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The '40s witness the creation of Molecular Biology. This domain of biology creates the link between the formal nature of the gene and molecules. This establishes the molecular scale as the lower level needed for analysis of life processes, placing a limit to further reductionism (except perhaps in the domain of electron transfers and photon capture during photosynthesis). During this period the phage group played a major role in constructing the techniques and concepts of molecular biology. At this tme two distinct approaches to understanding the nature of life prevail. Geneticists (Delbrück, Hershey, Luria...) and some physiologists or biochemists (Avery, Chargaff, Monod...) place emphasis on the actions witnessed in living processes, stressing the concept of function, while others (Astbury, Bernal, Bragg, Pauling...) place emphasis on the structural, chemical structure of macromolecules, trying to unravel their chemical sequences and to reconstruct their three-dimensional architecture. Some relevant aspects of the conceptual bases which led to the creation of molecular biology have been described in L'œuf et la poule (in French, in Portuguese and in Japanese).
1940 Pauling and Delbrück publish an article, The nature of the intermolecular forces operative in biological processes, where they expose the role of non-covalent bonds in macromolecules (electrostatic interactions, hydrogen bonds, van der Waals attraction and repulsion, etc.). Pauling further tries to understand the interaction between antigens and antibodies in terms of weak interactions, stressing the importance of complementarity. They comment on the paper by Ernst Pascual Jordan (Hanover, 1902 - 1980), one of the founders of quantum dynamics, where he proposes that complementarity is a basic property of all natural phenomena. Pauling suggests, in support of the immunochemical template theory, that the specificity of an antibody is the result of complementarity between its structure and a portion of the surface of the homologous antigen. However, forgetting the selective principles at work in biological processes, he assumes that this complementarity is induced by the antigen into the variable folding patterns and noncovalent bonds of the antibody after protein synthesis has already taken place.
1940 Also in the domain of immunology, Landsteiner and Alexander Solomon Wiener (1907 - 1976) discover the Rhesus (Rh) blood factor.
1940 Ernst (Ernesto) Gustav Gotthelf Marcus (Berlin, Deutschland, 1893 - São Paulo, Brasil, 1968) publishes the bryozoan volume of Danmarks Fauna. Initially an assistant of Karl Heider in Berlin, he was dismissed in 1935 after the death of Hindenburg, who had protected those jews who had been awarded the First Class Iron Cross during World-War I. In 1936, he was appointed as professor at the New University of São Paulo where he worked with his wife Eveline Marcus (1901 - 1990) on Bryozoa.
1940 Following the work of Dubos, the pathologist Howard Walter Florey (Adelaide, Australia, 1898 - 1968) and the biochemist Ernest Boris Chain (Berlin, 1906 – 1979) who initially worked together on lysozyme, produce an extract of penicillin, and purify the molecule, further demonstating the therapeutic effect of the first powerful antibiotic. They isolate the antibiotic from Fleming’s mold cultures and demonstrate that it can cure infections in animals. With Edward Penley Abraham (1913 - 1999), Chain further describes an enzyme from bacteria able to destroy penicillin: this discovery paved the way to the observation that resistance to antibiotics was to become soon a matter of concern.
1940 Ethel Brown Harvey (1885 - 1965) places unfertilized sea urchin eggs into a sucrose solution having the same osmolarity as the eggs cytoplasm. The eggs are separated into two types by centrifugation. The lighter half contained the nucleus, while the heavier half was enucleated. Following the procedure for successful parthenogenetic cleavage, Harvey then activated the enucleated halves by placing them into hypotonic sea water.These activated enucleated halves ("parthenogenetic merogones") cleaved, formed abnormal blastulae (which lacked a blastocoel), and hatched (under abnormal forms). This demonstrated that the initial stages of the development plan of the egg were present in the cytoplasm, paving the way for the concept of a "message" presence out of the nucleus.
1940 Norbert Wiener (1894 - Stockholm, Sweden, 1964), who was an excellent mathematician and a polymath (he spent the academic year 1935-1936 in China as a visiting professor at Tsing Hua University in Peking, which gave him the opportunity to learn putonghua, Mandarin Chinese) proposed building vacuum-tube electronic computers which would make totally preprogrammed digital calculations using binary mathematics on magnetic tape): "In the summer of 1940, I turned a large part of my attention to the development of computing machines for the solution of partial differential equations."
1940 Helmut Ruska (1908 - 1973) (Ernst Ruska's brother) publishes the first pictures of a virus uses an electron microscope Die Sichtbarmachung der Bakteriophagen Lyse im Ubermikroskop (Naturwissenschaaften. 28: 45-46). With Gustav A Kausche (?-?) he also publishes the first electron microscope pictures of chloroplasts .
1940 Charles E Smith (? - 1973) and his colleagues demonstrate the usefulness of a tuberculin-like preparation of the pathogenic fungus Coccidiodes immitis in detecting prior exposure to the fungus. This preparation allowed for the delineation of the endemic area for the fungus.
