The controversy between John H. Northrop and Max Delbrück on the formation of bacteriophage: Bacterial synthesis or autonomous multiplication?

References

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• Because of the equilibrium between extracellular and intracellular phage, this statement was held to be true, with different numerical values of course, for log intracellular P/B, log extracellular P/B, or log total P/B. That is, there was no conclusive experimental evidence as to which phage fraction constituted ‘the essential conditioning agent for lysis’. See Krueger A.P. Northrop J.H. The Kinetics of the Bacterium-Bacteriophage Reaction Journal of General Physiology 1931 14 223 254 (p. 242).
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• Kunitz , M. and Northrop , J.H. 1933 . Isolation of a Crystalline Protein from Pancreas and its Conversion into a New Crystalline Proteolytic Enzyme by Trypsin . Science , 78 : 558 – 559 . M. Kunitz and J. H. Northrop, ‘The Isolation of Crystalline Trypsinogen and its Conversion into Crystalline Trypsin’, ibid., 80 (1934), 505–6; R. M. Herriott and J. H. Northrop, ‘Isolation of Crystalline Pepsinogen from Swine Gastric Mucosae and its Autocatalytic Conversion into Pepsin’, ibid., 83 (1936), 469–70. See also S. S. Cohen, ‘Moses Kunitz’, in Dictionary of Scientific Biography—Suppl. II, edited by F. L. Holmes (New York, 1990), pp. 515–18.
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• Bordet , J. and Gengou , O. 1903 . Recherches sur la Coagulation du Sang . Annales de l'Institut Pasteur , 17 : 822 – 833 . L. T. Troland, ‘Biological Enigmas and the Theory of Enzyme Action’, American Naturalist, 51 (1917), 321–50; A. W. Ravin, ‘The Gene as Catalyst; The Gene as Organism’, Studies in the History of Biology, 1 (1977), 1–45. As was pointed out by Robert Olby, the concept of autocatalysis played an important role in explanations offered for gene duplication in the first half of the twentieth century. Olby generalized this particular approach for explaining vital phenomena in the phrase ‘The enzyme theory of life’. However, I am hesitant to characterize the work of Northrop on bacteriophage as a study of a ‘living process’. Northrop recognized that phage produced more of itself in the clearing of broth cultures of bacteria, but he was careful not to speak of bacteriophage as a bacterial virus and therefore not of phage multiplication or phage growth; instead, Northrop used the phrase ‘formation of phage’ or its ‘production by bacteria’. Furthermore, as Olby himself indicated, the ‘enzyme camp’ in the Rockefeller Institute in the mid-1930s was not influenced by an analogy between viruses and genes. See Olby (footnote 6), 143–52 (p. 151); T. van Helvoort, ‘What is a Virus? The Case of Tobacco Mosaic Disease’, Studies in History and Philosophy of Science, 22 (1991), 557–88 (pp. 568–70).
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• Paul Zamecnik, who worked with Max Bergmann, recalled how Fritz Lipmann shocked him by asking whether Zamecnik ‘really thought the proteolytic enzymes had anything to do with protein synthesis’. See Zamecnik P. The Machinery of Protein Synthesis Trends in Biochemical Sciences 1984 9 464 466 (p. 464). The work of Max Bergmann is discussed in J. S. Fruton, ‘Early Theories of Protein Structure’, in P. R. Srinivasan, J. S. Fruton, and J. T. Edsall, editors, ‘The Origins of Modern Biochemistry: A Retrospect on Proteins’, Annals of the New York Academy of Sciences, 325 (1979), 1–375 (pp. 1–18). The research on the mechanism of protein synthesis is described in, for instance, P. Zamecnik, ‘Historical Aspects of Protein Synthesis’, op. cit., pp. 269–301; D. Bartels, ‘The Multi-Enzyme Programme of Protein Synthesis—Its Neglect in the History of Biochemistry and Its Current Role in Biotechnology’, History and Philosophy of the Life Sciences, 5 (1983), 187–219; F. Lipmann, ‘A Long Life in Times of Great Upheaval’, Annual Review of Biochemistry, 53 (1984), 1–33. In the essay by Ditta Bartels it is pointed out that in the 1940s and 1950s the genetically oriented template research programme of protein synthesis (DNA, mRNA, and the genetic code) competed with a biochemically oriented ‘multi-enzyme programme’. In the latter programme it was thought that protein synthesis was accomplished by a cascade of reactions by a complex set of enzymes. Therefore, Northrop's ideas on the role of proteolytic enzymes and the ‘multi-enzyme programme’ both belong to the same biochemical conception of the involvement of enzymes in protein synthesis. However, Northrop's ideas addressed the breakdown of large precursor molecules, while the other programme addressed synthesis of protein from single amino acid building blocks.
