. A nematode worm passing through one of these traps triggers its closure. The cells triple in volume in a tenth of a second, constricting and ensnaring the worm for consumption (453).


Alfred Edwards Emerson (US), based on his work with termites, wrote the first of many articles defending the use of behavioral traits as taxonomic characters (512).


Per Fredrik Thorkelsson Scholander (SE-NO-US), Laurence Irving (US), Wilhelm Bjerknes (NO), Edda Bradstreet (US), Stuart W. Grinnell (US), Herschel V. Murdaugh, Jr. (US), Bodil M. Schmidt-Nielsen (DK-US), J.W. Wood (US), William L. Mitchell (US), Harold Theodore Hammel (US), David Hugh LeMessurier (AU), Edvard A. Hemmingsen (NO-US), and Walter F. Garey (US) investigated the physiology of deep diving mammals and found that: seals exhale prior to a dive, thus decreasing the nitrogen content of their lungs and avoiding the “bends.” The oxygen-carrying capacity of the blood is much greater in a seal than in man. The seal’s blood volume is relatively large, and both blood and muscles contain much larger amounts of hemoglobin, and thus hold more oxygen, than in mammals in general. A seal’s most characteristic response to an experimental dive is to slow the heart down to a few beats per minute (diving bradycardia is typical of all animals investigated; that is mammals, birds, reptiles, amphibians, and even fishes which had been taken out of water); the blood is diverted to the most vital organs, notably the central nervous system and eyes. The muscles, which can function anaerobically through the formation of lactic acid, receive no blood and thus acquire an oxygen debt that is repaid when oxygen is again available at the termination of the dive.

For these investigations Scholander developed new methods for continuous recording of the respiratory metabolism of diving animals (124; 807; 808; 1120; 1399-1406; 1408; 1409).


Julia Bell (GB) and John Burdon Sanderson Haldane (GB) described the first example of linkage in humans in X-linked pedigrees transmitting both hemophilia and color blindness (104).


Max Theiler (ZA-US) isolated and characterized a new virus disease, spontaneous encephalomyelitis of mice (1568).


Jacob Furth (US) and Morton Kahn (US) were the first to allude to cancer stem cell (CSC) or tumor-initiating cell principles. Using cell lines, they provided the first quantitative assay for the assessment of the frequency of the malignant cell maintaining the hematopoietic tumor. They showed that a single leukemic cell can transmit the systemic disease when transplanted into a mouse (587).

Robert Bruce (CA) and Hugo Van der Gaag (CA) used the spleen colony-forming assay (CFU-S) to show that only a small subset of primary cancer tissue can proliferate in vivo (210).

Tsvee Lapidot (CA), Christian Sirard (CA), Josef Vormoor (CA), Barbara Murdoch (CA), Trang Hoang (CA), Julio Caceres-Cortes (CA), Mark Minden (CA), Bruce Paterson (CA), Michael A. Caligiuri (US), Dominique Bonnet (CA) and John E. Dick (CA) showed that when isolated from acute myeloid leukemia (AML) patients, only a small fraction of the tumor cells with a characteristic marker signature is able to establish leukemia in recipient mice (164; 924).

Muhammad Al-Hajj (US), Max S. Wicha (US), Adalberto Benito-Hernandez (US), Sean J. Morrison (US), Michael F. Clarke (US), Sheila K. Singh (CA), Cynthia Hawkins (CA), Ian D. Clarke (CA), Jeremy A. Squire (CA), Jane Bayani (CA), Takuichiro Hide (CA), R. Mark Henkelman (CA), Michael D. Cusimano (CA), and Peter B. Dirks (CA) revealed that the cancer stem cell (CSC) concept extends beyond hematopoietic malignancies. They showed that human breast and brain tumors are not homogeneous, but rather contain a small subset of cells that can be prospectively isolated and are able to initiate phenotypically heterogeneous cancers in vivo (10; 1448).


Hans Popper (AT-US), Emil Mandel (AT), and Helene Mayer (AT) developed the creatinine clearance test for assessing kidney function (1220).


William Warrick Cardozo (US) concluded that sickle cell anemia is inherited following Mendelian law and is more frequent among black people or people of African descent (256).


Samuel Soskin (US) and Rachmiel Levine (PL-CA-US) espoused the concept of a hepatic threshold for glucose, defined as the blood glucose level at which glucose production and utilization by the liver exactly balance each other. They believed that the hepatic threshold for glucose is elevated in diabetes and lowered by insulin (1490).


Ludvig G. Browman (US) showed that the exposition of rats to continuous light interrupts the estral cycle inducing the state of persistent estrous (198).

