A Selected Chronological Bibliography of Biology and Medicine — Part III

1925 — 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:

John D. Tiftickjian, Jr., Ph.D., Professor of Biology
Delta State University
Box 3262, Cleveland, MS 38733
e-mail: jtift@deltastate.edu




1925

"The key to every biological problem must finally be sought in the cell." Edmund Beecher Wilson(1).

“When we consider what religion is for mankind, and what science is, it is no exaggeration to say that the future course of history depends upon the decision of this generation as to the relations between them.” Alfred North Whitehead(2).

“Almost all new ideas have a certain aspect of foolishness when they are first proposed.” Alfred North Whitehead(2).

Richard Adolf Zsigmondy (AT-DE) received the Nobel Prize in Chemistry for his demonstration of the heterogeneous nature of colloid solutions and for the methods he used, which have since become fundamental in modern colloid chemistry. He developed a dark field ultramicroscope which could detect particles with diameters below the wavelengths of visible light.

Sir Ronald Aylmer Fisher (GB-AU) invented the statistical method known as analysis of variance(3).

Alfred James Lotka (US) presented mathematical models of energy transformations within the biosphere thus forming the basis of physical biology(4, 5).

Vladimir I. Vernadsky (RU) made a similar biogeochemical approach to ecology about this time(6).

Walter S. Abbott (US) developed a method for computing the effectiveness of insecticides(7).

William S. Hoffman (US) isolated adenine nucleotide in crystalline form from pig blood(8).

John Mason Gulland (GB) and Sir Robert Robinson (GB) worked out the structure of morphine(9).

Bernhard Zondek (DE-IL) and Benno Brahn (DE) isolated an estrogenic hormone from the ovarian follicle(10, 11).

Treat Baldwin Johnson (US) and Robert D. Cogshill (US) discovered the occurrence of 5-methylcytosine in nature (tubercle bacteria)(12).

Rollin Douglas Hotchkiss (US) and Gerard R. Wyatt (CA) discovered 5-methylcytosine in plant and animal tissues(13, 14).

Gottfried Koller (DE), Earle B. Perkins (US), Theodore Snook (US), and Benjamin Kropp (US) found that there is produced in the eye stalks of crustaceans a hormone which, when carried in the blood stream, is effective in inducing chromatophore changes. Koller named this hormone contractin(15-20).

Edouard Chatton (FR) first used the terms procaryote and eucaryote in his 1925 paper when he suggested that the most significant taxonomic distinction among life forms today is not between plants and animals but between cells with nuclei, eukaryotes, and cells without them, prokaryotes. Pro means before and eu means true, karyote refers to a nut or kernel(21, 22).“Protozoologists agree today in considering the flagellated autotrophs the most primitive of the Protozoa possessing a true nucleus, Eucaryotes (a group which also includes the plants and the Metazoans), because they alone have the power to completely synthesize their protoplasm from a mineral milieu. Heterotrophic organisms are therefore dependent on them for their existence as well as on chemotrophic Procarytotes and autotrophs (nitrifying and sulphurous bacteria, Cyanophyceae.” This is a translation by Jan Sapp (CA) from the 1938 reference(23).

Eukaryotes are now placed in the domain Eucarya while prokaryotes are placed in either the domain Bacteria or Archaea.

André Michel Lwoff (FR) used the word eukaryote(24).

Ellsworth C. Dougherty (US) proposed the prokaryotic-eukaryotic dichotomy. He used the words eukaryon (Greek: true kernel) for the nucleus of “higher organisms” and prokaryon (Greek: before kernel) for the moneran nucleus.(25).

Roger Yate Stanier (CA) and Cornelis Bernardus Kees van Niel (NL-US) later defined bacteria by conceptualizing two new biological entities, "prokaryotes" and "eukaryotes." They argued that the cells of all living things were either prokaryotic or eukaryotic, depending on their pattern of cellular organization. They defined eukaryotes as cells containing membrane-bound structures called organelles, the most important of which was the nucleus. By this definition, all cells of multi-cellular plants and animals were eukaryotes. Cells that lacked membrane-bound cell nuclei, like bacteria and blue-green algae, were designated prokaryotes. The term prokaryote implicitly elevated bacteria to equivalent biological status with all other organisms, to be known as eukaryotes(26). This represents the resurrection and embellishment of an idea first conceived by Edouard Chatton (FR).

Robert George Everitt Murray (CA) proposed Procaryotae as a taxon “at the highest level” and described it as “a kingdom of microbes…characterized by the possession of nucleoplasm devoid of basic protein and not bounded from cytoplasm by a nuclear membrane.” He suggested Eucaryotae as a possible taxon at the same level to include other protists, plants, and animals(27).

Erwin Broun Fred (US), Ira Lawrence Baldwin (US) and Elizabeth McCoy (US) published the definitive text on nitrogen fixation(28).

Agnes Robertson Arber (GB) authored Monocotyledons; a Morphological Study which developed the thesis, first suggested by A.P. de Candolle, that the monocot leaf is derived from a dicot petiole (phyllode theory )(29).

Emil-Karl Frey (DE) observed in 1925 a considerable reduction in arterial blood pressure when he injected human urine into dogs. Unlike many other contemporary scientists he did not attribute this effect to a toxic action of urine, but rather as the specific activity of an unknown substance with potential biological functions(30, 31). 

Heinrich Kraut (DE), Emil-Karl Frey (DE) and Eugen Werle (DE) reasoned that, “It is a substance that probably originates from several organs, is eliminated by the kidneys and has a pronounced cardioactive and vasoactive effect: a substance that is assigned the role of a hormone in the organism”. This F-substance was then called kallikrein, since it was considered to have originated in the pancreas (Greek synonym: kallikreas)(32). 

Eugen Werle (DE), W. Götze (DE), A. Keppler (DE), and M. Grunz (DE) discovered kinins when they gave evidence that a smooth muscle stimulating substance KLK (tissue kallikrein) is a proteolytic enzyme, which liberates the biologically highly active basic polypeptide kallidin (KD) from the plasma protein, kallidinogen or kininogen(33, 34). Its name was later changed to kallidin and that of the precursor to kallidinogen. This work laid the foundation for understanding the system that we refer to today as the kallikrein-kinin system (cascade).

George Edward Briggs (GB) and John Burdon Sanderson Haldane (GB-IN) made important refinements in the theory of enzyme kinetics with their steady-state derivation of the single-substrate enzyme saturation curve(35). 

Earl Perry Cark (US) and James Bertram Collip (CA) reported an important improvement in the methodology for the determination of blood serum calcium(36).

Cyrus Hartwell Fiske (US) and Yellapragada Subbarow (US) developed a colorimetric method useful for the detection of phosphorus in organic material(37).

Evert Gorter (NL) and Francois Grendel (NL) determined that the area of the monomolecular film formed on a Langmuir trough by the membrane lipids was double the surface area of the erythrocyes from which the lipids had been extracted, suggesting that the cell membrane is bimolecular(38). This was the first evidence that cell membranes are bi-layered.

Hans Molisch (CZ), in 1925, obtained the evolution of oxygen by illuminating preparations of dried leaves(39).

William Rowan (CH-CA) used dark-eyed juncos, Junco hyemalis, to demonstrate that changes in ambient photoperiod can profoundly affect the activity of the bird’s reproductive system. He proved that the annual cycle of changing day-length is the major stimulus for bird migration and is associated with profound physiological change within birds(40-42).

Robert Kyle Burns, Jr. (US) established the adequacy of the hormonal theory of sex determination as a general mechanism for vertebrates(43-48). See Frank Rattray Lillie, 1916.

Ernest Henry Starling (GB) and Ernest Basil Verney (GB) isolated dog kidneys which they supplied with oxygenated blood at controlled flow rates, temperature, and pressure. They found they could produce regular flow rates of normal urine. From their analysis of the urine they determined that the glomeruli generate a protein-free filtrate. They artificially blocked tubular metabolic activity with hydrocyanic acid, collected ureter filtrate, and found that water, chloride, bicarbonate, and glucose are normally reabsorbed from the glomerular filtrate by the tubular cells. They also found that pituitrin (a proprietary preparation of the posterior lobe of the pituitary gland) influenced the re-absorption mechanisms for water and chloride and that without it the mammalian kidney reverted to a urine characteristic of fish and amphibian classes(49). Vasopressin would later be isolated as the active ingredient in pituitrin

Edwin B. Hart (US), Harry Steenbock (US), Conrad Arnold Elvehjem (US), and James Waddell (US) demonstrated that when rabbits were induced into a state of anemia by a milk diet, the addition of ferric salts alone was insufficient to bring about recovery. They discovered that the additional presence of copper was necessary for the animals to synthesize the pyrrol nucleus of hemoglobin(50, 51).

Louis Sigurd Fridericia (DK) and Eiler Holm (DK) demonstrated that vitamin A (retinol) is necessary for normal night vision in rats. They also found that both the retinas of A-deficient rats and of rats whose eyes had been strongly illuminated were depleted of visual purple(52).

Gaston Ramon (FR) and Pierre A. Descombey (FR) produced a tetanus vaccine from formaldehyde-treated tetanus toxin(53).

Simeon Burt Wolbach (US), Otto A. Bessey (US), and Percy R. Howe (US) concluded that vitamin A (retinol) deficiency in diets led to improper development of teeth and retardation of the growth of the skeleton and that vitamin C deficiency led to a deficiency of formation of intercellular cement substance leading to fragility of blood capillaries(54-59).

J.H.C. Ruyter (BE) was the first to call attention to the structural peculiarities of unique cells lining the afferent arteriole as it approaches the glomerulus. He suggested that by swelling these cells could occlude the lumen of the afferent arterioles and thereby regulate blood flow to the glomerular capillaries(60).

Norbert Goormaghtigh (BE) named the juxtaglomerular apparatus  and suggested that it might have an endocrine function(61).

Norbert Goormaghtigh (BE) and Keith S. Grimson (US) confirmed that the modified cells in the afferent arteriolar wall of the juxtaglomerular apparatus are endocrine in nature(62-69).

George White Pickering (US), Myron Prinzmetal (US), Juan Carlos Fasciolo (AR), Bernardo Alberto Houssay (AR), and Alberto C. Taquini (AR) rediscovered renin from the kidney as an inducer of hypertension(70, 71). See Tigerstedt, 1898. 

Eduardo Braun-Menéndez (AR), Juan Carlos Fasciolo (AR), Luis Federico Leloir (AR), Juan M. Muñoz (AR), and Irvine Heinly Page (US) determined that renin is an enzyme which acts on a substrate (hypertensinogen) in the plasma converting it to a decapeptide (angiotensin I)(72, 73).

Leonard T. Skeggs, Jr. (US), Kenneth E. Lentz (US), Joseph R. Kahn (US), Norman P. Shumway (US), and Kenneth R. Woods (US) determined that a serum enzyme (angiotensinase) converts the inactive decapeptide (angiotensin I) to the active octapeptide (angiotensin II)(74). This activity occurs primarily in the lungs.

Sir William Stanley Peart (GB) demonstrated that the juxtaglomerular apparatus cells produce renin within the kidney(75).

Edward M. East (US) and Albert J. Mangelsdorf (US), using Nicotiana tabacum as their research material, laid the foundation for understanding gametophytic self-incompatibility(76).

Thomas Hunt Morgan (US), Calvin Blackman Bridges (US) and Alfred Henry Sturtevant (US) showed that chromosome imbalance can produce intersex types in Drosophila.

They also observed that occasionally crosses produced female-biased sex ratios, a clear violation of Mendel’s first law. Daughters from the distorted brood produced an equal number of males and females, but half of their sons produced female-biased sex ratios, whatever the origin of their mates. The remaining grandsons produced normal sex ratios and were shown to have lost the trait(77).

David Policansky (US) and John Ellison (US) showed that in the Drosophila males producing biased sex ratio offspring there is a high mortality among sperm bearing the Y chromosome. They concluded that in some way a gene on the X chromosome kills sperm bearing a Y chromosome(78).

Felix Bernstein (DE) proposed that the human ABO blood group is inherited in a multiple allele pattern(79).

Hermann Joseph Muller, Jr. (US) reported on the mental traits and heredity as studied in a case of identical twins reared apart(80).

Horatio H. Newman (US), Frank N. Freeman (US), and Karl J. Holzinger (US) presented a large study of heredity and environment in the development of 100 pairs of twins(81).

Sears P. Doolittle (US) and Lewis Ralph Jones (US) demonstrated that Macrosiphum pisi Harris (pea aphid) acts as a vector for pea mosaic virus(82).

Carl Hamilton Browning (GB) defined substances that incite the formation of antibodies and react with them as antigens(83).

John Cunningham (GB), working in India, found that the organism, Borrelia carteri, occurs in two antigenic varieties in human infections of relapsing fever(84). John Cunningham (GB), J.H. Theodore (GB), and A.G.L. Fraser (GB) extended the number of antigenic varieties to nine(85).

Sir William George Savage (GB) and Philip. Bruce White (GB) laid the groundwork for antigenic analysis of the Salmonella group(86).

Fritz Kaufmann (DK) greatly extended and refined Savage and White’s work(87).

Gaston Ramon (FR) demonstrated that it was possible to augment the antitoxin response to diphtheria and tetanus by administering vaccines with pyogenic bacteria or with various additional compounds. This represents the first occasion on which immunological adjuvants were used. Ramon called them adjuvantes et stimulantes de l’immunite(88).

William C. Boeck (US) and Jaroslav Drbohlav (US) were the first to develop in vitro cultures of Endamoeba histolytica. They grew it in a diphasic egg slant medium they developed for isolation of intestinal flagellates(89).

Alfred Stock (DE) wrote about the danger of mercury vapor and concluded that mercury is a poison which can accumulate in the tissues over a considerable period of time(90).

Martha Schmidtmann (DE) by following the spread of dye in cardiac cells presented the first evidence for a direct intercellular pathway permeable to molecules(91).

Walther Vogt (DE) prepared a fate map that showed where the cells on the surface of an early gastrula would be in the later embryo. That is, he determined the destiny, or fate, of the gastrula cells(92, 93).

Nicole Le Douarin (FR), Claude Le Lièvre (FR), and Marie-Aimée Teillet (FR) used chick-quail chimeras to track the fate of neural crest cells and found that many of them migrate to form a variety of structures(94-96).

John Thomas Scopes (US) was the defendant in Tennessee v. John Thomas Scopes, the so-called monkey trial held in Dayton, Tennessee in July, 1925, in which a science teacher was arrested for teaching evolution in violation of the state laws at that time. Two-time presidential candidate William Jennings Bryan led the prosecution. Labor lawyer Clarence Darrow led the defense and goaded Bryan into declaring that humans are not mammals(97).

George Hoyt Whipple (US), Frieda Saur Robscheit-Robbins (US), C. Arthur Elden (US), Warren M. Sperry (US), and George B. Walden (US) found that liver, heart, skeletal muscle, ash of liver, ash of kidney, and ash of pineapple promotes regeneration of hemoglobin following severe anemia(98-103). These results suggested that iron in the diet is important for hemoglobin formation.

Thomas Benton Cooley (US) and Pearl Lee (US) reported on two Italian children with symptoms of severe anemia, enlarged spleens and livers, discolored skin and bone alterations(104). Thalassaemia or thalassemia

George Hoyt Whipple (US) and William Leslie Bradford (US) coined the word thalassaemia deriving it from two Greek words - Thalassa meaning the sea and haima meaning blood, literally "sea water in the blood"(105).

Gustav Riehl (DE) described a therapy for deep burn wounds(106).

Arnold Rice Rich (US) concluded that hemoglobin, derived from destroyed erythrocytes, is the sole source of bile pigment; its normal site of origin being in reticuloendothelial cells alone, especially the Kupffer cells, and the epithelial liver cells having no role in the formation, but only in the excretion of the bile pigment(107).

Percival Bailey (US) and Harvey Williams Cushing (US) postulated that medulloblastomas (Bailey coined this name) are derived from embryonic undifferentiated cells in the ependymal lining of the fourth ventricle. They described the characteristic gross and microscopic structure of this tumor; its reddish-gray color, extremely cellular nature, numerous mitotic figures, and the formation of pseudorosettes. The tendency of this tumor to spread to the leptomeninges, which proved valuable in terms of treatment considerations, was noted. They recommended radiotherapy in the post-operative care of patients with medulloblastomas(108, 109).

Erich Urbach (AT-US) presented a diagnostic procedure for demonstrating antibodies in allergics. Allergen administered by either the percutaneous, cutaneous, or intracutaneous routes causes a local reaction, which will develop into a blister when a cantharidal dressing is placed on it(110).

Walter Edward Dandy (US) reported a case in which he totally removed an acoustic neuroma (AN). He used a unilateral suboccipital approach during which, following gutting of the tumor, he gently drew the capsule away from the brainstem(111). Dandy's success was due in part to his innovation called ventriculography, which involved x-rays and injecting a gas into the brain's cerebral ventricles for visualizing the tumor. See, Dandy 1918.

Percy Sargent (GB) was the first to remove a suprarenal tumor thus reversing virilism in the patient. Gordon Morgan Holmes (GB) described the operation(112).

Henry S. Soutter (GB) performed a "digital" mitral commissurotomy (closed mitral valvulotomy)(113). 

Sir Geoffrey Jefferson (GB) performed the first successful embolectomy in Britain(114).

Konstantine Michaelovich. Bykov (RU) was the first to demonstrate experimentally that the bilateral synergic activity of the hemispheres of the brain may be dependent on the corpus collosum, and indicated the part the corpus collosum plays in the development of symmetrical reproduction of function in the hemispheres. He severed the corpus callosum in dogs and then used Ivan Pavlov's classical conditioning methods to assess the effects of his surgeries. His experiments showed the importance of the corpus callosum for interhemispheric communication(115, 116).

Howard J. Curtis (US) and Archibald Philip Bard (US) used electrical stimulation to prove the point-to-point connection of one side of the cortex to the other by way of the corpus callosum(117).

Andreas Vesalius (Flemish) gave the corpus callosum its name(118).

Howard Christian Naffziger (US) described the phenomenon of the pineal shift on skull x-rays, an important sign for brain tumor localization(119). 

Egas Moniz (PT) developed cerebral angiography, the technique of using x-rays to visualize arteries and veins thus permitting the diagnosis of several kinds of neurological disorders, such as tumors and arteriovenous malformations(120).

John Silas Lundy (US), in 1925, developed the concept of balanced anesthesia. He introduced the idea of combining more than one anesthetic technique—for example, using morphine preoperatively, a regional block to the surgical site, alongside an inhalational anesthetic of ethylene(121)(Lundy 1926).

Hermann Ludwig Blumgart (US) and Otto Christian Yens (US), in 1925, performed the most famous of all radiotracer experiments on humans, the well-known study of arm-to-arm circulation time(122). This ushered in the field of nuclear medicine.

Wolfgang Köhler (DE) showed that instead of learning simply by trial and error chimpanzees are able to solve problems by grasping the relations between means and ends, i.e., they displayed insight(123).

Merritt Lyndon Fernald (US) proved that in the northeastern United States some species of plants and animals persisted in areas that escaped glaciation during the Pleistocene(124).

Fritz Berckhemer (DE) found a fossil skull of a young female in the Sigrist gravel pit north of Stuttgart, Germany and gave it to Karl Sigrist(125, 126). This, so called, Steinheim skull can be considered a Homo erectus/Homo sapiens transitional form from the Middle Pleistocene; ca. 4000,000 B.P.

Raymond Arthur Dart (AU-ZA) found in material from a limestone quarry at Taung (place of the lion), South Africa a fossil cast of the inside of a primate skull, which fitted into another lump of stone which possibly contained a face. It took Dart about a month to remove enough stone to reveal the face and jaw of a young fossil primate, which would be nicknamed the Taung baby. Dart considered the fossil “an extinct race of apes intermediate between living anthropoids and man.” He described it and named it Australopithecus africanus (Southern ape from Africa) and dated it to between 3 and 2.3 Ma(127). It was placed in early Pleistocene or late Pliocene.

Australopithecus africanus existed between 3 and 2 million years ago. It is similar to A. afarensis, and was also bipedal, but body size was slightly greater. Brain size may also have been slightly larger, ranging between 420 and 500 cc. This is a little larger than chimp brains (despite a similar body size), but still not advanced in the areas necessary for speech. The back teeth were a little bigger than in A. afarensis. Although the teeth and jaws of A. africanus are much larger than those of humans, they are far more similar to human teeth than to those of apes. The shape of the jaw is now fully parabolic, like that of humans, and the size of the canine teeth is further reduced compared to A. afarensis(128, 129).

The American Type Culture Collection was founded. It is a repository and source of known strains of viruses, bacteria, fungi, algae, and eukaryotic cells. 

Archivos de Neurobiologia, Psichologia, Fisiologia, Histologia, Neurologia y Psiquiatria, now titled Archivos de Neurobiologia was founded.

1926

“Men fear thought as they fear nothing else on earth—more than death. Thought is subversive, and revolutionary, destructive and terrible; thought is merciless to privilege, established institutions, and comfortable habits; thought is anarchic and lawless, indifferent to authority, careless to the well-tried wisdom of the ages. Thought looks into the pit of hell and is not afraid.…Thought is great and swift and free, the light of the world, and the chief glory of man.” Bertrand Russell(130).

“Life is bottled sunshine” William Winwood Reade(131).

“The striking similarity established by Meyerhof between the changes of carbohydrates in muscle and in the yeast cell is seen to be much closer than has been believed. The remarkable phenomena accompanying alcoholic fermentation are now duplicated in the case of lactic acid production, and it may reasonably be expected that most of the fermentative decompositions of sugars will be found to be initiated in a similar manner.” Arthur Harden(132).

“The characters of the individual are referable to paired elements (genes) in the germinal matter that are held together in a definite number of linkage groups…. The members of each pair of genes separate when germ cells mature…. Each germ-cell comes to contain only one set…. These principles…enable us to handle problems of genetics in a strictly numerical basis, and allow us to predict…what will occur…. In these respects the theory [of the gene] fulfills the requirements of a scientific theory in the fullest sense.… It is difficult to resist the fascinating assumption that the gene is constant because it represents an organic chemical entity. This is the simplest assumption that one can make at present, and since this view is consistent with all that is known about the stability of the gene it seems, at least, a good working hypothesis.” Thomas Hunt Morgan(133).

Theodor Svedberg (SE) was awarded the Nobel Prize in Chemistry for his work on disperse systems.

Johannes Andreas Grib Fibiger (DK) was awarded the Nobel Prize in Physiology or Medicine for research indicating that a nematode, Spiroptera carcinoma, caused gastric cancer in rats(134). The hypothesis was later rejected but, none the less, had an important role in the development of experimental research on cancer.

Gilbert Newton Lewis (US) coined the term photon for the smallest unit of radiant energy(135)(Lewis 1926).

The Commission on Units and Measurements defined the roentgen at the Second International Congress of Radiology in Stockholm, Sweden. It was based on ionization of air.

Sir Walter Norman Haworth (GB), William Charlton (GB), Stanley Peat (GB), John Vaughan Loach (GB), John Herbert Geoffrey Plant (GB), and Charles William Long (GB) had, by 1928, evolved and confirmed, among others, the structures of maltose, cellobiose, lactose, gentiobiose, melibiose, gentianose, raffinose and the glucoside ring structure of normal sugars(136-138).

Leopold Stefan Ruzicka (HR-CH) analyzed civetone and muscone, two active compounds in natural musk perfumes and found that they consist of very large rings of atoms. He showed that civetone is composed of a 17 membered, and muscone a 15 membered carbon ring. At this time it was thought that rings with over 6 members were to unstable to exist for long(139). This paper was submitted in 1924.

Karl Lohmann (DE) and Lorand Jendrassik (HU) developed a colorimetric determination of phosphoric acid in muscle extracts(140).

Hans Karl August Simon von Euler-Chelpin (DE-SE), Christian Barthel (LU), and Karl Myrbäck (SE) found that dried yeast possess practically the same power of fermentation as fresh yeast although they retain only 1% of the reproductive power(141, 142).

Julio Caesar Tello (PE) was inspired by the discovery in 1910 of the Paracas Textile (ca. 100 B.C.E.) at the site of Cabeza Larga on the Paracas Peninsula on the South coast of Peru. In his 1925 excavations Tello found coca leaves placed in an urn which accompanied the burial of a Peruvian priest, noble, or king from the Nazca period. This is the earliest record of the use of cocoa leaves(143).

Albert Jan Kluyver (NL) and Hendrick Jean Louis Donker (NL) wrote their treatise on the unity of biochemistry in which they stressed that biochemical mechanisms can be investigated using mutant strains of microorganisms and that hydrogen transfer is a basic feature of all metabolic processes(144).

Juda Hirsch Quastel (GB-CA) and Barnet Woolf (GB) published the first reported measurement of the equilibrium constant of an enzyme-catalyzed reaction. It was on the aspartate ammonia-lyase reaction(145).

James Batcheller Sumner (US) was the first to obtain an enzyme in pure crystalline form. This was the enzyme urease, which catalyzes the hydrolysis of urea to yield carbon dioxide and ammonia. Sumner had used a 32% solution of acetone in water to precipitate much of the organic material in a jack-bean extract rich in urease activity, while leaving most of the urease activity in solution. After filtering off this precipitate and letting the filtrate stand overnight in the cold, he found that crystals of protein had formed in the filtrate. Study of these protein crystals revealed that they are pure urease enzyme endowed with a specific enzymatic activity enormously greater than that of the original jack-bean extract. It was thus proven that the enzyme urease is a protein and that a polypeptide chain is capable of acting as a catalyst in the facilitation of a chemical reaction.

Sumner’s proof was an important milestone along the road to understanding the chemical basis of cell function(146).

John Jacob Abel (US) crystallized insulin(147).

Anna L. Sommer (US) and Charles B. Lipman (US) experimentally demonstrated the essential nature of zinc, copper, and boron for plant growth(148, 149). 

Alfred Henry Sturtevant (US) found that inversion of a section of the third chromosome in Drosophila melanogaster reduces crossover frequency(150).

Lord Edgar Douglas Adrian (GB) and Yngve Zotterman (SE), using the afferent nerve of a stretch receptor in a frog muscle, showed that it is possible by amplification to record the impulses in single nerve cells to a natural stimulus (tension). They postulated the concept of adaptation of receptors to stimuli and predicted that other units of the nervous system would also exhibit adaptation(151).

Lord Edgar Douglas Adrian (GB) and Yngve Zotterman (SE), established beyond doubt that the nerve impulse is invariant, that the intensity of sensation is conveyed by the frequency of impulses and the quality by the type of nerve fiber in action(151).

Eugene Markley Landis (US), Schack August Steenberg Krogh (DK), and Abbey H. Turner (US), in an elegant series of experiments, determined that the rate of net fluid movement across the capillary wall is proportional to the difference between capillary hydrostatic pressure and the osmotic pressure of the plasma proteins, thus providing the first experimental proof of Ernest Starling’s hypothesis of fluid exchange. Landis’s constant of proportionality was the first quantitative measurement of the hydrodynamic conductance of the capillary wall (cubic microns of fluid per second per centimeter water pressure difference per square micrometer of capillary wall). These papers included the first measurements of the pressure drops along the vascular tree and localization of the separate components of the peripheral resistance to blood flow, in mammals as well as frogs(152-165). See, Starling 1896.

John Belling (GB-US) perfected the aceto-carmine staining method by adding iron. This technique was especially important because it allowed a clear differentiation between chromosomes and cytoplasm(166).

Walter Bradford Cannon (US) coined the word homeostasis: the maintenance of balance in the body’s state via chemical feedback mechanisms(167, 168). . Claude Bernard (FR) had originated this concept as milieu intérieurr in 1865. See, Claude Bernard 1865.

Gaston Ramon (FR) and Pierre A. Descombey (FR) described the flocculation reaction and observed that flocculation may occur in zones which do not correspond to the point at which the toxin and antitoxin neutralize each other(169).

Kenjiró Fujii (JP) observed the coiled structure of the chromosome for the first time. In certain stages of the cell cycle, two filaments were seen to be coiled around each other(170).

Frantisek Vejdovsky (CZ) showed that nuclear fission in an ovule is preceded by the splitting of the centrosome (which he called the periplast); he was apparently the first to observe the centriole in 1866(171).

Félix Hubert d’Herelle (CA) described the three-step process for the life history of the bacteriophage virus: (1) attachment to the susceptible bacterium, (2) multiplication in the cell, and (3) disintegration of the cell to set free the progeny virus particles and attachment of the progeny to other susceptible bacteria, if such are present. These conclusions were based on the plaque-count, and dilution methods of assay that he had invented(172).

Louis Otto Kunkel (US) demonstrated that Cicadula sexnotata ( a leafhopper) can acted as a vector of aster yellows virus(173).

Thomas Clifford Vanterpool (CA) was the first to discover that mixed infections, the simultaneous occurrence of two viruses within a host plant acting together, could produce a distinct severe disease. He showed that tomato mosaic virus and potato mosaic virus acting together caused the severe disease of tomatoes called streak or winter blight while either virus acting alone was shown to cause mild symptoms(174).

Andre Paillot (FR) discovered granulosis virus (GV) infection in an insect, Pieris brassicae (cabbage buterfly). He was the first to describe a new group of diseases, the granuloses, which are characterized by the formation of virus inclusion bodies called granules within tissues of infected insects(175). }. These are now considered Baculovirus.

Kenneth Fuller Maxcy (US) identified an "endemic" form of typhus fever (Brill’s disease) in the Southeastern United States and suggested that some parasite of the rat might be its vector(176).

Edson Sunderland Bastin (US) succeeded in culturing sulfate-reducing bacteria from groundwater samples extracted from an oil deposit that was hundreds of meters below the surface. Since this discovery over 9,000 strains of bacteria and fungi have been isolated from diverse subsurface environments(177, 178).

Heinrich Bernward Prell (DE) reported an amoebic infection of an insect, Apis mellifera Linn. (honeybee). The etiological agent he described and named Malpighamoeba mellificae attacks the Malpighian tubules causing a dysentery(179, 180)(Prell 1926a; Prell 1926b).

Walter H. Burkholder (US) observed that halo blight of beans is caused by Pseudomonas phaseolicola (181).

Frederic Parker, Jr. (US) and N. Paul Hudson (US) isolated Streptobacillus moniliformis as the causative agent of rat-bite fever (also known as erythema multiforme, erythema arthriticum epidemicum, and Haverhill fever) and demonstrated its serological relation to the disease(182).

Everitt George Dunne Murray (CA), Robert Alexander Webb (GB), and Meredith Blake Robson Swann (GB) isolated and characterized Listeria monocytogenes as the etiological agent of an epizootic among laboratory rabbits and guinea pigs which was characterized in part by monocytosis(183).

Walter F. Schlech III (US), Pierre M. Lavigne (US), Robert A. Bortolussi (US), Alexander C. Allen (US), E. Vanora Haldane (US), A. John Wort (US), Allen W. Hightower (US), Scott E. Johnson (US), Stanley H. King (US), Eric S. Nicholls (US), and Clare V. Broome (US) established that human consumption of Listeria-contaminated foodstuffs causes a disease called listeriosis(184).

Louis Edmond den Dooren de Jong (NL) demonstrated that a strain of Pseudomonas putida can proliferate on a mineral medium to which any one of some eighty compounds was added as the sole organic substance available(185).

Maurice Lemoigne (FR) originally discovered poly-beta-hydroxybutyric acid (PHB) as a major component of the cells of the bacterium Bacillus megaterium(186).

Frederick P. Delafield (US), Michael Doudoroff (US), Norberto J. Palleroni (US), Carol Jean Lusty (US) and Rebecca Contopoulos (US) later honored Lemoigne by naming Pseudomonas lemoigne, an active oxidizer of extracellular PHB, for him(187).

Frank W. Tilley (US) and Jacob M. Schaffer (US) determined that the germicidal activity of the aliphatic alcohols increases regularly from methyl through octyl alcohol for each additional methyl group in the straight chain(188, 189).

Samuel Ottmar Mast (US) proposed the tail contraction model to explain sol-gel amoeboid movement(190).

John Nathaniel Couch (US) described for the first time the existence of physiologically distinct and separate male and female strains in an oomycete (Dictyuchus )(191).

Friedrich Seidel (DE), using eggs of the dragonfly, Platycnemis pennipes, determined that embryonic development in insects is typified by the presence of a special kind of germ-band formation. Because of the distribution of cytoplasm and yolk in the egg the germ band is limited to a particular region. The ventral portion of the developing embryo is special because it is the carrier of the main system of organs. The ventral part of the embryo precedes the dorsal side in development(192-194).

Alden B. Dawson (US) carried out the first successful skeletal staining when he used alizarin red S(195).

Henry Allan Gleason (US) argued that every plant association is the unique product of the fluctuating environmental conditions of a particular time and place(196).

Sir Gavin Rylands De Beer (GB) observed that certain cartilage and bone cells are derived from the outer ectodermal layer of the embryo; calling into question the germ-layer theory(197).

Lloyd R. Watson (US) devised instrumental methods to artificially inseminate the honey bee(198-200). This instrument greatly improved genetics of the honeybee. 

Sergei S. Chetverikov (RU) concluded that populations in nature maintain within themselves the variants which arise within them by mutation. This would provide them with a supply of potential but hidden variability out of which the adaptiveness of the population to a changing environment could arise(201, 202).

William Bloom (US) worked out the early stages of the embryogenesis of human bile capillaries(203).

William Bloom (US) described the transformation of small lymphocytes into myelocytes in germinal centers(204).

George Ellett Coghill (US), in his studies of the amphibian Amblystoma punctatum , established that innervation develops in a cephalo-caudal (head-tail) direction, and that limb movements emerge from a more general pattern of trunk movement. He then theorized that behavior develops as the expansion of a "total pattern," rather than simply as the combination or coordination of reflexes, and suggested strongly that this might well be true for higher vertebrates, including man(205-208).

Serge Metalnikov (RU-FR) and V. Chorine (FR) provided an important paper in psychoneuroimmunology when they adapted Pavlov’s procedures of stimulant conditioning to activate and enhance cellular and antibody immune responses to foreign substances, particularly to otherwise lethal doses of cholera and anthrax bacteria(209).

Ralph Milton Waters (US) authored a landmark article on carbon dioxide (CO2) absorption in anesthesiology(210).

Giovanni Di Guglielmo (IT) described a syndrome of unknown origin characterized by enormous numbers of nucleated erythrocytes appearing in the bone marrow and blood (acute erythroblastosis)(211).

Erik Adolf von Willebrand (FI) described a previously unknown form of hemophilia with a prolonged bleeding time course as its most prominent sign. He named it pseudo-hemophilia(212-214). Willebrand’s disease I.

Nikolai Mikhailovich Itsenko (RU) described glucocorticoid excess syndrome in which the hypersecretion of glucocorticoids is secondary to hypersecretion of adrenocorticotrophic hormone from the pituitary. It may also be caused by a basophilic adenoma of the pituitary(215).

Harvey Williams Cushing (US) described this syndrome six years later(216). It is often called Cushing’s syndrome I but should be called Itsenko-Cushing syndrome.

Felix Mandl (AT) was the first to undertake parathyroid surgery, successfully removing a parathyroid adenoma in a patient with osteitis fibrosa cystica(217).

Sir Henry Head (GB) presented his theory of aphasia as a condition with ”a disorder of symbolic formulation and expression”(218).

César Roux (CH) performed the first surgical resection of a pheochromocytoma, in 1926(219). Later the same year, Charles Horace Mayo (US) performed the first surgical resection in the United States and described medical and surgical management of pheochromocytoma(220).

Percival Bailey (US) and Harvey Williams Cushing (US) wrote a book which formed the basis of modern day neurooncology. It completely revolutionized the understanding of neurooncology, and for first time the neurosurgical community was presented with an orderly classification of gliomas based on the tumor's natural history and clinical course. This work changed antiquated thinking by showing that the microscopic structure of a tumor is important for prognosis. It completely revamped the understanding of these tumors. In fact, the histopathological basis of brain tumors in relation to patient survival rate and outcome still influences present-day neurosurgical thought(221).

Percival Bailey (US) simplified, refined, and made the concepts presented in the 1926 book more practical(222, 223).

Harvey Williams Cushing (US) and William T. Bovie (US) conceived and introduced electrosurgery which allowed the cutting of tissue with almost no bleeding. During 1927, Cushing removed a number of brain tumors previously considered inoperable(224, 225).

Maximilian Carl-Friedrich Nitze (DE), in 1896, developed an operating cystoscope fitted with an electric cautery(226).

Francis Bertody Sumner (US) made a thorough study of coat color among the mainland and Santa Rosa Island mice, and concluded that both isolation and natural selection probably operated in the origin of species, but that environmental mechanisms could not be ruled out. Though still not conclusive, Sumner’s reading of nature’s experiments on Santa Rosa came closer than any other study at the time — field or lab — to providing empirical evidence of the mechanism of evolution. Santa Rosa is an island off the Florida panhandle(227).

Knud Haraldsen Krabbe (DK) founded the journal Acta Psychiatrica et Neurologica Scandinavica.

1927

Heinrich Otto Wieland (DE) was awarded the Nobel Prize in Chemistry for his investigations of the constitution of the bile acids and related substances.

Julius Wagner-Jauregg (AT) was awarded the Nobel Prize in Physiology or Medicine for his discovery of fever therapy for paresis (dementia paralytica). He shared the honor with the pathologist Johannes Andreas Grib Fibiger (DK), who was awarded the prize "for his discovery of the Spiroptery carcinoma."

 

Alexander Logie Du Toit (ZA) compared the geology of South America and South Africa and found them to be similar in many ways(228).

Hans Busch (DE) theorized that magnetic fields can act as lenses by focusing electron beams to a point(229). This was vital to the invention of the electron microscope.

Hermann Joseph Muller, Jr. (US) and Lewis John Stadler (US) discovered that x-rays induce mutations in animals and plants respectively. They found that the dose-frequency curve is linear(230-232).

Albert Charles Chibnall (GB) and Harold John Channon (GB) discovered the exact structure of phosphatidic acid; described for the first time in living materials(233).

Otto Fritz Meyerhof (DE-US) discovered that the first step in the fermentation of glucose (glucose to glucose-6-phosphate), catalyzed by an enzyme he called hexokinase, does not require inorganic phosphate but rather organic phosphate transferred from its terminal, or g position on adenosine triphosphate (ATP)(234).

Otto Fritz Meyerhof (DE-US) and Fritz Albert Lipmann (DE-US) discovered that sodium fluoride strongly inhibits the fermentation and phosphorylation of hexoses(234, 235).

Hans Karl August Simon von Euler-Chelpin (DE-SE), Erich Adler (), Otto Fritz Meyerhof (DE-US), Sidney P. Colowick (US), and Herman Moritz Kalckar (DK-US) partially purified hexokinase then established the reaction which it catalyzes as: glucose + adenosine triphosphate (ATP) going to glucose 6-phosphate + adenosine diphosphate (ADP)(236-238)

Hans Karl August Simon von Euler-Chelpin (DE-SE) showed for the first time a combination between an enzyme and a substrate that was traced back to a certain atomic group (carbonyl group). He was experimenting with dipeptidases(239).

Otto Paul Hermann Diels (DE), Willy Gädke (DE), and Anna Karstens (DE) used selenium to dehydrogenate cholesterol thus yielding Diels’ hydrocarbon, an aromatic hydrocarbon closely related to the skeletal structure of all steroids, of which cholesterol is one(240, 241).

Otto Paul Hermann Diels (DE) and Hermann Klare (DE), in 1934, put forth the correct structure of Diels’ hydrocarbon as 3'-methyl-1,2-cyclopentaphenanthrene. This work represents a dramatic turning point in the understanding of the chemistry of cholesterol and other steroids.

Juda Hirsch Quastel (GB-CA) and Walter Reginald Wooldridge (GB) studied dehydrogenases from Escherichia coli and further developed the concept of the active center, or site of activation, a term earlier coined by Quastel (1926). This work stressed the importance of using in vitro results to understand in vivo activities of enzymes(242). They also discovered that malonic acid is a powerful inhibitor of succinic dehydrogenase(243).

Philip Eggleton (GB) and Marion Grace Palmer Eggleton (GB) found an organic acid-labile phosphate in muscle tissue. They named it phosphagen (creatine phosphate) and established the fact that muscular contraction is accompanied by removal of phosphagen, and subsequent recovery in oxygen is characterized by a rapid restitution of the phosphagen—a phase of recovery apparently independent of the relatively slow oxidative removal of lactic acid(244).

Cyrus Hartwell Fiske (US) and Yellapragada SubbaRow (US) discovered the chemical nature of the phosphagen (creatine phosphate) present in muscles. They announced that voluntary muscle contains an unstable compound of creatine and phosphoric acid, which is hydrolyzed by stimulation, and resynthesized when the muscle is permitted to recover. They proposed a structure and pointed out some of the physiological properties of phosphocreatine (later changed to creatine phosphate)(245-247). Note: Michel-Eugène Chevreul (FR), in 1832, determined that muscle contains creatine(248).

Bernhard Zondek (DE-IL) and Selmar Aschheim (DE) isolated estrogenic hormone from the urine of pregnant women in amounts averaging 12,000 mouse units per liter(249). They found that the urine of pregnant women, when injected into female animals, causes hyperemia of the overies, growth of the follicles, and, in some species ovulation(250, 251). This became the basis of the Ascheim-Zondek and Friedman-Lapham tests for pregnancy.

Maurice H. Friedman (US) and Maxwell Lapham (US) developed the rabbit test for early diagnosis of pregnancy. Two morning samples of urine were injected into the marginal ear vein of a virginal female rabbit that had been isolated from male rabbits. The result was available 48 hours after the first injection. Of all the biologic tests, Friedman's was the most accurate. This procedure tested for the presence of human chorionic gonadotropin (hCG; a hormone released from the implantation site of a blastocyst that prevents menstruation) in the urine of women. If hCG was present in the urine, the rabbit's ovaries would form corpora lutea (ovarian endocrine structures formed following ovulation) within 48 hours(252, 253).

Julius Moses Rogoff (US) and George Neil Stewart (US) demonstrated that a chemical extract of the adrenal glands of dogs greatly prolongs the lifespan of adrenalectomized dogs. They found that the active ingredient was not epinephrine(adrenaline)(254). They experienced some success in using adrenal extract to treat human patients suffering from Addison’s disease(255). Charles-Édouard Brown-Séquard (FR) had proved that removal of both suprarenal (adrenal) glands invariably proved fatal. See, Brown-Séquard, 1856.

Walter Bradford Cannon (US), Andries Querido (NL), Sydney W. Britton (US), and Elizabeth M. Bright (US) demonstrated that the adrenal glands produce more adrenaline (epinephrine) in animals exposed to the cold. The adrenaline (epinephrine) causes an increase in heat production(256). 

Sir Joseph Barcroft (GB) and J.G. Stephens (GB) demonstrated the spleen's role as a blood reservoir in the dog(257).

Thomas Milton Rivers (US) clearly distinguished between bacteria and viruses, thereby, giving rise to the field of virology(258).

Nicolaas Louis Söhngen (NL) was probably the first to report bacteria which lyse other bacteria; in some cases with a high degree of parasite-host specificity. Bacterium bacteriovorus which lyses Bacillus danicus he found to grow only in the presence of its host(259).

Sir Ronald Aylmer Fisher (GB-AU) explained the evolution of Batesian mimicry by a series of small evolutionary steps. He proposed that the phenotypic expression of genes could be modified by the action of other genes. Rare imperfect mimetic forms when they appeared in a population would vary due to the action of modifier genes. Selection would favor those modifier genes that produced an increase in the accuracy of the mimicry(260).

Sir Cyril Astley Clarke (GB), Philip Macdonald Sheppard (GB), and Lawrence M. Cook (GB) provided experimental evidence to support Fisher’s explanation(261-267). 

John Charles Walker (US) pioneered research on genetic resistance in yellows disease of cabbage. He showed the scientific community that disease control through genetic resistance could be an effective and relatively inexpensive approach to solving plant disease problems(268, 269).

Bernard Ogilvie Dodge (US) worked out the life cycle of the pink bread mold, Neorospora crassa, an ascomycete(270). Cornelius Lott Shear (US) and Bernard Ogilvie Dodge (US) named the fungal genus Neurospora(271).

Emil Bozler (DE-US) demonstrated that the nerve net of cnidarians is made up of separate cells connected by synaptic junctions. He also studied electrical aspects of muscle contraction and the role of calcium and magnesium in contraction and relaxation(272).

Nadine Dobrovolskaia-Zavadskaia (FR) and Nicolas Kobozieff (BE) identified t-haplotypes in mice because they contain the gene tct (t-complex tail interaction factor) that interacts with a spontaneous dominant mutation Brachyury (T). Brachyury produces short tails in T/+ mice, but interacts with tct to produce a tailless phenotype in T/t mice(273, 274).

James R. Archer (GB), Steven J. Self (GB), and Bryan G. Winchester (GB) explained the t-complex in mice as a genetic entity which alters meiosis is such a way that its transmission into gametes is favored(275). The t-complex is located on the proximal third of chromosome 17 in the house mouse. Naturally occurring variant forms of the t-complex, known as complete t-haplotypes, are found in wild mouse populations. The t-haplotypes contain at least four nonoverlapping inversions that suppress recombination with the wild-type chromosome, and lock into strong linkage disequilibrium.

Barbara C. Turner (US) and David D. Perkins (US), working with Neurospora, discovered spore killer, a chromosomal factor that kills meiotic products in which it is not contained(276).

Laurence Sandler (US) and Kent G. Golic (US) discovered segregation distorter (Sd), a meiotic drive system which operates in males of Drosophila melanogaster. Males heterozygous for Sd, a dominant neomorphic (gain-of-function) mutation on chromosome 2, can transmit their progeny in greater frequencies than expected on a Mendelian basis(277).  

Evgenii Nikanorovich Pavlovsky (RU) outlined his theory of landscape epidemiology and initiated modern concepts of parasite epidemiology(278).

Jesse Amos (GB), Ronald George Hatton (GB), R.C. Knight (GB), and Arthur Morel Massee (GB) suggested that eriophyid mites (gall mites) could have some connection with plant virus transmission(279).

Arthur M. Massee (GB) was the first to demonstrate this to be the case(280).

Erwin Stresemann (DE) wrote an important volume on bird biology as part of Kükenthal and Krumback’s Handbuch der Zoologie. It contains thorough discussions of avian physiology, anatomy, and other phases of avian biology(281).

Theophilus Shickel Painter (US) studied the Japanese Waltzer mouse and concluded that its phenotype results from a chromosomal deletion(282) This was the first cytological identification of a deletion producing a specific genetic effect and the first case in mammals of locating a definite gene on a definite chromosome.

Sir Thomas Lewis (GB) originally described the wheal and flare reaction. He described how he believed histamine to be crucially involved in the central area of the weal, where it then stimulates an axon reflex or antidromic reflex which transmits the signal to more distant parts, i.e., the flare(283).

Karl Landsteiner (AT-US) and Philip Levine (RU-US) characterized the M, N, P and Jay blood antigens(284-287).

Matthew Walzer (US) and Sampson J. Wilson (US) demonstrated that the ingestion of foods would allow food antigens to penetrate the gastrointestinal barrier, which are then transported in the circulation to IgE-bearing mast cells in the skin(288, 289). The IgE class of immunoglobulin was not discovered until 1967.

David Marine (US) and Emil J. Baumann (US) found that administration of Ringer’s solution and isotonic solutions of sodium chloride and sodium acetate increased the life span of suprarenalectomized cats about three fold(290).

Soma Weiss (HU-US) developed the first practical method of measuring circulation in time(291).

Wallace Osgood Fenn (US) was the first to measure the quantity of oxygen required by a nerve to conduct an impulse(292).

Otto Heinrich Warburg (DE), Harry Goldblatt (US), Gladys Cameron (US), Fritz Kubowitz (DE), Karlfried Gawehn (DE), August-Wilhelm Geissler (DE), Detlev Kayser (DE) and Siegfried Lorenz (DE) provided the very unexpected and fundamental fact, that tissue culture is carcinogenic and that a too low oxygen pressure is the intrinsic cause. Anaerobiosis of cancer cells was an established fact by 1960 when methods were developed to measure the oxygen pressure inside of tumors in the living body(293-297).

Mark W. Woods (US), Katherine K. Sandford (US), Dean Burk (US), and Wilton R. Earle (US) found that cancer cells, descended in vitro from one single normal cell, were in vivo the more malignant, the higher their fermentation rate(298).

Dean Burk (US), Mark W. Woods (US), and Jehu Hunter (US) found that when different carcinogens were used to induce in vivo hepatomas there was a direct correlation between malignancy and fermentation rate(299). 

Thomas Benton Cooley (US), E.R. Witwer (US), and O. Pearl Lee (US) described the disease which later became known as Cooley erythroblastic anemia(300).

Guido Fanconi (CH) reported a family in which three brothers had died in childhood from a condition which resembled pernicious anemia. He observed that these children had slight stature, hypogonadism and skin pigmentation. In subsequent reports defects of the thumb and radius were recognized as additional but variable syndromic components(301). This became known as Fanconi’s anemia.

Leo Loeb (US) and Sewall Wright (US) demonstrated genetics of transplant specificity in mammals(302).

Philip Edward Smith (US) perfected the surgical production of hypophysectomized rats and described the symptoms resulting as inhibition of growth in the young animal, weight loss, atrophy of the genital system with loss of libido sexualis, cessation of the female sex cycle, atrophy of the thyroid, parathyroids and suprarenal (adrenal) cortex, lowered resistance to injury, loss of appetite, weakness, and flabbiness. Smith found that he could reverse the atrophied functions in these animals only by injection of fresh hypophyseal tissue from adults. These animals have been widely used in studies of the endocrine system(303).

Manfred Joshua Sakel (PL-AT-US), in 1927, introduced hypoglycemic coma produced by muscular injections of insulin as a treatment for psychotic disorders (e.g. schizophrenia) and drug addiction(304, 305).

Ladislaus Joseph von Meduna (HU) started seizure therapy by intravenous injection of cardiazol (in depressive states), a therapy that was abandoned in 1938(306, 307).

Ugo Cerletti (IT) and Lucio Bini (IT) introduced electric convulsive therapy (E.C.T.) for severe mental states. This treatment was first used in schizophrenia, but severe depressive states very soon proved to be the main indication(308, 309).

Jean Delay (FR) and Pierre Deniker (FR) demonstrated success with the first neuroleptic—coined by Delay— drug, the phenothiazine derivative chlorpromazine (thorazine). Chlorpromazine has a remarkable effect on patients with schizophrenia. In particular highly agitated, anxious, and psychotic patients. It softens the effects of hallucinations and voices. Patients became quiet and much more manageable. It has effects on all types of patients(310).

Fritz Eichholtz (DE) and Otto Butzengeiger (DE) carried out the first experimental use of avertin (2,2,2-tribromoethanol) as an anesthetic in animals(311).

Otto Butzengeiger (DE) introduced avertin (2,2,2-tribromoethanol) as a rectal anesthetic in the clinic(312).

Major Greenwood (GB) and Janet Elizabeth Lane-Claypon (GB) developed a key type of epidemiological investigation, the so-called "case-control study". They tracked down 500 women with a history of breast cancer- the “cases” - and compared them with 500 women who were free of the disease but otherwise broadly similar, known as “controls”. The detailed survey that emerged constituted, as far as is know, the first published epidemiological questionnaire. This yielded results that enabled them to identify many of the risk factors for breast cancer that are still considered valid today. Their conclusions (or their data reworked by later researchers) agreed with those of modern reviewers: breast cancer was associated with age at menopause, artificial menopause, age at first pregnancy (age at marriage used as a proxy), number of children, and lactation.

They published what is now considered the first “end results” study. It followed a large sample of women with pathologically confirmed breast cancer for up to 10 years after their surgery. The study confirmed that women who were surgically treated at an early stage of the disease had a much better chance of surviving three, five, or 10 years longer than those operated on at any later stage. They showed that breast cancer risk increased for childless women, women who married later than average, and women who did not breast feed. The overall breast cancer risk decreased according to the number of children. For all cases, rapid treatment held the key to survival among women with breast cancer. In reviewing the family histories of their cases, they anticipated the role that genes might play in the development of breast cancer. “There appear to be some families,” they wrote, “in which for reasons not certain at present, cancer plays havoc with the members, and there is (some) slight evidence in some instances that it attacks the same organs”(313). 

Charles Sutherland Elton (GB) redefined the species niche by emphasizing its functional role in the community: the niche is “the status of an animal in its community.” His concept idealized what the species does rather than where it lives—the functional niche concept(314).

Erik Anderson Stensiö (SE) reconstructed a fossil Cephalaspis (an ostracoderm) and suggested its status as a vertebrate prototype replacing amphioxus(315). It is generally believed that living Agnatha (hagfishes and lampreys) and the ostracoderms are descended from a common ancestor.

Arthur Keith (GB) discovered a human upper jaw in Southern England and initially diagnosed it as Upper Palaeolithic modern human(316).

Tom Higham (GB), Tim Compton (GB), Chris Stringer (GB), Roger Jacobi (GB), Beth Shapiro (US), Erik Trinkaus (US), Barry Chandler (GB), Flora Gröning (GB), Chris Collins (GB), Simon Hillison (UK), Paul O'Higgins (GB), Charles FitzGerald (UK), and Michael Fagan (UK) tested the jaw Keith found by a Bayesian analysis of new ultrafiltered bone collagen dates in an ordered stratigraphic sequence at the site dated to 44.2–41.5 kyr cal BP. This makes it older than any other equivalently dated modern human specimen and directly contemporary with the latest European Neanderthals.

Arturo Palma di Cesnola (IT), in 1964, found two deciduous molars in the so-called Uluzzian archaeological layers unearthed from the Grotta del Cavallo (Southern Italy). They were classified as Neanderthal and dated to 45,000 years ago. These fossils are the oldest known human remains on the continent. ref

Stefano Benazzi (AT), Katerina Douka (GB), Cinzia Fornai (AT), Catherine C. Bauer (DE), Ottmar Kullmer (DE), Jiří Svoboda (CZ), Ildikó Pap (HU), Francesco Mallegni (IT), Priscilla Bayle (FR), Michael Coquerelle (ES), Silvana Condemi (FR), Annamaria Ronchitelli (IT), Katerina Harvati (DE) and Gerhard W. Weber (AT) reanalysed the deciduous molars from the Grotta del Cavallo (Southern Italy), associated with the Uluzzian and originally classified as Neanderthal. Their new chronometric data for the Uluzzian layers of Grotta del Cavallo obtained from associated shell beads and included within a Bayesian age model show that the teeth must date to ~45,000–43,000 calendar years before present. The Cavallo human remains are therefore the oldest known European anatomically modern humans, confirming a rapid dispersal of modern humans across the continent before the Aurignacian and the disappearance of Neanderthals(317).

1928

“Error is modern while truth is ancient.” Ramón y Cajal(318).

"Only when some important function... lends itself to ready observation or quantitative measurement are the conditions suitable for making progress..." Edwin B. Hart, et al.,(51).

“As I view my contribution to the writing of our time, it seems to me to consist of a double affirmative, saying first that an awareness and experience of Nature is necessary to Man if he is to have his humanity, and saying in the second place that that same awareness must have something of a religious quality, the Italian pieta, if you will.

Nature is a part of our humanity, and without some awareness and experience of that divine mystery man ceases to be man. When the Pleiades and the wind in the grass are no longer a part of the human spirit, a part of the very flesh and bone, man becomes, as it were, a kind of cosmic outlaw, having neither the completeness and the integrity of the animal nor the birthright of a true humanity.” Henry Beston(319).

Adolf Otto Rheinhold Windaus (DE) was awarded the Nobel Prize in Chemistry for research into the constitution of the sterols and their connection with the vitamins.

Charles Jules Henri Nicolle (FR) was awarded the Nobel Prize in Physiology or Medicine for his work on typhus.

Kurt Heinrich Meyer (DE) and Herman Francis Mark (DE) proved the existence of polymeric chain molecules by examining the crystalline structure of polymers with x-rays(320-322).

Otto Fritz Meyerhof (DE-US) and Karl Lohmann (DE) isolated argininephosphoric acid from arthropod (crustacean) muscle. It was found to be the invertebrate analogue of the vertebrate phosphagen (creatine phosphate)(323-325).

Karl Lohmann (DE) and Hermann Lehmann (DE) demonstrated that phosphagen (creatine phosphate) reacts with ADP in minced crustacean muscle(326, 327). This provided, for the first time, a mechanism for utilization of phosphate energy. This became known as the Lohmann reaction.

Marjory Stephenson (GB) obtained the first cell-free preparation of non-NAD dependent lactic dehydrogenase which oxidized lactate to pyruvate in the presence of methylene blue(328). 

Bengt Andersson (SE) provided evidence for identifying the coenzyme necessary for reducing pyruvate with NAD(329, 330). 

Donald Dexter Van Slyke (US) and James A. Hawkins (US) presented a gasometric method for determination of reducing sugars, and its application to analysis of blood and urine(331).

Robert Robison (GB) and Walter Thomas James Morgan (GB) isolated crystalline trehalose from trehalosemonophosphate(332).

F. Gottwalt Fischer (DE) and Kurt Löwenberg (DE) determined the structure of phytol (the major esterifying alcohol of chlorophyll at position 7 of the macrocycle )(333).

F. Gottwalt Fischer (DE) and Kurt Löwenberg (DE) synthesized phytol from pseudoionone(334).

Bertil Hanstöm (SE) discovered that the X-organ, located in the eyestalk of crustaceans, secretes neurohormones(335-337). Neurosecretory cells in the X-organ (part of the brain) produce a molt-inhibiting hormone that is stored in the sinus gland of the eyestalk, while a molting hormone is produced in the Y-organ. Interactions of these two hormones control the molting process.

Bernhard Zondek (DE-IL) and Selmar Aschheim (DE) isolated from the anterior pituitary gland a gonadotropic hormone they named prolan (it was luteinizing hormone-LH-and/or follicle stimulating hormone-FSH)(338). Prolan is a term no longer in use.

Fritz Albert Lipmann (DE-US), Vladimir Aleksandrovich Engelhardt (RU), and A.P. Barkash (RU) presented evidence for the metabolic pathway from glucose-6-phosphate to triose phosphate by way of ribose-5-phosphate. They called it the hexose monophosphate shunt(235, 339). 

Hans Sachs (DE) and Ernst Witebsky (DE-US) developed a precipitation reaction for serological diagnostics of syphilis(340).

Oliver Kamm (US), Thomas B. Aldrich (US), Irvine W. Grote (US), Louis W. Rowe (US), and Edwin P. Bugbee (US) reported obtaining posterior lobe pituitary preparations with high oxytocic activity and low pressor activity and, conversely, preparations with high pressor activity and low oxytocic activity(341). These would later be associated with oxytocin and vasopressin.

Frederick Griffith (GB) discovered the transforming factor while working with Diplococcus pneumoniae (Streptococcus pneumoniae). He demonstrated that this factor, which he isolated from smooth colonies, is a chemical that is present in the extract of dead smooth colonies, but missing from live rough colonies. When mixed with living rough colonies the transforming factor converted many of them to living smooth colonies(342).

James Lionel Alloway (US), working in the laboratory of Oswald Theodore Avery (CA-US), broke open cells of the smooth form of pneumococcus and collected the cell contents which were passed through a filter that would remove all wall material. When this extract was added to a culture of growing rough cells some of them were transformed into smooth cells.When the transforming extract was treated with alcohol a thick syrupy precipitate formed(343).

Oswald Theodore Avery (CA-US) would later show that the transforming factor is DNA. See Sanfelice, 1893 and Avery, 1944.

Andrew C. Ivy (US) and Eric Oldberg (US) discovered and named the hormone cholecystokinin (CCK) which controls gall bladder function(344).

Viktor Mutt (EE) and J. Erik Jorpes (SE) determined the structure of cholecystokinin (CCK)(345).

Julian Walawski (PL) and Jerzy Kaulbersz (PL) discovered enterogastrons produced in the large intestine which inhibit the stomach secretion(346, 347). 

Elisabeth Baroness af Ugglas von Euler-Chelpin (DE), Hans Karl August Simon von Euler-Chelpin (DE-SE), Harry Hellström (SE), and Thomas Moore (GB) offered proof that carotene is provitamin A(348-352).

Albert Imre Szent-Györgyi (HU-US) using the adrenal cortex, cabbage, and orange as raw material isolated and crystallized a factor which he knew was in some way involved in the mechanism of biological oxidation. He named this acidic carbohydrate hexuronic acid(353).

Charles Glen King (US) and William A. Waugh (US) succeeded in obtaining Szent-Györgyi’s hexuronic acid in crystalline form then equated it with vitamin C(354, 355). Today it is known as ascorbic acid (ascorbic meaning, no scurvy) or vitamin C.

Szent-Györgyi (HU-US) and Walter Norman Haworth (GB) suggested that vitamin C be renamed ascorbic acid(356). 

Walter Norman Haworth (GB), Luszló von Vargha (HU), Sir Ernest G. Cox (GB), Edmund Langley Hirst (GB), and Reginald John William Reynolds (GB) would contribute to the determination of its chemical structure(357-359).

Walter Norman Haworth (GB) and Edmund Langley Hirst (GB) synthesized ascorbic acid(357).

Cornelis Bernardus Kees van Niel (NL-US), working with propionic acid bacteria, provided the first quantitative picture of the products derived by these bacteria from lactate, glycerol, glucose, and starch. His taxonomic treatment determined the veracity of the genus Propionibacterium. During these studies he identified diacetyl as the compound responsible for the characteristic aroma of high quality butter(360).

Pierre Stricker (FR) and Fritz Grüeter (FR) induced mammary gland development and the secretion of milk by injecting anterior pituitary extract into castrated virgin rabbits(361, 362). This strongly suggested the presence of a lactation hormone (prolactin).

Herbert McLean Evans (US) and Miriam E. Simpson (US) found that extracts from the anterior pituitary cause hypertrophy of the mammary glands in virgin rats(363).

Oscar Riddle (US) and Pela Fay Braucher (US) showed that extracts of the anterior lobe of the pituitary gland could cause the enlargement and functioning of the crop-glands in pigeons(364).

Oscar Riddle (US), Robert Wesley Bates (US), and Simon William Dykshorn (US) reported their discovery of a hormone produced in the anterior pituitary gland which stimulates the crop-gland in pigeons and is lactogenic in guinea pigs; they named it prolactin(365, 366). 

Henry George Friesen (CA), Harvey J. Guyda (CA), and Jules Hardy (CA) discovered prolactin in humans(367, 368).

Eva Nagy (HU-CA) and Istvan Berczi (HU-CA) reported that regulation of the immune response by the neuroendocrine hormone prolactin (PRL) occurs via its interaction with the prolactin receptor. Interference with this ligand-receptor interaction inhibits both in vitro and in vivo immune responses(369).

Charles V. Clevenger (US), Amy L. Sillman (US), Michael B. Prystowsky (US), Yi-Ping Rao (US), Donna J. Buckley (US), Mark D. Olson (US) and Arthur R. Buckley (US) showed that prolactin is able to physically enter the cell, travel straight to the cell’s DNA, and directly activate the process that turns on genes and triggers the growth of breast cancer cells. It does this by binding to a protein called cyclophilin B, or CYPB for short(370, 371).

Charles V. Clevenger (US), Tracey L. Plank (US), Susan E. Hankinson (US), Walter C. Willett (US), Dominique S. Michaud (US), JoAnn E. Manson (US), Graham A. Colditz (US), Christopher Langcope (US), Bernard Rosner (US), Frank E. Speizer (US), Marcela V. Maus (US), and Sean C. Reilly (US) presented evidence that the somatolactogenic hormone prolactin, a naturally occurring peptide hormone needed for milk production following pregnancy, stimulates the movement, or motility of breast cancer cells causing the cells to essentially pick up and move, and actually trigger invasive potential of these cells(372-374).

Georg von Békésy (HU-US) elucidated all the physical events at every strategically important point in the transmission system of the ear by recording events in this fragile biological miniature system, microdissection, advanced teletechniques for stimulation and recording, and high magnification stroboscopic microscopy. He elucidated the vibration patterns of the eardrum and the interplay of the ossicle movements, provided experimental and clinical data confirming Helmholtz’s assumption that the frequency of the sound waves determines the location along the basilar membrane at which stimulation occurs. He found that movements of the stirrup footplate evokes a wave complex in the basilar membrane, which travels from the stiffer basal part to the more flexible part in the apex of the cochlea. The crest of the largest wave first increases, thereafter quickly decreases. The position of the maximal amplitude was found to be dependent on the frequency of the stimulating sound waves in such a way that the highest crest of the travelling wave appears near the apex of the cochlea at low-frequency tones and near its base at high frequencies(375-379).

Donald Dexter Van Slyke (US) and Julius Sendroy, Jr. (US) reported studies of gas and electrolyte equilibria in blood in which they present line charts for graphic calculations by the Henderson-Hasselbalch equation, and for calculating plasma carbon dioxide content from whole blood content(380). Van Slyke continued to improve this method through eleven more papers.

Thomas Hunt Morgan (US) presented the theory of the gene when he said, “The theory states that the characters of the individual are referable to paired elements (genes) in the germinal material that are held together in a definite number of linkage groups; it states that the members of each pair of genes separate when the germ-cells mature in accordance with Johann Gregor Mendel’s first law, and in consequence each germ-cell comes to contain one set only; it states that the members belonging to different linkage groups assort independently in accordance with Johann Gregor Mendel’s second law; it states that an orderly interchange—crossing over— also takes place, at times, between elements in corresponding linkage groups; and it states that the frequency of crossing over furnishes evidence of the linear order of the elements in each linkage group and of the relative position of the elements with respect to each other”(381).

Hermann Joseph Muller, Jr. (US) and Theophilus Shickel Painter (US) using Drosophila, carried out parallel investigations in which phenotypic variations brought about by x-rays were related to physical changes in the chromosomes, e.g., deletions and translocations(382, 383).

Johann Heinrich Emil Heitz (DE) coined the terms euchromatin and heterochromatin(384).

Eggert Hugo Heiberg Møller (US), John F. McIntosh (US), and Donald Dexter Van Slyke (US) determined that a constant volume of blood is being cleared of urea in each minutes time course. This came to be referred to as standard blood urea clearances(385).

Adrian Stokes (GB), Johannes H. Bauer (US), N. Paul Hudson (US), Constant Mathis (FR), Andrew Watson Sellards (US), and Jean Laigret (FR), working in West Africa, proved that yellow fever is caused by a virus and transferable to monkeys(386-388). Stokes died of a yellow fever infection.

Renjiro Kaneko (JP) and Yoshio Aoki (JP) determined that the etiological agent of Japanese B encephalitis was probably a virus(389).

M. Hayashi (JP) transmitted Japanese encephalitis— one of the leading causes of acute encephalopathy— from an infected human to monkeys by way of an intracerebral injection to prove the viral etiology of the disease(390).

Itsuma Takaki (JP), Tenji Taniguchi (JP), M. Hosokawa (JP), and S. Kuga (JP) isolated the viral etiological agent of Japanese B encephalitis(391, 392).

Arthur T. Henrici (US) reported that the average size of bacterial cells may vary considerably from one growth phase to another during a growth cycle(393).

Clifford Dobell (US) was the first to describe encystment of a parasitic amoebic form, Entamoeba histolytica(394). 

Kenneth L. Burdon (US) described Bacteroides melaninogenicus in the stools of patients suffering from chronic amebic dysentery, and in puerperal sepsis. This bacterium is often associated with the mouth, tonsils, infected abdominal wounds, and focal infections of the kidneys(395).

Henry E. Meleney (US) presented clear evidence of the development of six immunologically distinct strains of Borrelia recurrentis (396).

Karl Johannes (Hans) Kniep (DE) and Arthur Henry Reginald Buller (CA) had previously presented the broad picture of the genetic control system and the developmental sequence from spore to spore in the basidiomycetes(397, 398). Buller was also a poet. One of his most recognized works is this limerick, first published in the Dec. 19, 1923 issue of Punch:

There was a young lady named Bright

Whose speed was far faster than light;

She set out one day,

In a relative way

And returned on the previous night.

John Robert Raper (US), Carlene Allen Raper (US), Chiu-Sheng Wang (US), John H. Perkins (US), Thomas J. Leonard (US), Yigal Koltin (IL), Giora Simchen (IL), Philip J. Snider (US), Dana H. Boyd (US), Albert H. Ellingboe (US), Stanley Dick (US), Yair Parag (IL), Margery G. Baxter (US), Gladys S. Krongelb (US), James P. San Antonio (US), Philip G. Miles (US), and Richard B. Middleton (US) thoroughly elucidated the genetic mechanisms underlying the sexuality of the small wood-rotting basidiomycete, Schizophyllum commune(399-425).

Émile Eugène Aldric Topsent (FR), spongiologist, described the Atlantic and Mediterranean collections of Prince Albert of Monaco in three monumental volumes and erected many genera and families. His work is the basis for the current classification system of the Porifera(426). Topsent is commemorated by Acheliderma topsenti Burton, 1932, Axinyssa topsenti Lendenfeld, 1897; Chondropsis topsenti Dendy, 1895; Corticium topsenti Pouliquen, 1972; Cryptotethya topsenti Thiele,1900, Desmacella topsenti Burton, 1930; Desmanthus topsenti Hentschel,1912; Dragmatyle topsenti Burton, 1954; Dysideopsis topsenti Hentschel, 1912; Echinodictyum topsenti De Laubenfels, 1936; Erylus topsenti Lendenfeld, 1903; Eurypon topsenti Pulitzer-Finali, 1983; Grayella topsenti Babic, 1922; Haddonella topsenti I. Sollas, 1903; Halichondria topsenti De Laubenfels, 1936; Hymenotrocha topsenti Burton, 1930; Hymerhabdia topsenti Lévi, 1952; Jaspis topsenti Thiele, 1900; Leucandra topsenti Breitfuss, 1929; Raspailia topsenti Dendy, 1924; Reniera topsenti Thiele, 1905; Rhabderemia topsenti Van Soest & Hooper, 1993; Rhabdoploca topsenti Hentschel, 1912; Spongosorites topsenti Dendy, 1905; Stelletta topsenti Thiele,1903; Suberella topsenti Burton, 1929; Tedania topsenti De Laubenfels, 1930; Topsentia Berg, 1899; and Tylaspis topsenti Lévi & Lévi, 1983.

Remington Kellogg (US) wrote The History of Whales—Their Adaptation to Life in the Water; still one of the best summaries of the subject(427).

John Walton (GB) presented evidence of mosses and liverworts from the Carboniferous deposits in England(428).

Thomas M. Harris (GB) presented excellent evidence of mosses in the Triassic of England(429, 430).

Royal N. Chapman (US) used flour beetles (Tribolium confusum Duval) to devise a experimental single-species model for studying the growth and regulation of closed, single-species systems(431).

Jerzy Neyman (US), Thomas Park (US), and Elizabeth L. Scott (US) later christened it the Tribolium model(432).

Herbert Friedmann (US) described social parasitism among birds and wrote, The Cowbirds: A Study in the Biology of Social Parasitism, a definitive treatment of brood parasitism(433, 434). This type of behavior is seen among the cuckoos, cowbirds, honey guides, and weaver birds.

Archibald Philip Bard (US) discovered that the emotion we call rage depends on neurons in the caudal half of the hypothalamus(435-438).

Edgar Allen (US), Jean Paul Pratt (US), Q.U. Newell (US), and Leland J. Bland (US) used dogs to develop surgical methods of recovering embryos for application in humans(439).

John F. Fulton (US) reported on a patient presenting with an arteriovenous malformation of the occipital cortex. Surgical removal of the malformation was attempted but was unsuccessful, leaving the patient with a bony defect over the primary visual cortex. Fulton elicited a history of a cranial sound audible to the patient whenever he engaged in a visual task. Based on this history Fulton pursued a detailed investigation of the behavior of the sound that he could auscultate and record over the occipital cortex. Remarkably consistent changes in the character of the sound could be appreciated depending upon the visual activities of the patient. Although opening the eyes produced only modest increases in the intensity of the sound, reading produced striking increases(440). Cortical blood flow is thus related to the complexity of the visual task and the attention of the subject to that task.

Niels A. Lassen (DK), Kai Hoedt-Rasmussen (DK), S.C. Sorensen (SE), Erik Skinhøj (SE), Sten Cronquist (SE), Bengt Bodforss (SE), David H. Ingvar (SE) and Jarl Risberg (SE) were the first to directly demonstrate in normal human subjects that cerebral blood flow changes regionally during changes in brain functional activity(441-443).

Hans Zinsser (US) and H. Yu (US) were among the first to suggest that diseases such as rheumatic fever and glomerulonephritis result from hypersensitivity to toxins produced by certain strains of streptococci(444, 445).

George Nicholas Papanicolaou (Greek-US) and Herbert Frederick Traut (US) developed the cervical smear (Pap smear for Papanicolaou) test for the detection of uterine cancer. It is based on the cytological examination of cells exfoliated from the uterus(446-448).

Bernhard Zondek (DE-IL) and Selmar Aschheim (DE) reported their pregnancy test (Aschheim-Zondek pregnancy test) for humans, “Our test is carried out with morning urine…. The urine is injected subcutaneously into the infantile [female mice]…. Only the ovarian findings are of significance for the pregnancy reaction [enlargement with follicular maturation]…. We have examined 78 cases of pregnancy. In 76 cases the reaction was definitely positive…. In [the] 198 control cases the reaction was positive twice…. The reaction thus has a precision that one cannot hope to surpass with a biologic method”(449-451).

Cecil James Watson (US) described the first case of disseminated histoplasmosis reported in the continental United States(452).

Owen Harding Wangensteen (US) and George W. Waldron (US) did studies in intestinal obstruction which led to the development of the Wangensteen suction technique to relieve increased internal viscus pressure in the stomach and intestine resulting from excess gastric and intestinal secretions in an atonic intestine(453).

Walter Edward Dandy (US) devised an operation to relieve Ménière’s disease (inflammation and congestion of the semicircular canals)(454, 455).

Harvey Williams Cushing (US) and Percival Bailey (US) provided the first extensive classification and description of angiomatous malformations and hemangioblastomas(456).

Percival Bailey (US) and Harvey Williams Cushing (US) were the first to describe the condition known as fugitive acromegaly, in which patients may exhibit physical stigmata of acromegaly without biochemical evidence of the disease(457).

Howard Christian Naffziger (US) devised an operation to relieve severe malignant exophthalmos using orbital decompression(458).

Jörgen H. Vogt (NO) and Arne Torkildsen (NO) named this Naffziger’s operation(459).

Andrew Ellicott Douglass (US) discovered that annual growth of tree rings could be used to construct a window on the weather of the past. Trees add a layer of wood to their trunks every year - a wide ring during wet years and a thin one during dry years. By matching ring patterns in living trees to the patterns in old timbers, the record could be extended further back into history, i.e., dendrochronology(460). This method is most accurate from the present to 12,000 years ago.

Adolf Remane (DE), working in the Kiel Bight (Baltic Sea) in 1928, discovered the new phylum Gnathostomulida (jaw worms), a small (0.5 mm long) marine worm-like form with worldwide distribution(461).

Peter Ax (DE) originally described Gnathostomulida as an order of the Platyhelminthes(462, 463).

John Burdon Sanderson Haldane (GB-IN), in 1928, wrote the essay, On Being the Right Size, which Jane Jacobs and others have since referred to as Haldane's principle. This is that sheer size very often defines what bodily equipment an animal must have: “Insects, being so small, do not have oxygen-carrying bloodstreams. What little oxygen their cells require can be absorbed by simple diffusion of air through their bodies. But being larger means an animal must take on complicated oxygen pumping and distributing systems to reach all the cells”(464).

1929

“Everything is determined… by forces over which we have no control. It is determined for the insect as well as for the star. Human beings, vegetables, or cosmic dust—we all dance to a mysterious tune, intoned in the distance by an invisible piper.” Albert Einstein(465, 466).

Sir Arthur Harden (GB) and Hans Karl August Simon von Euler-Chelpin (DE-SE) were awarded the Nobel Prize in Chemistry for their investigations on the fermentation of sugar and fermentative enzymes.

Christiaan Eijkman (NL) for his discovery of the antineuritic vitamin (thiamine, vitamin B1) and Sir Frederick Gowland Hopkins (GB) for his discovery of the growth-stimulating vitamins shared the Nobel prize in physiology and medicine.

Dame Kathleen Yardley Lonsdale (GB) was the first to use x-ray diffraction to solve the structure of an organic molecule, she showed that hexamethylbenzene is planar and hexagonal - and gave its precise dimensions(467).

Sergei Yakovievich. Sokolov (RU) suggested the concept of the pulse-echo ultrasonic metal flaw detector(468). This instrument was the precursor of subsequent pulse-echo medical ultrasonic (ultrasound) devices operating in the uni-directional A-mode and were used as early as 1949 by Lars Leksell (SE) and J.C. Turner (GB) for examining brain lesions(469, 470).

George Döring Ludwig (US), Francis W. Struthers (US), Richard H. Bolt (US), Theodor F. Hueter (US), and Henry Thomas Ballantine, Jr. (US) made significant progress toward understanding the usefullness and limitations of ultrasound for clinical examination(471-476). 

George Andrew Douglas Gordon (GB), J.C. Turner (GB), William Valentine Mayneord (GB), Stigg Jeppson (SE), Brita Lithander (SE), Marinus de Vlieger (NL), Kenji Tanaka (JP) and Toshio Wagai (JP) were among the first practitioners to use ultrasound in clinical settings.

Sir Walter Norman Haworth (GB) determined that a number of stereoisomeric structures are possible for the pyranose ring of each sugar and showed that glucose in the six-membered (pyranose) form is more stable than when it is in the five-membered (furanose) form or in the Fischer form, i.e., Haworth structures for sugars(477).

Karl Lohmann (DE), Cyrus Hartwell Fiske (US), and Yellapragada SubbaRow (US), found a new organic phosphate related to muscle adenylic acid and named it adenylpyrophosphate(478, 479).

Karl Lohmann (DE) determined its structure and recognized it to be adenosine-5’-triphosphate (ATP). Lohmann (DE) also characterized adenosine-5’-diphosphate (ADP)(480).

John Howard Northrop (US) isolated swine pepsin in pure crystalline form by techniques which were later used by him and other workers to crystallize trypsin, chymotrypsin, carboxypeptidase, and pepsinogen(481).

Marjorie Martland (GB) and Robert Robison (GB) observed that during the hydrolysis of fructosediphosphate (fructose-1,6-diphosphate) by preparations of bone phosphatase, a part of the sugars liberated, following the removal of the phosphoric acid groups, suffered an intramolecular change and gave rise to a mixture of aldolase and ketose sugars(482).

Ernst Waldschmidt-Leitz (CZ) and Arnulf Purr (CZ-US) identified the enzyme carboxypolypeptidase (carboxypeptidase) in bovine pancreatic extracts. They found that it cleaves C-terminal amino acids from acetylated peptides(483).

Phoebus Aaron Theodor Levene (RU-US) and Efim Semenovich London (RU) isolated and described 2-deoxyribose (they called it thyminose because it came from thymus nucleic acid, i.e., DNA, as belonging to a group of pentoses lacking an oxygen atom, and hence named desoxypentoses then later named deoxypentoses(484, 485).

George Oswald Burr (US), Mildred M. Burr (US), and Elmer S. Miller (US) demonstrated the existence and necessity of the so-called essential fatty acids. At that time, essentiality meant promotion of growth and prevention of the dermatitis observed when a fat-free diet was fed to rats(486-488).

Osmo Turpeinen (US) later proved that arachidonic acid is an essential fatty acid(489).

Adolf Friedrich Johann Butenandt (DE) isolated the hormone estrone (3-hydroxy 17-keto delta 1,3,5-estratriene) from the urine of pregnant women(490).

Clement D. Veler (US), Sidney Allen Thayer (US), and Edward Adelbert Doisy (US) independently isolated estrone (3-hydroxy 17-keto delta 1,3,5-estratriene) from the urine of pregnant women. They called it Theelin(491).

Sidney Allen Thayer (US), Louis Levin (US), and Edward Adelbert Doisy (US) characterized estrone (Theelin)(492).

Michel Macheboeuf (FR) isolated the first plasma lipoprotein to exhibit a constant composition(493). This fraction was later characterized as an alpha-1-globulin that we now recognize as high density lipoprotein (HDL).

Charles Robert Harington (GB) and Sydney Stewart Randall (GB) isolated 3,5, di-iodotyrosine from thyroglobulin of the thyroid gland(494).

Karl Paul Gerhard Link (US), Herbert Raleigh Angell (GB-AU), Allan D. Dickson (US), and John Charles Walker (US) established for the first time a specific chemical difference between a resistant host (pigmented onion) and a non-resistant host (the white onion). They determined that the brown pigmented onion produces the antifungal agent protocatechuic acid, which the white onion lacks(495-497).

Leo Loeb (US) and R.B. Bassett (US) isolated thyroid-stimulating hormone (TSH) from the anterior pituitary gland of cattle and demonstrated its effect on guinea pigs(498).

Max Aron (DE) independently isolated thyroid-stimulating hormone (TSH) from the anterior pituitary(499).

Carl Richard Moore (US) Thomas F. Gallagher (US) and Fred C. Koch (US) obtained male sex hormone in relatively pure form. Moore and his colleagues introduced the term testosterone(500, 501). 

George Washington Corner (US) and Willard Myron Allen (US) found, ….” that alcoholic extracts of the corpus luteum, freed of phospholipids, contains a substance which when injected into castrated adult female rabbits induces a characteristic alteration of the endometrium identical with the progestational proliferation previously shown to be due to the presence of corpora lutea in the ovaries.” They called this substance progestin (progesterone)(502).

Barnet Woolf (GB) was the first to site an example of an enzyme forming a complex with two substrates; later called ternary complexes(503). He proposed a theory of enzymatic action in which the binding of substrate or substrates leads to chemical transformation of the substrate at the specific binding site of the enzyme(504).

Carl Ferdinand Cori (CZ -US) and Gerty Theresa Cori, née Radnitz (CZ -US) concluded from work begun in 1925 that, “Formation of liver glycogen from lactic acid is thus seen to establish an important connection between the metabolism of muscle and that of the liver. Muscle glycogen becomes available as blood sugar through the intervention of the liver, and blood sugar in turn is converted into muscle glycogen. There exists therefore a complete cycle of the glucose molecule in the body which is illustrated by the diagram: blood glucose — muscle glycogen — blood lactic acid — liver glycogen — blood glucose.

Epinephrine (adrenaline) was found to accelerate this cycle in the direction of muscle glycogen to liver glycogen and to inhibit it in the direction of blood glucose to muscle glycogen; the result is an accumulation of sugar in the blood. Insulin, on the other hand, was found to accelerate the cycle in the direction of blood glucose to muscle glycogen, which leads to hypoglycemia and secondarily to a depletion of the glycogen stores of the liver … There is also a possibility that other hormones besides epinephrine [adrenaline] and insulin influence this cycle”(505).

Carl Peter Henrik Dam (DK) discovered vitamin K while working with chickens on synthetic diets. It seemed to be necessary for normal blood clotting so he named it vitamin K, for koagulation (the German spelling). Dam, Fritz Schönheyder (DK), and Erik Tage-Hansen (DK) discovered that the blood of chickens became depleted of prothrombin when they were placed on a vitamin K deficient diet(506-511).

Sidney Allen Thayer (US), Donald W. MacCorquodale (US), Stephen B. Binkley (US), and Edward Adelbert Doisy (US) crystallized vitamin K(512).

Donald W. MacCorquodale (US), Lee C. Cheney (US), Stephen B. Binkley (US), Walter F. Holcomb (US), Ralph W. McKee (US), Sidney Allen Thayer (US), and Edward Adelbert Doisy (US) determined the constitution of vitamin K and synthesized it(513-517).

Ernst Franz Moro (AT-DE) introduced the use of raw apples as well as a carrot soup in the treatment of diarrheic conditions in infants(518). This was based on an old custom among German peasants.

Tobias L. Birnberg (US) reported the successful treatment of diarrhea, dysentery, colitis, and celiac disease in children by restricting their diet to raw apple(519).

Michael Heidelberger (US) and Forrest E. Kendall (US) established the principle of quantitative immunochemistry when they perfected the quantitative precipitin reaction(520).

William Hay Taliaferro (US) wrote The Immunology of Parasitic Infections, a pioneering book in this branch of immunology(521).

Theodosius Grigorievich Dobzhansky (UA-US), Theophilus Shickel Painter (US), and Hermann Joseph Muller, Jr. (US) showed that while the linear sequence of genes is the same for genetic and cytological maps, physical distances and crossover map distances did not coincide(522-525).

Sir Frank Macfarlane Burnet (AU) and Margot McKie (AU) attributed the permanency of the lysogenic character in bacteria to the presence of an entity they called anlage which is capable of liberating bacteriophage. Anlage was conceived as a normal hereditary constituent of lysogenic bacteria and, unless activated, no liberation of bacteriophage resulted(526). 

C. Eugene Woodruff (US) and Ernest William Goodpasture (US) supplied the first direct evidence of the relation of viral inclusion bodies and elementary bodies to virus(527, 528).

Francis O. Holmes (US) arrived at the first practical and accurate method for the quantification of plant virus infectivity by counting the local lesions developing in the leaves of tobacco (Nicotiana species)(529).

Aage Nyfeldt (DK) reported that Listeria monocytogenes is capable of causing an infection in man (listeriosis) although it had been known to be infectious for domestic and feral animals since 1911. The organism derives its name from the striking monocytic blood reaction it causes in the infected host(530).

Clifford Dobell (GB) and Ann Bishop (GB) described the life cycle of Entamoeba histolytica(531).

Warren Harmon Lewis (US) and Margaret Reed Lewis (US) were the first to develop time-lapse microscopic motion pictures to record observations on living cells in culture. Their films became important teaching resources in cytology, and led them to develop mechanical theories of cell motion. In one of their first films they were able to see the early development of rabbit embryos, from the first ovum cleavage to the blastocyst stage.

Max Hartmann (DE) and Bjorn Føyn (NO) discovered alternation of isomorphic generations in the green algae(532, 533).

E. Juller () discovered alternation of heteromorphic generations in the green algae(534). 

Alfred Henry Sturtevant (US) was the first to use genetic mosaics (Drosophila simulans) for developmental studies(535).

Eli Kennedy Marshall, Jr. (US) described the aglomerular kidney of the toadfish (Opsanus tau)(536).

Sybil Cooper (GB), Charles Scott Sherrington (GB), and Derek Ernest Denny-Brown (NZ-GB-US) observed and defined the distinctive properties of red and white muscles(537, 538).

Derek Ernest Denny-Brown (NZ-GB-US) developed the technique of antidromic stimulation for the analysis of motor neuron responses(539).

Edgar Douglas Adrian (GB-US) and Detlev Wulf Bronk (US) developed an electromyograph. Bronk’s invention of the coaxial needle electrode greatly enhanced electromyography(540).

Derek Ernest Denny-Brown (NZ-GB-US) introduced electromyography (EMG) as a clinical tool and initiated the procedure of muscle biopsy as a means of seeking a direct tissue diagnosis of neuromuscular diseases(541).

Hans Piper (DE) authored the first extensive clinical EMG study(542).

George Bernays Wislocki (US) and James Peter Hill (GB) determined that all the primates, except the lemurs, have discoidal or doubly discoidal placentas of hemochorial type. In Old World forms, the shape of the placenta in the Ceropithecidae (macaques, langurs, etc.) is usually doubly discoidal; the baboons, in which it is singly discoidal, are the exception. In the Hylobatidae, Pongidae, and Hominidae (anthropoid apes and man) it is always singly discoidal. A completely villous discoidal placenta is seen only in the gorilla, orangutan, and man(543, 544). At this point in history the placenta of the chimpanzee had not received a thorough microscopic study.

Moriz Oppenheim (AT) and Erich Urbach (AT-US) described a new metabolic skin condition: necrobiosis lipoidica diabeticorum(545-547). 

Heinrich Pette (DE) proposed that inflammatory diseases of the nervous system be divided into two groups: (1) acute inflammatory diseases predominantly of the gray matter, and (2) acute inflammatory diseases predominantly of the white matter(548).

Fuller Albright (US), Walter Bauer (US), Marian Ropes (US), and Joseph C. Aub (US) found that an increased phosphorus excretion is the primary effect of parathormone(549).

Maxwell Myer Wintrobe (CA-US) invented what became known as the Wintrobe hematocrit(550).

Donald Macomber (US) and Morris B. Sanders (US) reported their results of analyzing the spermatozoa count to determine its value in the diagnosis, prognosis and treatment of sterility. They reported the normal sperm density to be 100 million sperm/mL. Their number was based on the sperm counts of 294 individuals without regard to fertility status. In addition, they reported that men with sperm densities less than 60 million/mL rarely were capable of initiating a pregnancy(551).

Philip Duryeé McMaster (US) and Douglas R. Drury (US) revealed that the liver is the source of blood fibrinogen(552, 553).

Edgar Otto Conrad von Gierke (DE) described a common member of a group of hereditary glycogen-storage diseases. This progressive disease is an inborn error of glycogen metabolism due to glucose-6-phosphatase (G6P) deficiency, involving chiefly the liver and kidneys(554). The liver may become huge and contain as much as 15 percent of glycogen. It is sometimes called Gierke's disease.

Otto Hermann Krayer (DE-US) mastered the heart-lung-preparation (HLP) originally developed by Starling in England. He used the HLP to show that an oxidation product of Neosalvarsan is toxic to vascular beds in a number of organs(555, 556). This is one of the reasons that this anti-syphilitic arsenical drug ceased to be used.

Otto Hermann Krayer (DE-US) perfected the management of the heart-lung-preparation (HLP) to the point that he could make quantitative measurements of the activity of cardioactive drugs. He also developed a standard HLP procedure to study drug effects on the failing heart(557-563).

Wilhelm Sigmund Feldberg (DE-GB) and Otto Hermann Krayer (DE-US) used both intact dogs and cats, as well as, dog and cat HLPs to show that an “acetylcholine-like substance” is released into the coronary circulation of mammals upon electrical stimulus of the vagus nerve(564). 

Albert Wollenberger (DE) and Otto Hermann Krayer (DE-US) demonstrated a method for quantitatively determining the limits of cardiac sufficiency in response to specific measured changes in right arterial pressure. They developed a specific “competence index” to express the heart’s response numerically. This method allows a clear distinction to be made between drugs that primarily affect heart rate and those (like digitalis) that truly improve the work capacity of the impaired muscle(565). 

Sergei S. Brukhonenko (RU) demonstrated successful total body perfusion after removal of animal hearts(566).

Philip Drinker (US) and Charles F. McKhann (US) invented a new apparatus (the iron lung) for the administration of artificial respiration over prolonged periods of time(567).

Walter Edward Dandy (US) introduced the practice of removing an intervertebral disk to alleviate lower back pain, sciatica, and other symptoms caused by a ruptured disk(568).

Harold Brunn (US) reported six lobectomies (removals of lung lobes) for bronchiectasis with only one death. In bronchiectasis one or more bronchi or bronchioles are chronically dilated and inflamed, with copious discharge of mucus mixed with pus. The secret of Brunn's success was the use of intermittent suction after surgery to keep the cavity free of secretions until the remaining lobes of the lung could expand to fill the space(569).

Jacques Forestier (FR) introduced gold therapy for rheumatoid arthritis(570).

Frederic Edward Clements (US), John Ernst Weaver (US), and Herbert C. Hanson (US) stated that one of the important processes directing plant succession is competition between similar plants leading ultimately to a climax community(571).

Percival Bailey (US) and Paul Clancy Bucy (US) were the first to confirm the existence of tumors that were, in fact, composed of oligodendroglia and to establish this type of glioma as a definite entity(572).

Karl S. Lashley (US) promulgated the theory of cortical specialization for sensory and motor functions. He challenged the ongoing concept of cortical localization. The controversy between localization and holistic emphasis of brain function was brought into focus by Lashley. He is remembered as a great psychologist who approached learning and memory by assessing the effects of brain damage in laboratory animals(573, 574).

Wolfgang Köhler (DE) and Kurt Koffka (DE) promoted a pattern theory of memory. Diffuse neural groupings mediated memory. They hypothesized that multiple memory traces were formed in the cortex. Visual memories involved successive and simultaneous stimuli in different parts of the visual field. They postulated that new records might be inscribed on top of old patterns these could affect one another leading to a newly organized group-unit(575, 576).

Johanna Gabrielle Ottilie Edinger (DE-US) demonstrated that the evolution of the brain can be studied directly from fossil cranial casts(577). She later showed that the progression of brain structure does not proceed at a constant rate in a given family but varies over time; also that the enlarged forebrain evolved several times independently among advanced groups of mammals and there was no single evolutionary scale(578).

1930

“The most beautiful thing we can experience is the mysterious. It is the source of all art and science,” Albert Einstein(579, 580).

“The scientific attitude of mind involves a sweeping away of all other desires in the interest of the desire to know—it involves suppression of hopes and fears, loves and hates, and the whole subjective emotional life, until we become subdued to the material, without bias, without any wish except to see it as it is, and without any belief that what it is must be determined by some relation, positive or negative, to what we should like it to be or to what we can easily imagine it to be.” Bertrand Russell(581).

“No myth of miraculous creation is so marvelous as the fact of man’s evolution.” Robert Briffault(582).

Hans Fischer (DE) was awarded the Nobel Prize in Chemistry for research into the constitution of hemin and chlorophyll and especially for the synthesis of hemin.

Karl Landsteiner (AT-US) was awarded the Nobel Prize in Physiology or Medicine for his discovery of human blood groups.

A.A. Lebedeff (RU) designed and built the first interference microscope(583).

Sterling Brown Hendricks (US) and William H. Fry (US) presented what is arguably the most important elucidation of the nature and properties of soils. They conclusively proved the crystalline nature of colloidal clay with the prevalence of negative charges that will absorb and release cations. These findings led to an understanding of the chemistry necessary to maintain high potential in soil productivity, and in providing a valid chemical basis for the reclamation of the alkali soils of arid regions(584).

William Thomas Astbury (GB), Henry J. Woods (GB), and A. Street (GB), using x-ray diffraction, demonstrated for the first time a measurable change in protein structure at the most intimate molecular level—interatomic shifts of a few ångströms. This change was found to be reversible. They called the two forms alpha-keratin and beta-keratin(585-587).

Hermann Bortels (DE) reported that nitrogen fixation by Azotobacter has a requirement for molybdenum(588)(Bortels 1930).

Rudolph J. Anderson (US) reported myoinositol as a lipid constituent in the phospholipids of mycobacteria(589).

Edward Adelbert Doisy (US), Sidney Allen Thayer (US) and Clement D. Veler (US) crystallized the ovarian hormone, estrogen, which induces estrus from the urine of pregnant women(590). Probably 17 beta estradiol.

Hans Karl August Simon von Euler-Chelpin (DE-SE), Karl Zeile (SE), and Harry Hellström (SE) showed that catalase contains a hemin residue(591).

John Tileston Edsall (US) and Alexander L. von Muralt (US) isolated myosin from muscle(592-594).

Wilbur Willis Swingle (US), Joseph J. Pfiffner (US), Frank A. Hartman (US), and Katherine A. Brownell (US) were the first to prepare extracts from the adrenal cortex which successfully controlled the symptoms of adrenal insufficiency both in adrenalectomized animals and in patients who had Addison’s disease(595-597).

Leonard George Rowntree (CA-US), Carl H. Greene (US), Wilbur Willis Swingle (US), and Joseph J. Pfiffner (US) proved the medical efficacy of the Swingle-Pfiffner extract(598).

C.L. Ruiz (AR), L.L. Silva (AR), and L. Libenson (AR) were the first to report the hypoglycemic effect of some sulphonamide-like compounds(599).

William Smith Tillett (US), Walther Frederick (US), and Oswald Theodore Avery (US) discovered C-polysaccharide (the C-fraction), a non-capsular antigenic component of pneumococci(600).

William Smith Tillett (US) and Thomas Francis, Jr. (US) discovered that the C-fraction carbohydrate from pneumococci stimulates the production of a non-antibody globulin which they dubbed C-reactive protein (CRP)(601).

Subsequently it was found that C-reactive protein appears in the blood of patients in response to many infections. During recovery from infection the C-reactive protein (CRP) diminishes in amount and within a few days disappears entirely. The serum of an animal immunized to CRP is used in a precipitation test to detect CRP in sera of persons suspected of having one of the diseases in which the protein appears, e.g. staphylococcal infection. 

Vladimir Aleksandrovich Engelhardt (RU) recognized that nucleated erythrocytes catalyze an aerobic process linked to phosphorylation, i.e., oxidative phosphorylation. This experiment initiated the history of oxidative phosphorylation(602, 603).

Ejnar Lundsgaard (DK) discovered that frog muscle poisoned with iodoacetic acid—which inhibits glycolysis—can contract without the formation of lactic acid, but with the disappearance of creatine phosphate. Once the creatine phosphate was exhausted the muscles went into a rigor mortis like condition. He wrote, “… phosphagen (creatine phosphate) is the substance directly supplying the energy for contraction, while lactic acid formation in the normal muscle continually provides the energy for its resynthesis”(604). Lundsgaard had discovered that the muscle machine can be driven by phosphate-bond energy.

Ragnar S. Nilsson (SE) isolated phosphoglyceric acid from natural sources. Based on the action of dried yeast on a mixture of glucose, hexosephosphate, and acetylaldehyde he suggested that glyceraldehyde-phosphate might play a role in the glycolytic breakdown of carbohydrate(605).

Fritz Breinl (CZ) and Felix Haurowitz (CZ-US) published their template theory of antibody formation(606). Although incorrect, this theory and others stimulated research.

Sir Gustav Joseph Victor Nossal (AU), Gordon Leslie Ada (AU), Caroline M. Austin (AU), John Pye (AU), and Gail M. Williams (AU) demonstrated that antibody making cells do not contain any antigen around which to shape an antibody(607-610).

H. Lyndhurst Duke (GB) and James Montague Wallace (GB) gave the first description of a complement receptor activity on erythrocytes(611).

James Montague Wallace (GB) and Arthur Wormall (GB) proposed that complement is required for this adherence reaction(612).

Haldan Keffer Hartline (US) and Clarence H. Graham (US) used tiny electrodes to determine how single retinal nerve cells in horseshoe crabs and frogs receive information and transfer it to the brain(613).

Haldan Keffer Hartline (US) mapped the activity of the visual receptive field to reveal a system of many convergent pathways from many photoreceptors(614). This work laid the foundation for modern concepts of parallel processing by specialized channels.

Yandell Henderson (US), Howard W. Haggard (US), Pol N. Coryllos (GR-US) and George L. Birnbaum (US) found that in dogs with experimentally induced pneumonia the lungs may be cleared and the pneumonia cured by placing the animals in an atmosphere of about 8% carbon dioxide for 12 to 24 hours. In support of the claim that these are real cures is the fact that pneumococci are inhibited in growth or even killed by a lowering of pH no greater than carbon dioxide may induce. A lowering of the pH by carbon dioxide contributes also to the autolysis and liquefaction of the exudate responsible for the consolidation of the lungs in pneumonia. Many cases of pneumonia have now been treated with inhalation of carbon dioxide in oxygen; and a special tent for this treatment was introduced by Yandell Henderson (US) and Haggard. It is believed by those who have used this treatment that it is decidedly superior to that with oxygen alone(615).

Ernest Glen Wever (US) and Charles W. Bray (US) discovered the cochlear microphonic potential, i.e., the bioelectric signals generated in the inner ear in response to sound stimuli(616-619). 

Benjamin Freeman Kingsbury (US) in his studies of neuroembryonic development provided the first detailed discussion of the possible functions of the floor plate in neural development(620).

Sir Ronald Aylmer Fisher (GB-AU) wrote The Genetical Theory of Natural Selection. This book contained his fundamental theorum of natural selection: “The rate of increase in fitness of any organism at any time is equal to its genetic variance in fitness at that time.” Natural selection is viewed as always tending to increase fitness, in the sense of reproductive fitness, and the course of evolution being determined by the momentary advantage of one allele over the other. This work formalized the relation of particulate genes to the evolutionary process. It overturned the old theory of heredity as blending, on which Charles Robert Darwin (GB) had based his views of the operation of natural selection(621).

Lewis John Stadler (US) devised and perfected methods for determining rate of spontaneous mutation in maize, finding that different genes mutate at widely different rates(622-624).

Norman H. Giles, Jr. (US) found that in Neurospora crassa quantitative mutability of different loci varies in spontaneous mutation(625).

Milislav L. Demerec (HR-US), Zlata Hartman (US), Philip Emile Hartman (US), Takashi Yura (JP), Joseph S. Gots (US), Haruo Ozeki (JP), and Stuart W. Glover (GB) found that in bacteria, quantitative mutability of different loci varies in spontaneous mutation(626). 

Herbert Friedmann (US) studied the honey-guides—family Indicaroridae—of Southern Rhodesia (Zimbabwe) and South Africa. He confirmed, first hand, that these birds do indeed lead a symbiont, often man, who opens the hive and removes some of the honey, the bird, then feeds on the wax comb(627-631).

Herbert Friedmann (US) and Jerome Kern (US) determined that honey-guides possess a digestive enzyme and a microbial symbiont both of which attack the beeswax, thus making it available for further digestion(632, 633). Wax eating is called cerophagy.

J. Marchal (GB) discovered the mousepox (Poxvirus muris) virus and called it infectious ectromelia(634). Marchal bodies are cell inclusion bodies observed in infectious ectromelia.

