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Dissolution of hypotheses in biochemistry: three case studies

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Abstract

The history of biochemistry and molecular biology is replete with examples of erroneous theories that persisted for considerable lengths of time before they were rejected. This paper examines patterns of dissolution of three such erroneous hypotheses: The idea that nucleic acids are tetrads of the four nucleobases (‘the tetranucleotide hypothesis’); the notion that proteins are collinear with their encoding genes in all branches of life; and the hypothesis that proteins are synthesized by reverse action of proteolytic enzymes. Analysis of these cases indicates that amassed contradictory empirical findings did not prompt critical experimental testing of the prevailing theories nor did they elicit alternative hypotheses. Rather, the incorrect models collapsed when experiments that were not purposely designed to test their validity exposed new facts.

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References

  • Allchin, D. (1997). A twentieth century phlogiston: Constructing error and differentiating domains. Perspectives in Science, 5(1), 81–127.

    Google Scholar 

  • Allchin, D. (2002). To err and win a Nobel Prize: Paul Boyer, ATP synthase and the emergence of bioenergetics. Journal of the History of Biology, 35(1), 149–172.

    Article  Google Scholar 

  • Allchin, D. (2015). Correcting the “self-correcting” mythos of science. Filosofia e História da Biologia, 10(1), 19–35.

    Google Scholar 

  • Alper, T., Cramp, W. A., Haig, D. A., & Clarke, M. C. (1967). Does the agent of scrapie replicate without nucleic acid? Nature, 214(5090), 764–766.

    Article  Google Scholar 

  • Altmann, R. (1889). Ueber nucleinsäuren. Archiv für Anatomie Physiology (pp. 524–536). Leipzig: Physiologische Abteilung.

    Google Scholar 

  • Alvargonzález, D. (2013). Is the history of science essentially Whiggish? History of Science, 51(1), 85–99.

    Article  Google Scholar 

  • Ascoli, A. (1900). Ueber ein neues spaltungsprodukt des hefenukleïns. Hoppe-Seyler’s Zeitschrift für Physiologische Chemie, 81, 161–164.

    Google Scholar 

  • Astbury, W. T., & Bell, F. O. (1938a). Some recent developments in the X-ray study of proteins and related structures. Cold Spring Harbor Symposia on Quantitative Biology, 6, 109–121.

    Article  Google Scholar 

  • Astbury, W. T., & Bell, F. O. (1938b). X-ray study of thymonucleic acid. Nature, 141(3573), 747–748.

    Article  Google Scholar 

  • Avery, O. T., Macleod, C. M., & McCarty, M. (1944). Studies on the chemical nature of the substance inducing transformation of pneumococcal types: Induction of transformation by a desoxyribonucleic acid fraction isolated from pneumococcus type Iii. The Journal of Experimental Medicine, 79(2), 137–158.

    Article  Google Scholar 

  • Bachenheimer, S., & Darnell, J. E. (1975). Adenovirus-2 mRNA is transcribed as part of a high-molecular-weight precursor RNA. Proceedings of the National Academy of Sciences USA, 72(11), 4445–4449.

    Article  Google Scholar 

  • Beadle, G. W., & Tatum, E. L. (1941). Genetic control of biochemical reactions in Neurospora. Proceedings of the National Academy of Sciences of the USA, 27(11), 499–506.

    Article  Google Scholar 

  • Berget, S. M., Moore, C., & Sharp, P. A. (1977). Spliced segments at the 5′ terminus of adenovirus 2 late mRNA. Proceedings of the National Academy of Sciences of the USA, 74(8), 3171–3175.

    Article  Google Scholar 

  • Bergmann, M. (1942). A classification of proteolytic enzymes. Advances in Enzymology, 2, 49–68.

    Google Scholar 

  • Bergmann, M., & Fraenkel-Conrat, H. (1937). The rôle of specificity in the enzymatic synthesis of proteins: Synthesis with intracellular enzymes. The Journal of Biological Chemistry, 119(2), 707–720.

    Google Scholar 

  • Bergmann, M., & Fruton, J. S. (1938). Some synthetic and hydrolytic experiments with chymotrypsin. The Journal of Biological Chemistry, 124(1), 321–329.

    Google Scholar 

  • Bergmann, M., & Fruton, J. S. (1941). The specificity of proteinases. Advances in Enzymology, 1, 63–98.

    Google Scholar 

  • Bergmann, M., & Niemann, C. (1936). On blood fibrin: A contribution to the problem of protein structure. The Journal of Biological Chemistry, 115(1), 77–85.