1940 Hans Gaffron (1902 - 1979) shows that algae can utilize molecular hydrogen for photosynthesis and coins the term photoreduction to characterize that part of the photosynthetic pathway.
1940 Paul Fildes (1882 - 1971) and independently Donald O Woods (?-?) propose an antimetabolite theory to explain the action of antibacterial chemicals, and that the similarity in structure of para-aminobenzoate with the active group of sulfanilamide is responsible for its antibacterial action, interfering with the synthesis of folic acid.
1940 Selman Abraham Waksman (Priluka, Russia, 1888 - 1973) and H Boyd Woodruff (1917 - ), soil microbiologists, stimulated by the discovery made the year before by René Dubos of bactericidal substances in soil, focus their work on the medical uses of antibacterial soil microbes and discover actinomycin, the first antibacterial obtained pure from an actinomycete, leading to the discovery of many other antimicrobial products from that group of microorganisms.
1940-1941 Torbjörn Oskar Caspersson (1910 - 1997) shows that cell growth is associated to RNA synthesis.
1940-1943 Albert Claude (Longlier, Belgique, 1899 - 1983) isolates a mitochondrial fraction from liver by differential centrifugation.
1941 Barry Commoner (1917 - ) and Thimann, using auxin, find that early oat plant growth in sucrose and auxin solutions is inhibited by various substances which are known to act as dehydrogenase inhibitors. Potassium iodoacetate can halt growth but produces no effect on cellular respiration. The conclusion is that growth and respiration are not tightly linked together.
1941 Carl and Gerty Cori work out the lactic acid metabolic cycle.
1941 Publication of Charles Manning Child (Ypsilanti, Michigan, 1869 - 1954) Patterns and Problems of Development, an analysis of development and regeneration from the viewpoint of the gradient concept.
1941 Haldane speculates that the self-reproduction of a gene could be demonstrated by labelling the gene and then seeing if the copy gene contained the label while the original did not .
1941 Frank McFarlane Burnet (Traralgon, Victoria, Australia, 1899 - 1985) and his colleagues propose in The production of antibodies that the progeny of antigen reacting cells produce antibodies specific to the antigen, thus reviving ideas of Metchnikoff, focused on two experimental facts incompatible with Pauling's template hypothesis: "the continued production of antibody in the absence of antigen, and the presence of the secondary response, in which a second inoculation with an antigen elicits a host response qualitatively more rapid than that which followed the first inoculation."
1941 A Gustaffson (?-?) and coworkers produce new strains of cereals with better agricultural traits by selection from mutants produced by X-rays.
1941 William T Astbury (1898-1961) establishes that DNA has a semi-crystalline structure.
1941 Beadle and Edward Lawrie Tatum (Boulder, Colorado, 1909 - 1975) publish an article on their experiments using the fungus Neurospora crassa to establish that particular genes are expressed through the action of correspondingly specific enzymes; i.e., one gene controls one enzyme so a mutation in a gene will change the enzymes available, causing the blockage of a metabolic step. The first gene to be identified controlled the synthesis of an enzyme in a series that led to generation of nicotinamide. This report is the genesis of the "one gene-one enzyme" concept. A major advantage of Neurospora over Paramecium, used until then in studies of microorganisms, is that the former can be grown on defined synthetic medium, e.g., manufactured vitamins and amino acids, whereas the latter must have bacteria as food source.
1941 At the request of Howard Florey, the young doctor Charles Fletcher (1911 - 1995) injects penicillin to a police officer, Albert Alexander, suffering with a lethal infection. Because they lacked enough penicillin (the team had even to recover some from the urine of the patient) the patient eventually died, after a dramatic improvement of his condition, providing the first demonstration that penicillin is non-toxic to humans.
1941 David Ezra Green (Brooklyn, NY, 1910 - 1983) in the first volume of Advances in Enzymology states "The thesis which we shall develop in this article is that any substance which occurs in traces in the cell and which is necessary in traces in the diet or medium must be an essential part of some enzyme. We shall define a trace concentration as one where the uppermost limit is less than 5 micrograms per gram dry weight of the cell." a thesis that had a considerable impact on the identification of coenzymes and prosthetic groups.
1941 George K Hirst (?-?) reports that when allantoic fluid from flu virus infected eggs is mixed with red blood cells in ice the cells become very heavily agglutinated. If these agglutinated cells are warmed to 37 degrees they disperse and can no longer be re-agglutinated in the cold by fresh virus. Hirst took this to mean that the virus has an enzyme which destroys binding sites for the virus on the red cell. Since the cell attachment proteins of most viruses also agglutinate red blood cells, this property provides a rapid, accurate and quantitative method of counting virus particles.
1941 The Manhattan Project (atomic bomb development) is organized with Oppenheimer in overall charge of the scientists involved. Within the project, Karl Lark-Horowitz, Seymour Benzer (New York, 1921 -), and others developed germanium crystal rectifiers, the semiconducter later used in transistors.
1941-1942 Charlotte Auerbach (Berlin, 1899 - 1994) with AJ Clark and JM Robson discovers that mustard gas, a highly toxic substance that had been used in trench warfare in 1914-1918, causes mutations in Drosophila altering its progeny in an hereditary fashion.