Wilbur A. Sawyer (US), Stuart F. Kitchen (US), Martin M. Frobisher, Jr. (US), and Wray Lloyd (US) determined the relationship of yellow fever of the Western hemisphere to that of Africa and leptospiral jaundice(635). 

Charles Cyril Okell (GB) and Adelaide V. Blake (GB) determined that the Shiga exotoxin is released following autolysis or disruption of the bacterial cells; suggesting that it is an endotoxin(636).

Bert Cyril James Gabriel Knight (GB) and Sir Paul Gordon Fildes (GB) initiated studies which led to the understanding that some heterotrophic bacteria can grow on a simple medium containing inorganic ions, ammonium as nitrogen source and glucose as source of carbon and energy. Other species are unable to grow on such a medium unless it is supplemented by an amino acid or one of the B group of vitamins. Still others, particularly those found in chemically complex habitats, require several amino acids and several vitamins before they could grow. Fildes and his colleagues postulated that the nutritional requirements are a reflection of the synthetic disabilities of the organisms concerned: that an organism that requires a specific amino acid for growth has, in the course of its evolution, lost the ability to synthesize that amino acid which is nevertheless an essential part of its cellular material. This postulate meant that nutritional studies could be used to study stages in biosynthesis(637).

Max Theiler (ZA-US) and Hugh H. Smith (US) grew the yellow fever virus in rhesus monkeys (Macacus rhesus), then passed it to mice. In mice, it developed as encephalitis. They passed it from mouse to mouse, then eventually back to monkeys. By this time it had attenuated, producing a very mild attack in the monkeys, but producing a full immunity to the most virulent form of the virus. This attenuated strain could also be used to vaccinate man(638, 639).

Gail Monroe Dack (US), William E. Cary (US), Oram C. Woolpert (US), and Hazel Wiggers (US) ingested filtered supernatant fractions of Staphylococcus aureus cultures to demonstrate that it is capable of producing an extracellular enterotoxin which causes gastroenteritis(640).

Sir Samuel Phillips Bedson (GB), George T. Western (GB), Samuel Levy Simpson (GB), and John O.W. Bland (GB) were outstanding early students of the Bedsonia —later called Chlamydiae. They discovered that Chlamydia psittaci is the etiological agent of parrot fever (psittacosis)(641, 642).

Walter Levinthal (DE), Ralph Dougall Lillie (US), and Alfred C. Coles (GB) discovered the causal agent of psittacosis; independently of each other(643-646).

M. Ruiz Castañeda (MX) developed an excellent method for staining rickettsia(647).

Attilio Macchiavello (EC) developed an excellent differential stain for observing rickettsia and chlamydia. ref

Bernard Schlesinger (GB) showed that hemolytic streoptococcal infection can cause acute rheumatism in children(648).

Homer William Smith (US) determined that in order for marine teleosts to maintain their blood salinity below that of the surrounding waters they rely upon a relatively impermeable skin, drink sea water to replace water lost through the gill membranes, and secret salt using a special transport mechanism located in the gills. Elasmobranch fishes solve this problem by making their tissues isosmotic or slightly hyperosmotic to sea water using a build-up of urea. He found that the elasmobranch kidney conserves urea by tubular reabsorption(649-651).

Malcolm S. Gordon (US), Knut Schmidt-Nielsen (US), and Hamilton M. Kelly (US) found that the crab eating frog (Rana cancrivora) is the only known amphibian which can tolerate sea water. It does so by raising its blood osmolarity using urea(652).

Homer William Smith (US) found that in order to prevent desiccation, lung-fishes burrow deep into the mud and form a cocoon with a breathing channel to the surface. They may remain dormant for up to two years during which time course their body proteins are gradually utilized and their tissue urea levels may reach 3 percent(653).

Charles Haskell Danforth (US) established the basic conditions for understanding the mechanisms for production of sex plumage in birds. He found in Ring-necked pheasants the sex characteristics of the plumage are dependent upon simultaneous action of both genic and hormonal factors. A single gene difference leads to divergent reactions to hormone in two races, Campines and Brown leghorns(654).

Hayes E. Martin (US) and Edward B. Ellis (US) introduced the technique of fine needle biopsy(655).

Ernest Laurence Kennaway (GB) and Izrael Hieger (GB) showed for the first time that single polycyclic aromatic hydrocarbons (PAHs), such as dibenz[a,h]anthracene, are tumorigenic in mouse skin(656).

James W. Cook (GB), Colin L. Hewett (GB), and Izrael Hieger (GB) discovered that pure benzo[a]pyrene induces skin cancer in mice(657).

Grover A. Kempf (US) and Frederick S. McKay (US) determined that high levels of water-borne fluoride causes the discoloration of tooth enamel now called fluorosis(658).

Margaret Cammack Smith (US), Edith M. Lantz (US), and Howard V. Smith (US) performed experiments which strongly supported the idea that excessive fluoride ingestion causes the hypoplasia characteristic of mottled teeth(659).

Henry Trendley Dean (US) recalled from reading Frederick S. McKay's and Green Vardiman Black’s studies on fluorosis in Colorado that mottled tooth enamel is unusually resistant to decay.  Dean wondered whether adding fluoride to drinking water at physically and cosmetically safe levels would help fight tooth decay.

Henry Trendley Dean (US), Frederick S. McKay (US), and Elias Elvove (US) made a critical discovery. Namely, fluoride levels of up to 1.0 ppm in drinking water did not cause enamel fluorosis in most people and only mild enamel fluorosis in a small percentage of people(660).

Henry Trendley Dean (US), Francis A. Arnold, Jr. (US), and Elias Elvove (US) performed a statistical survey which confirmed that the incidence of dental caries is significantly lower in communities where the water contains fluorine above certain concentrations(661).

In 1945, Grand Rapids, MI became the first city in the world to intentionally fluoridate its drinking water. During the 15-year project, researchers monitored the rate of tooth decay among Grand Rapids' almost 30,000 schoolchildren.  After just 11 years, Francis A. Arnold, Jr. (US), Henry Trendley Dean (US), Philip Jay (US), and John W. Knutson (US) announced an amazing finding. The caries rate among Grand Rapids children born after fluoride was added to the water supply dropped more than 60 percent(662, 663).

Bernardo Alberto Houssay (AR) and Alfredo Biasotti (AR) removed the anterior lobe of the pituitary gland and pancreas from animals. They showed that the anterior lobe of the pituitary gland affects the course of sugar metabolism in the human. The anterior lobe seemed to produce one hormone which had the opposite effect of insulin(664-667). Their work explained spontaneous remission of diabetes mellitus – vanishing diabetes – by a destructive lesion in, or surgical removal of, the anterior pituitary gland.

József Baló (AT-HU) was the first to describe this phenomenon (vanishing diabetes) in humans(668).

Ludvig Hektoen (US) determined the infectious nature of acute endocarditis(669).

Donald Dexter Van Slyke (US), Edgar Stillman (US), Eggert Hugo Heiberg Møller (US), William E. Ehrich (US), John F. McIntosh (US), Louis Leiter (US), Eaton M. MacKay (US), R. Roger Hannon (US), Norman S. Moore (US), and Christopher D. Johnson (US) related the changes occurring at different stages of renal deterioration to the quantitative changes taking place in kidney function(670).

Sir John Carew Eccles (AU) and Sir Charles Scott Sherrington (GB) showed central inhibition of flexor reflexes(671-677).

Arnold Rice Rich (US) separated jaundice into two types on the basis of pathogenesis. The first, retention jaundice, results from the overproduction of the bile pigment in conditions that are associated with a decrease in excretory power of the liver, such as fever, anoxemia, and immaturity. The second type—regurgitation jaundice—is caused by reflux of bile from the liver canaliculi into the blood stream in the presence of duct obstruction or liver cell necrosis(678).

Arnold Rice Rich (US) demonstrated that acquired resistance in the host is independent of the hypersensitive inflammatory reaction, and the latter, injurious to the host, may be eliminated by desensitization without impairment of immunity(679, 680).

James Wenceslas Papez (US) and Grant L. Rasmussen (US) determined that the superior olivary complex (SOC) exhibits a descending projection directed to the cochlea. Axons of SOC neurons build the so-called olivo-cochlear bundle (Bundle of Rasmussen)(681, 682).

Alexander A. Maximow (RU-US) posthumously authored A Textbook of Histology which was one of the most influential histology texts of the twentieth century(683). After Maximow’s death his book was completed and edited by William Bloom (US).

Anton Elschnig (AT) developed the method of corneal grafting introduced by Eugen von Hippel (DE) and produced good results on the human eye(684).

Magnus Hirschfield (DE) was the first true sex change pioneer. He coined the word transsexualism and founded, in Berlin, the first sexology institute. It was here that the first complete male-to-female sex change operation was performed in 1930. The patient was a Danish painter, Einer Wegener-Andreas Sparre, who had his genital organs removed, ovaries transplanted into him, and attempts made to furnish him with an artificial vagina. He died as a result of the series of operations, but before his death his marriage was annulled by the Danish authorities, who issued him a new birth certificate as a female, withand the name  of Lili ElIbe(685).

Sir Harold Delf Gillies (NZ-GB) and Ralph Millard (GB), in 1945, performed the first woman-to-man sex change operation(686).

Louis Wolff (US), John Parkinson (GB), and Paul Dudley White (US) discovered what became known as the WPW (Wolff-Parkinson-White) Syndrome. This is a bundle-branch block with short P-R interval in healthy young people prone to paroxysmal tachycardia(687).

Agustin Castellanos, Jr. (CU), Eduardo Chapunoff (CU), Cesar Castillo (CU), Orlando Maytin (CU), and Louis Lemberg (CU) made major contributions to understanding the WPW-Syndrome(688).

Owen S. Gibbs (CA) demonstrated an artificial heart consisting of two bellows within a round brass container(689, 690).

Tetsuzo Akutsu (JP) and Willem Johan Kolff (NL-US) reported the development of a totally artificial heart in an animal model. They implanted a totally artificial heart into a living dog that subsequently survived for 90 minutes(691).

Lyle D. Joyce (US), Willem C. DeVries (US), W. Larry Hastings (US), Don B. Olsen (US), Robert K. Jarvik (US), and Willem Johan Kolff (NL-US) reported on the response of the human body to the first permanent implant of the Jarvik-7 Total Artificial Heart. In 1982, the heart was implanted into Barney Clark who lived 112 days following the implantation(692). 

The United States Congress passed the Plant Protection Act (PPA) which provided for the patenting of asexually reproducing varietes. In 1970, the Plant Variety Protection Act (PVPA) was extended to include breeder’s rights to sexually reproducing varieties.

Sydney Savory Buckman (GB), published dozens of papers on ammonites, named hundreds of them, and invented a new way of dating rocks by time zones called hemera, each with their characteristic ammonites. His hemeral scheme for the Jurassic Period contained 370 hemera and 47 ages, the latter roughly corresponding to Oppel's sediment Zones(693).

1931

“Concern for man himself and his fate must always be the chief interest of all technical endeavors … in order that the creations of the mind shall be a blessing and not a curse to mankind. Never forget this, in the midst of your diagrams and equations.” Albert Einstein(694).

Otto Heinrich Warburg (DE) was awarded the Nobel Prize in Physiology or Medicine for his discovery of the nature and mode of action of the respiratory enzyme (Atmungsferment). A system of cytochromes and their oxidases that participate in the respiratory process; often, specifically, cytochrome oxidase.

William Joseph Elford (GB) and Christopher H. Andrewes (GB) developed the first filters (graded collodion membranes) in which pore size could be precisely determined. They used these to determine that viruses range in size from large protein molecules to tiny bacteria(695, 696).

Linus Carl Pauling published his first essays on The Nature of the Chemical Bond, detailing the rules of covalent bonding(697).

Sterling Brown Hendricks (US), William L. Hill (US), K.D. Jacob (US), and Merrill E. Jefferson (US) showed the structural characteristics of apatite-like substances and composition of phosphate rock and bone as determined from microscopic and x-ray diffraction examinations(698).

Paul Karrer (RU-CH) and Alois Helfenstein (CH) determined the chemical formula for squalene(699).

Hans Fischer (DE) and Richard Hess (DE) determined that the structure of bilirubin and strongly implied that it is derived from hemin(700).

Hans Fischer (DE) and Hans Plieninger (DE) effected the complete synthesis of bilirubin(701).

Otto Heinrich Warburg (DE) and Walter Christian (DE), and Alfred Griese (DE) found that adenine, nicotinamide, pentose, and phosphate were present in the ratio 1:1:2:3 in what was being called co-ferment or cozymase. They began referring to it as hydrogen-transporting co-ferment and stated, “The pyridine component of the co-ferment is its active group, because the catalytic action of the co-ferment depends on the alteration of the oxidation state of the pyridine part”(702-706). It was called Wasserstoffübertragendes Co-ferment or hydrogen transport coenzyme then later referred to as triphosphopyridine nucleotide (TPN) then finally nicotinamide adenine dinucleotide phosphate (NADP) or coenzyme II. The location of the third phosphate was established after 1950 in the laboratory of Arthur J. Kornberg (US).

Adolf Friedrich Johann Butenandt (DE) and Kurt Tscherning (DE) isolated, crystallized, and identified androsterone (andro = male, ster = sterol, one = ketone) from male urine. They presented this discovery at a Hamburg chemical meeting on October 23, 1931. Using microanalysis techniques they were able to learn enough about it to predict its structure and draw up the full constitutional formula(707). Androsterone is now called testosterone.

Karoly Gyula David (NL), Elizabeth Dingemanse (NL), Janos Freud (NL) and Ernst Laqueur (NL) crystallized male hormone from testicles, coining the name testosterone for their newly identified hormone (testo = testes, ster — sterol, one = ketone)(708).

Adolf Friedrich Johann Butenandt (DE), Günter Hanish (DE), Leopold Stefan Ruzicka (HR-CH), and Albert Wettstein (CH) partly synthesized the sex hormone testosterone from cholesterol(709-713). This was the first synthesis of a sex hormone and the first proof of the relationship between cholesterol and sex hormones.

Joseph L. Svirbely (US), Frederick L. Smith (US) and Charles Glen King (US) isolated vitamin C and reported its anti-scorbutic activity just two weeks ahead of Albert Imre Szent-Györgyi (HU-US)(714, 715).

Gertrude Maud Robinson (GB) and Sir Robert Robinson (GB) were among the first to isolate, separate, and identify the anthocyanin and anthoxanthin plant pigments(716-718).

Phoebus Aaron Theodor Levene (US) and Lawrence Bass (US) introduced the chemical components and the basic structure of DNA(719).

Ernst Friedheim (CH-US) and Leonor Michaelis (DE-US) found that at acidic pH values, the oxidation-reduction of the natural pigment pyocyanine involves the step-wise transfer of one electron, with the intermediate formation of a free radical which Michaelis termed a semiquinone(720).

Bene Elema (NL) discovered that the green coloring matter from Bacillus chloraphis represents a natural two-stage oxidation-reduction system(721).

James Gordon Horsfall (US) found that dusting tomato seed with copper sulfate monohydrate combated damping-off(722).

Harry Leonard Fevold (US), Frederick Lee Hisaw (US), and Samuel Leeson Leonard (US) discovered that the anterior lobe of the hypophysis (pituitary gland) produces follicle-stimulating hormone (FSH) and interstitial cell-stimulating hormone (ICSH). The interstitial cell-stimulating hormone (ICSH) is also known as luteinizing hormone (LH)(723).

Elsa R. Orent (US), Elmer Verner McCollum (US), Arthur R. Kemmerer (US), Conrad Arnold Elvehjem (US), and Edwin Bret Hart (US) demonstrated that mammals require manganese as a nutrient(724, 725).

Lucy Wills (GB) described treatment of pernicious anemia of pregnancy and tropical macrocytic anemia, with special reference to yeast extract (folic acid) as a curative agent(726).

Tom Douglas Spies (US), Carl F. Vitter (US), Mary B. Koch (US), Margaret H. Caldwell (US) experimentally proved that folic acid from yeast extract is the curative agent for macrocytic anemia(727).

Otto Fritz Meyerhof (DE-US) and Karl Lohmann (DE) stated that the role of adenylpyrophosphate (ATP), “ … appears to consist in the fact that the esterification of phosphate, which precedes the cleavage of carbohydrate to lactic acid, occurs with the simultaneous cleavage of adenylpyrophosphate, which is resynthesized during the further cleavage [of carbohydrate]. In this manner, the adenylpyrophosphate cycle maintains the lactic acid formation. The synthesis of phosphagen (creatine phosphate) is therefore made possible … by the cleavage energy of the adenylpyrophosphate, while the energy of lactic acid formation (from phosphate esters) serves to resynthesize the cleaved pyrophosphate”(728).

Cornelis Bernardus Kees van Niel (NL), after elucidating the nature of bacterial photosynthesis, proposed that bacterial and plant photosynthesis are special cases of a general process in which light energy is used to photodecompose a hydrogen donor, H2A, with the released hydrogen in turn reducing carbon dioxide by dark, enzymatic reactions. The hypothesis envisaged that in plant photosynthesis H2A is water, whereas in green sulfur bacteria, e.g., H2A is H2S, with the results that oxygen becomes the by-product of plant photosynthesis and elemental sulfur the by-product of bacterial photosynthesis(729-731).

Keita Shibata (JP), in 1931, independently proposed the photodissociation of water during oxygenic photosynthesis and a metabolism of anoxygenic photosynthetic bacteria very similar to the scheme proposed by van Niel(732).

Heinz Ohle (DE) postulated that the anaerobic breakdown of glucose begins with its phosphorylation to glucose-6-phosphate, which is converted into fructose-1,6-diphosphate (via fructose-6-phosphate); the hexose diphosphate was considered to undergo a series of oxidations and reductions leading to the formation of glyceraldehyde-3-phosphate and dihydroxyacetone phosphate(733).

Otto Fritz Meyerhof (DE-US) would establish the formation of phosphoglyceraldehyde in hexosediphosphate cleavage(734).

Harold S. Olcott (US) and Henry A. Mattill (US) fractionated the oil of lettuce and found that one fraction had high antioxidant power and high potency as a source of vitamin E(735).

Herbert McLean Evans (US), Oliver H. Emerson (US), and Gladys A. Emerson (US) isolated alpha-tocopherol from wheat germ oil and discovered that it is synonymous with vitamin E(736).

Elsa R. Orent (US) and Elmer Verner McCollum (US) performed experiments with rats which demonstrated that magnesium is essential to that animal’s diet. Deficiency symptoms included, dilatation of cutaneous blood vessels, extreme hyperirritability, and tetanic seizures initiated by sound(724).

Bishop C. Hsien Wu (CN) proposed that in addition to peptide covalent linkages between amino acids the native organization of proteins was due mainly to polar groups(737).

Alfred Ezra Mirsky (US) and Linus Carl Pauling (US) stated, “Our conception of a native protein molecule (showing specific properties) is the following: The molecule consists of one polypeptide chain which continues without interruption throughout the molecule (or in certain cases, of two or more such chains) ; this chain is folded into a uniquely defined configuration, in which it is held by hydrogen bonds between the peptide nitrogen and oxygen atoms and also between the free amino and carboxyl groups of the diamino and dicarboxyl amino acid residues…. The characteristic specific properties of native proteins we attribute to their uniquely defined configuration. The denatured protein molecule we consider to be characterized by the absence of a uniquely defined configuration”(738).

Walter J. Kauzmann (US) concluded that the most important energetic driving force behind the three-dimensional structure of proteins is hydrophobic bonds(739). 

Albert Jan Kluyver (NL) in his treatise, The Chemical Activities of Microorganisms, recognized the potential significance of the ideas that Neuberg, Wieland, Warburg, Harden, and a few others had advanced to account for more or less specific biochemical events. Soon it became evident to him that these concepts could be welded together into a very few general principles, applicable to all biochemical phenomena. The most basic of these generalizations is the extension of the ideas of Neuberg and of Wieland to their ultimate limits. Thus, any biochemical process, whether oxidation, fermentation, or synthetic reaction, was considered as a chain of step reactions, each one of which represented a simple mechanism in which hydrogen is transferred from one molecule, the H-donor, to another, the H-acceptor. The apparent exception to this principle was exhibited in the metabolism of complex molecules, composed of a number of simple entities, for example the polysaccharides (complexes of simple sugars), proteins (complexes of amino acids), and fats (complexes of fatty acids and glycerol). Such complexes would first be converted to their constituent units by hydrolytic cleavages, with the products subsequently undergoing the various hydrogen-transfer reactions. In this manner the existence of the many hydrolytic enzymes—glucosidases, proteinases, lipases, etc.—could be fitted into the general picture.

He advocated the use of microorganisms for comparative biochemical studies because of the ease of handling them under controlled and reproducible conditions, and because of the enormous biochemical versatility encountered within this group. It is often possible to select a specific microorganism as singularly appropriate for a given problem because it carries out a certain type of reaction to the exclusion of almost any other. But it is equally important to realize that one may find among these creatures the best examples of seemingly quite different biochemical properties with respect to the conversion of a particular substrate. 

The recognition of this unity at the molecular level is Kluyver’s great contribution; it is also the starting point of comparative biochemistry(740).

Warren Harmon Lewis (US) characterized the process of pinocytosis(741).

Johann Heinrich Emil Heitz (DE) and Barbara McClintock (US) demonstrated that the nucleolus in somatic cells is regularly associated with a particular locus on one or more chromosomes. McClintock defined this region as the nucleolar organizer(742, 743).

John Charles Walker (US) developed and released peas resistant to Fusarium wilt and near-wilt disease(744).

Karl Friedrich Meyer (US), Clarence M. Haring (US), and Beatrice Howitt (US) isolated the virus of Western equine encephalomyelitis from the brains of infected horses during an outbreak in California(745, 746).

Wilbur A. Sawyer (US) and Wray Lloyd (US) developed a serum neutralization test for the presence of yellow fever(747).

Fred L. Soper (US), Elmer R. Rickard (US), and Peter J. Crawford (US) perfected the postmortem diagnosis of yellow fever by viscerotomy (histological examination of the liver)(748). This greatly aided in field surveys of yellow fever.

Alice Miles Woodruff (US) and Ernest William Goodpasture (US) developed the first practical method for cultivating large quantities of a virus in the laboratory—by growing it on the exposed membrane of a chick embryo(749).

Charles E. Clifton (US), Edwin William Schultz (US), and Louis P. Gebhardt (US) used ultrafiltration collodion membranes to estimate that poliomyelitis virus is less than 50 nanometers in diameter(750). Subsequent work by them placed its size at close to 25 nanometers.

Richard E. Shope (US) and Paul A. Lewis (US) found that two infectious agents are necessary to induce the most severe form of swine influenza, the influenza virus and a bacterium he called Hemophilus influenzae suis. The virus alone produced a mild form of the disease(751-753). He later speculated that survival of the virus during inter-epidemic periods involves virus persisting in a latent form in the parasitic pulmonary nematode (lung worm) of the pig. The virus is incorporated in the ova of the nematode which is later eaten by an earthworm which serves as its intermediate host. After the lung worm reaches a certain stage of development the earthworm is eaten by the pig and influenza virus inside the nematode returns to the lungs of the same or another pig(754-758).

Perrin H. Long (US), Eleanor A. Bliss (US), and Harriet M. Carpenter (US) succeeded in producing influenza in chimpanzees using material which had passed though a filter capable of stopping bacteria(759).

Wilson Smith (GB), Christopher H. Andrewes (GB), and Sir Patrick Playfair Laidlaw (GB) successfully induced influenza in ferrets by inoculating them intranasally with filtrates of throat washings obtained from patients early in the course of the disease(760). This work proved that human influenza is caused by a virus. Later this would be referred to as type A.

Max A. Lauffer (US) and Wendell Meredith Stanley (US) purified the influenza virus then determined its biophysical properties(761).

Robert Daubney (GB), J.R. Hudson (GB), and Percy Cyril Claude Garnham (GB) were the first to isolate the Rift Valley fever virus (RVFV); a type of bunyavirus (Phlebovirus). They found it in East African sheep(762).

Rolla Eugene Dyer (US), Elmer T. Ceder (US), Adolph S. Rumreich (US), and Lucius F. Badger (US) made the first isolation of murine typhus from rat fleas. The fleas were collected at an outbreak of typhus fever in Baltimore, MD(763). Along with Elmer T. Ceder (US) and Ralph Dougall Lillie (US) they showed that the rickettsia of murine typhus persisted in rat fleas for at least nine days and were present in feces of infected fleas. They were also successful in experimental transmission of murine typhus from rat to rat with the flea Xenopsylla cheopis Rothschild(764).

Sara E. Branham (US), Clara Enola Taft (US), and Sadie A. Carlin (US) identified a new organism, Neisseria flavescens, as a rare cause of meningitis and septicemia in humans, but one requiring careful differentiation from meningococcus(765, 766). In 1970 Branham was honored posthumously by the name of a new genus, Branhamella.

Ernst Lowenstein (DE) and Kai Adolf Jensen (DK) developed a culture medium for the isolation and cultivation of mycobacteria and as bases for selective, differential, and enriched media for mycobacteria. Malachite green is used to inhibit non-mycobacterial organisms(767, 768).

J.S. Anderson (GB), Frank C. Happold (GB), James Walter McLeod (GB), and J.G. Thomson (GB) discovered that severe cases of diphtheria were nearly always caused by a genetic variety of Corynebacterium diphtheriae referred to as gravis. The mild cases were usually associated with the variety called mitis. The two varieties were easily distinguishable from one another because of their characteristic colonies formed on solid media(769).

Margaret Pittman (US) determined that pathogenicity in Hemophilus influenzae is influenced by variation in encapsulation types(770).

René Jules Dubos (US) and Oswald Theodore Avery (CA-US) discovered Bacillus brevis, an organism that breaks down the capsular polysaccharide of Type 3 Streptococcus pneumoniae and protects mice against pneumonia(771).

Lucius F. Badger (US) and Adolph S. Rumreich (US) isolated Rickettsia rickettsii from the American dog tick(Dermacentor variabilis Say) and determined that it is the vector for the rickettsia of Rocky Mountain spotted fever (eastern type)(772).

A.S. Michailoff (DE) was the first to report on a mutation in the honeybee, Apis mellifera Linn. It was the ivory eye color which he referred to as white(773).

Harriet B. Creighton (US) and Barbara McClintock (US), working with corn (Zea mays), obtained cytological proof that the inheritance of novel gene combinations during crossing over is due to the physical exchange of specific chromosome segments(774).

Curt Stern (DE-US), using cytologically abnormal X-chromosomes of Drosophila, one with the X-Y translocation, and one with an X-IV translocation, demonstrated that the genetic phenomenon of crossing over is accompanied by a physical exchange between the chromosomes(775).

Franz Schrader (DE-US) and Sally Hughes-Schrader (US) observed coccids (scale insects and mealybugs) in which one set of chromosomes of the diploid male undergoes heteropycnosis, leading they surmised, to inactivity and ultimately to effective haploidy of the nominally diploid male. They pointed out that all of one haploid set in these cases may be viewed as a compound X chromosome (an X chromosome consisting of more than one element), and all of the other set as a compound Y. On this basis a hypothesis for the evolutionary origins of haplo-diploid parthenogenesis was formulated(776).

G.K. Chrustschoff (RU), A.H. Andres (RU), W.I. Iljina-Kakujewa (RU), E.A. Berlin (RU), and P. Zhivago (RU) were the first to use cultures of peripheral blood cells for the study of chromosomes(777-779).

P. Zhivago (RU), B. Morosov (RU), and A. Ivanickaya (RU) discovered that a much better spread of chromosomes occurs if water is used instead of isotonic solutions during the preparation of a chromosome squash(780).

Tao-Chiuh Hsu (US), Sajiro Makino (JP), Isao Nishimmura (JP), and Arthur Hughes (GB) rediscovered the use of water instead of isotonic solutions in 1952(781-783).

Sewall Wright (US) presented the first unified picture of evolution in terms of Mendelism by illustrating the relations between selection pressure, mutation rates, inbreeding, and isolation(784).

Leonard H. Snyder (US) and Albert Francis Blakeslee (US), based on experiments using phenyl thiocarbamide (PTC), concluded that tasting is inherited as a Mendelian recessive trait, with "taste" being dominant to "non-taste." In addition Blakeslee showed that there is a threshold concntration below which "tasters" cannot detect PTC(785, 786).

John Punnett Peters (US) and Donald Dexter Van Slyke (US) wrote the two volume Quantitative Clinical Chemistry, for many years the world authority(787, 788). 

Leopold Heine (DE) performed work which made the manufacture of modern contact glasses possible(789).

Philip Duryeé McMaster (US) and Stephen S. Hudack (US) proved that lymphatics instead of being passive drainage canals, are very active in the process of fluid exchange. Their walls respond rapidly to various influences such as sunlight, warmth, or a state of shock that does not break the skin(790-797).

Maxwell Myer Wintrobe (CA-US) developed the methodology for direct calculation of the average erythrocyte size, mean corpuscular volume (MCV) in cubic microns, mean hemoglobin content (MCH) in picograms, and mean corpuscular hemoglobin concentration (MCHC) in percent—quantifications that are standard clinical procedure today(798). 

Samuel S. Shouse (US), Stafford L. Warren, II (US), and George Hoyt Whipple (US) provided descriptions of the anatomic and functional effects of radiation injury(799).

António Caetano Abreau Freire De Egas Moniz (PT) conceived visualization of cerebral blood vessels by roentgenography. The medium he developed with comparative safety used sodium iodide. When colloidal thorium dioxide was developed he followed up this lead with cerebral angiography to visualize intracranial tumor, vascular abnormalities, and aneurysms(800, 801).

Harvey Williams Cushing (US) removed a pituitary tumor from a patient on April 15, 1931. This was the 2000th verified brain tumor removed by Cushing in his remarkable career during which he reduced the mortality rate in brain surgery from more than 90 percent to a little over 8 percent. Cushing operated for an additional fifteen months before retiring(225). In a supreme irony he died in 1939 of a brain tumor.

Harvey Williams Cushing (US) reported on the surgical-mortality percentages pertaining to the two thousand operations he had performed for the removal of intracranial tumors(802).

Christian Georg Schmorl (DE) established the modern basis for understanding the intervertebral disc, by providing very clear discussions of herniations as well as degenerations(803).

James Rognvald Learmonth (IR) observed that if the hypogastric nerve is stimulated the result is contraction of the ipsilateral ureteral orifice; tightening of the trigone; contraction of the internal sphincter; and contraction of the musculature of the prostate, seminal vesicles and ejaculatory ducts. Sectioning the hypogastric nerve produces relaxation of the ureteral orifice, trigone and internal sphincter, with no appreciable effect on the dome or lateral walls of the bladder(804).

Derek Ernest Denny-Brown (NZ-GB-US), E. Graeme Robertson (AU), and Alex E. Roche (GB) studied the events of voiding and the volumetric changes of the bladder in relation to sphincter activity. They found spontaneous waves of pressure in the bladder during filling. As these increased in amplitude, subjective sensations of fullness or urinary urgency developed in the subjects. The subjects, when asked, could voluntarily suppress the summation of these pressure waves(805-807). 

Michael S. Burman (US) carried out the first extensive academic research in arthroscope usage in the United States. Arthroscopy being the direct visualization of joints(808).

Rudolf Nissen (DE) successfully removed an entire bronchiectatic (irreversible dilatation of part of the bronchial tree) lung(809).

Paul Dudley White (US) virtually created the specialty of cardiology in the United States when he published his book, Heart Disease(810).

Another outbreak of polio swept the U.S. during the summer of 1931, killing more than 4,000 people, about 12 percent of the reported cases(811).

George Gaylord Simpson (US) united the two families of anthropoid apes, Pongidae (Simiidae), and men, Hominidae, into a Superfamily, which he called Hominoidea, and distinguished from the two other superfamilies of the sub-order Anthropoidea, which he called the Cercopithecoidea and the Ceboidea. The superfamily Hominoidea includes the hominoids (gibbons, great apes, and humans). The term hominids refers only to humans(812).

Marius Pièry (FR), Julien Roshem (FR), and Vilhelm Moller-Christensen (DK) gave accounts of Stone Age homonoid skeletons diagnosed as exhibiting signs of tubercular damage. Evidence of pulmonary tuberculosis remains but, in the nature of the case, it is meager(813, 814).

Erik Andersson Stensiö (SE) and Gunnar Säve-Söderbergh (SE), of the 1929-1930 Danish scientific expeditions, found ichthyostegid fossils in the upper Devonian sediments in eastern Greenland. They appear to be intermediate between lobe-finned rhipidistians (Osteolepis) and early amphibians. These are the oldest known fossils that can be classified as amphibians(815, 816).

Arthur Tindell Hopwood (GB), in 1931, discovered the fossils of three hominids near Lake Victoria, he would name them Proconsul in 1933(817, 818). This was the oldest known ape found up to this time.

Sir Wilfred E. Le Gros Clark (GB) and Louis Seymour Bazett Leakey (GB-KE), reported on a hominid skull and jaw found by Mary Douglas Nicol Leakey (GB-KE), in 1948, in Miocene deposits on Rusinga Island in Lake Victoria, Western Kenya. It was an excellent sample of Proconsul africanus (sometimes called Dryopithicus africanus or "woodland ape"). The specimen is approximately 16 million years old. Proconsul is a candidate for the distant ancestor from which all modern species of apes and all hominids—human beings included—evolved.

Henry Bryant Bigelow (US) cnidariologist; founded Woods Hole Oceanographic Institution (WHOI) in 1931 and became its first director until 1940. He is commemorated by Haliscera bigelowi Kramp, 1947, Bathyplotes bigelowi Deichmann, 1940, Braarudosphaera bigelowii Gran et Braarud Deflandre, 1947, Casco bigelowi Blake, 1929, Lucaya bigelowi Chace, 1939, Euphysora bigelowi Maas, 1905, Neoturris bigelowi Kramp, 1959, Calycopsis bigelowi Vanhöffen, 1911, and Octophialucium bigelowi Kramp, 1955.

1932 

“If a patient is poor he is committed to a public hospital as psychotic; if he can afford the luxury of a private sanatorium, he is put there with the diagnosis of neurasthenia; if he is wealthy enough to be isolated in his own home under constant watch of nurses and physicians he is simply an indisposed eccentric.” Pierre Marie Félix Janet(819).

Sir Charles Scott Sherrington (GB) and Lord Edgar Douglas Adrian (GB) were awarded the Nobel Prize in Physiology or Medicine for their discoveries regarding the functions of neurons.

Max Knoll (DE) and Ernst August Friedrich Ruska (DE) originated the concept of a transmission electron microscope (TEM)(820).

Ernst August Friedrich Ruska (DE) and Max Knoll (DE) built the first transmission electron microscope (TEM) at the Technische Hochschule of Berlin-Charlottenburg. 

Albert F. Prebus (CA) and James Hillier (CA-US) made the TEM a practical instrument(821). see M.M. Freundlich. 1963. Origin of the electron microscope. Science 142: 185-188.

Harold Clayton Urey (US), Ferdinand G. Brickwedde (US), and George M. Murphy (US) were the first to prove that hydrogen gas contains a few atoms in which the nuclear proton is accompanied by a neutron. This so called heavy hydrogen was given the name deuterium(822, 823).

Martin Gerhard Behrens (DE) used differential centrifugation to separate chloroplasts, nuclei, and cytoplasm(Behrens 1932; Behrens 1939).

S. Furukawa (JP) isolated four terpenes in his quest to determine the active constituents of the Ginkgo extracts used in folk medicine(824-826).

Koji Nakanishi (JP) determined the structures of the ginkgolides(827).

Elias James Corey (US), Myung-Chol Kang (US), Manoj C. Desai (US), Arun K. Ghosh (US), and Ioannis N. Houpis (US) carried out the complete synthesis of ginkgolide B(828).

Wendell Meredith Stanley (US), Gerald H. Coleman (US), C.M. Greer (US), J. Sacks (US), and Roger Adams (US) elucidated and synthesized chaulmoogric and hydnocarpic acids, the active ingredients of chaulmoogra oil, a folk remedy for leprosy(829).

Werner Schulemann (DE), Fritz Schönhöfer (DE), and August Wingler (DE) announced the synthesis of plasmoquine (pamaquine, plasmochin) for the treatment of malaria(830).

Leonor Michaelis (DE-US) presented the first example of a reversible two-stage oxidation-reduction system(831).

Heinrich Otto Wieland (DE) and Elisabeth Dane (DE) described the correct structure for cholesterol(832).

Sigmund Otto Rosenheim (GB) and Harold King (GB) worked out the correct structure for the rings found in bile acids and sterols (including cholesterol)(833-836). 

Cecil James Watson (US) crystallized stercobilin from human feces and proved that it is different from urobilinogen and mesobilirubinogen. In the process he discovered mesobiliviolin in nature for the first time(837).

Manayath Damodaran (GB), Gunnar Jaaback (GB), and Albert Charles Chibnal (GB) isolated glutamic acid from the hydrolysate of a protein(838).

Joseph K. Tillmans (DE), Paul Hirsch (DE), and Johannes Jackisch (DE) were the first to introduce a quantitative chemical test for the presence of vitamin C. If was based on the relationship between the vitamin C content of a food and its reducing power(839).

Robert Emerson (US) and William A. Arnold (US) articulated the concept of a photosynthetic unit (photosystem), that includes the two components, the antenna and the reaction center(840, 841).

Robert F. Parker (US) and Ralph S. Muckenfuss (US) adapted the complement fixation test for the detection of smallpox antigen in lesion fluid. This represents the first immunological test for viral antigens(842).

Max Schlesinger (DE-GB) used the adsorption capacity of the bacterial cell for bacteriophages and the sedimentation velocity of bacteriophages to determine that the bacteriophage particle has a maximum linear dimension of about 0.1 micrometer and a mass of about 4 x 10-16 g. His studies of the kinetics of bacteriophage attachment imply that Brownian movement brings bacteriophage particles into random collisions with the bacterial surface. He purified a weighable amount of T-even bacteriophage by differential centrifugation and graded filtration; then by direct chemical analysis found that they consisted mainly of protein and DNA, in roughly equal proportions(843-845).

Max Bergmann (DE-US) and Leonidas Zervas (DE-US) developed a method for synthesis of polypeptides which was superior to the Fischer synthesis because it allowed the inclusion of complex amino acids in the polymer(846).

Otto Heinrich Warburg (DE) and Walter Christian (DE) isolated, from yeast, a yellow-red protein which they called oxygen-transporting-ferment and concluded that, “The yellow ferment is therefore not only an oxygen-transporting ferment but also a ferment of oxygen-less respiration. … It is probable that in life, the yellow ferment does not transfer molecular, but bound oxygen. Probably, in life, it is not an oxygen-transporting ferment but an oxidation-reduction ferment.” They went on to show that the pigment is a small molecule which is released when the protein portion of the complex is denatured. The pigment was found to belong to the class of substances that Richard Johann Kuhn (AT-DE) had named flavins(847, 848).

Kurt Guenter Stern (GB-US) and Ensor Roslyn Holiday (GB) determined the chemical structure of the flavins(849).

Richard Johann Kuhn (AT-DE), Karl Reinemund (DE), Friedrich Weigand (DE), Rudolf Ströbele (DE) and Paul Karrer (RU-CH) synthesized many flavins including this one which was designated vitamin B2 or riboflavin(850-853). Riboflavin alone was found to be inactive.

Axel Hugo Theodor Theorell (SE) showed that the coenzyme associated with Warburg’s yellow enzyme had a structure like riboflavin (vitamin B2), to which a phosphate group was attached(854).

Richard Johann Kuhn (AT-DE), Hermann Rudy (DE), and Friedrich Weygand (DE) found that the active form had a phosphate group at the five prime position (vitamin B2 is riboflavin phosphate or flavin mononucleotide) and behaves as a prosthetic group carrying out its catalytic function while complexed with protein as a flavoprotein(855).

Joachim Hämmerling (DE) performed a series of classic experiments using the alga Acetabularia spp. as his material. He concluded that there must be intermediate stages between the genetic information of the cell nucleus and expression of the genetic information in the cytoplasm. Furthermore these intermediate stages must be represented by chemically defined substances (m-RNA) which were called morphogenetic substances and even in darkness the nucleus continues to supply the cytoplasm with morphogenetic substances. In the 1934 reference Hämmerling found that chloroplasts divide in anucleate cells(856-862). Note: This work is remarkable as a harbinger of molecular biology.

Sir Hans Adolf Krebs (DE-GB) and Kurt Henseleit (DE) worked out the way in which the body eliminates waste nitrogen, usually from deamination reactions, by breakdown and regeneration of a portion of the amino acid arginine. This urea cycle (or ornithine cycle), as it is called, ultimately leads to the excretion of waste nitrogen as urea. In their own words, “The primary reaction of urea synthesis in the liver is the addition of 1 molecule of ammonia and 1 molecule of carbonic acid to the d-amino group of ornithine, with the elimination of one molecule of water and the formation of a d-ureido acid, citrulline … The second reaction of urea synthesis is the combination of 1 molecule of citrulline with an additional molecule of ammonia, with the loss of a second molecule of water and the formation of a guanidino acid, arginine … The third reaction is the hydrolytic cleavage of arginine to ornithine and urea”(863).

Sir Rudolph Albert Peters (GB), Nicolai Gavrilescu (HU), Arnold Peter Meiklejohn (GB), and Reginald Passmore (GB) were the first to demonstrate in vitro that a vitamin (thiamine) has a specific enzymatic aiding action(864, 865).

V. Albrecht Bethe (DE) introduced the concept of ectohormones, now known as pheromones(866). See Karlson, 1959. These chemicals are excreted by one member of a species to effect the physiology or behavior of another member of the same species.

Hermann Otto Laurenz Fischer (DE) and Erich Baer (DE) synthesized DL-glyceraldehyde-3-phosphate to be tested as an intermediate in alcoholic fermentation(867).

Carl Vincent Smythe (DE) and Waltraut Gerischer (DE), in 1933, showed that yeast could ferment DL-glyceraldehyde-3-phosphate; consuming only one of the isomers(868). Later work showed that it was the D isomer being metabolized.

Edwin Martin Case (GB) discovered that muscle extract produced pyruvic acid from hexosediphosphate or glycogen(869).

Marcus Morton Rhoades (US) demonstrated in maize that crossing over among chromosomes occurs at the four-strand stage(870).

Franz Schrader (DE-US) concluded that spindles in living cells do indeed have a fibrous structure, albeit an invisible one. In bipolar spindles he described these fibrous arrays as consisting of: 1) those running from a spindle pole to each chromosome or chromatid, namely, chromosomal fibers or half-spindle components; 2) continuous fiber systems from pole to pole; and, in some organisms 3) interzonal fibers of quite different nature connecting the ends of separating chromatids at anaphase(871, 872).

William Henry Chandler (US), Dennis Robert Hoagland (US), and Paul Llewellyn Hibbard (US) discovered that zinc deficiency causes a number of physiological disorders in plants, including little leaf in peaches, mottle leaf in citrus, and rosette in apples(873).

Howard S. Reed (US) and Jean Dufrenoy (US) described the signs and symptoms of zinc deficiency in plants(874).

Richard Edwin Shope (US) showed that mad itch, a violent, distressing, and fatal disease of cattle in the American Midwest is caused by a virus transmissible to rabbits, and endemic among pigs. He identified mad itch as being identical to pseudorabies in Europe(875).

Richard Edwin Shope (US) discovered the viral etiology of rabbit fibroma disease found in wild cotton tail rabbits (Sylvilagus) in the United States(876-880). This is often called Shope fibroma.

Francis Peyton Rous (US), and Joseph W. Beard (US) successfully induced a tumor in mammals using a virus. The virus causes a papilloma in rabbits. Today it is called the Shope papilloma virus(881, 882).

Chester Hamlin Werkman (US) and George Francis Gillen (US) proposed the bacterial generic term Citrobacter for the citrate-positive, coli-aerogenes intermediates, with Citrobacter freundii Braak as the type species(883).

Henry Pinkerton (US) and George M. Hass (US) grew rickettsia in tissue culture(884).

Carl Clarence Lindegren (US) worked out much of the basic genetics of the fungus, Neurospora(885).

Margaret Newton (CA-US) and Thorvaldur Johnson (CA) developed techniques to allow them to hybridize the rust fungus while it grew on barberry. They discovered that pathogenic characters segregated in a Mendelian fashion while some other characters appeared to be inherited in a maternal pattern(886-889).

Robert A. Stewart (US) and Karl Friedrich Meyer (US) demonstrated that the soil is a reservoir for Coccidioides immitis(890).

Frans Verdoorn (NL) edited an excellent manual on the bryophytes (liverworts and mosses) which, among other things, discussed their classification, ecology, distribution, morphology, physiology, cytology, and genetics(891).

Helmuth Weese (DE) and Walther Scharpff (DE) reported on their first experiences with hexobarbital (the first short-acting barbiturate) for intravenous induction of general anesthesia. It is also called evipan and evipal(892). 

William F. Hamilton (US), Jack Walker Moore (US), James M. Kinsman (US), and Roy G. Spurling (US) performed experiments which exposed hemodynamics under physiological and pathological conditions(893).

Eliot R. Clark (US) and Eleanor Linton Clark (US) placed glass-windowed chambers in the rabbit ear and made exquisite drawings of the branching patterns of the blood vessels that entered the wound. Their work established the field of vascular biology(894).

Philip Duryeé McMaster (US), Stephen S. Hudack (US), and Francis Peyton Rous (US) found that there is a relation of hydrostatic pressure to the gradient of capillary permeability(895). 

James Augustine Shannon (US), Norman  Jolliffee (US), Homer W. Smith (US), and Saul Fisher (US), in their studies of the kidney, developed a way to precisely measure the rate of formation of glomerular filtrate (i.e., the volume per unit time of plasma ultrafiltrate that, under the hydrostatic pressure in the arterial circulation, enters the kidney tubules and flows toward the urinary bladder) in a variety of species—amphibians, reptiles, birds, and mammals, including Homo sapiens. They went on to illuminate passive reabsorption from tubular lumen back across the tubular epithelium to the peritubular blood, simple diffusion along a chemical concentration gradient of urea created by the reabsorption of water, active reabsorption, and active secretion(896-907). See, Eli Kennerly Marshall, Jr., 1923, and Joseph Treloar Wearn, 1924.

James Augustine Shannon (US), Saul J. Farber (US), and Leonard Troast (US) determined the transport maximum (Tm) for glucose in the normal dog kidney tubule. The value was found to be stable over months and not influenced by blood levels of glucose or insulin. They proposed that it be used as a marker of reabsorption capacity(908).

Allen Dudley Keller (US) and William Kendrick Hare (US) gave the heat regulating function of the brain a more precise location in the hypothalamus(909).

James Gray (GB) produced three papers which represent the cornerstone of our understanding of aquatic locomation by animals(910-912).

Burrill Bernard Crohn (US), Leon Ginzburg (US), and Gordon D. Oppenheimer (US) described Crohn’s disease, a disease of the terminal ileum, affecting mainly young adults, characterized by a subcutate or chronic necrotizing and cicatrizing inflammation(913).

Antoni Lesniowski (PL), among others, had previously reported this condition(914).

Marius von Senden (DE) reported that if congenital cataracts in children were removed then replaced by glass lenses the return to vision was long and arduous even though the retina seemed perfectly normal. Return to normal vision was exceptional(915, 916). 

Walther Kikuth (DE) introduced atebrin (mepacrine) for the treatment of malaria(917)(Kikuth 1932).

Jan Friedrich Tönnies (DE) developed the multichannel ink-writing EEG machine(918, 919). 

Alfred Bielschowsky (DE-US) wrote Die Lähmungen der Augenmuskeln, a standard work on motility disturbances of the muscles of the eye(920).

Edgar Alphonso Hines, Jr. (US) and George Elgie Brown (US) introduced a test designed to detect latent states of hypertension(921). It became known as the Hines-Brown test.

Albert S. Hyman (US) is credited with originating the concept of the artificial heart pacemaker. He stimulated the heart in animal experiments by inserting a transthoracic needle into the right ventricle, the other end of which was attached to a mechano-electrical pacemaker. He later employed the same technique in a human patient(922).

John Alexander Hopps (CA) devised a cardiac pacemaker. Hopps was trained as an electrical engineer at the University of Manitoba and joined the National Research Council in 1941, where he conducted research on hypothermia. While experimenting with radio frequency heating to restore body temperature, Hopps made an unexpected discovery: if a heart stopped beating due to cooling, it could be started again by artificial stimulation using mechanical or electric means.

Wilfred Gordon Bigelow (CA), John C. Callaghan (CA), and John Alexander Hopps (CA) developed and tested the first artificial cardiac pacemaker for human use(923, 924). This device was far too large to be implanted inside of the human body. It was an external pacemaker.

Paul Maurice Zoll (US) used the application of electric stimuli from an artificial external cardiac pacemaker by way of subcutaneous needle electrodes to produce effective ventricular beats in 2 patients with ventricular standstill after complete heart block(925). Some consider this the invention of the cardiac pacemaker. Dr. Zoll's later studies showed that externally applied, alternating current counter shocks are similarly effective in stopping ventricular fibrillation, and also in correcting a number of other serious, potentially lethal, abnormalities of rhythm. He developed the theory and technique of continuous cardiac monitoring of heart rhythm, and was the first to apply this method clinically.

Earl E. Bakken (US), in 1957, at the suggestion of Clarence Walton Lillehei (US) developed the world's first transistorized, battery-powered, external, wearable cardiac pacemaker. Very shortly thereafter Clarence Walton Lillehei (US), Vincent L. Gott (US), Paul Chesley Hodges (US), and David M. Long (US) installed this pacemaker on a patient to treat complete atrioventricular dissociation(926). This gave patients mobility and eliminated concerns about a power failure.  Bakken later formed the Medtronics Corporation which developed the first fully implantable, self-contained, transistorized, wearable, battery operated pacemaker in 1960.

Rune Elmquist (SE) developed the first fully implantable pacemaker. Ake Senning (SE), on 10/8/1958, implanted this devise into Arne H.W. Larsson (SE) who suffered from up to twenty fainting attacks per day(927). Mr. Larsson died on 12/38/2001.

William Chardack (US), Andrew Gage (US), and Wilson Greatbatch (US), devised a workable transistorized, implantable, pacemaker using primary cells as a power source. It was known as the Chardack-Greatbatch implantable pacemaker. It was the first to be implanted in a patient with AV block(928)(Greatbatch 1960).

Yves Bouvrain (FR) and Fred I. Zacouto (FR) described a combination of devices they called a “resuscitation device”. This consisted of a heart monitor, a defibrillator, and a pacemaker(929).

Orestes Fiandra (UY) and Roberto Rubio (UY), in February 1960, inserted a totally implantable pacemaker into a 34 year old patient with AV block. Its battery life was approximately 12-18 months(930).

David A. Nathan (US), Sol Center (US), Chang-You Wu (US), and Walter Keller (US) reported the first implantable atrial-synchronous ventricular pacemaker (VAT), which sensed atrial activity and paced the ventricle accordingly(931).

Heinz-Joachim Sykosch (DE), Sven Effert (DE), K.G. Pulver (DE), and Fred I. Zacouto (FR) introduced the ventricular demand pacemaker (VVI)(932).

Philippe Coumel (FR), Christian Cabrol (FR), Alexandre Fabiato (US), René Gourgon (FR), and Robert D. Slama (US)  used programmed atrial and ventricular stimulation to unravel the mechanism and diagnosis of permanent junctional reciprocating tachycardia in a drug-refractory patient. They showed that tachycardia was sustained by a reentrant or reciprocal rhythm, then postulated that the process involved dual AV nodal pathways with a slow conducting retrograde pathway. They installed a permanent bipolar pacemaker in such a way as to relieve the tachycardia(933). 

Barouh V. Berkovits (US), Agustin Castellanos, Jr. (US), Louis Lemberg (US), George Callard (US), and James R. Jude (US) introduced the bifocal pacemaker(934).

Mieczyslaw Mirowski (PL-IL-US), Morton M. Mower (US), Alois A. Langer (US), and Marlin Stephen Heilman (US) designed the first automatic implantable defibrillator(935, 936).

Mieczyslaw Mirowski (PL-IL-US), Philip R. Reid (US), Morton M. Mower (US), Levi Watkins, Jr. (US), Vincent L. Gott (US), James F. Schauble (US), Alois A. Langer (US), Marlin Stephen Heilman (US), Steven A. Kolenik (US), Robert E. Fischell (US), and Myron L. Weisfeldt (US) implanted the first automatic implantable cardioverter/defibrillator into a human. This was done to terminate a malignant ventricular arrhythmia(937).

Hermann D. Funke (DE) introduced the first DDD pacemaker, a device that senses intrinsic activity in the atrium as well as the ventricle, and can likewise pace both chambers(938).

Benjamin Befeler (US), Barouh V. Berkovits (US), Juan M. Aranda, Jr. (US), Ruey J. Sung (US), Federico Moleiro (VE), and Agustin Castellanos, Jr. (US) performed a biventricular stimulation in humans by using a QRS triggered pacemaker connected by way of the great or middle cardiac veins(939).

Alexander Wirtzfeld (DE), Thomas Bock (DE), Anthony Francis Rickards (GB), Fawaz Akhras (GB), and David W. Barron (GB) were among the first to introduce a pacemaker capable of responding to a changing biological variable(940, 941).  

Eric F.D. Wever (NL), Richard N.W. Hauer (NL), Frans J.L. Capelle (NL),  Jan G.P. Tijssen (NL), Harry J.G.M. Crijns (NL), Ale Algra (NL), Ans C.P. Wiesfeld (NL), Patricia F.A. Bakker (NL) and Etienne O. Robles de Medina (NL) demonstrated the clinical benefit of biventricular pacing in patients who have survived heart failure(942).

Werner Jung (DE) and Berndt Lüderitz (DE) successfully installed an implantable atrial defibrillator in a 64-year old female patient with symptomatic, drug-refractory atrial fibrillation(943).

Werner Jung (DE) and Berndt Lüderitz (DE) successfully installed an implantable atrioventricular defibrillator in a 61-year-old female patient. This device automatically detects atrial and ventricular signals and delivers electrical therapy in the appropriate chamber to terminate the arrhythmia(944).

John Burdon Sanderson Haldane (GB) points out the importance of knowledge about the age/stage of gene expression - gametophytes and gametes to zygotes, embryos and immature and mature organisms in evolutionary studies(945).

1933

“If all the arts aspire to the condition of music, all the sciences aspire to the condition of mathematics.” George Santayana(946).

“It is common sense to take a method and try it. If it fails, admit it frankly, and try another. But by all means, try something.” Franklin D. Roosevelt, Fireside Chat, March 12, 1933.

Thomas Hunt Morgan (US) was awarded the Nobel Prize in Physiology or Medicine for his discoveries concerning the role played by the chromosome in heredity.

Georges Edouard Lemaitre (BE) proposed the Big Bang theory of the origin of the universe. He visualized a primal atom, an incredibly dense egg containing all the material for the universe within a sphere about 30 times larger than the Sun. This primal atom exploded some 20-60 Ga scattering matter and energy in all direction(947, 948).

Niels Henrik David Bohr (DK) introduced the idea of complementarity to biology. All properties of physical entities exist only in pairs, which Bohr described as complementary or conjugate pairs (which are also Fourier transform pairs). Physical reality is determined and defined by manifestations of properties which are limited by trade-offs between these complementary pairs(949).

John Desmond Bernal (GB) and Ralph Fowler (GB) created their model of the structure of liquid water(950).

John Desmond Bernal (GB) and Helen Dick Megaw (IE) introduced the notion that hydrogen atoms in bulk liquid water can jump in concerted fashion between the two oxygen atoms that they link together(951). 

Dinitrophenol compound was introduced in France as a herbicide for the control of annual broadleaf weeds in cereals. ref

Roger J. Williams (US), Carl Morris Lyman (US), George H. Goodyear (US), John H. Truesdail (US), and Duncan Holaday (US) discovered and partially synthesized pantothenic acid (vitamin B5)(952).

Reginald William Herbert (GB), Edmund Langley Hirst (GB), Edmund George Vincent Percival (GB), Reginald John William Reynolds (GB), and Fred Smith (GB) determined the structure of ascorbic acid (vitamin C)(953).

Tadeus Reichstein (PL-CH), Andreas Grüssner (CH), Rupert Oppenauer (CH), R.G. Ault (GB), D.K. Baird (GB), H.C. Carrington (GB), Walter Norman Haworth (GB), Reginald William Herbert (GB), Edmund Langley Hirst (GB), Edmund George Vincent Percival (GB), Fred Smith (GB) and Maurice Stacey (GB) synthesized ascorbic acid (vitamin C)(954-957).

André Félix Boivin (FR) Ion Mesrobeanu (RO), and Lydia Mesrobeanu (RO) developed a method for isolating endotoxin(958).

André Félix Boivin (FR) discovered that the somatic antigen (endotoxin) is present in all Enterobacteriaceae regardless of their pathogenicity(959).

Rudolf Schoenheimer (DE-US) and Fritz Breusch (DE-US) concluded that cholesterol is continually destroyed as well as formed in the animal body(960).

Karl Lohmann (DE) discovered glucose-6-phosphate isomerase, one of the phosphoglucose enzymes which were subsequently found to catalyze the breakdown of sugar phosphates according to the glycolytic scheme(961).

Morna MacLeod (GB) and Robert Robison (GB) isolated fructose-1-phosphate from the partial hydrolysis of fructose diphosphate by bone phosphatase(962).

Jakov Borissovich Goldman (RU) developed a method for staining lipids in histologic slides and peripheral blood films using Sudan III(963).

William Smith Tillett (US) and Raymond L. Garner (US) found that certain strains of hemolytic streptoccci produce a substance capable of inciting the rapid fibrinolysis of human plasma clots. They named the lytic agent fibrinolysin(964-966). This represents the beginning of investigations of streptokinase.

Haskell Milstone (US) suggested that a plasma factor, which he called plasma lysing factor, is responsible for streptococcal mediated fibrinolysis(967).

L. Royal Christensen (US) and Colin Munro MacLeod (US) were able to describe the entire mechanism of streptococcal fibrinolysis. They showed that human plasma contains the precursor of an enzyme system, which they called plasminogen, and that the streptococcal fibrinolysin, which they named streptokinase, is an activator which can convert plasminogen to the proteolytic and fibrinolytic enzyme plasmin(968-970). 

Stuart D. Elliott (US) was the first to extract streptokinase and its proenzyme (zymogene) in the crystallyzed form(971).

William Smith Tillett (US), Alan J. Johnson (US), and W. Ross McCarty (US) achieved an intravascular lytic state in man following streptokinase administration(972).

Sol Sherry (US) started using streptokinase in patients with acute myocardial infarction and changed the focus of treatment from palliation to “cure”(973).

Streptokinase (SK) has been used in medicine as fibrinolytic enzyme system - plasminogenous activator. SK is used for myocardial infarctions, vein thrombosis, lung artery emboly, occlusions of extremity arteries, retinal blood-vessel thrombosis and priapism.

Maurice W. Goldblatt (GB) and Ulf Svante von Euler (SE) independently discovered that extracts of human semen, monkey, sheep and goat seminal vesicular glands respectively cause contraction of smooth muscle in vitro and sharp decreases in the blood pressure in experimental animals(974-978). von Euler called these substances prostaglandins because they were mistakenly believed to be made in the prostate gland.

Lárus Einarson (DK) suggested that the chromatic material of the Nissl Granules or Bodies in neurons is formed around the nucleolus and then diffuses out into the cytoplasm(979).

Paul Runar Collander (FI) and Hugo Bärlund (FI) made quantitative measurements of cell membrane permeability to non-electrolytes of varying molecular size and lipid solubility. Their results contributed enormously to our understanding of membrane structure(980).

George Wald (US) found vitamin A (retinol) in the retina(981, 982).

George Wald (US) discovered retinene (retinal), an intermediate in the bleaching of rhodopsin, on the way to vitamin A (retinol). He concluded that rhodopsin in the retina, under the influence of light, engages in a cycle of reactions with retinene and vitamin A(983, 984).

George Wald (US) and Anna-Betty Clark (US) presented evidence that visual purple is a conjugated protein in which vitamin A (retinol) is a prosthetic group(982, 985).

George Wald (US) discovered that visual pigment from freshwater fish differs from that of mammnals, birds, amphibia, and marine fish. He named it porphyropsin(986, 987).

George Wald (US), Paul K. Brown (US), and Patricia H. Smith (US) determined that all known visual pigments are built upon a common plan. Retinal is bound as chromatophore to a type of protein, called an opsin, found in the outer segments of vertebrate rods and cones and the analogous rhabdomeres of invertebrates. There are four major pigments known in vertebrate vision: 1) retinal 1 + rod opsin = rhodopsin, 2) retinal 1 + cone opsin = iodopsin, 3) retinal 2 + rod opsin = porphyropsin, and 4) retinal 2 + cone opsin = cyanopsin(988-990).

Sadie Brenner (US), Lydia J. Roberts (US), John Elliott Dowling (US), and George Wald (US) demonstrated that night blindness is the earliest manifestation of vitamin A (retinol) deficiency(991, 992). 

S. Ball (GB), Trevor Walworth Goodwin (GB), and Richard Alan Morton (GB) showed that retinine 1 is vitamin A aldehyde(993). Retinene was later renamed retinal and vitamin A renamed retinol.

George Wald (US) and Ruth Hubbard (US) demonstrated that the visible pigment (rhodopsin) from the cones of the eye contains a protein (opsin) in combination with retinene (retinal). Retinene is very similar in structure to vitamin A (retinol) and is formed from vitamin A in the body. When light strikes rhodopsin, the protein and the retinene separate; they recombine in the dark(994, 995).

Ruth Hubbard (US) and George Wald (US) identified the initial molecular event in vision by showing that when 11-cis retinal absorbs a photon, it is converted to the all-trans form(996).

Paul K. Brown (US) and George Wald (US) demonstrated that two different proteins, two opsins, are needed to form the red- and green-sensitive pigments suggesting that two genes are involved in red- and green-blindness(997).

William B. Marks (US), William H. Dobelle (US), Edward F. MacNichol (US), Paul K. Brown (US), and George Wald (US) found that primate retinas possess, in addition to rod cells with their rhodopsin, three kinds of cone cells, blue-, green- and red sensitive, each containing predominantly or exclusively one of three color pigments with maximum absorption at 435, 540, and 565 micrometers respectively(998, 999).

George Wald (US) predicted that light activated rhodopsin might trigger a cascade of reactions much like the blood clot cascade(1000).

George Wald (US) discovered the primary event in vision to be when light triggers visual excitation by isomerizing the 11-cis retinal chromophore of visual pigments to the all-trans form(1001-1003).

Moses Kunitz (RU-US) and John Howard Northrop (US) were the first to crystallize the enzyme chymotrypsin and its precursor chymotrypsinogen. They isolated and crystallized a new protein from the pancreas. It separated as elongated prisms and had no proteolytic action. However, when acted upon by a trace of active trypsin it was converted into a second protein, crystallizing in plates, which had a proteolytic activity about a third as great as crystalline trypsin-1. The new enzyme had less hydrolytic action on gelatin than trypsin-1, but had a powerful action on coagulating milk. They called the inactive form chymotrypsinogen and the trypsin activated form chymotrypsin(1004, 1005). They also isolated and crystallized trypsinogen, a trypsin inhibitor, and an inhibitor-trypsin compound(1006).

Roger John Williams (US), Carl M. Lyman (US), George H. Goodyear (US), John H. Truesdail (US), Duncan Holaday (US), Donald Herbert Saunders (US), Harry H. Weinstock, Jr. (US), Ewald Rohrmann (US), Hershel K. Mitchell (US), and Curtis B. Meyer (US) separated and named pantothenic acid (Greek pantos or pan meaning ubiquitous), vitamin B5, from other components of extracts of natural foods, secured a concentrated preparation of the acid, validated it as a vitamin using a yeast strain, found its approximate molecular weight and ionization constant, and further characterized its chemical properties. They isolated it as a pure calcium salt of the acid(952, 1007-1009).

Richard Johann Kuhn (AT-DE), Paul György (HU-DE-GB-US), and Theodor Wagner-Jauregg (DE) discovered riboflavin (vitamin B2 or vitamin G)(1010, 1011).

Franklin E. Allison (US), Sam R. Hoover (US), and Dean Burk (US) isolated a vitamin which is an indispensable nutrient for Rhizobium spp. They named the vitamin coenzyme R (biotin)(1012).

Fritz Kögl (NL) and Benno Tönnis (NL) isolated and crystallized a vitamin from the boiled yolks of duck eggs. They named it biotin(1013).

Paul György (HU-DE-GB-US) and Thomas William Birch (US) isolated a vitamin in pure form which would cure raw egg white injury (harm done when raw egg whites are the sole protein source in a diet). They named it vitamin H (biotin)(1014, 1015).

Paul György (HU-DE-GB-US), Donald B. Melville (US), Dean Burk (US) and Vincent du Vigneaud (US) proved that vitamin H, biotin, and coenzyme R are one and the same substance(1016).

Carl Alexander Neuberg (DE) and Maria Kobel (DE) demonstrated that phosphoglyceric acid is converted to pyruvic acid and phosphoric acid by Lactobacillus delbruckii(1017). 

Dietrich Hans Franz Alexander Bodenstein (DE-US), working with caterpillars of the butterfly Vanessa urticae, concluded that the time course of molting is not determined by autonomous changes in the hypodermis, but rather that factors situated elsewhere within the caterpillar, most likely blood borne hormones, determine the time course of molting(1018).

Evelyn Mary Anderson (CA) and James Bertram Collip (CA) were the first to successfully isolate a tropic substance. It was thyrotropic hormone (TSH) from the anterior pituitary gland(1019).

James Bertram Collip (CA), Evelyn Mary Anderson (CA), and David Landsborough Thomson (GB-CA) prepared and tested extracts from the anterior pituitary gland and found that they contained a potent adrenotropic hormone (ACTH)(1020).

James Bertram Collip (CA), Hans Hugo Bruno Selye (AT-HU-CA), and David Landsborough Thomson (GB-CA) purified a highly potent extract of growth hormone (somatotropic hormone/STH) from the anterior pituitary lobe(1021).

Gustav Georg Embden (DE), Hans-Joachim Deuticke (DE), and Gert Kraft (DE) proposed that in muscle cell glycolysis, fructose-1,6-diphosphate is cleaved directly to glyceraldehyde-3-phosphate and dihydroxyacetone phosphate. These products were considered to undergo a Cannizzaro (mutase) reaction to yield 3-phosphoglycerol and 3-phosphoglyceric acid, and the latter was thought to be converted into pyruvic acid and phosphate. A second mutase reaction between pyruvic acid (which is reduced to lactic acid) and phosphoglycerol (which is oxidized to glyceraldehyde-3-phosphate) completed the balance of equations, and provided for the conversion of all the hexose into lactic acid(1022).

Gustav Georg Embden (DE), Hans-Joachim Deuticke (DE), and Gert Kraft (DE) proposed a anaerobic glycolytic scheme within muscle cells which begins with the conversion of hexosediphosphate into triosephosphate which, by the oxidation reduction process, yields alpha-phosphoglycerol plus 3-phosphoglyceric acid; phosphoglyceric acid breaks down to pyruvic and phosphoric acids. In muscle extract, pyruvic acid is reduced to lactic acid at the expense of the phosphoglycerol which is oxidized to triosephosphate. In yeast juice, pyruvic acid is converted by carboxylase into carbon dioxide plus acetylaldehyde. The latter was then believed to take part with glucose and inorganic phosphate in a rapid reaction in which hexosediphosphate plays the part of a catalyst and phosphorylation is coupled with an oxidation-reduction; the primary esterification product is oxidized to phosphoglyceric acid while the acetylaldehyde is reduced to alcohol(1022). This evidence suggested that it is pyruvic rather than lactic acid which represents the true end product of anaerobic glycolysis.

Otto Fritz Meyerhof (DE-US) offered proof that, in isolated but otherwise intact frog muscle, the lactic acid formed is reconverted to carbohydrate in the presence of oxygen. He also prepared a KCl extract of muscle which could carry out all the steps of glycolysis with added glycogen and hexose-diphosphate in the presence of hexokinase derived from yeast. In this system glucose was also glycolysed and this was the foundation of the Embden-Meyerhof-Parnas theory of glycolysis (glyco, sugar; glykis, sweet). The specific sequence of reactions from glucose to pyruvate is often called the Embden-Meyerhof-Parnas pathway(1023-1026). In the 1935c article give the first description of phosphoglyceric acid mutase (phosphoglycerate mutase).

Otto Fritz Meyerhof (DE-US) and Wilhelm Kiessling (DE) isolated alpha-glycerophosphoric acid from a reaction mixture of animal muscle and either glycogen or hexose-phosphate(1027-1030).

Otto Fritz Meyerhof (DE-US) and Wilhelm Kiessling (DE) published a detailed study of the intermediary phases of fermentation in yeast juice(1028).

Otto Fritz Meyerhof (DE-US) worked out the chemical scheme of the cellular breakdown of sugar into alcohol(1030).

Ernst Wolfgang Caspari (DE-US), working with the flour moth Ephestia kuhniella Zeller, provided an example of how a gene can control hormone action during development(1031, 1032).

Bryan H.C. Matthews (GB) described nerve endings in mammalian muscle(1033).

Richard Benedikt Goldschmidt (DE-US) interbred various geographical races of the gypsy moth, Lymantria dispar. The moths that resulted from this cross showed that characters distinguishing local varieties are transmitted to the offspring and, therefore, can be explained in terms of Mendelian laws as being determined by genes. This was the first genetic explanation of geographic variety(1034).

Teikichi Fukushi (JP) was the first to provide experimental evidence of plant virus multiplication in insects. He was also the first to demonstrate transmission of a plant virus through the eggs of the vector (transovarial passage)(1035-1037).

Richard E. Shope (US) and E. Weston Hurst (US) discovered the cottontail rabbit papillomavirus (CRPV)(1038).

Ralph S. Muckenfuss (US), Charles Armstrong (US), and Howard A. McCordock (US) proved that the etiological agent of St. Louis encephalitis is a virus. They successfully infected monkeys with the virus of St. Louis encephalitis by intracerebral inoculation with human brain tissue from a patient who had succumbed to the disease(1039).

F.M. Muller (NL) reported on the anaerobic use of organic sources of reducing power by the purple sulfur photosynthetic bacteria. Growth was accompanied by the production or utilization of CO2 depending on the ‘redox level’ of the organic substrate(1040).

Ernest Witebsky (DE-US) and Werner Henle (DE) discovered that bacteria indistinguishable morphologically and in culture can be subdivided by immunological tests(1041).

Arthur T. Hendrici (US) noted the tendency of aquatic bacteria to colonize submerged surfaces (1042).

Robert E. Foster (US) and Carlton Earl Burnside (US) described a new disease found within broods of the honeybee, Apis mellifera Linn., which they named parafoulbrood(1043). In 1935, they named and identified the etiological agent Bacillus para-alvei.

Alexander Thomas Glenny (IE), Mollie Barr (GB), Mona Llewellyn-Jones (GB), Sir Thomas Dalling (GB), and Helen E. Ross (GB) discovered that the alpha toxin of Clostridium perfringens type A contains lethal, hemolytic, and necrotic activities(1044).

Roger-Jean Gautheret (FR) reported a 50 to 150 fold increase in initial length of 0.5 to 1.0 mm excised tips of corn roots cultured 3 months in a dilute Knop's solution containing, 2% glucose and cysteine hydrochloride(1045)(Gautheret 1933).

Philip Rodney White (US) obtained potentially unlimited growth of excised tomato root tips in a liquid medium(1046).

Fritz Kögl (NL), Arie Jan Haagen-Smit (NL), Hanni Erxleben (NL), Désiré George Florent Rudolphe Kostermans (NL), Kenneth Vivian Thimann (GB-US), and Joseph B. Koepfli (US) identified the first known plant hormone—indoleacetic acid (IAA)(1047-1049).

James Frederick Bonner (US) discovered that the most important growth constituent of the yeast extract is thiamine (vitamin B1) and subsequently White found that the effect of the yeast extract could be obtained by substituting the B-group—thiamine, pyridoxine and niacin—instead(1050). 

Roger-Jean Gautheret (FR) successfully cultured wound tissue or callus from the excised cambial tissue of Salix capraea and Populas alba. He used nutrient media solidified with agar but found that after 6 months the activity of the cultures ceased(1051)(Gautheret 1934). By including indoleacetic acid (IAA) and the vitamins B in his media Gautheret extended the culture period of the Salix callus to 18 months and was able to subculture. However after 18 months once again growth ceased.

George Robert Sabine Snow (GB) demonstrated that indoleacetic acid stimulates cell division within the cambium layer(1052).

Roger-Jean Gautheret (FR), Philip Rodney White (US), and Pierre Nobécourt (FR), had by 1939, independently established long-lived cultures of carrot root, carrot (Daucus carotus), and tobacco (Nicotiana tabacum) respectively(1053-1056).

Frederick Campion Steward (GB-US), Marion O. Mapes (US), Jakob Reinert (DE), Kath Mears (US), and Lawrence M. Blakely (US) showed that in vitro plant culture can, starting with one carrot cell, produce a callus and from it a new carrot plant (Daucus carotus)(1057-1059).

Hiroyuki Kato (JP) and Masayuki Takeuchi (JP) obtained a complete carrot plant (Daucus carotus) from a single carrot root cell in tissue culture(1060).

Toshiyuki Nagata (JP) and Itaru Takebe (JP) showed that protoplasts isolated enzymatically from tobacco (Nicotiana tabacum) leaves regenerated cell walls and divided to form cell clusters under suitable conditions. Plants were developed from the cell clusters(1061, 1062).

H.J. Gambow (), K.N. Kao (CA), Raymond A. Miller (CA), and Oluf L. Gamborg (DK-CA) developed whole carrot plants (Daucus carotus) from carrot protoplasts(1063).

H.J. Wilson (US), Herbert W. Israel (US), and Frederick Campion Steward (GB-US) developed methods to grow whole carrots (Daucus carotus) from single carrot cells rather than from the seed(1064).

Nikolai Wladimirovich Timoféeff-Ressovsky (RU) experimentally measured the viability of strains of Drosophila funebris of different geographical origin.

Alexander Ivanovitch Petrunkevitch (RU-US) wrote, An Inquiry Into the Natural Classification of Spiders, Based on a Study of Their Internal Anatomy which is the first comparative anatomy for any group of arthropods that can be used in classification(1065).

Johannes Friedrich Karl Holtfreter (DE-US)) performed experiments where gastrula tissue from young embryos was transplanted into ectoderm of older embryos. He found that the reacting tissue developed according to its surroundings. The conclusion is that the whole is controlling the events in its parts(1066-1068).

Johannes Friedrich Karl Holtfreter (DE-US) performed exogastrulation studies wherein the dorsal mesoderm failed to make contact with the overlying ectoderm. In these instances, the ectoderm did not acquire a neural character, again suggesting that the inducing signal appeared to be transmitted vertically from the mesoderm to the ectoderm(1069).

Conrad Hal Waddington (GB), Noel Joseph Terence Montgomery Needham (GB), Dorothy Moyle Needham (GB), Wiktor W. Nowinski (US), and Max Rudolf Lemberg (DE) showed that the ether extracts of adult newts could act as an organizer. Since this activity could turn presumptive epidermis into non-specific neural tissue. Waddington referred to this substance as evocator(1070, 1071).

Conrad Hal Waddington (GB), Noel Joseph Terence Montgomery Needham (GB), and Jean Louis Auguste Brachet (BE) hypothesized that the evocator substance was produced throughout the embryo, but it was just released or activated in one particular region(1072).

Jean Louis Auguste Brachet (BE), Taina Kuusi (FI), and Simone Gothie (BE) suggested that movements of microsomes/ribosomes (which contain ribonucleic acid) from the archenteron roof to the overlying ectoderm are involved in neural induction(1073).

Lauri Saxén (FI) demonstrated that neural induction could occur through a 150 micron thick, 0.8 micron pore size filter, strongly suggesting that the inducer was diffusible(1074).

Scott F. Gilbert (US) reports that follistatin, chordin, noggin, Xenopus nodal-related-3, and cerberus all have organizer function(1075).

Aaron Bodansky (RU-US), Lois F. Hallman (US), and Kissel Bonoff (US) described the factors which influence accuracy during the determination of serum phosphatase(1076). Elevated levels of this enzymes can be a useful index of abnormal conditions in certain tissues. 

Rudolpho Margaria (IT), Harold T. Edwards (US), and David Bruce Dill (US) defined the components of the oxygen debt and described what become known as the anaerobic threshold, i.e., the rate of appearance of lactic acid in the blood and its influence on ventilation during exercise(1077).

Karl Landsteiner (AT-US) and James van der Scheer (US), discovered that antibodies can be formed to and subsequently bind with exquisite specificity to completely synthetic compounds(1078, 1079).

Lionel Sharples Penrose (GB) was the first to show the significance of the mother’s age in Down’s syndrome. He determined that birth order, parity, and length of interval between pregnancies are not significant etiological factors(1080).

John Burdon Sanderson Haldane (GB-IN) suggested that the immune response of mice allowing them to reject tumors which arose in a different strain would be directed against normal cellular antigens unique to that strain rather than against tumor-specific antigens unique to the tumor(1081).

Louis Barkhouse Flexner (US) proved that cerebro-spinal fluid is produced by a secretory process in the choroid plexuses(1082, 1083).

Cicely D. Williams (GB) described a nutritional disease among the children of the Gold Coast of Africa which the natives called Kwashiorkor, meaning the red or brown boy. The symptoms of the disease are: (1) edema of the hands and feet, (2) profound wasting, (3) dry, scaly skin with patches devoid of pigmentation, (4) hair which is dry, sparse, and often a dull reddish, muddy color, (5) diarrhea and irritability, (6) fatty degeneration of the liver at necropsy. The disease was common to children between one and four years of age who typically had been weaned following a long period of breast feeding. The diet of these children was mostly cereal, maize, with no milk(1084, 1085).

Joseph Clarence Hinsey (US) and Joseph E. Markee (US) proposed that “pathways from the hypothalamus must activate the posterior lobe of the hypophysis which in turn may exert an influence on the anterior lobe by hormonal transamission"(1086).

Joseph E. Markee (US), Charles Henry Sawyer (US), W. Henry Hollingshead (US), Geoffrey Wingfield Harris (GB), Barry Albert Cross (GB), John D. Green (GB), Bernard Dufy (FR), Luce Dufy-Barbe (FR), and Dominique Poulain (FR) later proved this experimentally(1087-1090).

Norman McOmish Dott (GB) performed the first planned intracranial operation for aneurysm(1091).

Andrei Vasilevich Martynov (RU) discovered the oldest undoubted fossils of Coleoptera (beetles) in Upper Permian deposits in North Russia(1092).

Jesse D. Figgins (US) found large, heavy fluted stone points near Clovis, New Mexico. They were accompanied by mammoth bones in a deposit beneath a layer containing Folsom points and bison skeletons. The robust points, now named Clovis, were recognized as even older than the Folsom points. Characteristic of both points is a flute, a flake struck off the base along the length of the point, presumably to facilitate hafting(1093).

In 1964, C. Vance Haynes, Jr. (US) used radiocarbon dating to place the Clovis points at about 9,500-9,000 B.C.E., and none before 10,000 B.C.E.

Rene Neuville (FR), in 1933, was the first to excavate fossil remains of  Homo sapiens sapiens. The source was a cave site near Nazareth, Israel, on the southwest flank of Mount Qafzeh(1094). Subsequently more human fossil remains have been discovered at this site, all dated ca. 100,000 B.P.

1934

"No single feature of man's past equals in importance his attempt to understand the forces of Nature and himself. It is a safe prediction that the historian of the future will be concerned increasingly with the chronicle of the intellectual acquisitions of man, for this deeper story includes not merely improvement in material comforts but mental enlargement which transcends every other feature of human evolution." Herbert McLean Evans(1095).

"Long ago I learned from my father to put old people to bed only for as short a time as was absolutely necessary, for they were like a foundered horse, if they got down it was difficult for them to get up, and their strength ebbed away very rapidly while in bed." Charles Horace Mayo(1096). 

Harold Clayton Urey (US) was awarded the Nobel Prize in Chemistry for his proof that hydrogen gas contains a few atoms in which the nuclear proton is accompanied by a neutron. This so called “heavy hydrogen” was given the name deuterium.

George Hoyt Whipple (US), George Richards Minot (US) and William Parry Murphy (US) were awarded the Nobel Prize in Physiology or Medicine for their discoveries concerning liver therapy in cases of anemia.

Irène Joliot-Curie (FR), Hans von Halban (AT), Peter Preiswerk (CH) and Frédéric Joliot (FR) discovered that radioactivity can be induced artificially using alpha ray bombardment from radium. This methodology rapidly made available such valuable isotopes as 32P and 35S(1097-1099).

Marcus Laurence Oliphant (AU), Paul Harteck (GB), and Sir Ernest Rutherford (NZ-GB) bombarded deuterium with the nuclei of deuterium atoms and produced tritium (hydrogen-3), the only radioactive form of hydrogen known. Tritium is much used in biochemical research(1100).

The first organic fungicide dithiocaramae was introduced. It proved valuable in foliar sprays for the control of a range of pathogenic fungi such as the scabs and rots of fruit and potato blight. ref

John Desmond Bernal (GB), and Dorothy Mary Crowfoot-Hodgkin (GB) were the first to take an x-ray diffraction photograph of a crystalline protein. It was of the enzyme pepsin(1101).

Dorothy Mary Crowfoot Hodgkin (GB) used x-rays crystallography to illuminate the structure of the protein, insulin(1102).

Alfred Clarence Redfield (US) discovered that the atomic ratios between the chemical components of marine plankton, specifically nitrogen, phosphorus, and carbon are identical with their relative proportions in the open ocean. For every atom of phosphorus there are fifteen atoms of nitrogen and 105 atoms of carbon (carbonate and bicarbonate carbon are not considered organic)(1103).

Karl Meyer (US) and John W. Palmer (US) isolated hyaluronic acid in pure form from vitreous humor, and determined its correct composition(1104).

Sir Robert Robinson (GB) hypothesized that cholesterol is formed by the cyclization of squalene, a polyisoprenoid hydrocarbon(1105). See, E.A. Rudolph, 1925.

A.P. Kiesel (RU) and Andrei Nikolaevitch Belozerskii (RU) were the first to isolate thymine and then DNA (thymonucleic acid) from higher plants(1106, 1107).

Andrei Nikolaevitch Belozerskii (RU) and I.I. Dubrovskaya (RU) isolated DNA in the pure state for the first time(1106).

Leopold Stefan Ruzicka (HR-CH), Moses Wolf Goldberg (EE), Jules Meyer (), Heinrich Brüngger (CH), and E. Eichenberger () synthesized the sex hormone androsterone from epidihydrocholesterol. This was not only the first synthesis of a sex hormone, but also the first complete structural elucidation of such a compound, and the first exact proof of the relationship between a sex hormone and a sterol(1108).

Hans Andersag (DE) discovered chloroquine, long the drug of choice in treating malaria(1109).

Hans Lineweaver (US) and Dean Burk (US) determined that if the reciprocal of the velocity of an enzyme catalyzed reaction is plotted against the reciprocal of the substrate concentration a straight line is obtained, and that this cuts the two axes at the reciprocal of V (velocity) and the reciprocal of Km respectively. This is commonly referred to as a Lineweaver-Burk plot(1110). Curiously enough this type of plot was first published in Kurt Guenter Stern’s German translation of John Burdon Sanderson Haldane’s book Enzymes (1932) where it was credited to Barnet Woolf (GB). Woolf likely failed to publish due to illness.

John R. Marrack (GB) proposed the lattice theory of antigen-antibody coupling with its fundamental requirement that antibody must have at least two antigen-combining sites(1111).

Adolf Friedrich Johann Butenandt (DE) and Ulrich Westphal (DE), Willard Myron Allen (US), Oskar Wintersteiner (US), Max Hartmann (CH), Albert Wettstein (CH), Karl Heinrich Slotta (DE), Heinrich Ruschig (DE), and Erich Fels (DE) isolated and characterized progesterone in pure form(1112-1116).

Russell Earl Marker (US) and John Krueger (US), in 1939, developed a method for synthesizing progesterone in large quantities from fats and oils of plants. They developed the process, initially for Parke Davis and Co., for degrading sapogenins to C21 steroids(1117). This process was applied by Marker, in 1941, to convert diosgenin from the wild Mexican yam into progesterone.

Sir Vincent Brian Wigglesworth (GB) proved by experiment that during larval stages the corpus allatum (corpora allata) secretes a metamorphosis hormone, commonly called the juvenile hormone or neotenin, or youth substance. Under the influence of this hormone the larval characters are retained. When the larva is fully grown, the corpus allatum (corpora allata) no longer secretes the hormone, the adult characters are developed, and metamorphosis occurs. His experimental animal was the large South American blood-sucking hemipteran Rhodnius prolixus(1118-1120). This physiological behavior has now been shown in almost all groups of insects.

Sir Vincent Brian Wigglesworth (GB) found that the metamorphosis hormone is not genus specific and that egg formation in Rhodnius is dependent on the secretory function of the adult corpus allatum (corpora allata)(1121).

Jean-Jacques Bounhiol (FR) discovered that removal of the corpus allatum (corpora allata) results in precocious metamorphosis of the immature larval insect(1122). By removing the corpus allatum (corpora allata) a conservative factor or status quo hormone—whose function is to stabilize the larval tissues as larval tissues and the imaginal discs as imaginal discs—is removed. This status quo hormone became known as the juvenile hormone.

Sir Vincent Brian Wigglesworth (GB) used implantation experiments to show that protocerebral neurosecretory cells are the source of the insect hormone that initiates the molting cycle(1123). This was the first experimental demonstration of an endocrine role for neural cells in any animal.

Edward Calvin Kendall (US), Harold L. Mason (US), Bernard F. McKenzie (US), Charles S. Myers (US), and Giles A. Koelsche (US) isolated and crystallized the adrenal cortical hormone, cortisone(1124).

Harold L. Mason (US), Charles S. Myers (US), and Edward Calvin Kendall (US) were the first to separate cortisone as a new compound(1125).

Tadeus Reichstein (PL-CH), Oscar Paul Wintersteiner (US), Joseph J. Pfiffner (US), Harold L. Mason (US), Willard M. Hoehn (US), and Edward Calvin Kendall (US) determined the chemical structure of cortisone(1126-1128).

Note: During the period 1934-1936, the Kendall group, the Reichstein group, and the Pfiffner-Swingle-Wintersteiner group were all purifying steroid hormones from the adrenal cortex. They were designating them with letters of the alphabet which created confusion because A in one group was not necessarily A in another group. The Kendall group isolated and crystallized five would be hormones. As the structure of these compounds was worked out, it became possible to name them. In the Kendall series Compound A is 11-dehydrocorticosterone, Compound B is corticosterone, Compound E is 17-hydroxy-11-dehydrocorticosterone (cortisone), and Compound F is 17-hydroxy-corticosterone (cortisol or hydrocortisone). In 1949, Edward Calvin Kendall (US), and Phillip Showalter Hench (US) gave the name cortisone to17-hydroxy-11-dehydrocorticosterone(1129).

Marguerite Steiger (CH) and Tadeus Reichstein (PL-CH) synthesized desoxycorticosterone(1130).

H. Reich () and Tadeus Reichstein (PL-CH) synthesized 11-dehydrocorticosterone(1131).

Lewis Hastings Sarett (US), working in the laboratory of Merck & Co., developed a method for synthesizing cortisone in quantities sufficient for clinical testing(1132).

Hans Hugo Bruno Selye (AT-CA) coined the group names glucocorticoids for the 11-oxy steroid hormones of the adrenal cortex and mineralocorticoids for the hormone(s) of the adrenal cortex affecting the metabolism of electrolytes and water. ref

Robert Russell Bensley (US) and Normand Louis Hoerr (US) used centrifugation to fractionate cell contents and isolate mitochondria(1133).

Jakub (Jacob) Karol Parnas (PL), Pawel Ostern (PL), and Thaddeus Robert Rudolph Mann (PL-GB) resolved that, “… the resynthesis of phosphocreatine and adenosine triphosphate (ATP) is not linked to glycolysis as a whole, but to definite partial processes: and this leads further to the conclusion that this resynthesis does not involve a relationship that might be termed energetic coupling, but more probably involves a transfer of phosphate residues from molecule to molecule.” In this article they describe for the first time the presence of pyruvate kinase (phosphoenol transphorylase) and the fact that it catalyzes the magnesium- and potassium-dependent transphorylation between phosphoenolpyruvate and ADP(1134).

Otto Fritz Meyerhof (DE-US) and Karl Lohmann (DE) isolated the enzyme from muscle extracts which cleaves fructose-1,6-diphosphate into two triose phosphates. They initially called it zymohexase but later Meyerhof, Lohmann, and Philipp Schuster (DE) changed it to fructose-biphosphate aldolase. They also recount their discovery of triose-phosphate isomerase(1026, 1135, 1136).

Paul K. Stumpf (US) purified and characterized plant aldolase(1137).

Karl Lohmann (DE) and Otto Fritz Meyerhof (DE-US) showed that the formation of pyruvic acid involves the enzyme catalyzed migration of the phosphoryl group from the 3-position to the 2-position of glyceric acid, followed by the dehydration of 2-phosphoglyceric acid to 2-phosphoenolpyruvic acid (PEPA) by the enzyme enolase (phosphopyruvate hydratase). This enzyme was found to be strongly inhibited by fluoride, thus explaining the effect of fluoride on alcoholic fermentation and glycolysis(1138). 

Otto Heinrich Warburg (DE) and Walter Christian (DE) isolated and crystallized the enzyme enolase (phosphopyruvate hydratase)(1139).

Wilhelm Kiessling (DE) found that a ketotriose identical to synthetic dihydroxyacetone phosphate is a reaction product when hexosediphosphate is split into two trioses(1140).

Harland Goff Wood (US) and Chester Hamlin Werkman (US) were the first to isolate and identify pyruvic acid as an intermediate in the propionic acid fermentation(1141).

Karl Lohmann (DE) used dialyzed muscle extracts and found that the hydrolysis of creatine phosphate to creatine and phosphate is promoted by the addition of ATP, which is cleaved to adenylic acid (adenosine monophosphate) and two equivalents of inorganic phosphate. He concluded that the ATP acts as a coenzyme in the hydrolysis of creatine phosphate. He identified ATP as the coferment (coenzyme) of lactic acid formation in muscle and determined that it required the presence of the magnesium ion(1142).

Isaac McKinney Lewis (US) measured the frequency of lactose-negative tolactose-positive mutations in Escherichia coli mutabile and found it to be on the order of one/hundred thousand cells/cell generation(1143).

Phineas W. Whiting (US), working with Habrobracon, was the first to study what would later be called conditional lethal mutants(1144).

Norman Harold Horowitz (US) and Urs Leupold (CH) were the first to isolate temperature-sensitive mutants of bacteria. Such mutants are only able to grow at temperatures lower than that at which the wild-type is able to grow(1145).

Ernst Hadorn (CH) coined the term conditional lethal mutant to describe mutants of Drosophila which were either lethal, or allowed relatively normal development to occur, depending upon the growth conditions imposed by the experimenter(1146).

Sir Henry Hallett Dale (GB) and Wilhelm Sigmund Feldberg (DE-GB) reasoned that the substance released by stimulated nerves which provokes the contraction of eserinized (eserine blocks acetylcholinesterase) leech muscle must be acetylcholine(1147). 

Ragnar Arthur Granit (FI-SE) and Per-Olof Therman (SE) established that details of the visual image are elaborated by the interplay of excitation and inhibition in the nervous center of the retina, i.e., that light can both excite and inhibit and that the two opposite processes are antagonistic. They did this by recording the mass discharge in the optic nerve together with the electroretinograph(1148, 1149).

Charles Armstrong (US), Ralph Dougall Lillie (US) appear to be among the first to describe an infection caused by the virus of lymphocytic choriomeningitis (acute aseptic meningitis, idiopathic meningitis). It appeared as a contaminant in monkeys inoculated with the virus of St. Louis Encephalitis(1150).

T.F. McNair Scott (US) and Thomas Milton Rivers (US) isolated and identified this virus from human cases(1151-1153).

Claud D. Johnson (US) and Ernest William Goodpasture (US) filtered the mumps agent through Berkefeld V and N filters then with the filtrate produced the disease in monkeys. This was proof that mumps (epidemic parotitis) is caused by a virus(1154).

Ivan Claude Jagger (US) and N. Chandler (US) were the first to describe the big vein disease of lettuce and reported that it was soil-borne and infectious(1155).

Carl Clarence Lindegren (US) found that in Neurospora all asci in a single perithecium arise from a single pair of nuclei associated at the initiation of the perithecium(1156).

Wendell H. Tisdale (US) and Ira Williams (US) working for the Du Pont Chemical Company discovered the dialkyldithiocarbamates as fungicides(1157). This group includes thiram, ferbam, maneb, zineb and mancozeb which are all surface acting agents.

Ladislaus Laszlo Marton (US), Stuart Mudd (US), and David Lackman (US) were among the first to publish electron photomicrographs of biological specimens in the United States(1158-1160). In 1937 Marton published the first electron micrograph of bacteria.

Arthur Felix (PL-GB) and Margaret R. Pitt (GB) discovered the heat labile Vi somatic antigen of the Salmonellae(1161).

Alice Catherine Evans (US), using the Clark phage which she renamed B563, was the first person to utilize a phage to classify bacterial strains, thus founding the analytical field of phage typing(1162).

Roy T. Fisk (US) developed the method of typing staphylococci with bacteriophages(1163).

Per Fredrik Thorkelsson Scholander (SE-NO-US) revised the lichen family, the Umbilicariaceae(1164).

Sanford B. Hooker (US) and Edna M. Follensby (US) discovered that the erythrogenic toxin of scarlet fever is really two closely related toxins which they called erythrogenic toxins A and B(1165).

Florence Barbara Seibert (US) prepared purified protein derivative (PPD) from tuberculin. This enabled the first reliable tuberculin test(1166).

Florence Barbara Seibert (US) and John T. Glenn (US) prepared a large batch of PPD that has served as the standard reference material (PPD-S) in the United States(1167).

Louis Alphonse Julianelle (US) and Charlotte W. Wieghard (US) introduced the first classification of the staphylococci based on differences in antigenic structure. They recognized two serological types of staphylococci based of specific carbohydrates obtained by chemical fractionation of the organisms. Type A strains were found to be pathogenic and capable of fermenting mannitol, while type B was comprised of strains which failed to ferment mannitol and had little, if any, pathogenicity(1168). 

Chester W. Emmons (US) modernized the taxonomic scheme of Sabouraud and others and established the current classification of the dermatophytes on the basis of spore morphology and accessory organs(1169).

James E. Knott (US) and Mikhail Khristoforovich Chailakhyan (RU) independently discovered that the flowering process is prompted not by a substance(s) in the bud but rather by a substance(s) produced in the leaves. Knott said, “Though the response of the plant may be localized in the bud, the leaves appear to function in some way to hasten the reproductive response to the appropriate photoperiod….Accordingly, the part played by the foliage of spinach in hastening the response to a photoperiod favorable to reproductive growth may be in the production of some substance, or stimulus, that is transported to the growing point.” Chailakhyan studied Saratov millet, Perilla nankinesis, Helianthus annuus and Helianthus tuberosus (sunflower) concluding, “the processes induced by the changes in the length of daylight and leading to the reproductive development of plants (flowering and fruiting) occur within the leaf tissues. The formative process occurring in the zones of growth (growing points) are secondary changes dependent upon the functional activity of the leaf.” Chailakhyan further demonstrated that the chemical promoter of flowering is not specific to a species but can stimulate a number of species. He named this hormone florigen, flower former(1170-1173).

Ferdinand Gustav Julius von Sachs (DE), in 1880 and 1882, had guessed that leaves produce a promoter of flowering but never demonstrated it experimentally.

Eric T.B. Francis (GB) authored The Anatomy of the Salamander (Salamander musculosa); an example of outstanding descriptive zoology(1174).

William T. Heron (US), William M. Hales (US), and Dwight Joyce Ingle (US) reported that repetitive contraction of skeletal muscle requires the activity of a substance(s) which can be extracted from the adrenal cortex(1175). This knowledge was developed into a bioassy for adrenal hormones that facilitated the purification of cortisone.

Balduin Lucké (US) suggested a viral etiology for a renal adenocarcinoma he observed in the Northern Leopard Frog, Rana pipiens. This is the first postulation of a virus infection of an amphibian(1176, 1177)(Lucké 1934; Lucké 1938).

Wallace Osgood Fenn (US), Doris M. Cobb (US), Albert H. Hegnauer (US), Burton Sanford Marsh (US), Jeanne F. Manery (US), Walter R. Bloor (US), Thomas R. Noonan (US), Lorraine F. Haege (US), Lorin J. Mullins (US), and Robert B. Dean (US) made the first determinations of potassium, sodium, magnesium and calcium in nerve. They showed that intracellular potassium is mobile and that muscle potassium shifts in response to various environmental factors. They found that during muscle contraction potassium is lost from muscle in exchange for sodium, and that the process is reversed in recovery. This was the first time that sodium was shown to penetrate muscle. This work laid the foundation for the Hodgkin-Huxley hypotheses concerning initiation and propagation of nerve and muscle impulses and the magnitude and polarity of electrical potential differences across cell membranes. Fenn said, “The explanation for a loss of potassium from a muscle during activity is a matter of fundamental theoretical importance. In terms of the theory which I have been using as a guide, it is interpreted as an increase in the permeability of the muscle membrane of sufficient extent to permit sodium which enters then displaces one molecule of potassium”(1178). They showed that potassium escapes from muscle during contraction in situ and that a large part of this potassium appears in the liver. Potassium uptake was linked with carbohydrate metabolism, particularly with glycogen deposition, and tends to follow the Cori cycle. Radioactive potassium was ingested as part of the first study of the kinetics of potassium metabolism and the demonstration that it is taken up by erythrocytes. Nearly all muscle potassium was found to be exchangeable, supporting the notion that it is maintained by an active energetic process(1178-1198).

Philip Duryeé McMaster (US), Stephen S. Hudack (US), and John G. Kidd (US) demonstrated that lymph nodes, draining skin sites injected with bacteria or viruses, formed antibodies against these agents in very high concentrations(1199-1203).

Frederick W. Madison (US) and Theodore L. Squier (US) defined the etiology of primary granulocytopenia (agranulocytic angina). They suggested that the primary granulocytopenia following the use of such drugs amidopyrine with a barbiturate may be the result of an allergic or anaphylactoid drug reaction(1204).

John Silas Lundy (US) brought to a climax a long series of trials by many workers when he used the intravenous introduction of Pentothal (thiopental sodium, a barbiturate) to put a patient peacefully to sleep on June 18, 1934. Pentothal rapidly became the standard induction agent, being much more pleasant than inhaling the pungent ether. It was not until the 1990s that propofol, a more rapidly metabolized agent with fewer side effects, finally replaced pentothal. Lundy (US) is best known for introducing intravenous anesthesia into clinical practice(1205). 

Ralph Milton Waters (US) and Erwin R. Schmidt (US) published their paper on the physiologic and pharmacologic effects of cyclopropane on the human body(1206).

J. Roswell Gallagher (US) described an outbreak of bronchopneumonia in a group of 16 boys living at a preparatory school (a closed community). He especially stressed that these children did not have pneumococcal pneumonia but something different--something "atypical"(1207).

Robert A. Reimann (US) described a group of eight patients with chest infection but atypical clinical presentations and no chest pain. He coined the term "atypical pneumonia" because the manifestations in these patients differed greatly from those in patients presenting with acute pneumococcal pneumonia. Reimann's initial impression was that this illness was caused by a filterable agent, most likely a virus, but to this date the cause of his patients' illnesses remains unknown(1208).

Clive M. McCay (US), Mary F. Crowell (US), and Leonard Amby Maynard (US) studied the effects of food restriction on the life span of rats. They concluded that if an animal ate what it should and little more its life span was increased(1209, 1210).

Ernst Klenk (DE) identified sphingomyelin as the stored phospholipid in cells from patients with Niemann-Pick disease(1211).

Ivar Asbjørn Følling (NO) described phenylketonuria (PKU) and called attention to its association with serious mental deficiency. He developed a test for demonstrating phenylpyruvic acid found in the urine of a person with PKU(1212).

Fuller Albright (US), Esther Bloomberg (US), Benjamin Castleman (US), Edward D. Churchill (US), Walter Bauer (US), and Joseph C. Aub (US) gave the initial clinical description of hyperparathyroidism(1213, 1214).

William Jason Mixter (US) and Joseph S. Barr (US) discovered herniated intervertebral disks as a pathological condition(1215).

Lillian Lauricella (US), on April 17, 1934, gave birth to twin daughters, conceived by artificial insemination using donor sperm (AID)(1216).

Walter Edward Dandy (US) outlined his theory of vascular compression as a cause of trigeminal neuralgia (TN), and pointed to the main problem with that theory; namely, that vascular contact occasionally occurs without the production of pain and may be absent when neuralgia is present(1217).

Peter J. Hamlyn (GB) and Thomas T. King (GB) confirmed that vascular compression of the fifth cranial nerve is an anatomical abnormality specific to TN(1218).

Alexandra Adler (AT-US) suggested that the thalamic arcuate nucleus of the brain is associated with taste(1219).

Harry Dickson Patton (US), Theodore Cedric Ruch (US), and A. Earl Walker (US) subjected monkeys to lesions of the thalamic arcuate nucleus and confirmed Adler’s suggestion(1220).

Harry Dickson Patton (US) found evidence that the most important part of the taste area lay buried in the operculum, just below the facial regions(1221).