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• The note ‘Preliminary Write-up’ was reprinted as an appendix with Delbrück's Nobel Lecture: A Physicist's Renewed Look at Biology: Twenty Years Later Science 1970 168 1312 1315 (pp. 1314–15). A strong influence from the research on plant viruses, e.g. the work of Wendell Stanley on tobacco mosaic virus, can be recognized in Delbrück's view on the nature of viruses. See also Kay (footnote 14); L. E. Kay, ‘Laboratory Technology and Biological Knowledge: The Tiselius Electrophoresis Apparatus, 1930–1945’, History and Philosophy of the Life Sciences, 10 (1988), 51–72; van Helvoort (footnote 32).
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• Ellis , E.L. and Delbrück , M. 1939 . The Growth of Bacteriophage . Journal of General Physiology , 22 : 365 – 384 . Ellis and Delbrück discussed the reproducibility of their assay and reported that over a 100-fold range of dilution, the plaque count was linearly proportional to the phage concentration. They concluded that this finding was contrary to the findings of Georges Dreyer and Margaret L. Campbell-Renton [‘The Quantitative Determination of Bacteriophage Activity and Its Application to the Study of the Twort-d'Hérelle Phenomenon’, Journal of Pathology and Bacteriology, 36 (1933), 399–423] who reported a complicated dependence of plaque count on dilution but were using a different species of bacteria, different phages, and a different technique. In the study by Ellis and Delbrück, variation of the agar concentration from 0·75% to 3·0% had little influence on the number of plaques produced, though the size of the plaques decreased noticeably with increasing agar concentration [see also Bronfenbrenner and Korb (footnote 24) who observed a very pronounced reduction in plaque counts when the agar concentration was increased from 1% to 2·5%]. Later on, the steps in the one-step growth curve would be defined more precisely as the ‘latent period’ or ‘constant period’ during which no increase of phage particles was observed, the ‘rise period’ during which the number of phage particles increased and the ‘saturation period’ in which one could define the ‘burst size’. See also A. H. Doermann, ‘The Intracellular Growth of Bacteriophages: I. Liberation of Intracellular Bacteriophage T4 by Premature Lysis with Another Phage or with Cyanide’, Journal of General Physiology, 35 (1952), 645–56; Ellis (footnote 9); Brock (footnote 22), 120–2.
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• Delbrück , M. 1940 . The Growth of Bacteriophage and Lysis of the Host . Journal of General Physiology , 23 : 643 – 660 . Gunther Stent thought it probable that ‘lysis-from-without’ was the result of digestion of the bacterial cell wall by lytic enzymes present in the added lysate either in ‘soluble’ form or attached to phage particles; see G. S. Stent, Molecular Biology of Bacterial Viruses (San Francisco, 1963), p. 80.
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• Delbrück , M. 1942 . Bacterial Viruses (Bacteriophages) . Advances in Enzymology , 2 : 1 – 32 . (pp. 2–4)
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• Luria started his radiation experiments during his stay in Paris and the results were published as Wollman E. Holweck F. Luria S. Effects of Radiations on Bacteriophage C 16 Nature 1940 145 935 936 F. Holweck, S. Luria, and E. Wollman, ‘Recherches sur le Mode d'Action des Radiations sur les Bactériophages’, Comptes Rendus Hebdomadaires des Séances de l'Académie des Sciences, 210 (1940), 639–42 and 799. See also S. E. Luria, A Slot Machine, A Broken Test Tube: An Autobiography (New York, 1984), pp. 64–70.
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• Delbrück , M. and Luria , S.E. 1942 . Interference between Bacterial Viruses: I. Interference between Two Bacterial Viruses Acting upon the Same Host, and the Mechanism of Virus Growth . Archives of Biochemistry , 1 : 111 – 141 . (pp. 136–8); S. E. Luria and M. Delbrück, ‘Interference between Inactivated Bacterial Virus and Active Virus of the Same Strain and of a Different Strain’, ibid., 207–18. Interference is nowadays attributed to a phage-induced change in the bacterial ‘envelope’; see Fischer et al. (footnote 6), 168.