1941-1942 Gustave Malécot (1911 – 1998) introduces new probabilistic concepts in quantitative genetics, considering the probabilities that two genes are descended from various ancestral genes, using Mendel's laws of inheritance (coefficients de parenté). He also studies "zygotic kinship chains", which measure the probability that a certain chain of (diploid) ancestors occurred, a complete and mathematically rigorous probability theory for pedigree analysis, based on the degrees of relatedness among individuals in a pedigree and their probabilities of occurring in the pedigree.
1941-1943 Ludwik Rajchman is named advisor to the Bank of China. He becomes intimate with several members of Roosevelt's "Brain Trust". In collaboration with TV Soong, then Chinese Minister of Foreign Affairs (and brother of de Tchang Kaï-chek), he obtains a loan of 500 million dollars for China. He then becomes the unofficial director of the China Defense Supplies from which he resigns when Soong is pushed aside.
1941-1944 Archer John Porter Martin (London, 1910 - 2002) and Richard Laurence Millington Synge (Liverpool, 1914 - 1994) develop different modes of partition chromatography, including paper chromatography and apply it to amino acid analysis.
1942 With a very Lamarckian flavour, similar to that proposed by Piaget in his thesis in zoology (and later named accomodation), Waddington names canalization the capacity to respond to an external stimulus by some developmental reaction, such as the formation of an ostrich's calloses, which are under genetic control. "Once a developmental response to an environmental stimulus has become canalized, it should not be too difficult to switch development into that track...by the internal mechanism of a genetic factor...; the same considerations which render the canalization advantageous will favor the supercession of the environmental stimulus by a genetic one. By such a series of steps, then, it is possible that an adaptive response can be fixed without waiting for the occurrence of a mutation which...mimics the response well enough to enjoy a selective advantage."
1942 Brachet, after having established histochemical means to follow nucleic acids in situ, shows that the non-nucleated daughters of enucleated cells survive for some time during which specific proteins were synthesized unless the cells were treated with ribonuclease.
1942 Julian Huxley publishes Evolution, The Modern Synthesis, still a reference today. This book lends its name to the modern synthesis of evolutionary studies created by Fisher, Haldane, and Wright. Its name "[gathers] under one theory – with population genetics at its core – the events in many sub-fields that had previously been explained by special theories unique to that discipline. Such an occurrence marks scientific 'progress' in its truest sense – the replacement of special explanations carrying little power in prediction or extension with general theories, rich in implications and capable of unifying a diverse set of phenomena that had seemed unrelated."
1942 Ernst Mayr (Kempten, Deutschland, 1904 - 2005), in writing Systematics and the Origin of Species Mayr champions allopatric speciation, whereby new species form only in physical isolation. It was not a new idea, as even Darwin had entertained the notion before settling on the opposite, sympatric view: that speciation does not require geographical separation. In his later reflection, he insisted the it was most unlikely that any gene remained selectively neutral, i.e., available for random drift, for any length of time.
1942 Waksman coins the term antibiotic (proposed as antibiote in 1889 by Vuillemin) to describe compounds produced by microorganisms which kill bacteria after JE Flynn, the editor of Biological Abstracts asked him to suggest a term for chemical substances, including compounds and preparations that are produced by microbes and have antimicrobial properties. Waksman recalled the incident in his book The Antibiotic Era. Antibiotics are: "toutes les substances chimiques produites par des micro-organismes capables d'inhiber le développement et de détruire les bactéries et d'autres micro-organismes". The word was accepted quickly but its meaning became confused, Waksman published a comprehensive definition in 1947: "an antibiotic is a chemical substance produced by microbes that inhibits the growth of and even destroys other microbes and is active in dilute solutions".
1942 Albert H Coons (1912 - 1978), HJ Creech (?-?), RN Jones (?-?), and Ernst Berliner (?-?) synthesize fluorescein isocyanate. They succeed in demonstrating the feasibility of putting fluorescent tags on antibodies and using them to localize foreign antigens in host tissues.They chemically bind the fluorescent group to antipneumococcus type III antibody and use a fluorescence microscope to locate the antibody in histologic sections. They also provided some basic data on sensitivity and specificity: Demonstration of pneumoccocal antigen in tissues by use of fluorescent antibody. J. Immunol. 45:159-170.
1942 Thomas Foxen Anderson (1911 - 1991) and Edoardo Salvatore Luria (Torino, 1912 - Lexington (Massachussetts) 1991) get excellent photographs of bacteriophages with an electron microscope, confirming earlier work by Ruska. They demonstrate that an E. coli alpha (T2) phage has a head and a tail: The identification and characterization of bacteriophages with the electron microscope. Proc. Natl. Acad. Sci. USA. 28: 127-130.
1942 Jules Freund (Budapest, Hungary, 1890 - 1960) and Katherine McDermott (? - ?) discover adjuvants, such as paraffin oil, that can significantly boost antibody production. The preparation is composed of heat killed tubercule bacilli in a water-in-oil emulsion: Sensitization to horse serum by means of adjuvants. Proceedings of the Society for Experimental Biology and Medicine 49: 548-553.