Virginia Mayo Fiske (US) reported on the effect of light on sexual maturation, estrous cycles, and anterior pituitary in the rat (548).


Fuller Albright (US), Allen M. Butler (US), Aubrey Otis Hampton (US), and Philip H. Smith (US) described a syndrome (later to become Albright’s syndrome) distinguished by precocious puberty in girls, cystic bone disease, and brownish pigmentation of the skin (12).


Raphael Issacs (US), using careful cytological study of the cell types in lymphosarcoma leukemia, found that the cells are not lymphocytes, but lymphosarcoma cells, so that the condition is true lymphosarcoma cell leukemia (809).


Abraham Albert Hijmans van den Bergh (NL) and Wilhelm Grotepass (NL) gave the first clinical and biochemical picture of variegate porphyria (VP) (1602).

Jan Gosta Waldenström (SE) described over one hundred patients with acute intermittent porphyria (AIP), most of who originated from a small village in Northern Sweden (1639). AIP is characterized by recurrent episodes of abdominal pain, vomiting, constipation, hypertension, tachycardia, and neurologic involvement including muscle weakness, mental changes, and even seizures.

Since this early observation, specific inherited deficiencies of enzymes within the heme synthetic pathway have been delineated that allow improved understanding of classification, pathogenesis, and genetic screening.

L. James Strand (US), Bertram F. Felsher (US), Allan G. Redeker (US), and Harvey S. Marver (US) determined that acute intermittent porphyria is characterized as an autosomal dominant condition resulting from decreased levels of porphobilinogen deaminase (PBG) or hydroxymethylbilane synthase (HMB) (1537).


Robert Alexander McCance (GB), Elsie M. Widdowson (GB), Norman M. Keith (GB), Arnold E. Osterberg (GB), and Harry E. King (GB) observed that renal potassium clearances in excess of glomerular filtration rate often occurred (846; 1041). This implied tubular secretion of potassium.


Robert Alexander McCance (GB) and Elsie M. Widdowson (GB) concluded that no physiologic mechanism of iron excretion exists. Consequently, absorption alone regulates body iron stores (1042).


Vittorio Erspamer (IT), Maffo Vialli (IT), Giuseppe Boretti (IT), and Biagio Asero (IT) isolated and characterized a hormone substance from enterochromaffin cells they named enteramine (524-526).

Maurice M. Rapport (US), Arda Alden Green (US), and Irvine Heinly Page (US) isolated and chemically characterized this vasconstrictor indole (5-hydroxytryptamine) and named it serotonin (1264-1267).

Betty Mack Twarog (US), Irvine Heinly (US), A.H. Amin (GB), Tom B.B. Crawford (GB), John Henry Gaddum (GB), and John Henry Welsh (US) determined that serotonin was a neurotransmitter in invertebrates and the central nervous system of higher animals (26; 1593; 1594; 1674-1676).

Dilworth Wayne Woolley (US) and Elliott Shaw (US) suspected that serotonin might be a neurotransmitter involved in mental illness (1743; 1744).


James Wenceslas Papez (US) published work on the limbic circuit and conceived a mechanism of emotion (hypocampo-thalamo-cingulate-hippocampal circuit) associated with this region of the brain (1173). Note: Limbic means border.

Paul D. MacLean (US) coined the phrase limbic system and distinguished three limbic circuits based on function; emotions related to self-preservation (amygdala and hippocampus), emotions related to pleasure (cingulate gyrus and septum), and emotions related to social cooperation (parts of the hypothalamus and anteriorthalamus) (1012; 1013).

Paul D. MacLean (US) proposed that our skull holds not one brain, but three, each representing a distinct evolutionary stratum that has formed upon the older layer before it, like an archaeological site: the triune brain. The three levels are 1) the Reptilian Brain, 2) the Limbic System (Paleomammalian brain), and 3) the Neocortex (Neomammalian brain) (1014).


Tracy Jackson Putnam (US) and Hiram Houston Merritt (US) were the first to discover that phenytoin (PHT) (also diphenylhydantoin) is a therapeutically effective substance when it counteracts electrically induced hyperexcitability and convulsions in the cat. They reported their clinical trial of sodium diphenyl hydantoinate made in 200 patients with frequent convulsive seizures which had not been relieved by the previous modes of therapy. In 142 such patients who have received the treatment for periods varying from two to eleven months, grand mal attacks were relieved in 58 per cent and greatly decreased in frequency in an additional 27 per cent; petit mal attacks were relieved in 35 per cent and greatly decreased in frequency in an additional 49 per cent, and psychic equivalent attacks were relieved in 67 per cent and greatly decreased in frequency in 33 per cent. There were no fatalities (1072; 1241).