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• Luria , S.E. , Delbrück , M. and Anderson , T.F. 1943 . Electron Microscope Studies of Bacterial Viruses . Journal of Bacteriology , 46 : 57 – 77 . See also T.F. Anderson, ‘Electron Microscopy of Phages’, in Cairns et al. (footnote 5), 63–78.
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• Delbrück , M. 1946 . Experiments with Bacterial Viruses (Bacteriophages) [Lecture delivered on 17 January 1946.] . Harvey Lectures , 41 : 161 – 187 . (pp. 171–2).
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• Ellis , E.L. and Spizizen , J. 1940 . Glycine—An Essential Factor for the Growth of Bacteriophage . Science , 92 : 91 – 91 . J. Spizizen, ‘Biochemical Studies on the Phenomenon of Virus Reproduction: I. Amino Acids and the Multiplication of Bacteriophage’, Journal of Infectious Diseases, 73 (1943), 212–21; J. Spizizen, ‘Biochemical Studies on the Phenomenon of Virus Reproduction: II. Studies of the Influence of Compounds of Metabolic Significance on the Multiplication of Bacteriophage’, ibid., 222–8; J. Spizizen, ‘Some Preliminary Studies on the Mechanism of Virus Multiplication’, Proceedings of the National Academy of Sciences, 29 (1943), 109–14. See M. Delbrück, ‘Bacterial Viruses or Bacteriophages’, Biological Reviews, 21 (1946), 30–40.
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• Delbrück . 1942 . Bacterial Viruses (Bacteriophages) . Advances in Enzymology , 2 : 1 – 32 . Delbrück (footnote 61), 171–2; Delbrück (footnote 62), 37–8. Robert Olby compared Delbrück's ambivalent feelings towards biochemistry with the love/hate relationship between the young Max and his father. See R. Olby, ‘From Physics to Biophysics’, History and Philosophy of the Life Sciences, 11 (1989), 305–9.
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• Cohen , S.S. 1968 . Virus-Induced Enzymes 6 – 7 . New York Brock (footnote 22), 156–7.
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• The interference experiments used ‘indicator strains’ which were, for instance, susceptible to bacteriophage alpha (renamed as T1) but not to bacteriophage gamma (renamed as T2). This specific susceptibility of the bacteria was hereditary and the origin of such insusceptible bacterial strains was analysed in a 1943 article by Luria and Delbrück. They concluded that phage-resistant bacteria originated by a mutation of susceptible cells and that the occurrence of resistant bacteria was independent of the presence and action of the bacterial virus. The experiments were performed by Luria while Delbrück worked out the mathematical theory. The experimental technique became known as the fluctuation test. See Luria S.E. Delbrück M. Mutations of Bacteria from Virus Sensitivity to Virus Resistance Genetics 1943 28 491 511 The importance of the fluctuation experiment for the emergence of bacterial genetics is emphasized in, for example, Stent (footnote 50), 39; Hayes (1984) (footnote 43), 651; Brock (footnote 22), 58–63.
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• Hershey , A.D. 1946 . Mutation of Bacteriophage with Respect to Type of Plaque . Genetics , 31 : 620 – 640 . A. D. Hershey, ‘Spontaneous Mutations in Bacterial Viruses’, Cold Spring Harbor Symposia on Quantitative Biology, 11 (1946), 67–77. The activity of bacteriophage with respect to a certain bacterial indicator strain (its host range) could also be used as a genetic marker. Therefore, Delbrück and Luria's interference experiments from 1942 can be conceived as genetic experiments. N.B. In bacteriophage the superscript plus sign refers to the wild type of the virus, while in bacteria the superscript plus sign denotes the presence of the property in question (e.g., Lac + refers to a bacterium able to ferment lactose); see Stent (footnote 50), 178.
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• Delbrück , M. and Bailey , W.T. Jr . 1946 . Induced Mutations in Bacterial Viruses . Cold Spring Harbor Symposia on Quantitative Biology , 11 : 33 – 37 . See also Delbrück (footnote 61). As was stated in a commemorative article on Delbrück, the term ‘induced mutation’ shows how cautious one was in the mid-1940s of thinking in terms of Mendelian crossings for viruses. See Winkler (footnote 43), 256.