1942 Roman Jakobson (Moscow, Russia 1896 - 1982) one of the founders of the Prague Linguistic Circle in the '20s, proposes that the sounds of all human languages are composed of atomic units.This is developed in his Six Lectures on Sound and Meaning. He assumes that these features (now known as phonemes), are innately available by humans, individual languages being built on subsets of them. modified views of these first suggestions that there is an innate structure for language and learning have been later developed by Noam Chomsky, and they can be based on the structure of learning processes.
1942 Ferenz B Straub (1914 -) and Szent-Györgi show that myosin is not the sole structural protein in muscle, but shared that role with actin. They discover that raising the salt concentration causes actin to polymerise into filaments. They also show that threads of myosin and actin, in the presence of magnesium and potassium ions, contract with the addition of adenosine triphosphate (ATP). They name the complex actomyosin.
1942 Turing goes to the US and write a report on the secret speech encypherment system that was being built at Bell Laboratories in New York for high-level transatlantic communication.
1942 Maxime Lamotte (1921 -) departs for French Guinée, where he discovers in Mount Nimba the viviparous frog Nectophrynoides occidentalis, starting a passion for ecology.
1942 Norbert Wiener, Julian Bigelow (Nutley, NJ, 1913 - Princeton, NJ, 2003) and Arturo Rosenblueth (Chihuahua, Mexico, 1900 - Mexico City, 1970) basing their model on electrical engineering, propose that all voluntary action involve feedback, that "the processes of communication and control are based on the much more fundamental notion of message, [that] the nervous system [is an] array of feedback loops in active communication with the environment, [and that] through feedback...a mechanism could embody purpose" (Waldrop 2001:56). This is a basis of a view of the mind-body problem based on the concept of automata. These automata, interestingly, are not purely mechanical as they have a dimension involving messages and communication.
1942 D McClean (?-?) and IM Rowlands (?-?) discover hyaluronidase in mammalian sperm and its role in fertilization of the egg.
1942 Konrad Emil Bloch (Neisse, Silesia (Nysa, Polska) 1912 – 2000) and David Rittenberg (1906 -1970) using the isotope approach developed by the latter, discover that acetate is the precursor of cholesterol.
1943 Commoner, Seymour Fogel (1919 - 1993) and Walter H Muller (? - ?) demonstrate that the auxin indole-3-acetic acid promotes water absorption against an osmotic gradient. The effect is inhibited by iodoacetate.
1943 Severo Ochoa (Luarca, Spain, 1905 - 1993) demonstrates the 3:1 phosphorus to oxygen ratio of oxidative phosphorylation in the citric acid cycle.
1943 Pierre Denoix (Paris, France, 1912 - 1990), who had collected 35,000 case files provided in part by the Parisian welfare service, the first French survey of cancer-related diseases, publishes the first Tumour -Node -Metastasis (TNM) catalog of cancer progression and diagnostic, which he develops at the Institut Gustave Roussy till 1952.
1943 Holtfreter demonstrates that dissociated cells from the same tissue will resynthesize that tissue if they are kept in contact with each other. He provides a detailed analysis of the three kinds of region-specific morphogenetic activities of cells in the amphibian gastrula and the integration of this information into a unified view of gastrulation
1943 Joachim Hämmerling (1901-1980) demonstrates by a series of transplantation experiments that the cap morphology of two related species of the unicellular alga Acetabularia depends on the species of the nucleus.
1943 Luria and Delbrück, both belonging to the core of the phage group provide a statistical demonstration that inheritance in bacteria follows darwinian principles. This work marks the birth of bacterial genetics. They show that bacteria acquire resistance to phage through mutation, not adaption and that mutation is revealed through its selection: "When a pure bacterial culture is attacked by a bacterial virus, the culture will clear after a few hours due to destruction of the sensitive cells by the virus. However, after further incubation for a few hours, or sometimes days, the culture will often become turbid again, due to the growth of a bacterial variant which is resistent to the action of the virus." Particular mutants, such as viral resistance, occur randomly in bacterial populations, even in the absence of the virus. More importantly, randomless is proven because after several hours of cultivation in independent tubes they occur in small numbers in some populations and in large numbers in other cultures. The results, known as fluctuation analysis, show that resistance occurs before exposure to the phage and argues against the idea that mutations are induced as an adaptation to the presence of the virus.
1943 Nine months later Jacques Lucien Monod (Paris, France, 1910 - Cannes, 1976) and Alice Audureau (?-?) obtain similar results, which were only published at the end of the war. At the time bacteria were supposed to have special genetic characteristics (they were assumed to have many mutations and Escherichia coli was named mutabile, for that reason). It was commonly believed the resistance of bacteria to antibiotics was the result of some sort of adaption induced by the antibiotic, which implied the lamarckian view that acquired characteristics could be inherited.