    Google Scholar 

  • Bergmann, M., & Niemann, C. (1937a). Newer biological aspects of protein chemistry. Science, 86(2226), 187–190.

    Article  Google Scholar 

  • Bergmann, M., & Niemann, C. (1937b). On the structure of proteins: Cattle hemoglobin, egg albumin, cattle fibrin, and gelatin. The Journal of Biological Chemistry, 118(1), 301–314.

    Google Scholar 

  • Berk, A. J. (2016). Discovery of RNA splicing and genes in pieces. Proceedings of the National Academy of Sciences of the USA, 113(4), 801–805.

    Article  Google Scholar 

  • Berk, A. J., & Sharp, P. A. (1978). Structure of the adenovirus 2 early mRNAs. Cell, 14(3), 695–711.

    Article  Google Scholar 

  • Borsook, H. & Dubnoff, J. W. (1940). The biological synthesis of hippouric acid in vitro. The Journal of Biological Chemistry, 132(1), 307–324.

    Google Scholar 

  • Borsook, H., & Huffman, H. H. (1938). Some thermodynamical considerations of amino acids, peptides and related substances. In C. L. A. Schmidt (Ed.), Chemistry of the amino acids and proteins (p. 865). Springfield, IL: H. M. Thomas.

    Google Scholar 

  • Breathnach, R., Mandel, J. L., & Chambon, P. (1977). Ovalbumin gene is split in chicken DNA. Nature, 270(5635), 314–319.

    Article  Google Scholar 

  • Brenner, S., Jacob, F., & Meselson, M. (1961). An unstable intermediate carrying information from genes to ribosomes for protein synthesis. Nature, 190(4776), 576–581.

    Article  Google Scholar 

  • Chargaff, E. (1950). Chemical specificity of nucleic acids and mechanism of their enzymatic degradation. Experientia, 6(6), 201–209.

    Article  Google Scholar 

  • Chargaff, E. (1971). Preface to a grammar of biology. A hundred years of nucleic acid research. Science, 172(3984), 637–642.

    Article  Google Scholar 

  • Chargaff, E. (1978). Heraclitean fire: Sketches from a life before nature. New York: Rockefeller University Press.

    Google Scholar 

  • Chargaff, E., & Saidel, H. F. (1949). On the nucleoproteins of avian tubercle bacilli. The Journal of Biological Chemistry, 177(1), 417–428.

    Google Scholar 

  • Chargaff, E., & Vischer, E. (1948). Nucleoproteins, nucleic acids, and related substances. Annual Review of Biochemistry, 17, 201–226.

    Article  Google Scholar 

  • Chargaff, E., Vischer, E., Doniger, R., Green, C., & Misani, F. (1949). The composition of the desoxypentose nucleic acids of thymus and spleen. The Journal of Biological Chemistry, 177(1), 405–416.

    Google Scholar 

  • Chow, L. T., Gelinas, R. E., Broker, T. R., & Roberts, R. J. (1977). An amazing sequence arrangement at the 5′ ends of adenovirus 2 messenger RNA. Cell, 12(1), 1–8.

    Article  Google Scholar 

  • Cohen, S. S., & Chargaff, E. (1944). studies on the composition of Rickettsia prowazeki. The Journal of Biological Chemistry, 154(3), 691–704.

    Google Scholar 

  • Consden, R., Gordon, A. H., & Martin, A. J. (1944). Qualitative analysis of proteins: A partition chromatographic method using paper. Biochemical Journal, 38(3), 224–232.

    Article  Google Scholar 

  • Crawford, I. P., & Yanofsky, C. (1958). On the separation of the tryptophan synthetase of Escherichia coli into two protein components. Proceedings of the National Academy of Sciences of USA, 44(12), 1161–1170.

    Article  Google Scholar 

  • Creager, A. N. (2013). Life atomic: A history of radioisotopes in science and medicine. Chicago: Chicago University Press.

    Book  Google Scholar 

  • Crick, F. H. (1958). On protein synthesis. Symposium of the Society for Experimental Biology, 12, 138–163.

    Google Scholar 

  • Darden, L. (2006). Reasoning in biological discoveries: Assays on mechanisms, interfield relations, and anomaly resolution (Cambridge studies in phylosophy and biology). Cambridge, NY: Cambridge University Press.

    Book  Google Scholar 

  • Darnell, J. E., Jr. (1999). E. B. Wilson Lecture, 1998. Eukaryotic RNAs: once more from the beginning. Molecular Biology of the Cell, 10(6), 1685–1692.

  • Darnell, J. E., Philipson, L., Wall, R., & Adesnik, M. (1971a). Polyadenylic acid sequences: Role in conversion of nuclear RNA into messenger RNA. Science, 174(4008), 507–510.