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• Although Delbrück expected that the interference phenomenon would elucidate the multiplication of bacteriophage, it is hardly mentioned in textbooks of bacterial genetics and bacterial physiology. See et al. Thinking about Science: Max Delbrück and the Origins of Molecular Biology New York 1989 168 168
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• Stent , G.S. and Calendar , R. 1978 . Molecular Genetics: An Introductory Narrative , 2nd edition 301 – 305 . San Francisco H. Fraenkel-Conrat and P.C. Kimball, Virology (Englewood Cliffs, N.J., 1982), pp. 30–4. There are, however, bacteriophages (e.g. some filamentous phages) in which bacteriophage is secreted by the bacterium without lysis of the latter. See, for instance, E. C. C. Lin, R. Goldstein, and M. Syvanen, Bacteria, Plasmids, and Phages: An Introduction to Molecular Biology (Cambridge, Mass., 1984), pp. 193–5.
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• Northrop . 1939 . Increase in Bacteriophage and Gelatinase Concentration in Cultures of Bacillus megatherium . Journal of General Physiology , 23 : 73 – 73 . It is interesting to mention the microscopical observations by Stanhope Bayne-Jones and Leslie A. Sandholzer on the lysis of B. coli and B. megaterium by the action of phage. They reported that enlargement or swelling of cells of B. coli usually, but not always, preceded lysis. Enlargement did not occur before lysis in B. megaterium. Furthermore, the terminal stage of lysis of B. coli was found to be explosive, taking 1/2 to 7/8 second, while the terminal stage of lysis of B. megaterium was a slow, disintegrative process, extending over 2-10 minutes. See S. Bayne-Jones and L. A. Sandholzer, ‘Changes in the Shape and Size of Bacterium Coli and Bacillus megatherium under the Influence of Bacteriophage—A Motion Photomicrographic Analysis of the Mechanism of Lysis’, Journal of Experimental Medicine, 57 (1933), 279–305. I traced this report by coincidence and, to my knowledge, it has not been cited by Northrop, Krueger, or Delbrück.
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• Delbrück . 1940 . Adsorption of Bacteriophage under Various Physiological Conditions of the Host . Journal of General Physiology , 23 : 637 – 639 .
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• et al. Thinking about Science: Max Delbrück and the Origins of Molecular Biology New York 1989 125 125 Some of the experimental work from this article was published in Delbrück's review of bacterial viruses from 1942. See Delbrück (footnote 53), 16–17. The correspondence between Delbrück and Northrop on this question is filed in the Delbrück archive of the California Institute of Technology. See Brock (footnote 22), 122.
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• Delbrück . 1942 . Bacterial Viruses (Bacteriophages) . Advances in Enzymology , 2 : 16 – 17 .
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• Krueger , A.P. , Scribner , E.J. and Brown , B.B. 1946 . Further Observations on the Mechanism of Phage Action . Journal of General Physiology , 30 : 25 – 39 . This publication addressed in particular Max Delbrück's ‘Adsorption of Bacteriophage under Various Physiological Conditions of the Host’ (footnote 49) and ‘Bacterial Viruses (Bacteriophages)’ (footnote 53).
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• Delbrück . 1946 . Bacterial Viruses or Bacteriophages . Biological Reviews , 21 : 34 – 34 .
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• Northrop , J.H. , Kunitz , M. and Herriott , R.M. 1948 . “ Bacteriophage ” . In Crystalline Enzymes , 2nd edition 196 – 208 . New York in
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• See Lwoff A. Danger of Hypothetical Secretions Bacteriological Reviews 1953 17 330 331 in
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• Formation of Viruses Crystalline Enzymes , 2nd edition et al. New York 1948 238 242 (p. 239). See also J. H. Northrop, ‘Enzymes and the Synthesis of Proteins’, in The Chemistry and Physiology of Growth, edited by A. K. Parpart (Princeton, New Jersey, 1949), pp. 3–48.
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• Northrop . 1949 . “ Enzymes and the Synthesis of Proteins ” . In The Chemistry and Physiology of Growth Edited by: Parpart , A.K. 7 – 7 . Princeton, New Jersey See also I. Langmuir and V. J. Schaefer, ‘Activities of Urease and Pepsin Monolayers’, Journal of the American Chemical Society, 60 (1938), 1351–60.