1943 Sonneborn demonstrates cytoplasmic heredity (factor Kappa) in Paramecium.
1943 Robert E Hungate (1908 - 2004) who specializes in work on life under anaerobic conditions, describes an anaerobic cellulose digesting bacterium in cattle.
1943 Jean-Paul Sartre (Paris, 1905 - 1980) publishes L'Etre et le Néant: Essai d'ontologie phénoménologique (approximate translation: Being & Nothingness: An Essay on Phenomenological Ontology) where he explores the perception of phenomena by the possibility of negation, or absence.
1943 Thomas Francis (1900 - 1969) and his student Jonas Edward Salk (1914 - 1995) develop a formalin-killed-virus vaccine against type A and B influenzas.
1943 During his stay at the MIT Radiation Laboratory, where he helped develop advanced radar systems that adapted the Norden Bomb Sight for “bombing through overcast” and made possible electronic and memory devices used in ENIAC and EDVAC computers, Britton Chance (Wilkes-Barre, Pennsylvania, 1913 -) demonstrates the existence of an enzyme-substrate complex for horseradish peroxidase using spectrophotometry: The kinetics of the enzyme-substrate compound of peroxidase J. Biol. Chem.151: 553-577.
1943 Hofmann accidentally ingests some of the lysergic acid he had synthesized through his fingertips on April 16 and discovers its hallucinogenic properties. Three days later, Hofmann deliberately consumes 250 µg of LSD, and experiences far more intense effects. This is followed by a series of self-experiments conducted by Hofmann and his colleagues.
1943 Vladimir Prelog (Sarajevo, Bosnia, 1906 - 1998) succeeds in degrading cinchotoxine to optically active homo-meroquinene and reconstructing quinotoxine, a precursor of quinine from this degradation product.
1943 Kenneth Craik (1914 -) publishes The Nature of Explanation in which he proposes bold ideas about the structure of the mind while comparing it to what machines could do, well before a similar reflection by Turing.
1943 Warren S McCulloch (1898 - 1969) and Walter H Pitts (1923 - 1969) publish A logical calculus of the ideas immanent in nervous activity, where they publish the first example of conceptual neuronal networks. They further claim that the brain can be modelled as a network of logical operators on a Turing machine. This marks the beginning of models and theories which led to the use of computational metaphors and Boolean functions in the study of cognition as well as the flourishing field of neuronal networks.
1943-1947 Luis Federico Leloir (Paris, France, 1906 - Buenos Aires, Argentina, 1987) and Juan Maria Muñoz (?-?) demonstrate fatty acid oxidation in cell-free liver systems.
1944 Oswald Theodore Avery( Halifax, Canada, 1877 - 1955), Colin MacLeod (?-?) and Maclyn McCarty (1911 - ) demonstrate that bacterial transformation is caused by DNA. They use the observations of Griffith who had shown that dead pneumococci can transform the bacteria now known as Streptococcus pneumoniae from an avirulent phenotype to a virulent phenotype. They show that the transforming principle is destroyed by pancreatic deoxyribonuclease, which hydrolyzes DNA, but is not affected by pancreatic ribonuclease or proteolytic enzymes. In other words, even though they were dead, the cells could transfer their genes as long as their DNA remained intact. This was a strong element to suggest that DNA, not protein, is the hereditary material, but most scientists at the time were not convinced, owing partly to the cautious tone of the publication. Until that date, most biologists thought genes were probably protein and nucleic acid, a repeated structure according to Levene, was some sort of skeletal material for the chromosomes. Studies on the chemical nature of the substance inducing transformation of pneumonococcal types: Induction of transformation by a deoxyribo-nucleic acid fraction isolated from pneumococcus type III. J. Exp. Med. 79: 137-157.
1944 Erwin Schrödinger (Vienna, 1887 - Vienna, 1961) publishes What is life? a reflection on biology that was extremely influential in the birth of Molecular Biology.
1944 Peter Brian Medawar (Rio de Janeiro, Brazil, 1915 - 1987) reports that in rabbits a second graft from the same donor undergoes accelerated rejection. He links the observation to the immune system.
1944 Waksman and his colleagues discover streptomycin: Streptomycin, a substance exhibiting antibiotic activity against gram-positive and gram-negative bacteria. Streptomycin has the same specific antibiotic effect against gram negative microorganisms as penicillin does on gram positives. William Hugh Feldman (1892 - 1974) and Horton Corwin Hinshaw (Iowa Falls, Iowa, 1902 -1994) at the Mayo Clinic are the first to demonstrate successful treatment of guinea pigs tuberculosis with streptomycin with a suppressive effect on the development of the disease.
1944 George Gaylord Simpson (1902 - 1984) publishes Tempo and Mode in Evolution one of the few books that had to have a strong impact on modern biology. Simpson divides the phenomena of evolutionary change into to classes: those bearing on evolutionary "tempo" and those bearing on "mode." Tempo "has to do with evolutionary rates under natural conditions, the measurement and interpretation of rates, their acceleration and deceleration, the conditions of exceptionally slow or rapid evolutions"; "Mode involves the study of the way, manner, or pattern of evolution, a study in which tempo is a basic factor, but which embraces considerably more than tempo."