Michael Ellis DeBakey (US), four years after entering medical school, designed the first roller pump, which remains the basis for all cardiac by-pass surgery performed today(1222).

Ralph A. Colp (US) was the first to describe a granulomatous inflammation of the terminal ileum and cecum called ileo-colitis(1223).

Arthur Evans (GB) was the first to successfully operate on the thoracic region of the esophagus for cancer. He reported a 23-year cure of cancer of the cervical esophagus by radical excision of the cervical esophagus and larynx(1224).

Philippe l'Héritier (FR) and Georges Teissier (FR) devised the population cage method for the experimental study of natural selection. They showed, among other things, that unfavorable mutations (such as bar) could be maintained in a population of Drosophila in a stable balanced polymorphism in spite of the deleterious effects of the mutation on the flies that carried it(1225-1227).

Nikolai Wladimirovich Timoféeff-Ressovsky (RU) experimentally measured the viability of strains of Drosophila funebris of different geographical origin(1228).

Francis Bertody Sumner (US) experimentally showed the selective value of protective coloration in fishes(1229).

G. Edward Lewis (US) found the first Ramapithecus (Ramapithecus brevirostris), the earliest known hominid fossil, in deposits in the Siwalik Hills of Northern India(1230).

William Beebe (US) and Otis Barton (US) developed the deep diving bathysphere. This round steel submersible was used on August 5, 1934 for a drop to 3,028 feet into the ocean off Nonsuch Island(1231, 1232). Beebe is commemorated by Protopelagonemertes beebei Coe, 1936, Metapenaeopsis beebei Burkenroad, and Aeginura beebei Bigelow, 1940.

Auguste Piccard (CH-BE) developed this type of equipment into what he referred to as a bathyscaphe, i.e., a more maneuverable submarine balloon, but looking somewhat like a conventional submarine. In 1954 his second bathyscaph the Trieste descended 10,330 feet into the Mediterranean and in 1960 his third vessel Trieste II was lowered to 35,800 feet (10,900 m) when it touched bottom in the Marianas Trench.

ca. 1935

Otto Heinrich Warburg (DE), Otto Fritz Meyerhof (DE-US), Einar Lundsgaard (DE) and Hermann Karl Felix Blaschko (DE-GB) demonstrated that ATP is generated from ADP in coupled enzymatic reactions during the anaerobic breakdown of glucose to lactic acid in muscle(1233). need Warburg ref

1935

Hans Spemann (DE) was awarded the Nobel Prize in Physiology or Medicine for his discovery of the organizer effect in embryonic development.

Max Knoll (DE) demonstrated the feasibility of the scanning electron microscope; three years later a prototype was built by Manfred von Ardenne (DE)(1234, 1235).

Alexis Carrel (FR-US) and Charles A. Lindbergh (US) described an all-glass system for the perfusion of whole organs(1236).

Arthur Lindo Patterson (NZ-US) developed an analytical method for determining interatomic spacings from x-ray data(1237).

Rudolf Schoenheimer (DE-US) and David Rittenberg (US) introduced the use of deuterium as an isotopic tracer into biochemical research in animals(1238). This methodology marked a milestone in biochemistry because for the first time an isotope was systematically introduced into an organic compound so that a defined reaction or pathway could be studied. See, Georg Charles de Hevesy, 1923.

Wolfgang Schott (DE), inspecting findings of the German Meteor oceanographic expedition of 1925-27, realized that the species whose shells were found in the muck of the seabed depended sensitively on the temperature of the water where the creatures had lived. The mix of foraminifera species could serve as a thermometer of past climates(1239).

Harold Clayton Urey (US), Samuel Epstein (US), Heinz A. Lowenstam (US), and Charles R. McKinney (US) were able to prepare a history of changing ocean temperatures over long geologic periods. This work was based on the knowledge that heavy isotopes of oxygen react more slowly than normal atoms. Thus the proportion of oxygen isotopes in a seashell depends upon the temperature of the ocean at the time the shell was formed(1240-1242).

David Rockwell Goddard (US) and Leonor Michaelis (DE- US) found that reducing agents such as thioglycolic acid can break the disulfide linkages in keratin (hair, wool, feathers). They did not patent this discovery(1243). Thioglycolic acid and other thiol compounds became the basic ingredients of the permanent wave solutions used in the cosmetic industry.

Harry Bender (US) discovered that technical benzene hexachloride (BHC) is a potent insecticide. He added benzene to chlorine in a Dewar flask in the open air and noticed that part of the product which spilled on the ground “attracted and killed flies and bees”(1244). See Michael Faraday, 1825 and Van der Linden, 1912.

Eric John Underwood (AU), John Francis Filmer (AU), and Hedley Ralph Marston (AU) showed that cobalt is a necessary element in the diet of animals(1245, 1246).

Ernst Klenk (DE) characterized a new type of acidic glycolipid—naming it substance X—from the brains of patients suffering from amaurotic familial idiocy(1247).

Ernst Klenk (DE) coined the term ganglioside to name substance X which he characterized in 1935(1248).

Paul Rothemund (US) synthesized the simple chlorophyll-like substance protochlorophyll(1249).

Robert H. Sifferd (US) and Vincent du Vigneaud (US) synthesized carnosine, a naturally occurring small peptide(1250).

Charles Robert Harington (GB) and Thomas Hobson Mead (GB) were the first to synthesize glutathione, a small naturally occurring polypeptide(1251)(Harington and Mead 1935b).

Richard H. McCoy (US), Curtis E. Meyer (US), and William Cumming Rose (US) isolated the amino acid threonine from hydrolysates of fibrin and demonstrated that it is one of the essential amino acids in rats(1252, 1253).

Herbert E. Carter (US) synthesized all isomers of threonine and found that the L-isomer is the essential form in rats(1254).

Charles Robert Harington (GB) reported that enlargement of the thyroid gland in hyperthyroidism was found to be associated with heart dysfunction, exophthalmos, and increased metabolic rate(1255)(Harington 1935a).

Ya-Pin Lee (US), Akira E. Takemori (US), Henry Arnold Lardy (US), Ching-Yuan Su (US), Nancy Kneer (US), and Susan Wielgus (US) found that thyroid hormone and also dehydroepiandrosterone induced the synthesis of mitochondrial glycerol-3-phosphate dehydrogenase to as much as 20 times the normal concentration and formed part of the thermogenic system(1256-1259).

Harold King (GB) purified and determined the structure of d-tubocurarine, one of the many alkaloids present in curare preparations(1260, 1261)(King 1935a; King 1935b).

A.J. Everett (GB), L.A. Lowe (GB), and S. Wilkinson (GB) made one minor correction in its structure(1262).

Kurt Guenter Stern (GB-US) using optical methods (a spectrophotometer) made the first direct observation of an enzyme-substrate complex(1263).

Béla Tankó (HU) and Robert Robison (GB) announced the discovery of phosphohexose kinase(1264).

Karl Zeile (DE) and Axel Hugo Theodor Theorell (SE) performed work which led to the complete purification of cytochrome c and its characterization as a protein unit of molecular weight 13,000 with a porphyrin unit covalently linked to the protein by way of two cysteine residues(1265, 1266).

Otto Heinrich Warburg (DE), Walter Christian (DE), Alfred Griese (DE), Frank Dickens (GB), Gertrude E. Glock (GB), Bernard Leonard Horecker (US), Pauline Z. Smyrniotis (US), Jarvis Edwin Seegmiller (US), Paul A. Marks (US), Howard H. Hiatt (US), Hans Klenow (US), Efraim Racker (PL-AT-US), and Dan Couri (US) extensively studied and purified all of the enzymes found in the type of glycolysis called the phosphogluconate pathway, also known as the pentose phosphate pathway or hexose monophosphate shunt. This is a multifunctional pathway specialized to carry out four main functions: (1) generate reducing power in the form of NADPH, needed for the synthesis of fatty acids and steroids from acetyl-CoA, (2) to convert hexoses to pentoses, particularly D-ribose 5-phosphate, required for the synthesis of nucleic acids, (3) the oxidative degradation of pentoses by converting them into hexoses, which can then enter the glycolytic sequence, and (4) it is modified so as to participate in the formation of glucose from CO2 in the dark reactions of photosynthesis(705, 1267-1276). Horecker (US) coined the phrase hexose monophosphate shunt in his 1951b paper mentioned above.

Paul A. Srere (US), Jack R. Cooper (US), Vida Klybas (US) and Efraim Racker (PL-AT-US), discovered xylulose-5-phosphate, a new intermediate in the pentose phosphate cycle(1277).

Paul A. Srere (US), Hans Leo Kornberg (GB-US), and Efraim Racker (PL-AT-US) demonstrated that transaldolase and transketolase, highly purified, were able to effect the conversion of pentose phosphate to hexose phosphate(1278).

Hans Leo Kornberg (GB-US) and Efraim Racker (PL-AT-US) found that erythrose 4-phosphate is an intermediate in that process(1279).

Harland Goff Wood (US), Joseph Katz (US), and Bernard R. Landau (US) used carbon-14 to estimate the proportion of carbohydrate metabolized in the pentose pathway and glycolysis. These studies helped determine the stoichiometry of the pentose pathway(1280).

Percy W. Zimmerman (US) and Frank Wilcoxon (US) discovered several synthetic substances with hormone activity in plants(1281). 

Hermann James Almquist (US) and E.L. Robert Stockstad (US) demonstrated that fecal microorganisms are capable of synthesizing vitamin K. They purified the vitamin under a high vacuum(1282-1286).

Phoebus Aaron Theodor Levene (RU-US) and Robert Stuart Tipson (US) determined that “…in desoxy-ribose nucleic acid the positions of the phosphoric acid radicals are carbon atoms (3) and (5) of the desoxyribose”(1287).

Otto Fritz Meyerhof (DE-US) and Wilhelm Kiessling (DE) found that muscle extract contains an isomerase which catalyzes the conversion of synthetic D-3-phosphoglyceraldehyde to dihydroxyacetone phosphate(1024).

Otto Fritz Meyerhof (DE-US) and Wilhelm Kiessling (DE) showed that in glycolysis it is the oxidation of the aldehyde to the acid that balances the reduction of acetylaldehyde to ethanol (in alcoholic fermentation) or of pyruvic acid to lactic acid (in glycolysis), and that phosphoglycerol is not a necessary participant in the dismutation as Embden had proposed. They also demonstrated that in iodoacetate poisoned muscle extracts, the phosphoryl group of 2-phosphoenolpyruvic acid is transferred to glucose by way of ATP to yield hexose phosphates and pyruvic acid(1023).

Jakub (Jacob) Karol Parnas (PL) and Tadeusz Baranowski; Tadeush Baranowski (PL) found that in muscle extracts glycogen and inorganic phosphate can react to form hexose monophosphates if the oxidation-reduction process is blocked using iodoacetic acid and no ATP is being generated(1288). This was of importance because it established beyond doubt the participation of inorganic phosphate in the splitting of glycogen and the discovery of phosphorylase activity in muscles.

Harland Goff Wood (US), Chester Hamlin Werkman (US), Allen Hemingway (US) and Alfred Otto Carl Nier (US) demonstrated that many heterotrophic forms of life assimilate carbon dioxide. They proposed that carbon dioxide and pyruvate combine to form oxaloacetate, which subsequently is reduced to succinate—the Wood-Werkman reaction(1289-1294).

Arthur Kaskel Solomon (US), Birgit Vennesland (DE-US), Friedrich W. Klemperer (US), John Machlin Buchanan (US),  and A. Baird Hastings (US) determined that higher organisms utilize carbon dioxide as a substrate of reactions(1295). 

Hutton D. Slade (US), Harland Goff Wood (US), Alfred Otto Carl Nier (US), Allen Hemingway (US), and Chester Hamlin Werkman (US) reported that fixation of carbon dioxide by C3 and C1 addition is apparently a very general reaction among the heterotrophic bacteria(1296). At this time, it was dogma that carbon dioxide is an inert end product of the metabolism of all living forms except the specially adapted chemosynthetic and photosynthetic autotrophs.

Henry Arnold Lardy (US) and Julius Adler (US) found that propionate can be metabolized by carbon dioxide addition to ultimately yield succinate(1297). 

Sir Hans Adolf Krebs (DE-GB) found that the kidney contains separate oxidative deaminases for D- and L-amino acids and that both kidney and brain tissue will convert ammonium glutamate to glutamine and hydrolyze it back as well(1298, 1299).

Henry Borsook (US) and Geoffrey Keighley (US) concluded from nutritional studies that there is a continuing metabolism of protein, and that tissue proteins are constantly being synthesized from amino acids(1300).

Charles Herbert Best (US-CA) and M. Elinor Huntsman (CA) reported that choline is a lipotropic agent that prevents deposition of fat in the liver(1301).

Kenneth Bryan Raper (US) identified the slime mold, Dictyostelium discoideum, then with Theo M. Konijn (US) laid the groundwork for the later use of this organism as a model system for the study of intercellular communication(1302, 1303).

Hugh A. Davson (GB) and James Frederic Danielli (GB) proposed a protein-lipid sandwich model for the structure of cell membranes. This Davson-Danielli model proposed the idea of two layers of phospholipids sandwiched in between two outer layers of protein. The phospholipids were oriented with their hydrophilic ends at the two surfaces and their hydrophobic tails towards the interior of the membrane. This structure explained the stability of plasma membranes because of the strong hydrophilic and hydrophobic interactions. It also accounted for the fact that lipid-soluble substances could pass through a plasma membrane easily. They proposed that this membrane was approximately eight nanometers thick, and had small pores in the protein coat to allow the passage of certain molecules and ions(1304, 1305).

John Burdon Sanderson Haldane (GB-IN) was the first to estimate the spontaneous mutation rate of a human gene(1306).

Sterling Howard Emerson (US) and George Wells Beadle (US), using the attached-X chromosome in Drosophila melanogaster, were able to show that each crossover between chromosomes at the first division of meiosis could, with equal likelihood, involve either one of the two chromatids into which each chromosome is divided(1307, 1308).

George Wells Beadle (US) and Boris Ephrussi (RU-FR) implanted embryonic eye tissue from larvae of vermilion and cinnabar mutants into larvae of normal Drosophila flies and observed that, upon metamorphosis of these larvae into mature flies, the implanted eye tissue developed into supernumerary eyes with normal eye color. It could be concluded, therefore, that the body tissues of the normal flies supply some substance that the vermilion and cinnabar mutant eye tissues are unable to synthesize, but one they can convert into the brown eye pigment. Beadle and Ephrussi then implanted the same embryonic mutant tissues into the larvae of vermilion and cinnabar mutant flies and observed that vermilion eye tissue implanted into cinnabar host larvae developed the normal eye color, whereas cinnabar eye tissue implanted into vermilion host larvae developed the mutant cinnabar eye color. Beadle and Ephrussi inferred from these observations that the synthesis of the brown eye pigment arises by the metabolic chain: Precursor tosubstance I to substance II tobrown pigment.

The vermilion mutant would thus carry a block in the reaction that converts the precursor to substance I, whereas the cinnabar mutant would carry a block in the reaction that converts substance I to substance II. Thus in the wild-type host larva, both of the mutant eye-tissue transplants are provided with substance II, which they can convert to the brown pigment. The vermilion mutant eye-tissue transplant in the cinnabar host larva is provided with substance I, which it can convert to substance II and to brown pigment. But the cinnabar mutant eye-tissue transplant in the vermilion host larva is not provided there with the substance II, which it lacks, and hence fails to form the brown pigment. Within a few years biochemical studies showed that the precursor is the amino acid tryptophane and that substances I and II are formylkynurenin and hydroxykynurenin, respectively. The genetically controlled metabolic eye color sequence could thus be written as: Tryptophane toFormylkynurenin (substance I) toHydroxykynurenin (substance II) toBrown pigment.

The stage was now set for formulating more clearly the physiological role of genes. The normal, wild-type allele of the vermilion gene of Drosophila could be envisaged as presiding over the formation of an enzyme that catalyzes the conversion of tryptophane to formylkynurenin. The mutant allele, by contrast, has lost the capacity to form that enzyme. Hence the tissues of a homozygous mutant fly carrying the vermilion mutant gene on both of its homologous chromosomes lack the enzyme, and the metabolism of such flies is blocked at the reaction step normally catalyzed by that enzyme. The tissues of a heterozygous fly, carrying one mutant and one wild-type allele of the vermilion gene, would contain the enzyme, however, and hence are capable of forming formylkynurenin. Similarly, the mutant gene of the cinnabar gene has lost the capacity to form the enzyme that catalyzes the conversion of formylkynurenin to hydroxykynurenin, the enzyme that is normally formed under the direction of the wild-type allele. From this viewpoint, the recessive character of both the vermilion and cinnabar mutations is accounted for by the absence of an enzymatic function that the dominant, wild-type allele can supply(1309-1312).

Alfred Kuhn (DE), Adolf Friedrich Johann Butenandt (DE), Wolfhard Weidel (DE), and Erich Becker (DE) did very similar work in Ephestia, studying the biochemical genetics of eye-pigment synthesis(1313, 1314). These works represent the first step toward the one gene, one enzyme, hypothesis.

Nikolai Wladimirovich Timoféeff-Ressovsky (RU), Karl Günter Zimmer (DE), and Max Ludwig Henning Delbrück (DE-US) formulated a target theory of gene mutation which says that a mutation can be induced if a single electron is detached by high energy radiation(1315). 

Calvin Blackman Bridges (US) showed that in Drosophila salivary gland chromosomes certain sequences recur in different regions and that these tend to be found paired in the form of synapsis of somatic chromosomes. He referred to these regions as repeats and assumed that they had arisen as duplications of the same segment (tandem repeats)(1316, 1317).

Erwin Bünning (DE) proved the genetic origin of biological rhythms. He found that circadian rhythms persisted in the bean plant Phaseolus and the fruit fly Drosophila, even though generation after generation had been raised in environments completely lacking cues to the passage of time(1318, 1319).

Sven Dijkgraaf (NL) and Ad J. Kalmijn (NL) provided the first evidence of electrosensitivity in elasmobranchs in 1935 when Dijkgraaf, working on Scyliorhinus canicula, noticed the animal's sensitivity to a rusty steel wire(1320).

Theodore H. Bullock (US), Susumu Hagiwara (US), Kiyoshi Kusano (JP), Koroku Negishi (JP), and Ad J. Kalmijn (NL) reported that Hans Lissmann (GB) in 1958 formally suggested, based on behavioral evidence, that a group of receptors and central processes, called the ampullae of Lorenzini, aid in the detection and analysis of electric fields by certain fish in the marine environment. Later, experimenters verified the existence of the new class of specialized receptors through physiological experiments. They named them "electroreceptors" because their adequate stimuli were electric fields(1321, 1322).

Sven Dijkgraaf (NL), Ad J. Kalmijn (NL), Robert C. Peters (NL) and Frédéric van Wijland (NL) discovered that many fishes not equipped with electric organs of any kind nevertheless have electrical sensitivities equaling or even exceeding those of species specialized for electrical orientation(1323-1325).

Wendell Meredith Stanley (US) reported the crystallization of pure tobacco mosaic virus to the world. This gave rise to the controversy of whether a virus is alive or dead. Most microbiologists today consider that they are not alive, because they are acellular(1326-1329).

J.P. Cleary (US), Paul J. Beard (US), and Charles E. Clifton (US) concluded that the population of a bacterium in continuous culture will not exceed a specific maximum cell number even when the effects of inhibitory substances are reduced to a low level because the major population limiting factor appears to be the amount of energy and building material available per cell per unit time(1330).

Sir Frank Macfarlane Burnet (AU) and Diana H. Bull (AU) grew the influenza virus in chick embryos(1331, 1332).

St. Louis encephalitis was first recognized as a unique clinical entity in association with a large outbreak of the disease at St. Louis, MO in the summer of 1933(1333).

Leslie T. Webster (US), Anna D. Clow (US), and Johannes H. Bauer (US) found that the Anopheles quadrimaculatus (mosquito) will harbor the virus of St. Louis encephalitis for 21-42 days following a blood meal from an infected animal(1334).

Kenneth M. Smith (GB) and John G. Bald (GB) were the first to describe tobacco necrosis disease as being caused by a virus(1335).

William Trager (US) performed the first successful infection of insect tissue in vitro by an insect virus (grasserie). He inoculated primary cultures of ovarian tissue from Bombyx mori with dilutions of hemolymph from diseased larvae(1336).

Meredith Hoskins (US) reported that when rhesus monkeys (Macacus rhesus) were inoculated simultaneously with neurotropic and viscerotropic strains of yellow fever virus the neurotropic strain appeared to have a very definite protective effect by reducing the virulence of the viscerotropic strain. This is referred to as the interference phenomenon and was first demonstrated in animals by Hoskins(1337). 

Leonell C. Strong (US) established the C3H inbred strain of mice for the study of spontaneous carcinoma of the mammary gland(1338).

Emmy Klieneberger (GB) discovered L form bacteria when she found them growing in association with Streptobacillus moniliformis. Originally she thought they represented a unique organism but other workers subsequently showed them to be a bacterial variant of organisms such as Streptobacillus moniliformis(1339). These organisms lack cell walls but are not mycoplasmas. 

Gerhard J. Domagk (DE) discovered that a red dye compound, Prontosil rubrum (4-sulfonamido-2,4-diamino-azobenzene hydrochloride) is very low in toxicity to animals but very active against streptococcal infections in animals(1340).

Jacques Gustave Marie Tréfouël (FR), Thérèse Tréfouël, née Boyer (FR), Filomena Nitti (IT-FR), and David Bovet (CH-FR), working at the Pasteur Institute, discovered that the antibacterial action of the drug prontosil is due to it being converted to sulfanilamide within the animal body (1341).

Leonard Colebrook (GB), Méave Kenny (GB), and Anthony W. Purdie (GB) provided overwhelming evidence of the efficacy of both Prontosil and sulfanilamide in streptococcal septicemia (bloodstream infection), thereby ushering in the sulfonamide era(1342-1344).

 

Gerhard J. Domagk (DE) discovered that the germicidal properties of quaternary ammonium compounds required that at least one of the four radicals consist of a long-chain aliphatic group(1345).

Jerome T. Syverton (US), George Packer Berry (US), R.W. Harrison (US) and Elizabeth Moore (US) successfully cultured the virus of St. Louis encephalitis in tissue culture(1346, 1347).

Albert Spear Hitchcock (US) and Mary Agnes Chase (US) prepared the Manual of Grasses of the United States (1935). Its usefullness continues through today in the form of a 2nd edition in 1950(1348, 1349).

An easy way to store blood plasma was discovered. It was first frozen, then dried into flakes in a vacuum. Packed in tiny ampullae, the plasma was shipped with a pint of sterile water and tubing. ref

Dempsie B. Morrison (US), Alan Hisey (US), and Erich Peters (US) established that the combination of oxygen with hemoglobins takes place according to the ratio, Fe/O2, one gram-atom of pigmentary iron per gram-molecule of oxygen fixed(1350).

William Frederick Windle (US) and Marvin F. Austin (US) described the routes of the earliest axons in the central nervous system of the chick embryo, assessed at several stages between the second and sixth days of incubation. They focused on the descending, or reticulospinal, axons arising from hindbrain nuclei(1351).

William L.R. Cruce (US), Sherry L. Stuesse (US), and R. Glenn Northcutt (US) used retrogradely transported axonal tracers (horseradish peroxidase and Fluoro-Gold) to identify groups of brainstem neurons that projected to the spinal cord, in two cartilaginous fishes, the Thornback Guitarfish, and the Horn Shark. They identified numerous distinct reticular nuclei in these elasmobranchs, consistent with a complex organization similar to the reticular formation in other vertebrates(1352).

John G. New (US), Bethany D. Snyder (US), and Katherine L. Woodson (US) traced axons descending to the spinal cord in the Channel Catfish, and found that the majority of neurons projecting to the spinal cord are located in the reticular formation of the hindbrain. Both ascending and descending reticular formation projections are of great clinical importance in humans, as they can be damaged or destroyed by strokes, spinal cord injuries, and astrocytomas(1353).

Eli Kennerly Marshall, Jr. (US) and Morris Rosenfeld (US) observed that in respiratory depression anoxia provides a major ventilatory drive mediated through the sino-aortic mechanism. Their observation recognized that often when the mammal is threatened with anoxemia, “it may adapt itself … to a primitive type of respiratory control (the sino-aortic rather than central) which is normal for lower vertebrates”(1354, 1355). See, Corneille and  Jean Francois Heymans, 1927.

Note: It is a prime rule in accident rooms not to give oxygen to patients depressed with morphine, barbiturates, or allied drugs.

Carlyle F. Jacobsen (US) first discovered that damage to the primate prefrontal cortex (PF) appeared to cause a short-term memory deficit(1356, 1357).

Shintaro Funahashi (US), Charles J. Bruce (US), and Patricia S. Goldman-Rakic (US) found evidence to strengthen the evidence that the dorsolateral prefrontal cortex of the monkey participates in the process of working or transient memory and further indicate that this area of the cortex contains a complete “memory” map of visual space(1358).

Armand James Quick (US), Margaret Stanley-Brown (US), and Frederic W. Bancroft (US) developed the one-stage prothrombin-time technique using rabbit brain extract. This test detects the amount of prothrombin present in blood plasma and determines prothrombin clotting time(1359, 1360). The technique was based on the assumption that, given enough tissue, calcium, and fibrinogen, there is only one factor limiting the time course of clotting: prothrombin. It is now recognized that this result is limited by deficiencies of factors additional to prothrombin, but this does not diminish the importance of this technique in the control of coumarin therapy. See, Whipple, 1913.

The one-stage prothrombin-time made possible the immediate differentiation between the coagulation defect in hemophilia and that in obstructive jaundice.

Emory D. Warner (US), Kenneth M. Brinkhous (US), and Harry P. Smith (US) developed a method of measuring prothrombin which became known as the two-stage technique(1361).

Hugh Leslie Marriott (GB) and Alan Kekwick (GB) introduced the continuous drip blood transfusion method, in which blood flows from a flask(1362). This was made possible by Luis Agote’s discovery in 1914. Earlier transfusions were directly from donor to recipient.

Claude Schaeffer Beck (US) presented his technique for development of a blood supply to the heart by operation. It prescribed grafting a flap of the pectoralis muscle over the exposed epicardium to provide a new blood supply(1363).

Frank Mason Sones, Jr. (US) accidently performed the first selective coronary angiography when he accidently injected dye into the right coronary artery instead of into the cardiac valve as intended. Instead of fibrillating, the man's heart went into asystole, and Sones shouted at the patient to cough, which successfully restarted the heart beating(1364, 1365).

Arthur M. Vineberg (CA) introduced the Vineberg procedure, which consists of the revascularization of the entire heart by internal mammary artery implantation, epicardiectomy and free omental graft(1366, 1367).

Vasilii I. Kolessov (RU) performed the first internal mammary artery-coronary artery anastomosis(1368).

Donald B. Effler (US), Rene Gerónimo Favaloro (AR), Laurence K. Groves (US), Chalit Cheanvechai (TH), Robert A. Quint (US), and Frank Mason Sones, Jr. (US), beginning in 1967, performed some of the first coronary by-pass operations using the patients’ native saphenous veins as autografts(1369, 1370).

W. Dudley Johnson (US), Robert J. Flemma (US), Derward Lepley, Jr. (US), and Edwin H. Ellison (US) introduced modern coronary by-pass surgery with their method of myocardial revascularization. Veins are usually inserted into an area of normal artery; however, if a second area of atherosclerosis occurs (commonly in the mid-anterior descending artery), the arteriotomy extends across the plaque into normal artery on each end. The vein is sutured as a patch graft always extending the anastomosis to normal artery proximally and distally. With progressive atherosclerosis this maneuver preserves bidirectional flow(1371).

H. Edward Garrett (US), Edward W. Dennis (US), and Michael Ellis DeBakey (US) performed an autogenous saphenous vein by-pass from the ascending aorta to the anterior descending coronary artery. The patient was a 42-year-old man who had extensive occlusive disease of the coronary artery and angina pectoris(1372). The operation was first performed by this team in 1964.

Allen Oldfather Whipple (US), William Barclay Parsons (US), and Clifton R. Mullins (US) introduced a two-stage radical pancreaticoduodenectomy to treat carcinoma of the ampulla of Vater(1373). Twenty-eight months was the longest survival time course of the three cases reported. This was not the first time such an operation was performed.

Allen Oldfather Whipple (US) described the first reported case of a one-stage pancreaticoduodenectomy for a carcinoma of the head of the pancreas(1374).

Arnold Rice Rich (US) found carcinoma of the prostate in 14% of all autopsies and in 28% of those aged over 70 years(1375).

Burrhus Frederic Skinner (US), a leading behaviorist and proponent of operant conditioning, invented the Skinner box for facilitating experimental observations. His main scientific works include The Behavior of Organisms (1938), and Verbal Behavior (1957). He founded behaviorism(1376-1379).

John Ridley Stroop (US) was the first to think of combining a word with object/property dimensions, creating the now famous situation of response conflict(1380). An example of this phenomenon is that when asked to name the color of ink in which an incompatible color word is printed (e.g., to say "red" aloud in response to the stimulus word GREEN printed in red ink), people take longer than to name the same ink color in a suitable control condition (e.g., to say "red" to the stimulus XXXXX printed in red ink). This has been called the Stroop effect.

Arthur George Tansley (GB) coined and defined the term ecosystem. "The weakness of Clements is. . . that vegetation is an organism and therefore must obey the laws of development of what we commonly know as organisms. . . . But the more fundamental conception is, as it seems to me, the whole system (in the sense of physics) including not only the organism-complex, but also the whole complex of physical factors forming what we call the environment of the biome…Though the organism may claim our primary interest, when we are trying to think fundamentally we cannot separate them [organisms] from their special environment, with which they form one physical system"(1381).

Julia Anna Gardener (US), T. Wayland Vaughan (US), and Willis Parkison Popenoe (US) helped establish standard stratigraphic sections for Tertiary rocks in the Southern Caribbean, Coastal Plain of Texas, and the Rio Grande Embayment in Northeast Mexico(1382, 1383).

1936

Sir Henry Hallett Dale (GB) and Otto Loewi (DE-US) were awarded the Nobel Prize in Physiology or Medicine for their discoveries relating to chemical transmission of nerve impulses.

Harold Clayton Urey (US), Adriaan H.W. Aten, Jr. (US), Albert S. Keston (US), George B. Pegram (US), John R. Huffman (US), Harry G. Thode (US), and Marvin Fox (US) devised laboratory procedures for preparing high concentrations of such isotopes as carbon-13, oxygen-18, and nitrogen-15(1384-1386).

Lewis John Stadler (US) and George F. Sprague (US) discovered that ultraviolet light is mutagenic in maize(1387).

John Tileston Edsall (US) used Raman spectroscopy to show that both the amino and carboxyl groups of amino acids are charged at isoelectric pH(1388-1390).

Reynold C. Fuson (US), Robert E. Christ (US), Richard Johann Kuhn (DE) and Colin John Owen Rhonabwy Morris (GB) synthesized vitamin A (retinol)(1391, 1392).

Thomas William Birch (AU-GB) and Paul György (GB) discovered vitamin B6 (pyridoxine hydrochloride)(1393). 

Barend Coenraad Petrus Jansen (NL) authored a quantitative chemical test for vitamin B1 based on the oxidation of the vitamin into a yellow substance with intense blue fluoresence (thiochrome) as discovered by George Barger (GB), Franz Bergel (AT-GB), Alexander Robertus Todd (GB), and Sir Rudolph Albert Peters (GB)(1394-1396).

Hans Christian Hagedorn (DK), B. Norman Jensen (DK), Niels B. Krarup (DK), and I. Wodstrup (DK) developed protamine insulinate, one of the first successful longer-acting exogenous insulins(1397).

Douglas McClean (GB) discovered and isolated hyaluronidase (spreading factor) from Clostridium perfringens(1398).

Douglas McClean (GB) found that some streptococci are capable of producing hyaluronidase(1399).

Douglas McClean (GB) and I. W. Rowlands (GB) discovered hyaluronidase in mammalian sperm(1400). This enzyme dissolves the cement substance of follicle cells that surround mammalian eggs and facilitates passage of sperm to eggs.

Linus Carl Pauling (US) and Charles Dubois Coryell (US) demonstrated that in deoxyhemoglobin the bonds between iron and nitrogen are ionic and weak whereas in oxyhemoglobin they are covalent and stronger(1401). 

Daniel Bovet (CH-FR-IT) and Anne Marie Staub (DE) synthesized the first histamine receptor antagonists (popularly referred to as the classical antihistamines but now called H1-receptor antagonists). These early studies of the antihistamines were qualitative, for example, the demonstration of their effectiveness in protecting against bronchospasm produced in guinea pigs by anaphylaxis or administration of histamine. Though qualitative, these studies yielded compounds that remain major ligands to define histamine receptors, e.g., mepyramine (pyrilamine)(1402).

André Michael Lwoff (FR), Marguerite Lwoff (FR), Bert Cyril James Gabriel Knight (FR), and John Howard Mueller (FR) demonstrated that nicotinic acid is an essential growth factor for some bacteria(1403-1406). This led to the use of bacterial growth as a quantitative assay of growth factors.

Klaas Tammo Wieringa (NL) discovered Clostridium aceticum, the first acetogenic bacterium found to grow with hydrogen as an energy source and carbon dioxide as a carbon source(1407, 1408).

Carl Ferdinand Cori (CZ-US) and Gerty Theresa Cori, née Radnitz (CZ -US) discovered that glucose-1-phosphate is formed naturally in muscle. This was evidence for the presence of glycogen phosphorylase(1409). They presented evidence for phosphoglucomutase, the enzyme which converts glucose-1-phosphate to glucose-6-phosphate.

Chester Hamlin Werkman (US), E.A. Zoellner (US), Henry Gilman (US), and Howard Reynolds (US) were the first to isolate phosphoglyceric acid from bacteria(1410). Along with Robert William Stone (US) and Wilbur Paul Wiggert (US) they reported the formation of phosphoglyceric acid and related intermediary compounds in the dissimilation of glucose by a variety of heterotrophic bacteria(1411-1414).

Franz Knoop (DE) and Carl Martius (DE) established some of the intermediate stages of the oxidation of citric acid when they discovered the following sequence of reactions in liver tissue: citrate — cis-aconitate — isocitrate — oxalosuccinate — alpha-ketoglutarate.

The end-product of these sequences, lpha-oxoglutaric acid (alpha-ketoglutaric acid), was already known as an intermediate product because it is formed from the amino acid glutamate and had been shown to be oxidized to succinic acid(1415).

Carl Martius (DE) and Franz Knoop (DE) demonstrated that citric acid can be formed from pyruvic acid(1416). Carl Martius (DE) worked out the sequence citric-aconitic-isocitric-oxalosuccinic acid by the action of aconitase and isocitrate dehydrogenase(1417).

Erich Adler (SE), Hans von Euler (SE), Gunnar Günther (SE), and Marianne Plass (SE) determined that triphosphopyridinenucleotide (TPN) is the coenzyme for isocitrate dehydrogenase(1418). Synonyms for TPN are Warburg's coenzyme II and codehydrogenase II.

Edward Lawrie Tatum (US), Harland Goff Wood (US), William Harold Peterson (US), Milton Silverman (US) and Chester Hamlin Werkman (US) were among the first to demonstrate the role of vitamin B1 and co-carboxylase in bacterial metabolism(1419-1421).

Béla Tankó (HU), Gladys Macphail James (GB), William Owen James (GB), Arthur Hugh Bunting (GB), C.R.C. Heard (GB), and Charles Samuel Hanes (GB) demonstrated that glycolytic systems in higher plants are essentially the same as those discovered in animals, and yeast(1422-1426).

David Bodian (US) developed a new method for staining nerve fibers and nerve endings in mounted paraffin sections(1427).

Peter A. Gorer (GB), using inbred strains of mice, discovered four blood group antigens. The growth and rejection of a tumor correlated with the expression of antigen II. Gorer formulated the concept of tissue transplantation as, “normal and neoplastic tissues contain iso-antigenic factors which are genetically determined. Iso-antigenic factors present in the grafted tissue and absent in the host are capable of eliciting a response which results in the destruction of the graft.” This represents the discovery of what came to be known as the H-2 genetic region in mice(1428, 1429).

Clara J. Lynch (US), Thomas P. Hughes (US), Leslie T. Webster (US), and Anna D. Clow (US) were the first to demonstrate that a host gene can control resistance to disease induced by an animal virus(1430, 1431). This resistance was directed against flaviviruses.

Cyril Norman Hugh Long (GB-US) and Francis D.W. Lukens (US) found that removing the adrenal gland and pituitary gland of a diabetic animal reduced the blood level of glucose and thus the severity of its diabetic state(1432). This would later be linked to adrenocorticotropic hormone (ACTH) of the anterior pituitary gland. ACTH stimulates the release of other hormones which encourage the conversion of amino acids to glucose.

Torbjörn Oskar Caspersson (SE) demonstrated that the so called euchromatin bands on chromosomes represent areas which are very rich in nucleic acids(1433).

Carl D. LaRue (US) successfully established embryo cultures of different gymnosperms(1434).

George Henry Hepting (US) and Dorothy J. Blaisdell (US) described the mechanisms with which trees restrict the development of decay and discoloration in stems to “tissues extant at time of wounding.” This phenomenon is now known as compartmentalization(1435).

John Zachary Young (GB) discovered the giant nerve fibers of the squid, Loligo forbesi. This made possible many important experiments in neurophysiology(1436).

Alfred Newton Richards (US), Arthur M. Walker (US), Charles L. Hudson (US), and Thomas Findley (US) developed the technique of kidney tubule micropuncture which they used to examine tubular content in the amphibian renal tubule. They found that the chemical composition of the fluid in Bowman’s capsule corresponds closely to that of plasma filtrate, that most of the filtered glucose is reabsorbed along the proximal tubule, that creatinine concentration increases along the proximal tubule, that the osmotic pressure of the fluid remains roughly equal to that of plasma in the proximal tubule in spite of salt and water reabsorption (indicating high tubular permeability to water), and that the permeability to water is very low in the distal tubule since the osmotic pressure of the tubular fluid drops progressively along the distal segment as a result of salt reabsorption(1437-1439). 

Herald Rea Cox (US), Peter Kosciusko Olitsky (US), Joseph W. Beard (US), and Harold Finkelstein (US) developed vaccines for equine encephalomyelitis(1440, 1441).

Curt Stern (DE-US), while working with several sex-linked alleles of Drosophila, revealed a previously unrecognized phenomenon, mitotic crossing over(1442). 

Sir Frederick Charles Bawden (GB), Norman Wingate Pirie (GB), John Desmond Bernal (GB), and Isadore Fankuchen (US) demonstrated that tobacco mosaic virus contains phosphorus as a component of a phospho-ribonucleic acid(1443, 1444).

Sir Frederick Charles Bawden (GB), Norman Wingate Pirie (GB), Hubert S. Loring (US), Wendell Meredith Stanley (US), and Max Augustus Lauffer (US) demonstrated that all plant viruses tested up to this time were pure nucleoprotein. This was the first indication that nucleic acids, found in all cells, is found also in acellular "life"(1443, 1445-1449).

George P. Berry (US) and Helen M. Dedrick (US) reported the changing of rabbit fibroma virus (Shope) into infectious myxomatosis virus (Sanarelli). This Berry-Dedrick phenomenon has been referred to variously as transformation, recombination, multiplicity of reactivation, and non-genetic reactivation(1450).

Sir Frank Macfarlane Burnet (AU) and Dora Lush (AU) published a paper showing that bacteriophages can sport mutants whose plaques have a distinctly different appearance from those of the ordinary wild-type(1451).

Felix G. Gustafson (US) obtained the first successful growth of the parthenocarpic fruits (tomato, grape, fig) by applying auxin on unfertilised ovaries(1452).

K. Kanazawa (JP) was the first to grow the rabies virus in tissue culture(1453).

Henry Edward Shortt (GB), T. Ramachandra Rao (IN), and C.S. Swaminath (IN) reported culturing the virus of dengue fever (breakbone fever) on the chorioallantoic membrane of chick embryos(1454).

Henry Edward Shortt (GB), S. Ramachandra Rao (IN), C.S. Swaminath (IN), and C.G. Pandit (IN) reported culturing the virus of pappataci fever (phlebotomus fever, sand-fly fever, three-day fever) on the chorioallantoic membrane of chick embryos(1454, 1455).

Jean Cuillé (FR) and Paul-Louis Chelle (FR) reported that scrapie can be serially transmitted to sheep and that it passes bacterial filters. They noted that signs of the disease did not appear until more than one year had elapsed from the time of exposure to the contagious material(1456-1458). Scrapie gets its name from the tendency of affected animals to rub against fence posts during the excitable phase of the disease.

Josef Gerstmann (AT-US), Ernst Sträussler (AT), and Ilya Mark Scheinker (AT) described a disease characterized by degeneration of the nervous system, starting usually in the fourth or fifth decade of life with slowly developing dysarthria and cerebellar ataxia and then dementia, accompanied by spinocerebellar and corticospinal tract degeneration. Absence of leg reflexes. Death follows 2 to 10 years after the onset of symptoms(1459). Today this is known as Gerstmann-Sträussler-Scheinker syndrome, one of the amyloid dependent subacute spongioform encephalopathies associated with prion infection. It behaves in an autosomal dominant pattern.

Bjorn Sigurdsson (IS), Páll Agnar Pálsson (IS), and Halldór Grímsson (IS) determined that both visna and maedi are slow virus infections of sheep(1460, 1461). Visna means wasting and is characterized by progressive neurologic impairment and inanition. Maedi means shortness of breath and is characterized as a chronic pneumonia. Sigurdsson developed the concept of slow infection and described it as: (a) a long but rather predictable incubation period of months to years, during which the infectious agent produces clinically inapparent but progressive pathologic damage; and (b) a protracted course, once clinical signs have appeared, generally ending in serious disease or death(1462).

Daniel Carleton Gajdusek (US) and Vincent Zigas (AU) were the first to describe kuru (shivering or trembling), a human spongiform encephalopathy discovered among the Fore people of New Guinea(1463).

Wlliam J. Hadlow (US) pointed out the similarity in the neuropathology of scrapie in sheep with that of kuru in man. He arrived at this conclusion after observing brain sections of kuru victims prepared by Igor Klatzo (DE-US)(1464, 1465).

Herbert B. Parry (GB) suggested that scrapie, a spongiform encephalopathy of sheep, is an inherited but also transmissible disease(1466).

Daniel Carleton Gajdusek (US), Clarence Joseph Gibbs, Jr. (US), and Michael P. Alpers (US) were the first to transmit a human prion disease, kuru, to experimental animals(1467, 1468).

David C. Bolton (US), Michael P. McKinley (US), and Stanley Ben Prusiner (US) argued that a protein, not a virus or any other known parasite, was the infectious agent responsible for scrapie(1469). Prusiner named the infectious agents prions (proteionaceous infectious particle)(1470).

Stanley Ben Prusiner (US), Michael P. McKinley (US), Karen A. Bowman (US), David C. Bolton (US), Paul E. Bendheim (US), Darlene F. Groth (US), George G. Glenner (US), Hansruedl Büeler (CH), Adriano Aguzzi (CH), Andreas Sailer (CH), R.A. Greiner (CH), Peter Autenried (US), Michel Aguet (CH), Charles Weissmann (CH), Ana Serban (US), Ruth Koehler (US), Dallas Foster (US), Marilyn Torchia (US), Dennis R. Burton (US), Shu-Lian Yang (CN-US), Stephen J. DeArmond (US), Neil Stahl (US), and Ruth Gabizon (IL) found that a modified form of the normal prion protein (PrP) called protein prion scrapie (PrPsc) is essential for infectivity(1471-1475). It now appears that kuru, Creutzfeldt-Jakob disease (CJD), Gerstmann-Sträussler-Scheinker disease (GSS), and fatal familial insomnia (FFI) are all caused by a mutation of the normal gene PrPc to the abnormal gene PrPsc. The various disease phenotypes most likely arise from differences in familial genotypes and environmental factors.

Robert S. Sparkes (US), Melvin I. Simon (US), Vivian H. Cohn (US), R.E. Keith Fournier (US), Janice Lem (US), Ivana Klisak (US), Camilla Heinzmann (US), Cila Blatt (US), Michael Lucero (US), Thuluvancheri K. Mohandas (US), Stephen J. DeArmond (US), David Westaway (US), Stanley B. Prusiner (US), and Leslie P. Weiner (US) determined that prion protein (PrP) is encoded by a gene on the short arm of chromosome 20 in humans(1476).

Yu-Cheng Liao (US), Roger V. Lebo (US), Gary A. Clawson (US), and Edward A. Smuckler (US) identified and characterized a human complementary DNA whose protein product is considered to be the major component of scrapie-associated fibrils in Creutzfeldt-Jakob disease, kuru, and Gerstmann-Straussler syndrome. (1477).

Gerald A.H. Wells (GB), Anthony C. Scott (GB), C.T. Johnson (GB), R.F. Gunning (GB), R.D. Hancock (GB), Martin Jeffrey (GB), Michael Dawson (GB), and Raymond Bradley (GB) reported a new spongiform encephalopathy in cattle(1478).

James Hope (GB), Laura J.D. Reekie (GB), and Nora Hunter (GB), Gerd Multhaup (DE), Konrad Beyreuther (DE), Heather White (GB), Anthony C. Scott (GB), Michael J. Stack (GB), Michael Dawson (GB), and Gerald A.H. Wells (GB) showed that bovine spongiform encephalopathy (BSE), commonly called mad cow disease, is caused by a prion(1479).

Karen Hsiao (US), Harry F. Baker (GB), Tim J. Crow (GB), Mark Poulter (GB), Frank Owen (GB), Joseph D. Terwilliger (US), David Westaway (US), Jurg Ott (US), and Stanley Ben Prusiner (US) showed that in Gerstmann-Straüssler-Scheinker (GSS) syndrome prion protein (PrP) codon 102 is linked to the putative gene for the syndrome in two pedigrees, providing the best evidence to date that this familial condition is inherited despite also being infectious, and that substitution of leucine for proline at prion protein (PrP) codon 102 may lead to the development of Gerstmann-Straüssler-Scheinker (GSS) syndrome(1480).

Dmitry Goldgaber (US), Lev G. Goldfarb (US), Paul Brown (US), David M. Asher (US), W. Ted Brown (US), Scott Lin (US), James W. Teener (US), Stephen M. Feinstone (US), Richard Rubenstein (US), Richard J. Kascsak (US), John W. Boellaard (DE) and Daniel Carlton Gajdusek (US) found a mutation in the prion protein (PrP) gene of two patients with Creutzfeldt-Jakob disease (CJD) from one family and a second mutation in the same gene in three patients with Gerstmann-Straüssler-Scheinker (GSS) from another family. The mutation in two related familial CJD patients changed glutamine in position 200 to lysine(1481).

Matti Haltia (FI), Jussi Kovanen (FI), Lev G. Goldfarb (US), Paul Brown (US), and Daniel Carleton Gajdusek (US) found a new G-to-A mutation in codon 178 of the PRNP gene (resulting in a substitution of asparagine for aspartic acid) in the DNA of eight family members with typical Creutzfeldt-Jakob disease (CJD)(1482).

Rossella Medori (US), Pasquale Montagna (IT), Hans-Juergen Tritschler (DE), Andrea C. LeBlanc (CA), Pietro Cortelli (IT), Paolo Tinuper (IT), Elio Lugaresi (IT), Pierluigi Gambetti (US), Federico Villare (US), Valeria Manetto (US), Hsiao Ying Chen (US), Run Xue (US), Suzanne M. Leal (US), Patrizia Avoni (IT), Mirella Mochi (IT), Agostino Baruzzi (IT), Jean Jacques Hauw (FR), Jurg Ott (US), and Lucila Autilio-Gambetti (US) identified fatal familial insomnia (FFI) as a disease caused by a prion linked to a mutation in codon 178 of the prion protein gene (PRNP) resulting in the substitution of aspartic acid with asparagine (D178N)(1483, 1484). This disease is characterized by marked decrease or loss of the ability to sleep, dysautonomia and motor signs, and pathologically by preferential atrophy of thalamic nuclei.

Lev G. Goldfarb (US), Robert B. Petersen (US), Massimo Tabaton (IT), Paul Brown (US), Andrea C. LeBlanc (CA), Pasquale Montagna (IT), Pietro Cortelli (IT), Jean Julien (FR), Claude Vital (FR), William W. Pendelbury (US), Matti Haltia (FI), Peter R. Willis (US), Jean Jacques Hauw (FR), Paul E. McKeever (US), Lucia Monari (IT), Bertold Schrank (DE), Gary D. Swergold (US), Lucila Autilio-Gambetti (US), Daniel Carleton Gajdusek (US), Elio Lugaresi (IT), Pierluigi Gambetti (US), and Michael Steel (US) determined that familial Creutzfeldt-Jakob disease (CJD), subtype CJD 178, shares the D178N mutation with FFI although the clinical and pathological findings between the two are quite distinct. This is believed to be an example of phenotypic heterogeneity where both penetrance and expressivity are influenced by the familial genotypes and the environment(1485, 1486).

Stephen J. Sawcer (GB), Gerald M. Yuill (GB), Thomas F. Esmonde (GB), Peter Estibeiro (GB), James W. Ironside (GB), John E. Bell (GB), and Robert G. Will (GB) reported that two farmers who had cattle with bovine spongiform encephalopathy (BSE) or mad cow disease died of Creutzfeldt-Jakob Disease (CJD)(1487).

Stanley Ben Prusiner (US) and Michael R. Scott (US) suggested that mutant prions have the capacity to reshape normal prions into versions of themselves by causing a change in their folding pattern(1488).

John Joseph Bittner (US), in mice, discovered a naturally transferable cancer agent that is transmitted through the milk of the mother to her offspring(1489-1491).

Samuel Graff (US), Dan H. Moore (US), Wendell Meredith Stanley (US), Henry T. Randall (US), and Cushman D. Haagensen (US) isolated and characterized this agent as a virus(1492, 1493). Today it is called the Bittner mammary tumor virus.

Albert Jan Kluyver (NL) and Cornelis Bernardus Kees van Niel (NL-US) proposed that bacterial genera be defined both morphologically and biochemically(1494).

Sir Henry Hallett Dale (GB), Wilhelm Sigmund Feldberg (DE-GB), and Marthe Louise Vogt (DE-GB) found that in the presence of eserine (it blocks the action of acetylcholinesterase), curare does not block acetylcholine release from the motor nerve terminals upon electrical stimulation but, of course, blocks the effect of acetylcholine on the muscle membrane(1495). 

Sir Alister Clavering Hardy (GB) and Nora Ennis (GB) reported on the use of their plankton continuous recorder. Their aim was to develop a technique for estimating the numbers or weights of planktonic organisms beneath a unit area of sea surface or in a unit volume of water(1496).

Max Walker De Laubenfels (US) wrote an overview of all sponge genera. Presented as a monograph on the sponges of the Florida Keys, he revised almost casually all extant supraspecific taxa, erecting in the process several hundreds of new taxa. These paper taxa, i.e., erected by simply reading the descriptions in the previous literature, were mostly insufficiently established to be of use in sponge classification. Nevertheless, his book presented the first comprehensive overview of the genera and families of sponges, and it formed the basis for modern sponge classification(1497). He is commemorated by Delaubenfelsia Dickinson, 1945; Endectyon delaubenfelsi Burton, 1930; Holoplocamia delaubenfelsi Little, 1963; Rhaphidophlus delaubenfelsi Lévi, 1963; and Xestospongia delaubenfelsi Riveros, 1951.

Karl von Frisch (AT) was the first to suggest that the tightly coupled otic gas bladder in the mormyrid fishes can transmit the sound pressure component of the acoustic signal into the inner ear to enhance overall hearing ability(1498, 1499).

Richard Edwin Shope (US) found evidence that the virus which caused the 1918 influenza pandemic in humans and the swine influenza virus are one and the same(1500).

M. Robert Irwin (US) and Leon J. Cole (US) established that antigens are inherited using the Ring dove, Streptopelia risoria, and the Pearlneck dove, Spilopelia chinensis, as their experimental material. The term immunogenetics was coined in this article(1501).

Sir Ronald Aylmer Fisher (GB-AU) produced an article which represents a milestone in numerical taxonomy(1502).

Thore Edvard Brandt (SE) described a zinc deficiency syndrome in infants, characterized by acral dermatitis, alopecia, diarrhea, steatorrhea, and anal pustular eruptions on the face and around body orifices(1503). The syndrome is caused by the absence of the ligand essential for zing absorption, which is present in human but not cow milk. A similar disease picture may be seen in patients receiving artificial nutrition with low zinc content. Untreated, the disease is usually lethal.

Perrin Hamilton Long (US) and Eleanor A. Bliss (US) are credited with having introduced sulfonamides, which were the first effective antibacterial agents, to the United States. They used sulfanilamide in clinical applications at Johns Hopkins University in 1936(1504-1506).

Francis F. Schwentker (US), Sidney Gelman (US), Perrin Hamilton Long (US), and Eleanor A. Bliss (US) were the first to use antimicrobial therapy against meningococcal infections in demonstrating the efficacy of sulfonamides against meningococcus(1507, 1508).

Walter Thomas James Morgan (GB) and Stanley Miles Partridge (NZ-GB) were the first to describe the somatic antigen (endotoxin) of the Enterobacteriaceae as a toxin(1509-1511).

 

William Augustus Hinton (US) published the first major text on syphilis entitled Syphilis and Its Treatment(1512). Hinton developed the Hinton test to detect syphilis in blood and spinal fluids which reduced the number of false positive diagnoses of the disease. John A.V. Davies (US) improved the test to make it applicable to the cerebrospinal fluid. It then became known as the Davies-Hinton test.

Arthur M. Walker (US) and Charles L. Hudson (US) showed that glucose is reabsorbed from the proximal convoluted tubule, but not from the distal convoluted tubule, in both Necturus and frogs(1513).

Arthur J. Patek, Jr. (US), Richard P. Stetson (US), and F.H. Laskey Taylor (US) found that patients with hemophilia are lacking a factor present in normal plasma. They called it anti-hemophilic factor (AHF) or anti-hemophilic globulin (AHG)(1514, 1515). This deficiency now called hemophilia A (or factor VIII deficiency) is found almost exclusively in males and is one of the most common of the hereditary coagulation disorders

Yngve Zotterman (SE) isolated the single nerve units in the taste receptors of the tongue(1516, 1517).

Wilder Graves Penfield (US-CA) found that stimulation anywhere on the cerebral cortex could bring responses of one kind or another, but he found that only by stimulating the temporal lobes (the lower parts of the brain on each side) could he elicit meaningful, integrated responses such as memory, including sound, movement, and color. These memories were much more distinct than usual memory, and were often about things unremembered under ordinary circumstances. It seemed he had found a physical basis for memory, an engram. Penfield said, “there is hidden away in the brain, a record of the stream of consciousness”(1518-1521). In reality, however, the reported episodes of recall occurred in less than five percent of his patients, and these results have not been replicated by modern surgeons(1522).

Hans Hugo Bruno Selye (AT-HU-CA) proposed the concept of the stress syndrome after a twelve year study of the physiological effects of stress on animals. He promoted the complex topic of stress as applied to every aspect of daily life or medicine(1523-1529).

Guido Fanconi (CH), Erwin Uehlinger (CH), and Christian Knauer (CH) described cystic fibrosis (mucovidosis) also called Clarke-Hadfield syndrome(1530).

Paul Herbert Kimmelstiel (DE-US) and Clifford Wilson (GB) related that cases of kidney disease frequently, “show a striking hyaline thickening of the intercapillary connective tissue of the glomerulus. Evidence is presented which…suggests that arteriosclerosis and diabetes may play a part in its causation…. The characteristic clinical features are a previous history of diabetes, severe and widespread edema of the nephrotic type and gross albuminuria. Hypertension is frequently present.” This condition develops in about 20 to 25 percent of patients, in whom diabetes mellitus has been present for several years, usually beginning about 15 years after onset of diabetes and is often referred to as Kimmelstiel-Wilson syndrome(1531, 1532).

Robert Gesell (US), A. Kearney Atkinson (US), Richard C. Brown (US), Conway S. Magee (US), John W. Bricker (US), G. Stella (GB), Robert Franklin Pitts (US), Horace Winchell Magoun (US), and Stephen Walter Ranson (US) discovered that the respiratory center of the medulla is not a compact, sharply localized structure, but is scattered bilaterally in the gray matter of the ventral reticular formation of the medulla overlying the upper (cephalic) four-fifths of the inferior olive(1533-1543). The location is practically the same in the dog and cat(1533, 1539, 1541).

António Caetano Abreau Freire De Egas Moniz (PT) developed frontal leukotomy for treatment of certain clinical psychoses(1544, 1545).

Walter Jackson Freeman (US), with no qualifications for surgery, and James Winston Watts (US), in 1936, introduced a surgical technique for frontal lobe lobotomy into the U.S.A. The early 'technique' involved drilling burr-holes, later Freeman developed his famous/infamous transorbital approach, literally pushing an icepick into the brain via the eye sockets(1546, 1547).

Harold Neuhof (US) and Arthur S.W. Touroff (US) detailed the principles of operative treatment for acute putrid abscess of the lung in the era prior to antibiotic availability(1548).

Carl Gottfried Hartman (US) finally described the 28 day menstrual cycle and calculated the most fertile period for women as 11 to 14 days after the first day of the menstrual flow(1549). 

C.U. Ariens Kappers (US), G. Carl Huber (US), and Elizabeth Caroline Crosby (US) wrote their very important and influential book, The Comparative Anatomy of the Nervous System of Vertebrates, Including Man(1550).

Alvin John Elliott (US) invented the sterile evacuated tube for blood transfer(1551, 1552).

Henry Norman Bethune (CA) realized that a frequent cause of death on the battlefield is medical shock brought on by loss of blood and that a casualty whose wounds do not appear life-threatening could suddenly die. He conceived the idea of administering blood transfusions on the spot. He developed the world's first mobile medical unit. The unit contained dressings for 500 wounds, and enough supplies and medicine for 100 operations. Bethune organized a service to collect blood from donors and deliver it to the battlefront, thereby saving countless lives. His work during the Spanish Civil War in developing mobile medical units was a precursor to the later development of Mobile Army Surgical Hospital (MASH) units. ref

Georges Girard (FR) and Jean-Marie Robic (FR) developed an anti-plague (Yersinia pestis) vaccine known as the EV strain(1553).

Remington Kellogg (US) wrote Review of the Archaeoceti, a landmark in cetology(1554).

Alvan T. Marston (GB) found Homo sapiens fossil remains at Swanscombe, England(1555). This specimen, sometimes referred to as Swanscombe Man, was thermoluminescence dated at ca. 225,000 years old. 

Nikolaas Tinbergen (NL) devised many important and ingenious experiments to test aspects of animal behavior such as the releaser concept of Lorenz, sexual fighting in birds, social organization among vertebrates, begging response, and orientation mechanism(1556-1562).

Robert A. Broom (ZA) discovered the fossil remains of Australopithecus transvaalensis: Homo africanus at Sterckfontein dolomitic limestone cave deposit, northwest of Krugersdorp, near Johannesburg, Transvaal, Republic of South Africa(1563, 1564). It was dated at ca. 3.26 M.Y.B.P.

The California Institute of Technology established its Marine Station at Corona del Mar, California.

1937

“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(1565).

“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 in her biography of Madame Curie(1566).

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

Sir 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(1567).

Yasushige Ohmori (JP) reported a method for the determination of alkaline phosphatase in the blood(1568).

Tadeus Reichstein (PL-CH) discovered a steroid hormone from the adrenal cortex which he named substance M (cortisol)(1569).

Esmond Emerson Snell (US), Frank Morgan Strong (US), William Harold Peterson (US), and M. Swaminathan (IN) introduced microbial assays to estimation the concentration of growth factors, including vitamins(1570, 1571).

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(1572).

Arthur L. Schade (US) and Leona Caroline (US) identified transferrin as an abundant plasma iron transport protein(1573). 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(1574-1576).

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(1577).

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(1578).

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(1579-1581).

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(1582). 

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(1583, 1584).

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(1585).

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(1586).

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(1587).

Alwin Max Pappenheimer, Jr. (US) isolated, crystallized, and characterized diphtheria toxin(1588). This was the first bacterial toxin to be obtained in pure crystalline form.

William Charlton (GB), Sir Walter Norman Haworth (GB), Stanley Peat (GB), Edmund Langley Hirst (GB), Frederick A. Isherwood (GB), F. Smith (GB), William Zev Hazzid (GB), and Israel Lyon Chaikoff (GB-US) settled the basic structural features of the starch, and glycogen molecules(136, 1589-1591).

Otto Fritz Meyerhof (DE-US) proposed that the splitting of ATP might supply energy to initiate the succession of events in muscular activity(1592).

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)(1593, 1594). 

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(1595). 

Eugene I. Rabinowitch (US) and Joseph Weiss (US) provided evidence that chlorophyll a can be oxidized by light and ferric compounds(1596).

Michael Heidelberger (US), Kai O. Pedersen (SE), and Elvin Abraham Kabat (US) determined the molecular weight of antibodies(1597, 1598). 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 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(1599, 1600).

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 reenter 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”(1601-1604).

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(1605).

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)(1606-1609).

James A. Doull (US) carried out clinical trials on the efficacy of using diasone (Diamidin), 4-4’ diaminodiphenyl sulfone, 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)(1610).

Abraham White (US), Hubert Ralph Catchpole (GB-US), and Cyril Norman Hugh Long (GB-US) crystallized the lactogenic hormone prolactin(1611).

André Pirson (DE) discovered that manganese is essential for oxygenic photosynthesis(1612, 1613). 

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(1614, 1615).

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(1616).

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(1617).

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(1618).

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(1619).

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(1620).

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(1621)(Nakhimovskaia 1937).

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(1622).

Harry N. Holmes (US) and Ruth E. Corbet (US) crystallized vitamin A (retinol) from liver oil of mackerel and other fishes(1623).

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(1624, 1625).

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(1626).

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(1627, 1628).

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(1629-1632).

Albert Imre Szent-Györgyi (HU-US) drawing on the earlier observations of Torsten Ludvig Thunberg (SE), Federico Battelli (IT), Lina Salomonovna Stern (LT-CH) and others assembled a logical sequence for the cellular oxidation of succinate: succinate—fumarate—malate—oxaloacetate. Especially significant was Szent-Györgyi’s observation that adding small amounts of oxaloacetate or malate to minced muscle suspensions evokes the utilization of an amount of oxygen far beyond that required to oxidize the added dicarboxylic acid to CO2 and water. From this and other experiments Szent-Györgyi concluded that these acids stimulate the oxidation of some endogenous substrate in the tissue, presumably glycogen, one molecule of malate or oxaloacetate promoting the oxidation of many molecules of the endogenous substrate(1633).

Carl Martius (DE) and Franz Knoop (DE), somewhat later, found that citrate is enzymatically oxidized to succinate by animal tissues in the sequence: citrate—alpha ketoglutarate—succinate(1416).

Sir Hans Adolf Krebs (DE-GB), William Arthur Johnson (GB), and Leonard V. Eggleston (GB) observed that citric acid exerts a catalytic effect on the respiration of minced pigeon-breast muscle and that citrate is successively converted to alpha-ketoglutarate and succinate, and that oxaloacetate is converted into citrate by the addition of two carbon atoms from an unidentified source. From their conclusions and those of prior workers like Franz Knoop (DE), Carl Martius (DE), and Albert Imre Szent-Györgyi (HU-US) they proposed a citric acid cycle: citrate — isocitrate — oxalosuccinate — alpha-ketoglutarate — succinate — fumarate — malate —oxaloacetate — citrate(1634, 1635). This cycle has been found to exist in virtually all plants, animals, and aerobic microorganisms(1636) and has been called tricarboxylic acid cycle, citric acid cycle, and Krebs cycle.

Erwin Paul Negelein (DE) and Hans Joachim Wulff (DE) crystallized alcohol dehydrogenase from yeast(1637).

Mortimer Louis Anson (US) crystallized carboxypeptidase(1638).

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(1639). 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(1640-1642). Pellagra is the human equivalent of black-tongue.

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(1643).

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(1644, 1645).

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)(1646).

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)(1647).

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(1648, 1649). 

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(1650-1652). The elucidation of the feedback mechanism between the adrenal cortex and the pituitary became the model for similar studies. 

Sir 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(1653, 1654).

Edward Holbrook Derrick (AU), Sir Frank Macfarlane Burnet (AU), and Mavis Freeman (AU), as the result of a study of 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(1655-1660). 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(1661).

Fred R. Beaudette (US) and Charles B. Hudson (US) were the first to isolate Coronavirus. The source was chickens with infectious bronchitis(1662).

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(1663).

Jane Parry (GB) reported that severe acute respiratory syndrome (SARS) is likely caused by a strain of Coronavirus(1664). It was later called SARS-Associated Coronavirus (SARS-CoV).

Thomas Francis, Jr. (US) and Thomas P. Magill (US) produced evidence to indicate that the influenza virus exists in distinctly different serological strains. Among others they isolated influenza type B(1665-1667).

Joseph Stokes, Jr. (US), Aims C. McGuinness (US), Paul H. Langner, Jr. (US), and Dorothy R. Shaw (US) reported successfully immunizing human subjects to the influenza virus by subcutaneous inoculation of the vaccine(1668). Subcutaneous inoculation of man with active or formalized influenza virus increases the titer of serum antibody(1669).

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)(1670-1673).

Thomas Milton Rivers (US) devised a set of postulates, similar to 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(1674).

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(1675).

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(1676-1681). 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(1682).

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 as a result of the action of selection on a genetic system(1683).

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(1684-1687).

Gladwyn Kingsley Noble (US) and A.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(1688).

Theodore Holmes Bullock (US) and Friedrich P.J. Diecke (US) showed that pit vipers can detect long-wavelength infrared radiation(1689).

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(1690).

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(1691).

Walter Michel (DE) was the first to produce artificial heterokaryons. He fused plant protoplasts from different species and genera(1692).

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(1693, 1694). 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(1695).

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(1696).

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 (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 are able to 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(1697-1710).

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(1711).

Max Theiler (ZA-US), Hugh Hollingsworth Smith (US), Henrique A. Penna (BR), and Adhemar Paoliello (BR) carried out successful field trials of their yellow fever vaccine(1712, 1713).

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 is able to transmit the systemic disease when transplanted into a mouse(1714).

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 is able to proliferate in vivo(1715).

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 leukaemia (AML) patients, only a small fraction of the tumor cells with a characteristic marker signature is able to establish leukaemia in recipient mice(1716, 1717).

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(1718, 1719).

Hans Popper (AT-US), Emil Mandel (AT), and Helene Mayer (AT) developed the creatinine clearance test for assessing kidney function(1720).

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(1721).

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(1722).

Ludvig G. Browman (US) showed that the exposition of rats to continuous light interrupts the estral cycle inducing the state of persistent estrous(1723).

Virginia Mayo Fiske (US) reported on the effect of light on sexual maturation, estrous cycles, and anterior pituitary in the rat(1724).

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(1725).

Abraham Albert Hijmans van den Bergh (NL) and Wilhelm Grotepass (NL) gave the first clinical and biochemical picture of variegate porphyria (VP)(1726).

Jan Gosta Waldenström (SE) described over one hundred patients with acute intermittent porphyria (AIP), most of whom originated from a small village in Northern Sweden(1727). 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)(1728).

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(1729, 1730). 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(1731). 

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(1732). 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)(1733, 1734).

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)(1735). 

Tracy J. Putnam (US) and H. 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. (1736, 1737).

Riojun Kinosita (JP-US) found that liver tumors can be readily induced by ingestion of dimethylaminoazobenzene, a dye known as " butter-yellow "(1738).

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(1739-1741).

Walter Edward Dandy (US), in 1937, performed he first direct surgical approach and clipping of a cerebral aneurysm(1742).

Ugo Cerletti (IT) and Lucio Bini (IT), in 1937, treated schizophrenic patients with applications of electricity(1743). Electric eels and fish were used by people in ancient times to treat headaches and mental illness.

James Barrett Brown (US) achieved permanent survival of skin grafts exchanged between human monozygotic twins(1744).

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(1745, 1746). 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 effected 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(1747).

John Heysham Gibbon, Jr. (US) was the first to attempt a bypass of the heart using an external circulation. Partially replacing the circulation between the heart and the lungs, he managed to keep a cat alive in this way for four hours. Two years later, under sterile conditions, 3 out of 13 cats survived for more than 250 days following similar procedures, with the remaining animals living for between 1 and 23 days(1748, 1749). See, J.J.C. LeGallois, 1813, M. von Frey, 1885, and S. Brukhonenko, 1929.

Clarence Dennis (US), Dwight S. Spreng, Jr. (US), George E. Nelson (US), Karl E. Karlson (US), Russell M. Nelson (US), John V. Thomas (US), Walter Phillip Eder (US), and Richard L. Varco (US) reported the first case of open-heart surgery with machine-supported circulation and oxygenation. It was performed on April 1, 1951. This was apparently the first occasion for such an attempt to be made anywhere. The patient was a 4-year old child with a known inter-atrial septal defect who was previously operated upon with hope of repair by closed technique. When an attempt was made to take the patient off perfusion, the patient’s heart could not maintain the circulation, and the patient expired. Postmortem examination revealed that the lesion was not the simple secundum type of defect but rather an atrioventricular canal, a complicated set of anomalies(1750).

Forest Dewey Dodrill (US), Edward Hill (US), and Robert A. Gerisch (US) performed the first clinically successful total left-sided heart bypass in a human on July 3, 1952. The machine was used to substitute for the left ventricle for 50 minutes while a surgical procedure was carried out to repair the mitral valve; the patient's own lungs were used to oxygenate the blood(1751, 1752).

John Heysham Gibbon, Jr. (US) successfully applied extracorporeal circulation in a 18 year old female with an atrial septal defect. Unfortunately he was unable to repeat this success in other humans(1753).

John Heysham Gibbon, Jr. (US), Arthur R.C. Dobell (US), and George B. Voigt (US) reported the closure of interventicular septal defects on dogs during open cardiotomy with the maintenance of the cardio-respiratory functions by a pump oxygenator(1754).

Erwin Chargaff (AT-US) and Kenneth B. Olson (US) discovered that protamine can neutralize heparin’s function as an anticoagulant(1755).

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(1756).

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" (1757).

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(1758).

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)(1759).

These early versions of heart-lung machines were cumbersome and dangerous —often leaking blood, damaging blood cells and causing air embolisms(1760).

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(1761).

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(1762).

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(1763).

Dianne Edwards (GB) and E. Catherine W. Rogerson (GB) discovered Cooksonia pertonii near Brecon Beacons, England in 420 Ma rock(1764, 1765).

Ales Hrdlicka (CZ-US) proposed that America had been peopled from Asia via the Bering Strait(1766).

Dorothy Anne Elizabeth Garrod (GB), Dorothea Minola Alice Bate (GB), Theodore Doney McCowan  (GB), and Sir 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(1767, 1768). These specimens are dated at 30K-60K B.P. 

ca. 1938

James Gordon Horsfall (US) introduced chloranil as a fungicide for legume seed treatment(1769).

1938

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(1770-1772).

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(1773-1781).

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(1782). 

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(1783).

James R. Weisiger (US), Elizabeth A. Jacobs (US), John Clark Sheehan (US), and William A. Bolhofer (US) later synthesized hydroxylysine(1784, 1785).

Albert Neuberger (DE-GB) discovered that ovalbumin, a protein from chicken egg white, contains a carbohydrate moeity. This marks the beginning of modern glycoprotein research(1786).

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(1787-1789).

Sir Edward Charles Dodds (GB) discovered diethylstilbestrol (DES), a powerful synthetic hormone used to treat prostate conditions, to fatten cattle, to treat women at risk for miscarriage and as a morning-after contraceptive(1790, 1791).

In 1972 the prescribed form of diethylstilbestrol (DES) was proved carcinogenic in adult women as well as in fetuses, when unusual types of endometrial cancer, reminiscent of the adenocarcinomas of the vagina of DES daughters, developed in young women treated with DES for five years or longer.

Arthur Stoll (CH) and Albert Hoffman (CH-US), in 1938, produced lysergic acid diethylamide (LSD) while trying to synthesize a new drug for the treatment of headaches. It is one of the most potent psychoactive drugs known(1792). Later it was shown to block or inhibit the action of the brain’s neurotransmitter serotonin(1793).

David Keilin (PL-GB) and Edward Francis Hartree (GB) described the mechanism of the decomposition of hydrogen peroxide by catalase(1794).

Felix Haurowitz (CZ-US) discovered the drastic change in crystalline shape of deoxyhemoglobin from hexagonal plates to elongated prisms as oxygen is taken up(1795). This is sometimes cited as the first observation of an allosteric reaction.

Lionel Ernest Howard Whitby (GB) reported that 2-(p-aminobenzene sulphonamide) pyridine is chemotherapeutically active in experimental infections in mice against pneumococci of Types I, II, III, V, VII, VIII and especially against Types I, VII, and VIII. It was as active as sulphanilamide against hemoltyic streptococcus and meningococcus(1796).

Maxwell Finland (RU-US), Elias Strauss (US), and Osler L. Peterson (US) reported that the sulfonamide, “Sulfadiazine was used in the treatment of 446 patients with various infections. It appeared to be highly effective in the treatment of…pneumococcic, staphylococcic and…pneumonias; meningococcic infections; acute infections of the upper respiratory tract including sinusitis; erysipelas; acute infections of the urinary tract, particularly those associated with Escherichia coli bacilluria, and acute gonorrheal arthritis…. Toxic effects…were relatively mild and infrequent”(1797).

Emil L. Smith (US) demonstrated that chlorophyll is bound to proteins(1798).

Archibald Vivian Hill (GB) found that, even in "isometric" contractions, the muscle fibers initially shorten. He proposed that skeletal muscles have two distinct components in series with each other: a contractile component that shortens when stimulated and an elastic component that lengthens under tension. Hill proposed an empirical relation for the force-velocity curve that emphasized the hyperbolic form of the data. This equation is still commonly used today: (force + a)(velocity + b) = (forcemax + a)b, where a and b are constants. The functional importance of the Hill equation is that it allowed scientists to clearly distinguish between slow-twitch and fast-twitch muscles and, using this relationship, develop force-power curves and determine peak power(1799).

Herman Moritz Kalckar (DK-US) provided evidence for the production of phosphoenolpyruvate (PEPA) from fumaric or malic acids, observations that later provided an important clue to the mechanisms involved in the formation of glucose from non-carbohydrate sources in animal tissues(1800).

Carl Ferdinand Cori (CZ-US), Gerty Theresa Cori, née Radnitz (CZ-US), Sidney P. Colowick (US) and Gerhard Schmidt (DE-US) recognized that ATP is required to phosphorylate glucose and thus energize it for the biosynthesis of glycogen. They also discovered that if glycogen is broken down it is not hydrolyzed to glucose units but rather is converted to units of glucose-1-phosphate by phosphorylase in a readily reversible reaction. (Later it was discovered, by others, that the glycogen synthesis reaction is uridine-5’-triphosphate + glucose-1-phosphate yieldsuridine diphosphate glucose (UDPG)which yieldsglycogen in the presence of glycogen synthetase). They demonstrated the in vitro synthesis of amylose (the linear alpha 1,4-glycosidically linked polysaccharide) from glucose-1-phosphate. During breakdown the glucose-1-phosphate is converted to glucose-6-phosphate and this in turn undergoes other changes through a whole series of phosphate-containing compounds. Painstakingly the Coris detected these and fitted them into the proper niches of the breakdown course(1801-1803). Wilhelm Kiessling (DE) made very similar observations(1804, 1805). 

Arda Alden Green (US), Gerty Theresa Cori, née Radnitz (CZ-US), Carl Ferdinand Cori (CZ-US), and John L. Oncley (US) later crystallized phosphorylase(1806, 1807).

Charles Samuel Hanes (CA), in 1940, would show that higher plants are capable of carrying out the same reactions(1423).

William Cumming Rose (US) determined that ten amino acids are essential in the diet of the rat and dog (histidine, isoleucine, leucine. threonine, lysine, methionine, phenylalanine, tryptophane, valine, and arginine). The rat was found to survive in the absence of arginine but its growth was suboptimal(1808, 1809).

James Gordon Horsfall (US), Robert O. Magie (US), and Ross F. Suit (US) discovered that the Bordeaux mixture harms tomatoes by closing the leaf pores, weakening the cuticle around the pores, and hardening the lamella within the leaves and stunting the plants(1810).

Peter Wilhelm Joseph Holtz (DE), Rudolf Heise (DE), and Kathe Lüdtke (DE) determined that epinephrine (adrenaline) is made from norepinephrine (noradrenaline) in the chromaffin cells of the adrenal medulla(1811). 

Johannes Van Overbeek (US) reported that certain nongeotropic mutants in maize did not show the usual inequality of auxin distribution(1812).

Lewis Charles Chadwick (US) and Donald C. Kiplinger (US) discovered that auxins promote rooting of stem cuttings of ornamental plants(1813). 

Rudolf Signer (CH), Torbjörn Oskar Caspersson (SE), and Einar Hammarsten (SE) reported that the physical properties of calf thymus DNA suggested that the molecule is rod shaped, with a length approximately 300 times its width, and a molecular weight between 500,000 and 1,000,000(1814).

Erhard Robert Fernholz (US) determined the structure of alpha-tocopherol (vitamin E)(1815).

Paul Karrer (RU-CH), Hans Heinrich Fritzsche (CH), Beat Heinrich Ringier (CH), and H. Salomon (CH) synthesized alpha-tocopherol (vitamin E) and proved its biological role as a vitamin(1816).

Albert Edward Gillam (GB) and Isidore Morris Heilbron (GB), William Edward Jones (GB), Edgar Lederer (FR), and Franz H. Rathmann (FR) discovered that vitamin A (retinol) in the retinas of fresh water fishes differs from that found in other animals. This form is called vitamin A2(1817, 1818).

W. William Sebrell (US) and Roy F. Butler (US) used canine experiments to show that some pellagra patients who resisted treatment with nicotinic acid were in fact simultaneously suffering from riboflavin (vitamin B2) deficiency(1819). Joseph Goldberger (SK-US) and George A. Wheeler (US) had called this condition pellagra sine pellagra but did not appreciate its underlying cause.

Samuel Lepkovsky (US), John C. Keresztesy (US), Joseph R. Stevens (US), Paul György (US), Richard Johann Kuhn (DE), Gerhard Wendt (DE), A. Ichiba (JP), and K. Michi (JP) isolated and crystallized pyridoxine (vitamin B6)(1820-1824).

William C. Langston (US), William J. Darby (US), Carroll F. Shukers (US), and Paul L. Day (US) found that vitamin M (folic acid) is essential for the rhesus monkey (Macaca mulatta)(1825). 

Wilhelm Sigmund Feldberg (DE-GB) and Charles Halliley Kellaway (GB) discovered that cobra venom contains a substance which causes the contraction of smooth muscle in the guinea pig. They determined that it is distinct from histamine, another known factor in inflammatory reactions. Relative to histamine, this new mediator has a longer duration of action and thus was called the slow reacting substance (SRS)(1826).

Walter E. Brocklehurst (GB) refined its name to "slow reacting substance of anaphylaxis," or SRS-A(1827). See Dahlen, 1980.

Robert C. Murphy (US) Sven Hammerstrom (SE), and Bengt Samuelsson (SE) elucidated the structure of the "slow reacting substance of anaphylaxis" (SRS-A) as a derivative of arachidonic acid, leukotriene(1828).

Georg Charles de Hevesy (HU-SE), Jakub (Jacob) Karol Parnas (PL), Tadeusz Baranowski; Tadeush Baranowski (PL), A. Jerzy Gutke (PL), Pawel Ostern (PL), and Tadeusz W. Korzybski (PL) conducted experiments with tissues, eggs, milk, and yeast fermentations using synthetic radioactive adenylic acid, in which it was possible to trace radioactive phosphorus. After a period of incubation a considerable portion of the active phosphorus was found in the sugar phosphoric acid esters fraction. Evidence indicated that this also occurs in bacteria, muscle, and yeast cells(1829-1831). These experiments are likely the first to use radioactive phoshorus in biological studies.

Wilhelm Kiessling (DE) and Otto Fritz Meyerhof (DE-US) found that adenylic acid and its allied phosphates act as coenzymes in the transfer of phosphates from phosphopyruvic acid to glucose(1832, 1833). Among these adenosine nucleotides are: adenylic acid, adenosine diphosphate and adenosine triphosphate, diadenosine pentaphosphoric acid, diadenosine tetraphosphoric acid, and the pyrophosphate. All apparently function as phosphate carriers in cellular glycolysis.

Otto Heinrich Warburg (DE) discovered flavoproteins on the basis of simple observations on lactobacilli which lack the red cytochromes. On exposure to air the intact cells become yellow. He isolated dehydrogenases, flavoproteins, and identified their coenzymes(1834).

Otto Heinrich Warburg (DE) and Walter Christian (DE) working with a preparation of D-amino oxidase isolated a flavin derivative which would later be shown to be flavine-adenine-dinucleotide (FAD)(1835).

Erwin Haas (US) showed that this FAD is also the prosthetic group of a flavoprotein isolated from yeast(1836).

Michael Doudoroff (RU-US) discovered that riboflavin (vitamin B2) is directly involved in bacterial luminescence(1837).

Hans W. Doerr (DE) stated that herpes simplex virus infection in man resulted from the endogenous production of a virus-like agent by the cell under the influence of certain stimuli, and were not caused by exogenous infection. Once the agent had been produced, it would act on the cells of susceptible animals (not man) as a true virus(1838).

Sir Frank Macfarlane Burnet (AU) and Stan W. Williams (AU) stated that ‘Herpes simplex infections, however, once contracted, seem to persist for life. The virus remains for the most part latent; but under the stimulus of trauma, fever, and so forth it may at any time be called into activity and provoke a visible herpetic lesion”(1839).

Stephen Bartlett (GB), Anda G. Cotton (GB), Isaac Walker Rupel (US), Gustav Bohstedt (US), Edwin Bret Hart (US), Edwin C. Owen (GB), James Andrew Buchan Smith (GB), and Norman Charles Wright (GB) clearly established that bacteria of the rumen synthesize protein from nonproteinaceous material and are capable of obtaining nitrogen from sources such as urea. Significant amounts of protein is made available to the ruminant when the bacteria die and are digested(1840-1842).

Barbara McClintock (US) and Hermann Joseph Muller, Jr. (US) defined telomeres as special structures required for chromosome stability (prevention of fusion)(1843, 1844).

Herbert Göpfert (DE) and Hans Schaefer (DE) used extracellular electrodes to record, during synaptic transmission, the proper electrical response of the post-synaptic membrane, or endplate potential(1845).

Albert Claude (BE-US) reported RNA rich particles in the cytoplasm(1846-1848).

Torbjörn Oskar Caspersson (SE), Jack Schultz (US), Lennart Aquilonius (SE), and Jean Louis Auguste Brachet (BE) collected considerable evidence about the location of the nucleic acids within cells. Their work indicated that there is a correlation between high levels of protein synthesis and high levels of RNA synthesis. Caspersson also noted that most of the cytoplasmic RNA is concentrated in particles(1849-1858).

Edgar G. Anderson (US) and Leslie Hubricht (US) developed the concept of introgressive hybridization—usually termed “introgression”—and gave it its name. As the name implies, introgression refers to the gradual infiltration of germplasm of one species into another through repeated backcrossing(1859).

Theodosius Grigorievich Dobzhansky (RU-US) and Alfred Henry Sturtevant (US) published the first account of the use of inversions in constructing a chromosomal phylogenetic tree(1860).

Marcus Morton Rhoades (US) discovered the Dotted mutator gene in maize. It was found on a single ear of corn where it produced a phenotype of variegated endosperm characterized by purple dots on a colorless background(1861).

Barbara S. Burks (US) recorded the first case of autosomal linkage in man. It involved tooth deficiency and hair color(1862).

Warren Weaver (US) is credited with being the first person to use the phrase molecular biology in its modern context. In his 1938 report to the Rockefeller Foundation he said, "Among the studies to which the Foundation is giving support is a series in a relatively new field, which may be called molecular biology”(1863). See, Karl Friedrich Wilhelm Ludwig, 1858.

Harry Plotz (US) grew the measles virus in the Macacus rhesus monkey, transferred it to chick embryo culture, then induced the disease in monkeys(1864). This work essentially proved the viral etiology of measles.

John Franklin Enders (US) and Thomas C. Peeples (US) grew the measles (rubeola) virus in several cell lines including human kidney tissue culture and observed that it induced the formation of multinucleated syncytia with a foamy appearance in cell culture. It was during these experiments that foamy virus (a retrovirus) was discovered(1865).

Erich Traub (DE-US) showed that if you inject lymphocytic choriomeningitis virus into embryonic mice in utero, they grow up without making antibodies to it, even though it is very foreign. Mice infected as adults give a normal immune response(1866). Ray David Owen (US) would later call this phenomenon tolerance. See Owen, 1945.

James D. Trask (US), Alfred J. Vignec (US), and John R. Paul (US) isolated poliovirus from human feces(1867, 1868).

William Trager (US) was the first to successfully grow an arbovirus (equine encephalomyelitis) in insect tissue culture. He maintained fragments of tissue from the mosquito, Aedes aegypti for two to three weeks depending upon the tissue(1869).

LeRoy D. Fothergill (US), John Holmes Dingle (US), Sidney Farber (US), and Marion L. Connerley (US) isolated eastern equine encephalomyelitis virus from the brain tissue of several humans thus proving that it can infect man(1870).

Leroy D. Fothergill (US), John Holmes Dingle (US), and Jacksolt Cabot Fellow (US) confirmed birds as playing a role in the transmission cycle of eastern equine encephalitis(1871).

Beatrice F. Howitt (US) isolated the virus of equine encephalitis from the brain of a child(1872).

Beatrice F. Howitt (US) isolated western equine encephalomyelitis from a man infected with it during an epidemic in California. This proved that humans are susceptible(1873).

Chief Medical Officer (GB) reported jaundice in a small group of individuals who had received injections of measles convalescent serum(1874). This very likely represents the first recorded cases of serum hepatitis.

Bodo van Borries (DE), Ernst August Friedrich Ruska (DE), Helmut Ruska (DE), and Gerhard Piekarski (DE) applied the electron microscope to the study of bacteria and viruses for the first time(1875-1879).

Edgar William Todd (GB) discovered that streptococci produce at least two different hemolysins; streptolysin O and streptolysin S(1880).

Rodolfo Robles (GT) proved that Mal del Pinto o Carate is caused by a spirochete in the genus Treponema. ref

Alfonso Armenteros (CU) and Grau Trjana (CU) discovered that the spirochete Treponema carateum (herrejoni) is the etiological agent of Mal del Pinto o Carate. Their studies were based on earlier studies—1927—by Salvador Gonzalez Herrejon (MX). ref 

M. Ruiz Castañeda (MX) showed that large numbers of Rickettsiae mooseri appear in the lungs of rats following intranasal inoculation (1881).

Herald Rea Cox (US) described the successful cultivation of rickettsiae in the yolk sac of the developing chick embryo (1882). The family Coxiellaceae and the genus Coxiella, which contain the organism that causes Q fever, are named for him.

Ernest Charles Dickson (US) offered proof that the inhalation of the fungal chlamydospores of Coccidioides immitis can lead to the disease variously called coccidioidomycosis, coccoidioidal granuloma, valley fever, or desert fever(1883, 1884).

Sir Samuel Rickard Christophers (GB) and James D. Fulton (GB) were the first to investigate the metabolism of malarial parasites(1885).

Sterling Howard Emerson (US) studied the self-incompatibility system of Oenothera organensis and found that pollen rejection is a function of the style under control of a locus with multiple alleles(1886).

Dirkje E. Reinders (NL) found that auxin present in concentrations as low as 1mg/liter stimulated water uptake in potato discs along with an increase in respiration and loss in dry weight(1887).

John Nathaniel Couch (US) discovered that scale insects and the fungus Septobasidium have a mutually reliant relationship, but that together they destroy their host tree(1888).

Gottfried Samuel Fraenkel (DE-US) and John W.S. Pringle (GB) showed that the halteres, which replace the second pair of wings in the adult fly, actually function as miniature gyroscopes or balance organs(1889).

Hans Spemann (DE) proposed the first cloning experiment, transferring a nucleus from an adult cell to an enucleated egg. In 1928, he used the nucleus from a 16-cell salamander embryo to create an identical twin(1890).

Robert W. Briggs (US) and Thomas J. King (US), working on the frog Rana pipiens, successfully transplanted living nuclei in multicellular organisms. They transplanted blastula nuclei into enucleated eggs, which then developed into normal embryos(1891).

John Bertrand Gurdon (GB) transplanted intestinal epithelium-cell nuclei from Xenopus tadpoles into enucleated frog eggs and managed to produce 10 normal tadpoles. The logical consequence of Gurdon's success — that the nuclei of differentiated cells retain their totipotency — provided a key conceptual advance in developmental biology(1892, 1893). This work proved that genes are not lost or changed during cell differentiation — they are just differentially expressed. It became clear that the genes expressed in a nucleus are profoundly influenced by their cytoplasmic environment.

John Burdon Sanderson Haldane (GB-IN) used the word clone (from Greek for "twig") to describe Gurdon's frog experiments of 1962(1894).

John Bertrand Gurdon (GB) removed the nuclei from fertilized frogs’ eggs, replaced them with nuclei taken from cells of the gut of a single tadpole, and grew a number of frogs with identical genetic constitutions—an animal clone(1895, 1896).

Keith H.S. Campbell (GB), Jim McWhir (GB), William A. Ritchie (GB), and Ian Wilmut (GB) cloned identical lambs from differentiated, 9 day old embryo cells(1897).

Ian Wilmut (GB), Angelika E. Schnieke (GB), Jim McWhir (GB), Alex J. Kind (GB), and Keith H. Campbell (GB) reported the birth of live lambs from three new cell populations established from adult mammary gland, fetus and embryo, i.e., the lambs were clones of adults. The fact that a lamb was derived from an adult cell confirms that differentiation of that cell did not involve the irreversible modification of genetic material required for development to term. The birth of lambs from differentiated fetal and adult cells also reinforces previous speculation that by inducing donor cells to become quiescent it will be possible to obtain normal development from a wide variety of differentiated cells(1898).

W.W. Ferguson (GB), A.H. Lewis (GB), and S.H. Watson (GB) discovered that trace quantities of molybdenum in the diet of ruminants causes diarrhea. The disease is called teart(1899).

Lucy Wills (GB) and Barbara D.F. Evans (GB) determined that tropical macrocytic anemia could be treated successfully using autolyzed yeast extract and/or injections of crude liver extract but not with the purified liver extract (vitamin B12) used to treat pernicious anemia(1900).

Hugh R. Butt (US) and Albert M. Snell (US) reported that their clinical trials indicated a rough inverse relationship between prothrombin levels and coagulation time(1901). This led to the use of vitamin K for the treatment of hemorrhage in humans.

Hugh R. Butt (US), Albert M. Snell (US), and Arnold E. Osterberg (US) reported the first successful correction of a vitamin K deficiency in a patient with biliary obstruction (and intraluminal bile acid deficiency). They showed that a crude vitamin K preparation was absorbed and effective only when given together with conjugated bile salts(1902).

Maurice Bolks Visscher (US), Raymond C. Ingraham (US), Richard L. Varco (US), Charles W. Carr (US), Robert B. Dean (US), Dorothy Erickson (US), E. Stanton Fletcher, Jr. (US), Harry P. Gregor (US), Marian Sedin Bushet (US), and Dorothy Erickson Barker (US) demonstrated how the intestine handles electrolytes. They established that both anions and cations can be absorbed against a diffusion gradient and that there is a lengthwise gradient of absorption and secretion in the small intestine. They determined that there is a substantial two-way traffic of sodium between blood and lumen of the small intestine and colon and that there is a gradient of decreasing traffic from duodenum to colon.

Chyme is brought to isotonicity and neutrality in the duodenum and upper jejunum by a brisk flow of electrolytes in both directions across the intestinal mucosa. In the ileum there is net absorption of sodium, chloride, and water, with secretion of bicarbonate replacing chloride in the lumen. The colon performs the essential function of maintaining the volume of extracellular fluid by net absorption of the sodium that escapes absorption in the ileum. Ingraham and Visscher presented compelling evidence for the independence of absorptive and secretory fluxes(1903-1905).

Henry Hubert Turner (US) described a series of young women with failure of sexual maturation, short stature, and neck webbing. These are the clinical symptoms of what later became known eponymically as Turner’s syndrome. Turner believed the symptoms were due to a defect in the anterior pituitary gland(1906). Today, we know the underlying cause is a 45XO karyotype.

Charles Edmund Ford (GB), Ken W. Jones (GB), Paul Emanuel Polani (ES-GB), J. Carlos De Almedia (BR), and Joseph H. Briggs (GB) discovered that gonadal dysgenesis (Turner’s syndrome) in humans is associated with a 45XO karyotype(1907).

Alexander Benjamin Gutman (US) and Ethel Benedict Gutman (US) pointed out the increased serum activity of acid phosphatase in metastasizing prostate carcinoma and demonstrated the usefulness of measuring serum acid phosphatase levels in the diagnosis and management of patients with prostatic malignancy(1908).

David Bruce Dill (US) noted that reductions in maximal heart rate were as great as 40 to 50 beats per minute at an altitude of 17,500 feet; documented the phenomenon of hemoconcentration during both acute and chronic exposure to high altitude; discovered that the ability of some animals to adapt to high altitudes is more the result of quality than the quantity of their circulating hemoglobin; and showed that one way the human body adapts to higher temperature is by producing more perspiration which contains less salt per unit volume(1909).

Sid Robinson (US) in his doctoral dissertation performed the first study ever done describing the effect of age and of strenuous physical training on the aerobic capacity of man. Here for the first time appeared the relationship between age and maximal heart rate as approximately 220 minus age; a finding confirmed many times since(1910).

Jerome W. Conn (US), Louis Harry Newburgh (US), Margaret W. Johnston (US), and Elizabeth S. Conn (US) were among the first to clearly recognize the relationship between obesity and adult-onset diabetes by showing the resumption of normal carbohydrate tolerance after attainment of normal weight in twenty of twenty-one patients(1911).

Julius Lempert (US) performed successful surgery for hearing restoration; now called Lempert's fenestration operation(1912). 

Samuel Rosen (US) mobilized the footplate of the stapes to restore hearing in otosclerosis--a procedure attempted by Jean Kessel (DE) in 1876(1913).

John J. Shea, Jr. (US) developed the modern technique of footplate mobilization, soft tissue grafting of the oval window, and ossicular replacement. Shea is also credited with the first stapedotomy(1914, 1915).

Frederic Edward Mohs (US) developed the Mohs micrographic surgery (MMS) technique in 1938 to remove skin cancer lesions. The Mohs procedure is considered the best method for treating certain types of skin cancer, especially of the head and neck, with cure rates approaching 100%(1916). Occasionally called chemosurgery.

Harvey Williams Cushing (US), Louise Charlette Eisenhardt (US), and Edward B. Schlesinger (US) published their milestone monograph on Meningiomas. Their Classification, Regional Behaviour, Life History and Surgical End Results(1917).

The Congress of the United States passed the Federal Food, Drug, and Cosmetic Act of 1938. This act contained provisions dealing with prohibition of economic adulteration of food, mandatory food standards, truth in food labels or labeling, labeling of imitation foods as such, required labeling of foods with manufacturer’s name, address, net quantity of contents, name of the food, and ingredients of the food(1918).

Harry Hatton (FR) and Joseph H. Connell (US) investigated the correlation between population age structures and severity of physical factors in the environment. They found that under very harsh conditions the population may be composed of a single dominant year class(1919-1921).

Heinrich Klüver (US) and Paul C. Bucy (US) performed experimental lesion studies in monkeys which demonstrated that large temporal lobe lesions that included the amygdala resulted in dramatic postoperative changes in behavior, including flattened affect, visual agnosia, hyperorality, and hypersexuality(1922).

South African fishermen, in 1938, netted a coelacanth off the coast of South Africa. It was identified as belonging to a group or subclass of fishes known as the Crossopterygia, or lobe-finned fish, which passed the heyday of their evolutionary history many millions of years ago and were thought to be extinct. It was named Latimeria chalumnae to honor Miss Courtenay Latimer, a museum curator, in East London, South Africa. Almost immediately living specimens were filmed in their native habitat(1923-1925).

Robert A. Broom (ZA) reported on and named the discovery of Australopithecus robustus: Paranthropus robustus (formerly Parathrops crassidens) by a schoolboy, Gert Terblanche, in 1938 at Kromdraai in South Africa. It had a body similar to that of A. africanus, but a larger and more robust skull and teeth. It existed between 2 and 1.5 million years ago. The massive face is flat or dished, with no forehead and large brow ridges. It has relatively small front teeth, but massive grinding teeth in a large lower jaw. Most specimens have sagittal crests. Its diet would have been mostly coarse, tough food that needed a lot of chewing. The average brain size is about 530 cc. Bones excavated with robustus skeletons indicate that they may have been used as digging tools(1926, 1927).

Zeitschrift für Tierpsychologie (Journal of Animal Psychology), nowadays Ethology was founded.

1939

“Already I was beginning to realize that a spectacle has no meaning except it be seen through the glass of a culture, a civilization, a craft.” Antoine de Saint Exupéry(1928).

"Upon this gilded age, in its dark hour

Rains from the sky a meteoric shower

Of facts…they lie unquestioned, uncombined,

Wisdom enough to teach us of our ill

Is daily spun, but there exists no loom

To weave it into fabric." Edna St. Vincent Millay(1929).

“As man is now changing the composition of the atmosphere at a rate which must be very exceptional on the geological time scale, it is natural to seek for the probable effects of such a change. From the best laboratory observations it appears that the principal result of increasing atmospheric carbon dioxide … would be a gradual increase in the mean temperature of the colder regions of the Earth.” Guy Stewart Callendar(1930).

“The fungi in their reproduction and inheritance follow exactly the same laws that govern these activities in higher plants and animals.” Bernard Ogilvie Dodge(1931).

Adolf Friedrich Johann Butenandt (DE), for his work on sex hormones, and Leopold Stefan Ruzicka (HR-CH), for his work on polymethylenes and higher terpenes, were awarded the Nobel prize in chemistry. Butenandt was caused by the authorities of his country to decline the award but later received the diploma and the medal.

Gerhard J. Domagk (DE) was awarded the Nobel Prize in Physiology or Medicine for the discovery of the antibacterial effects of prontosil. (Caused by the authorities of his country to decline the award, but later received the diploma and the medal.)

Siemens AG (DE) produced the first commercial transmission electron microscope.

Werner E. Bachmann (US), J. Wayne Cole (US), and Alfred L. Wilds (US) accomplished the total synthesis of equilenin, a sex hormone from pregnant mares. This was particularly significant because it confirmed many of the assumptions about the configuration of the steroid ring structure(1932).

Chester Wilson Emmons (US), Alexander Hollaender (US), Edgar Knapp (DE), A. Reuss (DE), Otto Risse (DE), and Hans Schreiber (DE) found that the maximum mutagenic response of bacteria to ultraviolet radiation corresponds with the peak absorption wavelengths for nucleic acid(1933, 1934). This represented strong circumstantial evidence for the concept that genes consist of nucleic acid.

Frank E. Gardner (US), Paul C. Marth (US), and Lawrence P. Batjer (US) pioneered the use of 1-naphthalene-acetic acid for pre-harvest drop control in apples(1935).

Vincent du Vigneaud (US), Joseph P. Chandler (US), Arden W. Moyer (US), Dorothy M. Keppel (US), Mildred Cohn (US), and George Bosworth Brown (US), through their studies of the amino acid methionine and related compounds, explained how the body shifts a methyl group from one compound to another. By such shifts the body sometimes completes the construction of a complicated molecule(1936, 1937).

Hermann Karl Felix Blaschko (DE-GB) was the first to propose a biosynthetic pathway for the production of catecholamines such as the hormone epinephrine (adrenaline)(1938).

Walter L. Halle () had proposed a very similar pathway in 1906(1939).

Toshiharu Nagatsu (US), Morton Levitt (US), and Sidney Udenfriend (US) confirmed Blaschko’s pathway(1940).

Linus Carl Pauling (US) and Carl George Niemann (US) discredited the theory that the amino acids of proteins exist in a cage like structure. Their evidence supported a chain structure(1941).

Jordi Folch (US) and Donald Dexter Van Slyke (US) identified phosphatidyl serine(Folch and Van Slyke 1939).

Henry Eyring (US) and Allen Edwin Stearn (US) suggested that denaturation of proteins involves breaking of salt linkages (formed by the mutual attraction of oppositely charged ions) and of covalent bonds (possibly the disulfide bonds of cystine units)(1942). 

Rufus Lumry (US) and Henry Eyring (US) proposed a feasible mechanism to account for protein denaturation(1943).

A. Calvin Bratton (US) and Eli Kennerly Marshall, Jr. (US) developed a method for the quantitative determination of sulfonamides in blood and tissues. This method was important because it permitted a rational basis for dosage(1944).

Samuel M. Ruben (US), William Zev Hassid (RU-GB-US), Martin David Kamen (CA-US), and Don DeVault (US) used the short lived radioactive carbon, C11, as an indicator, to study the assimilation of C*O2 by barley. They found that leaves kept illuminated or in complete darkness for less than two and one-half hours formed radioactive carbohydrates. Leaves kept in the dark for over two and one-half hours did not form radioactive carbohydrates. This work with carbon 11 paved the way for isotope tracer research(1945, 1946).