Riojun Kinosita (JP-US) found that liver tumors could be readily induced by ingestion of dimethylaminoazobenzene, a dye known as " butter-yellow " (861).


Wade H. Marshall (US), Clinton Nathan Woolsey (US), and Archibald Philip Bard (US) used the cathode ray oscilloscope and the evoked potential technique to develop detailed mapping of the somatic sensory area of the cerebral cortex of the cat and monkey (1028; 1029; 1749).


Walter Edward Dandy (US), in 1937, performed he first direct surgical approach and clipping of a cerebral aneurysm (375).


James Barrett Brown (US) achieved permanent survival of skin grafts exchanged between human monozygotic twins (204).


Edward Thomas Campbell Milligan (GB), C. Naunton Morgan (GB), Lionel E. Jones (GB), and R. Officer (GB) devised one of the most popular hemorrhoidectomy operations. It was named the Milligan-Morgan technique in their honor (1092). Note: It was associated with significant post-operative pain.

Antonio Longo (IT) invented a circular stapling device for treatmet of hemorrhoidal disease. The level of pain associated with this treatment was less than that of the Milligan-Morgan procedure .

Brian J. Mehigan (GB), John R.T. Monson (GB), and John E. Hartley (GB) performed one of the first randomized trials assessing post-operative pain in patients undergoing stapled hemorrhoidectomy versus the older excisional approach. They found that stapled hemorrhoidectomy is associated with a significant improvement in post-operative pain (1061).


Alfred Wiskott (DE), Robert Anderson Aldrich (US), Arthur G. Steinberg (US), and Donald C. Campbell (US) described a syndrome characterized by a triad of eczema, profound thrombocytopenia, and frequent infections due to immunological deficiency. It is a sex-linked recessive disorder with a defect in both T and B cell function (16; 1724). It is often called Wiskott-Aldrich syndrome.


Thomas Hale Ham (US) established that in chronic hemolytic anemia with paroxysmal nocturnal hemoglobinuria (PNH) the lysis is affected by complement. He demonstrated a dose-response relationship (limited because hemolysis disappears with even very little dilution of serum), and that inhibition or destruction of complement or components of complement abrogated the lytic reaction (669).


F.J. Neuwahl (GB) and C.C. Fenwick (GB) introduced an extract of Bulgarian belladonna (deadly nightshade) as a treatment for post-encephalitic Parkinsonism (1139; 1140).


Geoffrey Keynes (GB) perfected and championed the treatment of breast cancer with breast-sparing surgery followed by radiation therapy. After surgery to remove the tumor, long needles containing radium are inserted throughout the affected breast and near the adjacent axillary lymph nodes (855; 1052).


Helga Tait Malloy (CA) and Kenneth A. Evelyn (CA) described a method for the accurate photoelectric determination of both direct and indirect bilirubin in serum, in which protein precipitation and consequent loss of bilirubin by adsorption have been eliminated (1020).


Erwin Chargaff (AT-US) and Kenneth B. Olson (US) discovered that protamine can neutralize heparin’s function as an anticoagulant (282).

Bernard J. Miller (US), John Heysham Gibbon, Jr. (US), and Mary Gibbon (US) used protamine to reverse the anticoagulation effects of sodium heparin during open-heart surgery (1089).

Clarence Walton Lillehei (US), Morley Cohen (US), Herbert E. Warden (US), and Richard L. Varco (US) used controlled cross-circulation to correct a ventricular septal defect in an 11-year-old boy. The boy's anesthetized father served as the oxygenator. Blood flow was routed from the patient's caval system to the father's femoral vein and lungs, where it was oxygenated and then returned to the patient's carotid artery. The cardiac defect was repaired with a total pump time course of 19 minutes. Over the ensuing 15 months, Lillehei operated on 45 patients with otherwise irreparable complex interventricular defects; most of these patients were less than 2 years old. Although cross-circulation was a major advance, it was not adopted for widespread use because it posed a serious risk to the "donor” (974).

Clarence Walton Lillehei (US) and Richard A. DeWall (US), in 1955, advanced the concept of a heart-lung machine. They called it a helix reservoir bubble oxygenator, which bubbled oxygen through the blood during the operation (975).