    Article  Google Scholar 

  • Darnell, J. E., Wall, R., & Tushinski, R. J. (1971b). An adenylic acid-rich sequence in messenger RNA of HeLa cells and its possible relationship to reiterated sites in DNA. Proceedings of the National Academy of Sciences of the USA, 68(6), 1321–1325.

    Article  Google Scholar 

  • Davis, R. W., & Davidson, N. (1968). Electron-microscopic visualization of deletion mutations. Proceedings of the National Academy of Sciences of the USA, 60(1), 243–250.

    Article  Google Scholar 

  • Desrosiers, R. C., Friderici, K. H., & Rottman, F. M. (1975). Characterization of Novikoff hepatoma mRNA methylation and heterogeneity in the methylated 5′ terminus. Biochemistry, 14(20), 4367–4374.

    Article  Google Scholar 

  • Devlin, W. J., & Bokulich, A. (Eds.). (2000). Kuhn’s structure of scientific revoltions—50 years on. Heidelberg: Springer.

    Google Scholar 

  • Doel, M. T., Houghton, M., Cook, E. A., & Carey, N. H. (1977). The presence of ovalbumin mRNA coding sequences in multiple restriction fragments of chicken DNA. Nucleic Acids Research, 4(11), 3701–3713.

    Article  Google Scholar 

  • Dyson, F. J. (1999). The sun, the genome, and the internet: Tools for scientific revolution. Oxford: Oxford University Press.

    Google Scholar 

  • Ede, A. (2007). The rise and decline of colloidal science in North America 1900–1935: The neglected dimension. Oxford: Ashgale.

    Google Scholar 

  • Edmonds, M., & Abrams, R. (1960). Polynucleotide biosynthesis: Formation of a sequence of adenylate units from adenosine triphosphate by an enzyme from thymus nuclei. The Journal of Biological Chemistry, 235(4), 1142–1149.

    Google Scholar 

  • Edmonds, M., & Caramela, M. G. (1969). The isolation and characterization of adenosine monophosphate-rich polynucleotides synthesized by Ehrlich ascites cells. The Journal of Biological Chemistry, 244(5), 1314–1324.

    Google Scholar 

  • Edmonds, M., Vaughan, M. H., Jr., & Nakazato, H. (1971). Polyadenylic acid sequences in the heterogeneous nuclear RNA and rapidly-labeled polyribosomal RNA of HeLa cells: Possible evidence for a precursor relationship. Proceedings of the National Academy of Sciences of the USA, 68(6), 1336–1340.

    Article  Google Scholar 

  • Embden, G., & Schmidt, G. (1929). Über muskeladenylsaure und hefeadenylsiure. Hoppe-Seyler’s Zeitschrift für Physiologische Chemie, 181, 130–139.

    Article  Google Scholar 

  • Feulgen, R. (1935). Über a- und b-thymonucleinsäure und das die a-form in die b-form überfahrende ferment (nucleogelase). Hoppe-Seyler’s Zeitschrift für Physiologische Chemie, 237(5–6), 261–267.

    Article  Google Scholar 

  • Friedmann, H. C. (2004). From “butyribacterium” to “E. coli”: An essay on unity in biochemistry. Perspectives in Biology and Medicine, 47(1), 47–66.

    Article  Google Scholar 

  • Fruton, J. S. (1950). The role of proteolytic enzymes in the biosynthesis of peptide bonds. Yale Journal of Biology and Medicine, 22, 263–271.

    Google Scholar 

  • Fruton, J. S. (1958). General biochemistry (2nd ed.). Hoboken, NJ: Wiley.

    Google Scholar 

  • Fruton, J. S., Johnston, R. B., & Fried, M. (1951). Elongation of peptide chains in enzyme-catalyzed transamidation reactions. The Journal of Biological Chemistry, 190(1), 39–53.

    Google Scholar 

  • Fry, M. (2016). Landmark experiments in molecular biology. London: Elsevier/Academic Press.

    Google Scholar 

  • Furuichi, Y. (1974). Methylation-coupled transcription by virus-associated transcriptase of cytoplasmic polyhedrosis virus containing double-stranded RNA. Nucleic Acids Research, 1(6), 802–809.

    Article  Google Scholar 

  • Furuichi, Y., & Miura, K. (1975). A blocked structure at the 5′ terminus of mRNA from cytoplasmic polyhedrosis virus. Nature, 253(5490), 374–375.