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• Northrop . 1949 . “ Enzymes and the Synthesis of Proteins ” . In The Chemistry and Physiology of Growth Edited by: Parpart , A.K. 16 – 16 . Princeton, New Jersey in
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• Northrop , J.H. 1961 . Biochemists, Biologists, and William of Occam . Annual Review of Biochemistry , 30 : 1 – 10 . Northrop referred to a number of papers from the long tradition of explaining biological and chemical ‘growth’ with the help of autocatalysis, including Troland (footnote 32); N. K. Koltzoff, ‘Physikalisch-chemische Grundlage der Morphologie’, Biologisches Zentralblatt, 48 (1928), 345–69; Northrop, ‘The Formation of Enzymes’ (footnote 39); A. Gulick, ‘What are the Genes? II. The Physico-Chemical Picture; Conclusions’, Quarterly Review of Biology, 13 (1938), 140–68; Langmuir et al. (footnote 84); Stanley (1938) (footnote 35); L. Pauling, ‘A Theory of the Structure and Process of Formation of Antibodies’, Journal of the American Chemical Society, 62 (1940), 2643–57; C. D. Darlington, ‘Heredity, Development and Infection’, Nature, 154 (1944), 164–9; P. Jordan, ‘Zum Problem der Eiweiß-Autokatalysen’, Naturwissenschaften, 32 (1944), 20–6.
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• See Morgan N. The Strategy of Biological Research Programmes: Reassessing the “Dark Age” of Biochemistry, 1910–1930 Annals of Science 1990 47 139 150 (p. 140); Northrop (1961) (footnote 86).
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• Northrop . 1949 . “ Enzymes and the Synthesis of Proteins ” . In The Chemistry and Physiology of Growth Edited by: Parpart , A.K. 22 – 23 . Princeton, New Jersey in
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• Northrop , J.H. 1951 . Growth and Phage Production of Lysogenic B. Megatherium . Journal of General Physiology , 34 : 715 – 735 . (p. 732); A. Lwoff and A. Gutmann, ‘Recherches sur un Bacillus Megatherium Lysogène’, Annales de l'Institut Pasteur, 78 (1950), 711–39; translated as ‘Investigations on a Lysogenic Bacillus Megaterium’, in Papers on Bacterial Viruses, edited by G. Stent (Boston, 1960), pp. 312–31.
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• Delbrück . 1946 . Experiments with Bacterial Viruses (Bacteriophages) [Lecture delivered on 17 January 1946.] . Harvey Lectures , 41 : 162 – 162 .
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• Adams , H.M. , ed. 1950 . “ Methods of Study of Bacterial Viruses ” . In Methods in Medical Research Vol. 2 , 1 – 73 . (p. 1).
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• On the basis of a number of assumptions concerning the average weights of a nucleotide, an amino acid, and the encoded proteins, as well as several other assumptions, C. Arthur Knight calculated that tobacco mosaic virus has 7 genes while Coliphage T4 has 200 genes. See Knight C.A. Molecular Virology New York 1974 153 153 In 1957 André Lwoff defined viruses as ‘infectious, potentially pathogenic, nucleoproteinic entities possessing only one type of nucleic acid, which are reproduced from their genetic material, are unable to grow and to undergo binary fission, and are devoid of a Lipmann system’. See A. Lwoff, ‘The Concept of Virus—The Third Marjory Stephenson Memorial Lecture’, Journal of General Microbiology, 17 (1957), 239–53 (p. 246). A Lipmann system for the formation of peptide bonds can be defined as an integrated oxidation-reduction system consisting of enzymes (conjugated proteins in the oxidized or reduced state) that react with certain electron donors and electron acceptors, involving the transfer of free energy in every step of the electron transport.
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• Delbrück , M. 1949 . “ A Physicist Looks at Biology ” . In Transactions of the Connecticut Academy of Arts and Sciences Vol. 38 , 173 – 190 . reprinted in Cairns et al. (footnote 5), pp. 9–22 (pp. 13–14).
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• Sturtevant , A.H. 1965 . A History of Genetics New York E. A. Carlson, The Gene: A Critical History (Philadelphia, 1966); L. C. Dunn, A Short History of Genetics—The Development of Some of the Main Lines of Thought: 1864–1939 (Ames, 1965 reprinted 1991).