1944 Robert Burns Woodward (Boston, Mass, 1917 - 1979) and William E Doering (1917- ) perform several steps of the chemical synthesis of quinine, isolated more than one century before by Caventou and Pelletier, using 8-hydroxyisoquinoline as starting material, building on the first isoalation of an optically active compound resolved from the racemic mixture by Pasteur. Over the next eighteen years, Woodward synthesizes, in 1951, cholesterol and cortisone, in 1954, strychnine and lysergic acid, in 1956, reserpine, in 1960, chlorophyll, and, in 1962, a tetracycline antibiotic.
1944 Howard Hathaway Aiken (Hoboken, New Jersey, 1900 - 1973) and a team of engineers from IBM display a huge programmable calculator the Automatic Sequence Controlled Calculator, known as Mark I, which contains over 750,000 parts, is 51 feet long and weighs five tons.
1944 (Janos) John (von) Neumann (Budapest, Hungary, 1903 - Washington, DC, 1957) and Oskar Morgenstern (1902 - 1976), starting from games like poker and chess, apply their formulation of game theory to human economic behavior. The central assumptions are that the players are able to foresee the consequences of their actions and will behave rationally, and according to some criterion of their self-interest. As an application of their theory, von Neumann develop the model to the United States' nuclear strategy. Game theory was later applied to population studies and evolution.
1944 Friedrich August von Hayek (1899-1992) with his The road to serfdom proposes a polemical defense of laissez-faire, arguing that no central economic planner could possibly command the countless bits of localized and individual information necessary and that only the unorganized price system in a free market enables "spontaneous order" to arise from the myriad of individual plans. He claims, countering Lange and the Paretians, that prices are not merely "rates of exchange between goods", but rather "a mechanism for communicating information."
1945 Ray D Owen (? - ) notices a surprising fact about non identical cattle twins. Twins, who have therefore shared an in utero circulatory system, are unable, in adulthood, to mount an immune response to antigens produced by the twin. This is the first demonstration of immune tolerance.
1945 Edmund Brisco Henry Ford (1901 - 1988) publishes Butterflies in which he describes the biology of butterflies in the British Isles, integrating a view of population genetics, ecology and insect biology. This considerably contrasts with the lack of development of genetics in France (despite isolated attempts of similar integration later developed for some time by Lamotte, for example).
1945 Colin MacLeod, Richard Hodges (?-?), Michael Heidelberger (1888 - 1991) and William Bernard (?-?) show that an isolated capsular polysaccharide can immunize against Neisseria meningtidis. The vaccine is finally approved in 1977 after extensive international testing: Prevention of pneumococcal pneumonia by immunization with specific capsular polysaccharides. J. Exp. Med. 82: 445-465.
1945 Michael James Denham White (London, 1910 - 1983) writes a treaty on cytogenetics: Animal Cytology and Evolution. The book summarises, analyses and synthesises current information on animal chromosomes.
1945 Carl Cori demonstrates the effect of insulin on hexokinase. This is the first demonstration of such a regulatory effect.
1945 Lee R Dice (?-?) publishes an article: Measures of the amount of ecologic association between species. Ecology, 26:297-302, presenting a coefficient for discrete events to appear together.
1945 Wright creates the Coefficient of Relationship to represent the probability that any two individuals share a given gene by virtue of being descended from a common ancestor. This can happen for three possible reasons in a given individual, namely, that both, one only, and neither of his genes, at a given locus, are identical by descent, or c2+c1+c0=1. The relationship is completely specified by any two of them, e.g., 2c2+c1. One-half of this number, c2+1/2c1, may therefore be called the expected fraction of genes identical by descent in a relative.
1945 Keith Roberts Porter (1912 - 1997) describes the intracellular structure which was later to be named the endoplasmic reticulum.
1945 Luria and Alfred Day Hershey (1908-1997) demonstrate that bacteriophages mutate as do bacteria or other pathogenic organisms. They also introduce criteria for distinguishing mutations from other modifications: Mutation of bacterial viruses affecting their host range. Genetics 30: 84-99.
1945 Erwin Schrödinger (1887-1961) publishes What is Life? a book of reflection that triggered interest for biology at the molecular level for 30 years. His most famous inspiration was that of the "aperiodic crystal" meant to represent the matter of heredity. Also, in line with the concern of his time he poses the problem of Biology in terms of degradation.
1945 Inspired by similar practices in Italy at the time, Walter Freeman (Philadelphia, Pennsylvania, 1895 - 1972) following the work of Moniz, introduces the idea of the "ice-pick" or transorbital lobotomy. With the activism of Freeman and cooperation of other surgeons around 18,000 lobotomies were performed in the US between 1939 and 1951.
1945 In another type of analysis of phenomena, differing from the existentialism of Sartre, Maurice Merleau-Ponty (1908 - 1961), in the Phénoménologie de la Perception, tries to reformulate the mind vs body problem of knowledge. He states that the foundations of science are indeed based on perception and reformulates the question of objectivity, trying a middle way excluding both Cartesian rationalism and behaviourism.