Georg Borgström (SE-US) found that plant shoots exposed to ethylene exhibited positive geotropism associated with the predicted auxin distribution. Ethylene must in some way influence the transverse movement of auxin(1947).

Paul Jackson Kramer (US) found that, “Most, and possibly under some circumstances all, of the water absorbed by transpiring plants is absorbed as a result of forces set in motion by loss of water in transpiration.” Water absorption in plants occurs slowly by osmotic means at night when transpiration is negligible and results in “root pressure” in the vascular system often leading to formation of droplets around the margins of leaves (guttation). During the day water is absorbed by forces originating in the shoot because of the dehydration caused by transpiration, and these forces extend through the living tissues of the root into the soil water(1948).

Ferenc Bruno Straub (GB) isolated and purified dihydrolipoyl dehydrogenase from heart muscle tissue. It uses flavineadenine dinucleotide (diaphorase or coenzyme factor) as its prosthetic group(1949).  

Otto Heinrich Warburg (DE) and Walter Christian (DE) isolated an enzyme, glyceraldehyde-3-phosphate dehydrogenase, which catalyzes the oxidation of glyceraldehyde-3-phosphate to 1,3-diphosphoglyceric acid. They demonstrated that this reaction required the presence of inorganic phosphate and oxidized DPN (NAD) which was converted to reduced DPN (NAD) during the reaction. The reduced coenzyme subsequently donated hydrogens to acetylaldehyde to produce ethyl alcohol(1950). 

Otto Heinrich Warburg (DE), Walter Christian (DE), and Theodor Bücher (DE), isolated an enzyme which converts 1,3-diphosphoglyceric acid + adenosine diphosphate (ADP) to 3-phosphoglyceric acid + adenosine triphosphate (ATP)(1951, 1952). This was a particularly important discovery because for the first time it linked the release of chemical energy by oxidation to the substrate level synthesis of adenosine triphosphate (ATP), i.e., substrate level phosphorylation

Erwin Paul Negelein (DE) and Heinz Brömel (DE) determined that during glycolysis when glyceraldehyde-3-phosphate is acted upon by glyceraldehyde-3-phosphate dehydrogenase in the presence of inorganic phosphate the immediate product is 1,3-diphosphoglyceric acid(1953, 1954).

Leon A. Heppel (US) determined that K+ and Na+ are able to cross an animal cell membrane(1955-1957).

John Robert Raper (US) and Arie Jan Haagen-Smit (NL-US) discovered that hormones are used to control sexual behavior in species of Achlya, a common genus of aquatic fungi(1958-1968).

Trevor McMorris (US) and Alma Barksdale (US) isolated and characterized hormone A of Achlya. It was found to be a sterol and renamed antheridiol, the first steroid hormone found in either plants or the fungi(1969).

Daniel Israel Arnon (PL-US) and Perry R. Stout (US) discovered that molybdenum is essential for growth in all plants(1970).

George Wells Beadle (US) proposed the "Teosinte Hypothesis," in which maize was domesticated from teosinte by human selection(1971).

Paul Mangelsdorf (US) later suggested that maize was the product of a hybridization between an undiscovered wild maize and Tripsacum, the "Tripartite Hypothesis"(1972). Most scientists currently support the “Teosinte Hypothesis.”

Harry E. Warmke (US) and Albert Francis Blakeslee (US) described the sex mechanism in polyploids of Melandrium(1973).

John Charles Walker (US) found that internal black spot in beets is a disease due to a soil boron deficiency(1974).

Juda Hirsch Quastel (GB-CA) carried out one of the earliest studies of brain metabolism when he focused on the energy-yielding oxidative processes in slices and homogenates of brain(1975).

Vladimir Aleksandrovich Engelhardt (RU) and Militsa Nikolaevna Liubimova (RU) discovered that Kühne’s myosin, isolated in 1864, possesses an ATPase activity believed to catalyze the hydrolysis of ATP and thereby directly link muscle contraction with ATP hydrolysis(1976).

Frank A. Brown, Jr. (US) and Ona Cunningham (US) demonstrated the influence of the hormone from the sinus gland in the eyestalk of crustaceans on normal viability and ecdysis(1977). See, Zeleny, 1905.

George Widmer Thorn (US), Lewis L. Engel (US), and Harry Eisenberg (US) found that bilaterally adrenalectomized dogs, fed a constant diet of low sodium and chloride content, may be maintained in excellent condition, by means of the subcutaneous implantation of pellets of crystalline desoxy-corticosterone acetate. This demonstrated that Addison’s disease is due to a deficiency of adrenal cortical hormone(1978).

Thomas H. Jukes (US), Dilworth Wayne Woolley (CA-US), Harry A. Waisman (US), and Conrad Arnold Elvehjem (US) discovered that pantothenic acid prevents a type of dermatitis in chickens(1979, 1980).

Paul György (US) and C. Edward Poling (Amertican) found that a greying of the hair in rats is caused by a deficiency of pantothenic acid(1981).

Floyd S. Daft (US), William Henry Sebrell (US), Sidney H. Babcock, Jr. (US), and Thomas H. Jukes (US) found that a deficiency of pantothenic acid in rats produces hemorrhagic adrenal necrosis(1982, 1983).

William D. Salmon (US) and Ruben William Engel (US) reported that a deficiency of pantothenic acid causes lesions in the adrenal glands of rats(1984).

Sir Alan Lloyd Hodgkin (GB), Sir Andrew Fielding Huxley (GB), Howard J. Curtis (US), and Kenneth Stewart Cole (US) directly measured the action potential within the nerve fiber (cells)(1985-1987). “We have recently succeeded in inserting micro-electrodes into the giant axons of squids…. A small action potential was recorded from the upper end of the axon and this gradually increased as the electrode was lowered, until it reached a constant amplitude of 80-95 mv…. The axon appeared to be in a completely normal condition, for it survived and transmitted impulses for several hours…. These results…prove that the action potential arises at the surface”(1985).

Eric T. Stiller (US), John C. Keresztesy (US), Joseph R. Stevens (US), Stanton A. Harris (US), and Karl August Folkers (US) discovered the molecular structure of pyridoxine (vitamin B6) and synthesized it(1988-1990). Its molecular structure is designated 2-methyl-3-hydroxyl-4,5-di (hydroxymethyl)-pyridine. This vitamin is necessary for the synthesis and breakdown of amino acids, the building blocks of protein; aids in fat and carbohydrate metabolism; aids in the formation of antibodies; maintains the central nervous system; aids in the removal of excess fluid of premenstrual women; promotes healthy skin; reduces muscle spasms, leg cramps, hand numbness, nausea & stiffness of hands; and helps maintain a proper balance of sodium & phosphorous in the body. 

A deficiency of vitamin B6 may result in nervousness, insomnia, skin eruptions, loss of muscular control, anemia, mouth disorders, muscular weakness, dermatitis, arm and leg cramps, loss of hair, slow learning, and water retention.

David Keilin (PL-GB), Thaddeus Robert Rudolph Mann (PL-GB), Carl G. Holmberg (SE), Edwin L. Hove (NZ), Conrad Arnold Elvehjem (US), and Edwin Bret Hart (US) demonstrated that zinc is necessary in animal nutrition because it is a cofactor for certain enzymes(1991-1993).

Vladimir Aleksandrovich Belitzer; Vladimir Aleksandrovich Belitser (RU), Elena T. Tsibakova (RU), and Severo Ochoa (ES-US) made the first quantitative measurements of phosphorus and oxygen in the respiratory chain and determined that the P:O ratio is greater than one. Ochoa concluded that the P:O ratio during the oxidation of pyruvate to carbon dioxide is 3(1631, 1632, 1994, 1995).

George Otto Gey (US) and Frederick B. Bang (US) were the first to report a cytopathic effect caused by a virus in cell culture. The agent was lymphopathia venera virus(1996).

Morris Frank Shaffer (US) and John Franklin Enders (US) developed a quantitative virus indicator system using counts of foci on the chorio-allantoic membrane of the chick(1997).

Ernest Everett Just (US) wrote The Biology of the Cell Surface(1998).

Johannes Friedrich Karl Holtfreter (DE-US) showed that if embryonic amphibian cells from different tissues are dissociated then mixed together the cells re-associate into tissue specific masses—so called histotypic aggregates(1999-2001). This is an application to vertebrates of Wilson’s discovery with sponges. See, Wilson, 1907.

Sven Otto Hörstadius (SE) described the differences in the early development of regulative eggs (each blastomere can give rise to a whole embryo) and mosaic eggs (isolated blastomeres produce only fragments of an embryo, i.e., determinate cleavage). He discovered the existence of a double gradient of animalization and vegetalization in the echinoderm egg(2002, 2003).

Carey H. Bostian (US) and Phineas W. Whiting (US) worked out the mechanism for sex determination in the hymenopterean, Habrobracon. Homozygosity or hemizygosity at a particular multiply allelic locus produces a male while heterozygosity at this same locus produces a female(2004-2006). Whiting went on to show that nine different alleles are known for this locus(2007).

Henry Arnold Lardy (US) and Paul H. Phillips (US) developed a medium for the preservation of animal sperm(2008).

Gregory Goodwin Pincus (US) exposed a rabbit egg to high temperature, hormone treatments, and salt solution in vitro. The result was the first live mammalian birth via parthenogenesis(2009, 2010).

Schack August Steenberg Krogh (DK) found that the kidneys of whales and seals can produce a urine with a salt concentration higher than sea water, thus they are able to drink sea water to replace the water lost from their tissues to the surrounding ocean(2011). 

Emory Leon Ellis (US) and Max Ludwig Henning Delbrück (DE-US) demonstrated the one-step growth curve for phage. It showed that the progeny of the infecting phage particle appear only after a period of constant phage titer(2012).

James R. Dawson (US), Israel J. Kligler (IL) and Hans Bernkopf (IL) cultivated rabies virus in the chick embryo(2013, 2014).

Joseph I. Schleifstein (US) and Marion B. Coleman (US) were the first to recognize Yersinia enterocolitica as a human pathogen(2015).

Robert E. Black (US), Richard J. Jackson (US), Theodore F. Tsai (US), Michael Medvesky (US), Mehdi Shayegani (US), James C. Feeley (US), Kenneth I.E. MacLeod (US), and Adah M. Wakelee (US) first characterized Yersinia enterocolitica as food-borne(2016).

Mary E. Caldwell (US) and Dwight L. Ryerson (US) recovered members of the bacterial genus Arizona from cold-blooded animals(2017).

René Jules Dubos (FR-US) and Roland D. Hotchkiss (US) isolated the antibiotics tyrocidin and gramicidin from Bacillus brevis, a common soil bacterium. Tyrocidin is toxic to all living cells; gramicidin, which is active both in the test tube and in animals against gram positive bacteria, is, however, limited to external use because it destroys erythrocytes. Gramicidin was the first antibiotic to be produced commercially and employed clinically. It is still in use today(2018-2020).

Walter John Dowson (GB) named the bacterial genus Xanthomonas, but it had been known as a group for some time and its characteristics described(2021).

Ian H. MacLean (GB), Keith B. Rogers (GB), and Alexander Fleming (GB) reported the first cases where microorganisms (pneumococcus) had developed resistance to sulfonamide(2022).

Hans Gaffron (DE) found that if certain unicellular green algae are deprived of oxygen , they cease to be capable of ordinary photosynthesis but become capable of reducing carbon dioxide in light if hydrogen is provided as a substitute reductant to replace water(2023).

George Henry Hepting (US) identified the previously undescribed cause of wilt disease in mimosa as Fusarium. This was one of the first reports of tree disease caused by a fungal species in this taxonomic group(2024).

Carl G. Hartman (US), Chester Henry Heuser (US) and George Linius Streeter (US) followed macaque monkey embryonic development from the two-cell stage to the end of the embryonic period. Theirs is the first such complete description in a primate(2025, 2026).

Hugh G. Grady (US) and Harold L. Stewart (US) first identified the type 2 cell of the pulmonary alveolus as the cell of origin of the common alveologenic tumors of the lungs of mice(2027).

Carl Pfaffman (US) described directionally sensitive cat mechanoreceptors(2028).

A Committee for the Standardization of Blood Pressure Readings defined diastolic and systolic pressures as: “The systolic pressure is the highest level at which successive sounds are heard…. The point where the loud clear sounds change abruptly to the dull and muffled sounds should be taken as the diastolic pressure. The American Committee recommend that if there is a difference between this point and the level at which the sounds disappear completely the latter reading should be regarded also as a measure of the diastolic pressure”(2029).

Norman Macdonnell Keith (US), Henry P. Wegener (US), and Nelson W. Barker (US) created four groups for hypertension, ranging from the benign group 1 to the so-called malignant hypertension as belonging to Group 4(2030).

Karl Sune Detlof Bergström (SE), Rune Eliasson (SE), Hans Dunér (SE), Ulf Svante von Euler (SE), Jan Sjövall (SE), and Bengt Pernow (SE) performed the first study on the cardiovascular effects of the pure prostaglandins in humans(2031, 2032).

Konrad Schäfer (DE) and Hildegard Gisela Gennerich (DE) started the study of platelet antigens when they proved the presence of AB blood-group antigens on human platelets(2033).

Norman M. Keith (US), Henry P. Wagener (US), and Nelson W. Barker (US) described some different types of hypertension; their course and prognosis(2034).

Robert Edward Gross (US) and John Perry Hubbard (US) were the first to carry out a successful ligation of a patent ductus arteriosus (a fetal blood vessel between the pulmonary artery and the aorta)(2035). The operation was performed on August 28, 1938. The patient made an uneventful recovery.

John C. Munro (US) had justified and described (but did not perform) an operation for ligation of the ductus arteriosus to repair patent ductus arteriosus(2036).

Percival Bailey (US), Douglas Nisbet Buchanan (US), and Paul Clancy Bucy (US) wrote the first serious and detailed study of intracranial tumors of infancy and childhood(2037).

A. Gordon Ide (US), Norman H. Baker (US), and Stafford L. Warren (US) made the seminal suggestion that tumors might produce a vessel growth-stimulating substance(2038).

Glenn H. Algire (US), Harold W. Chalkley (US), Frances Y. Legallais (US), and Helen D. Park (US) postulated that the growth advantage of a tumor cell over its normal counterpart might not be due to "some hypothetical capacity for autonomous growth inherent within the [tumor] cell," but rather to its ability to continuously induce angiogenesis — that is, the formation of new blood vessels(2039).

Melvin Greenblatt (US), Philippe Shubik (GB-US), Robert L. Ehrmann (US), and Mogens Knoth (US) showed that tumor transplants stimulated the proliferation of blood vessels via a true diffusible substance that could, in theory, be identified(2040, 2041).

Moses Judah Folkman (US) introduced the concept that angiogenesis inhibitors could be used in the treatment of cancer(2042).

Moses Judah Folkman (US), Ezio Merler (US), Charles Abernathy (US), and Gretchen Williams (US) isolated just such a tumor angiogenic factor (TAF) from tumor extracts, and proposed that the growth of malignancies might be prevented if TAF activity were blocked(2043-2045).

Michael A. Gimbrone, Jr. (US), Stephen B. Leapman (US), Ramzi S. Cotran (US), and Moses Judah Folkman (US) reported that small balls of living tumor cells do not increase in size when suspended in the anterior chamber of the eye where they are deprived of vascularization. When such dormant balls of cells are moved from the anterior chamber to a nearby spot in the eye where they can attract vessels from the iris, they then grow exponentially. This is the first paper to provide direct evidence that the progressive growth of a tumor can indeed be absolutely dependent on angiogenesis(2046).

David W. Leung (US), George Cachianes (US), Wun Jing Kuang (US), David V. Goeddel (US), and Napoleone Ferrara (US) purified and subsequently identified the gene encoding vascular endothelial growth factor (VEGF) which is a secreted protein that can stimulate both vascular endothelial cell proliferation in vitro and angiogenesis in vivo(2047).

K. Jin Kim (US), Li Bing (US), Jane Winer (US), Mark Armanini (US), Nancy Gillett (US), Heidi S. Phillips (US), and Napoleone Ferrara (US) demonstrated that monoclonal antibody specific for vascular endothelial growth factor (VEGF) inhibited the growth of the tumors, but had no effect on the growth rate of the tumor cells in vitro(2048).

Douglas Hanahan (US) and Moses Judah Folkman (US) found that tumors appear to activate the angiogenic switch by changing the balance of angiogenesis inducers and countervailing inhibitors(2049).

Sir Julian Sorell Huxley (GB) introduced the concept of the cline in evolutionary variation(2050). Cline is the gradual and continuous variation in genetic character over an extensive geographical area because of adjustments to changing conditions.

ca. 1940

It was established by general consensus that the vast majority of proteins are built up from a mixture of no more than 20 amino acids. From 1819 through 1936 only 20 amino acids had been found to be constituents of proteins based on isolation from protein hydrolysates.

Elmer Verner McCollum (US) and his colleagues showed that a deficiency in calcium in the body leads to tetany. They also showed that the body requires no phosphorus-containing organic materials, simple inorganic forms are sufficient. ref

1940

“Men think themselves free, because they are conscious of their volitions and of their desires and are oblivious to the causes which dispose them to desire and to will.” Sir Charles Scott Sherrington(2051).

Samuel M. Ruben (US) and Martin David Kamen (CA-US) isolated carbon-14 which has a half life of 5730 years. It quickly became one of the most useful of all isotopes in biochemical research and has also been turned to historical and archaeological use. Carbon-14 did not become widely available for metabolic studies until after World War II(2052).

Alfred Otto Carl Nier (US) published the description of a mass spectrometer for routine isotope abundance measurements and suggested that the apparatus was sufficiently accurate to measure the 13C/12C ratio if separated 13C was used as a tracer in biological investigations(2053).

Charles Dubois Coryell (US) introduced the terms exergonic and endergonic to denote free-energy changes in chemical reactions(2054).

Ammonium sulfamate was introduced as a herbicide for control of woody plants. ref

Andrei Nikolaevitch Belozerskii (RU) found that both DNA and RNA are always present in bacteria(2055).

Doris Elaine Dolby (GB), Leslie Charles Nunn (GB), and Ida Smedley-MacLean (US) discussed the possibility that linoleic acid could be a physiological precursor to arachidonic acid(2056).

Roger J. Williams (US) and Randolph T. Major (US) determined the structure of pantothenic acid(2057).

Eric T. Stiller (US), Stanton A. Harris (US), Jacob Finkelstein (US), John C. Keresztesy (US), and Karl August Folkers (US), achieved the total synthesis of pure pantothenic acid(2058).

Robert E. Eakin (US), Esmond Emerson Snell (US), Roger John Williams (US), and William A. McKinley (US) isolated from raw egg white a protein called injury producing protein which they named avidin(2059-2061). This protein forms a strong union with biotin (vitamin H) and prevents its absorption from the intestinal tract.

Moses Kunitz (RU-US) described the isolation of bovine ribonuclease in crystalline form(2062).

Leslie A. Epstein (US); Leslie A. (Epstein) Falk; Leslie A. Falk (US) and Ernst Boris Chain (DE-GB) showed that lysozyme is an enzyme, that its substrate is peptidoglycan of bacterial cells, and that it hydrolyzes a beta-1,4-glycosidic bond in the glycan backbone chain(2063).

Heinz Ludwig Fraenkel-Conrat (DE-US), Choh Hao Li (CN-US), Miriam E. Simpson (US), and Herbert McLean Evans (US) biologically characterized then isolated the luteinizing hormone (LH), also known as interstitial cell-stimulating hormone (ICSH) in males(2064-2066).

Edward Lawrie Tatum (US) and George Wells Beadle (US) isolated and crystallized what was called the v+ hormone from a bacterial culture supplied with tryptophane(2067).

Willard F. Verwey (US) was the first to describe staphylococcal protein A (SPA). He characterized it as a protein antigen present in type A staphylococci (coagulase-positive, alpha toxin positive, mannitol fermenting, and pathogenic; i.e., S. aureus) but not in the type B staphylocci (those lacking these characteristics)(2068).

Arne Grov (NO), Berit Myklestad (NO), and Per Oeding (NO) proposed the designation protein A(2069).

Arne Forsgren (SE) and John Sjoquist (SE) showed that the well recognized ability of all human sera to agglutinate S. aureus, which had been attributed to the universal presence of so-called natural antibodies, did not in fact represent an immune reaction. They showed that purified SPA bound to the Fc fragment of the immunoglobulin molecule, not to the antigen-binding Fab fragment(2070). SPA became a valuable agent for immunochemistry and immunoassays.

Zacharias Dische (FR) discovered that the phosphorylation of glucose in erythrocytes is prevented by addition of phosphoglycerate. This may be the first example of end-product (negative feedback) inhibition(2071).

Ferenc Brunó Straub (HU) reported the crystallization of lactic dehydrogenase from beef heart muscle(2072).

Wilbur Paul Wiggert (US), Milton Silverman (US), Merton Franklin Utter (US), and Chester Hamlin Werkman (US) were the first to obtain soluble enzyme preparations capable of fermenting carbohydrates from bacteria(2073). This opened the way for bacteria to be used as experimental material in the study of metabolic pathways.

Merton Franklin Utter (US) and Chester Hamlin Werkman (US) demonstrated that bacteria have fermentative pathways involving many of the same reactions as yeast and muscle(2074, 2075). 

Otto Gsell (CH) performed the first important trial of sulphatiazole(2076).

Donald Devereux Woods (GB) and Sir Paul Gordon Fildes (GB) postulated that sulphanilamide acts by blocking the utilization of p-aminobenzoic acid by bacteria. This represents the origin of the essential metabolite inhibition hypothesis(2077-2079).

Sydney Dattilo Rubbo (AU) and J.M. Gillespie (AU) proved that p-aminobenzoic acid is a vitamin for bacteria(2080).

Edward Nielsen (US), J.J. Oleson (US), Conrad Arnold Elvehjem (US), Gustav Julius Martin (US) and Stefan Ansbacher (US) proved that for rats p-aminobenzoic acid is a vitamin(2081, 2082).

Dilworth Wayne Woolley (CA-US), Gertrude Gavin (CA), and Earle W. McHenry (CA) demonstrated that inositol is a vitamin in the diet of mice and rats(2083-2086).

Andrew J. Krog (US), and Charles G. Marshall (US) used a swab technique to establish the bactericidal action of Zephiran, a quaternary ammonium compound, against bacteria commonly found on eating and drinking utensils. A one-minute exposure to a 1: 5,000 dilution was apparently sufficient to reduce bacteria surviving on tumblers to less than 100 per rim (2087).

Sir Ernst Boris Chain (DE-GB), Sir Howard Walter Florey (AU-GB), Arthur Duncan Gardner (GB), Norman G. Heatley (GB), Margaret Augusta Jennings (GB), Jena Orr-Ewing (GB), A. Gordon Sanders (GB), Sir Edward Penley Abraham (GB), and Charles M. Fletcher (GB) developed the cultural and chemical methodology to produce pure penicillin from Penicillium and found that it displays potent in vivo antimicrobial activity against certain pathogens. This antibiotic was first used clinically on an Oxford, England policeman sufffering from staphylococcal pyemia(2088, 2089).

Kenneth Bryan Raper (US), working at the Northern Regional Research Laboratory, isolated Penicillium chrysogenum strain NRRL 1951 from a moldy cantaloupe brought to him by a Peoria, Illinois housewife in 1943. This strain could produce large quantities of penicillin in submerged culture and subsequently became the parent of most all strains used in the production of penicillin. Once larger quantities of the antibiotic were available it was used to treat war casualties in Tunisia and Sicily in 1943.

Selman Abraham Waksman (RU-US) and Harold Boyd Woodruff (US) isolated the antibiotic actinomycin D from Streptomyces antibioticus. This antibiotic, the first ever isolated from actinomyces, is too toxic for use in animals(2090, 2091). Actinomycin D binds to DNA and blocks the movement of RNA polymerase (prevents RNA synthesis) in both prokaryotes and eukaryotes.

Gustav A. Kausche (DE) and Helmut Ruska (DE) took the first electron photomicrographs of chloroplasts(2092).

Linus Carl Pauling (US) proposed his version of the template mechanism for antibody synthesis. This introduced the concept of complementariness in association with biological macromolecules(2093).

Linus Carl Pauling (US) and Max Ludwig Henning Delbrück (DE-US) suggested that the surface of a gene somehow acts as a positive mold, or template, for the formation of a molecule of complementary (negative) shape(2094).

Karl Landsteiner (AT-US), Alexander Solomon Wiener (US), Philip Levine (RU-US) and Rufus E. Stetson (US) discovered that if a rabbit is injected with the blood of a rhesus monkey, (Macacus rhesus), its blood in turn develops an immune substance which will agglutinate not only the monkey’s blood but also that of about 85 percent of humans. Thus there must be in some human blood a substance which is also present in the monkey; for convenience they called it “Rh” (from rhesus)(2095, 2096).

Sir Ronald Aylmer Fisher (GB) and Robert Russell Race (GB) postulated that the blood Rh factor is actually controlled by three pairs of closely linked genes leading to the possibility of 27 different Rh genotypes. They proposed a new nomenclature using the symbols C, c, D, d, E, e to designate the six antigens and anti-C, anti-c, anti-D, etc. to designate the antibodies specific for these antigens (Fisher's CDE hypothesis). In the 1944 paper Race also showed that in addition to the supposedly normal form of anti-Rh (anti-D) antibody, which agglutinated D-positive red cells directly, when they were suspended in a saline medium, there existed a variant, known as incomplete antibody(2097, 2098). The D or Rh0 antigen is by far the most antigenic of all the Rh factors therefore anti-D antiserum is typically used in Rh blood typing.

Louis Klein Diamond (US) and Alexander Solomon Wiener (US) also discovered incomplete antibodies at about the same time(2099, 2100).

Charles Richard Drew (US), medical supervisor of the "Blood for Britain Project," reported to the National Blood Transfusion Committee noting that for cases of shock, burns, and open wounds, plasma often worked better than whole blood. Plasma could also be stored and transported without refrigeration.

Øjvind Winge (DK) and Otto Laustsen (DK) showed that in the yeast Saccharomyces cerevisiae colonial characteristics, cell shape, and fermentative ability are under the control of genes that segregate during the reductive division(2101).

Charles Clemon Deam (US) produced his Flora of Indiana; a 1,236 page creation resulting from Deam personally collecting specimens in each and every one of the 1,016 townships in Indiana. This flora has excellent keys; Indiana distributional maps for all species and especially observational and/or critical notes about most. Deam's wife Stella faithfully worked along side her husband as a research assistant(2102).

Helmut Ruska (DE), U. Kottmann (DE), Edgar Pfankuch (DE), Gustav Adolf Kausche (DE), Salvador Edward Luria (IT-US), Thomas Foxen Anderson (US), Constantin Levaditi (FR), and Paul Bonet-Maury (FR) were the first to take electron photomicrographs of virus (bacteriophage), establishing their particulate nature and proving that specific bacteriophages have characteristic morphologies(2103-2109).

Richard O. Roblin, Jr. (US), James H. Williams (US), Philip S. Winnek (US), and Jackson P. English (US) discovered sulfadiazine which later proved especially good at treating epidemic cerebrospinal meningitis(2110).

Herald Rea Cox (US) and E. John Bell (US) developed a formalinized rickettsial vaccine for epidemic typhus(2111, 2112).

Kenneth C. Smithburn (US), Thomas P. Hughes (US), Alexander W. Burke (US), J.H. Paul (US), and Henry R. Jacobs (US) isolated the virus of West Nile Fever from the blood of an African native of Uganda(2113, 2114).

Ralph T. White (US) and Samuel R. Dutky (US) determined that type A white milky disease of insects and type B white milky disease of insects are caused by Bacillus popilliae and Bacillus lentimorbus, respectively(2115).

Sir Edward Penley Abraham (GB) and Sir Ernst Boris Chain (DE-GB) described a substance from Escherichia coli that could inactivate penicillin. They named it penicillinase (beta-lactamase)(2116).

Karl Meyer (US), Gladys Lounsberry Hobby (US), Eleanor Chaffee (US), and Martin Henry Dawson (US) discovered hyaluronidase in the supernatant fractions of cultures of hemolytic streptococci(2117).

Paul W. Miller (US), Walter Beno Bollen (US), Joseph E. Simmons (US), H.N. Gross (US), and Howard P. Barss (US) described Xanthomonas corylina (Xanthomonas campestris) as the causative agent of bacteriosis in filbert(2118).

Friedrich Seidel (DE), Eberhard Bock (DE), and Gerhard Krause (DE), working with the golden-eyed fly, Chrysopa (Neuroptera) discovered the existence of a primary embryonic inductor in insects, which is associated with a specific germ layer, the ectoderm. Inductive stimuli originate in the ectoderm, and the underlying mesoderm responds with specific differentiations(2119, 2120). These were primarily Bock’s discoveries.

Soichi Fukuda (JP) discovered the prothoracic gland while studying the induction of pupation in the Chinese bivoltine race of silkworm (Bombyx) and the Japanese bivoltine race. This gland was found to be the source of internal secretion which at a critical period releases into the blood a substance responsible for pupation(2121-2124).

Sir Gavin Rylands De Beer (GB) refuted the theory that the embryonic development of an organism repeats the adult stages of the organism’s evolutionary ancestors(2125).

Ruben A. Stirton (US) and George Gaylord Simpson (US) published phylogenetic studies of the North American horse. These are considered to be among the best and most complete phylogenetic studies ever written(2126, 2127).

Edmund Briscoe Ford (GB) defined genetic polymorphism(2128).

Lewis Victor Heilbrunn (US) and Floyd J. Wiercinski (US) demonstrated the contractile effect of calcium ions when injected into frog muscle cells(2129, 2130).

Lewis Victor Heilbrunn (US) put forward the calcium ion release theory of muscle contraction in 1943, stating that calcium ion released from internal storage sites into the muscle cytoplasm by electrical or chemical stimuli, was assumed to activate the contractile material(2131).

Adalbert Farkas (IL) and Joseph Aman (IL) were the first to report resistance of a plant pathogen to an organic fungicide(2132).

Thaddeus Robert Rudolph Mann (PL-GB) and David Keilin (PL-GB) determined that sulphanilamide is a potent inhibitor of carbonic anhydrase(2133).

William B. Schwartz (US) found that sulphanilamide produces an increased sodium, potassium and water excretion in patients with congestive heart failure. This likely results from inhibition of carbonic anhydrase in cells of the renal tubules(2134).

William Bloom (US), Margaret A. Bloom (US), Lincoln V. Domm (US), and Franklin C. McLean (US) were the first to demonstrate the importance of estrogens in laying down bone minerals in bone metabolism. They recorded the transformation of osteoblasts into osteoclasts(2135-2139).

Valy Menkin (US) demonstrated that adrenal cortical extract or Compound E (cortisone) will suppress inflammation in laboratory animals(2140, 2141).  See, Philip Showalter Hench, 1949.

Charles E. Smith (US) developed a skin test for detecting prior exposure to Coccidioides immitis. This permitted the determination of the endemic area for the fungus(2142).

Fuller Albright (US) and John D. Stewart (US) pointed out the role of steatorrhea in depleting the body of fat-soluble vitamins(2143).

Erik Waaler (NO) described agglutination by rheumatoid sera of sheep cells sensitized with a sub-agglutinating coating of gamma globulin. This represents the discovery of the rheumatoid factor (RF). RF is an antibody directed to the Fc part of antibodies of the human IgG class. This and the description of the same phenomenon by Harry Melvin Rose (US), Charles Ragan (US), Elizabeth Pearce (US), and Miriam Olmstead Lipman (US) laid the foundation of one of the most important tests in rheumatology. Charles M. Plotz (US) and Jacques M. Singer (US) refined the test(2144-2146).

Ralph Rossen (US), Herman Kabat (US), John P. Anderson (US), Lawrence M. Weinberger (US), Mary H. Gibbon (US), and John Heysham Gibbon, Jr. (US) determined that the cerebral cortex in humans is damaged irreversibly by relatively short periods of ischemia (a few minutes), while lower centers, such as the medulla, can survive for longer periods of temporary interruption in their supply of blood. They noted that a cessation of blood flow to the cerebral cortex for 6.8 seconds caused a loss of consciousness(2147, 2148).

Derek Ernest Denny-Brown (NZ-GB-US), W. Ritchie Russell (GB), Sir Hugh John Forster Cairns (GB-US-GB), and Denis Williams (GB) did extensive research on cerebral concussion, post-concussion syndrome, closed head injury, disability from head injury, “shell-shock” and the effect on the head of high explosives(2149-2159).

Douglas R. Drury (US), George E. Boxer (US), and DeWitt Stetten, Jr. (US) observed that the livers of diabetic or starved animals exhibited a large decrease in capacity to synthesize fatty acids(2160, 2161).

John Christian Krantz, Jr. (US), Jelleff C. Carr (US), Sylvan E. Forman (US), and William E. Evans, Jr. (US) introduced cyprome ether as an anesthetic(2162).

Oscar V. Batson (US) found it possible to explain most cases of aberrant malignant metastases, aberrant pyogenic metastases and aberrant embolism following air injections by the demonstrated role of the vertebral vein system(2163).

Henk Verbiest (NL) identified lateral spinal stenosis of the lumbar nerve canal(2164, 2165). His first description of lateral spinal stenosis was in 1940.

Robert Fiske Griggs (US) ) was perhaps the first to place plant rarity into an ecological context, acknowledging that plants do not statically interact with their surrounding environment.  He also observed a geographic component to rare species distributions: some occur only in very restricted sites while others are more widespread, but sparsely populated. Griggs speculated the former were relics that had previously covered a larger area, but had become “slowly dying vestiges of races once widespread."  In addition, he proposed that “habitat choice” or specificity was an ecological determinant of rare species occurrence and that certain types of habitats (e.g. rock outcrops, oceanic islands, and river margins) consistently harbored rare plant assemblages. The most resounding theory produced from this seminal paper was the notion that many plants are rare because they are poor competitors, predominantly existing in early successional or “ecologically young” environments where competitive pressures are low(2166).

Marcel Ravidat (FR), Jacques Marsal (FR), Georges Agnel (FR), and Simon Coencas (FR) discovered the cave at Lascaux, France where man produced representational art on the walls. It contains a great collection of Paleolithic art 10,000 to 15, 000 years old(2167).

There occurred a widespread epidemic of rubella (German measles) in Australia.

1941

“Men think themselves free, because they are conscious of their volitions and of their desires and are oblivious to the causes which dispose them to desire and to will.” Sir Charles Scott Sherrington.

Albert Hewett Coons (US), Hugh J. Creech (US), R. Norman Jones (US), and Ernst Berliner (DE) attached fluorescent dyes to antibodies then used them to detect antigens; the so-called direct fluorescent antibody technique. The first fluorescent dye they used was B-anthryl isocyanate which gives a blue fluorescence. Later they used fluorescein, to detect pneumococcal antigens. It gives a green fluorescence. This discovery made it possible to trace antigen and antibody within cells(2168, 2169).

Albert Hewett Coons (US) and Melvin H. Kaplan (US) improved the ability of the technique to localize antigens in tissue cells(2170). This immunofluorescent technique is so important because it permits the detection of antibodies, antigens, and virtually any antigenic substance.

Archer John Porter Martin (GB) and Richard Laurence Millington Synge (GB) introduced liquid-liquid partition (column) chromatography which depends on the establishment of an equilibrium between two liquid phases (e.g., chloroform and water), one of which (water) is immobilized by being held by a solid support (e.g., silica gel), as the other (chloroform) flows through the column. Note: both high pressure gas-liquid partition chromatography (GLC) and high pressure liquid chromatography (HPLC) were first proposed in this paper(2171).

Fritz Prior (AT) and Erika Cremer (DE) developed gas chromatography (GC). Prior, in 1947, succeeded in separating oxygen and carbon dioxide on a charcoal column - a technical achievement for which he received his Ph.D(2172, 2173).

Anthony T. James (GB) and Archer John Porter Martin (GB) developed high pressure gas-liquid (partition) chromatography (GLC). They used the new column with great success to separate a variety of natural products(2174).

Francis Peyton Rous (US) and George W. Wilson (US) concluded from experimental studies on dogs that loss of blood volume, not loss of erythrocytes, was the important consideration in hemorrhage. Even after gross hemorrhage, these workers were able to restore the blood pressure to normal, and maintain it at the normal level, by replacing the blood they had removed with an equal quantity of plasma(2175).

Edwin Joseph Cohn (US), Laurence E. Strong (US), Walter L. Hughes, Jr. (US), Dwight J. Mulford (US), John N. Ashworth (US), Marshall Melin (US), and F.H. Laskey Taylor (US) developed a cold ethanol fractionation of plasma; the process of breaking down plasma into components and products. Albumin, a protein with powerful osmotic properties, plus gamma globulin and fibrinogen were isolated and became available for clinical use(2176, 2177).

Walter L. Tatum (US), Alvin John Elliott (US), and Naurice M. Nesset (US) established the efficacy of the use of albumin in transfusion(2178, 2179).

Alvin John Elliott (US) and Naurice M. Nesset (US) perfected a sterile evacuated bottle containing chemical preservatives for the collection and preservation of blood(1552).

Douglas B. Kendrick, Jr. (US) reported on the use of human albumin to treat traumatic shock. “. . .This patient was 20 years of age and was admitted to the hospital 16 hours after injury. He had a bilateral compound continued fracture of the tibia and fibula. He had fractures of five ribs with associated pleural damage, pneumothorax and subcutaneous emphysema. At the time of admission, his blood pressure was 76/30. Two bottles of albumin, consisting of approximately 25 grams, were injected over 30 minutes. The blood pressure after injection was 106/70. . . his blood pressure remained above 130. . .he has had no evidence of circulatory failure since the albumin was administered. . . this patient appeared quite groggy and irrational when I first saw him, but 12 hours later he was very clear mentally and appeared to be feeling better"(2180).

Isidor Schwaner Ravdin (US) reported on the effectively of using Cohn’s albumin to treat victims of the Pearl Harbor attack for burns and shock. Injected into the blood stream, albumin absorbs liquid from surrounding tissues, preventing blood vessels from collapsing; the finding associated with shock. "All seven patients were given albumin, and all showed prompt clinical improvement, including one whose state was so critical that the administration of albumin to him was debatable. There was no question as to his response: He was unconscious in the morning when he was given 250 grams of albumin. In the afternoon, he was talking, but was disoriented. The following morning, he was given the same amount of albumin. Twenty-four hours later, the edema had disappeared and he was taking food by mouth"(2181).

Paul Hermann Müller (CH) discovered that 1,1,1-trichloro-2,2-bis (p-chlorophenyl) ethane or dichloro-diphenyl-trichloroethane (DDT) is a potent insecticide with low toxicity for higher organisms(2182-2185). This compound was originally synthesized in 1873 by Othmar Zeidler (Othmar Ziedler) (DE) for his Ph.D. thesis work. He knew nothing of its biological activity(2186).

Samuel B. Barker (US) and William H. Summerson (US) developed a colorimetric method for identifying lactic acid in biological materials. It is applicable to a wide variety of biological materials following deproteinization(2187).

Ernst Klenk (DE) isolated a product from a cerebroside fraction and named it neuraminic acid(2188). The predominant form in mammalian cells being N-acetylneuraminic acid.

Cecil James Watson (US) and Samuel Schwartz (US) developed the Watson-Schwartz test for the qualitative detection of porphobilinogen in urine. This test is to identify patients who carry the genetic trait for hepatic porphorias associated with neurologic lesions. It is a bedside urine test which can distinguish between cases of porphobilinogen (porphyria) and urobilinogen (pellagra)(2189).

Roger Adams (US) isolated and synthesized tetrahydrocannabinol and several of its analogues(2190). Tetrahydrocannabinol is the active chemical in cannabis and is one of the oldest hallucinogenic drugs known.

Hugh Brown (US), Lisa M. Eubanks (US), Claude J. Rogers (US), Albert E. Beuscher, IV (US), George F. Koob (US), Arthur J. Olson (US), Tobin J. Dickerson (US), Kim D. Janda (US) presented evidence that tetrahydrocannabinol has an anticholinesterase action which may implicate it as a potential treatment for alzheimer's and myasthenia gravis(2191, 2192).

Leonard Francis LaCour (GB) introduced the acetic orcein method for staining chromosomes(2193).

Edward Lawrie Tatum (US) and Arie Jan Haagen-Smit (NL-US) identified the v+ vitamin of Drosophila as l-kynurenine(2194). Kynurenine is ubiquitous in insects, despite its extremely low concentration. It is in the metabolic pathway which leads to the production of brown pigments (skotommins).

Adolf Friedrich Johann Butenandt (DE), Wolfhard Weidel (DE), Ruth Weichert (DE), and Waldemar Derjugin (DE) determined the structure of kynurenine(2195).

L-Kynurenine is a metabolite of the amino acid L-tryptophan used in the production of niacin.

Gilles J. Guillemin (AU), Bruce J. Brew (AU), Vincent Meininger (FR), Stephen J. Kerr (AU), Ka Ka Ting (AU), Lucie I. Bruijn (ZA-GB-US), Timothy M. Miller (US), Don W. Cleveland (US), M. Flint Beal (US), Wayne R. Matson (US), Kenton J. Swartz (US), Paul H. Gamache (US), Chai K. Lim (AU), George A. Smythe (AU), Roland Stocker (AU), Nicholas Stoy (GB), Gillian M. Mackay (GB), Caroline M. Forrest (GB), John Christofides (GB), Mark M. Egerton (US), Trevor W. Stone (GB), L. Gail Darlington (GB), Maria Zamanakou (GR), Anastasios E. Germenis (GR), and Vaios Karanikas (GR) demonstrated the kynurenine pathway to be involved in many diseases and disorders, including Alzheimer’s disease, amyotrophic lateral sclerosis, Huntington’s disease, AIDS dementia complex, malaria, cancer, depression and schizophrenia, where imbalances in tryptophan and kynurenines have been found(2196-2204).

Pieter J. Hoekstra (NL), G.M. Anderson (NL), Pieter W. Troost (NL), Cees G.M. Kallenberg (NL), and Ruud B. Minderas (NL) associated kynurenine with tics in humans(2205).

Yiquan Chen (AU) and Gilles J. Guillemin (AU) reported that the kynurenine pathway is an effective mechanism in modulating the immune response and in inducing immune tolerance. This is achieved by accelerating the degradation of tryptophan and the generation of kynurenines(2206).

Hershel K. Mitchell (US), Esmond Emerson Snell (US), and Roger John Williams (US) isolated folic acid from spinach (folium = leaf (Lat.)) and named it. They showed it to be a growth factor for Streptococcus lactis R (S. faecalis)(2207). It is also called folate, pteroylglutamic acid, and vitamin B9, vitamin M.

Robert B. Angier (US), James H. Boothe (US), Brian L. Hutchings (US), John H. Mowat (US), Joseph Semb (US), E.L. Robert Stokstad (US), Yellapragada SubbaRow (US), Coy W. Waller (US), Donna B. Cosulich (US), Marvin J. Fahrenbach (US), Martin E. Hultquist (US), Erwin Kuh (US), Elmore H. Northey (US), Doris R. Seeger (US), Jackson P. Sickels (US), and James M. Smith, Jr. (US) synthesized folic acid and determined its structure(2208, 2209).

Samuel M. Ruben (US), Merle Randall (US), Martin David Kamen (CA-US), and James Logan Hyde (US) used C18O2 and H218O containing 18O (heavy oxygen) to show that all oxygen liberated in photosynthesis originated in water; none came from carbon dioxide, and that the oxygen of CO2 enters into organic compounds(2210). Because 18O is not radioactive, Ruben used a mass spectrometer to find out where the oxygen from the water went.

Alexander Pavlovich Vinogradov; Aleksandr Pavlovich Vinogradov (RU) and R.V. Teis (RU) reached a similar conclusion(2211, 2212).

Robert Emerson (US) and Charlton M. Lewis (US) determined that a minimum of 10-12 quanta of light energy are needed for each molecule of oxygen released in photosynthesis(2213, 2214).

Samuel M. Ruben (US) and Martin David Kamen (CA-US) identified phosphoglyceric acid (PGA) as the first stable product of photosynthesis(2215).

Armin C. Braun (US) and Philip R. White (US) found that Agrobacterium tumefaciens introduces a factor into plant cells which permanently transforms them into cancer cells(2216-2219).

Selig Hecht (PL-US), Simon Shlaer (US), and Maurice Henri Pirenne (US) revealed that a retinal rod can be excited by a single photon(2220, 2221). 

Robert B. Dean (US) and Schack August Steenberg Krogh (DK) published articles in which the concept of the sodium pump was set forth(2222, 2223). Dean coined the phrase ion pump in his 1941 article.

Feodor Felix Konrad Lynen  (DE) and Marvin J. Johnson (US) proposed a key role for inorganic phosphate in the mechanism underlying the Pasteur effect (2224, 2225).

Fritz Albert Lipmann (DE-US) presented the general hypothesis for energy transfer in living cells, to which Herman Moritz Kalckar (DK-US) also made important contributions. Lipmann postulated that ATP functions in a cyclic manner as a carrier of chemical energy from the degradation or catabolic reactions of metabolism, which yield chemical energy, to the various cellular processes that require an energy input. ATP is generated from ADP by coupled or linked phosphorylation reactions at the expense of energy yielded by degradation of fuel molecules. The ATP so generated is postulated to donate its terminal phosphate group to specific acceptor molecules, to energize them for carrying out various energy-requiring functions in the cell, e.g., the biosynthesis of cell macromolecules (chemical work), the active transport of inorganic ions and cell nutrients across membranes against gradients of concentration (osmotic work), and the contraction of muscles (mechanical work). As the energy of ATP is delivered to these energy-requiring processes, the ATP undergoes cleavage to ADP and inorganic phosphate. The ADP is then rephosphorylated at the expense of energy-yielding oxidation of fuels to yield ATP, thus completing the cellular cycle. The terminal phosphate group of the ATP was thus visualized as undergoing constant turnover, being continuously transferred to acceptor molecules and continuously replaced by phosphate groups that become energized during the catabolic degradation of cell fuels. He gave the energy-rich phosphate bond its name and invented the mark, ~, called the squiggle, as in —O~P— by which it is shown(2226, 2227).

Konrad Emil Bloch (US) and Rudolf Schoenheimer (DE-US) carried out isotope tracer studies which demonstrated that creatine is synthesized by the transfer of an amidine group from arginine to glycine, with the formation of guanidinoacetic acid which is then methylated to give creatine(2228).

Carl Ferdinand Cori (CZ-US) and Gerty Theresa Cori, née Radnitz (CZ-US), Earl W. Sutherland (US), and Sidney P. Colowick (US) worked out the lactic acid metabolic cycle (Cori cycle) in which the breakdown of muscle glycogen, with formation of lactic acid, which enters the bloodstream, is converted to liver glycogen, which in turn breaks down and into glucose, which is carried to muscles where it is reconverted to muscle glycogen(2229-2233).

Barry Commoner (US) and Kenneth Vivian Thimann (GB-US) found that concentrations of 10-5 M of iodoacetate can halt coleoptile growth but produce no effect on cellular respiration. They assumed that only a small fraction of respiration might be involved in growth(2234).

Dean Burk (US) found that the metabolism of the regenerating liver, which grows more rapidly than most tumors, is not cancer metabolism, but perfect aerobic embryonic metabolism(2235).

Albert Imre Szent-Györgyi (HU-US), Ilona Banga (AT-HU), Tamas Erdös (HU), Mihály Gerendás (HU), Wilfred F.H.M. Mommaerts (US), and Ferenc Brunó Straub (HU),  demonstrated that artificial fibrils made from myosin and another protein, which they named actin, contracted when ATP was added. The combination of actin with myosin was named actomyosin(2236-2241).

Ferenc Brunó Straub (HU) separated the active components of muscle contraction into actin and myosin(2242, 2243).

George Feuer (HU), F. Molnár (HU), E. Pettkó (HU), and Ferenc Brunó Straub (HU) found that water extraction of an acetone-dried muscle residue yielded an actin solution with low viscosity, monomeric or globular (G) actin, that upon addition of salts (at physiological concentrations) polymerized to a highly viscous gel, filamentous or fibrous (F) actin(2244).

Ferenc Brunó Straub (HU) and George Feuer (HU) reported that G-actin contains bound ATP and during polymerization of actin the ATP is hydrolyzed to bound ADP and Pi. Straub postulated that the transformation of G-actin-ATP to F-actin-ADP plays a role in muscle contraction(2245).

Hans Hermann Weber (DE) and Hildegard Portzehl (DE) prepared single muscle fibers from glycerol treated psoas muscles that developed tension equal to the intact muscle and reproduced the entire contraction-relaxation cycle of the muscle. Thus, it was proven without doubt that the interaction between actin, myosin and ATP is the basic mechanism for the contraction-relaxation cycle in skeletal muscle(2246).

Wolfgang Kabsch (DE), Hans Georg Mannherz (DE), Dietrich Suck (DE), Emil F. Pai (DE), and Kenneth C. Holmes (DE) were the first to crystallize G-actin and determine its structure(2247).

John Desmond Bernal (GB) and Isidor Fankuchen (US) obtained clear x-ray diffraction patterns of tomato bushy stunt virus (TBSV) and tobacco mosaic virus (TMV)(1444).

Dorothy Mary Crowfoot (GB) and Gerhard M.J. Schmidt (IL) obtained an x-ray diffraction pattern using a single crystal of tobacco necrosis virus(2248). 

Johannes van Overbeek (NL), Marie E. Conklin (US) and Albert Francis Blakeslee (US) discovered that the addition of coconut milk (Cocos nucifera) causes a drastic increase in the growth of plant embryos and tissue cultures(2249).

John Bellows Alsever (US) and Robert B. Ainslie (US) developed an anticoagulant solution for storing test erythrocytes. It consists of 2.05 % glycoside, 0.42 % sodium chloride, 0.8 % tri-sodium citrate, and 0.055 % citric acid in distilled water(2250).

Harold A. Campbell (US), Mark Arnold Stahmann (US), Charles Ferdinand Huebner (US) and Karl Paul Gerhard Link (US) isolated and identified 3,3’-methylene bis-(4-hydroxycoumarin), later called dicumarol, as the anticlotting agent in spoiled clover hay which was causing cattle to bleed excessively (sweet clover disease). This contributed to our understanding of the mechanism of blood clotting and provided a method for the improved treatment of thromboembolic conditions(2251, 2252).

Miyoshi Ikawa (US), Mark Arnold Stahmann (US), Karl Paul Gerhard Link (US), and Ivan Wolff (US) synthesized comparable compounds including warfarin (Coumadin). It is one of the drugs used today to treat deep vein thrombosis as well as to limit the danger of blood clots in patients with artificial valve replacements. Large doses are used in rat poison because it leads to uncontrollable internal bleeding(2253, 2254).

George Wells Beadle (US) and Edward Lawrie Tatum (US), who had previously collaborated in efforts to establish the chemical identity of substances I and II in the synthesis of Drosophila eye pigment, developed a new experimental approach for the study of the genetic control of metabolic reactions. They had become discouraged over the difficulties they encountered with Drosophila as an object for biochemical studies and turned their attention to a fungus, the bread mold Neurospora crassa. According to Beadle: “With the new organism our approach could be basically different. Through control of the constituents of the culture medium we could search for mutations in genes concerned with the synthesis of already known chemical substances of biological importance. We soon found ourselves with so many mutant strains unable to synthesize vitamins, amino acids and other essential components of protoplasm that we could not decide which ones to work on first.”

Genetic crosses between the Neurospora wild-type and the many mutants isolated and characterized in this manner revealed that most of them owe their growth factor requirement to the mutation of a single gene in the Neurospora genome. Furthermore, detailed biochemical study of the aberrant metabolism of the mutants showed that most of them carry a block at a single step in the reaction sequence leading up to the synthesis of the amino acid, vitamin, purine, or pyrimidine required for growth.

George Wells Beadle (US) and Edward Lawrie Tatum (US) proposed what Norman Harold Horowitz (US) would call the one-gene one-enzyme theory of gene action(2255). This proposal was based on their studies of mutants of the mold Neurospora crassa. The approaches they developed were extremely important not only for study of the gene-enzyme relationship but also for the analysis of the pathways of intermediary metabolism. Wild-type, i.e., unmutated, Neurospora can grow on a simple medium containing glucose as sole carbon source and only ammonia as nitrogen source. However, exposure of Neurospora spores to x-rays yields some mutant cells no longer capable of growing on this simple medium. Such mutant cells will grow normally if the medium is supplemented with the specific metabolite whose biosynthesis was impaired by the mutation. For example, some mutants of Neurospora are unable to grow unless the medium contains arginine, suggesting that an enzyme required in the synthesis of arginine from ammonia is genetically defective in these mutants. For lack of arginine such mutant cells cannot manufacture their proteins. 

The mutant cells can utilize arginine for protein biosynthesis and show normal growth only when this amino acid is supplied in the medium. Further studies show that not all mutants of Neurospora defective in the capacity to make arginine are identical; they differ with respect to the specific step in the pathway of arginine biosynthesis that is genetically defective.

The one-gene-one-enzyme theory had nothing to say about how the gene actually manages to direct the formation of the enzyme under its dominion. Above all, it did not include the idea that the gene directs the assembly of amino acids into a polypeptide chain of given primary structure. Elucidation of the physical nature of the gene and of its role as the information element of the enzyme-cannot-make-enzyme paradox was to be the work of molecular genetics, the birth of which, it should be noted, was rendered valuable midwife service by the one-gene-one-enzyme theory(2256-2258).

Sir Kenneth Mather (GB) coined the term polygene and describes polygenic traits in various organisms(2259).

Carl Peter Henrik Dam (DK), Johannes Glavind (DK), Sigurd Orla-Jensen (DK), Anna D. Orla-Jensen (DK), Simon Black (US), Ralph S. Overman (US), Conrad Arnold Elvehjem (US), and Karl Paul Gerhard Link (US) have shown that Escherichia coli, Enterobacter aerogenes, and other intestinal microorganisms synthesize large amounts of the B complex vitamins; thiamin, riboflavin, nicotinic acid, pyridoxine, pantothenic acid, biotin, folic acid, inositol, and vitamin K(2260, 2261).

Tracy Morton Sonneborn (US) explained the complex life cycle of Paramecium including macronuclear regeneration and cytoplasmic exchange and the finding that autogamy—the uniparental nuclear reorganization that periodically occurs in many paramecia—is sexual(2262, 2263).

William F. Diller (US) was the first to report autogamy in Paramecium aurelia(2264).

Herbert J. Dutton (US), Winston M. Manning (US), and Benjamin Minge Duggar (US) were the first to demonstrate that light energy absorbed by accessory pigments (e.g., fucoxanthol) is transferred to chlorophyll a(2265, 2266).

Paul G. Smith (US), John Charles Walker (US), and William J. Hooker (US) proved for the first time that improper nutrition in plants is an important factor for initiation and eventual severity of vegetable diseases(2267-2271).

Ake Gustaffsson (SE) produced agriculturally superior new strains of cereals by selection from mutants produced by x-irradiation(2272, 2273).

Philip Levine (RU-US), Lyman Burnham (US), Eugene M. Katzin (US), and Peter Vogel (US) pointed out the great clinical importance of the anti-Rh antibody as a frequent cause of erythroblastosis fetalis(2274-2276). The antibodies probably act as opsonins promoting macrophage engulfment and lysis of red cells. Affected newborns die shortly after birth from bilirubin neurotoxicity.

Alvin Zipursky (CA), John Pollock (CA), Rebecca Yeow (CA), Lyonel G. Israels (CA), and Bruce Chown (CA) developed anti-Rh gamma globulin vaccine to prevent erythroblastosis fetalis(2277, 2278).

Arthur M. Walker (US), Phyllis A. Bott (US), Jean Redman Oliver (US), and Muriel C. MacDowell (US) used micropuncture of mammalian kidney tubules to show that the glomerular ultrafiltrate is entirely or nearly free of protein. That approximately two-thirds of the filtered fluid is reabsorbed in the proximal convolution of the renal tubule by an isosmotic process with extensive reabsorption of glucose(2279, 2280). These were the first kidney micropuncture studies on mammals (rodents).

Sir Frank Macfarlane Burnet (AU), Mavis Freeman (AU), Alan V. Jackson (AU), and Dora Lush (AU) proposed that descendents of cells reacting to antigen will produce antibodies specific to the antigen(2281).

Sally Hughes-Schrader (US) and Hans Ris (CH-US) discovered holokinetic (diffuse centromere) chromosomes(2282).

George K. Hirst (US), Laurella McClelland (CA) and Ronald Hare (CA) discovered that influenza virus will spontaneously agglutinate chicken erythrocytes in saline. Antibodies to the virus will inhibit the agglutination. This became a direct means of recognizing the presence of this virus and measuring its titer in cell culture(2283-2285). The reaction became known as the Hirst reaction

Stuart Mudd (US) and Thomas Foxen Anderson (US) used the electron microscope to visualize the combination of antibodies with the flagellar and somatic antigens of bacteria(2286).

Dorsey W. Bruner (US) and Philip R. Edwards (US) demonstrated that Salmonella paratyphi A grown in media containing suppressive antisera of one sort can shift to one of four different antigenic phases(2287).

Marjorie Griffen Macfarlane (GB) and Bert Cyril James Gabriel Knight (GB) discovered that the alpha toxin of Clostridium welchii is an enzyme (phospholipase C) which cleaves phosphatidylcholine(2288).

Louis Gershenfeld (US), Vera Elaine Milanick (US), and David Perlstein (US) discovered that acidity decreases the antibacterial efficiency of many quaternary ammonium compounds so decidedly that they are completely ineffective at pH 3, and only weakly bactericidal at pH 4(2289, 2290).

Zelma Baker (US), Robert W. Harrison (US), and Benjamin F. Miller (US) discovered that quaternary ammonium compounds are not very selective in their germicidal efficiency(2291).

William Trager (US) was the first to grow the malarial parasite (Plasmodium) in vitro in a procedure which proved repeatable(2292, 2293).

John Holmes Dingle (US), Lewis Thomas (US), and Allan R. Morton (US) established the efficacy of sulfadiazine in the treatment of meningococcal meningitis(2294).

Jacob Earl Thomas (US) developed a method for collection of bile under physiologic conditions by using a special cannula(2295).

Charles Brenton Huggins (CA-US), Clarence Vernard Hodges (US), and Roland E. Stevens (US) demonstrated the effects of castration, of estrogens, and of androgens on serum phosphatase levels in patients with extensive metastatic carcinoma of the prostate. They reported large clinical improvements in a significant number of these patients after orchiectomy and estrogen treatment. This was the first indication that a major type of cancer could be controlled by purely chemical means(2296, 2297).

Fuller Albright (US), Patricia H. Smith (US), and Anna M. Richardson (US) described post-menopausal osteoporosis(2298).

Eric George L. Bywaters (GB) and Desmond Beall (GB) were the first to describe a syndrome found in many air raid casualties. The syndrome was observed in patients who were buried for several hours with pressure on a limb. They went into shock some time later, and then, despite fluid replacement, developed renal damage and died within a week(2299).

Bernhard Zondek (DE-IL) reported that menstruation in women can be delayed (producing a limited amenorrhea) up to 70 days by the administration of estrogenic hormone. He realized that this had clinical significance(2300).

Frank W. Foote, Jr. (US) and Fred W. Stewart (US) initially diagnosed and described the related pattern of infiltrating lobular neoplastic breast disease in women. It is also referred to as lobular carcinoma in situ (LCIS). This has been considered a special type of premalignancy ever since(2301).

Paul E. Steiner (US) and Clarence C. Lushbaugh (US) presented maternal pulmonary embolism by amniotic fluid as a cause of obstetric shock and unexpected deaths in obstetrics(2302).

Paul Owen (NO) noted the correlation between diet and coronary thrombosis. ref

Robert Edward Gross (US) and William E. Ladd (US) wrote Abdominal Surgery of Infancy and Childhood, the first textbook on surgery in children(2303).

1942-1953

Polio continued to ravage the U.S., peaking in 1952 with about 60,000 cases(811).

1942

“At that subtle moment when man glances backward over his life, Sisyphus returning toward the rock, in that slight pivoting he contemplates that series of unrelated actions which becomes his fate, created by him, combined under his memory’s eye and soon sealed by his death. Thus, convinced of the wholly human origin of all that is human, a blind man eager to see who knows that night has no end, he is still on the go. The rock is still rolling.

I leave Sisyphus at the foot of the mountain! One always finds one’s burden again. But Sisyphus teaches the higher fidelity that negates the gods and raises rocks. He too concludes that all is well. This universe henceforth without a master seems to him neither sterile nor fertile. Each atom of that stone, each mineral flake of that night-filled mountain, in itself forms a world. The struggle itself toward the heights is enough to fill a man’s heart. One might imagine Sisyphus happy.” Albert Camus(2304).

“To think that physics or chemistry ought to be defined in terms of matter or physiology in terms of life is more than an egregious blunder; it is a threat to the existence of science. It implies that people know what matter is without studying physics or chemistry, and what life is without studying physiology.” Robin George Collingwood(2305). 

Harold H. Strain (US), Winston M. Manning (US) and Garrett Hardin (US) showed that chlorofucine, later known as chlorophyll c is not an artifact(2306, 2307).

Jordi Folch (ES-US) showed that cephalin is not a single lipid but rather a mixture of at least three lipids (phosphatidyl ethanolamine, serine and inositol). Folch was the first to have elucidated the structure of phosphatidyl serine(2308, 2309).

Vincent du Vigneaud (US), Klaus Hofmann (CH-US), and Donall B. Melville (US) deduced the complicated two-ring structure of biotin(2310, 2311).

Albert Dorfman (US), Sam Berkman (US), and Stewart Arment Koser (US) discovered the role of pantothenic acid in pyruvate metabolism(2312).

Paul D. Boyer (US), Henry Arnold Lardy (US), and Paul H. Phillips (US) discovered the K+ activation of pyruvate kinase. This was the first demonstration of  a K+ requirement for an enzyme reaction(2313, 2314).

Albert Dorfman (US), Stewart Arment Koser (US), and Marjory H. Wright (US) discovered the role of biotin in aspartic acid biosynthesis(2315).

Otto Fritz Meyerhof (DE-US) presented what has become known as the Embden-Meyerhof-Parnas pathway(2316).

Konrad Emil Bloch (US) and David Rittenberg (US) used isotope labeling techniques to show that acetate contributes in a major way to the synthesis of fatty acids, as well as, both the aliphatic side chain and to the tetracyclic moiety of sterol molecules(2317-2320).

Henry N. Little (US) and Konrad Emil Bloch (US) predicted that a two-carbon metabolite of acetate is the principal if not the sole building block of cholesterol(2321).

Herman Moritz Kalckar (DK-US) and Sidney P. Colowick (US) discovered that muscle extracts of myokinase (adenylate kinase) catalyze the reaction ATP + AMP becomes 2ADP. This is a vital reaction because it returns AMP to ADP which can be phosphorylated to ATP. The absence of adenylate kinase leads to phosphate accumulating as AMP(236, 2322).

Karl Landsteiner (AT-US) and Merrill Wallace Chase (US) announced that delayed hypersensitivity can be transferred with cells(2323, 2324). Their findings resulted in a clear separation of the class of immune responses initiated by cells from those mediated by circulating immunoglobulins.

Anna M. Kulka (US) showed that soluble antigen-antibody complexes would induce smooth muscle contraction in vitro(2325, 2326). 

Hans Voegt (DE) determined the viral etiology of infectious hepatitis (hepatitis A) by inoculating psychiatric patients from the mental hospital in Breslau(2327).

Edgar William Todd (GB) demonstrated that streptolysin O has a powerful lytic action on leucocytes when tested at low oxygen tension(2328).

Max B. Lurie (US) and Peter Zappasodi (US) provided evidence that mononuclear phagocytes while unable to damage the tubercle bacillus in non-immune individuals acquired the ability to destroy it in immune individuals(2329).

Harold Joel Conn (US) described the genus Agrobacterium with Agrobacterium tumefaciens as the type species(2330).

Chester W. Emmons (US) discovered that soil is a reservoir for Coccidioides immitis(2331, 2332).

Gladys Lounsberry Hobby (US), Karl Meyer (US), and Eleanor Chafee (US) established that under certain conditions penicillin is bactericidal and that it kills growing, but not resting cells(2333).

Harold E. Clark (US) and Kenneth R. Kerns (US) used 1-naphthalene-acetic acid to induce synchronous flowering in pineapples (Ananas comosus)(2334).

Roland E. Slade (GB), William Gladstone Templeman (GB), Wilfred A. Sexton (GB), Percy W. Zimmerman (US), Alfred E. Hitchcock (US), John E. Lontz (US), Ezra Jacob Kraus (US), Franklin D. Jones (US), Philip S. Nutman (GB), H. Gerard Thornton (GB), Juda Hirsch Quastel (GB), Paul C. Marth (US), and John W. Mitchell (US) discovered that certain chlorophenoxyacetic acids act as hormone herbicides. This included 2,4-D, MCPA, and 2,4,5-T(2335-2343).

Amchem Corp. introduced 2,4-D as the first in a series of phenoxyacetic acid herbicides to control broadleaf weeds in corn (Zea mays), wheat (Triticum spp.), barley (Hordeum vulgare), sorgham, sugar cane (Saccharum officinarum), grass pastures, and in turf. ref

Samson R. Dutky (US), developed a way to produce spores of Bacillus popilliae to provide effective suppression of the Japanese beetle by inducing bacterial milky spore disease —the first commercial microbial pesticide(2344).

Sidney Fay Blake (US) and Alice C. Atwood (US) authored Geographical Guide to Floras of the World which is a valuable bibliographical resource(2345).

Sheldon C. Reed (US), Carroll Milton Williams (US), and Leigh E. Chadwick (US) found that individual flies from various inbred strains of Drosophila can beat their wings at 12,000 to 14,000 beats per minute during sustained flight until exhaustion sets in after as much as three hours, or more than 2 million double wing beats(2346, 2347).

Gordon Lynn Walls (US) wrote an important book on the eye of reptiles entitled, The Vertebrate Eye and Its Adaptive Radiation. He emphasized the profound differences between the eye of snakes and lizards, and suggested that snakes evolved from nocturnal lizards(2348).

William Cumming Rose (US), Julius E. Johnson (US), William J. Haines (US), M. Jane Oesterling (US), Morton Shane (US), Madelyn Womack (US), Leonard C. Smith (US), Byron E. Leach (US), Minor J. Coon (US), Haines B. Lockhart (US), G. Frederick Lambert (US), Donald T. Warner (US), Aleck Borman (US), Robert L. Wixom (US), and Eugene E. Dekker (US) demonstrated that humans require eight amino acids in their diet (isoleucine, leucine, threonine, lysine, methionine, phenylalanine, tryptophane, and valine) as opposed to the ten required by rats and dogs. They noted that all essential amino acids must be supplied in the L-isomeric form with the exception of methionine which can be used in either the D- or the L- form. They even calculated the minimum daily requirement for each of these essential amino acids. Cystine was found to spare part of the methionine requirement and tyrosine spare part of the phenylalanine requirement. Glycine, glutamic acid, urea, and ammonium salts could all supply nitrogen necessary for synthesis of the non-essential amino acids(2349-2366).

C.S. Swaminath (IN), Henry Edward Shortt (GB), and L.A.P. Anderson (GB) demonstrated transmission of Leiahmania donovani (the causative agent of kala-azar) by sandflies(2367).

Jules Freund (AT-US) and Katherine McDermott (US) made a variation in oil adjuvants which allowed them to be used with any antigen. They emulsified water in oil with the assistance of a water-miscible lanolin-like material to incorporate both dried inactivated tubercle bacilli and the target antigen in a single aggregate preparation. This was the original Freund’s complete adjuvant(2368). This provided a method for inducing antibody formation and cellular responses to substances which are weakly antigenic.

Rudolf Schoenheimer (DE-US) and Hans T. Clarke (US) applied radioactive tracers to the study of the biosynthesis of cell structures and concluded that the body is in a state of dynamic equilibrium with the continual release and uptake of chemical substances to and from a metabolic pool(2369). 

Charles H. Rammelkamp, Jr. (US) developed a method for determining the concentration of penicillin in body fluids and exudates(2370). At this time penicillin was a rare and precious commodity.

George K. Hirst (US) used penicillin to thwart bacterial contamination during the isolation of influenza virus from unfiltered throat washings inoculated into the amniotic sac of the developing chick embryo(2284).

William Smith Tillett (US), Margaret J. Cambier (US), Harold Dunn (US), William H. Harris, Jr. (US), and James E. McCormack (US) studied penicillin therapy in cases of pneumococcal pneumonia and concluded that: 1) tissue levels of penicillin are more important than serum levels, 2) it is not the total daily dose of penicillin which results in recovery from the disease, but its duration of therapy, 3) during recovery the patient develops type-specific antibodies by the seventh to the tenth day after infection, and 4) if penicillin therapy is interrupted before the 7-10 day period following infection the patient will relapse and experience a recurrence of the disease(2371-2375). These results represent the first clear-cut demonstration of a seminal principle of antibiotic therapy, namely, that the antibiotic serves to limit the growth of the infectious agent until the appropriate immune responses of the host can be marshaled and result in its eradication.

Elvin Abraham Kabat (US), Dan H. Moore (US), and Harold Landow (US) demonstrated that certain diseases are associated with a cerebrospinal protein pattern in which the gamma globulins are proportionally the predominant fraction(2376, 2377).

Elvin Abraham Kabat (US), Murray Glusman (US), and Vesta Knaub (US) found that immunoglobulin gamma (IgG) is the main component of the gamma fraction in normal cerebrospinal fluid(2378).

Hans Popper (AT-US), Frederick Steigmann (US), and Hattie A. Dyniewicz (US) discovered that vitamin A deficiency leads to liver damage(2379).

Wilhelm Sigmund Feldberg (DE-GB) and Alfred Fessard (FR) made the first experimental demonstration of the electrogenic action of acetylcholine(2380). 

Harold R. Griffith (CA) and G. Enid Johnson (CA) were the first to produce muscular paralysis by the injection of a purified preparation of curare (intocostrin) as an adjuvant to surgical anesthesia. They used it to facilitate access to the abdomen during an appendectomy(2381).

Harry Fitch Klinefelter, Jr. (US), Edward Conrad Reifenstein, Jr. (US), and Fuller Albright (US) described a clinical syndrome characterized by gynecomastia, aspermatogenesis without A-Leydigism, and increased excretion of follicle-stimulating hormone. This condition would become known as Klinefelter’s syndrome. The majority of Klinefelter’s individuals have an extra female chromosome, resulting in an 47XXY karyotype. Other patterns of chromosomal aberration such as XXYY, and some mosaic patterns may result in the same syndrome. It is the most frequent type of intersexuality, occurring in one per 500-700 live male births(2382).

Clinton Nathan Woolsey (US) and Edward M. Walzl (US) selectively stimulated localized regions of auditory nerve fibers in the cochlea of the cat and mapped the patterns of evoked responses on the auditory cortex of the brain’s temporal lobe. This was the first demonstration of tonotopic (actually cochleotopic) organization of the auditory cortex(2383).

Clinton Nathan Woolsey (US) and D. Fairman (US) found a second tonal map ventral to the first with the sound spectrum in reverse order(2384).

Harlow W. Ades (US) found a secondary acoustic area in the posterior ectosylvian gyrus of the cat(2385).

Werner Kuhn (CH) and Kaspar Ryffel (CH) hypothesized that the production of hypertonic urine by the kidney might result from a concentration mechanism by counter-current between descending and ascending limbs of Henle's loops(2386).

Heinrich Wirz (CH), Bartholomew Hargitay (CH), and Werner Kuhn (CH) proposed that the mammalian kidney concentrates urine by means of a counter-current mechanism. “These findings indicate that the concentration of the urine occurs without steep osmotic gradients. The loops of Henle are an example of a hair-pin counter-current system. They prepare a hypertonic surrounding for the collecting ducts so that the contents of the collecting ducts are being concentrated by loosing water in this hypertonic milieu.” The tubular urine becomes osmotically concentrated in its descending limb, diluted in its ascending limb, and finally concentrated in the collecting ducts by the diffusion of water into the hyperosmotic medullary interstitium(2387-2390).

Carl W. Gottschalk (US) and Margaret Mylle (US) determined the hydrostatic pressure in renal tubules and small vessels of the rat kidney(2391).

Carl W. Gottschalk (US), Margaret Mylle (US), William E. Lassiter (US), Karl J. Ullrich (US), Bodil Schmidt-Nielsen (US), Roberta O’Dell (US), and Gundula Pehling (US) used the micropuncture technique on various mammalian species with different kidney anatomies under three different conditions to show virtual equality of osmolarity in collecting ducts and at the bend of the thin loops of Henle during antidiuresis. These experiments provided definitive proof that urine is concentrated by countercurrent multiplication(2392-2394).

William E. Lassiter (US), Carl W. Gottschalk (US), and Margaret Mylle (US) found a large net addition of urea to the fluid in the loop of Henle, indicative of urea recycling in the renal medulla(2395).

Heinrich Pette (DE) coined the word panencephalitis when he realized that some forms of viral encephalitis having a different name in different regions of the globe were in fact worldwide(2396).

Fuller Albright (US), Charles H. Burnett (US), Patricia H. Smith (US), and William Parson (US) described pseudohypoparathyroidism, a hypoparathyroidism in which there is evidence that the cause of the disturbance is the failure of the target organ(s) to respond to the hormone(2397).

Harry Keil (US) was the first to propose that discoidal lupus erythematosus and systemic lupus erythematosus are forms of the same disease, and that they could even present transitional forms. It was also Keil who clearly outlined the differential diagnosis of cutaneous manifestations in order to distinguish between lupus erythematosus and dermatomyositis(2398).

Paul Klemperer (AT-US), Abou D. Pollack (US), and George Baehr (US) found that “the apparent heterogeneous involvement of various organs in disseminated lupus had no logic until it became apparent that the widespread lesions were identical in that they were mere local expressions of a morbid process affecting the entire collagenous tissue system…. A similar widespread alteration of collagen has also been noted in certain cases of diffuse scleroderma.” They defined the collagen diseases as chronic or acute processes, localized in connective tissue, especially in its intercellular components but with multiple locations throughout the organism. Due to this last phenomena they coined the phrase diffuse diseases of collagen(2399).

Arnold Rice Rich (US) and John E. Gregory (US) demonstrated that the lesions of periarteritis nodosa, rheumatic carditis, and pneumonitis, and some forms of glomerulonephritis are caused by the anaphylactic type of hypersensitivity(2400-2408).

Karl Theodore Dussik (AT) and Friederich Dussik (AT) are generally regarded as the first physicians to have employed ultrasound in medical diagnosis. They located brain tumors and the cerebral ventricles by measuring the transmission of ultrasound beam through the head, employing a transducer on either side(2409).

George D. Ludwig (US) and Francis W. Struthers (US) were among the first to use pulse-echo ultrasound on animal tissues. They investigated the detection of gallstones using ultrasound, the stones being first embedded in the muscles of animals(474).

John Silas Lundy (US) opened the first post-anesthesia recovery room in the world. Here patients were provided with specially trained personnel to monitor their recovery from the anesthetic agent(2410). 

Charles Sutherland Elton (GB) was a community ecologist. He did important early studies on food webs. His speculations on interaction of population dynamics and selection foreshadowed the founder effect principle(2411). 

Ernst Walter Mayr (DE-GB-US) wrote Systematics and the Origin of Species from the Viewpoint of a Zoologist in which he gave systematics the first adequate integration of taxonomy, genetics, and natural history. Here he also produced the biological species concept, stating that species are “groups of actually or potentially interbreeding populations which are reproductively isolated from other such groups.” The 1942 paper contains the first statement of the founder principle(2412-2414). See, Aristotle, ca. 350 B.C.E. on species.

Raymond L. Lindeman (US), while studying the cycling of nutrients through a lake, realized that organisms are ecologically linked to their abiotic environment. The lake was an integrated system of the biotic and abiotic, to which he gave the name ecosystem. His trophic-dynamic viewpoint was an attempt to demonstrate how the day-to-day processes within a lake affected the long-term changes of ecological succession(2415).

Edward Smith Deevey, Jr. (US) described the biostratonomy of Linsley Pond in Connecticut. From his data he could read the 12,000-year history of the changes of conditions and communities within the pond, changes in the climate above it, and some of the activities of human population around it(2416).

1943

Henrik Carl Peter Dam (DK) for his discovery of vitamin K and Edward Adelbert Doisy (US) for his discovery of the chemical nature and synthesis of vitamin K were awarded the Nobel Prize in physiology and medicine.

George Charles de Hevesy; Georg Charles von Hevesy (HU-DE-SE-DE) was awarded the Nobel Prize in Chemistry for introducing metabolic tracer methodology using radioactive lead and phosphorus.

Edward Joseph Conway (IE) determined that the oceans during the geological period when the original vertebrates evolved (Ordovician) had a salinity very similar to the oceans of today(2417). This is strong evidence against the blood-reflects-the-early-seas hypothesis.

Winston M. Manning (US) and Harold H. Strain (US) discovered chlorophyll d(2418).

A. Stanley Holt (CA) and H.V. Morley (CA) determined the chemical structure of chlorophyll d(2419).

Julius Hyman (US-GB) produced mono- and bis-adducts of hexachlorocyclopentadiene (hex) by reacting it with cyclopentadiene(2420).

Clyde W. Kearns (US), Lester Ingle (US), and Robert Lee Metcalf (US) tested these products and found that the mono-adduct’s (chlordene) insecticidal potency was about one-fourth that of dichloro-diphenyl-trichloro-ethane (DDT) or 2,2-di(4-chlorophenyl)-1,1,1-trichloroethane but that it was to volatile to be useful(2421).

Julius Hyman (US-GB) and Randolph Riemschneider (DE) solved this problem by chlorinating the reactive double bond thus producing chlordane(2422, 2423).

Leslie James Burrage (GB) and James Crosby Smart (GB), in 1943, showed that it is the gamma isomer of benzene hexachloride that is insecticidal(2424, 2425). See Michael Faraday, 1825 and Van der Linden, 1912.

Charles E. Clifton (US) reported that penicillin can be produced in good yield in continuous flow cultures, and that such a method is commercially feasible(2426). 

Britton Chance (US) deduced the mechanism of peroxidase action in great detail. His results strongly supported the theory that enzymes combine with their substrate forming a temporary enzyme-substrate complex(2427).

Frederick W. Barnes, Jr. (US), Rudolf Schoenheimer (DE-US), Konrad Emil Bloch (US), Charles Tesar (US), and David Rittenberg (US) established that purine compounds of the tissues and the excreta are rapidly synthesized from simple metabolic units and not from preformed substances such as arginine, urea, and histidine(2428-2430).

Barry Commoner (US), Seymour Fogel (US) and Walter H. Muller (US) demonstrated that auxin will promote water absorption against an osmotic gradient. The effect is inhibited by iodoacetate(2431).

Alfred A. Harper (GB) and H.S. Raper (GB) discovered pancreozymin, a hormone released from the small intestine, which stimulates the secretion of pancreatic enzymes(2432).

Choh Hao Li (CN-US), Herbert McLean Evans (US), Miriam E. Simpson (US), George Sayers (US), Abraham White (US), and Cyril Norman Hugh Long (GB-US) isolated the adrenocorticotropic hormone (ACTH) from the pituitary gland of sheep then tested its biological activity(2433, 2434).

Choh Hao Li (CN-US), Irving I. Geschwind (US), Anthony L. Levy (US), J. Ieuan Harris (US), Jonathan S. Dixon (US), Ning G. Pon (US), and Jerker O. Porath (SE) isolated and determined the properties of alpha-corticotropin (ACTH) from sheep pituitary glands(2435).

Paul H. Bell (US), Robert G. Shepherd (US), Stuart D. Willson (US), Katherine S. Howard (US), David S. Davies (US), Selby B. Davis (US), E. Ann Eigner (US), and Nancy E. Shakespeare (US) isolated then determined the structure of porcine beta- corticotropin (ACTH)(2436-2438).

Otto Heinrich Warburg (DE) and Walter Christian (DE) isolated and crystallized aldolase (zymohexase) from muscle(2439). 

Samuel M. Ruben (US) hypothesized that in photosynthesis the reduced pyridine nucleotide and the ATP needed to reverse the Embden-Meyerhof-Parnas pathway are generated by coupling to the light-dependent reduction of water(2440).

Michael Doudoroff (RU-US), Nathan Oram Kaplan (US), and William Zev Hassid (RU-GB-US) demonstrated that a glucosyl moiety of sucrose is transferred by enzyme to phosphorous. This was the first demonstration of such a sugar transfer. Glucose-1-phosphate and fructose were found to be the products of this sucrose breakdown by the bacterium Pseudomonas saccharophila. They found that this reaction was easily reversed leading to the synthesis of sucrose; the first such synthesis discovered(2441).

Robert Emerson (US) and Charlton M. Lewis (US) determined that during photosynthesis in Chlorella quantum yields, as measured by oxygen release, are high when exposed to 400-440 and 560-580 nanometer ranges of light with a dip at about 490 nanometers(2442).

Otto Fritz Meyerhof  (DE-US) and Renate Junowicz-Kocholaty (US) re-determined the equilibrium constant for the isomerase and aldolase reactions in the presence and absence of inorganic phosphate, cozymase, and Warburg's oxidizing enzyme. They found that their values agreed with those previously determined and that equilibrium is not influenced by the presence of inorganic phosphate, cozymase, or Warburg's enzyme. They were also unable to detect the formation of any substance that would break down into glyceraldehyde phosphate and phosphate(2443).

Carl Ferdinand Cori (CZ-US) and Gerty Theresa Cori, née Radnitz (CZ-US), using liver tissue extract, presented evidence for the enzyme which forms the one to six glycosidic linkages in amylopectin(2232).

Sir Walter Norman Haworth (GB), Stanley Peat (GB), Edward J. Bourne (GB), Alan Macey (GB), and S.A. Barker (GB) presented evidence for this same enzyme in higher plants(2444-2447).

David Nachmansohn (RU-DE-US), Richard Threlkeld Cox (US), Christopher W. Coates (US), and Adao L. Machado (BR) found that the production of very strong currents by electric eels is connected with the breakdown of phosphocreatine(2448).

David Nachmansohn (RU-DE-US) and Adao L. Machado (BR) proved that electric tissue contains enzymes capable of utilizing the energy of ATP for the acetylation of choline by choline acetylase(2449). This was the first time ATP had been shown to drive a synthetic reaction other than phosphorylation.

Juan M. Muñoz (AR) and Luis Federico Leloir (AR) demonstrated fatty acid oxidation in cell-free liver systems(2450, 2451).

Albert Lester Lehninger (US) showed that ATP is required for the oxidation of fatty acids and gave evidence that the fatty acid is enzymatically activated at the carboxyl group. He also found that fatty acids are oxidized to yield two-carbon units that can enter the tricarboxylic acid cycle(2452).

Donald Dexter Van Slyke (US), Robert A. Phillips (US), Paul B. Hamilton (US), Reginald M. Archibald (US), Palmer H. Futcher (US), and Alma Hiller (US) identified glutamine as source material for urinary ammonia(2453).

Alfred Ezra Mirsky (US) and Arthur Wagg Pollister (US) demonstrated that histones are common to all somatic nuclei(2454).

Salvador Edward Luria (IT-US) Max Ludwig Henning Delbrück (DE-US), and Thomas Foxen Anderson (US) were the first to see bacterial ribosomes. They did not, at the time, know what they were(2455).

Salvador Edward Luria (IT-US) and Max Ludwig Henning Delbrück (DE-US) published a paper entitled Mutations of Bacteria from Virus Sensitivity to Virus Resistance. This paper represents the birth of bacterial genetics. With their paper, Luria and Delbrück did for bacterial genetics what Mendel had done for general genetics—namely, to show for the first time what kind of experimental arrangements, what kind of data treatment, and, above all, what kind of sophistication are required for obtaining meaningful and unambiguous results(2456).

Bacteriophages (phages) are subcellular parasites that infect, multiply within, and kill bacteria. The T1 (T one) phage active on Escherichia coli—with which Luria and Delbrück were working— has a head and a tail and occupies about one-thousandth the volume of its Escherichia coli host. It is to small to be seen with a light microscope. Upon collision of such a T1 phage particle with an Escherichia coli cell, the particle is fixed to the cell surface by interaction with a T1-phage receptor site; such sites form part of the Escherichia coli cell wall. The interaction of a phage particle with its phage receptor site has the same high degree of specificity as the interaction of the active site of an enzyme with its substrate. Once fixed to the receptor site, the T1 phage particle invades the Escherichia coli cell and destroys it. Imagine an experiment in which about 105 Escherichia coli cells are spread on the surface of a nutrient agar plate containing 1010 T1 phage particles. Upon incubation of that plate, the agar surface will most likely remain completely blank: not a single Escherichia coli colony can be expected to appear on that plate, since every bacterium of the inoculum will be infected, and hence killed, by one or more of the 1010 phage particles on the plate. 

The point of departure of Luria and Delbrück’s paper was the observation that, upon spreading about109, rather than only about 105, Escherichia coli cells upon agar containing an excess of T1 phage particles, the chances are rather good that a few Escherichia coli colonies will appear on the agar surface. If one of these few surviving colonies is picked, and a sample of the cells making up the colony replated on agar containing T1 phage, it will be found that all of these cells grow into colonies. That is to say, all of the bacteria in one of the few surviving colonies are T1-resistant or Tonr. By convention of genetic nomenclature, Ton designates the infectious agent and the superscripts r or s designate resistance or sensitivity of the host. The T1 resistant bacteria retain their Tonr character upon further cultivation in the absence of any T1 phage, as can be demonstrated by spreading samples of the Tonr culture growing in the T1-free medium on T1-containing agar. Thus the Tonr bacteria perpetuate and pass on to their descendants the property of resistance to the phage, in contrast to the T1 sensitivity passed on by the normal Tons Escherichia coli cells. The physiological basis of the T1 resistance resides in the structure of the bacterial cell wall, in that the cell wall of Tonr bacteria does not feature the T1 receptor sites, to which the phage particles attach before they infect and kill the Tons cell. Hence the T1 phage particles cannot attach to, and, therefore, cannot kill the Tonr cells. Since the few Tonr cells isolated by plating the original Escherichia coli culture on the T1-containing agar have clearly descended from the Tons ancestors that make up the bulk of the population, they must represent stable variants of the normal Tons type. That is, an element of the bacterium that controls the synthesis of the T1 receptor sites in the cell wall of the normal Tons cell has changed in some way in the Tonr variant so that these receptor sites are no longer formed.

Such instances of the appearance of stable bacterial variants resistant to one or another antibacterial agent had been well known to bacteriologists for many years when Luria and Delbrück designed an experiment that was to enable them to decide between the following two fundamentally different views of the origin of stable Tonr variants in cultures on Tons Escherichia coli: 1) the Tonr character is induced as a consequence of the exposure of the Tons bacterial culture to T1 phage, 2) the Tonr character pre-exists in a few cells before exposure of the bacterial culture to T1 phage (2456). This great experiment is often referred to as the fluctuation test. It gave proof that mutations are usually not induced by the environment.

Luria and Delbrück’s statistical proof of the spontaneous nature of bacterial mutation and measurement of mutation rate represents not only the beginning of bacterial genetics, but also the first of several fortunate choices of experimental material that were to aid the further development of this field. Their finding of spontaneous mutation to phage resistance turns out to have depended on their use of the T1 phage, a phage that is a virulent bacteriophage. Had they happened to have picked one of the phage types that came to be known as temperate bacteriophages, they would have had to conclude (wrongly) that the bacterial variants acquire their resistant character by contact with the antibacterial agent (2456).

Carl Clarence Lindegren (US) and Gertrude Lindegren (US) discovered heterothallism with two mating types in Saccharomyces(2457). 

Frederick Kroeber Sparrow (US) authored Aquatic Phycomycetes Exclusive of the Saprolegniaceae and Pythium, the first comprehensive systematic treatment of the aquatic Phycomycetes(2458).

Jacob S. Light (US) and Horace L. Hode (US) were probably the first to report clinical cases of rotaviral gastroenteritis(2459, 2460).

Curt Stern (DE-US) and Elizabeth White Schaeffer (US), using the recessive cubitus interruptus (ci) allele in Drosophila, demonstrated isoalleles(2461). 

Ragnar Granit (FI-SE) proposed a physiological theory of color perception. “The mechanism of color reception is organized by the peripheral visual apparatus, the number of color-sensitive elements is relatively limited, and these elements represent widely different regions of the visible spectrum(2462).” He also made the first ganglion cell recordings from a mammalian retina, the cat retina(2463).

Paul R. Dumke (US), Carl Frederic Schmidt (US), and Harry H. Pennes (US) made the first quantitative measurements of the cerebral blood flow in lightly anesthetized macaque monkeys and determined cerebral oxygen consumption in the same state and under deeper anesthesia as well as convulsive activity(2464, 2465).

Seymour Solomon Kety (US) and Schmidt described a quantitative method for measuring cerebral blood flow in humans using nitrous oxide (Kety-Schmidt technique)(2466-2468). The method is based upon the uptake by the brain of the diffusible nitrous oxide supplied by way of the arterial blood. These works led directly or indirectly to the development of current methods for the measurement of regional blood flow, metabolism, and the visualization of functional activity throughout the human brain.

Albert Claude (BE-US) used differential centrifugation to isolate a mitochondrial fraction from liver(2469). 

H. Nakamura (JP) and H. Tsumagari (JP) were the first to describe the tobacco stunt disease(2470).

Victor Assad Najjar (LB-US) and L. Emmett Holt, Jr. (US) discovered that bacteria in the bowl of man are synthesizing thiamine (vitamin B1) which is being absorbed into the blood stream(2471).

Robert Edward Hungate (US) described an anaerobic cellulose digesting bacterium from the rumen of cattle(2472). 

Frank Baker (GB), S.T. Harris (GB), R.M. Pearson (GB), and J.A.B. Smith (GB) used histochemical and histophysical methods to identify cellulose cleaving microorganisms in the rumen of cattle and sheep, and in the caeca of the horse, guinea pig, rabbit, and hen. They observed that each host species tends to harbor a characteristic microbiota(2473-2477).

Robert Williams (GB), G.J. Harper (GB), and Sir Arnold Ashley Miles (GB) developed a slide agglutination reaction using human plasma to identify coagulase positive staphylococci(2478).

Wilson Smith (GB) and J.H. Hale (GB) determined that pathogenic strains of Staphylococcus aureus and also of the albus variety regularly produce coagulase while nonpathogenic strains do not(2479).

Tracy Morton Sonneborn (US) showed that various cases of non-Mendelian inheritance can be classified into distinct groups, most involving interactions between nuclear genes and the cytoplasm(2480, 2481). 

Maxwell E. Power (US) began his very important contribution to insect neuroanatomy by studying the distribution of nerve tracts and specific fibers in the brain of Drosophila as well as its thoracico-abdominal nervous system(2482-2484).

Carroll Milton Williams (US), and Muriel Voter Williams (US) demonstrated the neuromuscular network in the thorax that controls the wing-beat in Drosophila(2485).

Wilton R. Earle (US), Emma Shelton (US), Edward L. Schilling (US), Thomas H. Stark (US), Nancy P. Straus (US), Mary F. Brown (US), and Anderson Nettleslip (US) were the first to establish a permanent mammalian cell line in vitro. The cells were originally derived from an explant of subcutaneous tissue from the C3H strain of mice and after many subculturings designated the L strain. They found they could alter the morphology and growth characteristics of these cells by treatment with a carcinogen. When these altered cells were injected into healthy mice, tumors were produced. Earle and Nettleship (US) noted that all of these normal cells maintained in vitro, even those not treated with a carcinogen, eventually became malignant and reverted (transformed) to a more primitive morphology(2486-2492).

Paul Bruce Beeson (US) published the classic description of transfusion-transmitted hepatitis. He linked the occurrence of jaundice in seven cases to blood or plasma transfusions the patients had received a few months prior, providing the quintessential description of transfusion-transmitted hepatitis(2493).

Clinton Nathan Woolsey (US) discovered a second somatic sensory receiving area in the cortex of the cat, dog, and monkey(2494).

Edgar Douglas Adrian (GB) independently made the same discovery at a slightly later time in the Shetland pony(2495). 

Min Chueh Chang (CN-US) discovered that applying ice to the scrotum of sheep causes severe disintegration of sperm from the lower end of the of the epididymis. He referred to this as cold shock(2496).

Paul Hahn (US) observed that within 1 minute after injection of 250 units of the anticoagulant heparin into lipemic dogs, the lipemia (due principally to chylomicrons, the lowest density lipoproteins in blood) had totally cleared,  as observed visually in samples of drawn blood(2497).

Norman Gulack Anderson (US) and Blake Fawcett (US) found that heparin injection causes the appearance in plasma of a "lipemia clearing factor" or "antichylomicronemic substance" that can clear lipemic plasma in vitro(2498).

Edward D. Korn (US) found that the “clearing factor” is, in fact, a heparin-activated lipoprotein lipase that occurs in and is released by heparin from heart and adipose tissues. It hydrolyzes the triacylglycerols of lipoproteins but not simple oil emulsions; the latter could, however, be converted to substrate by complexing with a high density lipoprotein(2499-2501).

Jan Gosta Waldenström (SE) described three patients with an elevated erythrocyte sedimentation rate (ESR) who had hyperproteinemia and petechiae of their lower extremities without evidence of malignancy(2502). Although he coined the term purpura hyperglobulinaemica, this entity is now recognized as benign hypergammaglobulinemic purpura of Waldenström (BHPW).

James Purdon Martin (GB) and Julia Bell (GB) were the first to describe the fragile X syndrome (Martin-Bell syndrome)(2503).

Herbert A. Lubs (US) reported the fragile site on the X chromosome(2504).

Annemiske J.M.H. Verkerk (NL), Maura Pieretti (US), James S. Sutcliffe (US), Ying-Hui Fu (US), Derek P. Kuhl (US), Antonio Pizzuti (US), Orly Reiner (US), Stephen Richards (US), Maureen F. Victoria (US), Fuping Zhang (US), Bert E. Eussen (NL), Gert-Jan B. van Ommen (NL), Lau A.J. Blonden (NL), Gregory J. Riggins (US), Jane L. Chastain (US), Catherine B. Kunst (NL), Hans Galjaard (NL), Charles Thomas Caskey (US), David L. Nelson (US), Ben A. Oostra (NL), and Stephen T. Warren (US) identified a gene for fragile X syndrome (FMR-1) containing a CGG repeat coincident with a breakpoint cluster region and determined that its transcriptional silence is due to heavy methylation(2505, 2506).

Eric J. Kremer (AU), Melanie A. Pritchard (AU), Michael Lynch (AU), Sui Yu (AU), Katherine Holman (AU), Elizabeth Baker (AU), Stephen T. Warren (AU), David Schlessinger (AU), Grant R. Sutherland (AU), and Robert I. Richards (AU) determined that fragile X syndrome is caused by a massive expansion and concomitant methylation of a CCG repeat located in the 5’-untranslated region of the FMR1 gene, which results in transcriptional silencing of the gene(2507, 2508). Fragile X syndrome is one of the most common forms of inherited mental retardation.

John Freeman Loutit (GB) and Patrick Loudon Mollison (GB) devised a disodium-citrate-glucose mixture as a blood preservative which made possible the storage of whole blood for up to three weeks(2509).

Thomas Gibson (GB) and Peter Brian Medawar (GB) defined the immunologic nature of skin allograft rejection in humans, confirmed subsequently with controlled rabbit experiments(2510, 2511).

Sir Kenelm Digby (GB), and M.A. Hupka (), and Josephus Wolff () provided evidence of a skin graft rejection on a patient's nose in the year 1661(2512). 

F. Gerard Allison (CA) described restless legs syndrome and offered a treatment(2513).

Edwin Bennett Astwood (US) found that hyperthyroidism can be successfully treated with thiourea and thiouracil(2514).

Clarence Crafoord (SE) and Gustav Nylin (SE) surgically repaired congenital coarctation of the aorta in a human(2515).

Robert Edward Gross (US) and Charles A. Hufnagel (US) performed the successful corrective surgery of coarctation of the aorta. In infants this narrowing of the aorta is typically proximal to its junction with the ductus arteriosus. The adult type is at or distal to the junction. This condition is usually fatal(2516-2518).

Jay Tepperman (US), John Raymond Brobeck (US), and Cyril Norman Hugh Long (US) described hypothalamic hyperphagia in the albino rat(2519).

David Lambert Lack (GB) wrote The Galapagos Finches (Geospizinae) a Study in Variation; Darwin’s Finches; The Life of the Robin; and Swifts in a Tower, all important contributions to ornithology and an introduction of competition theory into animal ecology, stressing the importance of ecological isolation in speciation, and providing a cogent model for adaptive radiation(2520-2523).

1944

“From Type III pneumococcus a biologically active fraction has been isolated…which in exceedingly minute amounts is capable…of inducing the transformation of unencapsulated R variants of Pneumococcus Type II into fully encapsulated cells of the same specific type as that of the heat-killed microorganisms from which the inducing material was recovered…. The active fraction…consists principally…of a highly polymerized, viscous form of desoxyribonucleic acid.” Oswald Theodore Avery(2524).

Joseph Erlanger (US) and Herbert Spencer Gasser (US) shared the Nobel Prize in Physiology or Medicine for their determination of how different nerve fibers (cells) conducted their impulses at different rates. All else being equal, the velocity of the impulse varies directly with the thickness of fiber.

Raphael Consden (GB), Arthur Hugh Gordon (GB), and Archer John Porter Martin (GB) developed the technique of paper chromatography and stated that, “the separation depends on the differences in partition coefficient between the mobile phase and the water-saturated cellulose, instead of differences in adsorption by the cellulose”(2525).

Lyman Creighton Craig (US) developed liquid-liquid countercurrent distribution as a separation and purification technique(2526).

Charles M. Brewer (US) reported that the phenol coefficient technique is unsatisfactory for evaluating quaternary ammonium compounds because the results are to inconsistent(2527).

George A. Buntin (US) produced the first samples of toxaphene, a potent insecticide which could kill a wide range of cotton (Gossypium spp.) insect pests. Pilot plant production began in 1945(2420).

Vincent du Vigneaud (US), Glen W. Kilmer (US), Julian R. Rachele (US), and Mildred Cohn (US) determined that all the sulfur and none of the carbon in newly formed cysteine originates from methionine(2528).

Robert Burns Woodward (US) and William von Eggers Doering (US) performed the total synthesis of quinine from very simple molecules(2529, 2530). 

Stanton A. Harris (US), Donald E. Wolf (US), Ralph Mozingo (US), R. Christian Anderson (US), Glen E. Arth (US), Nelson R. Easton (US), Dorothea Heyl (US), Andrew N. Wilson (US), and Karl August Folkers (US) achieved the first synthesis of biotin(2531).

Henry Arnold Lardy (US), Richard L. Potter (US), and Conrad Arnold Elvehjem (US) found that the function of biotin is to fix carbon dioxide in heterotrophic organisms(2532). 

Pat N. Confalone (US), Giacomo Pizzolato (US), Enrico G. Baggiolini (US), Dianne Lollar (US), and Milan R. Uskokovic (US) carried out a total synthesis of biotin, an essential vitamin that functions as an indispensable coenzyme in a range of biocarboxylation reactions related to crucial physiological processes such as glucogenesis and fatty acid synthesis(2533, 2534).

Albert Schatz (US), Elizabeth Bugie (US), and Selman Abraham Waksman (RU-US) isolated a new antibacterial substance, they designated streptomycin. It was isolated from two strains of an actinomycetes related to an organism described as Actinomyces griseus(2535, 2536). It was first used on humans May 12, 1945. Waksman is credited with coining the word antibiotic (against life)(2537). See, Papacostas, 1928. Streptomycin prevents the transition from initiation complex to chain elongating ribosome and also causes miscoding in prokaryotes only.

Frederick A. Kuehl, Jr. (US), Karl August Folkers (US), Robert L. Peck (US), Alphonse Walti (US), and Charles E. Hoffhine, Jr. (US) crystallized then determined the structure of streptomycin(2538, 2539).

Oswald Theodore Avery (CA-US), Colin Munro MacLeod (US), and MacLyn McCarty (US) discovered that genetic information is contained in, and transmitted by DNA(2524). Avery was 67 years old when this paper appeared. It is a mystery to many that he was never awarded the Nobel prize. Erwin Chargaff (AT-US) commented, “the ever rarer instance of an old man making a great scientific discovery. It had not been his first. He was a quiet man; and it would have honored the world more, had it honored him more”(2540).

Bernice E. Eddy (US) reported that based on serological typing reactions seventy-five varieties of pneumococcal capsules had been discovered(2541, 2542).

Eugene F. Jansen (US), and Doris J. Hirschmann (US) discovered the antibiotic subtilin, produced by Bacillus subtilis. It was later shown by others to be antagonistic chiefly to gram-positive bacteria. It also inhibits Mycobacterium spp. and a number of pathogenic higher fungi(2543).

Albert Edward Oxford (GB) isolated the antibiotic diplococcin from milk streptococci(2544).

Maud Leonora Menten (CA), Josephine Junge (US), and Mary H. Green (US) coined the phrase active site as it refers to the site of enzyme activity(2545).

Fritz Kubowitz (DE) and Paul Ott (DE) reported isolating pyruvate kinase from human muscle(2546).

David Rockwell Goddard (US) demonstrated that cytochrome oxidase operates with the cytochrome c from plants(2547).

Allen H. Brown (US) and David Rockwell Goddard (US) had shown that cytochrome oxidase is photoreversibly inhibited by carbon monoxide(2548).