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• Evans , E.A. Jr . 1956 . “ The Biochemistry of the Bacterial Viruses ” . In Essays in Biochemistry Edited by: Graff , S. 94 – 105 . New York (p. 94)
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• Seifriz , W. 1939 . A Materialistic Interpretation of Life . Philosophy of Science , 6 : 266 – 284 . This essay was markedly influenced by Northrop's views on the study of living processes.
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• Delbrück . 1949 . A Physicist Looks at Biology . Transactions of the Connecticut Academy of Arts and Sciences , 38 : 14 – 14 . and p. 22, respectively.
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• Cohen , S.S. 1984 . The Biochemical Origins of Molecular Biology—Introduction . Trends in Biochemical Sciences , 9 : 334 – 336 . S. S. Cohen, ‘Finally, the Beginnings of Molecular Biology’, ibid., 11 (1986), 92–3; R. Olby, ‘Biochemical Origins of Molecular Biology: A Discussion’, ibid., 303–5.
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• The full quotation expressing Delbrück's feelings towards Northrop and Krueger (already partly quoted in section 1, footnote 6) runs like this: ‘Northrop, and especially his associate Krueger, basing their experiments on [the] preconceived notion of converting precursor into product, had done very bad experiments and published them, for several years, and had loused up the literature, and really confused the issue. So when we came along, the first thing we had to do was clean up this mess. And since these were people associated with the Rockefeller Institute…it took some hammering away…I finally got their strain and did experiments on their strain, and showed that they were wrong, but I never got that published. I still have it in my file. For several years, I mean, my papers were largely directed at destroying Northrop and Krueger’. See et al. Thinking about Science: Max Delbrück and the Origins of Molecular Biology New York 1989 125 125
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• Furthermore, they concluded from these photographs that it was now proven that Krueger's precursor did not exist. See et al. Electron Microscope Studies of Bacterial Viruses Journal of Bacteriology 1943 46 65 65 and Anderson (footnote 57). It is to be noted that Northrop and Krueger had always stated that it was not certain whether phage was produced by a hydrolytic cleavage of a preformed protein precursor (as was the case with, for instance, the autocatalytic transformation of trypsinogen) or whether it involved the completion of a complex protein synthesis by the cell under the stimulus of contact with phage.
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• Delbrück , M. 1952 . “ Virus Multiplication and Variation ” . In Poliomyelitis: Papers and Discussions Presented at the Second International Poliomyelitis Conference 13 – 19 . Philadelphia (p. 15).
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• Stent . 1966 . Phage and the Origins of Molecular Biology 393 – 393 . Cold Spring Harbor
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• In 1962 Northrop was to argue in a discussion on infectious macromolecules that he had had the correct point of view because he had not compared bacteriophage with cellular parasites but had thought of it as a product of the bacterium. He claimed that, all in all, the bacteriophage showed more similarities with the nucleic acids of the ‘transforming principles’ which had been studied by, among others, Theodor Avery. See Northrop J.H. Infectious Macromolecules Archives of Biochemistry and Biophysics 1962 1 7 11 (Supplement) See also M. McCarty, The Transforming Principle: Discovering That Genes are Made of DNA (New York, 1985).
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• See, for instance, Jacob F. Monod J. Genetic Regulatory Mechanisms in the Synthesis of Proteins Journal of Molecular Biology 1961 3 318 356 F. Lipmann, ‘Polypeptide Chain Elongation in Protein Biosynthesis: A Protein Grows by Single Unit Addition on the Ribosome-Reactor with Messenger RNA as Conveyer Belt’, Science, 164 (1969), 1024–31; ‘Gene Expression and Regulation’, in Brock (footnote 22), 265–324; the literature cited in footnote 33. For a history of the research on the synthesis of nucleic acids (RNA and DNA) see, for instance, A. Kornberg, B. L. Horecker, L. Cornudella, and J. Oro, Reflections on Biochemistry: In Honour of Severo Ochoa (Oxford, 1976); A. Kornberg, For the Love of Enzymes: The Odyssey of a Biochemist (Cambridge, Mass., 1989).
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• The term ‘informational school’ was introduced by Gunther S. Stent for the contributions by the scientists of the ‘Phage Group’. See Stent Phage and the Origins of Molecular Biology Cold Spring Harbor 1966
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• See Bartels The Multi-Enzyme Programme of Protein Synthesis—Its Neglect in the History of Biochemistry and Its Current Role in Biotechnology History and Philosophy of the Life Sciences 1983 5 187 219
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