John W. Kirklin (US), James W. Dushane (US), Robert T. Patrick (US), David E. Donald (US), Peter S. Hetzel (US), Harry G. Harshbarger (US), and Earl H. Wood (US) began a successful series of open-heart surgeries utilizing an extracorporeal circulation machine (a modified Mayo-Gibbon-IBM pump oxygenator) (863).

These early versions of heart-lung machines were cumbersome and dangerous —often leaking blood, damaging blood cells and causing air embolisms (602).

Clarence Walton Lillehei (US), Vincent L. Gott (US), Richard A. DeWall (US), and Richard L. Varco (US) used a pump oxygenator while correcting a pure mitral regurgitation with suture plication of the commissures under direct vision. Heart-lung machines had come of age (976).


Arne Torkildsen (NO), in 1937, performed the first ventriculocisternostomy to relieve obstructive hydrocephalus. This is the surgical formation of an opening between the ventricles of the brain and the cerebellomedullary cistern (1585).


Andrew W. Contratto (US) and Samuel A. Levine (US) studied 180 cases of aortic stenosis, unassociated with other significant valve disease, 53 of which were examined post mortem. Among the cases an early history of rheumatic fever was common. A loud basal systolic murmur, a systolic thrill near the aortic area, and calcification of the valve were common. Disturbances in conduction such as bundle branch block and auriculoventricular block were common. Angina pectoris occurred in 22.7 % of the cases. There were 21 instances of syncope (335).


William H. Lang (GB) positioned Cooksonia pertonii as the earliest known land-living vascular plant found in England and one of the earliest in the world (921).

Dianne Edwards (GB) and E. Catherine W. Rogerson (GB) discovered Cooksonia pertonii near Brecon Beacons, England in rock 420 M (497; 498).


Ales Hrdlicka (CZ-US) proposed that America had been peopled from Asia via the Bering Strait (778).


Dorothy Anne Elizabeth Garrod (GB), Dorothea Minola Alice Bate (GB), Theodore Doney McCowan (GB), and Arthur Keith (GB) reported the discovery at Mugharet et-Tabun, Mount Carmel, southeast of Haifa, Israel of a fossilized female skeleton likely to be Homo sapiens neanderthalensis; Homo neanderthalensis. They also discovered Homo remains from roughly the same time period in a nearby cave named Mugharet es-Skhül (592; 1049). These specimens are dated at 30-60 K BP


The National Cancer Institute was formed.


c. 1938

James Gordon Horsfall (US) introduced chloranil as a fungicide for legume seed treatment (769).



Richard Johann Kuhn (DE) was awarded the Nobel Prize in Chemistry for his work on carotenoids and vitamins. He was caused by the authorities of his country to decline the award but later received the diploma and the medal.


Corneille Jean Francois Heymans (BE) was awarded the Nobel Prize in Physiology or Medicine for the discovery of the role played by the sinus and aortic mechanisms in the regulation of respiration.


William Thomas Astbury (GB), and Florence Ogilvy Bell (GB) presented the first x-ray diffraction pictures of DNA. They were of calf thymus DNA sent to them by Torbjörn Oskar Caspersson, the Swedish biochemist (40-42).


Max Ferdinand Perutz (AT-GB), John Desmond Bernal (GB), Isadore Fankuchen (US), Michael George Rossmann (US), Ann F. Cullis (GB), Hilary Muirhead (GB), Georg Will (GB), and Anthony C.T. North (GB) were among the first to report the tertiary and quaternary structure of a protein—hemoglobin and chymotrypsin. Perutz began this work as part of his Ph.D. thesis in 1937 (120; 1192-1199).

Guilio Fermi (GB), Max Ferdinand Perutz AT-GB), Boaz Shaanan (IL), and Roger Fourme (FR) determined the crystal structure of human deoxyhemoglobin at 1.74 Å resolution (542).


Donald Dexter van Slyke (US), Alma Hiller (US), Robert T. Dillon (US), and Douglas A. MacFadyen (US) announced the discovery of the amino acid hydroxylysine, which they isolated from gelatin (1608).

James R. Weisiger (US), Elizabeth A. Jacobs (US), John Clark Sheehan (US), and William A. Bolhofer (US) later synthesized hydroxylysine (1428; 1667).


Albert Neuberger (DE-GB) discovered that ovalbumin, a protein from chicken egg white, contains a carbohydrate moiety. This marks the beginning of modern glycoprotein research (1138).


Virginia Clementine Irvine (US), Sydney Charles Bausor (US), Percy W. Zimmerman (US), Alfred E. Hitchcock (US), and Frank Wilcoxon (US) demonstrated that beta-naphthoxyacetic acid is an auxin (81; 806; 1766)