Sidney Weinhouse (US), Grace S. Medes (US), and Norman F. Floyd (US) proved the correctness of Knoop's hypothesis that ketone bodies are synthesized from two carbon fragments that are generated by the oxidation of fatty acids in the liver(2549).

Grace S. Medes (US), Sidney Weinhouse (US), and Norman F. Floyd (US) proved decisively that beta-oxidation of a fatty acid occurs with some of the product undergoing oxidation via the tricarboxylic acid (TCA) cycle and the residue condensing into ketone bodies, acetoacetic acid and beta-hydroxybutyric acid(2550). 

See, Knoop, 1904.

Folke Karl Skoog (SE-US) produced in vitro cultures of tobacco tissue to study adventitious shoot formation(2551).

Folke Karl Skoog (SE-US) and Cheng Tsui (US) achieved the formation of adventitious shoots and roots with in vitro cultures of tobacco tissue(2552). 

Reginald Ernest Balch (GB-CA) and Frederick Theodore Bird (CA) provided one of the first reports on the use of a virus to control an arthropod pest, i.e., the European spruce sawfly(2553).

Charles H. Gray (US), Edward Lawrie Tatum (US), Raymond R. Roepke (US), Raymond L. Libby (US), and Margaret H. Small (US) described bacterial mutants in Escherichia coli which they characterized as auxotrophs, from the Greek aux-, increase (not from the Latin auxi-, help), and trophe, food. The normal or wild-type cells he called prototrophs, from protos, first, or minimal.

In order to isolate rare bacterial mutants that have a nutritional requirement for their growth with which the parent Escherichia coli can dispense, they followed essentially the same procedure that had yielded the Neurospora mutants in 1940. For this procedure large numbers of Escherichia coli cells were plated on nutrient agar—that is, on complete medium. The colonies which appeared after overnight incubation on the complete medium were then picked, and part of each bacterial clone was tested to ascertain whether it would grow on a minimal medium—that is, agar containing a synthetic medium deficient in all components except the minimum necessary to grow the prototroph. In this way Gray and Tatum found that, whereas the overwhelming majority of colonies consisted of bacterial clones capable of growing on both media, about 1% of the colonies that grew on the complete medium were made up of bacteria that were unable to grow on the minimal medium. That is, these rare colonies were made up of clones of nutritional Escherichia coli mutants, which require for their growth some factor present in the complete medium but absent from the minimal medium.

The exact nature of the growth requirement of any particular auxotrophic mutant strain could be established by placing samples of the auxotrophic bacterial clone into a series of minimal media to which various putative growth factors, such as amino acids, vitamins, purines, and pyrimidines, had been added. The growth requirement is then inferred to be that substance whose addition to the minimal medium is necessary and sufficient to allow growth of the auxotroph.

Gray and Tatum established that many of their Escherichia coli auxotrophs responded to the addition of just one single factor to the minimal medium. (By convention the auxotrophic mutants are designated with a minus sign and a three letter abbreviation for the specific synthetic deficiency, e.g., Thr -, Pro -,Trp -. The prototrophic condition carries a plus sign , e.g., Thr +, Pro +, Trp +. It is noted that the minus or plus superscripts affixed to these symbols mean inability or ability to synthesize the substances represented by the three-letter abbreviation, and not, as with sugar-fermentation mutants, inability or ability to utilize the substance as a source of carbon and energy)(2554, 2555).

Victor Assad Najjar (LB-US), George A. Johns (US), George C. Medairy (US), Gertrude Fleischmann (US), and L. Emmett Holt, Jr. (US) discovered that bacteria in the large intestine of man are synthesizing riboflavin (vitamin B2) which is being absorbed into the blood stream(2556).

Roger Buvat (FR) noted that in vitro plant tissue will, with time, tend toward dedifferentiation(2557).

Lothar Szidat (CL) found eggs of the fish tapeworm, Diphyllobothrium latum, in the intestines of two human bodies preserved in a peat bog in East Prussia since the early glacial period, i.e., Weichselian at 10- 110 Ka(2558).

J. Zed Young (GB), Paul Alfred Weiss (AT-US), and Helen B. Hiscoe (US) discovered that axoplasm of neurons is continuously flowing down nerve fibers at the rate of 0.2 mm per day(2559, 2560). 

William Hugh Feldman (US) and Horton Corwin Hinshaw (US) were the first to demonstrate successful in vivo treatment of tuberculosis with streptomycin(2561, 2562).

Sir Peter Brian Medawar (GB), Leslie Brent (GB), Rupert Everett Billingham (GB-US), and Elizabeth M. Sparrow (GB) established the immunological basis of the allograft reaction including an explanation of the second-stage phenomenon, i.e., an animal which has been grafted with foreign skin from the same donor on two successive occasions will reject the second graft more rapidly than the first(2511, 2563-2566).

Sir Peter Brian Medawar (GB) observed that presensitization of a recipient with leucocytes from the graft donor accelerated skin graft rejection, whereas erythrocytes had no effect. He therefore concluded that the search for histocompatibility antigens (coined in 1948) should be focused on the white cells, not the red cells, of the blood(2564).

William Christopher Stadie (US), Benjamin C. Riggs (US), and Niels Haugaard (US) wrote a series of papers on the oxygen poisoning of enzymes and tissues at hyperbaric pressures(2567-2575).

Aristides Azevedo Pacheco Leão (BR), while studying the epileptiform after discharge response of the cerebral cortex to electric stimulation in rabbits, discovered the spreading depression reaction—a response of the dorsolateral neocortex to electric or mechanical stimuli applied to its surface. This visible aura frequently precedes migraine headaches(2576-2578).

DeWitt Stetten, Jr. (US) and George E. Boxer (US) concluded from their experiments that in animals fed a high carbohydrate diet, fatty-acid formation is a more important pathway in glucose utilization than glycogenesis.

Johann Justus Freiherr von Liebig (DE) proposed that carbohydrates can serve as precursors to fats. He suggested this based on his observation that farmers fattened their cattle by feeding them grains. He noted that to make fat from sugar would simply require the removal of oxygen from sugar molecules.

John Friend Mahoney (US), Richard C. Arnold (US), Burton L. Sterner (US), Ad Harris (US), Margaret R. Zwally (US) described the use of penicillin to treat syphilis(2579). One long-term result of this discovery was the virtual elimination of tertiary syphilis of the brain, once a leading cause of insanity throughout the world.

Theodore B. Steinhausen (US), Clarence E. Dungan (US), Joseph B. Fürst (US), John T. Plati (US), S. Willard Smith (US), A. Perry Darling (US), E. Clinton Wolcott, Jr. (US), Stafford L. Warren (US), and William H. Strain (US) introduced the use of ethyl iodophenylundecylate (Pantopaque) compounds as contrast media to perform radiographic diagnosis(2580).

John McMichael (GB), Edward P. Sharpey-Schafer (GB), Rajane M. Harvey (US), M. Irené Ferrer (US), Richard T. Cathcart (US), Dickinson Woodruff Richards (US), André Frédéric Cournand (FR-US), Richard A. Bloomfield (US), Bernard Rapoport (US), J. Pervis Milnor (US), Walter K. Long (US), J. Gilmer Mebane (US), Laurence B. Ellis (US), and M. Rita Lavin (US) established that digitalis glucosides act favorably only upon ventricles over-dilated, with excessive filling pressures and inadequate emptying; that in such hearts it acts rapidly to increase the energy of contraction, increase stroke volume, and promote adequate emptying, thus relieving the congestive state; that it performs with regular as well as irregular cardiac rhythms(2581-2583).

Arnold Rice Rich (US) clarified the pathogenesis of the spread of the tubercle bacilli in the body(2584).

Jan Gosta Waldenström (SE) described two patients with oronasal bleeding, lymphadenopathy, normochromic anemia, increased erythrocyte sedimentation rate, thrombocytopenia, hypoalbuminemia, low serum fibrinogen, and increased numbers of lymphoid cells in the bone marrow. Prolonged bleeding after lymph node biopsy and bone marrow aspiration, lobar pneumonia, and retinal hemorrhages were observed. His initial description remains to this day characteristic of the clinical presentation and laboratory abnormalities of Waldenström's macroglobulinemia related to excess IgM(2585).

John Rock (US) and Miriam Menkin (US) announced the first successful human in vitro fertilization (IVF) experiment(2586).

Grantly Dick-Read (GB) developed the concept of natural childbirth: that by elimination of fear and tension, labor pain could be minimized and anesthetics, which can be hazardous to both mother and child, rendered unnecessary(2587).

David H. Rosenberg (US) and Philip A. Arling (US) were the first to successfully treat meningitis with intravenous and intrathecal penicillin(2588). Since then, penicillin has remained the drug of choice for the treatment of meningococcal meningitis.

Paul Jackson Kramer (US) and John P. Decker (US) determined that the eventual transformation of pine forests to hardwood forests results from the inability of pine seedlings to grow in the low light intensities under deciduous trees(2589). This work is one of the first explanations of the succession of plant species in natural communities.

1945

Artturi Ilmari Virtanen (FI) was awarded the Nobel Prize in Chemistry for his research and inventions in agricultural and nutrition chemistry, especially for his fodder preservation method.

Sir Alexander Fleming (GB), Sir Ernst Boris Chain (DE-GB), and Lord Howard Walter Florey (AU-GB) were awarded the Nobel Prize for physiology and medicine for the discovery of penicillin and its curative effect in various infectious diseases.

Erwin Schrödinger (AT) wrote his little book What is Life?, which had a profound effect on physical scientists. Since many of these physical scientists were suffering from a general professional malaise in the immediate post-war period, they were eager to direct their efforts toward a new frontier which, according to Schrödinger, was ready for some exciting developments. He tantalized physicists by suggesting that while the study of the gene would not elude the laws of physics, as established up to that date, it was likely to involve other laws of physics hitherto unknown. Their knowledge of biology was generally confined to stale botanical and zoological lore, and having one of the founding fathers of the new physics put the question, what is life? provided for them an authoritative confrontation with a fundamental problem worthy of their mettle. Schrödinger’s book became a kind of catalyst of the revolution in biology that, when the dust had cleared, left molecular biology as its legacy. It is in this book that Schrödinger proposes the existence of an aperiodic solid polymer with potential as a miniature code containing information which is transmitted from one generation to the next(2590).

Robley Cook Williams (US) working with the electron microscopist Ralph Walter Greystone Wyckoff (US) developed the technique of metal shadow casting. This allows tiny objects to take on a three dimensional quality when viewed through the electron microscope(2591).

Gösta Karpe (DK) made electroretinography a useful clinical method(2592).

Gordon R. Baldock (GB) and William Grey Walter (GB-US) developed automated spectral analysis of EEG traces. A standard method for EEG analysis since its discovery has been to measure the power in various frequency bands, including alpha and delta, also beta (15-30 Hz), and theta (3-7 Hz). Walter used his skills in analog electronics to build a device that displayed the frequency content in an EEG trace, even as the trace was displayed with an ink-writing oscillograph, a pen whose fluctuations left a trace on moving paper that became the mainstay of electroencephalographers(2593, 2594).

Gerhard Schmidt (US) and Siegfried Joseph Thannhauser (US) presented a method for the determination of desoxyribonucleic acid, ribonucleic acid, and phosphoproteins in animal tissues(2595).

Willard A. Krehl (US), Lester J. Teply (US), Padman S. Sarma (US), and Conrad Arnold Elvehjem (US) presented evidence that tryptophane is very likely a metabolic precursor to niacin (vitamin B3)(2596, 2597).

Harland Goff Wood (US), Nathan Lifson (US), and Victor Lorber (US) demonstrated the pathway of carbon dioxide incorporation into specific carbon atoms of glucose derived from rat hepatic glycogen(2598).

Percy Wragg Brian (GB), Harold George Hemming (GB), and J.C. McGowan (GB) reported that griseofulvin is antifungal because it inhibits Botryti allii and produces distortions in its germ tubes(2599).

Albert Edward Oxford (GB), Harold Raistrick (GB), and Paul Simonart (GB) discovered griseofulvin as a product of Penicillium griseofulvum(2600).

James C. Gentles (GB) reported the successful treatment of dermatophytosis in guinea pigs with griseofulvin(2601). It was introduced for clinical use in 1959.

Alastair Campbell Frazer (GB) and Herbert G. Sammons (GB) demonstrated that the formation of mono- and diglycerides from triglycerides results from the action of pancreatic lipase (pancreatic triacylglycerol lipase) both in vitro and in vivo, with no free glycerol appearing during the first five hours of the reaction(2602).

Clause Silbert Hudson (US), Nelson K. Richtmyer (US), and James W. Pratt (US) elucidated the structure of sedoheptulose(2603-2605).

Linus Carl Pauling (US) speculated that the biological action of a protein is related to the shape of the surface into which the polypeptide folds(2606).

Erwin Brand (US), Leo J. Saidel (US), William H. Goldwater (US), Beatrice Kaseel (US), and Francis J. Ryan (US) reported the first complete amino acid analysis of a protein by chemical and microbiological methods. The protein was beta-lactoglobulin(2607). Beta-lactoglobulin is the major whey protein in the milk of ruminants and some non-ruminants.

Choh Hao Li (CN-US), Herbert McLean Evans (US), Miriam E. Simpson (US), and Kai O. Pederson (US) isolated and determined the properties of anterior hypophyseal growth hormone known as somatotropin or growth hormone (GH) from the ox(2608, 2609).

Choh Hao Li (CN-US) and Harold Papkoff (US) prepared and tested the properties of growth hormone from human and monkey pituitary glands(2610).

Frederick Sanger (GB), Hans Tuppy (GB), Edward Owen Paul Thompson (GB), Andrew P. Ryle (GB), Leslie F. Smith (GB), Ruth Kitai (GB), and Henry Brown (GB) developed a method for determining the nature and amount of the amino-terminal amino acid residues in a protein by using dinitrofluorobenzene. When they applied this methodology to insulin they concluded that each 12,000 molecular weight unit contained two amino-terminal glycine residues and two amino-terminal phenylalanine residues. Sanger postulated that, “The presence of four alpha amino groups suggests that the submolecule is built up of four open polypeptide chains bound together by cross-linkages, presumably chiefly disulfide linkages. It is, of course, possible that other chains may be present in the form of a ring structure with no free amino groups”. They later found that insulin was likely to be composed of two polypeptide chains, succeeding in determining the exact amino acid sequences for both chains of bovine insulin. This was the first demonstration that proteins contain a precise amino acid sequence(2611-2620).

Donald Frederick Steiner (US), Ronald E. Chance (US), Robert M. Ellis (US), William W. Bromer (US), Ole Hallund (DK), Arthur Harold Rubenstein (US), Sooja Cho (US), Claudia Bayliss (US), Jeffrey L. Clark (US), Chris Nolan (US), Emanuel Margoliash (IL), Bradley Aten (US), Philip E. Oyer (US), James D. Peterson (US), and Franco Melani (US) found that insulin is synthesized first in the islet cells as a single-chained precursor, proinsulin. In the pancreatic duct proinsulin is subsequently converted to the two-chained form by the enzymatic removal of a segment from its middle after the formation of the three disulfide bonds(2621-2627). This represents the first evidence for the existence of a novel family of endoproteolytic processing enzymes called proprotein convertases. See Roebroek, 1986.  

Otto Fritz Meyerhof (DE-US) demonstrated the need for ATPase during glycolysis(2628).

Walter C. Schneider (US) described methodology by which DNA, RNA, and cellular protein can be separated from one another(2629, 2630).

Fritz Albert Lipmann (DE-US) discovered how pyruvate is oxidized to the intermediate formation of a reactive two-carbon fragment (active acetate) by studying a model system. He showed that pigeon-liver extracts, in the presence of added ATP, also affected the acetylation of the amino group of the drug sulfanilamide with acetate as the source of potential active acetate. He found that this reaction required—in addition to thiamine pyrophosphate—the presence of a heat-stable dialyzable factor which he named cofactor coenzyme A (A for acetylation)(2631).

Fritz Albert Lipmann (DE-US), Nathan Oram Kaplan (US), G. David Novelli (US), L. Constance Tuttle (US), and Beverly M. Guirard (US) tested coenzyme A for vitamin activity and indeed found that it contains pantothenic acid (Greek, pantothen, from every side)(2632).

Joseph Richard Stern (US), Severo Ochoa (ES-US), G. David Novelli (US), Fritz Albert Lipmann (DE-US), Willard B. Elliott (US), George Kalnitsky (US), and Feodor Felix Konrad Lynen  (DE) reported the synthesis of citrate from acetate, ATP, CoA, and oxaloacetate in pigeon liver, yeast, Escherichia coli, and kidney tissue. It was shown that citrate rather than cis-aconitate or isocitrate is the product of the "acetate"-oxaloacetate condensation(2633-2637). This is citrate synthase.

Fritz Albert Lipmann (DE-US), Nathan Oram Kaplan (US), G. David Novelli (US), L. Constance Tuttle (US), and Beverly M. Guirard (US) isolated coenzyme A(2638).

G. David Novelli (US) and Fritz Albert Lipmann (DE-US) confirmed the catalytic function of coenzyme A in citric acid synthesis using cell-free extracts of Saccharomyces cerevisiae and Escherichia coli(2634).

Seymour Korkes (US), Joseph Richard Stern (DE-US), Irwin Clyde Gunsalus (US) and Severo Ochoa (ES-US) elucidated the enzymatic synthesis of citrate from pyruvate and oxalacetate in Escherichia coli(2639).

Fritz Albert Lipmann (DE-US), Nathan Oram Kaplan (US), G. David Novelli (US), L. Constance Tuttle (US), and Beverly M. Guirard (US) isolated coenzyme A(2638).

Feodor Felix Konrad Lynen (DE), Ernestine Reichert (DE), and Luistraud Kröplin-Rueff (DE) established the precise chemical mechanism by which coenzyme A carries acyl groups. They isolated an active form of acetate from yeast and showed it to consist of a thioester of acetic acid with the thiol or sulfhydral group of coenzyme A. The function of coenzyme A is to serve as a carrier of acyl groups in enzymatic reactions involved in fatty acid oxidation, fatty acid synthesis, pyruvate oxidation, and biological acetylations(2640-2642).

Sir James Baddiley (GB), Eric M. Thain (), G. David Novelli (US), and Fritz Albert Lipmann (DE-US) worked out the structure of coenzyme A(2643).

Severo Ochoa (ES-US), Joseph Richard Stern (DE-US), Morton C. Schneider (US), and Feodor Felix Konrad Lynen  (DE) demonstrated that acetyl-CoA is the substance that reacts with oxaloacetate to form citrate in the presence of the condensing enzyme crystallized by Severo Ochoa’s laboratory(2637, 2644).

Horace Albert Barker (US) and Earl Reece Stadtman (US) found that coenzyme A participates in the metabolism of fatty acids(2645).

Roscoe O. Brady (US) and Earl Reece Stadtman (US) detected three distinctly different thioltransacetylases in pigeon liver extracts; namely, thioltransacetylase A which catalyzes the transfer of the acetyl group of acetyl CoA to reduced lipoic acid, 2-mercaptoethanol, and to a lesser extent to some other mercaptans, thioltransacetylase B which catalyzes the acetylation of 2-mercaptoethanol and 2-mercaptoethylamine, and a hydrogen sulfide thioltransacetylase that catalyzes the acetylation of hydrogen sulfide with the formation of thioacetic acid(2646).

John Gilbert Moffatt (US) and Har Gobind Khorana (IN-US) synthesized coenzyme A(2647). NAD and lipoic acid were found to be requirements for coenzyme A activity. See, Lester J. Reed.

Herman Moritz Kalckar (DK-US) and Manya Shafran (US) discovered that phosphorolytic cleavage of nucleosides is similar to that of glycogen, e.g. ribose-hypoxanthine + Pi is converted to ribose-1-P + hypoxanthine. The equilibrium of this reaction lies to the left. This was the first demonstration of enzymatic synthesis of a nucleoside(2648, 2649).

Gerty Theresa Cori, née Radnitz (CZ-US), Milton Wilbur Slein (US), and Carl Ferdinand Cori (CZ-US) crystallized glyceraldehyde-3-dehydrogenase from skeletal muscle(2650).

Winston H. Price (US), Carl Ferdinand Cori (CZ-US), and Sidney P. Colowick (US) demonstrated that hexokinase activity is promoted by insulin but checked by another hormone in extracts from the anterior lobe of the pituitary gland, i.e., the hypophysis(2651). This first demonstration of a regulatory effect of hormone on enzyme opened a whole new field of investigation.

David Shemin (US) and David Rittenberg (US) observed that if 15N-labelled glycine molecules are given to human subjects it leads to hemin (ferriprotoporphyrin) molecules in which all four nitrogens are 15N. Serendipitously they found that the data allowed them to calculate the average life-span of a human erythrocyte at 127 days(2652-2654).

David Shemin (US), Irving M. London (US), David Rittenberg (US), Jonathan B. Wittenberg (US), Kenneth D. Gibson (US), William Graeme Laver (AU), and Albert Neuberger (DE-GB) elucidated the basic aspects of heme biosynthesis and showed that glycine and succinyl CoA are the source of all the heme(2655-2660).

Gunnar Östergren (SE) formulated the concept of selfish DNA. Speaking of non-coding B chromosomes, he stated that: “I think reasonable support may be given to the view that in many cases these chromosomes have no useful function at all to the species carrying them, but they often lead an exclusively parasitic existence”(2661).

Norman Harold Horowitz (US) and Jerry S. Hubbard (US) postulated how complex sequential metabolic pathways may have arisen as the result of selective pressure, i.e., the retrograde model.

Suppose that a contemporary cellular pathway makes a required substance such as an amino acid through the sequence A to B to C to D to E, in which A is a simple inorganic substance and E is the final organic product. Initially E was plentiful in the environment and was absorbed directly by primitive aggregates. Later, as E became scarce because of use, chemical selection favored pre-cells that could make E from D, a slightly less complex organic substance still found in abundance in the environment. As D became exhausted, selection favored assemblies that developed the pathway C to D, in which the even simpler substance C could be absorbed and used as raw material to make D. This process continued until the entire synthetic pathway, based on an essentially inexhaustible inorganic substance, was established(2662, 2663).

Milislav L. Demerec (HR-US) and Ugo Fano (US) collected the group of seven bacteriophages later to be called the T-set. Their host is E. coli strain B. They were numbered consecutively as they were collected (most likely from sewage or feces)(2664, 2665). Of the seven, the so-called T-even strains (T2, T4, and T6), which are similar structurally, antigenically, and genetically, proved the most useful for biochemical and genetic studies.

Sir Alan Lloyd Hodgkin (GB) and Sir Andrew Fielding Huxley (GB) were able to measure the resting and action potentials in single nerve fibers (cells)(2666).

Keith Roberts Porter (US), Albert Claude (BE-US), and Ernest F. Fullam (US) produced the first electron micrograph of an intact eukaryotic cell. The cell was a cultured fibroblast originating from a chick embryo, which was grown by Porter on polyvinyl film, then peeled off and transferred to a wire specimen grid. The cell was fixed with osmium tetroxide, washed and then dried in order to prevent evaporation in the electron microscope's vacuum chamber. Magnified 1600 times, this first electron micrograph of a cell reveals mitochondria, the Golgi apparatus and a lace-like reticulum which Porter later named the endoplasmic reticulum. The electron microscope used for this historic image was an RCA EMB model, operated by Fullam at the Interchemical Corporation in New York City(2667).

George Emil Palade (RO-US), Keith Roberts Porter (US), Frances Kallman (US) and Fritiof Stig Sjöstrand (SE) developed methods for fixation and thin sectioning that enabled many intracellular structures to be seen for the first time(2668-2671).

Keith Roberts Porter (US), working with Albert Claude (BE-US), named the endoplasmic reticulum(2672).

H. Stanley Bennett (US), Keith Roberts Porter (US), and George Emil Palade (RO-US) identified the sarcoplasmic reticulum(2673, 2674). Porter and Palade described the transverse channels so vital to conduction.

Keith Roberts Porter (US) and Joseph Blum (US) developed the ultramicrotome. The invention took place in 1952(2675).

Fritiof Stig Sjostrand (SE), Leonard G. Worley (US), Ernest Fischbein (US), and Jennie E. Shapiro (US) discovered the ciliary rootlet as an anatomical structure(2676, 2677). The cross-linking between the rootlets and other cytoskeletal elements indicate its important role as an anchor and support structure for the cilia.

Hermann Joseph Muller, Jr. (US) made an exceptionally farsighted interpretation of Oswald Theodore Avery’s work on the transformation of pneumococci(2524). Muller stated, “There were, in effect, still viable bacterial ‘chromosomes’ or parts of chromosomes floating free in the medium used. These might, in my opinion, have penetrated the capsuleless bacteria and in part at least have taken root there.

A method appears to be provided whereby the gene constitution of these forms can be analyzed, much as in the cross-breeding tests on the higher organisms. However, unlike what has so far been possible in higher organisms, viable chromosome threads could also be obtained from these lower forms for in vitro observation, chemical analysis, and determination of the genetic effects of treatment”(2678, 2679).

Max Ludwig Henning Delbrück (DE-US) organized the first annual summer phage course at Cold Spring Harbor, New York. This course persuaded many young scientists to adopt phage as a tool for solving problems of a biological nature; especially the problem of defining a gene and its relationship to DNA.

Michael Doudoroff (RU-US) proposed that the utilization of sugars is controlled by permeability mechanisms involving sugar-specific carrier proteins(2680, 2681).

Salvador Edward Luria (IT-US) discovered that bacteriophages can sport host-range mutants. These host-range mutants are able to overcome the resistance of phage-resistant mutant bacteria because the structure of the attachment organs of the mutant phage differs in some subtle way from that of the wild-type phage (2682).

Alfred Day Hershey (US) reported the isolation of r (rapid lysis) and h (host-range) phage mutants. This along with Luria’s work demonstrated to existence of various mutant forms(2683).

Max Ludwig Henning Delbrück (DE-US) developed a technique permitting the assay of the relative proportion of h and h plus types in a single plating of a bacteriophage suspension. h is a mutant T2 phage that can infect and grow on cells normally resistant to the T2 phage. The wild-type T2 phage is h plus which is capable of infecting normal cells but not Tto resistant cells. Ref

Edward B. Lewis (US) designated that in genetics there are two different types of position effects, S-type (stable) and V-type (variegated)(2684).

Karl Habel (US) succeeded in growing the mumps virus in the chick embryo. He also demonstrated a good correlation between the skin reactions to virus grown in the chick allantoic sac and in the monkey parotid gland. Because of the greater availability of egg-grown virus, the wider use of this reaction then became possible(2685).

Marjorie Griffen Macfarlane (GB) and John D. MacLennan (GB) isolated a collagenase (kappa toxin) from Clostridium perfringens(2686).

Cyril Leslie Oakley (GB), G. Harriet Warrack (GB), William E. van Heyningen (GB), and Marion E. Warren (GB) discovered that Clostridium welchii produces a collagenase which they named the kappa toxin(2687, 2688).

Josef Fried (US) and Oscar Paul Wintersteiner (US) isolated the antibiotic streptothricin from Actinomyces lavendulae(2689).

Henry Mcllwain (GB) found that iodinin produced by Chromobacterium iodinum (Brevibacterium iodinum) is antimicrobial(2690).

Herman C. Lichstein (US) and Virginia F. van de Sand (US) isolated the antibiotic violacein from Chromobacterium violaceum(2691).

Balbina A. Johnson (US), Herbert Anker (US) and Frank L. Meleney (US) first described the antibiotic bacitracin which they isolated from Bacillus licheniformis. It was found to be to toxic for internal use(2692).

André Félix Boivin (FR), Albert Delauney (FR), Roger Vendrely (FR), and Yvonne Lehoult (FR) reported a transformation phenomenon in Escherichia coli which was very similar to Oswald Theodore Avery’s 1944 transformation in pneumococcus(2693, 2694).

Barbara McClintock (US) determined that the chromosomes of Neurospora and their behavior in the ascus are typically eukaryotic. She outlined the details of meiosis and described the seven chromosomes, noting that despite their small size they are individually recognizable by their distinctive morphology at pachytene. Pachytene pairing in a translocation heterozygote with the ascus types resulting from different modes of segregation when the translocation was heterozygous were described(2695).  

Donald Frederick Poulson (US) studied embryonic development in Drosophila melanogaster by using deficiencies involving the entire X chromosome or reasonably large portions thereof. The results of one such deficiency, known as Notch-8, were detailed. “The most striking feature of such eggs is that they contain very little or no endoderm or mesoderm... the process of germ layer formation has been interfered with seriously... The ectoderm proliferates especially along the ventral mid-line and produces what appears to be a semblance of the early nervous system”(2696).

Donald Frederick Poulson (US) clearly demonstrated that the closely coordinated yet separate developmental steps involved in Drosophila embryogenesis are under the control of specific genes(2697).

Christopher Q. Doe (US) and Corey S. Goodman (US) studying the neural ectoderm of grasshoppers, suggested a mechanism that we now know as lateral inhibition. Using laser microbeams to ablate one or more ectodermal cells in a group, they found that neuroblasts are specified by cell interactions. Initially, each undifferentiated cell within a sheet of neural ectodermal cells has an equal chance of becoming a neuroblast, but only one cell within a group takes on this role. Interactions between the cells of a group allow this one cell to enlarge into the neuroblast, which somehow prevents its neighboring cells from taking on the same identity; these cells instead become support cells or die(2698).

Kristi A. Wharton (US), Kristen M. Johansen (US), Tian Xu (US) and Spyros Artavanis-Tsakonas (US) presented the primary structure of the major embryonic Notch transcript which shows homology to the epidermal growth factor (EGF) and other proteins containing EGF-like repeats. Hydropathy plots suggest that the putative Notch protein may span the membrane. They relate these findings to the developmental action of Notch and speculate that the locus may be involved in a cell-cell interaction mechanism that is essential for the differentiation of the ectoderm into neural and epidermal precursors(2699).

Philippe l'Héritier (FR) and Georges Teissier (FR) reported the symptoms exhibited by Drosophila when infected with sigma virus(2700).

Mikhail Petrovich Chumakov (RU), in 1944, was the first to identify and establish the viral etiology of the disease the Soviets called Crimean Hemorrhagic Fever. He passed the virus through human volunteers but was unable to isolate it(2701).

David I. H. Simpson (IE), E.M. Knight (), Ghislaine Courtois (BE), Miles C. Williams (GB), M. Paul Weinbren (ZA), and John W. Kibukamusoke (AU) isolated and named Congo virus from several Congolese and Ugandan patients exhibiting a severe febrile illness(2702). The virus was eventually named Crimean-Congo hemorrhagic fever virus (CCHF); a member of the genus Nairovirus, family Bunyaviridae.

Jordi Casals (ES-US) found the Crimean virus indistinguishable from Congo virus, which was isolated in 1956 from a febrile child in Stanleyville (now Kisangani, Democratic Republic of the Congo), leading to the current designation, CCHF virus(2703). CCHF produces high mortalities, up to 60%, and has been found in over 30 countries.

Kenneth Bryan Raper (US) and Charles Thom (US) wrote their monograph, Manual of the Aspergilli(1964).

Georgiana B. Deevey (US) and Edward Smith Deevey, Jr. (US) wrote a paper on the hematology of the black widow spider. This paper was the first to use life table analysis in the study of an arachnid(2704).

Colin Munro MacLeod (US), Richard G. Hodges (US), Michael Heidelberger (US), and William G. Bernhard (US) conceived, produced, and field tested a type-specific pneumococcal vaccine(2705).

Charles H. Rammelkamp, Jr. (US), with the Commission on Acute Respiratory Diseases and the New York State Department of Health, helped determine the relationship between epidemics of acute bacterial pneumonia and influenza(2706). This is the basis for the influenza surveillance by the Centers for Disease Control which follows pneumonia prevalence as a surrogate for influenza.

Jeanette H. Levens (US)  and John Franklin Enders (US) developed a hemagglutination test to titer the mumps virus(2707).

They also showed that influenza A virus can be assayed by hemagglutination.

Robert Royston Amos Coombs (GB), Arthur Ernest Mourant (GB), and Robert Russell Race (GB) found that erythrocytes which had been sensitized with incomplete anti-Rh antibodies and then washed free of unbound human globulin could be agglutinated by an anti-human globulin serum prepared by immunizing a rabbit with human gamma globulin or whole human serum(2708, 2709). Erythrocytes sensitized by nonagglutinating incomplete anti-Rh antibodies will agglutinate when mixed with anti-globulin antibodies, i.e., the Direct Coombs Test. Suspected cases of erythroblastosis fetalis may be tested in this manner.

Ray David Owen (US) was the first to apply the term tolerance to an immunological phenomenon. He used it to describe results in his studies on binovular twin cattle sharing a common placenta (freemartin cattle). Owen noted that “erythrocyte precursors from each twin fetus had become established in the other and had conferred on their new host a tolerance towards … foreign cells that lasted a lifetime.” These twins of different sex were in fact red-cell chimeras or genetic mosaics(2710, 2711).

Sir Michael Francis Addison Woodruff (GB) and Bernard Lennox (GB) confirmed the freemartin concept in man when they found a pair of twins, one male the other female, who shared elements of different red cell types. Postulating a shared placental circulation between the two, they cross skin grafted them successfully(2712).

Sheila Callender (GB), Robert Russell Race (GB), and Zafer V. Paykoc (GB) discovered the lutheran blood group antigen in humans(2713).

Robert Franklin Pitts (US) and Robert S. Alexander (US) showed that the hydrogen ion secreted by the renal tubules is responsible for acidifying the urine of mammals(2714).

Robert Franklin Pitts (US), William D. Lotspeich (US), Martha Barrett (US), and Ilse Langer (US) defined the properties of renal bicarbonate transport by examining the relationship between bicarbonate reabsorption and excretion at varying plasma bicarbonate levels. A renal threshold for bicarbonate excretion was defined at 24mM. They established the kidney’s ability to generate significant transepithelial carbon dioxide gradients, which were explained by a lack of effective carbonic anhydrase activity in the lumen of distal nephron segments. They noted a relationship between bicarbonate transport and excretion of acid, based on the observation that during acidosis the excretion of titratable acid varied inversely with the amount of bicarbonate administered(2715).

George H. Chambers (US), Eleanor V. Melville (US), Ruth S. Hare (US), and Kendrick Hare (US) found that in conscious dogs the secretion of the antidiuretic hormone (vasopressin) depends on the osmotic pressure of the blood plasma(2716).

George Washington Corner (US), Carl G. Hartman (US), and George W. Bartelmez (US) described the development, organization, and breakdown of the corpus luteum in the rhesus monkey (Macacus rhesus)(2717).

George Gaylord Simpson (US) placed all apes in one family, the Pongidae and all members of the genus Homo, extinct and extant, in a separate family, the Hominidae(2718).

Gordon R. Baldock (GB) and William Grey Walter (GB-US) developed automated spectral analysis of EEG traces. A standard method for EEG analysis since its discovery has been to measure the power in various frequency bands, including alpha and delta, also beta (15-30 Hz), and theta (3-7 Hz). Walter used his skills in analog electronics to build a device that displayed the frequency content in an EEG trace, even as the trace was displayed with an ink-writing oscillograph, a pen whose fluctuations left a trace on moving paper that became the mainstay of electroencephalographers(2593, 2594).

Anthonie Van Harreveld (US) produced experimental evidence that after removal of part of the innervation of a muscle, the remaining motor units grow by adopting muscle fibers which originally belonged to the dennervated motor units(2719).

H. Hoffman (GB) provided histopathological evidence of local reinnervation in partially dennervated muscle(2720).

Clinton Nathan Woolsey (US), John L. Hampson (US), and C.R. Harrison (US) mapped the somatic sensory projections to the cerebellar cortex and the organization of projections from the cerebral cortex to the cerebellar cortex in the cat and dog(2721, 2722).

Stanley E. Bradley (US), Franz J. Ingelfinger (US), Geraldine P. Bradley (US), and John J. Curry (US) developed a method for measuring hepatic blood flow(2723).

Derek Ernst Denny-Brown (NZ-GB-US)  and Daniel Sciarra (US) described nervous system changes associated with porphyria(2724).

Cecil James Watson (US), Samuel Schwartz (US), Violet Hawkinson (US), Moisés Grinstein (US), and Robert A. Aldrich (US) revealed that in most cases of porphyria the excreted porphyrins are derived from the liver, suggesting a defect in heme synthesis within this organ(2725, 2726).

Cecil James Watson (US), Rudi Schmid (US), Samuel Schwartz (US), Robert A. Aldrich (US), Violet Hawkinson (US), and Moisés Grinstein (US) noted the exception, a rare condition resulting from a defect in hemoglobin synthesis in maturing normoblasts of the bone marrow(2727-2729).

Cecil James Watson (US), Victor Perman (US), Francis A. Spurrell (US), Harvey H. Hoyt (US), and Samuel Schwartz (US) named the rare condition congenital erythropoietic porphyria(2730).

Alfred Blalock (US), Helen Brooke Taussig (US), and Vivien Theodore Thomas (US) perfected what became known as the blue baby operation (Blalock-Taussig shunt)—subclavian artery attached to the pulmonary artery— to correct a defect of the large artery that supplies blood to the lungs. This defect allows so little blood to be pumped through the narrow passage that the oxygen intake is painfully curtailed. Blalock performed the operation on a human for the first time in 1946. Prior to this Vivien Theodore Thomas had performed this operation many times on dogs. Dr. Blalock, in collaboration with Dr. Taussig, developed procedures for the correction of a number of congenital heart lesions or anomalies of the great vessels of the heart, leading to morbus ciruleus, among them patent ductus arteriosis, tetrology of Fallot (blue baby syndrome), tricuspic atresia, and coarctation of the aorta(2731, 2732).

Hunter H. Comly (US) reported on cyanosis in infants caused by nitrates in well-water(2733).

Carl F. Vilter (US), Tom D. Spies (US), and Muiv B. Koch (US) reported that cases of sprue (celiac disease or gluten-sensitive enteropathy) and nutritional macrocytic anemia respond to treatment with pteroylglutamic acid (PGA, vitamin M, folic acid, or folate)(2734).

Robert Edward Gross (US), in 1945, reported the first successful case of surgical relief for tracheal obstruction from a vascular ring(2735).

Sir Paul H. Leslie (GB) showed how one simple mathematical technique can be used to make all the important demographic projections and how this technique can be applied to basic life table data of the sort that a laboratory or field ecologist usually obtains(2736).

1946

“Adapt or perish, now as ever, is Nature’s inexorable imperative.” Herbert George Wells(2737).

“Essential to a great discoverer in any field of nature would seem an intuitive flair for raising the right question…to ask something which the time is not yet ripe to answer is of little avail.” Charles Scott Sherrington(2738). 

James Batcheller Sumner (US) for his discovery that enzymes can be crystallized and John Howard Northrop (US) and Wendell Meredith Stanley (US) for their preparation of enzymes and virus proteins in a pure form were awarded the Nobel Prize in Chemistry.

Hermann Joseph Muller, Jr. (US) was awarded the Nobel Prize in Physiology or Medicine for the discovery of the production of mutations by means of x-ray irradiation.

Edward Mills Purcell (US), Henry C. Torrey (US), Robert V. Pound (US), Felix Bloch (CH-US), William Webster Hansen (US), and Martin Packard (US) found that when certain nuclei were placed in a magnetic field they absorbed energy in the radiofrequency range of the electromagnetic spectrum, and re-emitted this energy when the nuclei transferred to their original state. This is nuclear magnetic resonant absorption (NMR)(2739-2742).

Richard R. Ernst (CH) and Hans Primas (CH) designed and built advanced electronic equipment for improved nuclear magnetic resonance (NMR) spectrometers. In parallel, they developed the theoretical background for the optimum performance of the instruments(2743).

Albert Claude (BE-US) developed differential centrifugation for isolating and purifying cell parts. He and others would use this technique to separate ribosomes, mitochondria, lysosomes, peroxisomes, and the Golgi complex into distinct fractions. This paper contains the first full explanation of the fractionation of mammalian cells by differential centrifugation(2744).

George Hall Hogeboom (US), Walter Carl Schneider (US), and George Emil Palade (RO-US) significantly improved this methodology by carrying out the centrifugation in a concentrated solution of sucrose. This technique was considered to have made the method of isolating mitochondria complete(2745).

Erwin Brand (US) proposed that the first three letters in the name of an amino acid be used as an abbreviation for that acid, there being a few exceptions(2746).

George Hall Hogeboom (US), Albert Claude (BE-US), and Rollin Douglas Hotchkiss (US) showed that the site of intracellular respiration is the mitochondrion(2747).

George Emil Palade (RO-US) produced the first electron photomicrographs of mitochondria which revealed their cristae and outer membrane. He postulated that their structure was related to the function of such enzymes as succinic acid dehydrogenase and cytochrome c oxidase. These photomicrographs revealed that the enzymes of respiration reside within the inner membrane of the mitochondrion(2668).

Kenneth Bailey (GB) discovered tropomyosin(2748).

Setsuro Ebashi (JP), Fumiko Ebashi (JP), Ayako Kodama (JP), Makato Endo (JP), Iwao Ohtsuki (JP) and Takeyuki Wakabayashi (JP) isolated troponin (native tropomyosin) and found that when skeletal muscle is stimulated by depolarization of the muscle membrane the level of calcium ions in the muscle increases and this increases the amount of calcium ions bound to troponin. The sensitivity of calcium ion binding to calcium ion concentration, together with the observation that at low calcium ion levels the actin-myosin interaction is inhibited but that this inhibition is reversed at higher calcium ion levels, clearly indicated that regulation of actin-myosin activity must relate to the binding of calcium ions by troponin(2749-2754).

Setsuro Ebashi (JP), Ayako Kodama (JP), Makato Endo (JP), Iwao Ohtsuki (JP), Marion L. Greaser (US), John Gergely (US), James A. Spudich (GB-US), Hugh Esmor Huxley (GB-US), and John T. Finch (GB) proposed a mechanism to explain how the interaction of calcium with troponin and tropomyosin modulates the interaction of actin and myosin during skeletal muscle contraction(2755-2758).

Setsuro Ebashi (JP) and Makoto Endo (JP) used biochemical data to estimate the relative numbers of actin, tropomyosin, and troponin molecules in the F-actin filament(2752).

Philip Pacy Cohen (US) and Mika Hayano (US) were the first to successfully set up a cell-free system for urea synthesis(2759).

Lindsay H. Briggs (NZ), Harry T. Openshaw (GB), and Sir Robert Robinson (GB) determined the structure of strychnine(2760, 2761).

Cornelis Bokhoven (DE), Jean Chaques Schoone (DE), and Johannes Martin Bijvoet (DE) used crystallographic techniques to solve the structure of strychnine(2762).

Jörgen Lehmann (SE) discovered the anti-tubercular agent para-aminosalicylic acid (PAS)(2763). This drug when used along with streptomycin—discovered by Waksman—provided the first effective treatment of tuberculosis.

Harry Most (US), Irving M. London (US), Charles A. Kane (US), Paul H. Lavietes (US), Edmund F. Schroeder (US), and Joseph M. Hayman, Jr. (US) successfully used chloroquine for treatment of acute attacks of vivax malaria(2764).

Otto A. Bessey (US), Oliver H. Lowry (US), and Mary Jane Brock (US) described a method for determining alkaline phosphatase in blood serum(2765)(Bessey, Lowry et al. 1946).

Alma Joslyn Whiffen (US), J. Nestor Bohonos (US), and Robert L. Emerson (US) isolated the antifungal/antiprotozoal/antimammalian antibiotic cycloheximide (actidione) from Streptomyces griseus(2766). Cycloheximide blocks the translocation reaction on ribosomes.

John C. Sonne (US), John Machlin Buchanan (US), and Adelaide M. Delluva (US) determined that during the in vivo synthesis of inosinic acid (a purine) carbon dioxide is the precursor of carbon atom 6; formate, of carbon atoms 2 and 8; and the carboxyl carbon of glycine, of carbon atom 4(2767-2770).

Jon L. Karlsson (IS), Horace Albert Barker (US), David Shemin (US), and David Rittenberg (US) determined that carbon atom 5 and nitrogen atom 7 of inosinic acid are derived from the alpha carbon and nitrogen of glycine(2771, 2772).

John C. Sonne (US), I. Lin (US), and John Machlin Buchanan (US), demonstrated that two nitrogen atoms are derived from the amide nitrogen of glutamine and that aspartic acid (or glutamic acid) contributes one nitrogen to the synthesis of the purine ring(2773, 2774). 

Bruce Levenberg (US), Standish C. Hartman (US), and John Machlin Buchanan (US) demonstrated that within purines nitrogen 1 is derived from aspartic acid nitrogen and nitrogen atoms 3 and 9 from the amide nitrogen of glutamine(2775). 

Robert Allan Phillips (US), A. Yeomans (US), Vincent P. Dole (US), Lee E. Farr (US), Donald Dexter Van Slyke (US), and David Hogan (US) developed a simple method, based on specific gravity, for determining erythrocyte concentration in whole blood and protein concentration in blood plasma(2776).

Solomon Spiegelman (US) and Martin D. Kamen (US) suggested that copies of the information encoded within DNA are transmitted into the cell’s cytoplasm for protein synthesis(2777, 2778). This had great significance for future research into messenger RNA.

Maclyn McCarty (US) isolated, purified, and described for the first time the existence and properties of bovine pancreatic deoxyribonuclease(2779).

Johann Salnikow (US), Ta-Hsiu Liao (US), Stanford Moore (US), and William Howard Stein (US) isolated, then determined the composition and amino acid sequences of the tryptic and chymotryptic peptides of bovine pancreatic deoxyribonuclease A(2780, 2781).

Carroll Milton Williams (US) began a series of experiments with the silkworm, Hyalophra (Platysamia) cecropia which led to discoveries that at low temperatures the pupal brain becomes competent to secrete hormone. At high temperatures, which typically follow low temperatures in the seasons, specialized cells in the competent brain secrete a hormone which reacts with the prothoracic glands causing them to secrete a growth and differentiation hormone. This growth and differentiation hormone reacts with the pupal tissues to terminate diapause thus leading to development of an adult. 

He also found that a brain hormone produced by larvae early in the spinning process promotes the secretion of the prothoracic gland growth and differentiation hormone which promotes pupation(2782-2790). 

Philip Rodney White (US) was the first to attempt the production of a defined medium for the culturing of eukaryotic cells. The cells survived but did not multiply(2791, 2792).

Max Rubin (US) and Herbert R. Bird (US) discovered that an acid precipitate of a water extract of dried cow manure stimulates the growth of chicks. This would later be known as vitamin B12(2793-2795).

Georgii Frantsevitch Gause (RU) isolated the antibiotic litmocidin from Proactinomyces cyaneus antibioticus(2796).

Selman Abraham Waksman (RU-US), Albert Schatz (US), and H. Christine Reilly (US) isolated the antibiotic grisein from Streptomyces griseus(2797, 2798).

Herman C. Lichstein (US) and Virginia F. van de Sand (US) isolated the antibiotic prodigiosin from Serratia mercescens(2799).

Karl Sune Detlof Bergström (SE), Axel Hugo Theodor Theorell (SE), and Hans Davide (SE) isolated the antibiotic pyolipic acid from Pseudomonas aeruginosa(2800).

Georgii Frantsevitch Gause (RU) isolated the antibiotic colistatin from a yellow, aerobic, sporulating bacillus(2801).

Gaston Ramon (FR) and Rémy Richou (FR) isolated the antibiotic subtiline from Bacillus subtilis(2802).

Louis de Saint-Rat (FR) and Henri R. Olivier (FR) isolated the antibiotic endosubtilysin from Bacillus subtilis(2803).

Jackson W. Foster (US) and Harold Boyd Woodruff (US) isolated the antibiotic bacillin from Bacillus subtilis(2804).

Edwin A. Johnson (US) and Kenneth L. Burdon (US) isolated the antibiotic eumycin from Bacillus subtilis (Marburg strain)(2805).

Robert K. Callow (GB) and Philip Montagu d’Arcy Hart (GB) isolated the antibiotic licheniform from Bacillus licheniformis Weigmann emend. Gibson. It is especially effective against species of myxobacteria(2806).

Edgar S. McFadden (US) and Ernest Robert Sears (US) discovered that the amphiploid between Triticum turgidum (wheat) and Aegilops squarrosa (goat-grass) is phenotypically very close to Triticum spelta (wheat). This confirmed earlier inference from hybrids involving Aegilops cylindrica (goat-grass) that the seven pairs of chromosomes (genome) in hexaploid but absent in tetraploid wheat had been derived from Aegilops squarrosa (goat-grass)(2807).

Carl Lamanna (US), Henning W. Eklund (US), Olive E. McElroy (US), Adolph Abrams (US), Gerson Kegeles (US), and George A. Hottle (US) crystallized the exotoxin of Clostridium botulinum Type A and characterized it as a protein of the globulin type(2808, 2809).

Carl Lamanna (US) and Harold N. Glassman (US) isolated type B botulinus toxin in amorphous form(2810). 

Jean Louis Auguste Brachet (BE) hypothesized that proteins are synthesized on ribonucleoprotein granules within the cytoplasm(1857).

Linus Carl Pauling (US) proposed that enzymes may work by causing their substrate to assume the configuration of a transition form(2811). 

André Gratia (BE) and Pierre Frédéricq (BE) discovered colicine, a killer substance, produced by some strains of Escherichia coli(2812, 2813).

Pierre Frédéricq (BE) and M. Betz-Bareau (BE) showed that colicines behave as genetic factors independent of the chromosome(2814-2816).

James P. Duguid (GB) suggested that penicillin acts by interfering with the formation of a normal bacterial cell wall(2817).

Joshua Lederberg (US) used penicillin to induce the formation of bacterial protoplasts(2818).

Ian M. Dawson (GB) presented electron photomicrographs illustrating the physical appearance of the cell wall of Staphylococcus aureus(2819).

Milton R.J. Salton (US) and Robert W. Horne (GB) isolated and purified bacterial cell walls for chemical analysis and characterization(2820, 2821).

Milton R.J. Salton (US) demonstrated that the substrate for the lysis of Micrococcus lysodeikticus by lysozyme is the cell wall(2822).

Claes Weibull (US) observed that cells of Bacillus megaterium are transformed into wall-less, fragile, protoplasts when treated with lysozyme(2823).

Jean-Marie Ghuysen (BE) recounted how the molecular structure of bacterial cell walls was elucidated through a series of experiments utilizing various bacteriolytic enzymes which attack specific molecular structures(2818).

Mary Lynne Perille Collins (US) and Milton R.J. Salton (US) were among the first to utilize detergents to solubilize bacterial membrane proteins(2824).

Joshua Lederberg (US) and Edward Lawrie Tatum (US) demonstrated sexual recombination in Escherichia coli strain K-12. This recombination behavior strongly suggested that bacteria, like higher organisms, contain genes. Up to this point in time no bacterium of any sort had been shown to have genes. Lederberg was to name this phenomenon conjugation(2825-2828).

Max Ludwig Henning Delbrück (DE-US), Alfred Day Hershey (US), Raquel Rotman (US), and William T. Bailey, Jr. (US) presented evidence suggesting that when bacteria are simultaneously infected by two different varieties of bacteriophage the burst of daughter phage shows characteristics derived from both parents, as though phage genes have recombined inside the host bacterium. This represents the discovery of genetic recombination in bacteriophage and the birth of phage genetics(2683, 2829, 2830).

Kenneth M. Smith (GB) reported that two distinct viruses, tobacco vein-distorting and tobacco mottle, when co-infecting tobacco (Nicotiana tabacum) plants, caused the tobacco rosette disease. This is considered the discovery of the first luteovirus-associated aphid-transmitted virus complex(2831, 2832).

Kenneth C. Smithburn (US), Alexander John Haddow (GB), and Alexander Francis Mahaffy (CA) isolated the Bunyamwera (BUN) virus from Aedes mosquitoes in 1943 at the Enteebe East Africa Research Institute in Uganda. It would become the type virus for the Bunyaviridae family(2833). 

Jacques Lucien Monod (FR) and Alice Audureau (FR) demonstrated that Escherichia coli mutabile possesses the genetic information to produce the enzymes which allow utilization of lactose, whether lactose is present or not(2834).

Edward Lawrie Tatum (US) was the first to intentionally produce mutations in bacteria. He exposed Acetobacter and Escherichia coli to x-rays(2835).

Carl Clarence Lindegren (US) and Gertrude Lindegren (US) discovered that haplophase cultures of Sacharomyces cerevisiae contain two mating types which they designated a and alpha(2836).

Marcus Morton Rhoades (US) discovered the nuclear gene, iojap, a mutator gene which affects plastids. This is one of the first known cases of nuclear-cytoplasmic interaction. These alterations are heritable via the cytoplasm(2837).

Harold H. McKinney (US) was the first to report that oat mosaic disease has a viral etiology(2838).

A. Orlando (BR) and Karl Martin Silberschmidt (BR) demonstrated that the whitefly, Bemisis tabaci, serves as a vector for abutilon mosaic virus(2839).

Louis Pillemer (US), Ruth Wittler (US), and Donald B. Grossberg (US) crystallized the toxin of Clostridium tetani and characterized it as a protein(2840).

M.T. Dyar (US) and Erling J. Ordal (US) found that bacteria die rapidly when the negative charge on their surface is neutralized by the positive charge on a quaternary ammonium compound. This suggests a relationship between surface charge and disinfecting power(2841).

Ernest Aubrey Ball (US) excised Nasturtium and Tropaeolum shoot tips and grew them in a test tube. He excised the shoot tips with scalpels made of razor blade corners spot welded onto sewing needles which could be inserted into wooden holders. He also regenerated plantations of lupin (Lupinus) by culturing their shoot tips with leaf primordia(2842, 2843).

George Henry Hepting (US) and Elmer R. Roth (US) discovered the pitch canker disease of southern pines and identified the specific causal fungi(2844).

George Henry Hepting (US) found that pines inoculated with pitch canker fungus produced oleoresin flow with desirable results(2845).

Otto Rahn (DE-US) showed that the germicidal efficiency of quaternary ammonium compounds (quats) is diminished by agents which adsorb them. Examples are, filter paper, charcoal, bentonite, and agar. He further showed that fatty surfaces cause quats to orient themselves in a specific direction as they are adsorbed. The hydrophobic end of the molecule is directed toward the fatty material while the germicidal N—OH group faces the aqueous phase (2846).

Emery I. Valko (US) demonstrated that proteins combine with quaternary ammonium compounds, frequently producing a precipitate(2847).

Robert A. Quisno (US) and Milton J. Foter (US) reported that an increase in temperature increases the germicidal efficiency of quaternary ammonium compounds, the temperature coefficient between 20°C and 37°C, being less than 2. They also reported that somewhat larger doses are required to kill gram-negative enterobacteria than streptococci and staphylococci, but rarely more than double the amount. A striking exception is Pseudomonas aeruginosa for which ten to twenty times as much is needed as for staphylococci. Mycobacterium spp. are even more resistant(2848).

Sir Frank Macfarlane Burnet (AU), and Joyce D. Stone (AU) reported on how Vibrio cholerae damages the epithelial lining of the gastrointestinal tract(2849, 2850).

James Craigie (CA) discovered that typhoid bacilli can be grouped according to sensitivity to certain phages(2851).

Robert Joseph Huebner (US), Charles Pomerantz (US), William L. Jellison (US), and Peggy Stamps (US) isolated and named the etiological agent of rickettsialpox, Rickettsia akari, then determined the cycle of infection as mouse-mite-mouse, with man an occasional host(2852-2854).

Sydney Arthur Asdell (US) authored Patterns of Mammalian Reproduction in which he collected data bearing on reproductive behavior of wild as well as domestic mammals(2855).

William Barry Wood, Jr. (US), Mary Ruth Smith (US), and Barbara Watson (US) studied the lungs of animals infected with encapsulated pneumococci early in the course of the disease, before antibody was produced. They discovered surface phagocytosis. On smooth surfaces the phagocytes were unable to engulf bacteria, whereas on rough surfaces they were often able to wedge the slippery bacteria into a corner where they could be phagocytized(2856, 2857).

Richard Edwin Shope (US) developed a vaccine to rinderpest which was grown and attenuated in hen’s eggs(2858). 

Robert Royston Amos Coombs (GB), Arthur Ernest Mourant (GB), and Robert Russell Race (GB) discovered the Kell blood group antigen in man(2859).

Arthur Ernest Mourant (GB) discovered the Lewis blood group antigen in man. It is named for a Mrs. Lewis in which anti-Le was made(2860).

Eric A. Beet (GB), working in Northern Rhodesia, now Zimbabwe, suggested that sickle cell trait is caused by a mutant recessive gene, inherited in a Mendelian pattern (2861-2864).

James van Gundia Neel (US) proved that from the incidence of sickle cell disease and the trait in American Negro families that it is caused by a mutant recessive gene, inherited in a Mendelian pattern(2865).

Anthony Clifford Allison (GB-KE) performed an epidemiological study from which he concluded that the sickle cell trait protects carriers against malarial infection(2866). This balance of advantage and disadvantage helped to explain why the sickle cell allele had been preserved in certain communities rather than being eliminated by natural selection.

Charles C. Macklin (CA) determined that there is no difference at all between positive and negative pressure inflation of the lung, as long as one is careful to reference airway and vascular pressures to the pleural pressure(2867).

Solbert Permutt (US), Jack B.L. Howell (GB), Donald F. Proctor (US), and Richard L. Riley (US) rediscovered Macklin’s findings(2868). In their companion paper they found that the pulmonary vascular bed can be functionally separated into two parts—alveolar and extra-alveolar vessels— that have opposite responses to lung inflation(2869).

Kathleen Ethel Boorman (GB), Barbara Edith Dodd (GB), and John Freeman Loutit (GB) demonstrated the presence of autoantibodies on the erythrocytes of patients with acquired hemolytic anemia and the absence of rbc-bound antibodies in patients with congenital hemolytic anemia(2870). This test to detect antibodies that had sensitized rbcs in vivo became known as the direct antiglobulin test (DAT). A positive DAT is generally caused by the attachment of immunoglobulin (IgG, IgM, IgA) and / or components of complement (C3d, C3, C4 etc.) to the red cell surface.

Dwight Joyce Ingle (US) showed that characteristic damaging effects of stress are produced when adrenal steroids are supplied to adrenalectomized animals at a constant but not excessive rate of administration. He deduced that the role of the adrenal cortex in the stressed state appears to be a subtle “permissive” or supporting role rather than as the primary mediator of the stress reaction(2871).

Clinton Nathan Woolsey (US), Samuel A. Talbot (US), and J.M. Thompson (US) mapped the primary visual area of the rabbit cortex, demonstrated the detailed retinotopic organization, and mapped a second visual area(2872, 2873).

Wallace Osgood Fenn (US), Hermann Rahn (DE-US), Arthur B. Otis (US), and Leigh E. Chadwick (US) developed the pressure-volume diagram of the lung and thorax. Hermann Rahn (DE-US) and William Osgood Fenn (US) wrote, A Graphical Analysis of the Respiratory Gas Exchange: The O2-CO2 Diagram in which they were able to represent all variables of the alveolar gas ventilation equations in diagrammatic form. With the O2-CO2 diagram they could represent all possible compositions of alveolar gas and the arterial blood under any specified set of conditions. Although F. Rohrer (?) preceded them on the pressure-volume diagram they conceived it independently, elaborated it further, and distilled into it some ten years of work and thought. It defined the limiting values for muscle forces and the corresponding volumes of gas and blood(2874-2877). This work laid the foundation for respiratory mechanics.

Richard L. Riley (US) and André Frédéric Cournand (US) developed a three-compartment model of pulmonary gas exchange. This model was the standard for assessing ventilation-perfusion inequality in patients with lung disease until the introduction of the multiple inert gas elimination technique(2878, 2879).

Peter D. Wagner (US), Herbert A. Saltzman (US), and John B. West (US) introduced the multiple inert gas elimination technique which allowed VA/Q distributions to be described(2880).

John B. West (US) applied computer analysis to the solution of VA/Q distributions(2881).

Charlotte Auerbach (GB), John Michael Robson (GB), and John Gardner (GB) determined that nitrogen mustard gas, the chemical warfare agent, produces a high mutation rate in the fruit fly, Drosophila(2882-2884).

Gunnar Biörck (SE) and Clarence Crafoord (SE), in 1946, repaired an arteriovenous aneurysm on the pulmonary artery simulating patent ductus arteriosus botalli(2885).

Cecil James Watson (US) and Frederick William Hoffbauer (US) described cholangiolithic cirrhosis. Today it is known as primary biliary cirrhosis(2886).

Paul D. Keller (US) described a clinical syndrome following exposure to atomic bomb explosions(2887).

William E. Adams (US), in 1946, performed a lobectomy for carcinoma of the lung on Thomas Mann who authored the tuberculosis saga The Magic Mountain(2888).

Errol Ivor White (GB) discovered a fossil of Jamoytius kerwoodi in deposits of Silurian rock in Scotland. It is probably the most primitive chordate known and may throw some light on the early ancestry of vertebrates(2889).

1947

Sir Robert Robinson (GB) was awarded the Nobel Prize in Chemistry for investigations on plant products of biological importance, especially the alkaloids.

Carl Ferdinand Cori (CZ-US) and Gerty Theresa Cori, née Radnitz (CZ-US), for their discovery of the course of the catalytic conversion of glycogen, and Bernardo Alberto Houssay (AR), for his discovery of the part played by the hormone of the anterior pituitary lobe in the metabolism of sugar, shared the Nobel Prize in physiology and medicine.

Immanuel von Broser (DE) and Hartmut Kallman (DE) discovered that certain organic compounds (scintillators) fluoresce when exposed to ionizing radiation. Each fluorescence event is proportional to a radioactive decay event, and the frequency of these events is directly proportional to the number of 14C atoms present in the sample(2890). This discovery led to the development of liquid scintillation counters.

Norbert Weiner (US) conceived and developed a new kind of mathematics that he called cybernetics (negative feedback control). It was originally intended for the purpose of designing aiming devices for anti-aircraft guns and then later for guided missiles(2891). This concept quickly found acceptance in explaining the control of various biological phenomena. G. Evelyn Hutchinson (US) applied Weiner's cybernetics to Tansley's ecosystem leading to our modern concept of the ecosystem. Endocrinologists gradually realized that the language of feedback control provided an effective way of describing and thinking about endocrine interactions. Biochemists found that many metabolic pathways are controlled by feedback mechanisms.

Henry J. Buehler (US), Edward J. Schantz (US), and Carl Lamanna (US) determined the complete amino acid analysis of crystalline botulinus toxin, type A(2892).

Maurice M. Rapport (US), Arda Alden Green (US), and Irvine Heinly Page (US) isolated the vasoconstrictor, serotonin, from serum(2893, 2894).

Betty M. Twarog (US), Irvine Heinly Page (US) A.H. Amin (GB), T.B.B. Crawford (GB), and Sir John Henry Gaddum (GB) assigned roles in the central nervous system to serotonin (5-hydroxytryptamine)(2895, 2896).

A. Michael Michelson (GB), Sir James Baddiley (GB), and Lord Alexander Robertus Todd (GB) prepared ribonucleoside-5’-phosphates (AMP, ADP and ATP)(2897-2900).

A. Michael Michelson (GB), Lord Alexander Robertus Todd (GB), R.H. Hall (GB), and R.F. Webb (GB) were the first to successfully synthesize a oligonucleotides as found in DNA—thymidine dinucleotide—thus confirming DNA’s chemical structure(2900, 2901).

A. Michael Michelson (GB) and Lord Alexander Robertus Todd (GB) discovered that RNA like DNA has a highly regular backbone of 5’-3’ phosphodiester linkages between nucleotides. ref

Herbert E. Carter (US), William J. Haines (US), W.E. Ledyard (US) and William P. Norris (US) proposed the term sphingolipid as a convenient designation for lipids containing sphingosine (cerebrosides, sphingomyelin, gangliosides…)(2902).

Ronald Scarisbrick (GB) and Robert Hill (GB) discovered cytochrome f(2903, 2904).

Donald J. Hanahan (US) and Israel Lyon Chaikoff (CA-US) suggested that plant tissues contain an enzyme—later called phospholipase D—which produces phosphatidic acid from various phospholipids(2905).

Sam G. Wildman (US) and James Bonner (US) isolated fraction I protein from spinach leaves(2906).

Robert W. Dorner (US), Albert Kahn (US), and Sam G. Wildman (US) would declare this fraction I protein to be the enzyme ribulose-1,5-biphosphate carboxylase-oxygenase (Rubisco), arguably the world’s most abundant and important single species of soluble protein(2907). See, Weissbach, 1956.

Melvin Calvin (US), Andrew Alm Benson (US), and associates provided an important clue to the nature of the pathway from CO2 to hexose in photosynthetic organisms. They illuminated green algae in the presence of radioactive carbon dioxide (14CO2) for very short intervals (only a few seconds) and then quickly killed the cells, extracted them, and with the aid of chromatographic methods searched for those metabolites in which the labeled carbon was incorporated earliest. Melvin Calvin (US) and Andrew Alm Benson (US) determined that one of the compounds that became labeled very early in photosynthesis is 3-phosphoglyceric acid, a known intermediate of glycolysis; the carbon isotope was found predominantly in the carboxyl carbon atom. This carbon atom, which corresponds to the carboxyl carbon atom of pyruvate, is not labeled rapidly in animal tissues incubated with radioactive CO2(2908-2911).

Melvin Calvin (US) and Peter Massini (US) were the first to postulate that the carboxylation of a molecule of ribulose-1,5-diphosphate (RuDP) produces two molecules of 3-phosphoglyceric acid (PGA)(2912).

Alexander T. Wilson (NZ) and Melvin Calvin (US) gathered evidence that indeed ribulose 1,5-biphosphate is the first substance to react with carbon dioxide in the dark reactions of photosynthesis(2913, 2914).

James Al Bassham (US), Andrew Alm Benson (US), Lori D. Kay (US), Anne Z. Harris (US), Alexander T. Wilson (NZ), Martha R. Kirk (US), Melvin Calvin (US), Kazuo Shibata (JP), Kjell Steenberg (NO), and Jean Bourbon (?) proposed, then supported, the concept that the fixation of carbon dioxide is part of a carbon reduction cycle occurring during photosynthesis (now called the Calvin-Benson or C3 cycle)(2915-2918).

Arthur Weissbach (US), Pauline Z. Smyrniotis (US), and Bernard Leonard Horecker (US) were able to show that with crude extracts from spinach leaves ribose 5-phosphate was a unique substrate for the formation of phosphoglyceric acid, and they purified a kinase from spinach leaves that they used to prepare the barium salt of ribulose 1,5-bisphosphate (RUDP)(2919).

Bernard Leonard Horecker (US), Arthur Weissbach (US), Pauline Z. Smyrniotis (US) and Jerard Hurwitz (US) isolated spinach phosphoribulokinase, performed the enzymatic synthesis of ribulose 1,5-diphosphate, and the enzymatic formation of phosphoglyceric acid from ribulose diphosphate and carbon dioxide(2920-2922). The Weissbach article in 1956 represents the first purification of the enzyme ribulose-1,5-biphosphate carboxylase-oxygenase (Rubisco), arguably the world’s most abundant and important single species of soluble protein. 

William B. Jakoby (US), Dewey O. Brummond (US), and Severo Ochoa (ES-US) showed that 3-phosphoglyceric acid forms as the result of carbon dioxide fixation in spinach leaves(2923).

William A. Laing (NZ), William L. Ogren (US), and Richard H. Hageman (US) derived enzyme kinetic equations for a dual substrate enzyme and meticulously showed that the kinetic properties of the isolated Rubisco enzyme could explain the effects of both oxygen and temperature on photosynthesis and photorespiration(2924).

Chris R. Somerville (US), Archie R. Portis, Jr. (US), and William L. Ogren (US) while screening Arabidopsis thaliana for photorespiratory mutants discovered Rubisco activase which releases RuBP and other tight binding inhibitors from Rubisco sites(2925). 

R. Weismann (CH) reported the H. Speich of Geigy Chemicals observed insect (housefly) resistance to dichloro-diphenyl-trichloro-ethane (DDT) or 2,2-di(4-chlorophenyl)-1,1,1-trichloroethane in northern Sweden—a mere five years after it was first used there(2926).

Daniel Bovet (CH-FR-IT), France Depierre (FR), and Yvonne de Lestrange (FR) while searching for a synthetic substitute for curare (a muscle relaxant), discovered gallamine (Flaxedil) and other muscle relaxants(2927).

Pierre Huguenard (FR) and A. Boue (FR) were the first to use gallamine in clinical trials(2928).

Emily W. Emmart (US) isolated the antibiotic nocardine from Nocardia coeliaca(2929).

Robert G. Benedict (US), Asgar F. Langlykke (US), Philip G. Stansly (US), Robert G. Shepherd (US), Harry James White (US), Geoffrey Clough Ainsworth (GB), Annie M. Brown (GB), and George G. Brownlee (GB) isolated the family of antibiotics called polymyxins (aerosporin in England) from Bacillus polymyxa(2930-2932). Renal damage is a serious side effect of their administration to humans.

John Ehrlich (US), Quentin R. Bartz (US), Robert M. Smith (US), Dwight A. Joslyn (US), and Paul Rufus Burkholder (US) isolated the antibiotic chloromycetin (Chloramphenicol) from the actinomycete Streptomyces venezuelae, recovered from soil obtained near Caracas, Venezuela(2933, 2934). Chloramphenicol blocks the peptidyl transferase reaction on ribosomes of prokaryotes only. To this point in time chemists were convinced that nature could neither chlorinate nor nitrate its products. Chloramphenicol proved them wrong on both counts.

Otto Fritz Meyerhof (DE-US) and Peter Oesper (US) provided further proof that during glycolysis a diphosphoglyceric aldehyde intermediate does not exist. They also altered the equation for this step of glycolysis to reflect the fact that the reduction of cozymase is accompanied by the formation of an H+ ion(2935).

Theodor Bücher (DE) isolated and crystallized phosphoglycerate kinase (PGK) then demonstrated that it catalyzes the reversible reaction: d-1,3-diphosphoglyceric acid + adenosinediphosphate ↖ d-3-phosphoglyceric acid + adenosinetriphosphate(2936). Phosphoglycerate kinase or phosphoglycerokinase (PGK) is a metabolic enzyme functioning in the Embden–Meyerhof-Parnas pathway.

A.P. Kraus (US), M.F. Langston, Jr. (US), and B.L. Lynch (US) reported that PGK-1 deficiency is associated with hemolytic anemia(2937). 

Shi-Han Chen (US), L.A. Malcolm (PG), Akira Yoshida (US), Eloise R. Giblett (US), John L. VandeBerg (US), Desmond W. Cooper (US), and P.J. Close (US) noted two functional loci for the production of PGK in the mammalian genome. PGK-1 is an X-linked gene expressed constitutively in all somatic cells and premeitotic germ cells. PGK-2 is an autosomal gene expressed in a tissue-specific manner exclusively in the late stages of spermatogenesis(2938, 2939).  

Edgar Stedman (GB), and Ellen Stedman (GB) hypothesized that histones, basic proteins of cell nuclei, may act as regulators of gene activity and exhibit a cell specificity(2940, 2941).

James Frederick Bonner (US), Ru-Chih Huang (US), and Nirmala Maheshwari (US) discovered the synthesis of RNA from DNA in plants. They found that RNA transcription is inhibited by histones(2942, 2943).

Ru-chih C. Huang (US) and James Frederick Bonner (US) reported that histones influence the ability of DNA to function as primer for RNA synthesis in vitro(2944).

James Frederick Bonner (US), Ru-chih C. Huang (US), and Ray Guilden (US) provided experimental evidence that the inhibition of RNA synthesis by histones is specific(2945). This was experimental confirmation of the hypothesis by Stedman & Stedman in 1947. 

Derek Michael Phillips Phillips (GB) discovered that the amino-terminal tails of the four histones (H2A, H2B, H3, and H4) are post-transcriptionally modified by the addition of an acetyl group to the epsilon amino group of specific lysine side chains(2946).

Vincent George Allfrey (US), Robert D. Faulkner (US), and Alfred Ezra Mirsky (US) suggested that such a seemingly minor modification to histones could be involved in the control of gene expression via its “effect on the capacity of the histones to inhibit ribonucleic acid synthesis”(2947).

Giorgio Vidali (US), Lidia C. Boffa (US), Vincent George Allfrey (US), Edwin Morton Bradbury (US), and Gloria Lorick Pleger (US), Josephine Bowen Keevert (US), Carol A. Johmann (US), and Martin A. Gorovsky (US) demonstrated a positive correlation between addition of acetyl groups to core histones and transcriptional activity(2948, 2949).

James E. Brownell (US), Jianxin Zhou (US), Tamara Ranalli (US), Ryuji Kobayashi (US), Diane G. Edmondson (US), Sharon Y. Roth (US), C. David Allis (US), Jack Taunton (US), Christian A. Hassig (US), and Stuart L. Schreiber (US) showed that histone acetylases and deacetylases are, in fact, transcriptional regulators. These studies provided the first clear connection between histone acetylation and transcriptional regulation(2950-2952).

Stephen Rea (AT), Frank Elsenhaber (AT), Donal O'Carroll (AT), Brian D. Strahl (US), Zu-Wen Sun (US), Manfred Schmid (AT), Susanne Opravil (AT), Karl Mechtler (AT), Chris P. Ponting (GB), C. David Allis (US), and Thomas Jenuwein (AT) provided a functional link between histone methylation and chromatin structure(2953).

John Masson Gulland (GB) reported that undegraded calf thymus DNA contains large polynucleotide chains held together by hydrogen bonds(2954).

André Félix Boivin (FR) and Roger Vendrely (FR) were the first to express, in print, that DNA makes RNA makes protein(2955).

Michael Doudoroff (RU-US), Horace Albert Barker (US), and William Zev Hassid (RU-GB-US) studied the action of bacterial sucrose phosphorylase in what represents an outstanding early example of the use of radioisotopes for the study of enzyme mechanisms (2956).

Theodor Bücher (DE) discovered that during glycolysis when glyceraldehyde-3-phosphate is oxidized the immediate product is 1,3-diphosphoglycerate, which donates its phosphoryl group to ADP in the presence of 3-phosphoglycerate kinase(2936).

Milislav L. Demerec (HR-US) explained how bacteria can mutate to resist higher and higher concentrations of an antibiotic. Resistance to penicillin is a step-wise phenomenon due to mutants at three different genes being selected as the concentration of antibiotic rises. The probability of all three mutations appearing in the same cell are 10-7 X 10-7 X 10-7 =10-21. Mutation to various levels of streptomycin resistance occurs even at low levels of the antibiotic.

These discoveries taught lessons for the clinical application of antibiotics such as penicillin and streptomycin. If a patient afflicted with a bacterial infection is to be treated with penicillin, the physician must employ the highest possible concentration of the drug at the very outset; for in that way the chance that all the pathogenic bacteria are killed is maximized, and the chance that high-level resistant mutants are selected is minimized. The avoidance of stepwise mutants is less important in streptomycin treatment, since mutants with high resistance to that drug are selected even in the presence of low concentrations, and little can be done to avoid their appearance. The surest way to avoid the appearance of drug-resistant strains is to administer simultaneously two or more kinds of antibiotics, since the chance that a multiple-resistant mutant will appear is given by the product of the individual mutation rates(2957).

H. Christine Reilly (US), Dale A. Harris (US), and Selman Abraham Waksman (RU-US) discovered a virus (actinophage) which parasitizes some streptomycetes(2958).

Gernot Bergold (DE) demonstrated that many-sided crystalline polyhedra, characteristic of many insect virus diseases called polyhedroses, consist of virus particles(2959).

John Franklin Enders (US) succeeded in transmitting primary atypical pneumonia to human volunteers by means of filtered secretions from the respiratory tract. This strongly suggested a viral etiology for this disease(2960).

Joshua Lederberg (US) established the Lac locus in Escherichia coli(2827).

Edgar G. Anderson (US) and William Lacy Brown (US) published landmark monographs on the two ancestral maize types (Southern Dents and Northern Flints) that, when hybridized, gave rise to the North American race (Corn Belt Dent). Corn Belt Dent is the genetic foundation for all hybrid maize of the temperate zones(2961-2963).

Lemuel Roscoe Cleveland (US) gave accounts of how molting in Cryptocercus (a wood cockroach) affected the sexual cycles of its intestinal flagellates(2964, 2965).

Frederick E. J. Fry (CA) developed a model for the way fish respond to their physical and chemical environment. He divided all environmental effects on fish into five classes, controlling, limiting, lethal, masking and directive, increasing understanding of how environmental factors interact to affect performance of individual fish and their populations at any given time(2966).

Min Chueh Chang (CN-US) disproved the need for large amounts of hyaluronidase at the site of fertilization and the claim that phosphorylated hesperidin, a hyaluronidase inhibitor, had man antifertility action when given orally(2967, 2968).

Frederick O. MacCallum (GB), using human volunteers, differentiated hepatitis A, which is spread by contaminated food and water, from hepatitis B, which is spread by blood(2969).

Robert John Walsh (GB) and Carmel M. Montgomery (GB) discovered the Ss blood group antigen(2970).

Paul A. Owren (NO) discovered the activated form of factor V (Va) of the blood clotting mechanism(2971, 2972). This factor has also been called proaccelerin.

Paul A. Owren (NO) described a hemorrhagic disease in a young woman lacking a plasma protein that was called proaccelerin. This disease is referred to as parahemophilia (factor V deficiency)(2973).

Thomas Francis, Jr. (US) discovered a non-antibody serum factor which prevents the agglutination of erythrocytes by myxoviruses. It is referred to as the Francis’ inhibitor (equivalent to alpha-inhibitor)(2974).

C.M. Chu (GB) observed a similar factor, now called Chu’s inhibitor (equivalent to beta-inhibitor)(2975).

H. Shimojo (JP), A. Sugiura (JP), J. Akao (JP), and C. Enomoto (JP) discovered gamma inhibitor which is also a non-antibody serum factor capable of preventing the agglutination of erythrocytes by myxoviruses, specifically the A2 strain of influenza virus(2976).

Hurley L. Motley (US), Andre Cournand (US), Lars Werko (US), Aaron Himmelstein (US), and David Dresdale (US) found that short periods of induced anoxia (breathing 10% oxygen) in man rapidly induced pulmonary hypertension in subjects with normal blood pressure. Cardiac output was decreased slightly during anoxia, with a marked decrease in stroke volume. Pulmonary vascular resistance was almost doubled(2977).

Robert B. Howard (US) and Cecil James Watson (US) discovered that patients with evolving cirrhosis of the liver often have an antecedent transient episode of jaundice(2978).

Aaron Bunsen Lerner (US) and Cecil James Watson (US) discovered cryoglobulins in the sera of some patients with purpura(2979).

Isaac Berenblum (IL) and Philippe Shubik (GB) discovered that cancer caused by chemicals involves two distinct steps, initiation and promotion. The first step, initiation, was theorized to be a rapid mutational effect on the cellular DNA. The second step, promotion, was believed to be caused by a promoting agent, which altered cellular metabolism, growth, and transport(2980, 2981).

Robert James. Morton (US), Malcolm McCallum Hargraves (US), and Helen Robinson (US) discovered a mature neutrophilic polymorphonuclear leucocyte containing the phagocytosed nucleus of another cell and recognized it as a diagnostic aid in acute disseminated lupus erythematosus(2982, 2983). The L.E. (lupus erythematosus) cell discovery was the first clear sign that systemic lupus erythematosus could be an autoimmune disease, i.e., Hargraves’ cells.

Thomas Holmes Sellers (GB), in 1947, performed the first successful pulmonary valvulotomy. A systemic pulmonary artery shunt was planned on the left side, but the attempt was abandoned in this patient with severe tetralogy of Fallot and advanced bilateral pulmonary tuberculosis. The pericardium was opened. Dr. Sellers could feel the stenotic valve each time it pushed through the pulmonary trunk during ventricular systole. Sellers used a tenotomy knife, which he passed through the right ventricle to perform the valvulotomy. The patient made a good recovery and was markedly improved(2984).

Jean-Pierre Soulier (FR) and Jean Gueguen (FR) discovered the anticoagulant phenylidane-dione and the first successful preparation of a therapeutic fraction from blood to treat factor IX and prothrombin complex deficiencies(2985).

Sir Ludwig Guttman (DE-GB) established clean intermittent self-catheterization(2986-2988).

Derek Ernest Denny-Brown (NZ-GB-US), E. Harry Botterell (CA), Thomas E. Twitchell (US), Luis Saenz-Arroyo (MX), John S. Meyer (US), Simon Horenstein (US), Betty Q. Banker (US), Geoffrey Rushworth (GB), Sid Gilman (US), Joseph P. Van Der Meulen (US), Nobuo Yanagisawa (JP), and Edwin J. Kirk (US) between 1947 and 1972, conducted central nervous system (CNS) lesion experiments on about 450 monkeys and made films of the animals post-operatively. The result of this effort is 67,000 m (220,000 ft) of film depicting monkeys with lesions in virtually every major CNS structure(2989-3006).

Alexander Brunschwig (US), in 1946, performed a total pelvic exenteration (surgical removal of the pelvic organs and nearby structures) on a patient with recurrent carcinoma of the cervix(3007, 3008).

Gerhardt von Bonin (US) and Percival Bailey (US) were the first to define with precision the cytoarchitecture of the human brain cortex(3009, 3010).

Jens Christian Clausen (DK-US), David D. Keck (US), and William M. Heisey (US) used variation in the sticky cinquefoil (Potentilla glandulosa) and the yarrow (Achillea lanulosa) to perform the first documented experimental analysis of genetic differentiation in adjacent populations. During these experiments they introduced transplant experiments as an appropriate technique for distinguishing genetic from environmental effects(3011, 3012). These experiments clarified for certain species and under certain condition the question of heredity versus environment. 

Edward Smith Deevey, Jr. (US) introduced the concept of the life table to ecology(3013).

Reginald Claude Sprigg (AU) discovered Precambrian metazoan fossils in the Pound Quartzite at Ediacara Hills and in the Flinders Ranges of South Australia(3014, 3015). This represents the dawn of visible life forms.

Edwin H. Colbert (US), curator of the American Museum of Natural History, found a massive quarry of Coelophysis dinosaurs in New Mexico and concluded from their skeletons that these Triassic dinosaurs were swift runners with a bird-like posture(3016, 3017).

Alexander S. Watt (GB) related mosaic conditions of plant community growth to dynamic cyclic processes in the environment(3018).

The journal Biochimica et Biophysica Acta was founded.

ca. 1948

Julius Hyman (US-GB) discovered that cyclopentadiene reacts with acetylene to give bicyclo[2.2.1]hepta-2,5-diene (norbornadiene) as a stable product. It was then reacted with hexachlorocyclopentadiene (hex) to yield aldrin(2420).

1948

“The surgeon who is his own physician, though he often has a fool for a colleague, has the happiness of working in an atmosphere of mutual confidence and admiration.” Sir William Heneage Ogilvie(3019).

Arne Wilhelm Kaurin Tiselius (SE) was awarded the Nobel Prize in Chemistry for his research on electrophoresis and adsorption analysis, especially for his discoveries concerning the complex nature of the serum proteins.

Paul Hermann Müller (CH) was awarded the Nobel Prize in Physiology or Medicine for his discovery that dichloro-diphenyl-trichloroethane (DDT), also called 2,2-di(4-chlorophenyl)-1,1,1-trichloroethane, is a potent insecticide.

Lyman T. Aldrich (US) and Alfred Otto Carl Nier (US) provided absolute confirmation that 40Ar is the decay product of 40K when they measured significantly increased 40Ar/36Ar ratios on argon extracted from potassium-rich minerals relative to the atmospheric 40Ar/36Ar ratio(3020). This set the stage for the rapid development of the K-Ar dating method. This dating technique is most useful between 10,000 and 3 billion years.

Bernard Leonard Horecker (US) and Arthur J. Kornberg (US) determined the precise extinction coefficients of both reduced diphosphopyridine nucleotide (DPNH) (cozymase I) and reduced triphosphopyridine nucleotide (TPNH) (reduced coenzyme II) at 340 nanometers. The values proved to be identical(3021). This work made possible quantitative spectrophotometric measurements in reactions involving the pyridine nucleotides and became one of the most frequently cited papers in biochemical literature. Note: DPN became NAD and TPN became NADP.

Dorothy Mary Crowfoot-Hodgkin (GB) and Jack D. Dunitz (CH) determined the structure of calciferol (vitamin D)(3022).

Gui-Dong Zhu (US) and William H. Okamura (US) synthesized vitamin D(3023).

Bernard B. Brodie (US) and Julius Axelrod (US) investigated the fate of acetanilide in the human body and concluded that it exerts its analgesic actions through N-acetyl-p-aminophenol (now known as acetaminophen)(3024). In the early 1970s Johnson & Johnson marketed N-acetyl-p-aminophenol as Tylenol.

Daniel C. Pease (US) and Richard Freligh Baker (US) reliably prepared thin sections (0.1 to 0.2 micrometers thick) of biological material(3025-3027).

Linus Carl Pauling (US) proposed the principle of transition-state stabilization to explain enzyme catalysis(3028).

Stanford Moore (US) and William Howard Stein (US) introduced partition chromatography on starch gel columns(3029). This technique was quickly modified by the use of an ion-exchange resin (sulfonated cross-linked polystyrene), in 1951, and an automatic recording assembly to detect chemicals (amino acids) as they emerged from the column(3030, 3031). This apparatus for the first time allowed the complete amino acid analysis of protein hydrolysates.

Elvin Abraham Kabat (US) and Manfred Martin Mayer (DE-US) wrote Experimental Immunochemistry, the first great text in immunochemistry(3032). They revised it in 1961 to include, among other things, Mayer’s discoveries concerning the complement cascade.

Harry G. Albaum (US), and Milton Kletzkin (US) established conclusively the presence in Drosophila melanogaster adults of an ATP with the same physical, chemical, and physiological properties as vertebrate ATP(3033).

Moses Kunitz (RU-US) described the isolation of deoxyribonuclease in crystalline form from beef pancreas(3034).

Morris Friedkin (US) and Albert Lester Lehninger (US) provided experimental proof that electron transport from NADH to oxygen is the direct source of the energy used for the coupled phosphorylation of ADP. Pure NADH was incubated aerobically with water-treated mitochondria, phosphate, and ADP in the absence of tricarboxylic acid cycle intermediates or any other added organic metabolite. (The hypotonic water treatment was necessary to make the mitochondria permeable to NADH.) The NADH was rapidly oxidized to NAD+ at the expense of molecular oxygen; simultaneously, up to three molecules of ATP were formed from ADP and phosphate. Such experiments indicated that at three points in the chain of electron carriers leading from NADH to oxygen, oxidation-reduction energy is transformed into phosphate-bond energy(3035, 3036).

Benjamin Minge Duggar (US) discovered and introduced aureomycin (chlortetracycline), the first of the tetracycline antibiotics. It is produced by Streptomyces aureofaciens(3037). The tetracyclines block binding of aminoacyl-tRNA to the A-site of the ribosome in prokaryotes only.

Allan L. Grafflin (US), Dina E. Green (US), W. Eugene Knox (US), B. N. Noyce (US), and Victor H. Auerbach (US) discovered that the process of beta oxidation of fatty acids is localized in mitochondria(3038, 3039).

Peter Wilhelm Joseph Holtz (DE) and Hans-Joachim Schümann (DE) were the first to report the production of norepinephrine (noradrenaline) in the adrenal medulla(3040).

Seymour Stanley Cohen (US) found that the nucleic acid of T2 phage is exclusively of the DNA type and that within 7-10 minutes following its infection of an Escherichia coli cell the metabolic activity of the host cell is directed to production of virus DNA in large amounts. He also found that the phosphorus contained within the newly synthesized viral DNA is largely derived from inorganic phosphorus in the culture medium(3041-3043).

Edward B. Lewis (US) studied position pseudoallelism in Drosophila(3044-3047).

William Smith Tillet (US), Sol Sherry (US), and L. Royal Christensen (US) discovered that some strains of hemolytic streptococci produce a streptococcal deoxyribonuclease which they named streptodornase(3048, 3049).

Jacques Lucien Monod (FR), Madeleine Jolit (FR), and Anne-Marie Torriani (FR) isolated lactase (beta-galactosidase) and amylomaltase from Escherichia coli strain ML(3050).

Alexander A. Krasnovsky (RU) discovered that in the presence of appropriate chemical reagents, chlorophyll a in solution can be reversibly reduced in light(3051).

Stanford Moore (US), William Howard Stein (US), Christophe Henri Werner Hirs (US), Christian Boehmer Anfinsen (US), Robert R. Redfield (US), Darrel H. Spackman (US), Derek G. Smyth (US), Warren L. Choate (US), Juanita Page (US), William R. Carroll (US), John Thomas Potts, Jr. (US), Arieh Berger (US), and Juanita Cooke (US) determined the primary structure for ribonuclease. This was the first enzyme to have its primary structure solved(3052-3064).

Gopinath Kartha (US), Jake Bello (US), and David Harker (US) determined the tertiary structure of ribonuclease(3065).

Harold W. Wyckoff (US), Karl D. Hardman (US), Norma M. Allewell (US), Tadashi Inagami (US), Louise N. Johnson (GB), Frederic Middlebrook Richards (US), William D. Carlson (US), Byungkook Lee (US), and Yukio Mitsui (JP) determined the tertiary structure of ribonuclease-S at 3.5 angstrom resolution(3066, 3067).

Philip Pacy Cohen (US) and Santiago Grisolia (CL) demonstrated the fixation of carbon into the carbonyl group of citrulline and into urea and concluded that citrulline is an obligate intermediate in the urea synthesis cycle(3068).

Philip Pacy Cohen (US) and Santiago Grisolia (CL) concluded that in the synthesis of citrulline from ornithine, carbamyl-L-glutamic acid is an intermediate(3069, 3070).

E.S. Guzman Barron (US) and Theodore N. Tahmisian (US) provided sufficient evidence to establish that the Krebs cycle is present in the tissues of insects(3071).

Paul Bruce Beeson (US) discovered a factor released from polymorphoneuclear leucocytes into the blood which behaves as an endogenous mediator of fever. It would later be known as interleukin-1(3072).

Koloman Laki (HU-US) and Laszlo Lorand (HU-US) partially purified the plasma protein that became known as the Laki-Lorand factor or fibrin-stabilizing factor, and presently as factor XIII(3073).

Renne Chen (US) and Russell F. Doolittle (US) found that the stabilization of fibrin clots by activated factor XIII involves two different sets of cross-linked chains(3074).

Ethel Bidwell (GB) and William E. van Heyningen (GB) determined that the kappa exotoxin of Clostridium perfringens is a collagenase(3075).

Walter C. Schneider (US) developed a method for separating the various subcellular fractions by homogenizing tissues in isotonic sucrose and subjecting the homogenate to differential centrifugation(3076).

J. Walter Wilson (US) and Elizabeth H. Leduc (US) discovered the occurrence and formation of binucleate and multinucleate cells and polyploid nuclei in the mouse liver(3077).

Frank John Fenner (AU) studied the pathogenesis of ectromelia virus in mice (in which it causes fatal hepatitis)(3078, 3079). This work became a classic and has served as a model for such studies ever since. 

Gilbert Julias Dalldorf (US) and Grace M. Sickles (US) were the first to isolate the Coxsackie virus (named for Coxsackie, New York). It came from stools of two children exhibiting signs resembling poliomyelitis and was grown in newborn mice(3080).

Robert Joseph Huebner (US), Roger M. Cole (US), Edward A. Beeman (US), Joseph A. Bell (US), and James H. Peers (US) showed that Coxsackie virus type A is the etiological agent of herpangina(3081).

Carl F.T. Mattern (US) and Herman G. DuBuy (US) crystallized the Coxsackie virus(3082).

Roy Markham (GB), Richard Ellis Ford Matthews (NZ), and Kenneth M. Smith (GB) purified and characterized an isometric plant virus, Turnip yellow mosaic virus. They showed that its infectivity depends on the presence of viral RNA, thus concluding that nucleic acid is essential for virus multiplication. For the first time RNA was shown to be capable of genetic behavior independent of DNA(3083).

Heinz Ludwig Fraenkel-Conrat (DE-US) and Robley Cook Williams (US) conducted a classic group of experiments which demonstrated that tobacco mosaic virus can be reconstituted in the test tube from its isolated protein and RNA components. On simple remixing, infectious virus particles are formed that are structurally indistinguishable from the original virus. Therefore all information necessary for constructing the virus is inherent in its parts, which self-assemble spontaneously in solution(3084-3086).

Alfred Gierer (DE) and Gerhard Schramm (DE) independently reached the same conclusion(3087).

Thomas Huckle Weller (US), and John Franklin Enders (US) grew the mumps virus in cell culture consisting of fragments of chick amniotic membrane nourished with a balanced salt solution and ox serum ultrafiltrate. They succeeded, where others had failed, by incorporating the recently available penicillin into their cultures(3088).

Bernard David Davis (US), Joshua Lederberg (US), and Norton David Zinder (US) developed methodology for direct selection of bacterial auxotrophs(3089-3091).

Ludmila Andreevna Kuprianova (RU) illuminated the pollen morphology of the monocotyledons(3092). 

Harry Alfred Borthwick (US), Sterling Brown Hendricks (US), and Marion Wesley Parker (US) found that the action spectrum for floral induction in winter barley, a long-day plant, is very similar to that for the prevention of floral induction in soybean and cocklebur. In all three plants the active portion of the spectrum lies between 600 and 660 nm. The spectral sensitivity and energy requirements for stem elongation are very similar suggesting that the formation of flowers and stem elongation are linked to and dependent upon one another. They speculated that a particular light absorbing pigment is common to these processes(3093). Sterling Brown Hendricks constructed an absorption curve for C-phycocyanin and found it to be remarkably similar to the action spectra for floral initiation and leaf growth(3094).

Harry Alfred Borthwick (US), Sterling Brown Hendricks (US), Marion Wesley Parker (US), Eben Henry Toole (US), and Vivian Kearns Toole (US) showed that the photoreceptor is very likely a photoreversible pigment in which absorption of red light (R) converts it into a form which absorbs far red light (FR) and visa versa. The wavelengths to which the seeds were last exposed, either R or FR, determine whether they were induced to germinate or inhibited(3095).

Peter Herman Heinze (US), Albert Aloysius Piringer (US) and Harry Alfred Borthwick (US) determined that the photoperiodic pigment controls skin coloring in tomatoes(3096, 3097).

Harry Alfred Borthwick (US), Sterling Brown Hendricks (US), Eben H. Toole (US), and Vivian Kearns Toole (US) discovered that the action spectra for promotion and inhibition of germination of Grand Rapids lettuce seeds seemed to be identical to the one that controlled flowering and stem and leaf growth. Maximum induction was at 660 nm with maximum inhibition at 710-750 nm(3098). According to Hendricks, “One could hardly believe such an astounding result, showing that the control by light of a phenomenon at the start and termination of plant growth—the germination of the seed and the eventual flowering of the plant—were the same not only in a qualitative sense but on an absolute basis as well”(3099).

Warren Lee Butler (US), Karl H. Norris (US), Harold William Siegelmann (US), and Sterling Brown Hendricks (US) worked out methods for detection, assay, and preliminary purification of the pigment controlling photoresponsive development of plants. They named the R-absorbing form of the pigment P655 and the FR-absorbing form P735(3100). Shortly thereafter the pigment was named phytochrome (Greek=plant color) with the R-absorbing form called Pr and the FR-absorbing form called Pfr(3101, 3102).

David Pressman (US) and Geoffrey Keighley (US) attempted to create radiolabeled antibodies(3103). 

David Pressman (US) and Leonhard Korngold (US) demonstrated that antibodies can be artificially complexed with a toxic material then act as a carrier of the toxin to a target cell. They showed that labeled antibodies against Wagner osteosarcoma were concentrated in vivo in these tumors(3104, 3105).

David Pressman (US), Eugene D. Day (US), and Monte Blau (US) introduced the paired labeling method in which both antibodies and a control preparation of IgG, each labeled with a different isotope, are injected simultaneously into the same tumor-bearing animal. The measurement of radioactivity from each isotope in a dual channel scintillation counter allows one to distinguish the specific localization of antibodies in a tumor from the nonspecific accumulation of normal IgG, which is known to occur in the inflammatory and necrotic regions of the tumor(3106).

George Davies Snell (US) studied tissue transplantation among inbred strains of mice and coined the term histocompatibility antigens to describe those gene products responsible for tissue compatibility. The genes that code for these antigens he called histocompatibility genes(3107).

Peter A. Gorer (GB), Stewart D. Lyman (GB), and George Davies Snell (US) discovered the major histocompatibility complex in mice; later named the H-2 locus(3108).

Katherine K. Sanford (US), Wilton R. Earle (US), and Gwendolyn D. Likely (US) grew single isolated animal cells in vitro, thus proving that it is possible for a single somatic animal cell to give rise to a clonal population. The cell was from the murine L cell line and almost certainly transformed. The cloned cell line was designated NCTC-929(3109).

Sir Peter Brian Medawar (GB) found that the brain performs quite poorly when challenged to set up a primary immune response to a locally introduced antigen, i.e., the brain is a immunologically privileged site(3110).

A. Stanley Holt (US) and Charles Stacy French (US) showed the isotopic composition of oxygen liberated by the Hill reaction from 18O-enriched water to follow that of water—thus proving that this reaction is a photochemical oxidation of water(3111).

William Wayne Kielley (US) and Otto Fritz Meyerhof (DE-US) were the first to isolate sarcoplasmic reticulum as particulate material. It was found to possess ATPase activity stimulated by magnesium ions and inhibited by calcium ions(3112).

William F. Loomis (US) and Fritz Albert Lipmann (DE-US) were the first to discover a chemical which will allow electron flow in oxidative phosphorylation but uncouple it from the phosphorylation of ADP to ATP. The uncoupling agent was 2,4 dinitrophenol(3113).

Alfred Ezra Mirsky (US), Hans Ris (CH-US), André Félix Boivin (FR), Roger Vendrely (FR), and Colette Vendrely (FR) reported that the amount of DNA per set of chromosomes is in general constant in different cell types of an organism. Moreover, the DNA content per chromosome set is a characteristic of each particular species and the DNA content of haploid and diploid nuclei is roughly in the ratio of 1:2(3114-3118).

Gerald C. Mueller (US) and James A. Miller (US) were the first to demonstrate the oxidative metabolism of a carcinogen, 4-dimethylaminoazobenzene (DAB), in a cell-free system containing rat liver microsomes/ribosomes(3119).

Julius Axelrod (US) discovered a new class of enzymes, later called cytochrome P450 dependent monooxygenases (CYPs), which exert a profound influence in many areas of research, including metabolism of drugs, metabolism of normally occurring compounds, and investigations of carcinogenesis(3120-3126).

Allan H. Conney (US), Elizabeth C. Miller (US), and James A. Miller (US) provided the first evidence that certain carcinogens, such as poly-cyclic aromatic hydrocarbons (PAHs), are capable of promoting their own metabolism through induction of microsomal proteins(3127).

Tsuneo Omura (JP) and Ryo Sato (JP), David Y. Cooper (US), Otto Rosenthal (US), and Ronald W. Estabrook (US) discovered cytochrome P450 and suggested that this hemoprotein functions in the oxidation of certain chemicals(3128, 3129). Note: Martin Klingenberg published a paper reporting the presence of a redox pigment in liver microsomes/ribosomes in 1958.

Anthony Y.H. Lu (US) and Minor J. Coon (US) determined that cytochrome P450 dependent monooxygenases (CYPs) are associated with an NADPH-dependent reductase(3130). The initial step during conversion of organic xenobiotics into hydrophilic and excretable derivatives is mainly catalysed by CYP enzymes. Nucleophilic or chemically inert compounds such as aromatic and heterocyclic amines, aminoazo dyes, PAHs, N -nitrosamines, halogenated olefins, and others represent the great majority of human carcinogens. As these chemicals do not react directly with cellular constituents—they require enzymatic conversion into their ultimate carcinogenic forms—they are termed procarcinogens.

Astrid Fagraeus (SE) demonstrated the maturation of lymphocytes into antibody-secreting plasma cells(3131).

R. Pohl (DE) was the first to demonstrate a circadian rhythm in a unicellular organism, Euglena gracilis. The recorded variables were photoaccumulation in a beam of light, cell motility, and cell division(3132).

Elmer R. Roth (US), E. Richard Toole (US), and George Henry Hepting (US) determined that littleleaf disease in Southern pines results from a progressive deficiency of nitrogen brought about by complex interaction among certain soil conditions, feeder-root pathogens, land use practices, and stand density(3133).

Ignace H. Vincke (BE) and Marcel Lips (BE) isolated the first known rodent malarial parasite, Plasmodium berghei. It was found in the blood of a thicket rat in Katanga (now Zaire) Africa(3134).

Sir William D. M. Paton (GB) and Eleanor J. Ziamis (GB) while developing muscle relaxants using anesthetized cats and rabbits discovered hexamethonium, the first effective drug for the treatment of high blood pressure. Although this ganglionic blocker is effective in reducing blood pressure in humans it has undesirable side effects because of its action on many different nerve reflexes(3135).

Raymond Perry Ahlquist (US) graded the reaction of a series of six sympathomimetic amines on vasoconstriction, the pupil, heart, gut and uterus. He found their action to be inhibitory or excitatory depending on the site of action. He concluded that the relative density and location of two types receptors (alpha and beta) determined opposing responses at different locations(3136). Ahlquist conceived the theory that there must be two types of receiving mechanisms, or sites, in the cardiovascular system—one type prevailing in the heart, and the other in the blood vessels. These receptors, which receive "messages" from the sympathetic nervous system, were classified and named by him, alpha and beta. Because they are receptors for adrenaline and adrenaline-like substances, they are known as "adrenergic" receptors. Ahlquist further postulated that the predominant adrenergic receptors in the heart are of the beta type, and affect its contraction, its rate and its rhythm. See James Whyte Black, 1962.