1945 Erwin Brand (1891-1953), LJ Saidel, WH Goldwater, B Kassell, and Francis J Ryan report the first complete amino acid analysis of a protein, beta-lactoglobulin, determined by chemical and microbiological methods. Brand suggests a system of symbols for the amino acids, designating each amino acid by the first three letters of its name.
1946 Joshua Lederberg (1925 - ) and Tatum discover that the bacteria Escherichia coli sometimes exchange genes. The proof is based on the generation of daughter cells able to grow in media that cannot support growth of either of the parent cells. Their experiments show that this type of gene exchange requires direct contact between bacteria (the process is named conjugation). At that time it was believed that bacteria reproduced asexually, but from the work of Beadle and Tatum, it was known that fungi reproduced sexually, suggesting that bacteria did as well: Gene recombination in Escherichia coli. Nature. 58: 558.
1946 Willard Frank Libby (1908 - 1980) develops the natural radioactive carbon-14 dating technique, employing the known rate of decay, measured by its half-life, and relative proportion of its decay products to date archaeological artifacts.
1946 Reginald C Sprigg (1919 - 1994) discovers a rich deposit of Precambrian fossils (580 to 543 million years old), mostly fossilized imprints of what were apparently soft-bodied organisms, preserved on the undersides of slabs of quartzite and sandstone in the Ediacara Hills of South Australia.
1946 Errol Ivor White (1901 - 1985) discovers a fossil of Jamoytius kerwoodi, probably the most primitive known chordate from the Silurian of Lanarkshire (Scotland).
1946 André Boivin (Auxerre, France, 1895 - Strasbourg, 1949) and Roger Vendrely (?-?) report transformation with "highly polymerised" DNA involving the capsular polysaccharide of a strain of E. coli.
1946 Ulf von Euler (Stockholm, Sweden, 1905 - 1983) detects a neurotransmitter, noradrenaline, in the sympathetic nervous system.
1946 André Michel Lwoff (Ainay-le-Château, France, 1902 - Paris, 1994) studies spontaneous "hereditary" changes in bacteria suggesting that their behaviour depends on the medium, in Some problems connected with spontaneous biochemical mutations in bacteria, Cold Spring Harbor Symp., 11: 139-155.
1946 Jacques Oudin (Dreux, 1908 - Paris, 1985) describes for the first time an immunochemical method for the identification of antigens in solid plates: "Méthode d'analyse immunochimique par précipitation spécifique en milieu gélifié" CR Acad Sci 222:115-116. This method was later on refined by Orjän Ouchterlony (Gothenburg, Sweden, 1914 – ) and while it should be named after Oudin who invented it, it is often named after the latter only.
1946 von Neumann, Arthur Burks (1915 - ) and Herman Goldstine (1914 - 2004) present the Electronic Numerical Integrator and Computer (ENIAC), where they use biological metaphors, defining the concept of a software program, while showing how a computer can execute such a program, stored in a binary-code random-access memory unit, and obeying instructions of a central control unit: Preliminary discussion of the logical design of an electronic computing instrument. This ' von Neumann architecture,' drawing its circuit designs using McCulloch-Pitts neural-network notation with its sharp distinction between software and hardware, is the basis for almost all computers today. Interestingly the computer metaphore is now back to biology, with cells seen as Turing-von Neumann machines (including the particular property of the ability to construct such machines).
1946-1950 Georges Teissier who had been appointed at the head of the station biologique de Roscoff, is the director of the new Centre National de la Recherche Scientifique (CNRS), created by Jean Perrin to develop research in France.
1947 Alexander Romanovich Luria (Kazan, Russia, 1902 - 1977) publishes at the Academy of Sciences of USSR his observations on aphasia in soldiers wounded in Stalingrad. His work on a very large number of patients provides an enormous amount of data on the relationships between the structure of the brain and human performances.
1947 Bernal, in a lecture on The physical basis of life, revives the old idea of Darwin of the "warm little pond" in which life would have been born, and proposes that the lagoons and pools at the edge of the oceans served to concentrate the chemical building blocks needed to create life. He further raises the possibility of these chemicals being further concentrated by being absorbed on particles of clay. This idea, at the root of new theories of the origin of life, was later stressed by Sam Granick (1909 - 1977), Hyman Hartman, Graham Cairns-Smith and others to counter the inadequate idea of the "primordial soup", still popular and widely spread today.
1947 Peter Wilhelm Joseph Holtz (1902 - 1970) discovers that norepinephrine (noradrenaline) just found by von Euler in the sympathetic system is a normal component of the brain (today named a neurotransmitter).
1947 John Tyler Bonner (1920 - ) publishes a study on a biological oddity: the slime mold, Dictyostelium discoideum, a "fungus" which can aggregate and differentiate into a kind of animal. He demonstrates that the interaction of chemical messages and receptors produces their aggregation into a complex organization, first a worm-like structure, then a group of cells that differentiate into a stem and a sporangium, releasing spores in the environment.