Henry Edward Shortt (GB), Percy Cyril Claude Garnham (GB), Sir Gordon Covell (GB), and Percy G. Shute (GB) discovered the primary tissue phase, the exoerythrocytic cycle, of the malarial parasite, Plasmodium vivax(3137-3139).

Henry Edward Shortt (GB), Sir Neil Hamilton Fairley (AU), Sir Gordon Covell (GB), Percy G. Shute (GB), and Percy Cyril Claude Garnham (GB) used liver biopsy material from a human volunteer to discover the primary tissue phase, the exoerythrocytic cycle, of the malarial parasite, Plasmodium falciparum(3140, 3141).

Percy Cyril Claude Garnham (GB), Robert Stow Bray (AU-GB), W. Cooper (GB), Ralph Lainson (GB-BR), F.I. Awad (), and John Williamson (GB) discovered the primary tissue phase, the exoerythrocytic cycle, of the malarial parasite, Plasmodium ovale(3142, 3143).

Charles A. Owen, Jr. (US) and Jesse L. Bollman (US) discovered factor VII of the blood clotting mechanism(3144).

Seymour Solomon Kety (US) and Carl F. Schmidt (US) reported that the brain, which comprises only 2% of the body weight of man, receives for its nutrition one-sixth of the heart’s output of blood and consumes one-fifth of the oxygen utilized by the body at rest(2467).

Sir Austin Bradford Hill (GB) suggested that a statistical method of randomization be used to determine which treatment group each patient should be placed into in the streptomycin trial. It is as a result of Hill's efforts that the streptomycin trial is often cited as the first randomized controlled trial (RCT) in medical history; and that 1948 is celebrated as marking the beginning of a new era in modern medicine. See, Johannes Andreas Grib Fibiger, 1898.

In Britain, during the inter-war period, the Medical Research Council (MRC) collaborated with drug licensing bodies to systematize a methodology for making fair and reliable judgments about the efficacy of therapeutic interventions. By 1950 this methodology had evolved into the randomized controlled trial (RCT). It involved comparing different therapeutic interventions by casting lots to determine which patients would be assigned to which treatment groups. The MRC's Streptomycin Trial Committee was chaired by Philip D'Arcy Hart with Marc Daniels as Vice-Chairman and Austin Bradford Hill the statistician on the Committee(3145, 3146).

F. Estrade (MG) was the first to successfully treat pneumonic plague (Yersinia pestis) patients. He used streptomycin(3147).

Joseph E. Smadel (US), Theodore E. Woodward (US), C. Russell Amies (US), Kenneth Goodner (US), Fred R. McCrumb, Jr. (US), S. Mercier (), Jean-Marie Robic (FR) and M. Bouillot () successfully treated bubonic and pneumonic plague (Yersinia pestis) patients with the antibiotics chloramphenicol and terramycin (oxytetracycline)(3148, 3149).

Sidney Farber (US), Louis Klein Diamond (US), Robert D. Mercer (US), Robert F. Sylvester (US), and James A. Wolff (US) described the temporary remission of acute leukaemia in children following treatment with aminopterin(3150).

Martin Schneider (US), Edgar J. Poth (US), and William C. Levin (US) found that nitrogen mustard hydrochloride (mechlorethamine) has an antineoplastic effect in Hodgkin lymphoma(3151).

Vincent T. DeVita, Jr. (US), Arthur A. Serpick (US), Paul P. Carbone (US), Robert C. Young (US), Bruce A. Chabner (US), Susan P. Hubbard (US), George P. Canellos (US), Brian J. Lewis (US), Dan L. Longo (US), Susan M. Hubbard (US), Margaret N. Wesley (US), Richard I. Fisher (US), Elaine S. Jaffe (US), and Costan Berard (US) made outstanding contributions to the concept of combination therapy in the treatment of Hodgkin’s lymphoma. They demonstrated that MOPP (mechlorethamine, Oncovin [vincristine], procarbazine, and prednisone) chemotherapy could cure advanced Hodgkin lymphoma.(3152-3155). This was a major milestone in the modern chemotherapy era as it was the first demonstration that a previously incurable advanced disease could be cured by combination chemotherapy and provided the rationale for the use of combination chemotherapy in medical oncology. This type of therapy became the standard drug regimen used to treat advanced Hodgkin’s disease.  

Isaac C. Michelson (GB) gave the first description of an angiogenic activity, regulated by oxygen, elaborated by the retina and mediating abnormal, retinopathic vessel growth(3156). Michelson's 'factor X' was eventually identified as vascular endothelial growth factor (VEGF) and confirmed to be the underlying causal factor of retinopathies.

Louis Klein Diamond (US) successfully used umbilical vein replacement transfusion to treat erythroblastosis fetalis(3157).

Eleanor de F. Baldwin (US), André Frédéric Cournand (FR-US), and Dickinson Woodruff Richards, Jr. (US) studied a large number and variety of cases of chronic pulmonary disease in man. The cases were found to fall into broad categories of pulmonary insufficiency: 1) the gross ventilatory, with restrictive or obstructive aspects, 2) the alveolar-capillary, with primary disturbances in respiratory gas exchange, 3) pulmonary emphysema, with various combinations of these factors, and 4) diffusional insufficiency or alveolar-capillary block, with the major interference at the alveolar-capillary interface(3158-3160).

Fred W. Stewart (US) and Norman Treves (US) reported a rare secondary malignancy in 6 cases of angiosarcoma in post-mastectomy lymphedema. They recognized that an edematous arm after radical mastectomy for breast cancer may suggest recurrent breast cancer, but that long-standing chronic edema without recurrent cancer may occasionally produce "a heretofore unrecognized and unreported sequel... long after the malignant breast neoplasm has apparently been arrested... a new specific tumor"(3161). The term Stewart-Treves syndrome is broadly applied to an angiosarcoma that arises in a chronically lymphedematous region due to any cause, including congenital lymphedema and other causes of secondary lymphedema unassociated with mastectomy. Lymphangiosarcoma is a misnomer because this malignancy seems to arise from blood vessels instead of lymphatic vessels. A more appropriate name is hemangiosarcoma.

Ward S. Fowler (US) measured physiological dead space in lungs by simultaneous and continuous measurement of volume flow and nitrogen content of gas expired following the change from breathing air to breathing 99.6% oxygen. The average volume of the physiological dead space in 45 healthy males at rest was 156 cc. The volume of physiological dead space is affected by; a) anatomical volume of the bronchial tree, and  b) gas diffusion between terminal bronchioles and alveolar spaces and variation in the rate of inspiratory volume flow(3162).

The National Heart Institute, in 1948, initiated a study begun in Framingham, Massachusetts, known as the Framingham Study. This investigation involved 1,980 men and 2,421 women aged 30 to 62 who showed no signs of heart disease. Every two years, the participants underwent a complete physical examination. The study showed that high blood pressure, smoking, and high cholesterol levels are major factors in heart disease. Fifty years’ worth of data collected from the residents of Framingham has produced over 1,000 scientific papers; introduced the concepts of biologic, environmental, and behavioral risk factors; identified major risk factors associated with heart disease, stroke, and other diseases; created a revolution in preventive medicine; and forever changed the ways in which the medical community and the general population view the genesis of disease.

William B. Kannel (US), Thomas R. Dawber (US), Abraham Kagan (US), Nicholas Revotskie (US), and Joseph Stokes, III (US) reported the first results from the Framingham study(3163).

Edward Franklin Bland (US) and Richard Harwood Sweet (US) performed the first pulmonary-azygos shunt operation for relief of mitral stenosis(3164).

Henry Hancock (GB) performed the first recorded successful operation for peritonitis due to abscess in the appendix(3165).

Harris B. Schumacker, Jr. (US) reported the excision of a small descending thoracic aortic aneurysm with reanastomosis of the aorta(3166).

Robert Edward Gross (US), in 1948, performed surgical closure of an aortopulmonary window in a 4-year-old girl who had dyspnea with slight exertion and a cardiac murmur that was consistent with a patent ductus(3167). The patient made a satisfactory recovery.

Frank W. Preston (US) laid the mathematical foundation for discussions of species abundance patterns(3168, 3169).

Louis Charles Birch (AU), using the rice weevil, Calandra oryzae, made the first comprehensive analysis of the demography of a population growing exponentially under carefully controlled conditions(3170).

James Davidson (AU) and Herbert George Andrewartha (AU) used the method of partial regression to measure the degree of association between the numbers of thrips, Thrips imarginis, present during the spring and the weather experienced during the preceding months. The analysis showed that 78 per cent of the variance of the population could be related to: 1) the sum of effective temperatures between the date when the break of the dry season in autumn allows the seeds of the annual food-plants to germinate and the end of winter (31st August), 2) the amount of rainfall during September-October, 3) the temperature during the autumn and winter of the preceding year(3171).

Thomas Park (GB) deliberately chose two closely related species, Tribolium confusum Duval and Tribolium castaneum Herbst, for his long-term study of interspecies competition. In three different experiments Park found that one of the two species always became extinct. Park’s experimental results supported the tenet that two nearly identical species cannot coexist on a single limiting resource(3172).

The World Health Organization (WHO) was founded.

1949

“The curiosity remains, though, to grasp more clearly how the same matter, which in physics and in chemistry displays orderly and reproducible and relatively simple properties, arranges itself in the most astounding fashions as soon as it is drawn into the orbit of the living organism. The closer one looks at these performances of matter in living organisms the more impressive the show becomes. The meanest living cell becomes a magic puzzle box full of elaborate and changing molecules, and far outstrips all chemical laboratories of man in the skill of organic synthesis performed with ease, expedition, and good judgment of balance. The complex accomplishment of any one living cell is part and parcel of the first-mentioned feature, that any one cell represents more an historical than a physical event. These complex things do not rise every day by spontaneous generation from non living matter—if they did, they would really be reproducible and timeless phenomena, comparable to the crystallization of a solution, and would belong to the subject matter of physics proper. No, any living cell carries with it the experiences of a billion years of experimentation by its ancestors. You cannot expect to explain so wise an old bird in a few simple words.” Max Ludwig Henning Delbrück (3173).

“It is impossible to exaggerate the importance of the variability of the bacterial cell or the desirability of studying the laws regulating it. Biochemically, bacterial cells are the most plastic of living material … The bacterial cell by reason of its small size and consequently relatively large surface, cannot develop by maintaining a constant chemical environment, but reacts by adapting its enzyme systems so as to survive and grow in changing conditions. It is immensely tolerant of experimental meddling and offers material for the study of processes of growth, variation and development of enzymes without parallel in any other biological material.” Marjory Stephenson(3174).

" A recognized fact which goes back to the earliest times is that every living organism is not the sum of a multitude of unitary processes, but is, by virtue of interrelationships and of higher and lower levels of control, an unbroken unity." Walter Rudolf Hess(3175).

Walter Rudolf Hess (CH) for his discovery of the functional organization of the interbrain as a coordinator of the activities of the internal organs and Antonio Caetano de Abreu Freire Egas Moniz (PT) for his discovery of the therapeutic value of lobotomy in certain psychoses shared the Nobel prize for physiology and medicine.

Willard Frank Libby (US), Ernie C. Anderson (US), and James R. Arnold (US) developed the carbon-14 dating technique(3176, 3177). Carbon-14 has a half-life of 5730 years and is especially useful for dating objects from the last 40,000 years.

This is one of the most profound discoveries of the 20th century. J. Desmond Clark (GB) wrote that were it not for radiocarbon dating, "we would still be foundering in a sea of imprecisions sometime bred of inspired guesswork but more often of imaginative speculation"(3178).

Albert Kelner (US), working with Escherichia coli and conidia of Streptomyces griseus, discovered that light belonging to the visible range is capable of reactivating biological material that has been rendered inactive by ultraviolet radiation (UV)(3179-3184). This phenomenon is commonly referred to as photoreactivation. Note: Alexander Hollaender (US) and John T. Curtis (US) made the earliest known suggestion that there is likely to exist a natural DNA repair mechanism(3185).

Renato Dulbecco (IT-US) discovered the same phenomenon in bacteriophages associated with their host cell(3186, 3187).

Claud Stan Rupert (US), Solomon H. Goodgal (US) and Roger M. Harriott (US) confirmed that photoreactivation really is a DNA repair process catalyzed by a specific enzyme with a strict requirement for visible light(3188).

Claud Stan Rupert (US) discovered an enzyme from baker’s yeast capable of catalyzing photoreactivation of bacterial cells which had been inactivated by ultraviolet light(3189).

Rob Beukers (NL), J. Ijlstra (NL), W. Berends (NL), Adolf Wacker (DE), Hanswerner Dellweg (DE), Diether Jacherts (DE) and Dieter Weinblum (DE) determined that ultraviolet light produces dimers of thymine, thymine-cytosine, and cytosine in deoxyribonucleic acid(3190-3197).

Richard Burton Setlow (US), William L. Carrier (US), Richard P. Boyce (US) and Paul Howard-Flanders (US), David Pettijohn (US), and Philip Hanawalt (US) found that in Escherichia coli the onset of DNA synthesis is associated with thymine dimer removal. One step in the recovery of cells from the effects of UV may be the removal of the dimers from DNA(3198-3200). This helped explain what was called dark repair.

Ronald E. Rasmussen (US) and Robert B. Painter (US) presented evidence that this type of repair also operates in mammalian cells(3201).

Richard Burton Setlow (US), Jane K. Setlow (US), and William L. Carrier (US) determined the action spectrum for the splitting of thymine dimers and showed that wavelengths shorter than 254nm were most effective. The dimerization and monomerization reactions in pure DNA could thus be easily followed by observing changes in the absorption spectrum of DNA. This simple measurement allowed them to determine the kinetics of dimerization and monomerization as a function of wavelength. They found that wavelengths around 280nm preferentially resulted in the formation of dimers, whereas wavelengths around 240nm preferentially split them(3202-3205).

Daniel L. Wulff (US) and Claud Stan Rupert (US) went on to find evidence that both enzyme-catalyzed photoreactivation and short-wavelength direct reactivation operate on the same substrate, strongly suggesting that enzymatic photoreactivation effected the monomerization of pyrimidine dimers(3206). 

Paul Howard-Flanders (US), Richard P. Boyce (US), and Lee Theriot (US) found that Escherichia coli K-12 contains three genetic loci (uvrA, uvrB, and uvrC) that control the excision of pyrimidine dimers and certain other mutagen products from DNA(3207).

Norio Iwatsuki (JP), Cheol O. Joe (KR), and Harold Werbin (US) purified a photoreactivating enzyme. It is a low-molecular-weight, light-absorbing moiety, flavine adenine dinucleotide, with a chromophore(3208). Subsequently it was settled that all photoreactivating enzymes have two chromophores.

Aziz Sancar (TR-US) and Claud Stan Rupert (US) cloned the E. coli phr gene, the first DNA repair gene to be cloned(3209).

H.W. Park (US-CA), Aziz Sancar (TR-US), and Johann Deisenhofer (DE-US) solved the crystal structure of the E. coli photoreactivating enzyme(3210).

Erwin Chargaff (AT-US), Ernst Vischer (US), Ruth Doniger (US), Charlotte Green (US), Fernanda Misani (US), and Stephen Zamenhof (US) demonstrated that contrary to common belief the four bases in DNA are not always present in equal molar concentrations. They discovered that the molar concentration of adenine is always the same as that for thymine, and the molar concentration of guanine is always the same as that for cytosine, however, the ratio of adenine to guanine and that of cytosine to thymine vary considerably from one DNA to another(3211-3214).

Gerard Robert Wyatt (CA) studied the base ratios in the DNAs of wheat germ, herring sperm, and insect viruses. His results confirmed the findings of Chargaff and his colleagues, even though he found an unusual base, 5-hydroxymethyl-cytosine, in the viruses. The molar ratio of cytosine plus 5-methyl-cytosine to guanine was 1:1 in these viruses(3215).

Gerard Robert Wyatt (US) and Seymour Stanley Cohen (US) discovered 5-hydroxymethylcytosine in the DNA of T-even phages(3216, 3217).

George Scatchard (US) pointed out that some proteins have attractions for small molecules and ions(3218).

Daniel Israel Arnon (PL-US) discovered that chloroplasts of Beta vulgaris (common beet) contain an enzyme which requires copper as cofactor(3219).

George W. Kenner (GB), Harold J. Rodda (GB), and Lord Alexander Robertus Todd (GB) synthesized substrates for ribonuclease(3220).

Joseph H. Burchenal (US), Aaron Bendich (US), George Bosworth Brown (US), George Herbert Hitchings (US), Cornelius P. Rhoads (US), C. Chester Stock (US), and Gertrude Belle Elion (US) synthesized a purine that inhibited mouse leukaemia. This was the forerunner of 6-mercaptopurine(3221).

George Herbert Hitchings (US) and Gertrude Belle Elion (US) synthesized and developed 6-mercaptopurine (6-MP), also called purinethol, as an antitumor agent. They quantified the synergistic effects of purine antagonists with pyrimidine and folic acid antagonists(3222, 3223). Purinethol was used to treat childhood leukaemia. Elion later developed thioguanine, also for the treatment of leukaemia(3224).

Howard Gest (US) and Martin David Kamen (US) discovered light-dependent production of hydrogen gas and nitrogen fixation by the bacterium, Rhodospirillum rubrum. The enzyme nitrogenase catalyzes both of these activities(3225, 3226).

Earl Reece Stadtman (US), Horace Alber Barker (US), G. David Novelli (US), and Fritz Albert Lipmann (DE-US) discovered phosphotransacetylase while elucidating the role of acetyl-CoA in fatty acid metabolism(3227-3230).

John F. Speck (US) and William H. Elliott (US) demonstrated that glutamine is synthesized by a specific enzyme, glutamine synthetase, in the presence of glutamic acid, ATP, Mg++, and ammonia(3231-3233).

Dorothy Mary Crowfoot-Hodgkin (GB), Charles W. Bunn (GB), Barbara W. Rogers-Low (GB), and Annette Turner-Jones (GB) determined the three dimensional structure of penicillin G, largely through computer analysis of x-ray diffraction data. They did this before organic chemists had even determined its primary chemical structure. Their work represents the first use of the electronic computer in direct application to a biochemical problem(3234).

Sven Verner Furberg (GB) was the first to correctly determine, using x-ray diffraction data, that the bases in DNA are at right angles to the helical sugar-phosphate backbone and parallel to one another(3235-3239).

William Howard Stein (US) and Stanford Moore (US) reported the complete amino acid analysis of beta-lactoglobulin and bovine serum albumin, determined by starch column partition chromatography(3056). See, E. Brand1945.

Pehr Victor Edman (SE) described the phenylisothiocyanate procedure for the successive chemical removal of individual amino acids from the amino terminus of a peptide chain(3240, 3241). This technique permitted the determination of a polypeptide’s amino acid sequence.

Selman Abraham Waksman (RU-US) and Hubert A. Lechevalier (US) reported the isolation of the antibiotic neomycin from Streptomyces fradiae(3242).

Christopher Polge (GB), Audrey V. Smith (GB), and Sir Alan S. Parkes (GB) were the first to demonstrate that the addition of an antifreeze like compound (glycerol) to cell cultures enhances their survivability when frozen and later thawed(3243).

George Marmont (US) was the first to develop a voltage clamp. It was used to quantitatively measure ionic currents in cells(3244).

Henry Borsook (US), Clara L. Deasy (US), Arie Jan Haagen-Smit (NL-US), Geoffrey Keighley (US), Peter H. Lowy (US), and Tore Hultin (SE) discovered that ribonucleoprotein particles (now called ribosomes) are the sites of polypeptide bond formation(3245-3247).

Dana Irving Crandall (US) and Samuel Gurin (US) performed experiments which finally clarified the enzymatic mechanisms of fatty acid oxidation(3248).

Eugene Patrick Kennedy (US) and Albert Lester Lehninger (US) discovered that rat liver mitochondria contain the entire enzymatic apparatus of the citric acid cycle, whereas the enzymes of glycolysis are in the fluid portion of the cytoplasm. They noted that as mitochondria oxidize metabolites they simultaneously esterify phosphate groups. This represents the first experimental evidence of where oxidative phosphorylation resides within the cell(3249).

Sir Alan Lloyd Hodgkin (GB) and Sir Andrew Fielding Huxley (GB) determined that generation of the nerve impulse is accompanied by a leakage of potassium ions across the cell membrane with a resulting marked change in the membrane conductance, and that during the recovery the potassium ions are reabsorbed. They published equations which allowed the prediction of the conductance changes and the form and amplitude of the action potential during impulse transmission and allowed them to restrict the number of possible kinds of ionic events which might produce these changes. This work was the first to reveal the kinetic complexity and the ionic selectivity of permeability changes in nerve cells(3250-3255).

Sir Alan Lloyd Hodgkin (GB), Sir Andrew Fielding Huxley (GB), and Sir Bernard Katz (RU-GB) developed a model to explain the axon potential in the squid axon. The model was based on the movement of ions across a semipermeable nerve cell membrane(3256, 3257). This is often referred to as the sodium pump mechanism of nerve impulse transmission. See R.B. Dean, 1941.

Linus Carl Pauling (US), Harvey Akio Itano (US), Seymour Jonathan Singer (US), Ibert Wells (US), Max Ferdinand Perutz (AT-GB), and J. Murdoch Mitchison (GB) determined that the molecular defect that causes the human sickle cell anemia is due to chemically altered (mutant) hemoglobin molecules(3258, 3259). They used an electrophoretic method, developed by Sanger, which was later called protein fingerprinting.

Pauling got the idea for this research, in 1945, while listening to a report to a government committee, of which he was a member, charged with making recommendations for the direction of post-war medicine in the America. His brilliant insight is included here for your enjoyment.

“One of the members of the group, Dr. William Bosworth Castle, described some work that he was doing on the disease sickle cell anemia. When he mentioned that the red cells of patients with the disease are deformed (sickled) in the venous circulation but resume their original shape in the arterial circulation, the idea occurred to me that sickle cell anemia was a molecular disease, involving an abnormality of the hemoglobin molecule determined by a mutated gene. I thought at once that the abnormal hemoglobin molecules that I postulated to be present in the red cells of these patients would have two mutually complementary regions on their surfaces, such as to cause them to aggregate into long columns, which would be attracted to one another by van der Waals forces, causing the formation of a needle-like crystal which, as it grew longer and longer, would cause the red cell to be deformed and would thus lead to the manifestations of the disease”(3260).

John W. Harris (US) reported that David Waugh (US) identified microscopic hemo- globin tactoids as the actual physical basis of the sickling process(3261).

Ezio Silvestroni (IT), Ida Bianco (IT), and Giuseppe Montalenti (IT) developed methods for identifying ß-thalassemia heterozygotes in populations, and recorded their frequencies in different parts of Italy. In some regions heterozygote frequencies up to 10% were observed, and the strong geographic correspondence between the incidence of thalassemia and endemic malaria was noted, as documented by an Italian historian of science(3262).

John Burdon Sanderson Haldane (GB-IN) suggested that individuals heterozygous for the thalassemia allele may be resistant to malaria. Haldane and the individuals immediately above should be credited with originating the “malaria hypothesis"(3263, 3264).

Louis H. Miller (US), Simon J. Mason (US), David F. Clyde (GB), and Mary H. McGinniss (US) reported the resistance factor to Plasmodium vivax in blacks possessing the Duffy-blood-group genotype, Fya/Fyb(3265).

Jonathan Flint (GB), Adrian V. Hill (GB), Don K. Bowden (AU), Stephen J. Oppenheimer (GB), P.R. Sill (PG), Susan Wyber Serjeantson (AU), Joe Bana-Koiri (PG),  Kuldeep Bhatia (PG), Michael P. Alpers (PG), Anthony J. Boyce (GB), David J. Weatherall (GB), and John B. Clegg (GB) supported the hypothesis that protection against malaria is the major factor responsible for the high frequencies of hemoglobinopathies in many parts of the world(3266).

Stephen J. Allen (GB), Angela O'Donnell (GB), Neal D.E. Alexander (GB), Michael P. Alpers (GB), Timothy E.A. Peto (GB), John B. Clegg (GB), and David J. Weatherall (GB) determined that the homozygous state for alpha plus thalassemia offers considerable protection against the severe complications of Plasmodium falciparum malaria(3267).

Sarah A. Tishkoff (US), Robert Varkonyi (US), Nelie Cahinhinan (US), Salem Abbes (TN), George Argyropoulos (US), Giovanni Destro-Bisol (IT), Anthi Drousiotou (CY), Bruce Dangerfield (ZA), Gerard Lefranc (FR), Jacques Loiselet (LB), Anna Piro (IT), Mark Stoneking (DE), Antonio Tagarelli (IT), Giuseppe Tagarelli (IT), Elias H. Touma (LB), Scott M. Williams (US), and Andrew G. Clark (US) suggested that malaria has influenced human evolution since the introduction of agriculture approximately 10,000 years ago(3268).

Harold Garnet Callan (GB), Sir John Turton Randall (GB), and Stan G. Tomlin (GB) used electron microscopy to help provide the first descriptions of “pores” and “annuli” in nuclear envelopes. These studies described the structure of the nuclear membrane as a double membrane with pores possessing a large central channel(3269, 3270).

Paul Jackson Kramer (US) and Karl M. Wilbur (US), using radioisotopes, were the first to measure the uptake of phosphorus by mycorrhizal roots of trees(3271).

Haldan Keffer Hartline (US), Henry G. Wagner (US), and Floyd Ratcliff (US) found that if one ommatidium of Limulus is receiving bright light and a neighbor is receiving dim light, the first ommatidium will inhibit the signal from it's neighbor. The result is that the dimmer signal gets even dimmer and the result is an increased difference between the two which the eye would perceive as an increase in contrast(3272, 3273). This led to an understanding of the mechanisms of lateral inhibition. Lateral inhibition is a process that animals, including humans, use to better distinguish borders. When you look at the ocean horizon the ocean appears darker at the horizon, at the boundary between sea and sky. This apparent difference in light intensity is not actually there but is created by our visual receptors and is known as lateral inhibition.

Haldan Keffer Hartline (US), Henry G. Wagner (US), and Edward F. MacNichol, Jr. (US) recorded intracellular generator potentials in retinal nerve cells(3274).

These discoveries convinced researchers that the retina (the innermost layer of the eye that is light sensitive) and optic nerves themselves process many nerve signals before the signals are transmitted to the brain.

Walter Rudolf Hess (CH) pioneered the use of electrical stimulation to probe structures deep in the brain. Studying cats, he discovered that, depending on the location of the electrode, sleep, sexual arousal, anxiety, or terror could be provoked by the flick of the switch and turned off just as abruptly(3275).

Maurício Rocha e Silva (BR), Wilson T. Beraldo (BR), and Gastão Rosenfeld (BR) described the release of an active peptide from serum globulin by trypsin or snake venoms. They named the peptide bradykinin because it caused a relatively slow contraction of the isolated guinea-pig ileum(3276).

Choh Hao Li (CN-US), Miriam E. Simpson (US), and Herbert McLean Evans (US) isolated electrophoretically pure follicle stimulating hormone (FSH) from sheep(3277).

John Franklin Enders (US), Thomas Huckle Weller (US), and Frederick Chapman Robbins (US) were the first to grow poliovirus in high titer in cell culture. They used human embryonic extraneural tissue(3278-3280).

Alfred Day Hershey (US) and Max Ludwig Henning Delbrück (DE-US) discovered that when Escherichia coli is simultaneously infected with two or more bacteriophages that differ from each other in two genetic characters there issue from the infected cell some recombinant phages that have obtained one of these two characters from one parent phage and the other of the two characters from the other parent phage. Phages can therefore engage in genetic recombination within the host cell(3281).

Claude Ephraim ZoBell (US) and Frank H. Johnson (US) cultured bacteria brought up from great ocean depths and found that some are barophilic. These organisms are slow growing under these great pressures(3282).

Otto Heinrich Warburg (DE) defined the bacterial requirement for iron(3283). Prior to this work he had presented considerable evidence of the intracellular functions of iron.

Jacques Lucien Monod (FR) established the growth phases of a typical bacterial growth curve as lag, acceleration, exponential, retardation, stationary, and decline(3284).

Melvin M. Green (US) and Kathleen C. Green (US) were able to map mutations of the lozenge locus in Drosophila melanogaster into linear order(3285).

Murray Llewellyn Barr (CA) and Ewart George Bertram (CA) discovered that interphase cells of cats can be characterized as being of male or female origin solely by the absence or presence of a densely staining bit of chromatin at the nuclear periphery. The dense body soon became known as the Barr body. Keith Leon Moore (?), M.A. Graham (), and Murray Llewellyn Barr (CA) demonstrated the same phenomenon in humans(3286-3288). The term Barr body was introduced by Mary Frances Lyon. See, Lyon, 1962.

Pratima S. Karnik (IN) showed that phosphorylation of type 1 histone often accompanies aggregation of chromatin into heterochromatin as is the case with the Barr body(3289).

Boris Ephrussi (RU-FR), Hélène Hottinguer (FR), J. Tavlitzki (FR), Anne-Marie Chimenes (FR), Philippe L'Héritier (FR), Piotr P. Slonimski (PO-FR) demonstrated non-Mendelian determinants in yeast. They described the isolation and characterization of the "petite" (or ρ-) mutant. These initial studies demonstrated that the ρ- trait was inherited by a non-Mendelian determinant, that normal strains could be converted in mass to ρ- by acriflavine treatment, that ρ- was irreversible, and that ρ- mutants lacked cytochromes a • a3 and b and were deficient in respiration(3290-3296).

C.E. Palm (US) and P. Garman (US) reported early cases of arachnid resistance to an organophosphate. The resistant species was Tetranychus urticae (red spider mite or two-spotted spider mite)(3297, 3298).

Albert Frey-Wyssling (CH) and Kurt Mühlethaler (CH) published electron photomicrographs of chloroplasts in which the grana look like a scattered roll of coins(3299).

Pierre Limasset (FR), Pierre Cornuet (FR) and Yves Gendron (FR) noted the absence of virus in the meristems of tobacco (Nicotiana tabacum) with virus diseases. Based on this finding, meristem culture has been extensively used to eliminate viruses, bacteria and fungi from plants(3300).

Georges Morel (FR) and Claude Martin (FR) regenerated whole virus-free plants of dahlia using meristems from plantations infected by three different viruses. This is the first successful micro-graft(3301).

Georges Morel (FR) produced virus-free cymbidiums(3302).

Georges Morel (FR) accomplished protocorm formation in cymbidiums(3303).

Cecil Edmund Yarwood (US) reported that 6-(1-methylheptyl)-2,4 dinitro-phenyl crotonate is a good fungicide for powdery mildew(3304).

Saul Rich (US) and James Gordon Horsfall (US) also introduced it in 1949(3305).

John H. Lilly (US), John F. Stauffer (US), and Stanley D. Beck (US) were the first to develop an artificial diet for lepidopterous species(3306-3308).

G. Michael Chippendale (US) and Stanley D. Beck (US) demonstrated the necessity of ascorbic acid in the diet of a lepidopterous insect(3309).

Susumu Hagiwara (JP-US) performed a statistical analysis on the fluctuation of the interval of rhythmic excitation of neuronal firing(3310, 3311).

Kenneth Bryan Raper (US) and Charles Thom (US) wrote their monograph, Manual of the Penicillia(1965).

Edward Arthur Steinhaus (US) and Clarence G. Thompson (US) were the first to demonstrate that an insect pest can be controlled, under field conditions, by the use of a virus spray containing the nuclear polyhedral virus of the alfalfa caterpillar(3312).

Alfred Sherwood Romer (US) spent much of his adult career investigating vertebrate evolution and wrote The Vertebrate Body which is still a standard on the subject(3313).

Gustav Kramer (DE) demonstrated that the sun is utilized in orientation by certain diurnal bird migrants(3314, 3315).

Maurice J. Strauss (US), Ernest W. Shaw (US), Henry Bunting (US), and Joseph L. Melnick (US) observed virus-like particles in skin papillomas then identified human papilloma virus (HPV) as the cause of warts(3316, 3317). 

Sir Frank Macfarlane Burnet (AU) and Frank John Fenner (AU), based on Ray David Owen’s observations and on studies of lymphocytic choriomeningitis virus by Erich Traub, postulated that immunological self-recognition is not genetically determined but rather is learned by the immune system during the organism’s embryonic stages, i.e., immunological tolerance develops during embryonic life. They predicted that antigen introduced prior to maturity of the immune mechanism would be mistaken for self then and throughout the life of the individual(3318).

Rupert Everett Billingham (GB-US), Leslie Brent (GB), and Sir Peter Brian Medawar (GB) produced actively acquired donor specific tolerance to skin allografts in mice injected during late fetal life with donor hematolymphopoietic cells. This strongly supported the theory above(3319).

Leon Orris Jacobson (US), Edna K. Marks (US), Melba J. Robson (US), Evelyn O. Gaston (US), Raymond E. Zirkle (US), Egon Lorenz (DE), Delta E. Uphoff (US), T.R. Reid (US), Emma Shelton (US), Charles C. Congdon (US), Joan M. Main (US), and Richmond T. Prehn (US), using mice and rats, performed the first bone marrow transplants. They discovered that animals can be saved from the effects of an otherwise lethal dose of radiation by spleen shielding (Jacobson) or injecting them, after exposure, with extracts made from unexposed blood forming organs(3320-3325).

David W.H. Barnes (GB) and John Freeman Loutit (GB), Charles Edmund Ford (GB), and John L. Hamerton (GB) showed that the recovery was brought about because living hematopoietic cells rapidly colonized the irradiated animals, replacing their dead lymphoid tissue(3326, 3327).

Curt Stern (DE-US) and Delta E. Uphoff (US) examined the genetic effects of low intensity irradiation and concluded, “Viewing all experiments together, it appears that radiation at low doses, administered at low intensity, induces mutation in Drosophila sperm. There is no threshold below which radiation fails to induce mutations.” This is now one of the cornerstones of radiation genetics(3328).

Robert Armstrong Nelson, Jr. (US), Manfred Martin Mayer (DE-US), Judith A. Diesendruck (US), and John T. Eagan (US) developed the TPI-(Treponema pallidum-Immobilization)Test, a highly sensitive, specific reaction for serodiagnosis of syphilis, based on the demonstration of immobilizing antibodies in patients' serum(3329).

Joseph E. Smadel (US), Theodore E. Woodward (US), Herbert L. Ley, Jr. (US), and Raymond Lewthwaite (US) successfully treated tsutsugamushi disease (scrub typhus) with chloramphenicol (Chloromycetin)(3330).

William A. Altemeier (US) and Wesley L. Furste (US) found that in experimentally induced Clostridium welchii infections the virulence of the bacterium was increased one thousand times by the presence in the wound of crushed muscle, and one million times by having crushed muscle and sterile foreign material (street dirt, cinders, etc.) in the wound(3331).

Stephen D. Elek (GB) found in human volunteers that intradermal and subcutaneous inocula of more than one million Staphylococcus aureus were required to induce infections of the skin, but that in the presence of subcutaneous foreign bodies (infected silk sutures) pyogenic reactions occurred with much smaller doses of S. aureus(3332).

Heinz Kruse (US), Philip Duryeé McMaster (US), Ernest Sturm (US), and Joshua L. Edwards (US) used dyed antigens to reveal that antigens are taken up by cells of the reticuloendothelial system throughout the body including Kupffer cells of the liver, as well as macrophages and reticular cells of the spleen and lymph nodes. In this manner they revealed certain of the sites from which the first stimuli to antibody formation arise(3333-3338).

Andre De Vries (US), Benjamin Alexander (US), Robert Goldstein (US), Eunice Addelson (US), and Elaine Promisel (US) characterized serum prothrombin conversion accelerator (SPCA)(3339).

Benjamin Alexander (US), Robert Goldstein (US), Greta Landwehr (US) and Charles D. Cook (US) described Alexander’s syndrome, a congenital disorder of both sexes with onset in childhood or adult life. Like hemophilia but less severe this deficiency of serum prothrombin conversion accelerator (SPCA) results in hemophilia-like hemorrhagic diathesis with epistaxes, deep muscular hematomas, and internal hemorrhages(3340).

Fritz Koller (CH), Emil A. Loeliger (NL) and Francois Henri Duckert (CH) independently identified the same factor, which they named factor VII(3341). 

Kenneth M. Endicott (US), Theodore Gillman (US), Gerhard A. Brecher (US), Arthur T. Ness (US), F.A. Clarke (US), and Emil R. Adamik (US) found that the greatest iron uptake occurs in the duodenum(3342).

Carl Vernon Moore (US) and Reubenia Dubach (US) determined that iron absorption occurs directly into the blood stream rather than through the lymphatics(3343, 3344).

Jessie L. Ternberg (US) and Robert Edward Eakin (US) demonstrated the presence in normal gastric juice of a protein fraction, apoerythein, which is absent from the gastric juice of pernicious anemia patients. This substance is capable of combining with vitamin B12 (erythrotin) to form a vitamin-protein complex, erythein, in which the vitamin is resistant to digestive destruction. The substance is thus presumably identical with the “intrinsic factor” of Castle(3345). It has subsequently been shown that apoerythein is present in the saliva of both normal persons and pernicious anemia patients in amounts sufficient to account for that found in the gastric juice, but that the gastric juice of pernicious anemia patients contains a principle which inactivates apoerythein, unless the gastric juice is first treated with hydrochloric acid.

Sir Geoffrey S.W. Organe (GB), Sir William D.M. Paton (GB), and Eleanor J. Zaimis (GR) performed the first clinical trials of the anesthetic decamethonium(3346).

Joseph H. Burchenal (US), S. Johnson (US), Joan R. Burchenal (US), M.N. Kushida (US), Elaine Robinson (US), and Chester C. Stock (US) found that methotrexate can prolong survival in mice with leukaemia(3347).

Sidney Faber (US) used methotrexate to treat children with leukaemia(3348).

Robert H. Cress (US) and Nell L. Deaver (US) reported using methotrexate to manage psoriasis and arthritis(3349).

Eugene J. Van Scott (US) introduced the concept of "epithelial kinetics," the treatment of psoriasis with methotrexate(3350, 3351).

Philip Showalter Hench (US), Edward Calvin Kendall (US), Charles H. Slocumb (US), and Howard F. Polley (US) administered both Compound E (cortisone) and adrenocorticotropic hormone (ACTH) to fourteen patients suffering from rheumatoid arthritis. Both substances gave dramatically positive results(3352). See Valey Menken, 1941.

Philip Showalter Hench (US), Charles H. Slocumb (US), Arlie R. Barnes (US), Harry L. Smith (US), Howard F. Polley (US), and Edward Calvin Kendall (US) introduced Compound E (cortisone) in the treatment of rheumatic fever(3353).

Lloyd D. Felton (US), utilizing pneumococcal polysaccharides, demonstrated a phenomenon known as "immunological paralysis" or immune tolerance(3354).

Charles Henry Sawyer (US), John W. Everett (US), and Joseph E. Markee (US) discovered the locus in the nervous system at which sex hormones alter the sensitivity to extrinsic stimuli and thus alter hypophyseal secretion. Their opinion was that the hypothalamus appeared to be the most likely site (gonadotrophin sex center)(3355).

Jerzy E. Rose (US) and Clinton Nathan Woolsey (US) completed a detailed lesion-retrograde degeneration mapping of the projections from the auditory region of the thalamus (medial geniculate body) to the auditory cortex in the cat(3356). They had completed similar studies on the projections of the mediodorsal nucleus to the orbitofrontal cortex in rabbit, sheep, and cat and on the relations between the anterior thalamic nuclei and the limbic cortex in the rabbit and cat(3357, 3358).

Donald Olding Hebb (CA) wrote The Organization of Behavior; A Neuropsychological Theory. His fundamental idea was to assume that the brain is constantly making subtle changes in the synapses, the points of connection where nerve impulses make the leap from one cell to the next. He argued that these synaptic changes were in fact the basis of all learning and memory. Hebb suggested that the selective strengthening of the synapses would cause the brain to organize itself into cell assemblies (subsets) of several thousand neurons in which circulating nerve impulses would reinforce themselves and continue to circulate. Hebb considered these cell assemblies to be the brain's basic building blocks of information. Each one would correspond to a tone, a flash of light, or a fragment of an idea. And yet these assemblies would not be physically distinct. Indeed, they would overlap, with any given neuron belonging to several of them. And because of that, activating one assembly would inevitably lead to the activation of others, so that these fundamental building blocks would quickly organize themselves into larger concepts and more complex behaviors. The cell assemblies, in short, would be the fundamental quanta of thought”(3359). This hypothesis has been called Hebb's rule, Hebb's postulate, and cell assembly theory.

Lionel Sharples Penrose (GB) authored his very influential book, The Biology of Mental Defect. It is a thorough survey of the etiology of mental deficiency and an outstanding treatise on human genetics(3360).

Giuseppe Moruzzi (IT), Horace Winchell Magoun (US), Donald B. Lindsley (US), and J.W. Bowden (US) proposed that there is a diffuse system of ascending fibers arising in the reticular formation that is responsible for control of states of consciousness. They named it the ascending reticular activating system (the ARAS)(3361, 3362).

Sir Harold Ridley (GB) achieved the first implant of an intraocular lens in 1949, although it was not until 1950 that he left an artificial lens permanently in place in an eye(3363). He had been experimenting with the correction of aphakia (the loss of the human lens from cataract surgery) by implanting artificial lenses into animals. As World War II broke out, he treated many fighter pilots whose eyes were injured by shattered plastic from the windshields of their fighter planes damaged during air combat. He discovered that if the tiny pieces of plastic were left in the eye, they were very well tolerated. A medical student, Peter Choyce (GB), suggested that he use polymethylmethacrylate or Perspex CQ, as the material for a human intraocular lens implant. Thus the beginnings of the artificial lens implant to replace the cataractous lens removed at the time of cataract surgery.

John Frederick Joseph Cade (AU) observed the sedating effects of lithium in guinea pigs. He then determined that lithium was safe for human consumption by trying it himself. He administered lithium to ten manic patients, six schizophrenics, and three patients with major depressions. It didn’t affect the depressives and mildly calmed the schizophrenics, but it changed the manic patients dramatically(3364). Note: Current hypotheses concerning its mechanisms include the interference with the phosphoinositide signaling pathway by either reducing the synthesis of second messengers involved in the pathway or inhibiting inositol monophosphatase activities; its neuroprotection against excitotoxicity caused by glutamate hyperactivity; the suppression of intracellular calcium mobilization; its stimulatory effect on ATP-dependent dopamine uptake; its regulation of gene expression in long-term treatment; and the selective effect in G-protein subunit expressions in brain cells.

Lithium may be responsible for the reputed benefit of certain spring waters to patients with mental disease. 

Johan August Arfwedson (Arfvedson) (SE), in 1817, discovered lithium. Its name is from the Greek word lithos meaning stone, apparently because it was discovered from a mineral source.

Priscilla White (US) introduced the "White Classification of Diabetic Pregnancies", which classified patients according to their level of risk and tailored their treatment protocol accordingly(3365).

Richard Alan John Asher (GB) brought attention to the interaction between the brain and the thyroid gland which can lead to madness(3366). As a result, young and elderly psychiatric patients are now screened for thyroid malfunction. Some of the 'madness' cases are now thought to be the early descriptions of Hashimoto's encephalopathy, a rare neuroendocrine syndrome sometimes presenting with psychosis(3367).

Ray E. Umbaugh (US) was the first to transfer a fertilized bovine embryo(3368).

Elwyn L. Willett (US), W.G. Black (US), Lester Earl Casida (US), W.H. Stone (US), and P.J. Buckner (US) performed the first successful transfer of a fertilized bovine embryo which went to term(3369).

Robert A. Bruce (US), Frank W. Lovejoy, Jr. (US), Raymond Pearson (US), Paul N. G. Yu (US), George B. Brothers (US), and Tulio Velasquez (PE) aware of the tendency of people with coronary artery disease to experience angina (cardiac chest discomfort) during exercise, developed the first standardized method of "stressing" the heart, where serial measurements of changes in blood pressure, heart rate and electrocardiographic (ECG/EKG) changes could be measured under "stress-stress" conditions(3370, 3371).

Donald D. Matson (US) developed the lumbo-ureteral shunt to drain overabundant cerebrospinal fluid into a hydrocephalic patient’s bladder via the ureter. This allowed the fluid to pass from the body along with urine. The kidney removed during this operation (Matson kidney) is often made available to patients in need of a kidney transplant(3372).

William T. Mustard (CA) and A. Lawrence Chute (CA), in 1949, successfully performed the world's first open-heart operation on a dog using rhesus monkey lungs to oxygenate the animal’s blood(3373). 

William Mustard (CA), A. Lawrence Chute (CA), John Dowe Keith (CA), Anna Sirek (CA), Richard D. Rowe (CA), and Peter Vlad (CA), in 1952, used excised lungs from rhesus monkeys to oxygenate blood during pediatric surgery on a three month old girl with transposition of vessels. She only survived for a few hours(3374).

Edward C. Tolman (US) hypothesized that there at least six kinds of learning: cathexes (which employs reinforcement); equivalence beliefs (reinforcement plus a traumatic experience); field expectancies (primarily Gestalt principles of learning and forgetting); field-cognition modes; drive discriminations; and motor patterns (probably Guthrie's principle of simple conditioning)(3375). 

Aldo Starker Leopold (US) provided the intellectual and philosophical foundation for the discipline of wildlife ecology. His book of essays, A Sand County Almanac, gave form and voice to the land ethic that undergirds modern concepts of environmental sustainability. He fostered the idea that natural lands are more than a commodity, that nature is a human trust, and that there is inherent value in wilderness and wild things(3376).

Edward Smith Deevey, Jr. (US) reviewed the biogeography of the Pleistocene in an influential synthesis of existing knowledge. He coordinated climatic changes on both sides of the Atlantic Ocean(3377).

1950

“Pasteur was not only the great scientist who was largely responsible for the creation of the science of microbiology, he was its high priest, preaching and fighting for the recognition of its importance in health and in human welfare.” Selman Abraham Waksman(3378).

"Mother, mother I am ill,

Send for the doctor from over the hill; In comes the Doctor, In comes the Nurse,

In comes the lady with

the alligator purse.

Penicillin says the Doctor, Penicillin says the Nurse, Penicillin says the lady with the alligator purse." A parody on a jump-rope-rhyme which was written in response to the enormous popularity of penicillin.

Edward Calvin Kendall (US), Tadeus Reichstein (PL-CH) and Philip Showalter Hench (US) were awarded the Nobel Prize in Physiology or Medicine for their discoveries relating to the hormones of the adrenal cortex, their structure and biological effects.

Otto Paul Hermann Diels (DE) was awarded the Nobel Prize in Chemistry for his synthesis of organic molecules including a dehydrogenated version of cholesterol.

William Grey Walter (US-GB) developed an automatic devise which was so wired as to react in fashions that one usually associates with living creatures, i.e., a robot(3379).

James Hillier (CA-US) and Mark E. Gettner (US) devised one of the earliest ultramicrotomes(3380, 3381).

Paul Fatt (GB) and Sir Bernard Katz (RU-GB) originated the technique of using intracellular microelectrodes to record electrical potential and currents within the muscle fiber with which they discovered that in the absence of any form of stimulation, the end-plate region of the muscle fiber is not completely at rest, but displays electric activity in the form of discrete, randomly recurring <miniature> end-plate potentials. Each is only of the order of 0.5 mV in amplitude, but in other respects resembles the much larger end-plate potential evoked by the nerve impulse: it shows the same sharp rise and slow decay, and has the character of a discrete all-or-none phenomenon though on a much smaller amplitude scale(3382, 3383).

Paul Fatt (GB) and Sir Bernard Katz (RU-GB) concluded that in the synapse "small quantities of acetylcholine alter the end-plate surface in such a way that other ions can be rapidly transferred across it, not only sodium and potassium, but probably all free anions and cations on either side of the membrane. Apparently, we must think in terms of some chemical breakdown of a local ion barrier which occurs as soon as acetylcholine combines with it, and whose extent depends upon the number of reacting molecules"(3384).

Israel Doniach (GB), Alma Howard (GB), and Stephen R. Pelc (GB) were the first to apply autoradiography to the study of single cells. They established that most eukaryotic cells replicate their DNA in a narrow window of time course during the cell cycle called S phase(3385-3387).

Peter M.B. Walker (GB), Helen B. Yates (GB), and Hewson H. Swift (US), using spectrophotometric methods, discovered that doubling of eukaryotic cellular DNA occurs only during a portion of interphase(3388, 3389).

Alma Howard (GB) and Stephen R. Pelc (GB) devised the system whereby interphase of cell division is subdivided into G1, followed by S and G2(3390).

Phyllis Brewster (GB), Edward David Hughes (GB), Sir Christopher Kelk Ingold (GB), and P.A.D.S. Rao () demonstrated that the stereochemical standards for sugars (L-glyceraldehyde) and amino acids (L-serine) possess the same configurations(3391).

Louis Frederick Fieser (US) proposed that various substituents on the carbon atoms of the sugar molecule be designated alpha or beta, depending on whether they project above or below the plane in the Haworth structure(3392).

Martin Seidman (US) and Karl P. Link (US) synthesized o-nitrophenyl-beta-D-galactoside (ONPG) as a substrate for beta-galactosidase(3393). ONPG is cheap and colorless. Upon attack by beta-galactosidase it breaks down to colorless galactose and yellow o-nitrophenol. The yellow color can be determined quantitatively providing a sensitive test for the presence of beta-galactosidase. This test was important to the ultimate understanding of the lac operon. 

Jacques Lucien Monod (FR), Aaron Novick (US), and Leo Szilard (HU-US) invented the chemostat, an instrument that achieves an automatic continuous culture of suspended cells(3394).

George Brecher (US) and Eugene P. Cronkite (US) developed a way to enumerate human blood platelets(3395).

Howard Burlington (US) and V. Frank Lindeman (US) found that young roosters treated with DDT fail to develop normal male secondary sex characteristics, such as combs and wattles. The pesticide also stunts the growth of the animals' testes(3396).

Paul Charpentier (FR) synthesized the phenothiazine derivative encoded 4560 RP, later to be known as chlorpromazine (Thorazine); the first effective drug for the treatment of schizophrenia and a commonly prescribed antipsychotic drug(3397).

Jean Delay (FR) Pierre Deniker (FR), and Jean Marie Harl (FR) reported great success when they used chlorpromazine (Thorazine) on their patients(310, 3398). In 1954 it was approved by the U.S. Food and Drug Administration.

M. Lourau (FR) and O. Lartigue (FR) discovered that diet can influence the biological effects produced by whole body X-irradiation(3399).

Jean-Francois Duplan (FR) found that cabbage in the diet offers a pronounced protection against whole body X-irradiation(3400).

Harry Spector (US) and Doris Howes Calloway (US) reported that cabbage and broccoli reduce X-irradiation mortality(3401).

Doris Howes Calloway (US), Gordon W. Newell (US), William K. Calhoun (US), and A.H. Munson (US) confirmed previous findings that both cabbage and broccoli lowered mortality in irradiated animals. They found that a number of other carotene-containing foods also exerted some beneficial effects(3402).

Kayoko Shimoi (JP), Shuichi Masuda (JP), Michiyo Furugori (JP), S. Esaki (JP), and Naohide Kinae (JP) reported that some non-nutrient compounds such as lignans, indoles, coumarins and flavonoids protect mice from the effects of radiation(3403).

Alexander C. Finlay (US), Gladys Lounsberry Hobby (US), S.Y. P’an (US), Peter P. Regna (US), John B. Routien (US), Donald B. Seeley (US), Gilbert M. Shull (US), Ben A. Sobin (US), Isaiah Alexander Solomons III (US), John W. Vinson (US), and Jasper H. Kane (US) reported the isolation of the antibiotic terramycin (oxytetracycline) from Streptomyces rimosus(3404).

József Baló (AT-HU) and Ilona Banga (AT-HU) discovered the pancreas elastase enzyme when they described the properties of a purified enzyme obtained from defatted pancreatic powder, distinct from trypsin and chymotrypsin, and capable of dissolving elastic fibers either in tissues or in test tubes(3405).

Carl Widmer, Jr. (US) and Ralph T. Holman (US) discovered that linoleic acid fed to essential fatty acid deficient rats, is the precursor of arachidonic acid and that alpha-linolenic acid is the precursor of pentaene and hexaene acids(3406).

Otto Fritz Meyerhof (DE-US) and Harry Green (US) found that transphosphorylation occurs with biological phosphate compounds, with alkaline as well as with acid phosphatase, of animal origin, and that the transphosphorylation always goes from the phosphate of higher energy to those of lower energy(3407).

Charles Henry Sawyer (US), Joseph E. Markee (US), and John W. Everett (US) demonstrated that norepinephrine (noradrenaline) is involved in the release of gonadotropins (luteinizing hormone/LH or interstitial cell-stimulating hormone/ICSH and follicle stimulating hormone/FSH) from the anterior pituitary gland(3408).

Linus Carl Pauling (US), Robert Brainard Corey (US), Herman R. Branson (US), Harry L. Yakel, Jr. (US), and Richard E. Marsh (US) determined that the alpha-helix represents the secondary structure of many polypeptides(3409-3417). Pauling and Corey also predicted the antiparallel pleated sheet (beta sheet) conformation as the secondary structure of some polypeptides(3418-3420).

Linus Carl Pauling (US) introduced the use of molecular models, with precisely scaled representations of the atoms, as a method for solving molecular biology problems. On receiving the 1954 Nobel Prize in Chemistry he told the Swedish Academy. “The requirements are stringent ones. Their application to a proposed hydrogen-bonded structure of a polypeptide chain cannot in general be made by the simple method of drawing a structural formula; instead, extensive numerical calculations must be carried out, or a model must be constructed. For the more complex structures, such as those that are now under consideration for the polypeptide chain of collagen and gelatin, the analytical treatment is so complex as to resist successful execution, and only the model method can be used. In order that the principles of modern structural chemistry may be applied with the power that their reliability justifies, molecular models must be constructed with great accuracy. For example, molecular models on the scale of 2.5 cm = 1 angstrom unit, have to be made with a precision better than 0.01 cm”(3421).

Martin Rivers Pollock (GB) observed that the enzyme penicillinase is induced by the presence of penicillin(3422).

André Michael Lwoff (FR), Antoinette Gutmann (FR), Louis Siminovitch (CA), and Niels Ole Kjeldgaard (DK), using Bacillus megatherium, rediscovered and explained lysogeny in bacteria (See, Bordet, 1921). They reasoned that in lysogeny the genes of the original infecting phage merged into the chromosome of the bacterium, where it behaved indetectably like the neighboring genes along the string. Lwoff called this integrated form of the virus, prophage or provirus. In a rare cell the prophage would spontaneously disengage from the host chromosome and set into motion events which would lead to the release of new phage particles. They discovered that virus in the lysogenic state can be induced to change to the lytic state by certain environmental factors. In 1953, Lwoff predicted that induction of prophage might be a good test for carcinogenic, and anti-carcinogenic agents(3423-3426).

André Michael Lwoff (FR), Louis Siminovitch (CA), and Niels Ole Kjeldgaard (DK) found that ultraviolet light terminates the lysogenic state, which is then immediately followed by phage replication and lysis of the entire bacterial population(3427). This discovery made lysogeny more susceptible to detailed molecular analysis.

Esther M. Lederberg (US) isolated lambda virus from Escherichia coli K12. She demonstrated that it is a temperate virus and therefore capable of being induced. She also discovered that the lysogenic state of the host can be transmitted like a gene during bacterial crosses(3428, 3429).

Norton David Zinder (US), Joshua Lederberg (US), and Bernard David Davis (US) showed that bacteriophage virus particles can transfer bacterial genetic material from bacterium to bacterium without direct contact between the cells. They called this phenomenon transduction(3430-3433).

Thomas Foxen Anderson (US) found that bacteriophages lose their infectivity when subjected to osmotic shock which ruptures the phage head and releases the phage DNA into the ambient medium. The implication was that the phage attaches to the host with its protein coat, called the capsid(3434).

Kenneth M. Smith (GB) and Ralph Walter Greystone Wyckoff (US) discovered a distinct and major group of insect viruses, the spherical polyhedral viruses(3435).

Leslie H. Collier (GB), beginning about 1950, developed a commercially feasible process for large-scale production of a stable freeze-dried vaccinia vaccine(3436). Vaccinia vaccine was produced in large quantities, beginning in the 1950’s, for use by the Pan American Sanitary Organization and the World Health Organization. By 1979 the world was declared free of smallpox(3437).

Donald Ainslie Henderson (US) directed the decade-long World Health Organization global campaign that eradicated smallpox. He oversaw more than 700 advisors from 69 countries, as well as 200,000 national health staff and volunteers(3438). The last known case of smallpox was reported in Somalia in 1977. This effort stands as one of the greatest successes in preventative medicine.

Dorothy Hamre (US), Jack Bernstein (US), and Richard Donovick (US) were the first to report a chemical agent which can block the replication of a virus. The agent is a thiosemicarbazone and it inhibits viruses from various families(3439).

Robert Edward Hungate (US) developed the roll-tube technique for culturing strict anaerobes(3440).

Luigi Luca Cavalli-Sforza (IT-US) and William Hayes (GB) were the first to isolate high frequency recombinant (Hfr) strains of bacteria(3441, 3442).

William Hayes (GB) discovered that bacterial conjugation is unidirectional, in which one organism acts as donor and the other organism as the recipient. Based on his experiments and those of others, principally the Lederbergs, Hayes theorized that some Escherichia coli carry a fertility factor (F+) whereas others lack it (F-). For a cross to be fertile, the presence of the fertility factor is required in at least one of the parents. Thus the crosses F+ X F+ and F+ X F- are fertile, whereas F- X F- is sterile. The fertility factor is transmissible from F+ to F- by a process requiring cell contact. F+ cells may spontaneously loose the fertility factor. Once lost it can only be regained from an F+ cell. He further proposed that the F+ cell transfers only part of its genome to the F- recipient, so that the resulting zygote is not a complete but a partial zygote, or merozygote.

William Hayes (GB) also announced that he had discovered a new substrain of Escherichia coli, K12, which produced recombinants a thousand to ten thousand times more frequently than any previously known. He named it Hfr Hayes (Hfr = high frequency recombinant)(3442-3446).

William Hayes (GB), Joshua Lederberg (US), Luigi Luca Cavalli-Sforza (IT-US), and Esther M. Lederberg (US) discovered that bacteria have gender with the males containing a genetic element called a fertility factor (F factor), abbreviated F(3442-3445).

Joshua Lederberg (US) gave the name plasmid to all extrachromosomal genetic elements of bacteria(3447). Most of those found in eukaryotes (Eucarya) are now known to be intracellular symbiotic microorganisms.

Élie L. Wollman (FR) Francois Jacob (FR), and William Hayes (GB) discovered that the bacterial DNA of Escherichia coli Hfr cells is transferred with a definite directionality starting from what was called the origin and continuing on back around to the integrated F factor. This injection follows a strict schedule and, with any particular strain, the injection always starts at the same point. Because of their location on the chromosome it was logical that some genes would be transferred frequently, whereas others would be transferred only rarely. Usually the result is the formation of an incomplete zygote (merozygote). Using time of transfer of donor alleles they were able to construct a time course map of the Escherichia coli chromosome(3448-3450).

Élie L. Wollman (FR) and Francois Jacob (FR) described the chromosome of Escherichia coli as a closed, or circular, structure. They described the F factor of Escherichia coli as a plasmid. They pointed out that the F factor is a self-replicating, nonessential, extra-chromosomal, genetic element which may be present or absent. The phenotypic characters acquired through possession of the F plasmid are dispensable, since the plasmid is not a necessary cellular constituent. The F factor is capable of alternating between the integrated and autonomous state. Once a bacterium is cured of a plasmid (such as the change from F+ to F) the phenotypic character associated with the plasmid is irretrievably lost(3451, 3452).

Yukinori Hirota (JP) and Teiji Iijima (JP) found that the F factor can be eliminated from F+ strains of bacteria by treatment with acridine dyes. Hfr clones are unaffected by the dye(3453).

Francois Jacob (FR) and Élie L. Wollman (FR) proposed the term episome to describe genetic elements such as colicine, phage lambda, and F factor which can exist both in association with the chromosome and independent of it(3454).

Francois Jacob (FR), Jacques Lucien Monod (FR), Edward Allen Adelberg (US), and Sarah N. Burns (US) discovered that occasionally an F factor picks up a small fragment of the bacterial chromosome when it disengages to become autonomous. They referred to these agents as F prime plasmids. These modified fertility factors exhibited a great increase in the frequency of their insertion into the bacterial chromosome. Furthermore, the chromosomal site at which the F prime factor became attached was invariably the same(3455, 3456).

Kunitaro Ochiai (JP), T. Yamanaka (JP), K. Kimura (JP), and O. Sawada (JP) demonstrated that antibiotic resistance can be transferred between strains of Escherichia coli and Shigella via extrachromosomal plasmids (R-factor)(3457).

Tomoichiro Akiba (JP), Kotaro Koyama (JP), Yoshito Ishiki (JP), Sadao Kimura (JP), and Toshio Fukushima (JP) reported that multiple drug resistance was developing in a single step in patients with enteric infections(3458).

Robert Lavallé (FR) and Francois Jacob (FR) provided indirect radiobiological evidence suggesting that the F factor (plasmid) does contain DNA(3459).

Julius Marmur (US), Robert Rownd (US), Stanley Falkow (US), Louis S. Baron (US), Carl L. Schildkraut (US), and Paul Mead Doty (US) demonstrated conclusively that plasmids are DNA. They used the CsCl buoyant density separation of DNA based on nucleotide base composition to show that light density E. coli -like DNA appeared in Serratia marcescens (which has a somewhat heavier DNA) after transfer of the F-factor to Serratia(3460).

Tsutomu Watanabe (JP), Toshio Fukasawa (JP) and Keong Lyang (JP) showed that F factor plasmids are capable of carrying genes which endow the host cell with drug resistance; in some cases multiple drug resistance. Not only are these plasmids transferred to their own species but to a broad spectrum of taxonomically diverse genera. Today these are referred to as R plasmids. With the appearance of the R plasmids, drug resistance could spread like wildfire through the bacterial flora. Over a span of a few years these R plasmids made their appearance all over the world (3461, 3462).

Naomi Datta (GB) and Polyxeni Kontomichalou (GR) discovered genes conveying resistance to antibiotics in bacteria on small, infectious, supernumerary chromosomes called R factors (plasmids)(3463).

Francois Jacob (FR), Sydney Brenner (ZA-GB), and Francois Cuzin (FR) proposed that the O locus of the F factor represents what they called a replicator, or site at which replication of the DNA molecule can be initiated by DNA polymerase enzyme. Each replication cycle of the autonomous (i.e., nonintegrated) F factor present in an F+ cell was thought to begin at that replicator site, in the same way in which replication of the bacterial chromosome was imagined to begin at its own replicators, and then to proceed around the DNA circle by means of a replicating Y-fork. The F replicator at the O locus has one additional quality, however: it is activated upon contact of the donor with a recipient cell. This activation engenders a new round of semiconservative DNA replication of the fertility-factor DNA, in the course of which one of the two daughter duplexes is threaded, O locus first, into the conjugation bridge and driven toward the F- cell, while the daughter duplex remains in the donor cell. If the entire F genome is replicated in this way before the conjugation bridge is sheared the F- recipient will become an F+ cell(3464).

Jun-ichi Tomizawa (JP-US) and Naoyo Anraku (JP-US) determined the time course of the integration process in merozygotes formed in the cross Hfr Cavilli Lac+ Tsxs x F- Lac- Tsxr. They concluded that most of the recombinants that arise from the conjugational merozygote are seen to be formed within a time span comparable to one bacterial generation period(3465-3467).

Stanley Norman Cohen (US), Annie C.Y. Chang (US), and Leslie Hsu (US) used cold calcium chloride to induce Escherichia coli to take up R-factor DNA(3468).

Maurice Ralph Hilleman (US), Richard Patrick Mason (US), Edward L. Buescher (US), Frederick J. Flatley (US), Sally A. Anderson (US), Mary L. Luecking (US), and Doris J. Levinson (US) discovered what is now known as the "drifting" and "shifting" mutation of influenza virus, making it possible to predict the development of new strains of influenza and to develop vaccines effective against new strains(3469-3473).

Thomas Huckle Weller (US), John Franklin Enders (US), Margaret E. Buckingham (US), and John J. Finn, Jr. (US) linked a coxsackie virus to the etiology of epidemic pleurodynia(3474).

Theodore A. Olson (US) was the first to demonstrate the link between specific genera of cyanobacteria and animal deaths resulting from the consumption of these cyanobacteria (3475).

Marjorie Griffen Macfarlane (GB) identified the alpha toxin of Clostridium perfringens as the enzyme lecithinase C(3476).

Florence B. Roth (US) and Louis Pillemer (US) determined that of all the exotoxins produced by Clostridium perfringens the alpha exotoxin is the most damaging to humans(3477).

James B. Evans (US) and Charles F. Niven, Jr. (US) found that those strains of Staphylococcus aureus which produce food poisoning by means of an enterotoxin are usually coagulase positive(3478).

John Nathaniel Couch (US) discovered the bacterial genus Actinoplanes. He established it as family Actinoplanaceae, in the order Actinomycetales(3479).

Francis T. Haxo (US) and Lawrence Rogers Blinks (US) proposed that phycoerythrins are the chief photosynthetic pigments in red algae(3480).

Shih-Yi Chen (CN), Boris Ephrussi (RU-FR), and Helene Hottinguer (FR) discovered that nuclear genes are necessary for proper functioning of mitochondria(3481). 

Folke Karl Skoog (SE-US) demonstrated, in vitro, that growth and development of plant organs is under chemical control(3482).  

Marion Wesley Parker (US), Harry Alfred Borthwick (US), and Laura E. Rappleye (US) determined that poinsettia will produce its showy red bracts just in time for Christmas if cuttings started at the beginning of October are kept in the dark for 14-16 hours daily(3483).

Marion Owenby (US) demonstrated that two species of the genus Trapopogonan were produced by polyploidization from hybrids. She showed that Trapopogonan miscellus found in a colony in Moscow, Idaho was produced by hybridization of T. dubius and T. pratensis. She also showed that T. mirus found in a colony near Pullman, Washington was produced by hybridization of T. dubius and T. porrifolius(3484).

Emma Lucy Braun (US) wrote Deciduous Forests of Eastern North America in which she describes the evolution of forest communities and their survival during periods of glaciation(3485).

George Ledyard Stebbins, Jr. (US) published Variation and Evolution in Plants, the first book to provide a wide-ranging explanation of how evolutionary mechanisms operated in plants at the genetic level. Stebbins argued that evolution needed to be studied as a dynamic problem and that evolution must be considered on three levels: first, that of individual variation within an interbreeding population; second, that of the distribution and frequency of this variation; and third, that of the separation and divergence of populations as the result of the building up of isolating mechanisms leading to the formation of species(3486).

Miriam Elizabeth Simpson (US) and Choh Hao Li (CN-US) pointed out that hormonal coordination is necessary for the balanced development of tissue. ref

Rachmiel Levine (PL-CA-US), Maurice S. Goldstein (US), Bernice Huddlestun (US), Susan P. Klein (US) and Samuel Soskin (US) discovered the role of insulin in glucose metabolism. Contrary to the assumption that glucose molecules freely pass through the cell membrane, they proposed what became known as the Levine Effect or transport theory, in which they suggested that insulin serves as the key regulatory factor for the transport of glucose into the cells. They theorized that insulin stimulates the transport of glucose from blood to fat/muscle cells and thus lowers the blood glucose level(3487-3489).

Harry Harris (GB) studied familial patterns associated with 1241 diabetic propositi and concluded that diabetes tends to run in families(3490).

Marie Cutbush (AU-GB-CA) and Patrick L. Mollison (GB) and Dorothy M. Parkin (GB) discovered and named the Duffy blood group system(3491).

Roger P. Donahue (US), Wilma B. Bias (US), James H. Renwick (US), and Victor A. McKusick (US) showed that segregation of the Duffy blood group is linked to a dominantly inherited microscopically visible secondary constriction (at an uncoiler locus) on the long arm of chromosome 1 in man(3492).

John R. Haserick (US), Lena A. Lewis (US), and Donald W. Bortz (US) found a specific factor in the gamma fraction of serum associated with acute disseminated lupus erythematosus and responsible for inducing rosettes of leucocytes(3493).

Floyd W. Denny (US), Lewis W. Wannamaker (US), William R. Brink (US), Charles H. Rammelkamp, Jr. (US), Edward A. Custer (US), Harold B. Houser (US), Edward O. Hahn (US), and John Holmes Dingle (US) performed a meticulous analysis of the role and timing of streptococcal infection in the causation of rheumatic fever. Their subsequent introduction of penicillin prophylaxis at the onset of streptococcal infection produced a sharp reduction in the incidence of rheumatic fever and rheumatic heart disease(3494, 3495).

John W. Gofman (US), Hardin B. Jones (US), Frank T. Lindgren (US), Tom P. Lyon (US), Harold A. Elliot (US), Beverly Strisower (US), William Mantz (US), John Hewitt (US), and Virgil Herring (US) identified the low-density lipoprotein (LDL) cholesterol and high-density lipoprotein (HDL) cholesterol using the ultracentrifuge technique. In addition, they found that 101 of 104 men with myocardial infarction had elevated LDL molecules—a finding which they had also observed in their cholesterol-fed atherosclerotic rabbits. They also observed an inverse relationship between HDLs and risk of coronary artery disease(3496, 3497). These papers are the origin of the concept of “good” cholesterol and “bad” cholesterol.

Jean Clark Dan (US-JP) described the acrosome reaction of sperm during the penetration of the egg in echinoderms, annelids, and mollusks. The acrosome reaction is characterized by two major physiological events: the exocytosis of the acrosomal vesicle and the extension of the acrosomal process(3498-3500).

Victor D. Vacquier (US), Gary W. Moy (US), Kirk S. Zigler (US), and Harilaos A. Lessios (US) isolated a protein associated with the inner acrosomal membrane and responsible for adhesion of sperm to sea urchin eggs. They named it bindin (3501, 3502).

Lewis G. Tilney (US), Daniel P. Kiehart (US), Christian Sardet (US), and Mary Tilney (US) determined that the acrosomal process is formed by the pH-dependent polymerization of actin(3503).

Charles G. Glabe (US) and Victor D. Vacquier (US) found that the bindin receptor in the vitelline coat of the sea urchin egg is a glycoprotein of more than 5 million daltons(3504).

Charles G. Glabe (US) and William J. Lennarz (US) found that bindin mediates the species-specific adhesion of sperm to egg(3505).

Jeffrey D. Bleil (US) and Paul M. Wassarman (US) found that in the mouse the bindin receptor is a zona pellucida component named ZP3(3506).

Jan Gosta Waldenström (SE) reported the association of liver cirrhosis and hypergammaglobulinemia, which is now recognized as chronic active hepatitis or autoimmune hepatitis (AIH)(3507, 3508).

Kurt R. Reissmann (US) concluded that under experimental hypoxia, erythropoiesis is stimulated not by the partial pressure of oxygen in the bone marrow directly but by a humoral factor elicited by the hypoxemia(3509).

Eugene Roberts (US) and Sam Frankel (US) isolated and identified the inhibitor gamma-aminobutyric acid (GABA) in the brain(3510). GABA was already known to exist in plant and other animal tissues.

William Clouser Boyd (US) blood typed people from all over the earth and separated them into 13 groups(3511).

Wilder Graves Penfield (US-CA) and Andrew Theodore Rasmussen (US) developed a map of the brain, often portrayed as a cartoon called the motor homunculus (miniature human being). This cartoon character has features drawn according to how much brain space they take up. Therefore, lips and fingers with their high number of nerve endings are larger than arms and legs(3512).

Frank A. Bassen (US) and Abraham L. Kornzweig (US) described abetalipoproteinemia (Bassen-Kornzweig syndrome). Symptoms include atypical retinitis pigmentosa, diffuse disease of the central nervous system, and crenated red blood cells(3513).

Norman R. Barrett (GB) first described the columnar metaplasia associated with chronic peptic ulcer of the esophagus and esophagitis(3514).

Philip Rowland Allison (GB) and Alan Stewart Johnstone (GB) noted an association of columnar metaplasia with gastroesophageal reflux(3515).

Andre P. Naef (CH), Luciano Ozzello (CH), Marcel Savary (CH), and Philippe Monnier (CH) were the first to systematically explore, describe, and photograph what today is the well-known pathology of progressively ascending columnar reparation of erosions due to gastroesophageal reflux and its association with adenocarcinoma(3516-3518).

Richard J. Cross (US) and John V. Taggart (US) found that thin slices of rabbit kidney cortex are capable of accumulating p-aminohippurate (PAH) from a saline suspending medium against a considerable concentration gradient. This process appears to be closely related to the tubular excretion of PAH in the intact animal. Acetate, which exhibits a striking stimulatory effect on PAH accumulation, is suggested as a possible rate-limiting cellular component of the PAH transport mechanism(3519).

Wilfred Gordon Bigelow (CA), John C. Callaghan (CA), and John A. Hopps (CA) amputated a man's frost-bitten fingers, in 1941. Contemplation of this operation later led them, along with William K. Lindsay (CA) and William F. Greenwood (CA), to began animal experiments where they found that when dogs are cooled, open-heart surgery can be performed over long periods -- much longer than four minutes -- and they are likely to survive. They showed that at lower temperatures, the tissues of the body and brain didn't need as much oxygen, and can survive without oxygenated blood for longer intervals(923, 3520).

Alfred Blalock (US) and C. Rollins Hanlon (US) described a palliative procedure to improve arterial oxygen saturation in patients with complete transposition of the great arteries. A surgical atrial septectomy is accomplished through a right lateral thoracotomy, excising the posterior aspect of the interatrial septum to provide mixing of systemic and pulmonary venous return at the atrial level(3521). Transposition of the great arteries is characterized by reversal of the aorta and pulmonary artery. The aorta receives the oxygen-poor blood from the right ventricle, but it's carried back to the body without receiving more oxygen. Likewise, the pulmonary artery receives the oxygen-rich blood from the left ventricle but carries it back to the lungs.

Ake Senning (SE) performed an operation for complete transposition of the great arteries in which venous return is directed to the contralateral ventricle by means of an atrial baffle fashioned in situ by using right atrial wall and interatrial septum. As a consequence, the right ventricle supports the systemic circulation(3522).

Langford Kidd (CA) and William Thorton Mustard (CA) described the hemodynamic effects of a totally corrective procedure in transposition of the great vessels(3523).

William J. Rashkind (US) and William W. Miller (US) introduced balloon atrioseptostomy (BAS) as palliation for transposition of the great arteries(3524).

Sang C. Park (US), James R. Zuberbuhler (US), Williams H. Neches (US), Cora C. Lenox (US), and Richard A. Zoltun (US) introduced catheter blade atrial septostomy to be used in place of balloon atrial septostomy if the atrial septum is thickened(3525).

Jean Rubay (FR), Yves Lecompte (FR), Alain Batisse (FR), Yves Durandy (FR), Alain Dibie (FR), Georges Lemoine (FR), and Pascal Vouhe (FR) presented a surgical methodology for the anatomic repair of anomalies of ventriculo-arterial connection (REV) involving direct anastomosis of the pulmonary trunk to the right ventricle(3526).

Richard H. Lawler (US), James W. West (US), Patrick H. McNulty (US), Edward J. Clancy (US), and Raymond P. Murphy (US) surgically excised a (free) human kidney allograft then transplanted it to a recipient nephrectomy site. The recipient was not immunosuppressed(3527).

Vladimir Demikhov (RU) described more than 20 different techniques for heart transplantation(3528).

James D. Hardy (US), Carlos M. Chavez (US), Frederick D. Kurrus (US), William A. Neely (US), Sadan Eraslan (US), M. Don Turner (US), Leonard W. Fabian (US), and Thaddeus D. Labecki (US) transplanted a chimpanzee's heart into a man. The heart was to small to support the circulation and failed after 2 hours(3529).

Christiaan Neethling Barnard (ZA), on Dec. 3, 1967, performed the first successful transplantation of a human heart. He transplanted the heart of a 23-year-old woman killed in a motor vehicle accident into the chest of a middle-aged man, Louis Washkansky. The recipient lived for eighteen days, until the powerful drugs used to suppress rejection weakened him and he died of pneumonia(3530-3533).

Eugene M. Bricker (US) developed an intestinal conduit to convey urine from both kidneys to a watertight external appliance for patients following a radical operations for pelvic cancer that involved the removal of the rectum as well as the bladder(3534).

Nancy Catherine Keever (US) characterized succession in an old field after agricultural use had ceased. She observed a predictable shift in plant community composition following field abandonment, with horseweed (Erigeron canadense) dominating fields one year after abandonment, white aster (Aster pilosis) dominating in year two, and broomsedge (Andropogon virginicus) dominating in year three (Figure 5). She found that life history strategies of individual species, seed dispersal, allelopathy (biochemical production by a plant which alters growth and survival of other plants or itself), and competitive interactions among species, led to this predictable pattern of succession(3535).

The National Science Foundation was established in the United States.

1951

“I believe, therefore, that just as the role of iron in biological reactions is now made completely understandable by the work of Otto Warburg as being necessary for the catalysis of oxygen transfer, so the role of phosphate compounds in the organisms is made understandable by their importance for energy transfer.” Otto Fritz Meyerhof(3536).

"The Creator, if He exists, has a special preference for beetles, and so we might be more likely to meet them than any other type of animal on a planet that would support life." John Burdon Sanderson Haldane (GB-IN). A comment made by J.B.S. Haldane during a lecture on the biological aspects of space flight given in 1951. He was referring to the fact that 25% of all known animal species are types of beetles.

Max Theiler (ZA-US) was awarded the Nobel Prize in Physiology or Medicine for his discoveries concerning yellow fever and how to combat it.

Axel Hugo Theodor Theorell (SE) and Britton Chance (US) developed a rapid spectrophotometric method for measuring the formation and disappearance of the compound of alcohol dehydrogenase (ADH) and reduced nicotinamide adenine dinucleotide (NADH) without appreciable interference from the absorption of NADH(3537).

Oliver H. Lowry (US), Nira J. Rosebrough (US), A. Lewis Farr (US), and Rose J. Randall (US) devised a method for the determination of protein(3538). This has become the most cited paper in the biological sciences.

Marian M. Bradford (US) developed a rapid and sensitive method for the quantification of microgram quantities of protein utilizing the principle of protein-dye binding(3539).

Arthur Nobile (US), William Charney (US), Preston L. Perlman (US), Hershel L. Herzog (US), Constance C. Payne (US), Maryann E. Tully (US), Margaret A. Jevnik (US), and Emanuel Benjamin Hershberg (US) succeeded in using bacteria to oxidize cortisone to prednisone and hydrocortisone to prednisolone. They found that these crude extracts of the corticosteroid prednisone were more than four times more effective than natural cortisones against arthritis in mice(3540, 3541). Prednisone was soon used to prolong kidney transplant survival.

Lord Alexander Robertus Todd (GB) presented an argument that the ribonucleic acids exist as polynucleotides with recurring 3’—5’ glycosidic linkages(3542).

Robert Burns Woodward (US), Franz Sondheimer (US), and David Taub (US) performed the total synthesis of both cholesterol and cortisone(3543, 3544).

Luis E. Miramontes (MX), George Rosenkrantz (MX), and Carl Djerassi (AT-US), following the methods of Russel E. Marker (US), synthesized 19-nor-progsterone, a powerful synthetic progesterone(3545).  

George Wallace Kenner (GB) carried out the total synthesis of natural ribonucleosides(3546).

Jordi Folch (ES-US) was the first to describe the presence of special proteins in rat brain myelin which could be solubilized in organic solvents (chloroform / methanol / water mixtures). These substances were named proteolipides and were considered as a novel lipoprotein but quite different from the other known lipoproteins(3547).

Marco Rabinovitz (US) Melvin P. Stulberg (US), Paul D. Boyer (US), Henry Arnold Lardy (US), and Harlene Wellman (US) reported that cellular respiration rates varied with the availability of inorganic phosphorus and phosphate acceptor(3548, 3549).

Giulio L. Cantoni (US) established the role of ATP in the enzymatic synthesis of a new metabolic intermediate (S-adenosyl methionine) which proved to be the methyl donor in numerous biological transmethylation reactions(3550).

Giulio Leonardo Cantoni (US) showed that S-adenosyl-methionone formed from ATP and methionine can donate its methyl group to one of the hydroxyl groups of catecholamines(3551).

Elizabeth Lee Hazen (US) and Rachel Fuller Brown (US) isolated the antibiotic nystatin from Streptomyces noursei(3552).

Elizabeth Lee Hazen (US), Rachel Fuller Brown (US), and Alice Mason (US) developed the first useful antifungal antibiotic. This was initially known as fungicidin, then Nystatin (named for "NY STATe Dept. of Health"), and finally Mycostatin. Mycostatin was isolated from Streptomyces noursei(3553). Hazen and Brown were awarded U.S. patent #2,797,183 in 1957.

Alexander C. Finlay (US), Gladys Lounsberry Hobby (US), Frank A. Hochstein (US), Thomas M. Lees (US), Tulita F. Lenert (US), J.A. Means (US), S.Y. P’An (US), Peter P. Regna (US), John B. Routien (US), Ben A. Sobin (US), K.B. Tate (US), Jasper H. Kane (US), Quentin R. Bartz (US), John Ehrlich (US), James D. Mold (US), Mildred A. Penner (US), and Robert M. Smith (US) isolated the antibiotic viomycin from Streptomyces puniceus and Streptomyces floridae(3554, 3555). This antibiotic binds to RNA and inhibits prokaryotic protein synthesis and certain forms of RNA splicing.

John Desmond Bernal (GB) proposed that one way in which organic subunits may spontaneously combine into larger molecules is by adsorption of the reacting molecules onto the highly ordered negatively charged aluminosilicates of clays. The clay surface performs a catalytic function(3556, 3557).

Alexander Graham Cairns-Smith (GB), P. Ingram (), and Gregory L. Walker () later proposed that under primitive Earth conditions organic polymers could have condensed on extremely thin layers of negatively charged aluminosilicates separated by layers of water(3558).

Jacques Lucien Monod (FR) and Melvin Cohn (US) renamed the lactase Monod had isolated from Escherichia coli in 1948 as beta-galactosidase(3559).

Martin B. Mathews (US), Albert Dorfman (US), and Saul Roseman (US) discovered that chondroitin sulfate is a substrate for hyaluronidase(3560).

Francis P.W. Winteringham (GB), Patricia M. Loveday (GB), and A. Harrison (GB) carried out the first comparative metabolic studies in which insects resistant to DDT (dichloro-diphenyl-trichloro-ethane or 2,2-di(4-chlorophenyl)-1,1,1-trichloroethane) were compared with those sensitive to it. They treated the insects with isotopically labeled (82Br) DDT then analyzed the metabolites with paper chromatography and radiometric scanners(3561).

David Shemin (US) and Jonathan B. Wittenberg (US) used isotopically labeled acetates and determined that 26 of the carbons in protoporphyrin are derived from acetate(3562).

Jean-Marie Wiame (BE) and Michael Doudoroff (RU-US), while exploring oxidative assimilation in Pseudomonas saccharophila, discovered that both carbons of acetate, carbons 2 and 3 of lactate, and the two methylene carbons of succinate are largely assimilated, whereas the carbonyl carbons of lactate and succinate are mainly converted to carbon dioxide. This indicated that the acetyl moieties derived from various substrates are probably a major source of assimilated carbon(3563).

Wolf Vishniac (US), Severo Ochoa (ES-US), L. Jonathan Tolmach (US), and Daniel Israel Arnon (US) demonstrated the photochemical reduction of pyridine nucleotide NADPox. (then called TPNox.) in catalytic amounts which drives the reductive carboxylation of pyruvic acid to malic acid(3564-3566).

Andrew Alm Benson (US), James Al Bassham (US), and Melvin Calvin (US) reported that the phosphate ester of sedoheptulose is part of the carbon assimilation pathway in photosynthesis(3567).

Andrew Alm Benson (US) discovered that a phosphate of ribulose is part of this same mechanism(3568).

Adele Millerd (AU), James Frederick Bonner (US), Bernard Axelrod (US), and Robert Bandurski (US) succeeded in obtaining from the mung bean (Phaseolus aureus), a cell-free preparation which catalyzes the aerobic oxidation of all of the members of the Krebs cycle. This strongly suggested that higher plants contain the Krebs cycle and oxidative phosphorylation(3569).

Feodor Felix Konrad Lynen  (DE), Ernestine Reichert (DE), Luistraud Kröplin-Rueff (DE), Luise Wessely (DE), and Otto Wieland (DE) formulated the chemical reaction scheme for the beta oxidation of fatty acids. Lynen named it the fatty acid cycle and noted that the key reaction consists of the thiolytic cleavage of the beta-keto acid by coenzyme A(2640, 2641, 3570). See, Franz Knoop, 1904.

Efraim Racker (PL-AT-US) showed that the conversion of glyoxal to glycolic acid by glyoxylase proceeds through a carboxyl-S-glutathione intermediate. This is significant because it was the first time that an “energy-rich” thioester of biological relevance was identified(3571).

Bernard David Davis (US) elucidated the complete biosynthetic pathway of aromatic amino acids from a common precursor, shikimic acid(3572).

Lester J. Reed (US), Betty G. DeBusk (US), Irwin Clyde Gunsalus (US), and Carl S. Hornberger, Jr. (US) crystallized and named alpha-lipoic acid; a catalytic agent associated with pyruvate dehydrogenase(3573). This chemical entity had been called the acetate-replacing/pyruvate oxidation factor.

Milon W. Bullock (US), John A. Brockman, Jr. (US), Ernest L. Patterson (US), Jack V. Pierce (US), and E.L. Robert Stokstad (US) synthesized DL-lipoic acid and established that it is 6,8-dithiooctanoic acid or 1,2-dithiolane-3-valeric acid(3574).

Hayao Nawa (JP), William T. Brady (US), Masahiko Koike (JP), and Lester J. Reed (US) determined that the functional form of lipoic acid occurs when the carboxyl group of lipoic acid is bound in amide linkage to the epsilon-amino group of a lysine residue in the acyltransferase component of the alpha-keto acid dehydrogenase complexes(3575). 

Masahiko Koike (US), Lester J. Reed (US), William R. Carroll (US), Prefulchandra C. Shah (US), Robert M. Oliver (US), Henry R. Henney, Jr. (US), Charles R. Willms (US), Tsuyoshi Muramatsu (US), Barid B. Mukherjee (US), and Eiji Ishikawa (US) dissected the pyruvate and alpha-ketoglutarate dehydrogenase complexes (PDH and KGDH respectively) into their component enzymes, characterized them, and reassembled the large functional units from the isolated enzymes. They found that functional units are composed of multiple copies of three enzymes: 1) a pyruvate and an alpha-ketoglutarate decarboxylase-dehydrogenase, 2) a dihydrolipoamide acetyltransferase and a succinyltransferase, and 3) a flavoprotein, dihydrolipoamide dehydrogenase. These three enzymes, acting in sequence, catalyze the decarboxylation of the alpha-keto acid, the subsequent reductive acylation of the lipoyl moiety, the acyl transfer to CoA, and the reoxidation of the dihydrolipoyl moiety with NAD-plus as the ultimate electron acceptor(3576-3583).

Tracy C. Linn (US), Flora H. Pettit (US), and Lester J. Reed (US) observed that the PDH complex, but not the KDGH complex, underwent a time-dependent inactivation in the presence of ATP. The PDH complexes are regulated by a phosphorylation-dephosphorylation cycle. Phosphorylation and concomitant inactivation of the complex is catalyzed by an ATP-dependent kinase, and dephosphorylation and concomitant reactivation are catalyzed by a magnesium ion-dependent phosphatase(3584). 

Roger Moss Herriott (US) demonstrated that bacteriophage ghosts consist entirely of protein(3585). Herriott wrote Alfred Day Hershey saying, “I’ve been thinking—and perhaps you have, too—that the virus may act like a hypodermic needle full of transforming principles; that the virus as such never enters the cell; that only the tail contacts the host and perhaps enzymatically cuts a small hole through the outer membrane and then the nucleic acid of the virus head flows into the cell”(3586).

Salvador Edward Luria (IT-US) demonstrated that bacteriophage reproduce in an exponential fashion within the host cell(3587).

Jacques Lucien Monod (FR), Germaine Cohen-Bazire (FR), and Melvin Cohn (US) concluded that an enzyme inducer for beta-galactosidase does not induce because it is a substrate nor through its combination with pre-formed active enzyme, but rather at the level of another specific cellular constituent(3588, 3589). This paper disproved the hypothesis that the process of induction depends on an interaction of the inducer with the enzyme.

Gunnar Östergren (SE) explained the difference in chromosome movement seen in ordinary mitosis and the first division of meiosis by meticulous investigation of the first meiotic division in several plants where he found that a key difference lay in the arrangement of the kinetochore regions. In mitosis, the kinetochore is arranged on two opposite sides of the chromosome, but during the first meiotic division, the whole kinetochore is arranged on one side of the chromosome body. "Both the kinetochores of a bivalent can sometimes be seen to move actively towards the same spindle pole (during metaphase)", he wrote. "During these random movements the kinetochores of the paired chromosomes, sooner or later, happen to pull on their partners. This pull, in connection with the one-sided arrangement of the kinetochore on the chromosome body, results in an orientation of the partner kinetochores towards opposite spindle poles, i.e., it produces the co-orientation"(3590).

Jan Mohr (DK) discovered the Lutheran-secretor linkage in man as a linkage of the Lutheran blood group and the 'recessive' Lewis blood group. It was the first autosomal linkage identified in man(3591, 3592).

Myron K. Brakke (US) used density-gradient centrifugation in sucrose solutions to purify a plant virus(3593, 3594).

Thomas Foxen Anderson (US) described techniques for the preservation of three-dimensional structure in preparing specimens for the electron microscope(3595)(Anderson 1951). 

Theodosius Grigorievich Dobzhansky (Ukrainian-US) found that Drosophila pseudoobscura exhibited regular seasonal variations in different types of chromosomal inversions(3596, 3597). These flies were well known for their inversion polymorphism.

Theodosius Grigorievich Dobzhansky (Ukrainian-US), Natasha P. Spassky (US), Howard Levene (US), and Olga Pavlovsky (US) were able to show that a variety of factors which vary with season, including temperature, food type and amount of intraspecific competition, affects the fitness of these chromosomal arrangements, thus accounting for the seasonal variation in inversion types. The reason the polymorphism is maintained is because the various inversion heterozygotes generally have higher fitness than their homozygotes(3596, 3598-3600).

Victor J. Freeman (US) discovered that toxigenic diphtheria bacilli are infected by a specific bacterial virus called ß-phage(3601).

H. Herbert Fox (US) discovered that isoniazid (isonicotinic acid hydrazide) is antibacterial for Mycobacterium tuberculosis, M. bovis, M. africanum, and M. microti(3602, 3603).

Walsh McDermott (US), Carl Muschenheim (US), Richard B. Maxwell (US), Charles M. Clark (US), DuMont F. Elmendorf, Jr. (US), William C. Cawthon (US), Clarence Jordahl (US), Roger DesPrez (US), and Kurt Deuschle (US) established the great efficacy of isoniazid drugs in the treatment of tuberculosis, meningitis and generalized miliary tuberculosis(3604-3606).

Jack Bernstein (US), William A. Lott (US), Bernard A. Steinberg (US), Harry L. Yale (US), William Steenken, Jr. (US), Gordon M. Meade (US), Emanuel Wolinsky (US), and E. Osborne Coates, Jr. (US) introduced isoniazid (isonicotinic acid hydrazide) as a chemotherapeutic antimycobacterial agent(3607, 3608).

Hans Meyer (CZ) and Josef Mally (CZ) were the first to synthesize isoniazid (isonicotinic acid hydrazide)(3609). 

Leslie W. Mapson (GB) and David Rockwell Goddard (US) showed that tri-phospho-pyridine nucleotide (TPN; coenzyme II) serves as a hydrogen donor in the reaction of an enzyme they characterized and named glutathione reductase(3610, 3611).

Gottfried Samuel Fraenkel (DE-US) showed that, with some rare exceptions, insects have the same nutritional requirements as man(3612, 3613).

Edward Arthur Steinhaus (US) recognized the potential of Bacillus thuringiensis as a control agent for certain insect pests. He investigated its pathogenic characteristics, including the associated endotoxin(3614).

Ludwik Gross (Ludwig Gross) (PL-US) described the induction of leukaemia in newborn mice by means of a cell-free extract of tissues from mice suffering with spontaneous leukaemia(3615). By showing that a virus causes mouse leukaemia and can be passed naturally from generation to generation Gross gained the attention of scientists who had largely ignored the role of viruses in cancer, even though in 1908, researchers had suggested a viral cause by transmitting leukaemia and sarcomas in chickens.

Preben von Magnus (DK) reported the presence of noninfectious incomplete virus capable of interfering with influenza virus in chick embryos(3616-3618).

Jordi Casals (ES-US), Peter K. Olitsky (US), and Ralph O. Anslow (US) adapted type 2 poliomyelitis virus to suckling mice and showed that the brains of these animals contained antigen in sufficient concentration to fix complement with poliomyelitis antisera(3619).

Chester W. Emmons (US) discovered that soil and pigeon habitats are both natural reservoirs of Cryptococcus neoformans(3620, 3621).

Sajiro Makino (JP) was the first to introduce the use of the peritoneal cavity of animals as a place for growing cells in culture. These are frequently referred to as ascites tumor cultures(3622).

Libbie Henrietta Hyman (US) recommended using the phylum name Aschelminthes to include the classes: Rotifera, Gastrotricha, Kinorhyncha, Nematoda, Priapulida, and Nematomorpha(3623).

Stephen V. Boyden (GB) discovered that treatment of sheep erythrocytes with suitable concentrations of tannic acid renders them capable of adsorbing certain protein molecules from solution in saline. Red cells which have adsorbed proteins in this way are agglutinated after washing by the homologous antiprotein sera, even by high dilutions(3624).

D. Anderson (GB), Rupert Everett Billingham (GB-US), G.H. Lampkin (GB), and Peter Brian Medawar (GB) demonstrated mutual tolerance to skin grafts by freemartin cattle twins and speculated that actively acquired tolerance was responsible(3625).

Bodil M. Schmidt-Nielsen (US) and Knut Schmidt-Nielsen (US) reported that the kangaroo rat possesses interesting adaptations to the desert life including: no sweat glands, nocturnal behavior, reduced surface temperature in the nasal passages, exceptionally concentrated urine, lack of the need to drink, and coprophagic behavior(3626).

Leon L. Miller (US), Chauncey G. Bly (US), Michael L. Watson (US), and William F. Bale (US) developed an isolated rat liver perfusion apparatus, which along with 14C labeled lysine, allowed them to demonstrate that the rat liver plays a dominant role in the synthesis of albumin, fibrinogen, and plasma globulins(3627).

Leon L. Miller (US) and William F. Bale (US) would show that the liver does not synthesize gamma globulin(3628).

Lawrence G. Brock (AU), Jack S. Coombs (AU), Sir John Carew Eccles (AU), and Paul Fatt (AU) studied the chemical action at nerve synapses by means of microelectrodes inserted within the nerves themselves. They, along with P. Fatt (AU), were able to work out the chemical changes in considerable detail(3629-3631).

Viktor Hamburger (DE-US) and Howard L. Hamilton (US) presented their study of the normal development of the chick embryo. It summarizes the major developmental landmarks of the chick(3632).

Alfred Glücksmann (GB) proposed that cell death (apoptosis) occurs during the normal development and maintenance of the tissues and organs of vertebrates(3633). 

Min Chueh Chang (CN-US) and Colin R. Austin (GB) independently found that sperm must undergo an incubation period within the female reproductive tract before they acquire fertilizing capacity(3634-3636). Austin would name this phenomenon sperm capacitation. Chang and his associates would subsequently show that capacitation is common among mammals.

Arthur Davis Hasler (US), Allan T. Scholz (US), and Robert W. Goy (US), and Warren J. Wisby (US) proposed the "imprinting hypothesis" to explain homing of fishes such as the salmon. This hypothesis states that recognition of the home stream results from a relatively rapid odor learning process during a sensitive period called the smoltification process(3637, 3638).

Hans Nordeng (NO) presented another hypothesis in which he speculated that smolts that migrate to the ocean, release population specific odors called pheromones. It's these pheromones, in the end, that are used by mature adults as cues to guide them back to their home stream(3639). Evidence supporting both the imprinting and pheromone hypothesis has accumulated.

Min Chueh Chang (CN-US) found that of two million sperm deposited in the vagina of a rabbit only about 1% make it past the cervical barrier to the uterine cavity and only about 5,000 find their way past the utero-tubal junction. Fewer still reach the site of fertilization in the outer segment of the oviduct. These findings contradict the notion that swarms of sperm are necessary to penetrate the follicular cells surrounding the oocyte, the cumulus oophorus, and corona radiata. Chang showed that the physiological integrity of the individual sperm is the most important factor in its success in fertilizing the ovum. He found that a single sperm is capable of penetrating the cumulus mass of cells and reaching the zona pellucida, a thick mucoprotein membrane surrounding the ovum. Chang posited that every population of sperm is composed of some that are strong and others weak, morphologically defective, or aged. The larger the population the more likely a physiologically strong sperm is to reach the ovum(3635). 

Fred H. Allen, Jr. (US), Louis Klein Diamond (US), and Bevely Niedziela (US) discovered the Kidd blood group antigens(3640).

Frederic Crosby Bartter (US), Fuller Albright (US), Anne P. Forbes (US), Alexander Leaf (US), Eleanor Dempsey (US), and Evelyn Carroll (US) deduced that the common virilizing form of adrenal hyperplasia is fundamentally a type of adrenocortical insufficiency arising from a metabolic error in the biosynthetic pathway to corticol. They suggested that in an attempt to compensate the pituitary secretes even more ACTH leading to the secretion of excessive amounts of other classes of adrenal steroids. They successfully treated this condition using cortisone(3641).

Fritz A. Freyhan (US), Rachel B. Woodford (US), Seymour Solomon Kety (US), Darab K. Dastur (US), Mark H. Lane (US), Douglas B. Hansen (US), Robert N. Butler (US), Seymour Perlin (US), and Louis Sokoloff (US) concluded that cerebral circulation and oxygen consumption are not diminished in the normal elderly individual, but show a significant reduction, highly correlated with the degree of mental impairment, in senile dementia(3642, 3643).

John Julian Wild (GB-US) is considered by most to be the true founder of ultrasonic tissue diagnosis. Working with Donald Neal (US), an engineer, and John M. Reid (US) Wild published on uni-directional A-mode ultrasound investigations into the thickness of surgical intestinal material and later on the diagnosis of intestinal and breast malignancies(3644, 3645).

John Julian Wild (GB-US), Harry D. Crawford (US) and John M. Reid (US) used echocardiography to identify a myocardial infarction in vitro using both M mode and 2D echo(3646).

Ralph Milton Waters (US) penned his important book on chloroform anesthesia, Chloroform—A Study After 100 Years(3647). 

Hans von Brücke (AT), Karl Heinz Ginzel (DE), Hans Klupp (DE), F.A. Pfaffenschlager (DE), and Gerhard Werner (DE) performed the first clinical trials of the anesthetic succinylcholine (suxamethonium chloride )(3648). It is a nicotinic acetylcholine receptor agonist, used to induce muscle relaxation and short-term paralysis, usually to facilitate tracheal intubation. It is used as a paralytic agent for euthanasia/immobilization of horses. Despite its adverse effects, including life threatening malignant hyperthermia, hyperkalaemia, and anaphylaxis, it is perennially popular in emergency medicine because it arguably has the fastest onset and shortest duration of action of all muscle relaxants.

Derek Ernst Denny-Brown (NZ-GB-US) and Huntington Porter (US) reported the use of BAL (British anti-lewisite) treatment for Wilson’s disease (progressive hepatolenticular degeneration)(3649). Named for Samuel Alex Kinnier Wilson (GB). This discovery was one of the first effective treatments for a neurological condition.

Sheldon S. Waldstein (US), Hans Popper (AT-US), Paul B. Szanto (US), and Frederick Steigmann (US) introduced the technique of liver biopsy using a needle(3650).

Brian McArdle (GB) first described glycogen storage disease type 5, following his examination of a male patient, 30 years of age, who reported the condition as having been present "all his life"(3651). Symptoms are muscular pain, fatigability, and muscle cramping following exercise.

Wilfred F.H.M Mommaerts (US), Barbara Illingworth (US), Carl M. Pearson (US), Richard J. Guillory (US), and K. Seraydarian (US) found that this inborn abnormal accumulation of glycogen in muscle tissue is due to a phosphorylase B deficiency(3652).

Richard Alan John Asher (GB) described and named Munchausen syndrome by proxy (Baron von Munchausen). This is a form of child abuse in which a parent, usually the mother, induces or reports physical symptoms in a child and fabricates a corresponding history that results in unnecessary medical evaluation and treatment(3653, 3654).

C. Miller Fisher (US) discovered that carotid bifurcation occlusive disease is the major preventable cause of stroke and transient ischemic attack(3655, 3656).

Charles A. Hufnagel (US) developed and implanted artificial valves in the descending aortas of dogs(3657).

Charles A. Hufnagel (US), W. Proctor Harvey (US), Pierre J. Rabil (CA), Thomas F. McDermott (US), Paulo Diaz Vilkgas (US), and Hector Nahas (US) went on to perform the operation on humans(3658, 3659).

Nina Starr Braunwald (US), Theodore Cooper (US), and Andrew G. Morrow (US) reported the complete replacement of the mitral valve with a flexible polyurethane prosthesis(3660).

Albert Starr (US) and M. Lowell Edwards (US) replaced the mitral valve in a human with a cage-ball valve(3661).

Donald N. Ross (ZA-GB) reported a homograft replacement of the aortic valve(3662).

René Küss (FR), J. Teinturier (FR), and Paul Milliez (FR) transplanted free kidneys and kidneys from guillotined donors using no immunosuppression. Their surgical techniques were pioneering and became popular(3663). 

Fritz Zöllner (DE) and Horst Wullstein (DE) worked out the principles of the use of microscopy in operations on the eardrum and within the middle ear. ref

Ernst Walter Mayr (DE-GB-US) invented the concept of genetic revolution in which he concluded that the mere change of the genetic environment may change the selective value of a gene very considerably. Isolating a few individuals (the "founders" from a variable population which is situated in the midst of the stream of genes which flows ceaselessly through every widespread species will produce a sudden change of the genetic environment of most loci(3664, 3665).

John Gordon Skellam (GB) develops the reaction-diffusion model of invasion biology. This model describes the dynamics of populations, which simultaneously develops and spreads, and provides that the invasion front moves with constant speed(3666).

Ralph Stefan Solecki (US) and coworkers, from 1951-1960, examined the Shanidar cave in North Central Iraq for fossil remains. Nine partial Homo sapiens neanderthalensis; Homo neanderthalensis skeletons were removed(3667, 3668). The specimens have been dated between 25k-54k B.P. 

1952

“The pseudo prestige of long and difficult words transcends the useful scientific term and diffuses widely through our papers. Simple things are made complicated, and the complex is made incomprehensible. Chaos reigns. The so-called medical literature is stuffed to bursting with junk, written in a hopscotch style characterized by a Brownian movement of uncontrolled parts of speech which seethe in restless unintelligibility.” William Bennett Bean(3669).

Archer John Porter Martin (GB) and Richard Laurence Millington Synge (GB) were awarded the Nobel Prize in Chemistry for their invention of partition chromatography.

Selman Abraham Waksman (RU-US) was awarded the Nobel Prize in Physiology or Medicine for his discovery of streptomycin, the first antibiotic effective against tuberculosis.

Georges Nomarski (PL-FR) devised and patented the system of differential interference contrast (DIC) for the light microscope that bears his name(3670, 3671).

Robert Day Allen (US), George B. David () and Georges Nomarski (PL-FR) defined the basic principles of the differential interference contrast (DIC) technique and the interpretation of images. They assisted the Zeiss Optical Company in developing a working model of the Nomarski differential interference microscope(3672).

Robert Cooley Elderfield (US) and Eleanor Werble (US) synthesized primaquine (pamaquine, or plasmoquine), an antimalarial drug(3673).

Raymond J. Dern (US), Irwin M. Weinstein (US), George V. LeRoy (US), David W. Talmage (US), and Alf S. Alving (US) established that sensitivity to the hemolytic action of primaquine was due to an intrinsic abnormality of the erythrocytes of sensitive subjects(3674).

Prantosh K. Bhattacharyya (IN), Herbert E. Carter (US), Gottfried Samuel Fraenkel (DE-US), and Katharine R. Weidman (US) isolated, crystallized, and identified carnitine(3675).

Gottfried Samuel Fraenkel (DE-US), Stanley Friedman (US), Prantosh K. Bhattacharyya (IN), and Jon Bremer (NO) established the role of carnitine as a carrier of acetyl groups through the mitochondrial membrane(3676-3678).

Walter Voser (CH), M.W. Mijovic (), Hans Heusser (CH), Oskar Jeger (CH), and Leopold Stefan Ruzicka (HR-CH) synthesized lanosterol and showed that it is structurally 4,4,14-trimethylcholestane; similar to both cholesterol and squalene(3679, 3680). In the 1953 paper Ruzicka mentions that in 1925 Edwin Alfred.A. Rudolph (CH) in his doctoral thesis stated, “The hypothesis may be formulated that the steroids and the triterpenes have at least partially a common originancestor(3681).”

Hilary M. Grundy (CH), Sylvia A. Simpson (CH), James F. Tait (CH), Albert Wettstein (CH), Robert Neher (CH), Joseph von Euw (CH), Tadeus Reichstein (PL-CH), and Othmar Schindler (CH) identified, characterized, isolated, and named aldosterone; a highly active mineralocorticoid hormone from the beef adrenal gland(3682-3685).

John Norman Porter (US), Reginal I. Hewitt (US), Clifford W. Hesseltine (US), George Charles Krupka (US), James A. Lowery (US), Wyeth S. Wallace (US), Nestor Bohonos (US), and James H. Williams (US) isolated the antibiotic achromycin (puromycin) from Streptomyces alboniger(3686).

Michael B. Yarmolinsky (US) and Gabriel L. de la Haba (US) discovered that puromycin inhibits the incorporation of amino acids into proteins(3687). 

Puromycin causes the premature release of nascent polypeptide chains by its addition to the growing chain end in both prokaryotes and eukaryotes. 

F.I. Dessau (), Robert L. Yeager (US), F.J. Burger (), James H. Williams (US), and William G.C. Munroe (CA) described pyrazinamide (aldinamide) as an antituberculosis agent(3688-3690).

H.J. Robinson (US), H. Siegel (US), and Joseph J. Pietrowski (US) were the first to clinically employ pyrazinamide as an antimycobacterial agent(3691).

Efraim Racker (PL-AT-US) and Isidore Krimsky (US) showed that during glycolysis the aldehyde group of glyceraldehyde 3-P reacts with an enzyme-bound sulfhydryl group, resulting in a thio-hemiacetal which is oxidized to an energy rich thioester, and that this thioester is phosphorylated by inorganic phosphate to 1,3 diphosphoglyceric acid(3692). This explanation of the mechanism by which a biological oxidation is coupled to ATP formation still ranks as one of the most important biochemical discoveries of all time.

Daniel M. Brown (GB), Lord Alexander Robertus Todd (GB), Charles A. Dekker (US), and A. Michael Michelson (GB) described the precise phosphate-ester linkages that bond nucleotides together. They concluded that these linkages are always the same, with the phosphate group connecting the 5’ carbon of one deoxyribose residue to the 3’ carbon atom of the successive nucleotide. They reasoned that the polynucleotide chains of DNA are linear(3693, 3694).

Bernard David Davis (US) and Werner K. Maas (US) used temperature-sensitive pantothenate-requiring mutants to demonstrate that a mutation can alter an enzyme(3695, 3696). 

Alexander L. Dounce (US) proposed that the order of amino acids in a specific protein is determined by an order of nucleotides in a corresponding nucleic-acid molecule(3697, 3698).

Jacques Lucien Monod (FR), Germaine Cohen-Bazire (US), Alwin Max Pappenheimer, Jr. (US), David Swenson Hogness (US), and Melvin Cohn (US) used the synthesis of beta-galactosidase in Escherichia coli to demonstrate that proteins are synthesized completely anew rather than by adding a few amino acids to a pre-existing protein(3699, 3700).

Alfred Day Hershey (US), June Dixon (US), and Martha Cowles Chase (US) observed that a particular fraction of RNA molecules is rapidly synthesized and then degraded following the infection of Escherichia coli by T2 virus(3701). Others would later show that this fraction was messenger RNA.

James M. McGuire (US), Robert L. Bunch (US), Robert C. Anderson (US), Harold E. Boaz (US), Edwin H. Flynn (US), H.M. Powell (US), and J.W. Smith (US) isolated erythromycin among the metabolic products of Streptomyces erythreus waksman, from soil obtained in the Philippines(3702). Erythromycin blocks the translocation reaction on ribosomes in prokaryotes only.

Fred W. Tanner, Jr. (US), Arthur R. English (US), Thomas M. Lees (US), and John B. Routien (US) isolated the antibiotic carbomycin from Streptomyces halstedii(3703).

C. Stacy French (US) and Victoria M.K. Young (US) demonstrated the fluorescence spectra of red algae and the transfer of energy from phycoerythrin to phycocyanin then on to chlorophyll a(3704). 

Louis Nicole Marie Duysens (NL) quantitatively determined the efficiency of excitation energy transfer from various accessory pigments (chlorophyll b; phycocyanin; phycoerythrin; fucoxanthin) to chlorophyll a. He was the first to use “P” for pigment designating a few chlorophyll a or bacteriochlorophyll molecules—later to be called P870(3705).

Bessel Kok (NL-US) found that there exists a photosystem containing a pigment (a special form of chlorophyll a) absorbing light maximally at around 700 nanometers. He called it P700(3706-3708). This later became known as photosystem 1.

Bessel Kok (NL-US) and George Hoch (US) made the first explicit statement that there must be two photochemical reactions “the first sensitized by chlorophyll a and a direct photochemical bleaching of P700; the second sensitized by accessory pigment, acting indirectly via mediation of dark steps, and restoring P700”(3709). This paper, presented a year before publication, opened the modern era of thinking about photosynthesis.

Robert Lee Hill (GB), Fay Bendall (GB), Louis Nicole Marie Duysens (NL), Jan Amesz (NL), and Bert M. Kamp (NL) presented very strong evidence that the light reactions of photosynthesis contain two light absorbing photosystems working in series(1680, 3710).

Günter Döring (DE), Gernot Renger (DE), Joachim Vater (DE), and Horst Tobias Witt (DE) discovered photosystem 2 and noted that it contains a form of chlorophyll a absorbing light maximally around 680 nanometers (P680)(3711).

Dilworth Wayne Woolley (CA-US), G. Schaffner (US), and Armin C. Braun (US) determined that a toxin produced by Pseudomonas tabaci causes wild fire disease in tobacco (Nicotiana tabacum) and is an antimetabolite of methionine(3712).

George Henry Hepting (US), E. Richard Toole (US), and Jack S. Boyce, Jr. (US) discovered the role of mating types in the life history of the oak wilt fungus(3713).

Johannes M. Müller (CH), Emil Schlittler (CH), and Hugo J. Bein (CH) isolated from the Indian snakeroot (Rauwolfia serpentina) an alkaloid which has profound effects on the central nervous system. They named it reserpine(3714). Also called serpasil.

Louis Dorfman (US), Charles F. Huebner (US), Harold B. MacPhillamy (US), Emil Schlittler (CH), Arthur F. St. André (US), Andre Furlenmeier (CH), Robert A. Lucas (US), Johannes M. Müller (CH), Robert Schwyzer (CH), Ernest Wenkert (US), Liang H. Liu (US), Patrick A. Diassi (US), Frank L. Weisenborn (US), Christiane M. Dylion (US), Oskar Winterseiner (US), Eugene E. Van Tamelen (US), and Paul D. Hance (US) worked out the structure of reserpine(3715-3722). 

Robert Wallace Wilkins (US) and Walter E. Judson (US) introduced the use of reserpine to treat high blood pressure in 1953. They reported on its outstanding sedative and tranquilizing effects(3723). Reserpine depletes post-ganglionic adrenergic neurons containing norepinephrine as their neurotransmitter. This action is responsible for the usefulness of reserpine in the treatment of hypertensive, nervous, and mental disorders. It is without doubt the most valuable tranquilizer ever isolated from plants.

Robert Burns Woodward (US), F.E. Bader (CH), H. Bickel (CH), Albert J. Frey (CH-US), and Richard W. Kierstead (CA) synthesized reserpine(3724, 3725).

Nathan Entner (US) and Michael Doudoroff (RU-US) studied the enzymatic oxidation of glucose in Pseudomonas saccharophila and identified glucose-6-phosphate, 6-phosphoglunonate, D-glyceraldehyde-3-phosphate, 3-phosphoglycerate, and pyruvate as intermediate products. A novel feature of this pathway is the conversion of 6-phosphogluconate to pyruvate and glyceraldehyde-3-phosphate. 2-keto-3-deoxy-6-phosphogluconate was postulated to be an intermediate in this reaction(3726).

Joseph MacGee (US) and Michael Doudoroff (RU-US) proved that 2-keto-3-deoxy-6-phosphogluconate is an intermediate in this pathway(3727). This oxidative pathway became known as the Entner-Doudoroff pathway.

Harold R. Yust (US) and Frederick F. Shelden (US) reported that cyanide-resistant California red scale (Aonidiella aurantii) insects have a tissue-respiratory electron-transport system less dependent on cytochrome oxidase(3728). The resistance was found to be inherited as if it were due to a single sex-linked gene.

Sijiro Makino (JP) and Isao Nishimura (JP) were the first to expose cells to hypotonic solutions for the express purpose of enhancing chromosome analysis(783).

Tao-Chiuh Hsu (US) developed a technique which greatly improved the microscopic observation of chromosomes. It used a solution with a lower salt concentration than the cells it contains. This causes the cells to absorb water through their membranes and swell (but not burst). The swollen cells allow the chromosomes to readily separate, making them easier to count(781). Using this technique the correct chromosome number for man—46—was established by Tjio and Levan in 1956.

Hugh Esmor Huxley (GB) demonstrated that the myofibrils of striated (skeletal) muscle cells contain two major types of myofilaments arranged in such a manner that they present bands (I and A), lines (Z and M), and the H zone. Each thick myofilament is surrounded by six thin myofilaments with cross bridges between adjacent thick and thin myofilaments(3729-3732). 

Wolfgang Beerman (DE) interpreted chromosomal puffs in the midge Chironomus tentans as indicating gene activity and their tissue-specific patterns as indicating a differential genetic activity in different cell types, "the first direct cytological indication for the single elements of the genome reacting differentially to internal and external conditions" (3733).

Howard K. Schachman (US), Arthur Beck Pardee (US), and Roger Yate Stanier (CA) demonstrated that Escherichia coli cells contain microsomal (ribosomal) particles(3734).

C. Cosar (FR), Leon Ninet (FR), Sylvie Pinnert-Sindico (FR), and Jean Preud’homme (FR) isolated the antibiotic spiramycin from Streptomyces ambofaciens(3735, 3736). This antibiotic has been used to treat gonorrhoea, trachoma, and sinusitis. It inhibits the incorporation of [14C]amino acids into protein without affecting RNA synthesis.

James Theodore Park (US), Jack Leonard Strominger (US) and Richard E. Thompson (US) initiated the biochemical investigations which ultimately determined that penicillin acts by inhibiting murein synthesis in the bacterial cell wall(3737-3742). This is the first discovery of the mode of action of a natural antibiotic.

August H. Doermann (US) discovered that with bacteriophages the infectivity associated with the original parental phage is lost at the outset of the reproductive process, since no infective phages whatsoever were found in any of the infected bacteria lysed artificially within the first ten minutes following infection. The time course that elapses between infection and the first intracellular reappearance of infective phage particles is called the eclipse (3743).

Alfred Day Hershey (US) and Martha Cowles Chase (US) prepared virus particles that were isotopically labeled either in the protein or in the DNA by incubating the host bacteria in media containing appropriate labeled precursors. With such labeled virus particles they showed conclusively that viral DNA rapidly enters the host cell whereas viral protein does not. These observations were later followed by the demonstration that the viral nucleic acid alone is infectious, in the absence of viral protein, and can lead to the formation of complete viral progeny in the host cell(3744).

Joshua Lederberg (US) and Esther M. Lederberg (US) developed the replica plate technique to screen large populations of bacteria for rare mutants. This technique has remained one of the most important methodologies in the practice of bacterial genetics, finding wide application as an efficient way to isolate auxotrophic mutants(3745).

Hugh John Forster Cairns (GB-US-GB), Margaret Edney (AU), S. Fazekas De Saint Groth (AU), and P.J. Mason (GB) discovered that influenza virus is not released from the host cell in a burst but rather is released in a slow trickle through the cell membrane(3746, 3747).

Harriette Block Wasser (US) was the first to demonstrate an insect virus not associated with inclusion bodies(3748).

William M. Hammon (US) and William C. Reeves (US) were the first to isolate and identify the bunyavirus; etiological agent of California encephalitis in man(3749). La Crosse encephalitis is caused by a very closely related virus.

Renato Dulbecco (IT-US) was the first to demonstrate that an animal virus can produce lytic plaques in a lawn of confluent animal cells(3750). He and Marguerite Vogt (US) developed a method to plaque poliovirus in cell culture, i.e., to enumerate infectious virus particles in a stock of virus by detecting one focus of dead cells per infectious particle(3751). 

Marvin P. Bryant (US) isolated and characterized a small rumen spirochete of the genus Treponema which could move through agar and compete with cellulolytic bacteria for use of the soluble sugars produced by the cellulolytic bacteria. This was the first published work on fermentation products of a spirochete(3752).

René Jules Dubos (FR-US) states that the will-‘o’-the-wisp, perhaps better known as Jack O’ Lantern, is probably a microbial phenomenon and may result from the spontaneous ignition of phosphine in the presence of methane(3753).

Salvador Edward Luria (IT-US), Mary Human (US), Giuseppe Bertani (US) and Jean J. Weigle (CH-US) discovered host restriction of bacteriophage replication among certain strains of bacteria(3754, 3755). This work led to the discovery of restriction endonucleases.

Rhoda Benham (US), Margarita Silva (US), Libero Ajello (US), Lucille K. Georg (US), LaVerne B. Camp (US), and Harold E. Swartz (US) pioneered nutritional and physiological studies of the dermatophytes(3756-3761). This greatly simplified the identification of the dermatophytes.

George Otto Gey (US), Ward D. Coffman (US), and Mary T. Kubicek (US) established the first permanent in vitro human cell line. The cells were derived from a human cervical carcinoma in a patient named Henrietta Lacks née Pleasant (US). Later these cells became known as the HeLa cell line(3762, 3763).

Curt Stern (DE-US), Gweneth L. Carson (US), M. Kinst (US), Edward Novitski (US), and Delta E. Uphoff (US) established that the average viability of heterozygotes for sex-linked lethals is 96.5%(3764).

Anthony D. Bradshaw (GB) found evidence in grasses for natural selection of genotypes tolerant to high concentrations of heavy metals(3765).

Alexander Thomas Dick (AU) showed that an unknown dietary constituent besides molybdenum has an effect on copper storage in livers of sheep(3766). He subsequently found that inorganic sulfate is the component of alfalfa that lowers the blood molybdenum(3767) and that sulfate is also the factor in alfalfa that, in combination with molybdenum, impairs liver copper storage(3768, 3769).

Neville F. Suttle (GB) pointed out that the formation of cupric tetrathiomolybdate, a highly insoluble complex, could occur in the sulfide-rich environment of the rumen(3770).

Alexander Thomas Dick (AU) found that formation of copper thiomolybdates, particularly CuMoS4, in the rumen accounts for the poor absorption of copper when the intake of molybdenum is high(3771).

George J. Brewer (US), Robert D. Dick (US), Virginia Johnson (US), Yuxan Wang (US), Vilma Yuzbasiyan-Gurkan (US), Karen J. Kluin (US), and Alex M. Aisen (US) used tetrathiomolybdate to treat Wilson's disease in human patients. This genetic disease results in accumulation of copper in tissues, and thiomolybdate counteracts copper toxicity by complexing with the cupric ion thus preventing its absorption(3772).

Clinton Nathan Woolsey (US), Paul H. Settlage (US), Donald R. Meyer (US), W. Sencer (US), Teresa Pinto-Hamuy (CL), Ann M. Travis (US), William S. Coxe (US), Jean Francois Hirsch (FR), Robert M. Benjamin (US), Wally I. Welker (US), and Richard F. Thompson (US) mapped the primary and supplementary motor areas of the cerebral cortex and compared sensory and motor maps in both pre- and post-central cortical areas in primates and other animals(3773-3775).

Laurance W. Kinsell (US), John W. Patridge (US), Lenore A. Boling (US), Sheldon Margen (US), and George D. Michaels (US) demonstrated that the isoenergetic substitution of vegetable oils for animal fats significantly decreased serum cholesterol in humans(3776).

Alan M. Turing (GB) showed that developmental patterns could be generated by simple chemical reactions, together with diffusion, which marked a change in how the processes of development were viewed. In this work he made the first applications of computer modeling in biology(3777).

Rosemary A. Biggs (GB), Alexander Stuart Douglas (GB), Robert Gwyn Macfarlane (GB), John Vivian Dacie (GB), W. Robert Pitney (GB), Clarence Merskey (ZA), and John Richard O'Brien (GB) identified and named Christmas factor (factor IX) as one of the materials necessary for normal blood clotting(3778). Stephen Christmas, a five year old British boy was the first patient in whom this was recognized to be different from classical hemophilia. This disease is sometimes called hemophilia B.

Paul M. Aggeler (US), Sidney G. White (US), Mary Beth Glendening (US), Ernest W. Page (US), Tillie B. Leake (US) and George Bates (US) described this same condition almost simultaneously, in a 16-year old boy, calling the factor plasma thromboplastin component (PTC)(3779).

Irving Schulman (US) and Carl H. Smith (US) also independently reported this metabolic disease(3780). 

Ogden Carr Bruton (US) discovered the first scientifically established immunodeficiency disease. He reported on a young patient who was missing the gamma fraction of serum resulting in recurrent bacterial infections(3781). The disease was named Bruton’s agammablobulinemia in his honor. Subsequently, it was discovered that patients with agammaglobulinemia resisted viral infections and demonstrated normal delayed-hypersensitivity responses. These observations ultimately led to the recognition of the two main branches of interacting lymphocytes, the B and T cells.

Alexander Moisés Chédiak (CU) described a rare childhood autosomal recessive disorder that affects multiple systems of the body. Patients exhibit hypopigmentation of the skin, eyes, and hair; prolonged bleeding times; easy bruisability; recurrent infections; abnormal natural killer cell function; and peripheral neuropathy(3782). Today it is called Chédiak-Higashi syndrome.

Julius B. Kuhn, Jr. (US) and Jacob Furth (AT/HU-US) discovered that anemia associated with acute death from radiation is due to erythrocytes entering the lymph ducts following the destruction of blood platelets(3783). 

M.C. Woods (US), Frances N. Gamble (US), Jacob Furth (AT/HU-US), and R.R. Bigelow (US) found they could treat this radiation anemia by using transfusions of platelets(3784).

Karl Singer (US), Ben Fisher (US), and Meyer A. Perlstein (US) described and named acanthocytosis(3785).

Carl W. Walter (US), in 1952, a researcher under Harvey Cushing (US) and William P. Murphy, Jr. (US) described a system in which the blood was collected into a collapsible bag of polyvinyl resin(3786). These were first used by Murphy on the front lines during the Korean War. This innovation opened the way for safe and easy preparation of multiple blood components from a single unit of whole blood.

Francis Daniels Moore (US) published his research in the landmark text, The Metabolic Response to Surgery. This was the benchmark for the future of surgical metabolism and in nutrition for patients who are unable to eat(3787).

Bjorn Ibsen (DK) established the first hospital based intensive care unit. It was to treat patients with poliomyelitis during the 1952 epidemic. Ibsen examined some patients, studied their records, looked at specimens from four autopsies, and became convinced that the patients had died from lack of ventilation. He proposed to use hand-supplied positive pressure instead of the customary machine-generated negative pressure. This approach was found to be very successful. According to one account, in total, approximately 1,500 medical and dental students contributed 165,000 hours of life-preserving service, squeezing rubber bags(3788). This radical and effective way of treating seriously ill patients launched the proliferation of intensive care units and led to the inauguration of the now flourishing specialty of critical care medicine.

Roar Strøm (SE), Robert Milton Zollinger (US), and Edwin Homer Ellison (US) described a disease condition comprising a clinical triad of 1) hypersecretion of gastrin, 2) multiple, atypically located, often recurrent peptic ulcers, and 3) a non-insulin producing islet cell tumor of the pancreas(3789, 3790). It is called gastric hypersecretion-peptic ulceration-pancreatic tumor syndrome or Zollinger-Ellison-Strøm syndrome.

Bernard Lown (LT-US), William Francis Ganong, Jr. (US), and Samuel Albert Levine (US) described ECGs on 200 patients with short PQ intervals, a normal QRS complex, and a tendency to paroxysmal supraventricular tachycardia(3791). Today it is referred to as the Lown-Ganong-Levine syndrome.

William H. Sweet (US) and Manucher Javid (US) originated and encouraged the use of boron neutron capture therapy for brain tumors(3792).

Harold King (US) and Harris B. Shumacker, Jr. (US) found that even though their series of cases in which splenectomy was performed during the first six months of life is small, the subsequent development of serious infection was so constant as to suggest a cause-effect relationship.

Floyd John Lewis (US) and Mansur Taufic (US) performed the first successful open-heart surgery on a human. The patient was a five-year-old girl who had been born with a hole in her heart. Anaesthetized to stop her shivering, the girl was cooled by a special blanket until her body temperature reached 81 degrees F. At this temperature, she could survive without a pumping heart for ten minutes. Clamping the inflow to her heart so that it emptied of blood, Taufic and Lewis cut open her heart, which was still slowly beating, and quickly sewed up the hole. With the repaired heart working properly for the first time in her life, the girl was then immersed in a bath of warm water to bring her body temperature back to normal. The operation was a success(3793). See, Daniel Hall Williams, 1893.

Clarence Walton Lillehei (US) and Richard L Varco (US) were the first to describe surgical anastomosis of the right pulmonary veins to the right auricle and the IVC to the left auricle by using an allograft aortic tube to connect the IVC and the left aorta(3794). This operation provided partial physiologic correction in patients with complete transposition of the great arteries.

Anthony Andreasen (GB) and Frank Watson (GB), showed that dogs can survive for almost 40 minutes without brain damage when all blood flow is stopped except that through the azygos vein(3795).

Morley Cohen (US) and Clarence Walton Lillehei (US) applied these findings in their dog lab. They showed that dogs survive cardiac surgery when supplied with blood through the azygos vein-only; 10% of the normal supply(3796).

Morley Cohen (US) and Clarence Walton Lillehei (US) hypothesized that when blood supply was low, the blood vessels dilated to receive a larger share of the blood, while the tissues absorbed a much higher proportion of the oxygen than under conditions of normal circulation.

Clarence Walton Lillehei would remark that, "The single most important discovery that made clinical open-heart surgery successful was the realization of the vast discrepancy between the total body flow that was thought necessary, and what was actually necessary.”

William P. Longmire, Jr. (US) and John M. Beal (US) performed a total gastrectomy with the formation of a new stomach(3797).

Charles Dubost (FR), Michel Allary (FR), and Nicolas Oeconomos (FR) performed the first successful resection of an abdominal aortic aneurysm, replacing it with a homograft(3798).

Warren Herbert Wagner, Jr. (US) is widely regarded as the founder of modern day systematics for all groups of plants and animals, and was the first to argue that phylogenetic reconstruction can be made explicit and rational. Today, the phrase 'Wagner [phylogenetic] tree' is part of the lingua franca of systematic biologists around the world(3799-3806). Wagner’s work led directly to the cladistic analysis of evolutionary relationships among plants.

ca. 1953

Analysis of light transmitted or reflected by the atmospheres of other planets in our solar system or by dust clouds in interstellar space revealed that they contained reduced gases, e.g., methane and ammonia, thus supporting the Oparin-Haldane hypothesis. Ref

1953

“Francis winged into the Eagle [a pub] to tell everyone within hearing distance that we had found the secret of life.” James Dewey Watson(3807).

“It has not escaped our notice that the specific pairing [of bases in the double helical structure] we have postulated immediately suggests a possible copying mechanism for the genetic material.” James Dewey Watson and Francis Harry Compton Crick(3808).

“Antibody for all three immunologic types [of polio virus] was induced by the inoculation of small quantities of…vaccines incorporated in a water-in-oil emulsion…Levels of antibody induced by vaccination are compared with levels that develop after natural infection… These studies…should not be interpreted to indicate that a practical vaccine is now at hand.” Jonas Edward Salk in referring to his work in developing a polio vaccine(3809).

"It is better to ask some of the questions than to know all the answers!" James Thurber(3810).

Frederik (Frits) Zernike (NL) was awarded the Nobel Prize in Physics for his demonstration of the phase contrast method, which included his invention of the phase contrast microscope.

Leonard S. Lerman (US) invented affinity chromatography on columns to purify mushroom tyrosinase(3811).

Pedro M. Cuatrecasas (US), Meir Wilchek (IL), and Christian Boehmer Anfinsen (US) were early practitioners of affinity chromatography, a technique which frequently yields highly purified proteins in one step(3812).

Sir Hans Adolf Krebs (DE-GB) cited for his discovery of the citric acid cycle, and Fritz Albert Lipmann (DE-US) for his discovery of co-enzyme A and its importance for intermediary metabolism, were awarded the Nobel prize in physiology and medicine.

Clair Cameron Patterson (US), George Tilton (US), and Mark Inghram (US) used uranium decay in rocks from Earth and in meteorites that struck Earth to date our solar system at 4.55 ± 0.07 billion years old(3813-3816).

Wallace Henry Coulter (US) and Joe Coulter (US) were granted a patent in 1953 for their discovery of The Coulter Principle. Their actual discovery in 1948 was a method for counting and sizing microscopic particles (including blood cells) suspended in a fluid. This method became widely used and formed the first viable basis for flow cytometry. From it grew an industry that forever changed the world of diagnostic medical research(3817).

Stanley Lloyd Miller (US), working in Harold Clayton Urey’s (US) laboratory, showed that a wet mixture of methane, hydrogen, and ammonia, upon exposure to electrical discharge, formed traces of organic compounds, including organic acids including amino acids. These are regarded as exclusive products of living things(3818).

Gerry H. Cookson (GB) and Claude Rimington (NO) determined the chemical structure of porphobilinogen. Porphobilinogen is the chemical building block for a group of organic pigments which includes hemoglobin and chlorophyll(3819, 3820).

Alvin Nason (US) and Harold J. Evans (US) discovered nitrate reductase in Neurospora(3821).

Harold J. Evans (US) and Alvin Nason (US) identified the enzyme nitrate reductase (NR) in the leaves of vascular plants. Although NR had previously been described in Neurospora, this is the first report of NR in plants. The discovery of NR opened up the field of study of plant nitrogen assimilation(3822). 

Vincent du Vigneaud (US), Charlotte Ressler (US), Stuart Trippett (US), John Melvin Swan (AU), Carleton W. Roberts (US), Panayotis G. Katsoyannis (GR), and Samuel Gordon (US) determined the primary structure of oxytocin (a polypeptide hormone from the posterior pituitary gland), synthesized it in vitro, and demonstrated that it is identical to the natural material. Oxytocin was the first protein hormone ever synthesized(3823-3825).

Vincent du Vigneaud (US), H. Claire Lawler (US), Edwin A. Popenoe (US), Duane T. Gish (US), and Panayotis G. Katsoyannis (GR) determined the primary structure of vasopressin (antidiuretic polypeptide hormone from the posterior pituitary gland), synthesized it in vitro, and demonstrated that it is identical to the natural material(3826, 3827). 

Francis A. Hochstein (US), Charles R. Stephens (US), Lloyd H. Conover (US), Peter P. Regna (US), Richard Pasternak (US), Philip N. Gordon (US), Frederick J. Pilgrim (US), Karl J. Brunings (US), and Robert Burns Woodward (US) determined the structure of terramycin(3828).

Robert Burns Woodward (US) and Konrad Emil Bloch (US) suggested that the squalene chain might be folded—in a way unique at this time— to yield lanosterol as an intermediate in the synthesis of cholesterol(3829).

Robert G. Langdon (US) and Konrad Emil Bloch (DE-US) showed that squalene is a precursor to cholesterol in vivo(3830).

Rama Kant Maudgal (IN), Tche-Tsing Tchen (US), and Konrad Emil Bloch (DE-US) offered rigorous proof of this using chemically synthesized [13C] all-trans squalene(3831).

Sir John Warcup Cornforth (AU-GB) demonstrated the conversion of squalene to lanosterol(3832).

Tche-Tsing Tchen (US) and Konrad Emil Bloch (US) demonstrated the conversion of lanosterol to cholesterol(3833).

Sir John Warcup Cornforth (AU-GB), Gordon D. Hunter (GB), George Joseph Popják (GB), and Irene Youhotsky Gore (GB) performed a complete carbon by carbon dissection of the cholesterol nucleus(3834-3836).

Maurice Hugh Frederick Wilkins (GB), Rosalind Elsie Franklin (GB), Alexander Rawson Stokes (GB), Raymond George Gosling (GB), and Herbert Rees Wilson (GB) obtained the first high quality x-ray diffraction photographs of DNA. One of Franklin’s photographs revealed a dominant cross like pattern (B form), the telltale mark of a helix(3837, 3838).

James Dewey Watson (US) and Francis Harry Compton Crick (GB) postulated a double-helix structure for deoxyribonucleic acid (DNA), which not only accounted for the molar equivalence of the bases and the characteristic x-ray diffraction pattern of DNA, but also suggested a simple mechanism by which genetic information can be precisely transferred from parent to daughter cells. Crick had also deduced the antiparallel nature of the molecule from the work of Rosalind Elsie Franklin (GB) and Maurice Hugh Frederick Wilkins (GB)(3808, 3837-3841). The structure worked out by Watson and Crick is now known as the B form.

On February 28, 1953, in the Cavendish Laboratory, at Cambridge University, Oxford England, “That morning, Watson and Crick knew, although still in mind only, the entire structure: it had emerged from the shadow of billions of years, absolute and simple, and was seen and understood for the first time. Twenty angstrom units in diameter, seventy-nine billionths of an inch. Two chains twining coaxially, clockwise, one up the other down, a complete turn of the screw in 34 angstroms. The bases flat in their pairs in the middle, 3.4 angstroms and a tenth of a revolution separating a pair from the one above or below. The chains held by the pairing closer to each other around the circumference one way than the other, by an eighth of a turn, one groove up the outside narrow, the other wide. A melody for the eye of the intellect, with not a note wasted. In itself, physically, the structure carried the means of replication—positive to negative, complementary. As the strands unwound, a double template was there in the base pairing, so that only complementary nucleotides could form bonds and drop into place as the daughter strands grew. Edna St. Vincent Millay wrote a sonnet which is, or so I thought in my youth, as good a poem about science as any since Lucretius’—the sonnet begins, ‘Euclid alone has looked on Beauty bare.’ Perhaps the experience ought to have been like that: one doubts, of course, that Crick and Watson altogether realized, that morning, what they had seen. ‘We have discovered the secret of life,’ Crick told everyone within earshot over drinks that noon at the Eagle. It was not the entire secret of life, yet truly for the first time at the ultimate biological level structure had become one with function, the antimony dialectically resolved. The structure of DNA is flawlessly beautiful”(2665).

Roberta Ogilvie Day (US), John M. Rosenberg (US), Nadrian C. Seeman (US), Jung Ja Park Kim (US), Fred Leroy Suddath (US), Hugh B. Nicholas (US), and Alexander Rich (US) gave the first experimental evidence that Watson-Crick base pairs form when the molecule is constrained in a double helix. They did this by x-ray analysis, at 8 angstrom resolution, of two dinucleotide phosphate crystals, the RNA oligomers GpC and ApU(3842, 3843).

Alfred Day Hershey (US) found that there are minor species of RNA with high turnover rates produced during phage infection of bacteria(3844, 3845).

Waldo E. Cohn (US) and Elliot Volkin (US) found that a specific phosphodiesterase from snake venom yields 5'-mononucleotides from RNA thus establishing the link on one side of the internucleotide bond(3846).

Leon A. Heppel (US), Paul R. Whitfeld (AU), Russell J. Hilmoe (US), and Roy Markham (GB) proved that the linkage in ribonucleotides runs 5’ to 3’(3847-3850).

Luis Federico Leloir (AR), Carlos Eugenio Cardini (AR), and Jorge Chiriboga (PE) discovered the role of the sugar nucleotides in the synthesis of sucrose(3851, 3852).

Arthur J. Kornberg (US) and William E. Pricer, Jr. (US) discovered the long-chain kinase which catalyzes the ATP-requiring conversion of fatty acids—C8 to C18—to the corresponding acyl CoA esters(3853). 

Jack Gross (US) and Rosalind Venetia Pitt-Rivers (US) isolated the hormone 3:5:3'-triiodothyronine from ox thyroid gland and then synthesized it(3854).

Heinrich Klüver (DE-US) and Elizabeth A. Barrera (US) introduced Luxol fast blue MBS stain as a method for staining myelin sheaths. When it was combined with Nissl stain cresyl violet, they found that both the myelin sheath and the nerve cell could be seen(3855).

Albert Kelner (US), using Escherichia coli strain B/r, demonstrated that ultraviolet light of 2537 angstrom wavelength damages DNA, which leads to inhibition of growth and ultimate death(3183). 

Murray Strassman (US), Alice J. Thomas (US), and Sidney Weinhouse (US) discovered the first step in the pathway by which the yeast Torulopsis utilis converts pyruvate to valine(3856). This reaction is also the first step in the formation of acetoin (acetylmethylcarbinol), a property long used by bacteriologists as a diagnostic test to distinguish Aerobacter aerogenes from Escherichia coli.

Lester Orville Krampitz (US) established the role of acetolactate as an intermediate in the production of acetoin(3857).

Yeheskel S. Halpern (IL) and Harold Edwin Umbarger (US) showed that Aerobacter aerogenes synthesizes two enzymes that form acetolactate. One of them is synthesized when the pH of the growth medium falls below 6—the enzyme’s optimum—and forms acetoin, a neutral product of glucose catabolism. The other is synthesized when the pH is greater than 6—optimum near pH 8—and functions in the synthesis of valine(3858).

Allan J. Erslev (DK-US) concluded that plasma from rabbits rendered anemic by bleeding contains a factor capable of stimulating red cell production.

Rosemary A. Biggs (GB), Alexander Stuart Douglas (GB), Robert Gwyn Macfarlane (GB) proposed two pathways to blood clotting according to whether tissue juices or extracts are present or absent; Extrinsic-tissue extracts are present, Intrinsic- tissue extracts are absent(3859, 3860).

Gilbert Burnett Forbes (US) described glycogen storage disease type 3. This is an autosomal recessive inheritable deficiency of amylo-1,6 glucosidase which results in storage of short chained glycogen molecules in the liver and skeletal musculature. Sequelae include hepatomegaly, cardiomegaly and muscle weakness(3861). 

Bernard Leonard Horecker (US), Pauline Z. Smyrniotis (US), and Hans Klenow (DK) discovered that the coenzyme of thiamin (vitamin B1) participates in the direct metabolism of carbohydrates when transketolase, which requires thiamin pyrophosphate, effects transfer of a 2-carbon unit from a 2-keto sugar to C-1 of various aldoses(1273).

Selma E. Snyderman (US), L. Emmett Holt, Jr. (US), Rosario Carretero (US), and Kathryn Jacobs (US) established that pyridoxine and related compounds (vitamin B6) are essential for infants. Pyridoxine deprivation in two human infants resulted in an arrest of weight gain and failure of the ability to convert tryptophan to N1-methylnicotinamide in both. In one subject, it resulted in convulsive seizures; in the other, it provoked a severe microcytic hypochromic anemia. All of these symptoms and signs were corrected by the introduction of pyridoxine into the diet(3862).

Sidney Q. Cohlan (US) demonstrated that excessive intake of vitamin A (retinol) can cause congenital anomalies in the rat(3863).

A. Yasuma (JP) and T. Ichikawa (JP) introduced the alloxan-Schiff and ninhydrin-Schiff histochemical reactions as tests for the presence of protein(3864).

Thalidomide was first synthesized at Chemie Grünenthal G.m.b.H., Stolberg, West Germany in 1953. Named Contergan, it was advertized as a sedative(3865, 3866).

Clifford George Pope (GB) and Muriel F. Stevens (GB) isolated crystalline diphtheria toxin(3867).

Louis Pillemer (US), Livia Blum (US), Jack Pensky (US), Leona Wurz (US), Irwin H. Lepow (US), Oscar A. Ross (US), Earl W. Todd (US), Alistair C. Wardlaw (US), and Chester M. Southam (US) discovered the alternative pathway for the activation of complement along with properdin, factors A and B(3868-3873). 

Suzanna E. Lewis (US), Edward Charles Slater (AU-NL), and Bertram Sacktor (US) demonstrated the presence of oxidative phosphorylation in insect tissues(3874-3876).

Mabel Ruth Hokin (GB-US) and Lowell E. Hokin (GB-US) were the first to recognize that inositol phospholipids may play a role in transduction of signals initiated by first messengers. When they stimulated slices of pigeon pancreas with acetylcholine a remarkable movement of phosphorus into phospholipids was observed. This is called the phospholipid effect(3877, 3878).

Robert H. Michell (GB) was the first to propose that the phosphoinositide effect discovered by the Hokins plays a role in mobilization of cellular calcium(3879).

Robert H. Michell (GB), Christopher J. Kirk (GB), Lynne M. Jones (GB), C. Peter Downes (GB), and Judith A. Creba (GB) identified phosphotidylinositol-4,5-biphosphate as the main phospholipid subject to a turnover in stimulated cells in connection with calcium mobilization(3880). 

James Dewey Watson (US) and Francis Harry Compton Crick (GB) were the first to offer a molecular explanation for mutations(3840).

Max Alfert (US) and Irving I. Geschwind (US) described a selective staining method for the basic proteins of cell nuclei(3881).

James F. Riley (GB) and Geoffrey B. West (GB) discovered that tissue mast cells are a main storage site of histamine(3882). This discovery helped lay the foundation for an understanding of allergic and inflammatory disease.

Susumu Hagiwara (JP-US), Hiroo Uchiyama (JP), Akira Watanabe (JP), and Takeyuki Wakabayashi (JP) described the myogenic rhythm intrinsic to cicada muscles(3883-3885).

Jacques Lucien Monod (FR) and Germaine Cohen-Bazire (FR), using the bacterium Aerobacter aerogenes, presented evidence that the amino acid tryptophane can inhibit its own synthesis by activating its repressor at the gene level, i.e., enzyme repression(3886).

Arthur Beck Pardee (US), Harold Edwin Umbarger (US), Barbara Brown (US), Aaron Novick (US), Richard Alan Yates (US), Leo Szilard (HU-US), Georges N. Cohen (FR), Francois Jacob (FR), Jacques Lucien Monod (FR), John C. Gerhart (US), Earl Reece Stadtman (US), Gisele LeBras (FR), Huguette deRobichon-Szulmajster (FR), and Jean-Pierre Changeux (FR) produced additional examples of feedback control. Some of these are feedback inhibitions at the enzyme level. Others, like tryptophane, are feedback inhibitions at the gene level. A few are feedback controlled at both the enzyme and gene levels(3887-3897). See, Zacharias Dische 1940.

Nick Visconti (US) and Max Ludwig Henning Delbrück (DE-US) formulated a theory of genetic recombination in phages capable of accounting quantitatively for the recombinant frequencies obtained under various experimental conditions. This theory envisages that the vegetative phage genomes exist in an intracellular mating pool in which they undergo repeated pair wise matings. Each mating leads to an exchange of genetic material by one or more crossovers between the two mated individuals.

From the vantage point of the Visconti-Delbrück theory, the fraction of progeny phages recombinant for two genetic markers introduced into a phage cross depends on two things: the linkage of the mutant genes in question and the number of mating events within the mating pool prior to lysis(3898).

André Michael Lwoff (FR), Albert S. Kaplan (FR), and Evelyne Ritz (FR) established unequivocally that certain phage DNAs have the alternate possibility of being inserted in a prophage form into the chromosomes of their host. They can be transmitted from one cell generation to the next without external reinfection(3425, 3899).

Hans J. Schatzmann (CH) provided evidence that cardiac glycosides directly inhibit active transport of sodium and potassium ions through the red cell membrane(3900).

Rita Levi-Montalcini (IT-US), Viktor Hamburger (DE-US), Hertha Meyer (BR) and Stanley Cohen (US) were the first to describe and characterize nerve growth factor (NGF). They obtained it from mouse sarcoma cells and found tat it elicited extensive growth of chick embryo neurons(3901-3908). This was the first neurotrophin to be described and isolated.

NGF is critical for the survival and maintenance of sympathetic and sensory neurons. Without it, these neurons undergo apoptosis. See, Glücksmann, 1951.

John F.R. Kerr (AU), Andrew H. Wyllie (GB), and Alistair R. Currie (GB) coined the term apoptosis to mean genetically orchestrated cell death not involving inflammation(3909).

Neil Q. McDonald (GB), Risto Lapatto (GB), Judith Murray-Rust (GB), Jennifer Gunning (GB), Alexander Wlodawer (US), and Tom L. Blundell (GB) solved the structure of NGF by x-ray crystallography(3910).

Hugh Esmor Huxley (GB) and Jean Hanson (US) were the first to identify the thick myofilaments in muscle cells as myosin and the thin ones as actin(3911). 

William Hayes (GB) found from the study of his Hfr strain of E. coli that the high-frequency donor character pertains only to a limited portion of the donor genome. He interpreted these findings to mean that the F plus Hfr change is attributable to a permanent alteration of the fertility factor. At the same time this engendered a loss of its own transferability to an F minus strain and a very much greater transferability of a limited sector of the donor genome(3442, 3912).

S. Iseki (JP) and T. Saki (JP) observed that infection of Salmonella by a temperate bacteriophage led to a change in somatic antigens of the host bacteria(3913).

Ludwik Gross (PL-US) and Sarah Elizabeth Stewart (US) independently observed sarcomas in mice following inoculation with extracts of murine leukaemia virus(3914-3916).

Sarah Elizabeth Stewart (US), Bernice E. Eddy (US), Alice M. Gochenour (US), Ninette G. Borgese (US) and George E. Grubbs (US) demonstrated that polyoma virus, which had caused the sarcomas in the 1953 study described above, replicates in tissue culture(3917).

Bernice E. Eddy (US), Sarah Elizabeth Stewart (US), Ralph D. Young (US) and G. Burroughs Mider (US) discovered that inoculation of the polyoma virus into newborn hamsters led to tumor induction with a shorter latent period than in adult mice(3918).

GianPiero A. di Mayorca (IT-US), Bernice E. Eddy (US), Sarah Elizabeth Stewart (US), W.S. Hunter (US), Charlotte Friend (US), and Aaron Bendich (US) discovered that SE polyoma virus DNA and intact polyoma virus are capable of infecting embryonic tissue cultures of both the mouse and the hamster. These new infectious molecules proved to be both the first infectious DNA isolated and the first cancer-inducing nucleic acid(3919). The SE in SE polyoma is to honor Stewart and Eddy.

Wallace Prescott Rowe (US) and Worth I. Capps (US) found polyoma virus infection to be prevalent among wild mice(3920, 3921).

Michael J. Collins, Jr. (US) and John C. Parker (US) found the polyoma virus to be a common contaminant of transplantable murine tumors and stocks of murine leukaemia viruses(3922).


Katherine Esau (RU-US) became one of the world’s leading authorities on plant anatomy upon the publication of her outstanding book, Plant Anatomy. Her later book, The Phloem, is considered the definitive text on structure and development of phloem(3923, 3924).

Ernest Robert Sears (US), working with wheat, described the processes of genetic analysis enabling the identification of chromosomes carrying specific recessive alleles. In the process, he discovered the hemizygous ineffective condition meaning the inability of a single copy of a recessive allele to pass the threshold necessary for expression. Two copies of the recessive allele are required for expression of the recessive phenotype(3925).

Ernest Robert Sears (US), working with wheat, created the most complete aneuploid series known in any organism. Using nullisomic effects seen in this series, he was able to show the genetic effects of each chromosome(3926).

Michael Abercrombie (GB) and Joan E.M. Heaysman (GB) coined the phrase contact inhibition to describe the inhibition of cellular locomotion which commonly occurs when untransformed cell monolayers reach confluence(3927, 3928).


Thomas Huckle Weller (US) grew the virus of varicella (chickenpox) and of herpes zoster (shingles) in cultures of human tissue and found that they both produced the same type of cytopathogenic effect(3929).

Wallace Prescott Rowe (US), Robert Joseph Huebner (US), Loretta K. Gilmore (US), Robert H. Parrot (US), and Thomas G. Ward (US) recovered virus (adenovirus) from tissue cultures of human tonsillar and adenoid tissue(3930).

Robert Joseph Huebner (US), Wallace Prescott Rowe (US), Thomas G. Ward (US), Robert H. Parrott (US), and Joseph A. Bell (US) realized that these adenoidal-pharyngeal-conjunctival agents represented a newly recognized group of common viruses of the respiratory system(3931).

Maurice Ralph Hilleman (US) and Jacqueline H. Werner (US) grew the adenovirus 4, a major cause of acute respiratory disease in humans, in polyploid tissue culture(3932).

John Franklin Enders (US), Joseph A. Bell (US), John Holmes Dingle (US), Thomas Frances, Jr. (US), Maurice Ralph Hilleman (US), Robert Joseph Huebner (US), and Anthony Monck-Mason Payne (US) proposed the name adenoviruses for a newly recognized group of respiratory tract viruses(3933).

Masahiko Kuroya (JP), Nakao Ishida (JP) and Takehiko Shiratori (JP) isolated what would be called Sendai virus from cases of pneumonitis in newborn infants in Sendai, Japan(3934).

Roger W. Reed (CA), Charles H. Rammelkamp, Jr. (US), Harold I. Griffeath (US), Robert S. Weaver (US), and Alan C. Siegel (US) concluded that type 12, group A, hemolytic streptococcus is the most common etiological agent of acute hemorrhagic glomerulonephritis(3935-3938).

Hermann Karl Felix Blaschko (DE-GB), Arnold D. Welch (GB), Nils-Åke Hillarp (SE), Sten Lagerstedt (SE), and Bodil Nilson (SE) were the first to isolate secretory vesicles (chromaffin vesicles) of adrenal medullary cells. Using centrifugation of adrenal medullary homogenates, they sedimented catecholamines, the major part of the hormones of this organ(3939-3942).

Nicholas Avrion Mitchison (GB) provided the first evidence that transplantation immunity, the ability to maintain immunological individuality, is effected by regional lymph node cells(3943).

Sir Peter Brian Medawar (GB) was the first to point out the immunologically privileged nature of the fetal allograft(3944).

Eugene Aserinski (US) and Nathaniel Kleitman (US) found that rapid eye movements (REM) occur during some sleep periods and noted that dreaming typically occurs during REM sleep. Electroencephalograms (EEGs) showed that, during REM sleep, heart rate and breathing increased while brainwave activity was almost as high as that of the waking mind(3945, 3946).

William Grey Walter (GB -US) and his colleagues used their toposcope to extend temporal spectral analysis in which they visualized the spread of alpha waves across the surface of the brain in ways resembling the ebb and flow of tidal waves around the earth. Alpha activity has the peculiarity that it is most apparent when a human subject is at rest with eyes closed, and it disappears when the eyes are opened or if mental arithmetic is undertaken. Walter proposed that the alpha represented 'scanning' by the brain in search of local centers of activity when none was present, and that it stopped when a 'target' was found in the cortex. This 50 year old hypothesis was and still is controversial, but there is at present none better(3947).

Franz K. Bauer (US), Benedict Cassen (US), Elsie Youtcheff (US), and Lucille Shoop (US) performed a clinical study comparing needle and jet gun injection(3948).


Stephen William Kuffler (HU-US) published work on center-surround, on-off organization of retinal ganglion cell receptive fields(3949).

Robert L. Rosenthal (US), O. Herman Dreskin (US), and Nathan Rosenthal (US) described a new blood clotting factor in man, plasma thromboplastin antecedent (PTA). It was later designated factor XI(3950, 3951).

Robert D. Langdell (US), Robert H. Wagner (US) and Kenneth M. Brinkhous (US) developed the partial thromboplastin time test (PTT), a one-stage procedure that measures the intrinsic coagulation activity of plasma. This test aids in the detection of blood clotting disorders(3952).

Robert R. Proctor (US) and Samuel I. Rapaport (US) developed the activated partial thromboplastin time test (aPTT), a modification of the PTT test that dispenses with the variable of contact activation(3953).

Rosemary A. Biggs (GB) and Alexander Stuart Douglas (GB) developed the thromboplastin generation test, an important advance enabling a more detailed analysis and localization of clotting factors(3954).

Louis Lichtenstein (US) classified eosinophilic granuloma of bone along with Hand-Schuller-Christian disease (with the classic triad of exophthalmos, diabetes insipidus, and skull lesions) and Letterer-Siwe disease (lymphadenopathy, skin rash, hepatosplenomegaly, fever, anemia, and thrombocytopenia) as Histiocytosis X(3955).


Louis Michon (FR), Jean Hamburger (FR), Nicholas Oeconomos (FR), Pierre Delinotte (FR), Gabriel Richet (FR), Jean Vaysse (FR), and Bernard Antoine (FR) were the first to perform a human kidney transplantation in which the donor was a living relative of the recipient (mother to son); no immunosuppression was used and the kidney functioned for three weeks prior to rejection(3956).

Ian Aird (GB), Hugh H. Bentall (GB), and John Alexander Fraser-Roberts (GB) found that there is a relationship between cancer of the stomach and the ABO blood groups with the highest incidence occurring in blood group A(3957). Their published paper helped lead the way to our understanding of how disease is related to particular histocompatibility antigens.

Matthew Block (US), Leon O. Jacobson (US), and William F. Bethard (US) described twelve patients, most of whom developed overt acute leukaemia, preceded for as long as five years by hematopoietic disorders manifested as a combination of anemia, neutropenia, and thrombocytopenia. These patients had problems with thrombocytopenic bleeding or infection related to neutropenia, and many progressed to florid acute myeloblastic leukaemia. Some in several months, others over several years.

This paper brought attention to “threshold” leucoses that can occur at any age but which increase in incidence exponentially after age fifty years(3958).

Jonas Edward Salk (US) was the first to prepare a vaccine to the polio virus. It was a chemically inactivated form of the virus(3809, 3959-3961).

Virginia Apgar (US) developed a repeatable method (Apgar score) to quickly and summarily assess the health of newborn children immediately after birth. This method has drastically reduced infant mortality over the world(3962).

Leland C. Clark, Jr. (US), Richard Wolf (US), Donald Granger (US), and Zena Taylor (US) introduced the first clinically practical polarographic oxygen electrode for measurement of arterial PO2(3963).

John W. Severinghaus (US) and A. Freeman Bradley, Jr. (US) described the first clinically practical electrode for measuring PCO2 in blood(3964).

Sir Andrew Watt Kay (GB) developed a new and extremely consistent test for the presence of duodenal ulcer. It is based on the effect of increasing doses of histamine on the gastric secretion of hydrochloric acid(3965).

Gordon Brownell (US) and William H. Sweet (US) invented positron emission tomography (PET Scanning)(3966).

Michael Ellis DeBakey (US), Denton A. Cooley (US), E. Stanley Crawford (US), and George C. Morris, Jr. (US) developed Dacron as artificial arteries and Dacron-velour arteries as a surgical replacement of diseased arteries(3967). They actually began using artificial arteries made of Dacron in 1953.

Michael Ellis DeBakey (US) and Denton A. Cooley (US) performed the first successful removal and graft replacement of a fusiform aneurysm of the thoracic aorta, a swelling caused by a weakness in the arterial wall of the descending aorta in the chest(3968).

Michael Ellis DeBakey (US) performed the first successful carotid endarterectomy for the treatment of stroke in 1953 but did not report it until 1975(3969). Carotid endarterectomy remains one of the principle surgical treatments of carotid artery stenosis.

Robert H. Whittaker (US) demonstrated that plant species distribute themselves along nutrient and environmental abiotic gradients(3970). 

George Gaylord Simpson (US) originated the notion of the 'adaptive zone' and discusses the relation between adaptive zones and adaptive radiations at length. Here he relates the population/genetic/microevolutionary phenomena of concern to most of the ‘synthesists’ to macroevolutionary/deep time patterns evident in the fossil record(3971).

Sidney P. Colowick (US) and Stanley Oram Kaplan (US) founded Methods in Enzymology.

1954

“I believe with Schopenhauer that one of the strongest motives that leads men to art and science is escape from everyday life with its painful crudity and hopeless dreariness from the fetters of one’s own everyday desires…. A finely tempered nature longs to escape from personal life into the world of objective perception and thought.” Albert Einstein(3972).

“A grain of slightly mad recklessness, Might, in this domain as in others, Be the price you have to pay for great and noble findings.” Claude Levi-Strauss(3973).

“There are men who express the age and the milieu in which they are educated but who, by the intensity of their imagination, the sweep of their knowledge and their astounding versatility, rise above their era and their neighbors so that they inhabit both time and eternity at once. When we analyze their minds, we can identify nearly all the component elements tracing this to family and that to school and the other to social climate and yet the compound is far more than the sum of all these elements; richer, intenser, different in quality as a diamond is different from carbon." Gilbert Highet(3974).

“Metamorphosis is merely one type of polymorphism.” Sir Vincent Brian Wigglesworth(3975).

Linus Carl Pauling (US), was awarded the Nobel Prize in Chemistry for his research into the nature of the chemical bond and its application to the elucidation of the structure of complex substances.

John Franklin Enders (US), Thomas Huckle Weller (US), and Frederick Chapman Robbins (US) were awarded the Nobel Prize in Physiology or Medicine for their discovery of the ability of poliomyelitis viruses to grow in cultures of various types of tissue.

Alexander Pavlovich Vinogradov; Aleksandr Pavlovich Vinogradov (RU), S.I. Zykov (RU), and I.K. Zadorozhny (RU) put the age of the earth at five to six billion years(3976).

John Desmond Bernal (GB), Peter C. Sylvester-Bradley (GB), S. Ichtiaque Rasool (US), Donald M. Hunten (US), William M. Kaula (US), Egon T. Degens (DE), Kenneth M. Towe (US), Edward Anders (US), Gustaf Olaf Arrhenius (SE-US), Bibhas Ranjan De (US), Hannes Olof Gosta Alfvén (SE-US), Anne Benlow (GB), Arthur Jack Meadows (GB), Manfred A. Lange (DE), and Thomas J. Ahrens (US) proposed that impact accretions from extraterrestrial objects represented a significant source of the Earth's atmospheric and biogenic elements(3977-3985).

David W. Green (GB), Vernon M. Ingram (GB) and Max Ferdinand Perutz (AT-GB) solved the phase problem in protein crystallography by the addition of heavy metals such as uranium to the crystal preparation(3986). 

Harold Horace Hopkins (GB), Narinder S. Kapany (GB), and Abraham Cornelis Sebastiaan van Heel (NL) independently devised an optical unit which conveys optical images along a flexible glass axis. Hopkins and Kapany named it a fibrescope(3987, 3988). This concept fostered endoscopes.

Basil Hirschowitz (US), C. Wilbur Peters (US), and Lawrence E. Curtis (US) produced the first fiberoptic, fully flexible endoscope(3989).

Herbert A. Sober (US), Frederick J. Gutter (US), Elbert A. Peterson (US), and Mary M. Wyckoff (US) invented cellulose-based ion exchangers to separate individual proteins from complex mixtures(3990, 3991).

Robert Burns Woodward (US), Arthur Allan Patchett (US), Sir Derek Harold Richard Barton (GB), David A. J. Ives (US), and R.B. Kelly (US) accomplished the total synthesis of lanostenol(3992).

Du Pont Chemical Company introduced the herbicide diuron, a substituted urea, as a pre-emergence to crops such as cotton (Gossypium spp.), alfalfa, grapes, fruit and nuts. ref 

Robert Burns Woodward (US), Michael P. Cava (US), William D. Ollis (GB), A. Hunger (US), Hans U. Daeniker (CH), and Karl Schenker (CH) carried out a total synthesis of strychnine(3993, 3994).

Steven D. Knight (US), Larry E. Overman (US), and Garry Pairaudeau (US) would later carry out an updated total synthesis of strychnine(3995).

Hartmut Hoffmann-Berling (DE) reported that water-glycerol extracted amnion fibroblasts contract upon addition of ATP(3996). Subsequently Hoffmann-Berling showed that glycerinated epithelial cells, hen embryos, or Jensen tumor tissues could be contracted with ATP, similarly to the contraction of glycerinated muscle fibers. The idea that actin and myosin are present in mammalian cells, other than muscle, became a working hypothesis. By the middle of 1970s actin and myosin were acknowledged as regular components of non-muscle cells.

Ernst Klenk (DE) and Hildegard Debuch (DE) were the first to suggest the correct structure for plasmalogens(3997).

Jean Leclercq (FR) discovered that a small meal worm (Tenebrio molitor) needs carnitine as a "vitamin"(3998).

Irving B. Fritz (US) discovered that carnitine in muscle is active in increasing the oxidation of fatty acids by the liver, thereby increasing the energy supply to the liver and improving its function(3999).

Irving B. Fritz (US) and Norman R. Marquis (US), over the next twenty years along with colleagues, proved that carnitine acts to transport fatty acids across barriers to the specific sites of fatty acid oxidation. In the case of the heart, carnitine is necessary for the utilization of this foodstuff and for optimal cardiac function(4000, 4001).

Jack Leonard Strominger (US), Herman Moritz Kalckar (DK-US), Julius Axelrod (US), and Elizabeth S. Maxwell (US) discovered how the cell generates uridine diphosphate glucuronic acid (UDPGA) from uridine diphosphate glucose (UDPG) using uridine diphosphate glucose dehydrogenase(4002, 4003).

Julius Axelrod (US), Rudi Schmid (US), and Lydia Hammaker (US) then demonstrated that a deficiency of this microsomal fraction enzyme (uridine diphosphate glucose dehydrogenase ) results in failure to detoxify bilirubin which leads to jaundice(4004). 

Adolf Friedrich Johann Butenandt (DE) and Peter Karlson (DE) isolated and crystallized the insect prothoracic gland hormone which Karlson named ecdysone(4005, 4006).

Marthe Louise Vogt (DE-GB) identified the hypothalamus as a source of norepinephrine (noradrenaline) in the brain(4007).

Rollin Douglas Hotchkiss (US) extended transformation of bacterial characters beyond capsular qualities when he showed that DNA from Penr-S cells could convert Pens-R cells to Penr-S cells. He also demonstrated that bacterial cells are not equally susceptible to transformation during the entire division cycle. They enter a competent phase shortly after division and then return to a relatively noncompetent phase(4008, 4009).

Sarah Ratner (US) found that in the ornithine cycle, nitrogen is not transferred directly from ammonia to citrulline to form arginine but rather it is transferred by way of aspartic acid in the presence of ATP and magnesium. The aspartic acid complexes with citrulline to form argininosuccinic acid which in turn breaks down into arginine and fumaric acid(4010).

Harvey F. Fisher (US), Eric E. Conn (US), Birgit Vennesland (DE-US), Frank Henry Westheimer (US), Frank A. Loewus (US) and Peter Ofner (US) showed that in dehydrogenase-catalyzed reactions, the hydrogen atom added to the pyridine ring is transferred directly from the substrate, without mixing with the hydrogen ions of the solution(4011, 4012).

Efraim Racker (PL-AT-US) proposed that glucose-6-phosphate, which inhibits hexokinase activity, acts as a control mechanism helping to explain the Pasteur effect(4013).

Paul Berg (US) and Wolfgang Karl Joklik (AT-AU-US) discovered the enzyme that uses ATP to phosphorylate the four ribo- and deoxyribonucleoside diphosphates to their respective triphosphates; they dubbed the enzyme nucleoside diphosphokinase(4014). This enzyme plays a critical role in generating the "building blocks" for RNA and DNA synthesis.

Howard J. Saz (US) and Lester Orville Krampitz (US) performed work with Micrococcus lysodeikticus which strongly suggested that bacteria possess the tricarboxylic acid cycle(4015).

H. Earl Swim (US) and Lester Orville Krampitz (US) established that, in fact, Escherichia coli does possess the tricarboxylic acid cycle(4016).

Peter Dennis Mitchell (GB) gave the first adequate description of bacterial transport. He found that resting cells of Micrococcus pyogenes (Staphylococcus aureus) take up external 32Pi in exchange for internal phosphate by a reaction that is biased strongly to use of monovalent phosphate(4017). 

William Chefurka (CA) provided conclusive evidence for the existence of an Embden-Meyerhof-Parnas type glycolytic pathway in an invertebrate (Musca domestica Linnaeus). This Embden-Meyerhof-Parnas pathway is virtually identical with those observed in vertebrate tissues(4018). Chefurka also demonstrated that these houseflies possess the hexosemonophosphate shunt(4019).

Carlton E. Schwerdt (US), Robley C. Williams (US), Wendell Meredith Stanley (US), Fred L. Schaffer (US), and Mary E. McClain (US) determined the morphology of type 2 poliomyelitis virus (MEF) by electron microscopy(4020).

Yasuichi Nagano (JP), Yasuhiko Kojima (JP), and Y. Sawai (JP) saw an antiviral activity in rabbit skin after injection of inactivated vaccinia virus. They were the first to discover interferon(4021, 4022).

Alick Isaacs (GB) and Jean Lindenmann (CH) found that exposure of chick embryo chorioallantoic membranes to heat-inactivated influenza virus generated a factor that, when added to fresh membranes, rendered them immune to influenza virus infection(4023, 4024). This represents the second group to discover interferon, an inhibitor of viral replication. Lindenmann coined the name interferon.

Monto Ho (CN) and John Franklin Enders (US) were the third group to discover interferon(4025). 

Susanna Harris (US), Tzvee N. Harris (US), James C. Roberts, Jr. (US), and Frank James Dixon (US) showed that the production of antibody can be transferred from one animal to another by way of cells(4026, 4027).

Georgi Antonovich Gamow (RU-US) was among the first to deduce that DNA can act as a template for the orderly insertion of some twenty amino acids into a protein….”the hereditary properties of any given organism could be characterized by a long number written in a four-digital system. On the other hand, the enzymes (proteins), the composition of which must be completely determined by the desoxyribonucleic acid molecule, are long peptide chains formed by about 20 different kinds of amino-acids, and can be considered as long words based on a 20-letter alphabet. Thus the question arises about the way in which four-digital numbers can be translated into such words”(4028).

Ulf Svante von Euler (SE) and Otto Loewi (DE-US) proposed that adrenergic nerve transmitter is stored within intracellular granules(4029, 4030).

Eduardo Diego P. De Robertis (AR), H. Stanley Bennett (US), and Antonio Van Ferreira (US) suggested that these synaptic vesicles may represent a transitory form of storage of the transmitter in synapses and similar structures. On stimulation such vesicles may move toward the cell membrane and give off their contents(4031, 4032).

Keith Roberts Porter (US) was the first to describe a type of cell juncture called a desmosome or macula adherens (desmos = bond)(4033). confirm

Hugh Esmor Huxley (GB-US), Jean Hanson (US), Sir Andrew Fielding Huxley (GB), and Ralph M. Niedergerke (GB) proposed the sliding filament model of muscular contraction. According to this model force is generated between two types of muscle myofilament: one containing the protein actin, the other containing the protein myosin. The force causes the two types of myofilament to slide past each other and this, in turn, results in an overall shortening of the muscle(4034-4038).

Nicholas Avrion Mitchison (GB), James M. Weaver (US), Glenn H. Algire (US), and Richmond T. Prehn (US) discovered that sensitized cells and not antibodies are the primary agents of graft rejection(4039-4041)

Robert J. Rutman (US), Abraham Cantarow (US), and Karl E. Paschkis (US) observed that rat hepatomas exhibited greater utilization of uracil than did normal rat livers(4042).

John Rodney Quayle (GB), R. Clinton Fuller (US), Andrew Alm Benson (US), and Melvin Calvin (US) observed enzymatic carboxylation of ribulose biphosphate in crude extracts from Chlorella(4043).

Daniel Israel Arnon (PL-US), Mary Belle Allen (US), F. Robert Whatley (GB), John B. Capindale (GB), and Lois J. Durham (US) found that the assimilation of carbon dioxide in isolated chloroplasts is indeed a reversal of the carbohydrate breakdown reactions (respiration). They further showed that the energy necessary for this reversal is provided by ATP and reduced coenzyme (PNH2). When they illuminated isolated spinach chloroplasts in the presence of ADP and phosphate, ATP was formed. Since the yield of ATP in such experiments was rather high and comparable to the amount of light-induced electron flow, it was concluded that the formation of ATP must represent a major mechanism for the conservation of absorbed light energy, just as ATP formation is the major process by which the energy of respiration is conserved during electron transport in mitochondria. This process they named photosynthetic phosphorylation or photophosphorylation(4044-4048).

Independently and nearly simultaneously Albert W. Frenkel (US) discovered that a very similar phosphorylation process occurs on illumination of membrane vesicles from the photosynthetic bacterium Rhodospirillum rubrum. These observations suggested that the formation of ATP from ADP and phosphate results from the energetic coupling of the phosphorylation to the photoinduced electron transport, in much the same way that oxidative phosphorylation is coupled to electron transport in mitochondria(4049). This is the discovery of cyclic photophosphorylation in bacteria.

Aaron Novick (US) and Leo Szilard (HU-US) while analyzing the pathway of tryptophane synthesis in Escherichia coli discovered that the constituitive enzyme tryptophane synthetase in this pathway is subject to inhibition by tryptophane. Szilard referred to this as classic feedback control(3887, 4050). Henry James Vogel (US) later suggested that this type of pathway control be called enzyme repression(4051).

José del Castillo (ES) and Sir Bernard Katz (RU-GB) described impulse transmission across a synapse. They demonstrated that a chemical neurotransmitter substance is released from presynaptic terminals in discrete packets or quanta, each containing several thousand molecules(4052).

Johannes Arne Gosta Rhodin (SE), working with mouse kidney tissue, discovered a new class of small, relatively simple cytoplasmic organelles, which he named microbodies (peroxisomes)(4053).

Olga von H. Owens (US), Margaret Lewis Gey (US), and George Otto Gey (US) were the first to adapt a cell line to growth in suspension. The cells were a malignant lymphoblast line from the mouse(4054).

Betty Ben Geren (US) discovered that nonneuronal oligodendroglia are the source of the protective myelin wrapped around cerebral axons(4055).

Loren C. Bryner (US), Jay V. Beck (US), Delmar B. Davis (US), Dean G. Wilson (US) and Ralph Anderson (US) recognized for the first time that there is a relationship between the presence of bacteria and the dissolution of metals in copper-leaching mining operations(4056-4058). 

Susumu Hagiwara (JP-US), Ichiji Tasaki (US), and Akira Watanabe (JP) were the first to record action potentials from within Mauthner’s neuron in fish (catfish)(4059).

Helen K. Waltz (US), William W. Tullner (US), Virginia J. Evans (US), Roy Hertz (US), and Wilton R. Earle (US) demonstrated that in vitro tumor tissue—unlike in vitro normal tissue—has a tendency to continue to produce its specialized products(4060).

Franklin Hollander (US) formally proposed the concept of a two-component, self-regenerating barrier. According to his hypothesis, the gastric mucous barrier is a composite of two integrated structural units. The layer of viscous mucus constituted the first line of defense and the second was the layer of columnar and cuboidal cells of the surface of crypt epithelium(4061).

Ruth Sager (US) found mutations in Chlamydomonas which behaved in a non-Mendelian fashion suggesting that they resided within the chloroplasts(4062).

Richard Cawthon Starr (US) elucidated the sexuality of desmids and green algae. This was the first time the details of meiosis had been set forth for these groups(4063-4066).

Paul Charles Zamecnik (US), Elizabeth B. Keller (US), John W. Littlefield (US), and Jerome Gross (US) discovered that the microsomal (ribosomal) fraction of the cell contains the site of protein synthesis while the nucleus, mitochondria, and other organelles do not. In the process they developed the first cell-free system to carry out protein synthesis(4067-4071).

Rollin Douglas Hotchkiss (US) and Julius Marmur (US) discovered that in bacteria the frequency of joint transformation of two gene regions depended on their proximity to one another. It was later discovered by others that the probability of joint transformation of two linked genes is, in fact, an excellent measure of the physical distance between them in the DNA molecule(4072).

Norman Ernest Borlaug (US) helped develop disease-resistant, dwarf, wheat varieties which are adaptable to growing conditions, and exceedingly high-yielding(4073, 4074). These wheats saved millions of lives by improving wheat production in Mexico in the 1940s and 1950s and later in Asia and Latin America.

William Steen Gaud (US), in 1968, referred to this as the “Green Revolution”(4075, 4076).

Edmund Schulman (US) reported finding bristlecone pines (Pinus longaeva and Pinus aristata) thousands of years old(4077). He later found the oldest known specimen in this group and nicknamed it Methuselah. Its rings established its age at 4,723 years(4078). By combining ring patterns from living bristlecone pines with those of dead bristlecone tissue the historical record has been pushed back to 7000 B.C.E.

John A. Sheedy (US), Herman F. Froeb (US), Hugh A. Batson (US), Charles C. Conley (US), Joseph P. Murphy (US), Richard B. Hunter (US), David W. Cugell (US), Robert B. Giles (US), Sol C. Bershadsky (US), John W. Vester (US), Robert H. Yoe (US), Carl N. Ekman (US), Joe L. Stockard (US), Robert K. Kiyasu (US), George Entwisie (US), and David P. Earle (US), while working with United Nations soldiers in Korea, described the clinical course, sequential physiologic derangements, and sequelae of epidemic hemorrhagic fever(4079-4081). See Hao Wang Lee, 1978.

Zyun Hidaka (JP) reported that tobacco stunt disease is caused by a virus(4082).

Robert C. Rendtorff (US) determined tha a single cyst of Entamoeba coli is sufficient to establish an infection(4083).

John William Sutton-Pringle (GB) showed that the rapid wing-beats necessary for flight in insects are achieved by alternate sets of muscles which are alternately stretch activated. This is referred to as the myogenic property of insect flight muscle(4084-4087).

David Lambert Lack (GB) amassed considerable evidence relating geographic trends in resource availability and clutch size in birds. He suggested that a species reduces its clutch to maximize the number of young that survive and fledge(4088).

William H. Muir (US), Albert C. Hildebrandt (US) and Albert J. Riker (US) obtained plant cultures from single-cells for the first time. These were obtained by shaking submerged callus cultures(4089).

Ludwig Bergmann (DE) separated single plant cells from cultures by filtration. He transferred the resulting cell suspension onto agar culture dishes. This was the first cloning of plant cells(4090).

D. Eugene Becker (US), Stanley W. Terrill (US), Duane E. Ullrey (US), and Richard A. Notzold (US) performed extensive feed testing of carbohydrate sources to pigs ranging in age from 1 d to 16 wk. They were fed liquid diets containing casein and various sugars with ad libitum access. Seven pigs, 1 to 10d old, were fed each diet, six fed the sucrose diet died, five fed the fructose diet died, and only one fed the dextrose diet died. Among surviving pigs, those fed dextrose gained weight, whereas those fed sucrose or fructose lost weight. Pigs fed either sucrose or fructose also exhibited severe diarrhea. Of eight pigs 7 to 35 d of age, three of the eight pigs fed sucrose died, whereas mortality was minimal in pigs fed lactose, dextrose, dextrin or cornstarch. Although the surviving pigs fed sucrose gained body weight as effectively as those fed the other carbohydrate sources, the three pigs that died had severe diarrhea. This experiment suggested that at least some pigs by 7 d of age can effectively hydrolyze sucrose in the gut and can also utilize both glucose and fructose for energy. Pigs at 12-wks could effectively utilize sucrose (50% of dry diet), but depressed growth and moderate diarrhea resulted when the semipurified soybean meal diet contained 50% lactose(4091-4093).

C.B. Bailey (CA), Warren D. Kitts (CA), Alexander J. Wood (CA), and Donald Midgely Walker (GB) found that small intestinal and pancreatic extracts from pigs at various ages showed that intestinal sucrase activity is extremely low in newborn pigs and increases 10-fold at 1 wk, 60-fold at 2 wks and 200-fold at 5 wks of age. Intestinal lactase activity, on the other hand, was high at birth but declined thereafter(4094, 4095).

Jean Baptiste Gabriel Joachim Dausset (FR) and André D. Nenna (FR) discovered isoagglutinins for the human leucocyte during a search for an immunologic etiology of leukopenia(4096).

Jean Baptiste Gabriel Joachim Dausset (FR) reported the observation that the sera from 60 patients contained antibodies which agglutinated lymphocytes from certain individuals. He noted that 90% of these patients had received multiple transfusions. Dausset concluded that transfusion was responsible for creating antibodies against leucocytes as a result of an immune response toward the donor(4097).

Johannes Joseph van Rood (NL), J. George Eernisse (NL), Adriana van Leeuwen (NL), Rose Payne (US), and Mary R. Rolfs (US) found that pregnant mothers can be stimulated by their unborn child to produce leucocyte agglutinins (HLA antibodies). The child and the mother must differ from one another in a leucocyte membrane antigen inherited from the father by the fetus(4098, 4099). In 1967 the World Health Organization (WHO) named these human leucocyte antigens (HLA).

Jean Baptiste Gabriel Joachim Dausset (FR) introduced the first human histocompatibility antigen, MAC, named after the initials of three donors whose leucocytes did not agglutinate the test sera. This antigen is also known as HLA-A2. He showed that monozygotic twins exhibited identical agglutination patterns while dizygotic twins did not, which led him to hypothesize that leucocyte antigens are genetically controlled(4100).

Johannes Joseph van Rood (NL) and J. George Eernisse (NL) discovered additional leucocyte antigens which they designated antigens 2 and 3(4101).

Results from a workshop in Torino during 1967 provided the first evidence that leucocyte antigens are the products of closely linked genes located on the same chromosome(4102-4104).

Ruggero Ceppellini (IT), Emilia Sergio Curtoni (IT), Pier Luigi Mattiuz (IT), Vincenzo Miggiano (IT), Guido Scudeller (IT), and Antonio Serra (IT) coined the word haplotype to indicate the chromosomal combination of HLA alleles(4102).

Ans P.M. Jongsma (NL), Harry van Someren (NL), Andries Westerveld (NL), Ann Hagemeijer (NL), and Peter Pearson (NL) located the HLA genes on chromosome number 6(4105).

H. Brücke (DE) and H. Reis (DE) performed the first clinical trials of the anesthetic drug carbolonium (Imbretil)(4106).

Isadore Lampe (US) and Robert S. MacIntyre (US) revealed the curability of medulloblastomas of the cerebellum by roentgentherapy(4107, 4108).

Charles A. Janeway (US) and David Gitlin (US) described a fatal granulomatous disease of childhood that is due to severe quantitative and functional deficiencies of circulating neutrophils(4109).

John Holmes Dingle (US), Harold S. Ginsberg (US), George F. Badger (US), William S. Jordan, Jr. (US), Sidney Katz (US), Eli Gold (US) and Alexander D. Langmuir (US) performed outstanding studies which have added significantly to our knowledge and ability to control acute respiratory diseases(4110-4114).

Harry H.G. Eastcott (GB), Sir George White Pickering (GB) and Charles G. Rob (GB) reported a carotid endarterectomy. Most vascular surgeons consider this the first operation of this type(4115).

Michael Ellis DeBakey (US) and Denton A. Cooley (US) performed the first successful resection and graft replacement of an aneurysm of the distal aortic arch and upper descending thoracic aorta(4116).

Bernard Miller, Jr (US), John Heysham Gibbon, Jr. (US), Victor E. Greco (US), C. Harold Cohn (US), and Frank F. Allbritten, Jr. (US) developed the left ventricular vent thus solving intra-cardiac air embolisms during open cardiotomy(4117). 

James Olds (US) and Peter Milner (US) described the rewarding effects of stimulating the septal region of the hypothalamas. It became known as the reward center(4118).

Mogens Abelin Schou (DK), Niels Juel-Nielsen (DK), Erik Robert Volter Strömgren (DK), Holger Voldy (DK), Geoffrey P. Hartigan (GB) and Poul Christian Baastrup (DK) made observations on small numbers of manic and depressed patients which suggested that lithium treatment might ameliorate their disorders(4119-4121). A longer term study with more patients revealed several things. First, the start of long-term lithium treatment is associated with a marked (87 per cent) and long-lasting fall in the frequency of both manic and depressive recurrences. Secondly, the recurrences that do occur usually develop after interruption of the treatment. Thirdly, the prophylactic effect of lithium is equally good in unipolar and bipolar patients. And fourthly, the efficacy of lithium does not disappear with time or after interruption and subsequent resumption of the treatment(4122).

Inge Edler (SE) and Carl Hellmuth Hertz (SE) borrowed a shipyard sonar machine made by Siemens used for detecting structural flaws in boat hulls. They are credited with performing the first human echocardiogram, which they termed ultrasound cardiography (UCG). Images were crude, but the posterior left ventricular wall and anterior mitral leaflet were visualized (although the valve was initially thought to be the anterior left atrial wall). This was the first successful imaging of any organ for medical purposes, (4123).

Inge Edler (SE) described the use of the ultrasonic cardiogram for mitral valve diseases(4124).

Sven Effert (DE) and Erwin Domanig (DE) identified left atrial masses using cardiac ultrasound(4125).

John Cunningham Lilly (US), during 1953-1954, invented the isolation tank method for exploring consciousness. He found, "Within yourself you do have at least the circuitry to exert control over these systems. You can create a sense of well-being, or you can create a sense of fear out of the operation of your own bio-computer. That's the most important message we have in regard to self meta-programming. I saw that in the tank.

Somewhere, deep within the brain, was a mechanism capable of generating internal experiences completely independent of the outside world, and this settled the issue of what happens in profound physical isolation. The mind does not pass into unconsciousness, the brain does not shut down. Instead, it constructs experience out of stored impressions and memories. The isolated mind becomes highly active and creative”(4126-4129). This work led him to interspecies communication research projects between man and dolphin.

Peter Armitage (GB) and Richard Doll (GB) performed a re-analysis of age-related cancer death rates for adults in England and Wales. They demonstrated a nearly constant linear relationship between log transformed cancer mortality rates and age, thus indicating that the relationship between age and mortality rates was exponential, with a nearly constant power value across various types of cancer. From this, they inferred that cancers resulted from a sequence of independent “stages,” with the rate of occurrence of one or more stages increasing with age(4130).

Lamont C. Cole (US) outlined, as had others before him, noted how population growth is critically affected by even the slightest variation in demographic parameters such as fecundity, survival to reproductive age and age at first reproduction. However, Cole took this several steps further. He noted that evolutionary fitness must be equally strongly affected by such variation, leading on to a discussion, from a theoretical standpoint, of which types of life cycles we should expect to find in nature. He stressed that life history traits should be viewed as putative adaptations to specific environments, and it is in this sense that Cole’s paper marks the start of modern life history theory(4131).

Stanley A. Tyler (US) and Elso Sterrenberg Barghoorn (US) reported the discovery of fossil microscopic organisms in an outcropping of mid-precambrian rocks called the Gunflint Iron formation near Lake Superior in Ontario. Most of these fossils resemble present day bacteria and cyanobacteria. This was the first indisputable evidence of Precambrian life(4132).

Barghoorn, Tyler, and Preston Ercelle Cloud, Jr. (US) later confirmed these findings and discussed their significance(4133, 4134). 

Other Precambriam fossil sites include: the Fig Tree Group, Africa; the Bulawayan Formation, Africa; the Gunflint Iron Formation, Minnesota/Canada; the Belcher Group, Hudson Bay; Bitter Springs, Australia; and the Ediacaran Sites, Australia.

Camille Arambourg (FR) and Robert Hoffstetter (FR) discovered Homo erectus mandibles with teeth at Ternifine, near the village of Palikao, east of Mascara, Oran, Algeria(4135, 4136). They were dated to ca. 600K B.P.

ca. 1955

“There's nothing like technical progress! Ideas come and go, but technical progress cannot be taken away.” Alfred Day Hershey, cited in an article by William F. Dove(4137). 

1955

Vincent du Vigneaud (US) was awarded the Nobel Prize in Chemistry for his work on biochemically important sulfur compounds, especially for the first synthesis of a polypeptide hormone.

Axel Hugo Theodor Theorell (SE) was awarded the Nobel Prize in Physiology or Medicine for his discoveries concerning the nature and mode of action of oxidation enzymes.

Pierre Grabar (RU-DE-FR), Curtis A. Williams, Jr. (US) and Jeanine Courcon (FR) originated and named the technique of immunoelectrophoresis(4138-4141).

Lloyd H. Conover (US) was granted a patent for his discovery of tetracycline(4142).

Robert Burns Woodward (US) accomplished the total synthesis of tetracycline(4143).

Guy G.F. Newton (GB) and Edward Penley Abraham (GB) isolated, named, and determined the structure of the antibiotic cephalosporin C(4144, 4145). This antibiotic is produced by the fungus Cephalosporium.

Giuseppi Brotzu (IT), ca. 1945, was the first to use crude culture filtrates from Cephalosporium as a therapeutic agent. Patients with a variety of infections were treated successfully, especially typhoid fever. Brotzu forwarded a culture of Cephalosporium to Newton and Abraham at Oxford University for their study and subsequent great success.

Richard L. Potter (US) and Sondra Schlesinger (US) synthesized and characterized the four dNTPs (dTTP, dCTP, dGTP, and dATP)(4146).

Helmuth Hilz (DE), Phillips W. Robbins (US), and Fritz Albert Lipmann (DE-US) characterized "active sulfate" as 3'-phosphoadenosyl 5'-phosphosulfate(4147, 4148).

Leon A. Heppel (US), Paul R. Whitfeld (AU), and Roy Markham (US) announced an in vitro enzymatic method for the synthesis of ribo-oligonucleotides of known base sequence using pancreatic RNAase A and spleen phosphodiesterase(4149).

Robert H. Daines (US) discovered that the sulfonamides possess a fungicidal quality(4150, 4151).

Allen R. Kittleson (US) was the first to synthesize these compounds(4152, 4153). The discovery of captan, a potent fungicide, and the related phthaliamides captafol, and folpet would be the outcome of these efforts.

Raymond Urgel Lemieux (CA) and George Huber (CA) showed that when a sugar such as N-acetylglucosamine incorporates a carbonium ion at the carbon-1 position, it tends to take up the same conformation that is forced on the N-acetylmuramic acid ring when lysozyme cleaves peptidoglycan. This is believed to represent an example of substrate activation by distortion, an idea long a favorite of enzymologists(4154).

Aaron Bunsen Lerner (US) and Teh H. Lee (US) isolated melanocyte-stimulating hormone (MSH) from the porcine anterior pituitary gland(4155). This isolate was later called alpha-melanocyte stimulating hormone (alpha-MSH).

Jerker Olof Porath (SE), Paul Roos (SE), Frank W. Landgrebe (GB), and G.M. Mitchell (GB) isolated melanocyte-stimulating hormone (MSH) from the porcine anterior pituitary gland(4156). This isolate was later called beta-melanocyte-stimulating hormone (beta-MSH).

Gabriel L. de la Haba (US), and Irwin Gordon Leder (US), and Efraim Racker (PL-AT-US) isolated and purified yeast transketolase, a key enzyme of the pentose phosphate pathway(4157).

Tage Astrup (DK) and Ida Strendorff (DK) isolated plasminogen activator (urokinase), an enzyme that helps clear the urinary tract of blood clots from human urine(4158). 

Bert L. Vallee (CH-US) and Hans Neurath (AT-US) discovered that carboxypeptidase is a zinc metalloenzyme(4159). 

Fred H. Mattson (US) and Lloyd W. Beck (US) demonstrated the high specificity of pancreatic lipase for triacylglycerol primary esters(4160).

Kenneth D. Gibson (US), Albert Neuberger (DE-GB), J.J. Scott (US), David Shemin (US), Rudi Schmid (CH-US), and William Graeme Laver (AU) showed that labeled delta-aminolevulinic acid is an excellent precursor of protoporphyrin. This lead to a quick understanding of the biosynthetic pathway to all of the porphyrins(2660, 4161, 4162).

Christian Rene de Duve (GB-BE-US), Berton Charles Pressman (US), Robert Gianetto (CA), Robert Wattiaux (BE), and Francoise Appelmans (BE) proposed the existence of a new group of subcellular organelles with lytic properties, the lysosomes, and hinted at the existence of another subcellular organelle, the future peroxisome(4163).

Christian Rene de Duve (GB-BE-US) developed what became known as analytical fractional centrifugation(4164-4166). This paved the way for many discoveries concerning subcellular particles. See, Schneider, 1948.

Christian Rene de Duve (GB-BE-US) and Pierre Baudhuin (FR) used centrifugation to isolate lysosomes and, later, microbodies which they called peroxisomes because they oxidized cellular organics with the release of hydrogen peroxide(4167, 4168).

Pierre Baudhuin (FR), Henri Beaufay (BE), and Christian Rene de Duve (GB-BE-US) confirmed the identification of lysosomes as pericanalicular dense bodies and showed that the peroxisomes correspond to the particles known as microbodies(4169). 

Gunther Siegmund Stent (US) and Clarence R. Fuerst (US) found that if phosphorus 32 is incorporated into the DNA of bacteriophage its lethality increases with concentration of the radioactive isotope and decreases with temperature(4170).

Leonard T. Skeggs, Jr. (US), Walton H. Marsh (US), Joseph R. Kahn (US), Kenneth L. Lentz (US), Norman P. Shumway (US), and Kenneth R. Woods (US) determined the amino acid sequences and biological relationships of hypertensin (angiotensin) I and II(74, 4171, 4172).

David F. Elliott (GB) and William Stanley Peart (GB) determined the amino-acid sequence in hypertensin from oxen(4173). 

Sir Howard Walter Florey (AU-GB) isolated the antibiotics cephalosporin P, cephalosporin N (really a penicillin and previously isolated), and cephalosporin C(4174).

Gilbert M. Shull (US), Joseph L. Sardinas (US), Roger L. Harned (US), Phil Harter Hidy (US), and Eleanore Kropp LaBaw (US) isolated the antibiotic D-cycloserine (oxamycin) from Streptomyces lavendarles, Streptomyces orchidacens and Streptomyces garyphalus(4175, 4176).

John Vandeputte (US), Jacques L. Wachtel (US), and Eric T. Stiller (US) isolated the antibiotic amphotericin B from Streptomyces nodusus(4177).

Herman Hoeksema (US), James L. Johnson (US), and Jack W. Hinman (US) isolated the antibiotic novobiocin from Streptomyces niveus(4178).

S. Ross () isolate the antibiotic oleandomycin from Streptomyces antibioticus(4179).

Alfred Ammann (US), David Gottlieb (US), Thomas D. Brock (US), Herbert E. Carter (US), and George B. Whitfield (US) isolated the antifungal antibiotic filipin from Streptomyces filipinensis(4180).

Choh Hao Li (CN-US), Irving I. Geschwind (US), R. David Cole (US), Ilse Dorothea Raacke (US), J. leuan Harris (US), and Jonathan S. Dixon (US) determined the entire amino acid sequence of the alpha-corticotropin hormone (ACTH) of the anterior pituitary gland(4181).

Gunther Siegmund Stent (US) and Max Ludwig Henning Delbrück (DE-US) were the first to hypothesize that DNA replicates by a mechanism Stent called semi-conservative(4182-4184).

Francis Harry Compton Crick (GB) sent a letter to a select group of his fellow scientists calling themselves The RNA Tie Club. Crick himself was a member along with George Gamov (RU-US), the self-appointed president. In this letter we have the earliest record, in print, of the hypothesis that the genetic code is degenerate and that there existed in cells an adaptor molecule which would seek out an amino acid, react with it, and somehow bring it into the polypeptide being made. Arguably his letter displays the remarkable insight of a man who was, along with Linus Carl Pauling (US) and Jacques Lucien Monod (FR), one of the major architects and premier theorists of the molecular biology revolution. Since it is rare in print, excerpts are included here, “ In this note I propose to put on paper some of the ideas which have been under discussion for the last year or so, if only to subject them to the silent scrutiny of cold print. It is convenient to start with some criticisms of Gamov’s paper…as they lead naturally to the further points I wish to make.…Another proof…depends on the A chain of two species of insulin. (Frederick Sanger. Personal communication, and in press.) The sequences are identical except that one (sheep) has Gly where the other (bovine) has Ser. The change occurs roughly in the middle of the chain. Both sequences cannot be coded by a Gamov scheme, since changing one pair of bases necessarily alters at least two amino acids, and this cannot be corrected without making further changes in the base sequence…Thus to code both species of insulin A chains is impossible. A third method to disprove Gamov’s scheme, given sufficient data, is to count neighbors. This is particularly useful in a scheme which does not distinguish between neighbors-on-the-right and neighbors-on-the-left.

Using the data from the two insulin chains and beta-corticotropin one finds 10 amino acids having 8 neighbors or more. Gamov’s scheme (see his table III) allows only 8 amino acids to have more than 7 neighbors. Thus coding would be impossible…

I have set out these at length, not to flog a dead horse, but to illustrate some of the simplest ways of testing a code. It is surprising how quickly, with a little thought, a scheme can be rejected. It is better to use one’s head for a few minutes than a computing machine for a few days!

The most fundamental objection to Gamov’s scheme is that it does not distinguish between the direction of a sequence; that is, between Thr. Pro. Lys. Ala. and Ala. Lys. Pro. Thr.…There is little doubt that Nature makes the distinction, though it might be claimed that she produces both sequences at random, and that the wrong ones—not being able to fold up—are destroyed. This seems to me unlikely.

This brings us face to face with one of the most puzzling features of the DNA structure—the fact that it is non-polar, due to the dyads at the side; or put another way, that one chain runs up while the other runs down. It is true that this only applies to the backbone, and not to the base sequence, as Delbrück has emphasized to me in correspondence. This may imply that a base sequence read one way makes sense, and read the other way makes nonsense. Another difficulty is that the assumptions made about which diamonds are equivalent are not very plausible.…[Gamov’s idea] would not be unreasonable if the amino acid could fit on to the template from either side, into cavities which were in a plane, but the structure certainly doesn’t look like that. The bonds seem mainly to stick out perpendicular to the axis., and the template is really a surface with knobs on, and represents a radically different aspect on its two sides.…

What, then are the novel and useful features of Gamov’s ideas? It is obviously not the idea of amino acids, nor the idea of the bases sequence of the nucleic acids carrying the information. To my mind Gamov has introduced three ideas of importance:

(1) In Gamov’s scheme several different base sequences can code for one amino acid.…This degeneracy seems to be a new idea, and, as discussed later, we can generalize it.

(2) Gamov boldly assumed that code would be of the overlapping type.…Watson and I, thinking mainly about coding by hypothetical RNA structures rather than by DNA, did not seriously consider this type of coding.

(3) Gamov’s scheme is essentially abstract. It originally paid lip service to structural considerations, but the position was soon reached when coding was looked upon as a problem in itself, independent as far as possible of how things might fit together.…Such an approach, though at first sight unnecessarily abstract, is important.

Finally it is obvious to all of us that without our President the whole problem would have been neglected and few of us would have tried to do anything about it.

I want to consider two aspects of the DNA structure. Firstly its dimensions; secondly its chemical character.

The dimensional side is soon disposed of. In the paracrystalline form of DNA (Structure B) we have one base every 3.4 angstroms in the fiber direction. A fully extended polypeptide chain measured about 3.7 angstroms from one amino acid to the next. Therefore it is argued that not more than one base pair can, on the average, be matched with an amino acid. If we go up the outside of the helix the position is worse, since the distance per base-pair is now greater, perhaps twice as great.

I want to point out that this argument, though powerful, is not completely water-tight.

As regards chemical character, I want to consider not only the DNA structure, but also any conceivable form of RNA structure. Now what I find profoundly disturbing is that I cannot conceive of any structure (for either nucleic acid) acting as a direct template for amino acids, or at least as a specific template. In other words, if one considers the physical-chemical nature of the amino acid chains we do not find complimentary features on the nucleic acids. Where are the knobly hydrophobic [water-repelling] surfaces to distinguish valine from leucine and isoleucine? It is true that a Teller scheme, in which the amino acids already condensed act effectively as part of the template, might be a little easier, but a study of known sequences from this point of view is not encouraging.

I don’t think that anybody looking at DNA or RNA would think of them as templates for amino acids were it not for other, indirect evidence.

What the DNA structure does show (and probably RNA will do the same) is a specific pattern of hydrogen bonds, and very little else. It seems to me, therefore, that we should widen our thinking to embrace this obvious fact. Two schemes suggest themselves. In the first small molecules (phospholipids? ions chelated on guanine? [he was imagining small structures that might attach]) could condense on the nucleic acid and pad it suitably, and the resulting combination would form the template. I shall not discuss this further here. In the second, each amino acid would combine chemically, at a special enzyme, with a small molecule which, having a specific hydrogen-bonding surface, would combine specifically with the nucleic acid template. This combination would also supply the energy necessary for polymerization. In its simplest form there would be 20 different kinds of adaptor molecule, one for each amino acid, and 20 different enzymes to join the amino acid to their adaptors. Sydney Brenner, with whom I have discussed this idea, calls this the adaptor hypothesis, since each amino acid is fitted with an adaptor to go on to the template.

The usual argument presented against this latter scheme is that no such small molecules have been found, but this objection cannot stand. For suppose, as is probable, that the small adaptor molecules are in short supply. Then consider the experiment in which all amino acids except one, (say leucine) is supplied to an organism, so that protein synthesis stops. Why do not the intermediaries—the (amino acid + adaptor) molecules—accumulate? Simply because there is very little of them, and no more amino acid can combine with these adaptors until the amino acids, to which they are at that moment attached, have been made into proteins, thus releasing the adaptor molecule. Thus under these conditions free amino acids accumulate, not amino acids-plus-adaptor molecules.

In any case it seems unlikely that totally free amino acids actually go on to the template, because a free energy supply is necessary, especially when one bears in mind the entropy contribution needed to assemble the amino acids in the correct order. Free energy must be supplied to prevent mistakes in sequence being made too frequently.

The adaptor hypothesis implies that the actual set of twenty amino acids found in proteins is due either to a historical accident or to biological selection at an extremely primitive stage. This is not impossible, since once the twenty had been fixed it would be very difficult to make a change without altering every protein in the organism, a change which would almost certainly be lethal. It is perhaps surprising that an occasional virus has not done this, but even there a number of steps would be required.…

It is also conceivable that there is more than one adaptor for one amino acid, and the number 20 may be simply an accident (in any case we need a code for end chain, so perhaps 21 would be more reasonable).…

The adaptor hypothesis allows other general types [codes]; for example, depending on the sequence of four base pairs. The insulin A chain data makes this unlikely, but it is difficult to prove rigorously.

I have tacitly dealt with DNA throughout, but the arguments would carry over to some types of RNA structure. If it turns out that DNA, in the double-helix form, does not act directly as the template for protein synthesis, but that RNA does, many more families of codes are of course possible. (Incidentally the protein sequences we use to test our theories—insulin, for example—are probably RNA-made proteins. Perhaps a special class of DNA-made proteins exists, almost always in small quantities (and thus normally overlooked), except perhaps where there are giant chromosomes.)

In particular base pairing may be absent in RNA or take a radically different form.…Without a structure for RNA one can only guess.

Altogether the position is rather discouraging. Whereas on the one hand the adaptor hypothesis allows one to construct, in theory, codes of bewildering variety, which are very difficult to reject in bulk, the actual sequence data, on the other hand, gives us hardly any hint of regularity, or connectedness, and suggests that all, or almost all sequences may be allowed. In the comparative isolation of Cambridge I must confess that there are times when I have no stomach for decoding”(2665).

Mahlon Bush Hoagland (US) described how the energy is supplied to form peptide bonds during cellular protein synthesis(4185, 4186).

Severo Ochoa (ES-US), Marianne Grunberg-Manago (FR), and Priscilla J. Ortiz (US) were the first to carry out a cell-free synthesis of RNA. While investigating an aspect of energy metabolism they made the unexpected observation that one of the reactants, adenosine diphosphate (ADP), had been polymerized by cell juices into a chain of adenylates resembling RNA. They discovered that this polymerization was catalyzed by a magnesium ion requiring polynucleotide phosphorylase which they subsequently purified from Azotobacter vinelandii(4187, 4188). They quickly prepared additional polynucleotides and discovered that the nature of the product depended on the kind and variety of the nucleotide diphosphates present during the synthesis(4189, 4190).

Oliver Smithies (GB-US) invented starch gel electrophoresis for high-resolution separation of soluble proteins(4191-4193).

Dorothy Mary Crowfoot Hodgkin (GB), Alan W. Johnson (GB), Lord Alexander Robertus Todd (GB), Ray Bonnett (GB), Jennifer Kamper (GB), Maureen MacKay (GB), Jenny Pickworth (GB), Kenneth N. Trueblood (US), John G. White (US), June Lindsey (GB), John H. Robertson (GB), Clara Brink Shoemaker (GB), Ian O. Sutherland (GB), E. Lester Smith (GB), and Richard J. Prosen (US) used computer aided x-ray diffraction analysis to determine the structure of cyanocobalamin (vitamin B12) with full stereochemical and conformational detail(4194-4198).

Murray Saffran (CA), Andrew Victor Schally (PL-US), and Bruno G. Benfey (CA) coined the phrase corticotropin-releasing factor (CRF) for a product of the hypothalamus which stimulates the adrenal release of ACTH(4199).

Mary Ellen Jones (US) Leonard B. Spector (US), and Fritz Albert Lipmann (DE-US) showed that in the ornithine cycle, citrulline is formed by a reaction between ornithine and carbamoyl phosphate(4200).

Albert Lester Lehninger (US) discovered that reduced NAD is the true substrate of oxidative phosphorylation. He also showed that the mitochondrium is the seat of oxidative phosphorylation and that the oxidation of ascorbic acid via cytochrome c is linked to ATP formation(4201).