1947 Armin C Braun (?-?) shows that Agrobacterium tumefaciens introduces a factor (later known as T-DNA, transforming DNA) into plant cells that permanently transforms them into a tumor, "crown gall". He finds that crown galls, unlike normal plant tissue, are able to multiply on a simple medium of salts and sugar, no longer requiring the supplements needed for normal plant growth. He proposes that the plant cells have been permanently transformed into tumor cells by some tumor-inducing factor introduced by A. tumefaciens: Thermal studies on the factors responsible for tumour initiation in crown gall. Am. J. Botany 34:234-240.
1947 Dennis Gabor (Budapest, Hungary, 1900 - 1979), working on improving the electron microscope, invents "wavefront reconstruction" later named holography (which is the translation in Greek of the concept of rewriting in totality an image of an object in a different place). The method displays a three-dimensional image of an object (a hologram) by splitting a coherent light beam so that some of it falls on a photographic plate and the rest on the object which reflects back onto the photographic plate. The two beams form an interference pattern on the plate with alternating light and dark. The plate can subsequently be used to reconstitute the image in three dimensions. "The light is where the two images both relect light back and reinforce each other, while the dark is where the images do not match" (Inventing the 20th Century: 100 Inventions That Shaped the World by Stephen Van Dulken, Andrew Phillips (Introduction) 2000).
1947 Théodore Monod (Rouen, France, 1902 - Paris, 2000) creates the journal Cybium specialized in ichtyology.
1947 In a work that was to transform the world, John Bardeen (Madison, Wisconsin, 1908 - 1991), Walter Houser Brattain (Amoy, China, 1902 - 1987) and William Schockley (London, 1910 - 1989) at the Bell laboratories, invent the transistor amplifier, a voltage and current amplifier, which, in contrast to the vacuum tube it replaced, is an arrangement of semiconductor materials sharing common physical boundaries. A semiconductor is a solid material, e.g., silicon, in which certain induced impurities enhance and orients its conductive properties. Schockley was later infamous for his racist stand (and also for his participation in the creation of the "Nobel" sperm bank).
1947-1950 Lipmann and Kaplan isolate and characterize coenzyme A.
1948 Burnet and the virologist Frank Fenner (Ballarat, Australia, 1914 - ) propose that the immune system discriminates between 'self' and 'nonself'. The latter is known to have introduced the myxoma virus in Australia to control the explosion of the rabbitt population there.
1948 Anatolii Nikolaevich Svetovidov (1903 - 1985) establishes the systematics of gadid fishes (cod fish and related fishes) and analyses their ecology: Fauna of the USSR, Fishes, Vol. IX, no. 4, Gadiformes.
1948 The Centre National de la Recherche Scientifique (CNRS) organizes a colloquium entitled Unités Biologiques Douées de Continuité Génétique where several outstanding scientists (Max Delbrück, Boris Ephrussi, André Lwoff, Jacques Monod...) participate in the creation of the new trend of biology, Molecular Biology. Ephrussi postulates the existence in cells of cytoplasmic unit, the mitochondria, that would be genetically autonomous. The mitochondrial genetic stock was to be discovered only twenty years later.
1948 George Emil Palade (Iasi, Moldavia, 1912 - ) with George H Hogeboom (?-?) and Walter Carl Schneider (?-?) develop cytochemical studies of mammalian tissues, where, using sucrose gradients, they refine the differential centrifugation method for cell fractionation and use it to isolate mitochondria.
1948 Edward Penley Abraham (Southampton, England, 1913 - 1999) extracts cephalosporin C from Cephalosporium acremonium, a fungus isolated from seawater near a sewage outlet in Sardinia. Cephalosporin C is an acid-stable molecule with antibacterial activity from which other cephalosporins are synthesized. With the related penicillins, cephalosporins are the most frequently prescribed class of antibiotics. Toxicity and adverse reactions of cephalosporins are similar to those of penicillins.
1948 The bryozoologist Marcel Prenant (1893 - 1983) at the Centre de Biologie marine de Roscoff presents a systematic view of the "revolutionary" theory of acquired hereditary characters proposed by Lyssenko, while taking the classical stand of the Mendelian-Morganian genetics. One year later he is obliged to state that only "proletarian science" (that which supports Lyssenko) can be right and is excluded from the Comité Central of the Communist Party.
1948 George David Snell (Bradford, Massachusetts, 1903 - 1996) building on experiments started by Peter Gorer (1907- 1961) in UK, and transplanting tissues between mice, they discover a genetic factor, which they called H-2, for 'histocompatibility two' which decides whether tissues are compatible between donors and recipients.
1948 von Neumann shows that replication and metabolism are logically separable, and, in fact, are analogous processes associated to software (nucleic acid) and hardware (protein).
1948-1949 Hans Olof Brattström (1908 - 2000) and Erik Dahl (?-?) lead the Lund University Chile Expedition. Brattström then becomes professor of Zoology at the University of Bergen, Norway in 1949, where he entirely rebuilds the Biological Station.
Some significant dates 1955-1964