Edmond Henri Fischer (US), Edwin Gerhard Krebs (US), Earl Wilbur Sutherland, Jr. (US), Walter D. Wosilait (US),  Donald Paul Wolf (US), John D. Scott (US), Jacques G. Demaille (FR), Dean A. Malencik (US), Sonia R. Anderson (US). Michael F. Cicirelli (US), Nicholas K. Tonks (US), Curtis D. Diltz (US), and James E. Weiel (US) discovered reversible protein phosphorylation as a biological regulatory mechanism. They characterized a group of enzymes, called protein kinases, that change proteins from their inactive to active form by triggering the chemical bonding of a phosphate group to the protein. This phosphorylation is the underlying switch that starts and stops a variety of cell functions, from breakdown of fats to the generation of chemical energy in response to hormonal and other signals. They determined that adenosine triphosphate (ATP) is typically the donor of the phosphate group(4202-4208).

Niels Kaj Jerne (GB-DK) used the natural selection theory to explain the immune response. He postulated a large set of natural globulins that had been diversified in some random fashion. The function of antigen was to combine with those globulins with which it made a chance fit and then to transport these selected globulins into an antibody-forming cell. The cell would then make identical copies of the globulin presented to it. Although incorrect, this theory pointed the way to the clonal selection theory(4209).

Sir Frank Macfarlane Burnet (AU) and David W. Talmage (US) introduced the clonal selection theory of immunity, a modification of Jerne’s theory of antibody production. They independently hypothesized that antibodies sit on the surface of lymphocytes and that each lymphocyte bears only one kind of antibody(4210-4212).

Herbert H. Moorefield (US), and Clyde W. Kearns (US) found that resistance to dichloro-diphenyl-trichloro-ethane (DDT), also named 2,2-di(4-chlorophenyl)-1,1,1-trichloroethane, in insects is due to enzymatic dehydrochlorination(4213).

Seymour Benzer (US) brought the new concept of the molecular gene to bear directly on genetic experimentation. Benzer’s point of departure was a finding he made in 1953 that appeared to be of only mild interest to his fellow phage workers at the time: one class of closely linked r mutations of T-even phage, which Hershey had previously termed rII, possess another phenotype in addition to their typical r plaque morphology on agar plates seeded with the ordinary Escherichia coli strain. Phages carrying such rII mutations cannot grow at all on special Escherichia coli strains known collectively as K strains. On K strains the r+ wild-type phage, as well as other r mutants that do not belong to the rII class, can grow perfectly well. Benzer realized that this conditionally lethal growth defect of rII mutants can serve as a powerful selective agent for detecting the presence of a very small proportion of rII+ phages within a large population of rII mutants. It is known that K strains owe their inability to propagate rII phage mutants to the incorporation of the genome of another phage into their chromosome. That other phage is lambda.

Benzer proceeded with the construction of a fine-structure genetic map of the T4 genome. For this purpose he crossed members of his rII mutant collection two-by-two and collectively scored for the frequency of rII+ wild-type recombinants produced by plating the phage progeny of each cross on plates seeded with an Escherichia coli K strain. In this way he hoped to detect very rare recombinants between adjacent genetic sites, since the limit of resolution of this method would have allowed him to find rII+ recombinants in frequency as low as 0.0001%—a frequency so low that, if the nonselective method of simply hunting for r+ plaques on ordinary, rII permissive Escherichia coli were employed, 106 progeny r plaques would have to be inspected for every r+ recombinant found. Among the first set of 60 mutants, Benzer found some pairs that produced no r+ recombinants at all when crossed. He reasoned that such mutants must carry recurrences of a mutation at precisely the same site of the phage genome; they must be exact alleles.

It is assumed that genetic recombination is equally probable at all points of the phage DNA that represents that genome. His genetic map of the rII region showed that genetic recombination is a process that can separate genetic sites represented by contiguous nucleotides on the phage DNA molecule. He found that most genetic recombination (crossing over) occurs within genes rather than between genes (4214).

Benzer changed our concept of the gene, by demonstrating that it has a fine structure consisting of a linear array of subelements. When Benzer did this work most geneticists thought the gene to be indivisible and to be the smallest unit of recombination, mutation, and function(4215). 

Georges N. Cohen (FR) and Howard V. Rickenberg (DE-GB-AU-US) were the first to describe the beta-galactosidase or lac transport system in Escherichia coli(4216).

Peter Dennis Mitchell (GB) postulated that lactose transport occurs in symport (cotransport) with protons and that a proton electrochemical gradient is the immediate driving force for accumulation against a concentration gradient(4217). This is called a symport.

Ian C. West (GB) and Peter Dennis Mitchell (GB) offered proof of Mitchell’s 1963 proposal of a symport(4218).

Howard V. Rickenberg (DE-GB-AU-US), Georges N. Cohen (FR), Gérard Buttin (FR) and Jacques Lucien Monod (FR) discovered and named bacterial permeases in Escherichia coli. They realized that the genes for beta-galactosidase (gene z) and permease (gene y) are controlled as a unit by a third gene which they called I, because it controls inducibility. These were recognized as the membrane enzymes which control the entry of specific families of molecules into the cell. The genes are simultaneously induced by galactosides(4216, 4219, 4220).

Irving Zabin (FR), Adam Képès (FR), and Jacques Lucien Monod (FR) added the gene for thiogalactoside transacetylase to the two genes whose expression is governed by the I gene(2342, 4221). The gene for producing this enzyme was later found to be part of the lactose operon.

Arthur Beck Pardee (US) independently discovered bacterial permeases at a slightly later date(4222).

Benno Müller-Hill (DE), Howard V. Rickenberg (DE-GB-AU-US), Kurt Wallenfels (DE), Claude Burstein (FR), Melvin Cohn (FR), Adam Kèpés (FR), and Jacques Lucien Monod (FR) discovered that lactose is metabolized in part by beta-galactosidase to its isomer 1-6-beta-D-galactosido-glucose (allolactose). It is this allolactose which is the natural inducer of the lac operon(4223, 4224).

C. Fred Fox (US) and Eugene P. Kennedy (US) isolated the product of the lacY gene. They changed its name from Lac permease to M (membrane) protein(4225, 4226).

Milislav L. Demerec (HR-US) and Zlata Hartman (US) applied the gene mapping strategy based on phage transduction of bacterial genes to genes involved in tryptophan synthesis.They found that the genes are arranged on the bacterial chromosome in the same order as the biochemical steps that they control(4227).

Armin Dale Kaiser (US), George Streisinger (HU-US), Victor Bruce (US), Robert S. Edgar (US) and Georgette Harrar Denhardt (US), using genetic crosses, determined that the T-even bacteriophages contain only one linkage group(4228, 4229).

Albert Bruce Sabin (PL-US) developed a polio vaccine containing live attenuated viruses from the three known strains of poliovirus. He tried the vaccine on himself first then on prison volunteers. The vaccine did not displace the Salk vaccine until 1960 when its use abroad on more than 100 million people made it apparent that it was superior(4230, 4231).

Mary B. Mitchell (US), working with Neurospora, provided the first proof of gene conversion, a process by which DNA sequence information is transferred from one DNA helix (which remains unchanged) to another DNA helix, whose sequence is altered. This conversion is due to inappropriate base mismatch repair during recombination(4232).

Henry Bernard Davis Kettlewell (GB) used the interaction of birds with the melanic and mottled forms of the peppered moth (Biston betularia) to investigate whether birds eat cryptic day-resting moths, and whether they do so differentially with respect to morph. They demonstrated that they do both(4233, 4234). This study is one of the most cited examples of evolution being observed in action. The study confirmed a proposal by James William Tutt (GB) that the original, non-melanic form was well camouflaged on the bark of lichen encrusted trees until industrial pollution darkened the trunks of the trees thus favoring the survival of the black form (f. carbonaria)(4235). 

Britton Chance (US) and G.R. Williams (US) applied the oxygen electrode and difference spectrophotometry to give evidence for the sites where the reactions of oxidative phosphorylation occur within mitochondria(4236). 

Harry Eagle (US) made the first systematic investigation of the essential nutritional requirements of eukaryotic cells in culture and found that animal cells could propagate in a defined mixture of small molecules supplemented with a small proportion of serum proteins(4237-4241).

Rosalind Elsie Franklin (GB) proposed the arrangement of protein subunits in tobacco mosaic virus (TMV) based on x-ray diffraction studies(4242).

Francis Harry Compton Crick (GB) and James Dewey Watson (US), assuming a triplet code, deduced that viral protein coats must be composed of many identical protein subunits since the viral nucleic acid in the smaller viruses does not contain enough information to produce a shell to cover all the viral nucleic acid(4243, 4244).

Donald L.D. Caspar (US) used x-ray diffraction patterns of tomato bushy stunt virus (TBSV) to show a high degree of structural symmetry(4245).

Donald L.D. Caspar (US) and Sir Aaron Klug (ZA-GB) put forth principles of icosahedral virus structure(4246).

Fred L. Schaffer (US) and Carlton E. Schwerdt (US) purified then crystallized MEF-1 poliomyelitis virus particles. (4247). This was the first time an animal virus was crystallized.

Gertrude Henle (DE) and Friedrich Deinhardt (DE) propagated and performed primary isolation of mumps virus in monkey kidney tissue culture (4248).

Oscar D. Ratnoff (US) and Joan E. Colopy (US) discovered the Hageman blood clotting factor (factor XII), named for John Hageman (GB)(4249, 4250).

Joshua Lederberg (US) classified the various bacterial recombination processes as: sexuality, transduction (which includes transformation), lysogeny and lysogenic conversion(4251). 

Neal B. Groman (US) discovered that the virus-toxin relationship for toxigenic strains of Corynebacterium diphtheriae is an absolute one. That is, strains which harbor the virus produce the toxin, and those free of the virus do not produce toxin. Thus the virulence of the organism is directly dependent upon the presence of the beta phage in its chromosomes(4252).

Daniel A. Boroff (US) demonstrated that most botulism toxin is released from the bacterial cells by autolysis as the culture ages(4253).

Carlos O. Miller (US) and Folke Karl Skoog (SE-US) discovered that an old commercial preparation of herring sperm DNA was highly active in promoting cell division in pith tissue from the center of the tobacco (Nicotiana tabacum) stem. New DNA preparations did not yield the activity, but it was soon demonstrated that the cell division activity could be generated by heating the DNA preparations in weakly acid solutions in the autoclave.

Carlos O. Miller (US), Folke Karl Skoog (SE-US), Francis S. Okumura (US), Malcolm H. von Saltza (US), and Frank M. Strong (US) isolated, purified, and determined the structure of the compound responsible for the cell division activity of partially degraded DNA preparations. It was identified as 6-furfurylaminopurine (that is, N 6-furfuryladenine). The trivial name kinetin was given to this compound. This was the first example of a new class of plant growth substances that came to be known as cytokinins(4254, 4255).

The discovery of kinetin initiated intensive efforts to isolate and identify all naturally occurring compounds with equivalent activity in promoting cell division in plant tissues. D. Stuart Letham (NZ) and, almost simultaneously, Carlos O. Miller (US), successfully purified and identified a naturally occurring cytokinin from plant material and demonstrated that this compound was also an N 6-substituted adenine derivative. The isolation and identification of N 6-(trans-4-hydroxy-3-methyl-2-butenyl) adenine as the active cell division factor present in immature corn kernels was achieved by Letham. He gave this compound the trivial name of zeatin, and the compound that Miller had isolated from the same source was quickly shown to be identical to zeatin(4256, 4257).

Theodore Thomas Puck (US) and Philip I. Marcus (US) devised the now standard method for cloning animal cells in vitro(4258).

Philip L. Townes (US) and Johannes Friedrich Karl Holtfreter (DE-US) proposed that differential cell adhesion may be one of the key elements underlying epithelial morphogenesis. In this classic study, the epidermis and neural tube were isolated from early amphibian embryos and dissociated into single cells, and the two populations of cells were mixed together in explant culture. Over time, the two cell populations sorted out so that the epidermal cells reformed an epidermis with the correct polarity on the outside of the explant, and the neural cells reformed a neural tube with the correct polarity on the inside of the explant(4259). 

Libbie Henrietta Hyman (US) treated Deuterostomata, Enterocoela, and enterocoelous coelomates as synonymous and inclusive of the four phyla Chaetognatha, Echinodermata, Hemichordata, and Chordata(4260).

Artemij Vasilevich Ivanov (RU) created the phylum Pogonophora (beard worms) to contain protostomate worms found mostly in the abyssal depths of the oceans(4261, 4262). They were originally thought to be deuterostomes.

Göran C.H. Bauer (SE), Arvid Carlsson (SE), and Bertil Lindquist (SE) discussed, reviewed, and reevaluated the use of isotopes of calcium, phosphorus, and sodium in studying the metabolism of the skeleton in normal and pathological states in humans and animals (mainly rats). They found that these isotopes are taken up by the skeleton then released again independently of true anabolic and catabolic processes. Besides maintaining the normal architecture of the bones, their resorption process is mainly responsible for the role of the skeleton in the calcium homeostasis of the body(4263, 4264). 

John W. Saunders, Jr. (US), Mary T. Gasseling (US), Janice E. Errick (US), Eugene Bell (US), Edgar Zwelling (US), Cecelia Reuss (US), M. David Gfeller (), Jack M. Cairns (US), Richard N. Feinberg (US), Mary A. Repo (US), John F. Fallon (US), Arthur B. Maccabe (US), Jeffrey A. MacCabe (US), Marilyn Pickett (US), Dolores J. McWhinnie (US), and Leo Rubin (US) laid the foundation for our understanding of pattern formation in the vertebrate limb. Their experiments suggested that the apical ectodermal ridge (AER) is not only required for limb outgrowth, but it also provides signals that allow specific structures to form at different proximo–distal levels of the limb axis(4265-4291).

John W. Saunders, Jr. (US) and Mary T. Gasseling (US) identified a region at the posterior margin of the wing bud—later termed the zone of polarizing activity (ZPA)—which, when transplanted to an anterior position in the wing-bud margin, caused a mirror-image duplication of digits(4292).

Cheryl Tickle (GB), Dennis Summerbell (GB) and Lewis Wolpert (GB) proposed that the zone of polarizing activity (ZPA) releases a diffusible morphogen, establishing a gradient such that the posterior-most digit arises closest to the source of the morphogen, and the more anterior digits emerge at sites with progressively lower morphogen concentrations(4293).

Robert D. Riddle (US), Randy L. Johnson (US), Ed Laufer (US), and Cliff Tabin (US) showed that the zone of polarizing activity (ZPA) signal is Sonic hedgehog and that retinoic acid, which can convert anterior limb bud tissue into tissue with polarizing activity, concomitantly induces Sonic hedgehog expression in the anterior limb bud(4294). Sonic hedgehog is the best established example of a morphogen that diffuses to form a concentration gradient and has different effects on the cells of the developing embryo depending on its concentration.

Gail R. Martin (US), Philip H. Crossley (US), George Minowada (US), Craig A. MacArthur (US), Jin-Kwan Han (KR), Lee A. Niswander (US), Astrid Vogel (DE), Cheryl Tickle (GB), and Iain Booth (GB) subsequently attributed the signaling activity of the apical ectodermal ridge (AER) to molecules of the fibroblast growth factor (FGF) family(4295-4301).

Renward Mangold (US), Louis Sokoloff (US), Eugene Conner (US), Jerome Kleinerman (US), Per-Olof Therman (US), and Seymour Solomon Kety (US) found that during sleep there is no decrease in oxygen consumption by the brain(4302).

Jerome W. Conn (US) noted that patients with periodic severe muscular weakness, intermittent tetany with parathesis, polyuria, polydipsia and hypertension also showed in their blood a retention of sodium, diuresis of potassium, and increased capacity for carbon dioxide. Aldosterone was found in their urine in excess. Conn named the new disease primary aldosteronism. He found tumor of the adrenal cortex (adenoma) to be the cause(4303, 4304). This condition is also called hyperaldosteronism.

Richard J. Havel (US), Howard A. Eder (US), and Joseph H. Bragdon (US) described an accurate and efficient method for determination of the composition of the different types of lipoproteins in human blood(4305). This article is the origin of the terms: very low density lipoprotein (VLDL), low density lipoprotein (LDL), and high density lipoprotein (HDL). 

Miguel Layrisse (VE), Túlio Arends (VE), R. Dominguez Sisco (VE), Philip Levine (US) and Elizabeth A. Robinson (US) discovered and characterized the Diego blood group antigen(4306, 4307).

Sidney C. Truelove (GB) and Leslie J. Witts (GB) showed the value of cortisone treatment in patients with ulcerative colitis (though with a warning that penicillin and sulfonamides should be used to prevent pyogenic complications)(4308). 

Arthur C. Guyton (US), Arthur W. Lindsey (US), and Berwind N. Kaufmann (US) pioneered the use of analog computers and systems analysis to study the circulatory system. They found that venous return acts as a determinant of cardiac output. They also analyzed the various factors that influence venous return. They demonstrated, mathematically and experimentally in dogs, that venous return is proportional to the mean circulatory filling pressure minus the right atrial pressure, or the "pressure gradient for venous return." They also noted, however, that venous return increased to a greater extent than predicted to occur as a result of increased mean circulatory filling pressure because of the effect of elevated venous pressure to reduce the impedance to venous return(4309).  

William M. Landau (US), Walter H. Freygang, Jr. (US), Lewis P. Rowland (US), Louis Sokoloff (US), and Seymour Solomon Kety (US) provided the first glimpse of quantitative changes in blood flow in the brain related directly to brain function(4310, 4311).

Robert D. Langdell (US), Robert H. Wagner (US) and Kenneth M. Brinkhous (US) developed the first effective therapy for hemophilia: intravenous infusions of factor VIII(4312).

William M. Lougheed (US), William H. Sweet (US), James Clarke White (US), and William R. Brewster, Jr. (US) were the first to use hypothermia for neuroprotection during surgery(4313).

Cristopher S. Welch (US) was the first to transplant a liver. He described transplanting livers into the right paravertebral gutters of immunocompetent mongrel dogs. The allografts atrophied rather quickly, which Welch attributed to rejection(4314).

Charles G. Rob (GB-US) and Harry H.G. Eastcott (GB) reported the first successful surgical reconstruction of a tuberculous aortic aneurysm. They used an Orlon cloth graft(4315).

Michael Ellis DeBakey (US), Denton A. Cooley (US), and Oscar Creech, Jr. (US) performed the first successful resection and graft replacement of an aneurysm of the ascending aorta and the first successful resection of a dissecting aneurysm of the thoracic aorta(4316).

Denis Graham Melrose (GB), B. Dreyer (GB), Hugh H. Bentall (GB), and J.B.E. Baker (GB) solved the problem of the heart beating during open-heart surgery. Using potassium citrate and then potassium chloride, they succeeded in stopping the heart safely in anesthetized dogs on a heart-lung machine(4317). 

Hans J. Bretschneider (DE) introduced cold cardioplegia. This consists of protecting the asystolic heart during surgery by introducing a iced (4 degrees Celsius) solution of dextrose, potassium chloride, and other ingredients into coronary circulation via specialized cannulae(4318). 

David J. Hearse (GB), David A. Stewart (GB), and Mark V. Braimbridge (GB), using the isolated hearts of rabbits and rats, established optimum concentrations of potassium chloride to stop the heart, and ways of preserving the heart while starved of blood. This was achieved by bathing the heart in a solution of precise concentration of various salts and reducing the temperature to below 28 degrees C. This cold cardioplegia is used routinely today in open-heart operations(4319-4321).

Conrad R. Lam (US), Thomas E. Geoghegan (US), and Alfredo Lepore (US) coined the term cardioplegia in describing cardiac arrest via acetylcholine(4322).

1956

“A child’s world is fresh and new and beautiful, full of wonder and excitement. It is our misfortune that for most of us that clear-eyed vision, that true instinct for what is beautiful and awe-inspiring, is dimmed and even lost before we reach adulthood. If I had influence with the good fairy who is supposed to preside over the christening of all children I would ask that her gift to each child in the world be a sense of wonder so indestructible that it would last throughout life, as an unfailing antidote against the boredom and disenchantments of later years, the sterile preoccupation with things that are artificial, the alienation from the sources of our strength.” Rachel Carson(4323, 4324).

André Frédéric Cournand (FR-US), Werner Theodor Otto Forssmann (DE) and Dickinson Woodruff Richards (US) were awarded the Nobel Prize in Physiology or Medicine for their discoveries concerning heart catherization and pathological changes in the circulatory system.

Stellan Hjertén (SE), Östen Levin (SE), and Arne Vilhelm Kaurin Tiselius (SE) introduced column chromatography on hydroxyapatite(4325).

Philips S. Chen, Jr. (US),  Taft Y. Toribara (US), and Huber Warner (US) presented a method for phosphorus determination sufficiently sensitive to dispense with microtechniques and special glassware and apparatus(4326).

Ansul Chemical Company introduced the herbicide DMSA, an organic arsenical, first used for the control of crabgrass in turf. ref 

L.B. Rattree (GB) and W.E. Stephen (GB), in 1956, introduced reactive dyes. These dyes are usually formed by condensation of cyanuric chloride with various amino dyes thus leaving two free chlorines. ref Procion yellow M-4R is an example and has been used to stain nerve tissue.

Audrey M. Glauert (GB), George Ernest Rogers (AU), and Richard H. Glauert (GB) showed that the epoxy resin Araldite is a highly effective embedding agent for electron microscopy(4327, 4328).

Herbert E. Carter (US), Robert H. McCluer (US), and Edward Doyle Slifer (US) were the first to present evidence for the existence of glycosylated glycerides when they isolated two lipocarbohydrate fractions from wheat flour(4329).

Peter A. Tavormina (US), Margaret H. Gibbs (US), and Jesse W. Huff (US) discovered that mevalonic acid is incorporated quantitatively into cholesterol in cell-free systems with an accompanying loss of carbon dioxide(4330).

Raymond Urgel Lemieux (CA) and George Huber (CA) synthesized sucrose(4331).

Edmund C. Kornfeld (US), Eugene J. Fornefeld (US), G. Bruce Kline (US), Marjorie J. Mann (US), Dwight E. Morrison (US), Reuben G. Jones (US), and Robert Burns Woodward (US) synthesized lysergic acid(4332).

Linus Carl Pauling (US) and Robert Brainard Corey (US) were the first to emphasize, based on general structural considerations, that three hydrogen bonds likely existed between cytosine and guanine derivatives in DNA(4333).

Henry M. Sobell (US), Ken-Ichi Tomita (JP), and Alexander Rich (US) used co-crystals of cytosine and guanine derivatives to conclusively demonstrate that these derivatives are held together by three hydrogen bonds(4334). 

Douglas N. Rhodes (GB) and Andrew G.H. Lea (GB) were the first to demonstrate the occurrence of different species of phospholipids(4335, 4336).

Horace Albert Barker (US) published a generalized pathway for the formation of methane from acetate, methanol, or carbon dioxide(4337).

Paul Berg (US) explained how acetyl-CoA is produced from acetate in a two step reaction: 1) ATP + acetate yields acetyl adenylate + PPi, 2) acetyl adenylate + CoA yields acetyl-CoA + AMP(4338, 4339). 

Sir Hans Adolf Krebs (DE-GB) and Hans Leo Kornberg (GB-US) described the glyoxylate cycle. The purpose of this cycle is to enable plants and microorganisms to utilize fatty acids or acetate, in the form of acetyl-CoA, as sole carbon source, particularly for the net biosynthesis of carbohydrate from fatty acids. The glyoxylate cycle by-passes the CO2-evolving steps of the tricarboxylic acid cycle. Animals lack this shunt across the tricarboxylic acid cycle(4340, 4341).

Margaret G. Smith (US), Wallace Prescott Rowe (US), Janet W. Hartley (US), Samuel Waterman (US), Horace C. Turner (US), Robert Joseph Huebner (US), John M. Craig (US), John C. Macauley (US), Thomas Huckle Weller (US), and Pat Wirth (US) isolated human cytomegalovirus (CMV) strains(4342-4344). Newborns, or an adults with a compromised immune systems, are most likely to present with mononucleosis-like symptoms of infection.

Hans Noll (US), Hubert Bloch (US), Jean Asselineau (FR), and Edgar Lederer (FR) determined that the chemical structure of the cord factor of Mycobacterium tuberculosis is trehalose dimycolate(4345).

Anthony San Pietro (US) and Helga M. Lang (US) discovered the ability of isolated chloroplasts to catalyze the light driven accumulation of NADPred(4346).

Alexander Rich (US) and David R. Davies (US) discovered that some single stranded RNA molecules are capable of reacting with one another to form a double helix(4347).

Kenneth Burton (GB) developed a colorimetric method for the quantitative determination of deoxyribonucleic acid (DNA). Acidified diphenylamine reacts with DNA producing a dark blue color with a maximum absorbance at 660 nm(4348). This method allows laboratories without a UV spectrrophotometer to make DNA determinations.

Mack H. McCormick (US), W.M. Stark (US), G.E. Pittenger (US), R.C. Pittenger (US), and James M. McGuire (US) isolated vancomycin from Streptomyces orientalis(4349).

David Libermann (FR), Maurice Moyeux (FR), Noël Rist (FR), and Francoise Grumbach (FR) discovered the antibacterial agent ethionamide (ethylthiosonicotinamide)(4350). 

Vincent C. Barry (IE), Michael L. Conalty (IE), and Ethna E. Gaffney (IE) reported the chemotherapeutic activity of anilinoaposafranines and their derivatives(4351). They are most effective as antimycobacterial agents.

Hans Joachim Müller-Eberhard (DE-US-DE), and Henry George Kunkel (US) determined that gamma globulin and myeloma proteins contain a carbohydrate moiety(4352).

Henry Arnold Lardy (US) and Robert E. Parks, Jr. (US) proposed that ATP at high concentrations inhibits 6-phosphofructokinase activity. This inhibition would stop glycolysis and thereby modulate glycolysis(4353, 4354).

Edward C. Heath (US), Jerard Hurwitz (US), and Bernard Leonard Horecker (US) demonstrated that during the bacterial fermentation of pentoses xylulose 5-phosphate is cleaved phosphorolytically to acetyl phosphate and triose phosphate by a thiamine pyrophosphate-dependent enzyme that they called phosphoketolase(4355).

John L. Graves (US), Birgit Vennesland (DE-US), Merton Franklin Utter (US), and R.J. Pennington (GB) determined the mechanism of the reversible carboxylation of phosphoenolpyruvate(4356).

Lemuel D. Wright (US), Emlen L. Cresson (US), Helen R. Skeggs (US), Gloria D.E. MacRae (US), Carl H. Hoffman (US), Donald E. Wolf (US), and Karl August Folkers (US) discovered and established the chemical structure of mevalonic acid(4357). This led to the identification of mevalonic acid as a source of the pyrophosphate of isopentenol which acts as the metabolic isoprenoid unit used in a series of ATP-dependent reactions to produce squalene.

Edna B. kearney (US) and Thomas P. Singer (US) recovered succinate dehydrogenase from various animal tissues and Proteus vulgaris(4358).

Parithychery R. Srinivasan (US), Harold T. Shigeura (US), Milon Sprecher (US), David B. Sprinson (US) and Bernard David Davis (US) demonstrated that three of the carbon atoms of shikimic acid come from phosphoenolpyruvate and the other four from erythrose-4-phosphate(4359).

Richard E. Strange (GB), F.A. Dark (GB), and L.H. Kent (GB) described N-acetylglucosamine and N-acetylmuramic acid as the two major constituents of the glycan portion of bacterial cell walls(4360, 4361).

Carroll Milton Williams (US) is credited with being the first to suggest that juvenile hormone analogs would make good insecticides(4362, 4363).

Paul Berg (US), Francis Harry Compton Crick (GB), Mahlon Bush Hoagland (US), Robert William Holley (US), Kikuo Ogata (JP), Paul Charles Zamecnik (US), Hiroyoshi Nohara (JP), Jack P. Preiss (US), Mary Louise Stephenson (US), Jesse Friend Scott (US), Liselotte I. Hecht (US), E. James Offengand (US), Fred H. Bergmann (US), and Marianne Dieckmann (US) obtained experimental evidence to support Crick’s "adaptor theory". Their results suggested that during the synthesis of polypeptides, amino acids are first activated by ATP to form a high energy AA-AMP complex. Next these activated amino acid complexes are bonded to low molecular weight RNA molecules (sRNA or tRNA) which escort them to the microsomal (ribosomal) site(4364-4376)

George Emil Palade (RO-US) and Philip Siekevitz (US) found that the structures we now call ribosomes are rich in ribonucleic acids(4377, 4378). 

Elliot Volkin (US) and Lazarus Astrachan (US) isolated an RNA with unexpected properties which is produced when bacteria are infected with coliphage. This RNA has a high turnover rate, the ratios of its four bases resembles the phage DNA, not the bacterial, and it is neither microsomal (ribosomal) RNA, nor is it soluble (transfer) RNA(4379-4382). Some years later Sydney Brenner realized that this RNA must be the messenger RNA for protein synthesis.

Seymour Stanley Cohen (US) discovered that cytosine is replaced by glucosylated hydroxymethylcytosine in the DNA of T-even bacteriophage(4383).

Arthur J. Kornberg (US), Israel Robert Lehman (US), Maurice J. Bessman (US), and Ernest S. Simms (US) discovered and purified DNA polymerase I (first polymerase recognized) of Escherichia coli. This enzyme’s activities include polymerization, pyrophosphorolysis, pyrophosphate exchange, and two independent exonucleolytic hydrolyses, one of which degrades in the 3’—5’ direction and the other in the 5’—3’ direction. Remarkably all of these activities are contained within one polypeptide chain(4384, 4385). Later it was discovered that DNA polymerase I of E. coli plays an essential role in processing the nascent Okazaki fragments produced during the discontinuous replication of the lagging strand at the replication fork to prepare them for ligation. The multisubunit DNA polymerase III holoenzyme is actually the enzyme that catalyzes the synthesis of the E. coli chromosome.

Maurice J. Bessman (US), Arthur J. Kornberg (US), Israel Robert Lehman (US), and Ernest S. Simms (US) showed that naturally synthesized nucleotides containing cytosine or thymine join through a 5' linkage(4384, 4386, 4387).

Harold Edwin Umbarger (US) discovered that high levels of isoleucine inhibit the pathway used to produce isoleucine(3890).

Richard Alan Yates (US) and Arthur Beck Pardee (US) discovered that aspartate transcarbamylase is inhibited by the presence of pyrimidine nucleotides which are the end-product of the pathway containing this enzyme. They observed that when cytosine is plentiful, the enzyme is blocked(3891).

Vernon Martin Ingram (DE-GB-US) modified chromatographic techniques developed by Seymour Jonathan Singer (US) to carry out what Ingram called protein fingerprinting to analyze the alpha and beta chains of hemoglobin. He discovered that sickle cell hemoglobin differs from normal hemoglobin in that each beta chain has a single amino acid substitution at position 6: normal hemoglobin has a glutamic acid, sickle cell hemoglobin has a valine. This discovery suggested that mutations may result from a very slight change in hereditary material(4388, 4389). This was the first concrete evidence that genes specify the amino-acid sequence of proteins.

John A. Hunt (US) and Vernon Martin Ingram (DE-GB-US) found that the mutation in hemoglobin C turned out to be a substitution of a single amino acid at the same position as the hemoglobin S mutation. In the case of hemoglobin C, the change was glutamic acid to lysine, a net change of 2 charge units(4390).

Donald L.D. Caspar (US) and Rosalind Elsie Franklin (GB) independently established the location of ribonucleic acid within the protein capsid of tobacco mosaic virus(4391, 4392).

Rollin Douglas Hotchkiss (US) discovered that at high DNA concentrations (e.g. 10-4 mg/ml) DNA transformation plateaued. It has been deduced that the pneumococci have a limited number of DNA receptors, for which all DNA molecules compete(4009).

 

Francois Jacob (FR) and Élie L. Wollman (FR) produced the first timed course map of a bacterial chromosome by mechanically shearing mating pairs. They used Escherichia coli Hayes K12(4393-4395).

Palmer D. Skaar (US) and Alan Garen (US) performed a very similar mechanical shearing experiment using Escherichia coli(4396).

Francois Jacob (FR) and Élie L. Wollman (FR) demonstrated that the transfer of a phage-bearing chromosome (lysogenic state) to a sensitive cell often resulted in the maturation and aggressive growth of the phage resulting in lysis. On the other hand, the introduction of a sensitive chromosome (no integrated virus) into a lysogenic bacterium does not result in this induction(4393).

Rose Litman (US) and Arthur Beck Pardee (US) discovered that addition of 5-bromouracil to the culture medium of T2-infected bacteria results in the appearance of a very greatly increased proportion of mutants among the phage progeny (4397).

Robert Jack Downs (US) and Harry Alfred Borthwick (US) found that, “the photochemical reaction controlling germination and flowering and growth of herbaceous plants also controls onset of dormancy and the elongation of new structures of woody plants”(4398).

Sterling Brown Hendricks (US), Harry Alfred Borthwick (US), and Robert Jack Downs (US) used data from experiments with pinto beans, lettuce, and Lepidium (peppergrass) to calculate what fraction of the photoperiodic pigment is in the active form at any time and how efficiently each form absorbs and uses radiant energy(4399).

Anton Lang (RU-US) and James L. Liverman (US) found that gibberellin and indoleacetic acid are capable of inducing flowering in Hyoscymus niger and long-day plants respectively(4400, 4401).

Theodore Thomas Puck (US) and Harold W. Fisher (US) selected mutants with altered growth requirements from cultures of HeLa cells. They also demonstrated that, if the molecular environment is carefully controlled, mammalian cell stocks can be cultivated with genetic stability comparable to that of microorganisms(4402). 

Albert Tyler (US), Alberto Monroy (US), C.Y. Kao (US), and Harry Grundfest (US) discovered that polyspermy in starfish is prevented by an electrical change at fertilization—now called fertilization potential(4403).

Yasuhiro Iwao (JP) and Laurinda A. Jaffe (US) demonstrated that it is the sperm which sense the voltage(4404).

Robert Merritt Chanock (US) isolated—from infants with croup—a virus producing sponge-like syncytial areas in monkey kidney tissue culture. He called it CA virus (Croup-Associated Virus)(4405). Later the Committee on Viral Nomenclature classified CA virus as parainfluenza virus.

Tikvah Alper (GB), and P. Howard-Flanders (GB) showed that bacterial sensitivity to radiation can be modified by the presence or absence of oxygen(4406).

Theodore Sall (US), Stuart Mudd (US), John C. Davis (US), Akira Yoshida (JP), Masaatsu Koike (JP), and Atsushi Takagi (JP) demonstrated, using the electron microscope, the presence of cellular granules in bacteria. These were later to be called metachromatic granules(4407-4409).

Ki Yong Lee (FR), R. Wahl (FR), Eugen Barbu (FR), Andrei Nikolaevitch Belozerskii (RU), Alexander S. Spirin (RU) Noboru Sueoka (US), Julius Marmur (US), and Paul Mead Doty (US) showed that the base compositions of DNAs varied widely among the different bacterial species—while the RNAs hardly varied at all(4410-4412).

Montrose J. Moses (US) identified the synaptonemal complex(4413).

Virginia J. Evans (US), Jay C. Bryant (US), Mary C. Fioramonti (US), William T. McQuilkin (US), Katherine K. Sanford (US), Wilton R. Earle (US), and Benton B. Westfall (US) were the first to succeed in growing animal cells in a completely defined medium. The cells were L cells grown in medium NCTC109(4414, 4415).

Theodore Thomas Puck (US) and Philip I. Marcus (US) produced the first single cell survival curve for eukaryotic cells exposed to X irradiation(4416).

Loren Daniel Carlson (US), Walter H. Cottle (US), and Arnold C.L. Hsieh (CN) discovered that one of the ways in which rats adapt to cold by increased heat production is to alter their endocrine secretions, specifically an increase in the level of noradrenaline (norepinephrine)(4417, 4418).

Evelyn M. Witkin (US) presented evidence that bacteria have a mechanism in place to repair damaged DNA. This repair mechanism is affected by such parameters as time, temperature, and protein synthesis(4419).

Peter Henry Andrews Sneath (GB) pioneered the study of bacterial taxonomy using numerical taxonomy techniques(4420-4423).

Stephen Wilhelm (US), Edward C. Koch (US), L.C. Benson (US), James E. Sagen (US), Richard C. Storkan (US) and T. Carpenter (US) discovered that chloropicrin and methyl bromide are excellent soil fumigants to eliminate the parasite causing verticillium wilt of strawberries(4424-4426).

Joseph R. Goodman (US), Roger E. Moore (US), and Richard F. Baker (US) showed that phagocytes ingest bacteria by completely enveloping them with the cell membrane of the ingesting cell(4427, 4428). 

Ernest Robert Sears (US) produced leaf rust resistance in Triticum aestivum (wheat), a susceptible species, by transferring a chromosome into it from Aegilops umbellulata (goat-grass), a species resistant to the rust(4429).

Robert E. Snodgrass (US) produced an excellent book on the anatomy of the honeybee, Apis mellifera Linn(4430).

Ari van Tienhoven (NL-US), H.C. Thomas (US), and Lester J. Dreesen (US) found that a drug (sulfamethazine), which was introduced to treat diseases of poultry (coccidiosis and fowl cholera), was to have the side effect of stimulating comb and testes growth in Leghorn chicks(4431).

Bruce Glick (US), Timothy S. Chang (CN-US), and R. George Jaap (US) discovered that removal of the bursa of Fabricius— named for Giralamo Fabrizi (IT), 1533-1619 —from chickens leads to impaired immune function, i.e., the lack of antibody formation(4432).

Noel L. Warner (AU), Aleksander Szenberg () and Frank Macfarlane Burnet (AU) showed that elimination of the bursa of Fabricius in chickens caused a defect in antibody responses, whereas thymectomy crippled cellular immune responses(4433).

Charlotte Friend (US) characterized a murine virus which induces erythroleukaemia accompanied by anemia. This virus was named the Friend leukaemia virus (FLV) in her honor(4434, 4435). FLV would later be classified as a retrovirus.

Rupert Everett Billingham (GB-US), Leslie Brent (GB), and Sir Peter Brian Medawar (GB) concluded that in mice the transplantation antigens are developed many days before birth(4436).

Rupert Everett Billingham (GB-US), Leslie Brent (GB), and Sir Peter Brian Medawar (GB) proposed that all the nucleated cells of different tissues of an individual have exactly the same antigenic make-up and that neonatal mice given foreign tissue would later treat it as self— immunological tolerance— whereas older mice which had never experienced the same foreign material would treat it as non-self and respond immunologically(4437).

Curt Paul Richter (US) discovered mineralocorticoid-induced sodium hunger, i.e., the hormone (aldosterone) not only acts to conserve and redistribute sodium in the body, but also to generate the behavior of salt ingestion(4438).

Frederic Crosby Bartter (US), Grant W. Liddle (US), Leroy E. Duncan, Jr. (US), Joan K. Barber (US), and Catherine S. Delea (US) reasoned that extracellular fluid volume is a major determinant of aldosterone secretion(4439). This deduction ultimately led several groups to the discovery that the aldosterone regulatory influence of extracellular volume is mediated by the renin-angiotensin system.

Edmund Brisco Ford (GB) defined polymorphisms as “the occurrence together in the same habitat of two or more (inherited) discontinuous forms of a species, in such proportions, that the rarest of them cannot be maintained merely by recurrent mutation”(4440).

Robert Kyle Burns (US) and Lucile Moore Burns (US) collected original data on food, movement, breeding season, gestation period, number of young born and reared, pouch life, and folklore of the American opossum, Didelphis virginiana(4441, 4442).

Bodil M. Schmidt-Nielsen (US), Knut Schmidt-Nielsen (US), T. Richard Houpt (US), and S.A. Jarnum (DZ) reported that the camel’s adaptations to the desert climate include: highly variable body temperature, an insulating layer of fur, toleration of 24 -36 percent loss of body weight as water loss (man can tolerate 12-18 percent), constant blood volume during dehydration, and large water volume intake without water intoxication(4443, 4444). 

Joe-Hin Tjio (US) and Johan Albert Levan (US) were the first to establish with certainty that the diploid chromosome number of man is 46(4445, 4446).

Norman Bier (GB) introduced the plastic contact lens(4447).

Robert E. Blount, Jr. (US), J.A. Morris (US), and R.E. Savage (US) isolated respiratory syncytial virus and suspected that it was infectious to humans. They called it CCA (chimpanzee coryza agent)(4448). RSV is the most common cause of bronchiolitis (inflammation of the small airways in the lung) and pneumonia in children under 1 year of age in the United States. RSV is a negative-sense, single-stranded RNA virus of the family Paramyxoviridae.

Jack Levin (US) and Frederick Barry Bang (US) discovered that the lysate of amebocytes from the hemolymph of the horseshoe crab, Limulus polyphemus, clots in the presence of liposaccharides in the cell walls of gram negative bacteria. This discovery led to the development of an in vitro assay for pyrogens contaminating injectable products. This Limulus amebocyte lysate (LAL) assay replaced the rabbit pyrogen test(4449-4452).

Charles E. Smith (US), Margaret T. Saito (US), and Susan A. Simons (US) established the usefulness of serology in the diagnosis and prognosis of coccidioidomycosis(4453).

Gregory Goodwin Pincus (US), Min Chueh Chang (CN-US), Meyer X. Zarrow (US), Elsayed Saad Eldin Hafez (US), and Anne Merrill (US) discovered that 19-norsteroids prevent ovulation in women. This represents the origin of the contraceptive pill(4454).

Charles P. Emerson (US), Shu Chu Shen (US), Thomas Hale Ham (US), Eleanor M. Fleming (US) and William Bosworth Castle (US) concluded that the function of the spleen in hereditary spherocytosis may be normal and the inherited defect is limited to the red cells(4455).

Jean-Louis Beaumont (FR), Jacques P. Caen (FR), Jean Bernard (FR), and Charles E. Blatrix (FR) noted that aspirin, in relatively small doses, results in a prolongation of bleeding time(4456, 4457).

Harvey J. Weiss (US) and Louis M. Aledort (US) showed that prolongation of bleeding time course by aspirin (3 grams/day for two and a quarter days) is associated with a marked impairment of collagen-induced platelet aggregation(4458). 

Herman Moritz Kalckar (DK-US), Elizabeth P. Anderson (US), Kurt J. Isselbacher (US), and Kiyoshi Kurahashi (JP) found that the enzyme defect in the most serious form of galactosemia is in the uridyl transferase(4459, 4460).

Herman Moritz Kalckar (DK-US), Elizabeth P. Anderson (US), Kiyoshi Kurahashi (JP), and Kurt J. Isselbacher (US) developed a blood test for uridyl transferase which allowed early detection of severe galactosemia thus preventing the associated severe mental retardation and other developmental defects(4461).

Clinton Nathan Woolsey (US) and Ann M. Travis (US) showed that after bilateral removal of all neocortex in stages, monkeys could show considerable recovery of motor function and become capable of locomotion if given adequate post-operative physical therapy(4462).

George Henry Alexander Clowes, Jr. (US), Amos L. Hopkins (US), and William Evans Neville (US) designed and made a large flat multi-layered ethylcellulose membrane blood oxygenator; used clinically on several patients(4463).

Warren E.C. Wacker (US), David D. Ulmer (US), and Bert L. Vallee (US) demonstrated that blood levels of metalloenzymes can be used to diagnose myocardial infarction(4464).

Vincent Paul Dole (US) developed an efficient method to measure the concentration in plasma of non-esterified fatty acids, those fatty acids bound to protein(4465).

Alexander Solomon Wiener (US), Lester J. Unger (US), Laura Cohen (US), and J.D. Feldman (US) discovered the I blood group antigen in man(4466).

Newton E. Morton (US) detected and estimated the linkage between the genes for elliptocytosis and the Rh blood type in man(4467).

Frederick P. Moersch (US) and Henry W. Woltman (US) described and named the stiff-man syndrome(4468).

Michele Solimena (IT), Franco Folli (IT), Suzanne Denis-Donini (IT), Giancarlo C. Comi (IT), Guido Pozza (IT), Pietro De Camilli (IT), and Aurelio M. Vicari (IT) presented evidence that stiff-man syndrome is an autoimmune disease(4469).

Fredric Austin Gorin (US), Barbara A. Baldwin (US), Robert C. Tait (US), Rajiv Pathak (US), Masud Seyal (US), and Emiliano Mugnaini (US) determined that stiff-man disease is characterized by autoantibodies that react with cell bodies and axon terminals of gamma-aminobutyric acid (GABA)ergic neurons(4470). Neurons that produce GABA as their output are called GABAergic neurons, and have chiefly inhibitory action at receptors in the adult vertebrate.

Maurice Payet (SN-FR), Robert Camain (FR), Pierre Pene (FR), Paul E. Steiner (US), and Jack N.P. Davies (US) suggested that hepatitis could be the cause of primary hepatic carcinoma (PHC)(4471-4473).

Baruch Samuel Blumberg (US), Bernard Larouzé (FR), W. Thomas London (US), Barbara Werner (US), Jana E. Hesser (US), Irving Millman (US), Adrien Gérard Saimot (FR), Maurice Payet (SN-FR), Edward D. Lustbader (US), and Marc Sankalé (SN) established that there is a striking association of hepatitis B virus with primary hepatic carcinoma (PHC)(4474, 4475).

Edgar Zwillung (US) and Louis A. Hansborough (US) discovered that a typical polydactylous limb develops from the combination of mutant mesoderm and normal ectoderm in chick embryos(4476).

Fritz Fuchs (DK) and Povl Riis (DK) were the first to examine amniotic fluid to diagnose genetic disease. They determined fetal sex from cells found in amniotic fluid, based on the presence or absence of the Barr body(4477). This may be the first prenatal sex determination.

Henry M. Parrish (US), Frank R. Lock (US), and Mary E. Roundtree (US) reported the lack of congenital malformations in normal human pregnancies after transabdominal amniocentesis(4478).

Mark W. Steele (US), W. Roy Breg, Jr. (US), Cecil B. Jacobson (US), and Robert H. Barter (US) found that chromosomal abnormalities can be detected in the fetus, by karyotyping, without harm to the pregnancy(4479, 4480). This initiated the concept that cytological prenatal diagnosis may eventually lead to prenatal treatment. The Jacobson-Barter paper marked the beginning of prenatal genetic diagnostic procedures for detection of fetal chromosomal and enzymatic disorders.

Trevor P. Telfer (GB), Kenneth William Ernest Denson (GB), Donald R. Wright (GB), Cecil Hougie (US), Emily M. Barrow (US) and John B. Graham (US) discovered a previously unknown clotting factor, now known as factor X. This discovery provided the missing link in the blood clotting cascade, connecting the intrinsic and extrinsic pathways to the final steps in clot formation(4481-4483).

Noel R. Rose (US), Ernest Witebsky (DE-US), Kornel Terplan (US), John R. Paine (US), Richard W. Egan (US), Deborah Doniach (GB), Peter N. Campbell (GB), Rupert Vaughn-Hudson (GB), and Ivan Maurice Roitt (GB) established Hashimoto’s chronic thyroiditis as an autoimmune disease when they discovered its association with thyroglobulin autoantibodies(4484-4488). Hakaru Hashimoto (JP) first described this lymphoid goiter or struma in 1912.

Björn Sigurdsson (IE) described benign myalgic encephalomyelitis(4489).

Hans C. Engell (DK), Erik Kyvsgaard (DK), and Inge H. Rygg (DK) developed a low volume disposable pumpless bubble oxygenator(4490). This machine was soon used as a substitute lung for children with cystic fibrosis, respiratory distress syndrome (RDS), and cyanotic heart disease (CHD).

Bernice Grafstein (CA-US) reported that propagation of cortical spreading depression (CSD) depends on the liberation of potassium ions from depolarized neurons. She also demonstrated that recovery from spreading depression is an oxidative, energy-dependent process(4491). This conclusion is now central to concepts of the way in which acute brain injury evolves, both in experimental models and now increasingly in patients receiving neurocritical care.

Donald Walter Gordon Murray (CA), Walter Roschlau (CA), and William Lougheed (CA) performed the first successful transplant of a human heart valve homograft(4492).

Denton A. Cooley (US) and Michael Ellis DeBakey (US) performed the first successful resection and graft replacement of an aneurysm of the ascending aorta(4493).

Michael Ellis DeBakey (US), Oscar Creech, Jr. (US), and George C. Morris. Jr. (US) were the first to perform a successful resection with graft replacement of an aneurysm of the thoracoabdominal portion of the aorta between the chest and abdomen. This procedure was done with a graft replacement of the arteries leading from the aorta to the liver, spleen, stomach, gastrointestinal tract, and kidneys(4494).

Michael Boris Shimkin (US), Matthew H. Griswold (US), and Sidney J. Cutler (US) made the case for early diagnosis and treatment of cancer when, from 1935 to 1951, they examined a total of 75,494 cancer cases in the state of Connecticut. The state had 2,000,000 residents in 1950. They found that the five-year survival rate improved due to earlier diagnosis of the cases. The improvement has occurred in cancer that is diagnosed when it is clinically localized and when it involves regional areas, but not when it is disseminated. The most marked improvement is recorded for cancers of the colon and rectum in both sexes, and of the uterine cervix in women(4495).

Wliiiam L. Brown, Jr. (US) and Edward Osborne Wilson (US) described character displacement as the situation in which, when two species of animals overlap geographically, the differences between them are accentuated in the zone of sympatry and weakened or lost entirely in the parts of their ranges outside this zone. The characters involved in this dual divergence-convergence pattern may be morphological, ecological, behavioral, or physiological(4496).

1957 

“Humility and perspective are necessary ingredients of scientific craftsmanship; here they concur in stressing the far reaches of our ignorance.” Joshua Lederberg(4497).

“Discovery consists of seeing what everybody has seen, and thinking what nobody has thought.” Albert Szent-Györgyi(4498).

Lord 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(4499). 

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(4500).

Hal Oscar Anger (US) invented a type of gamma-camera. A scintillation camera which permits visualization of radiotracer distribution in biological systems and makes possible dynamic studies(4501).

Russell L. Steere (US) invented freeze-fracture specimen preparation for electron microscopy(4502).

Hans Moor (CH), Kurt Mühlethaler (CH), Heinz Waldner (CH), and Albert Frey-Wyssling (CH) perfected the freeze fracture technique(4503, 4504). 

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(4505).

Arthur J. Kornberg (US) reported that all four of the deoxynucleotide triphosphates must be present for DNA synthesis to take place(4506).

Julian E. Philip (US), Jay R. Schenck (US), and Martha P. Hargie (US) isolated the antibiotic ristocetin from Nocardia lurida(4507).

Gordon C. Mills (US) determined that glutathione peroxidase is an erythrocyte enzyme which protects hemoglobin from oxidative breakdown in the intact erythrocyte(4508).

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(4509).

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(4510, 4511). 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 reveled that this substance is a cyclic derivative of ATP, i.e., cyclic AMP(4512).

Earl Wilbur Sutherland, Jr. (US), Theodore W. Rall (US), and Tara Menon (US) discovered adenyl cyclase, the enzyme which converts ATP into 3’, 5’-cyclic AMP(4513).

David Lipkin (US), William H. Cook (US), and Roy Markham (US) determined the structure and molecular weight of adenosine-3', 5'-phosphate (cyclic AMP)(4514).

Gary Felsenfeld (US), David R. Davies (US), and Alexander Rich (US) discovered that RNA molecules are capable of forming triple helices(4515).

Michael Sela (IL), Frederick H. White, Jr. (US), Christian B. Anfinsen (US), and Edgar Haber (US) helped explain the connection between the amino acid sequence and the biologically active conformation in proteins(4516-4518).

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 culminated in the demonstration that the glyoxylate cycle of fat-storing seeds is located in a specific metabolic/cytoplasmic compartment, the glyoxysome(4519-4525). The glyoxysome turned
out to be the first of a new class of plant organelles called
microbodies(4526).

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(4527).

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 in the course of biosyntheses(4528).

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(4529, 4530).

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"(4531).

Leonard S. Lerman (US) and Leonard J. Tolmach (US) succeeded in labeling transforming DNA with 32P and demonstrated that the radioactivity was incorporated into a genetically transformed strain of pneumococcus(4532, 4533).

Sir Hans Adolf Krebs (DE-GB) and Hans Leo Kornberg (GB-US) proposed that a single enzyme in a biochemical pathway may act as a pacemaker that controls the supply of substrate for subsequent reactions(4534).

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(4535).

Hugh John Forster Cairns (GB-US-GB) calculated the mass of T2 bacteriophage DNA to be 110 X 106 daltons(4536).

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(4537).

Alvin Markovitz (US) and Albert Dorfman (US) concluded that the enzyme responsible for glycosyl transfer in group A streptococci is localized on the protoplast membrane(4538). 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(4539-4541).

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(4542). 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(4543-4546).

Charles Heidelberger (US), N.K. Chaudhuri (IN), Peter B. Danneberg (US), Dorothy Mooren (US), Lois Griesbach (US), Robert Duschinsky (US), Robert J. Schnitzer (US), Edward Pleven (US), J.  Scheiner (US), and Willi E. Oberhänsli (CH) synthesized 5-flurouracil (FU) and 5-fluoro-2’-deoxyuridine (FUdR) as antimetabolites to treat tumors(4547-4549).

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(4550-4554).

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(4555).

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)(4556).

John Clark Sheehan (US) and Kenneth R. Henery-Logan (US) synthesized Penicillin V(4557, 4558). 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(4559-4563).

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(4365, 4371, 4372, 4564).

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(4565). This method has found widespread use in clinical medicine.

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”(4566).

John E. Vogel (US), Alexis Shelokov (US), and Lotta Chi (US) developed the hemagglutination-adsorption (hemadsorption) technique for detecting myxoviruses(4567, 4568).

Jordi Casals (ES-US) grew the yellow fever virus in suckling mice(4569).

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)(4570).

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(4571).

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(4572-4574).

Hugo P. Kortschak (US), Constance E. Hartt (US), and George O. Burr (US) noted that some compounds other than 3-phosphoglyceric acid (3-PGA) were rapidly labeled during 14CO2 assimilation by sugarcane leaves(4575-4577).

Yuri S. Karpilov (RU) independently reported similar early labeling of malate and aspartate during 14CO2 assimilation by maize leaves(4578).

Marshall Davidson Hatch (AU), C. Roger Slack (GB), and David J. Goodchild (AU) discovered and worked out the metabolic details of the C4 pathway for photosynthetic carbon assimilation(4579-4581).

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(4582).

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(4583, 4584).

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.))(4585).

David W.H. Barnes (GB) and John Freeman Loutit (GB) made the first attempt to treat leukaemia in mice by bone marrow transplantation after lethal total body irradiation (TBI)(4586).

E. Donnell 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 leukaemia in humans using high dose chemotherapy or total body irradiation or a combination of both followed by bone marrow transplantation(4587, 4588).

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(4512, 4589).

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(4590).

Rosalyn Sussman Yalow (US), Solomon Aaron Berson (US), Arthur Bauman (US), Marcus A. Rothschild (US), and Katharina Newerly (US) while investigating the distribution of insulin in humans, discovered that people develop antibodies to injected animal insulin. In order to investigate this phenomenon, the researchers undertook to develop a tool for measuring circulating insulin levels. The radioimmunoassay was the result(4591-4596).

Joshua Lederberg (US) and Thomas Foxen Anderson (US) demonstrated that following bacterial conjugation the female generates a mixed clone, including recombinants, among the offspring(4597, 4598).

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 boundries, Escherichia coli K-12 to Shigella and Escherichia coli to Salmonella typhimurium(4599, 4600).

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(4601).

Frederick G. Germuth, Jr. (US) and G.E. 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 interstitual fluids, and are capable of reacting with complement(4602).

Sir James L. 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(4603-4607).

Helge Sjövall (SE) had earlier proposed this but thought the lymphocytes recycled mainly through the tissue spaces of the body generally(4608).

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(4603). 

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(4609). 

Heinz Ludwig Fraenkel-Conrat (DE-US), Beatrice Singer (US), and Robley Cook Williams (US) mixed viral coat proteins and RNA from two different viruses prior to infecting tobacco plants (Nicotiana tabacum). They found that the lesions on the tobacco plants are entirely dependent on the source of RNA in the reconstituted virus(4610).

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(4611, 4612).

Robert Paul Hanson (US) and Carl A. Brandly (US) worked out the epizootiology of vesicular stomatitis virus(4613).

James P. Duguid (GB) and Robert Reid Gillies (GB) discovered that Shigella flexneri adheres to epithelial surfaces by the use of fimbriae (pili)(4614).

Daniel Israel Arnon (PL-US), F. Robert Whatley (GB), and Mary Belle Allen (US) determined that triphosphopyridine nucleotide (TPN or NADP) acts as a catalyst in photosynthetic phosphorylation(4615).

Daniel Israel Arnon (PL-US), F. 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 can 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 they are ultimately accepted by oxidized NADP. 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(4616-4621). 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(4622). 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(4623).

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(4624).

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(4625, 4626). 

Klaus Schwarz (US) and Calvin M. Foltz (US) were the first to recognize that selenium (Se) is important to normal human metabolism(4627).

Vernon Benjamin Mountcastle (US) discovered and characterized the columnar organization of the cerebral cortex(4628).

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(4629). This is called the Jervell and Lange-Nielsen syndrome.

Cesarino Romano (IT), G. 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)(4630, 4631). This is called the Romano-Ward syndrome.

William Beecher Scoville (US) and Brenda Milner (US), 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(4632).

Roland Kuhn (CH) used clinical trials to prove the usefulness of imipramine as an antidepressant(4633).

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 an eczematoid dermatitis about the eyes, nose, and mouth(4634).

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)(4635).

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(4636).

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(4637).

George W. Comstock (US) found that Afro-Americans have higher blood pressures at all ages and in both sexes than do Caucasians(4638). 

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(811). Burke A. Cunha (US) reports that this pandemic of influenza A was the first to be studied using modern scientific techniques(4639).

Leslie Foulds (GB) proposed that the development of cancer is a multistep process(4640).

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(4641).

George Evelyn Hutchinson (US) developed the formal notion of the ecological niche as a geometric hypervolume with both biotic and abiotic dimensions, a concept which led to a revolution in niche theory(4642, 4643)}.

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)(4644).

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(4645).

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 combines 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 at a later time, so simultaneous optimization of more than one character is a problem also in nature(4646).

George C. Williams (US) conclude 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(4647).

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(4648).

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(4649).

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(4650). 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(4651).

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(4652).

1958

“A gifted man cannot handle bacteria or equations without taking fire from what he does and having his emotions engaged.” Jacob Bronowski(4653).

"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(4367).

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.

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(4654).

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(4655).

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(4656). 

Paul Divry (BE), Jean Bobon (BE), Jackie Collard (BE), Andre Pinchard (BE) and E. Nols (BE) performed the clinical trials of haloperidol which became a treatment for schizophrenia(4657).

Vernon Martin Ingram (DE-GB-US) developed the peptide fingerprinting technique(4658).

Herbert E. Carter (US), Donald B. Smith (US), and D.N. Jones (US), using egg yolk, were the first to isolate an ether phospholipid(4659).

Geigy Chemical Company introduced the herbicide atrazine, a symmetrical triazine, which is useful in corn (Zez 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 (Zez mays), and peanuts (Arachis hypogaea). ref

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(4660).

Tomomasa Misato (JP), Itaru Ishii (JP), Masaru Asakawa (JP), Y. Okomoto (JP), Kazuo Fukunaga (JP), and K. Hashimoto (JP) discovered that the antibiotic blasticidin S could be used to successfully treat rice blast(4661-4664).

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. (4665). 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 leukaemia. In those situations where hematologic remission was not achieved, tumor cell infiltrates have decreased in size(4666, 4667).

Anthony San Pietro (US) and Helga M. Lang (US) discovered ferredoxin and its role in photosynthesis(4668).

Joel Mandelstam (GB) showed that the breakdown as well as the synthesis of proteins occurs in intact bacteria(4669).

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(4670, 4671).

 S. Shiba (JP), A. Terawaki (JP), T. Taguchi (JP), and J. Kawamata (JP) showed that mitomycin C acts by specific damage to DNA(4672).

John Cowdery Kendrew (GB), Gerhard Bodo (GB), Howard Marvin Dantzis (GB), Robert Guy Parrish (GB), Harold Winfield Wyckoff (GB), Richard Earl Dickerson (GB), Bror E. Strandberg (GB), Robert George Hart (GB), David R. Davies (GB), 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(4673-4675). 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(4676, 4677).

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(4678).

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(4679, 4680).

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(4681, 4682).

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(4385, 4683, 4684).

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 as a result of diabetes mellitus and/or starvation. The mechanism is a metabolic cycle they called the HMG-CoA (hydroxymethylglutaryl-CoA) cycle(4685).

Otto Wieland (DE) successfully explained how this represented a deficiency in the citric acid cycle’s ability to handle excess acetyl-CoA(4686).

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(4687-4689). 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(4690, 4691).

Paul Talalay (US), H. Guy Williams-Ashman (US), and Barbara Hurlock (US) demonstrated that oxidoreductions of steroid hormones by hydroxysteroid dehydrogenases (HSDs) can promote reversible transfer of hydride groups between NAD(H) and NADP(H)(4692, 4693).

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(4694).

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(4367, 4695). Horace Freeland Judson says the 1958 paper by Crick “permanently altered the logic of biology”(2665).

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(4367).

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(4696). 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(4697).

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 (4367).

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(3455, 4698, 4699). The 1959 article by Jacob and Monod introduced the word operator as the target of the repressor.

Georges Cohen (FR) shortly thereafter demonstrated that in the case of tryptophane synthesis there is an inactive form of repressor which will not suppress the pathway unless it interacts with the end-product of the pathway (tryptophane), thereby being converted to the active form which shuts down the genes of the pathway(4700).

Liselotte I. Hecht (US), Mary Louise Stephenson (US), Paul Charles Zamecnik (US), Hans Georg Zachau (DE), George Acs (US), and Fritz Albert Lipmann (DE-US) discovered that all sRNA (tRNA) molecules have the same three terminal bases, CCA, on the free 3’ end which binds to the amino acid. Consequently all amino acids are transported while attached to the adenosine moiety(4368, 4369, 4701).

John R. McLean (US), George L. Cohn (US), Ira K. Brandt (US), Melvin V. Simpson (US), Donald B. Roodyn (GB), P.J. Reis (AU), and Thomas Spence Work (GB) presented evidence that mitochondria are capable of independent protein synthesis(4702, 4703).

Guido Pontecorvo (IT-GB) observed that the rule that genes controlling metabolically sequential enzymes constitute genetic clusters does not apply, in general, to organisms other than bacteria(4704). 

Richard Brooke Roberts (US) proposed that the name ribosome (ribonucleoprotein particles of the microsomal fraction) be used in place of what had heretofore been called microsomes(4705).

Alfred Tissières (CH), James Dewey Watson (US), David Schlessinger (US), and Barbara R. Hollingsworth (US) carried out the first physical characterization of ribosomes when they isolated four kinds of ribonucleoprotein particles from Escherichia coli cells. They were observed to have sedimentation coefficients of 30S, 50S, 70S, and 100S(4706, 4707).

John Spizizen (US) demonstrated DNA mediated genetic transformation in Bacillus subtilis. As this organism could grow in simple minimal media, it was possible to utilize a variety of auxotrophic markers(4708). This made it possible to investigate the genetic controls of biosynthetic pathways as was being done in Escherichia coli using other gene transfer systems found to be highly transformable. Refinements to achieve optimal conditions for transformation were later introduced.

Jakob Reinert (DE), Frederick C. Steward (US), Marion O. Mapes (US), Joan Smith (US) and Kathryn Mears (US) accomplished the formation of pro-embryonic tissue in callus clumps and cell suspensions of plant tissue(1058, 1059, 4709, 4710).

Peter C. Nowell (US), David A. Hungerford (US), and Carter D. Brooks (US) discovered that phytohemagglutinin (PHA) is mitogenic for peripheral lymphocytes of the blood. In this same work they were the first to see Giemsa banding of chromosomes(4711). This banding is now called G banding of chromosomes.

Nathan Kaliss (GB) discovered a special form of immunological unresponsiveness—immune enhancement—defined by the depression of cell-mediated immunity by circulating antibody(4712).

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(4713).

Kunio Tagawa (JP) and Daniel Israel Arnon (PL-US) found that a crystalline preparation of the iron-sulfur protein ferrodoxin from the nonphotosynthetic anaerobic bacterium Clostridium pasteurianum is also highly active in promoting photoreduction of NADP+ in spinach chloroplasts. This observation suggested that an iron-sulfur protein resembling bacterial ferrodoxin is one of the components carrying electrons from photosystem 1 to NADP+(4714).

Emanuel Riklis (IL) and Juda Hirsch Quastel (GB-CA) showed that the process of active transport of sugars (glucose, galactose, and fructose) by the isolated surviving guinea pig intestine is markedly affected by the cation concentrations present in the salt solutions bathing the intestine(4715).

Moselio Schaechter (US), Ole Maaløe (DK), and Niels Ole Kjeldgaard (DK) discovered that bacteria can grow in a continuum of physiological states determined by the growth rate(4716). This is a seminal paper in bacterial growth physiology.

Jacques C. Senez (FR) and Francis Pichinoty (FR) discovered a group of bacteria which are nutritionally halfway between autotrophs and heterotrophs when characterized metabolically. Desulfovibrio is a typical organism in this group. This organism can oxidize hydrogen with sulfate forming water and sulfide. The energy released can be coupled to the assimilation of organic materials(4717).

Marvin P. Bryant (US), Milton J. Allison (US), and Raymond N. Doetsch (US) were the first to show that many rumen bacteria, other heterotrophic bacteria, and most methanogenic anaerobic bacteria have a very limited ability to utilize organic nitrogen sources such as amino acids or peptides. Instead, they utilize ammonia as their essential and major nitrogen source and utilize carbon dioxide and various volatile fatty acids, such as acetate, as a source of carbon(4718). 

Sir Gustav Joseph Victor Nossal (AU) and Joshua Lederberg (US) discovered that a single lymphocyte can produce only one specific type of antibody(4719). Martin C. Raff (GB), Marc Feldmann (GB), and Stefanello de Petris (GB) offered an elegant proof of this by showing that incubation of lymphocytes with antigen can aggregate (cap) all the surface immunoglobulin on antigen-binding cells; this indicated that the only immunoglobulin on the surface of these cells is antibody of a single specificity(4720).

Sir Peter Brian Medawar (GB) coined the phrase immunologically competent cell to define a cell that is fully qualified to undertake an immunological response(4721).

Kimishige Ishizaka (JP) and Dan H. Campbell (US) showed that soluble antigen-antibody complexes produce cutaneous reactions of increased vascular permeability(4722).

Charles G. Cochrane (US) and William O. Weigle (US) found that soluble antigen-antibody complexes can produce vascular necrosis(4723).

Robert E. Kissling (US) grew the rabies virus in non-nervous tissue culture (hamster kidney)(4724).

Howard Martin Temin (US) and Harry Rubin (US) developed he first quantitative assay for viral transformation. In the mid 1950s Rous sarcoma virus, an avian retrovirus, was found to induce morphological changes and extend the life of chick embryo fibroblast cells in culture. Transformation was detected as foci of dense morphologically altered cells in monolayers of chick embryo fibroblasts. It depends on the loss of contact inhibition following transformation(4725).

Emilio Weiss (US), Harry R. Dressler (US), William F. Myers (US), Charles L. Wisseman, Jr. (US), Anna D. Waddell (US), and David J. Silverman (US) determined that Rickettsiae prowazekii microorganisms are truly bacteria and not life forms halfway between bacteria and viruses, and rickettsial membranes are not leaky. Relative to Escherichia coli, rickettsiae are about half the size, have a genome one-third as large, and grow twenty times slower(4726-4730).

P.R. Fry (NZ), Raymond G. Grogan (US), F.W. Zink (US), William Boright Hewitt (US), and K.A. Kimble (US) discovered that the soil fungus Olpidium brassicae serves as a host and vector of the lettuce big vein virus(4731, 4732).

Seventeen living specimens of bristle cone pine, Pinus aristata, from the White Mountains of California were found to be over 4,000 years old(4733).

Ernest Robert Sears (US) and Masasuke Okamoto (JP) discovered that chromosome pairing in wheat is genetically controlled. Consequently, the chromosomes of many other species, not ordinarily able to pair and recombine with those of wheat, could be induced to do so by removing chromosome 5B from commercially-grown hybrids(4734, 4735).

Sir Ralph Riley (GB) and Victor Chapman (GB) described the genetic systems by which pairing of wheat chromosomes at meiosis is limited to those which are fully homologous, and by which pairing between distantly related chromosomes is precluded. This basic knowledge allowed them to pair and recombine chromosomes in a way that is normally illegitimate(4736-4738).

Theodore Thomas Puck (US), Steven J. Cieciura (US), and Arthur Robinson (US) established that diploid human cells can be maintained in vitro for a maximum of one year (50 to 60 passages) before they degenerate and progress to aneuploid(4739-4741). This allowed persons with genetic defects to provide stocks with known markers, the underlying biochemistry of which can be studied in vitro.

Yoshio Okada (JP) and Jun Tadokoro (JP) showed that high concentrations of the HVJ (Sendai) virus (alive or dead) cause Ehrlich ascites cells to rapidly fuse(4742-4745).

Erwin Bünning (DE) proposed that the environment forms a plant’s natural internal rhythm into 24-hour cycles, each consisting of a 12 hour light-loving or photophile phase, in which light promotes flowering, followed by a 12 hour dark-loving or scotophile phase, in which light inhibits flowering(4746).

William Boright Hewitt (US), Dewey J. Raski (US), and Austin C. Goheen (US) discovered that the ectoparasitic nematode, Xiphinema index, serves as a vector for soil-borne fanleaf virus of grapevines(4747).

Gottfried Samuel Fraenkel (DE-US) discovered the reason for secondary plant compounds, “as only…to repel and attract insects”(4748-4750).

Miriam Rothschild (GB), Joseph von Euw (PL-CH), Lev Fishelson (IL), John A. Parsons (GB), and Tadeus Reichstein (PL-CH) offered the first proof of the sequestration and storage by brightly colored, aposematic, insect herbivores of toxic secondary plant substances and toxic, self-secretions(4751-4753). 

Hans Werner Lissman (DE-GB) and Kenneth E. Machin (GB) demonstrated that fish which are weakly electric can detect objects in their immediate vicinity by sensing changes in the electric fields produced by their own electric organs(4754, 4755).

Robert Helmer MacArthur (CA-US) made the first definitive study of community resource partitioning. He studied five species of warblers (MacArthur’s warblers) that breed in boreal forests of North America. He and Eric R. Pianka (US) concluded that feeding in different places and in different manners allowed these species to coexist in the same community(4756-4758).

Knut Schmidt-Nielsen (US) and Ragnär Fange (SE) found that marine turtles possess a salt-secreting gland to eliminate excess salt which collects in their tissues(4759).

Knut Schmidt-Nielsen (US) discovered that marine birds eliminate the salts taken in with food and water by a gland in the head which can be called the salt-excreting gland or simply the salt gland(4760). 

Denis Parsons Burkitt (GB) postulated that a lymphoma common among African children is caused by a mosquito-transmitted infectious agent. This lymphoma became known as Burkitt’s lymphoma(4761).

Sir Michael Anthony Epstein (GB), Bert G. Achong (GB), and Yvonne M. Barr (GB) cultured human lymphocytes from Burkitt’s lymphoma and in the process demonstrated the presence of a herpes virus(4762). These human herpes virus 4 (HHV-4) particles have since been called Epstein-Barr virus.

Sir Michael Anthony Epstein (GB) and Yvonne M. Barr (GB) were the first to grow human lymphocytes in continuous culture(4763).

Joseph H. Burchenal (US) promoted the use of Burkitt's tumor as a model for understanding leukaemia(4764, 4765).

George Klein (SE), Gary R. Pearson (US), Gertrude Henle (US), Werner Henle (US), Volker Diehl (US), and James C. Niederman (US) reported that infectious mononucleosis not only is caused by a herpetovirus, but is also caused by an agent that cannot be distinguished from the Epstein-Barr virus(4766, 4767). See, Nil Feodorovich Filatov, 1887.

Min Chueh Chang (CN-US) and Thorsteinn Thorsteinsson (US) found that rabbit sperm are not effected by being placed in Ringer’s solution from 0.5X to 2X in concentration. Furthermore, at isotonicity these sperm can tolerate a pH range from 5.57 to 10.94(4768). 

William Barry Wood, Jr. (US) and M. Kenton King (US) discovered the leucocytic origin of endogenous pyrogen in acute inflammatory exudates and investigated its role in the inflammatory process(4769-4772).

William F. Jarrett (GB), Frank W. Jennings (GB), W. Ian McIntyre (GB), William Mulligan (GB), B.A. Thomas (GB) and George MacDonald Urquhart (GB) developed an irradiation-attenuated vaccine against lungworm (Dictyocaulus viviparus) of sheep and cattle(4773, 4774). Its commercial name is Dictol.

Börje Larsson (SE), Lars Leksell (SE), Bror Rexed (SE), Patrick Sourander (SE), William George Parker Mair (SE), and Bengt Andersson (SE) developed the concept of radiosurgery. They first employed proton beams coming from several directions into a small area in the brain, in experiments in animals and in the first treatments of human patients(4775).

Lars Leksell (SE) later developed a special apparatus known as the Gamma Knife. It is a sterotactice device which contains multiple radioactive cobalt sources and is dedicated solely to radiosurgery(4776). Gamma Knife surgery is recognized worldwide as the preferred treatment for brain tumors, arteriovenous malformations and brain dysfunctions like trigeminal neuralgia.

Basil Isaac Hirschowitz (ZA-US), Larry E. Curtiss (US), C. Wilbur Peters (US), and H. Marvin Pollard (US) applied fiber optics in the development and construction of a completely flexible optical instrument which allowed direct visualization of the cavity of the duodenum, the esophagus, and stomach(4777).

Ian Donald (GB), John MacVicar (GB), and Tom Graham Brown (GB) produced what is considered the most important paper on obstetrical and gynecological sonography ever written. The paper deals with 100 patients. It contained B-mode sonograms of the gravid uterus, ovarian cysts, fibroids and ascites and various normal and pathological conditions. Other papers are included which emphasize the use of this technique to guide the amniocentesis needle, exclude twins, and avoid the anterior placenta(4778-4781).

Maurice Ralph Hilleman (US), Frederick J. Flatley (US), Sally A. Anderson (US), Mary L. Luecking (US), and Doris J. Levinson (US) introduced a vaccine to the Asian influenza(4782). 

Herman Moritz Kalckar (DK-US) proposed that fallout following atmospheric tests of nuclear weapons can be measured by analysis of the content of strontium-90 in the milk-teeth of young children(4783).

Endre Kelemen (HU), István Cserhati (HU), and B. Tanos (HU) coined the term thrombopoietin when they described the humoral substance responsible for the rebound thrombocytosis that follows states of thrombocytopenia(4784). Thrombopoietin (TPO) stimulates the development of megakaryocyte precursors of platelets, leading to an increase in the number of circulating platelets in a manner that is analogous to the erythropoietin (EPO) stimulation of erythroid precursors.

Bertha A. Bouroncle (US), Bruce K. Wiseman (US), and Charles A. Doan (US) gave a detailed description of twenty-six cases of leukemic reticuloendotheliosis (hairy cell leukaemia) which identified it as an independent hematologic and pathologic entity(4785).

Rudolf Rabl (DE) discovered the first example of gender dimorphism in the human brain, conferring to women greater thalamic connectivity in the region massa intermedia(4786).

Alice M. Stewart (GB), Josefine Webb (GB), and David Hewitt (GB) carried out an epidemiological study to see if there was a relationship between X rays during pregnancy and leukaemia in children(4787). This paper is significant because it prompted two important discoveries—that all childhood cancers have fetal origins and that cancers of the immune system can affect reactions to other diseases before they are themselves recognizable clinically. 

Ernest W. Walton (GB) provided the definitive description of Wegener’s granulomatosis(4788).

Theodore Brown Rasmussen (CA), Jerzy Olszewski (PL-CA), and Donald Lloyd-Smith (CA) described the features of a chronic neurological syndrome characterized by brain dysfunction, encephalitis, and intractable epilepsy, i.e., Rasmussen’s encephalitis(4789).

Scott W. Rogers (US), P. Ian Andrews (US), Lorise C. Gahring (US), Teri Whisenand (US), Keith Cauley (US), Barbara Crain (US), Thomas E. Hughes (US), Stephen F. Heinemann (US), and James O. McNamara (US) suggested that autoantibodies to glutamate receptor GluR3 may be the cause of Rasmussen's encephalitis(4790).

Carl Axel Gemzell (SE), Egon Diczfalusy (SE), and Karl Gunnar Tillinger (SE) used extracts of human pituitary gonadotropins (hPG), containing both follicle-stimulating hormone (FSH) and luteinising hormone (LH) to successfully induce ovulation in humans(4791).

Joaquin Barraquer (ES) and Joaquin Rutllan (ES) discovered that alpha-chymotrypsin can be used to enzymatically dissolve the zonules of the eye for removal of a lens with cataract(4792, 4793).

Manucher Javid (US) introduced osmotic diruetics for reduction of intracranial pressure(4794).

Charles E. Ford (GB), Patricia A. Jacobs (GB), and Lazlo G. Lajtha (GB) introduced chromosome analysis using fresh bone marrow(4795).

Paul S. Moorehead (US), Peter C. Nowell (US), William J. Mellman (US), D.M.A. Battips (US), and David A. Hungerford (US) developed a method for chromosome preparations of leucocytes cultured from human peripheral blood. The key ingredient was phytohaemagglutinin, added to remove red cells from plasma, which coincidently caused lymphocyte transformation(4796). This method largely replaced the bone marrow method.

G.K. Chrustschoff (RU) and E.A. Berlin (RU) had much earlier observed that autolysis of red cells induces cell division in lymphocytes(779).

Aubrey Leatham (GB) provided a new classification for heart murmur analysis. Prior to this work, systolic murmurs were seldom differentiated by their configuration or timing. Leatham's new classification of mid-systolic ejection murmurs versus pansystolic regurgitant murmurs, based on his graphic analysis, changed the way clinicians approached the bedside diagnosis of valvular disease and contributed to decision making for cardiac surgery(4797).

Charles Theodore Dotter (US) and Louis H. Frische (US) developed a new method to reliably and safely visualize the coronary vessels. The method employed a soft, double-lumen balloon catheter. Prior to this time, there had been no reliable way to visualize the coronary vessels(1364).

Hannibal Hamlin (US), William H. Sweet (US), and William M. Lougheed (US) performed one of the first successful carotid bifurcation reconstructions(4798).

Oscar Creech, Jr. (US), Edward T. Krementz (US), Robert F. Ryan (US), and James N. Winblad (US) developed a technique of regional perfusion found to be useful with cases of malignant melanoma, soft tissue sarcomas in the limbs, and some pelvic cancers(4799).

Konrad Zacharias Lorenz (AT) defined ethology as , “the application of orthodox biological methods to the problems of behavior” and credited Charles Robert Darwin with being its scientific father. His comparative studies showed that man and simpler animals have many behavioral patterns in common(4800, 4801).

Carl B. Huffaker (US) performed predator/prey experiments which suggested that in a sufficiently natural environment (of reasonable size for meaningful interaction), continuity is possible without stipulation of prey immigration or specific prey refuges(4802). 

Robert Ashley Couper (NZ) presented fossil evidence for the earliest undisputed angiosperm pollen. It is from the Barremian stage (late early Cretaceous), ca.120 Ma(4803).

Roland E. Beschel (AT) developed the method of using lichen growth to date rocks and other objects covered by lichens (lichenometry)(4804-4806). This method is most accurate within 100 to 9,000 years ago.

1959

“Pythagoras discovered the simple numerical relations of what we call musical intervals.…It has been suggested that the three intervals of the tuned string were compared with the three ways of life. While this must remain speculation it is certainly true that the tuned string henceforth plays a central part in Greek philosophical thought. The notion of harmony, in the sense of balance, the adjustment and combination of opposites like high and low, through proper tuning, the conception of the mean or middle path in ethics, and the doctrine of the four temperaments all of these go back in the end to Pythagoras’ discovery.…It is very likely that the discoveries in music led to the notion that all things are numbers. Thus, to understand the world around us, we must find the number in things.” Bertrand Russell(4807). 

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

E. Graham Bligh (CA) and William J. Dyer (CA) developed a rapid method of total lipid extraction and purification from biological materials(4808).

Stanford Moore (US), Darrel H. Spackman (US), and William H. Stein (US) described a procedure for the chromatographic fractionation of mixtures of amino acids by elution analysis on columns of Dowex-50, a sulfonated polystyrene resin. Compared to starch the resin columns possess higher resolving power, are more convenient to operate, are faster, and the separation is not adversely affected by the presence of inorganic salts in the material chromatographed(4809).

Albrecht K. Kleinschmidt (DE), H. Rüter (DE), Wilhelmine Hellmann (DE), Rudolf K. Zahn (DE), A. Docter (DE), E. Zimmermann (DE), Dimitri Lang (DE) and Diether Jacherts (DE) developed a method which allows the visualization of DNA molecules as smooth, flexible filaments(4810, 4811).

Adolf Friedrich Johann Butenandt (DE), Roland Beckmann (DE), Dankwart Stamm (DE), and Erich Hecker (DE) identified and determined the structure of the sex attractant (bombykol) of the silkworm, Bombyx mori, as (E,Z)-10,12-hexadecadien-1-ol. This was the first insect pheromone to be identified(4812, 4813).

Jakob Schreiber (CH), Willy Leimgruber (US), Mario Pesaro (CH), Peter Schudel (CH), Terry L. Threlfall (GB) and Albert Eschenmoser (CH) carried out the total synthesis of colchicine(4814, 4815).

Grant R. Bartlett (US) developed a method for assaying phosphorus using column chromatography(4816).

Louis Frederick Fieser (US) and Mary Fieser (US) coined the term steroid to denote any structure like cholesterol(4817).

Jon Bremer (NO) and David M. Greenberg (US), using in vivo labeled methionine, discovered that phosphatidylethanolamine may generate phosphatidylcholine via three successive methylation steps(4818).

Sydney Brenner (ZA-GB) and Robert W. Horne (GB) developed the negative staining technique, invented four years previously by Hall, into a generally useful technique for visualizing viruses, bacteria, and protein filaments(4819).

Juan Oró (US) Aubrey P. Kimball (US), R. Fritz (US), and F. Master (US) synthesized amino acids from formaldehyde and hydroxylamine under primitive Earth conditions(4820).

David F. Elliott (GB), Eric William Horton (GB), and Geoffrey P. Lewis (GB) isolated, purified, and determined the amino-acid composition of bradykinin(4821-4824). They later determined that it is a nonapeptide(4825, 4826).

Rodney Robert Porter (GB), Gerald Maurice Edelman (US), and Miroslav Dave Poulik (CZ-CA-US) discovered that antibody molecules are composed of four protein molecules called chains. Each antibody molecule possesses two identical heavy chains and two identical light chains(4827, 4828).

Baruj Benacerraf (VE-US) and Philip G.H. Gell (GB) found that immunization with conjugates (protein carriers linked to a hapten) is followed by the appearance of delayed hypersensitivity to the protein “carrier” in the absence of detectable antibodies against it, although antibodies are produced at that time against the haptenic group itself. Delayed hypersensitivity to the haptenic group has not been detected at any time; blocking it with specific antibody does not lead to the appearance of delayed hypersensitivity, but merely suppresses antibody formation against that group(4829).

Bernard B. Levine (US), Antonio Ojeda (US), and Baruj Benacerraf (VE-US) developed the concept of Ir (immune response) genes. Individuals with this gene would be able to recognize certain carriers and thereby synthesize antibodies or manifest delayed-type hypersensitivity to the target hapten(4830).

Ira Green (US), William E. Paul (US), and Baruj Benacerraf (US) found that hapten-poly-L-lysine conjugates behaved as complete antigens in genetic responder and as haptens in nonresponder guinea pigs(4831).

Sidney Walter Fox (US), Kaoru Harada (JP), Kenneth R. Woods (US), Charles Ray Windsor (US), and Allen Vegotsky (US) showed how amino acids can be heated under Earth conditions to form proteinoids or "thermal proteins," which when placed in water self-organize into microspheres or protocells, possible precursors of the contemporary living cell(4832-4835).

Siro Senoh (US), John Daly (US), Julius Axelrod (US), and Bernhard Witkop (US) discovered catechol-O-methyltransferase (CMOT) and determined that it is capable of catalyzing the methylation of a wide variety of natural catechols. They proposed a metabolic pathway for the metabolism of noradrenaline and adrenaline(4836).

O. Arunlakshana (US) and Heinz O. Schild (GB) demonstrated that drugs and drug antagonists compete for receptors according to the law of mass action(4837).

William H. Prusoff (US) reported on 5-iodo-2’-deoxyuridine (IDU), one of the first compounds tested and shown to be active against DNA viruses(4838). It was soon shown to be effective against herpes simplex virus in a rabbit eye model.

Feodor Felix Konrad Lynen (DE), Joachim Knappe (DE), Ekkehard Lorch (DE), Gerd Jütting (DE), Erika Ringelmann (DE), and Jean-Paul Lachance () discovered that biotin is a coenzyme acting along with enzymes such as carboxylase in the transfer of activated carbon dioxide(4839-4841).

Howard Rasmussen (US), Lyman Creighton Craig (US) and Gerty Hochster (US) isolated and characterized the main hormone produced by the parathyroid glands, parathyroid hormone (PTH)(4842, 4843).

Frank Ralph Batchelor (GB), Frank Peter Doyle (GB), John Herbert Charles Nayler (GB), and George Newbolt Rolinson (GB) discovered 6-aminopenicillanic acid (6-APA), the penicillin nucleus. It provided the ideal starting point for the preparation of new penicillins because different side chains could be attached to the nucleus, through the free amino group, by chemical means(4844). 

Federico Maria Arcamone (IT), Cesare Bertazzoli (IT), Mario Ghione (IT), and Tullio Scotti (IT) isolated the antibiotics melanosporin and elaiophylin from Streptomyces melanosporus(4845).

Federico Maria Arcamone (IT), Cesare Bertazzoli (IT), Mario Ghione (IT), and Tullio Scotti (IT) isolated the antibiotic gabbromycin or aminosidine sulfate from Streptomyces crestomyceticus(4846, 4847).

Theodore H. Haskell (US), James C. French (US), and Quentin R. Bartz (US) isolated the antibiotic paromomycin from Streptomyces rimosus(4848).

Christine O. Dawson (GB) and James C. Gentles (GB) discovered the teleomorphs (perfect or sexual state) of Trichophyton (Keratinomyces) ajelloi (4849).

Alvin Markovitz (US), Joseph A. Cifonelli (US), and Albert Dorfman (US) synthesized hyaluronic acid in a cell-free preparation of streptococci(4850). This was the first cell-free synthesis of a heterologous polysaccharide.

Jerker Olof Porath (SE) and Per Flodin (SE) introduced gel filtration using cross-linked dextran gels. This produced a so-called molecular sieving(4851, 4852).

Samuel Raymond (US) and Lewis S. Weintraub (US) introduced the polyacrylamide gel electrophoresis (PAGE) technique. It is superior to starch gels for separating proteins by electrophoresis(4853).

Baruch Joel Davis (US) and Leonard Ornstein (US) described the use of polyacrylamide gel for disc electrophoresis(4854, 4855). 

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

An Italian company, Lepetit, isolated and tested the antibiotic rifampicin (rifampin, rifamycin, or rifaldazine). It was isolated from Streptomyces mediterranei (Amycolatopsis mediterrani) found in a wooded area of Northern Italy. The antibiotic was named for a movie, Rififi, being filmed in the area at the time(4856). Rifamycin blocks initiation of RNA chains by binding to RNA polymerase (prevents RNA synthesis) in prokaryotes only.

Peter Karlson (DE) and Adolf Friedrich Johann Butenandt (DE) proposed the name pheromone to designate substances secreted by an animal to the outside and causing a specific reaction in a receiving individual of the same species. This term is synthesized from the Greek pherein (to carry) and horman (to excite)(4857).

Samuel B. Weiss (US) and Leonard Gladstone (US) were the first to describe the RNA-synthetic activity of a RNA polymerase. They used rat liver as experimental material(4858).

Audrey Stevens (US), using E. coli, almost simultaneously discovered RNA polymerase(4859).

Ru-chih Huang (US), Nirmala Maheshwari (IN), and James Frederick Bonner (US) discovered the synthesis of RNA from DNA in peas(2942, 2943).

Jerard Hurwitz (US), John J. Furth (US), Monika Anders (US), Priscilla J. Ortiz (US), and J. Thomas August (US) presented their studies with the E. coli RNA polymerase, which provided an enzymatic mechanism by which DNA supported RNA synthesis(4860).

Bention Nisman (FR), Hiroshi Fukuhara (FR), Tadanori Kameyama (JP), G. David Novelli (US), Alfred Tissieres (US), David Schlessinger (US), and Francoise Gros (FR) observed that DNAase inhibits in vitro incorporation of amino acids into proteins thus suggesting that protein synthesis depends on DNA templates(4861-4863).

Francois Jacob (FR) and Jacques Lucien Monod (FR) isolated and genetically analyzed many mutants in the lactose utilization pathway. Their studies of these mutants led to the conclusion that induction and repression are under the control of specific proteins, which are coded for by regulatory genes. They proposed that regulator genes are closely associated with the structural genes coding for specific enzyme proteins but are distinct from them. They visualized regulator substance interacting with a genetic element, an operator, which controlled expression of the structural genes(3455, 4864). The term operon was coined in the 1960 paper.

Milislav L. Demerec (HR-US) and Philip E. Hartman (US) noted that in bacteria the genes controlling enzymes of the same biochemical pathway tend to remain clustered because they are all controlled by the same operator gene(4865).

Alice L. Tuttle (US) and Howard Gest (US) discovered that the photosynthetic apparatus of the photosynthetic bacteria is associated with the cytoplasmic membrane and/or membranous extensions into the cytoplasm(4866).

Micheline M. Mathews (US) and William R. Sistrom (US) determined that the function of carotenoid pigments in non-photosynthetic bacteria is to diminish the harmful effects of light radiation(4867).

R. Clinton Fuller (US) and Martin Gibbs (US) found that purple bacteria contain the Calvin-Benson cycle of carbon fixation(4868).

Choh Hao Li (CN-US) and Phil G. Squire (US) purified and determined the properties of interstitual cell-stimulating hormone from sheep pituitary glands(4869).

Clement L. Markert (US) and Freddy Møller (US) proposed the term isozyme or isoenzyme to denote different enzymes which share functional specificity but which vary slightly reflecting their tissue of origin, their ontogeny, or their species of origin(4870).

Louis Barkhouse Flexner (US), Josefa B. Flexner (ES-US), Richard B. Roberts (US), and Gabriel L. de la Haba (US) independently discovered isoenzymes(4871).

Jennie Ciak (US) and Fred E. Hahn (US) showed that the antibiotic D-cycloserine, an analog of D-alanine, inhibits cell wall synthesis(4872).

Jack Leonard Strominger (US) and Robert H. Threnn (US) reported that the antibiotic novobiocin inhibits cell wall synthesis(4873).

Shimon Gatt (US), Ray Wu (US) and Efraim Racker (PL-AT-US) showed that glycolysis is dependent on the continuous regeneration of ADP and inorganic phosphate by an ATPase. This was the first indication that an ATPase is in the family of glycolytic enzymes(4874-4877).

Joshua Lederberg (US) theorized that lymphocytes pass through an obligatory paralyzable state early in their ontogeny during which an encounter with an antigen will silence or kill them. If they pass this point without antigenic stimulation they become inducible, i.e., capable of being activated(4878).

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

Most spontaneous mutations and those induced by dyes such as proflavine rarely reverted to the wild-type. He suggested that in these a purine was replaced by one of two pyrimidines or a pyrimidine by one of the two purines. He called this type of substitution a transversion(4879-4881).

Benjamin D. Hall (US), Paul Mead Doty (US), Uriel Z. Littauer (IL), Heini Eisenberg (IL), Serge N. Timasheff (US), Raymond A. Brown (US), John S. Colter (US), and Maurice C. Davies (US) reported that ribosomal RNA from higher organisms sedimented as two distinct components, 18S and 28S(4882-4884).

Joseph-Felix Heremans (BE), M.T. Heremans (BE), and Hermann E. Schultze (BE) described IgA and laid one of the foundations for our understanding of intestinal immunity(4885).

Kenneth McQuillen (US), Richard Brooke Roberts (US), and Roy John Britten (US) proved that in Escherichia coli protein synthesis occurs on ribosomes(4886).

Tracy Morton Sonneborn (US) established that the “kappa” particles of Paramecium aurelia represent the first known case of cytoplasmic inheritance in animals. He hypothesized that intracellular symbiotes and cell organelles have become inextricably combined during evolution(4887).

Lemuel Ruscoe Cleveland (US) and Albert Victor Grimstone (GB) described Mixotricha paradoxa, a protozoan symbiotic to Darwin’s termite (Mastotermes darwiniensis), as a very unusual protozoan that is a composite of a eukaryotic protozoan with three independent prokaryotic symbionts: spirochetes, bacteria associated with the spirochetes, and endosymbiotic bacteria(4888).

Lynn Margulis (US) proposed that the eukaryotic cell is an evolutionary chimera, put together from at least three quite different, previously prokaryotic, lineages(4889, 4890).

Tom Cavalier-Smith (US) coined the collective term Archezoa to include amitochondrial protists (the diplomonads, mastigamoebae and retortamonads) and microsporidians. He explained the origin of mitochondria and chloroplasts within eukaryotic cells by proposing what became know as the endosymbiotic or endosymbiont theory(4891, 4892). See Mereschkowsky, 1905.

Gordon Alastair Maclachlan (CA) and Helen K. Porter (CA) discovered that higher plants can also continue to produce ATP by photophosphorylation in the absence of CO2 for assimilation(4893).

Richard L. Wood (US) discovered septate junctions. They are found in invertebrate tissues where they participate in adhesion, sealing, and communication(4894).

Harry Eagle (US) introduced his minimum essential medium (MEM) for the cultivation of eukaryotic cells. With the exception of a small amount of dialyzed serum this medium is defined and can support cell multiplication(4895).

S. Jon Singer (US) used antibodies coupled to ferritin to detect cellular molecules in the electron microscope(4896).

Takashi Hayashi (JP) found that application of gamma-aminobutyric acid (GABA) strongly suppressed electrical activity in the mammalian nervous system(4897).

Edward A. Kravitz (US), Stephen William Kuffler (US), and David D. Potter (US) found large amounts of gamma-aminobutyric acid (GABA) in the inhibitory axons of Crustacea(4898).

David W. Krogmann (US), André Tridon Jagendorf (US), and Mordhay Avron (IL) presented evidence for the coupling of ATP synthesis to electron transport in illuminated chloroplasts(4899).

Peter Dennis Mitchell (GB) and Jennifer Moyle (GB) proposed that energy-yielding and energy-requiring reactions of oxidative phosphorylation are linked by a high-energy state, rather than by a compound. They theorized that an electrochemical gradient of protons across the mitochondrial inner membrane serves as the means of coupling the energy flow from electron transport to the formation of ATP. The membrane is an integral part of the coupling mechanism and must be intact in the form of a continuous closed vesicle for oxidative phosphorylation to take place. They postulated that it is the function of the electron carriers of the respiratory chain to serve as an active-transport system or pump to transport protons from the mitochondrial matrix across the inner membrane, thus generating a gradient of protons across the membrane, which they postulated to be impermeable to protons. The electrochemical gradient thus generated is then postulated to drive the synthesis of ATP by causing dehydration of ADP and Pi. They determined that mitochondria translocate approximately two protons across the mitochondrial membrane for each ATP generated by oxidative phosphorylation and demonstrated that in mitochondria ATP can be artificially generated by making the medium outside the inner mitochondrial membrane moderately acidic vis-à-vis the mitochondrial matrix. They were the first to realize that the buildup of protons in the thylakoid sac of chloroplasts might serve as a source of energy to drive phosphorylation of ADP to ATP and predicted that the thylakoid membrane should be asymmetrical(4217, 4900-4922). The four parts of the chemiosmotic coupling theory are stated in the 1966 article

Roger Yate Stanier (CA), Michael Doudoroff (RU-US), Riyo Kunisawa (US), and Rebecca Contopoulou (US) found that when photosynthetic bacteria oxidize organic substrates they use only a small portion of the reducing power gained to reduce carbon dioxide. Most of these substrates were found to be assimilated directly as poly-beta-hydroxybutyric acid (PHB) or as polysaccharide(4923).

Michael Doudoroff (RU-US) and Roger Yates Stanier (CA) used Pseudomonas saccharophilia and Rhodospirillum rubrum to show that excess substrate carbon accumulates within the cell as poly-beta-hydroxybutyric acid (PHB). When the external substrate is removed, the stored PHB is degraded intracellularly. PHB is therefore an important carbon and energy reserve for these bacteria(4924).

Albert Bruce Sabin (PL-US) grew the reovirus in monkey kidney tissue culture and coined the name reovirus to reflect the fact that viruses of this group had been isolated from the respiratory and enteric tracts and were orphan viruses without known associated disease (reo)(4925).

Björn A. Afzelius (SE-US) used 40% osmium tetroxide to treat preparations for the electron microscope and found that in the 9+2 pattern of the axoneme he could spot arms that reached from one outer doublet toward another. He suggested that the beating movements of eukaryotic flagella are produced by active microtubular sliding powered by arms extended from the microtubular doublets toward one another(4926).

Ian R. Gibbons (US) correlated the presence of the crossing arms with the ATPase activity of the cilia(4927).

Ian R. Gibbons (US) and Arthur J. Rowe (GB) subsequently named these connecting arms dynein(dynein, force protein)(4928).

Ian R. Gibbons (US) and Barbara H. Gibbons (US) discovered an ATPase activity in eukaryotic flagella(4929, 4930).

Ian R. Gibbons (US) stated that dynein arms are ATPases responsible for generating the sliding movements between microtubules that undergo ciliary and flagellar motility. The microtubules being arranged in 9 doublets surrounding two central tubules, the so called 9+2 arrangement(4931). Dynein was the first microtubule force-producing protein motor to be described, and has since been shown to be involved in intracellular trafficking as well as locomotion, including translocation of membrane-bounded vesicles in neurons, golgi vesicles, kinetochores, and mitotic spindle astral microtubules. 

Annemarie Weber (DE-US), Ruth Herz (DE), Ingrid Reiss (DE), Wilhelm Hasselbach (DE), Shinpei Yamada (JP), Taibo Yamamoto (JP), and Yiji Tonomura (JP), showed that the sarcoplasmic reticulum is a vesicular membrane possessing a calcium ion, magnesium ion-dependent ATPase system capable of reducing external calcium to micromolar concentrations and that, following the addition of permeate anions such as oxalate or phosphate, calcium ion precipitates can be detected within the sarcoplasmic reticulum vesicles. These observations clearly showed that calcium ion is being transported by the vesicular sarcoplasmic reticulum. Simultaneous measurements of ATP concentrations revealed that the hydrolysis of one mole of ATP results in the uptake of two moles of calcium ion. This intercellular calcium ion pump is the first known example of a cellular energy-driven counter transport mechanism. ATPase activity and the state of contraction of natural actomyosin and myofibrils are unique functions of free calcium ion concentration(4932-4945).

Richard H. Kessler (US), Klaus Hierholzer (US), Ruth S. Gurd (US), Robert Franklin Pitts (US), Lawrence P. Sullivan (US), Walter S. Wilde (US), Richard L. Marvin (US), John R. Jaenike (US), and Robert William Berliner (US) demonstrated that potassium accumulates in the more distal parts of the nephron, leaving little question that this is the site of potassium secretion(4946-4948).

Lewis Thomas (US) and Sir Frank MacFarlane Burnet (AU) proposed the immunosurveillance theory which holds that eliminating precancerous cells is one of the primary duties of patrolling lymphocytes(4949-4951). See, Paul Ehrlich, 1909.

Susumu Ohno (JP-US), William D. Kaplan (US), Riojun Kinosita (JP-US), and Sajiro Makino (JP) discovered that the chromatin body in cells of female mammals is a condensed heterochromatic X chromosome(4952, 4953). This suggested that the condensed X chromosome is inactive.

Mary Frances Lyon (GB) postulated that in nearly every cell of a woman’s body one or the other of her two X chromosomes is inactive. The tissues of the adult female are thus a mosaic in which about half of the cells contain an active paternal X and half contain an active maternal X. This phenomenon termed dosage compensation by X-inactivation is also called Lyonization(4954-4956).

Ronald G. Davidson (US), Harold M. Nitowsky (US), and Barton Childs (US) confirmed, by using gel electrophoresis, that some females had two forms of the enzyme glucose-6-phosphate dehydrogenase (G6PD), encoded by alleles on the two X chromosomes. However, when individual cells were cloned and tested, each clone now only expressed one form or the other, not both. Therefore, females clearly expressed only one G6PD gene in each cell, and the other appeared to be silenced(4957).

Carolyn J. Brown (US), Andrea Ballabio (US), James L. Rupert (US), Ronald G. Lafreniere (US), Markus Grompe (US), Rossana Tonlorenzi (US), and Huntington F. Willard (US) discovered that the Xist gene is only expressed from the inactive human X chromosome, so it presumably acts in cis on the chromosome that produces the Xist RNA(4958).

Neil Brockdorff (GB), Alan Ashworth (GB), Graham F. Kay (AU), Penny J.