    Article  Google Scholar 

  • Furuichi, Y., Morgan, M., Muthukrishnan, S., & Shatkin, A. J. (1975a). Reovirus messenger RNA contains a methylated, blocked 5′-terminal structure: m-7G(5′)ppp(5′)G-MpCp. Proceedings of the National Academy of Sciences of the USA, 72(1), 362–366.

    Article  Google Scholar 

  • Furuichi, Y., Morgan, M., Shatkin, A. J., Jelinek, W., Salditt-Georgieff, M., & Darnell, J. E. (1975b). Methylated, blocked 5 termini in HeLa cell mRNA. Proceedings of the National Academy of Sciences of the USA, 72(5), 1904–1908.

    Article  Google Scholar 

  • Galison, P. (1997). Image and logic. Chicago: The University of Chicago Press.

    Google Scholar 

  • Gamow, G. (1954). Possible mathematical relation between deoxyribonucleic acid and proteins. Biologiske Meddelelser Udviket af Det Kongelige Danske Videnskabernes Selskab, 22(3), 1–11.

    Google Scholar 

  • Gamow, G., Rich, A., & Ycas, M. (1956). The problem of information transfer from the nucleic acids to proteins. Advances in Biological and Medical Physics, 4, 23–68.

    Article  Google Scholar 

  • Gartler, S. M. (2006). The chromosome number in humans: A brief history. Nature Reviews Genetics, 7(8), 655–660.

    Article  Google Scholar 

  • Gelinas, R. E., & Roberts, R. J. (1977). One predominant 5′-undecanucleotide in adenovirus 2 late messenger RNAs. Cell, 11(3), 533–544.

    Article  Google Scholar 

  • Girard, M., Latham, H., Penman, S., & Darnell, J. E. (1965). Entrance of newly formed messenger RNA and ribosomes into Hela cell cytoplasm. Journal of Molecular Biology, 11(2), 187–201.

    Article  Google Scholar 

  • Goldberg, S., Nevins, J., & Darnell, J. E. (1978). Evidence from UV transcription mapping that late adenovirus type 2 mRNA is derived from a large precursor molecule. Journal of Virology, 25(3), 806–810.

    Google Scholar 

  • Goldberg, S., Weber, J., & Darnell, J. E., Jr. (1977). The definition of a large viral transcription unit late in Ad2 infection of HeLa cells: Mapping by effects of ultraviolet irradiation. Cell, 10(4), 617–621.

    Article  Google Scholar 

  • Gray, J. N. (2002). Straw dogs. London: Granta Books.

    Google Scholar 

  • Green, M. (1970). Oncogenic viruses. Annual Review of Biochemistry, 39, 701–756.

    Article  Google Scholar 

  • Gros, F., Hiatt, H., Gilbert, W., Kurland, C. G., Risebrough, R. W., & Watson, J. D. (1961). Unstable ribonucleic acid revealed by pulse labelling of Escherichia coli. Nature, 190(4776), 581–585.

    Article  Google Scholar 

  • Gulland, J. M., Barker, G. R., & Jordan, D. O. (1945). The chemistry of the nucleic acids and nucleoproteins. Annual Review of Biochemistry, 14, 175–206.

    Article  Google Scholar 

  • Gulland, J. M., & Jackson, E. M. (1938). The constitution of yeast nucleic acid. Journal of the Chemical Society, 1938, 1492–1498.

    Article  Google Scholar 

  • Harding, S. (Ed.). (1976). Can Theories be refuted? Essays on the Duhem–Quine Thesis (Synthese Library, Vol. 81). Dordrecht: Springer.

  • Hargittai, I. (2009). The tetranucleotide hypothesis: A centennial. Structural Chemistry, 20(5), 753–756.

    Article  Google Scholar 

  • Harris, H. (1959). Turnover of nuclear and cytoplasmic ribonucleic acid in two types of animal cell, with some further observations on the nucleolus. Biochemical Journal, 73(2), 362–369.

    Article  Google Scholar 

  • Harris, H. (1965). The short-lived RNA in the cell nucleus and its possible role in evolution. In V. Bryson & G. Vogel (Eds.), Evolving genes and proteins (p. 629). London: Academic Press.

    Google Scholar 

  • Harris, H. (1994). An RNA heresy in the fifties. Trends in Biochemical Sciences, 19(7), 303–305.

    Article  Google Scholar 

  • Harris, H., Fisher, H. W., Rodgers, A., Spencer, T., & Watts, J. W. (1963). An examination of the ribonucleic acids in the HeLa cell with special reference to current theory about the transfer of information from nucleus to cytoplasm. Proceedings of the Royal Society of London B, 157(967), 177–198.

    Article  Google Scholar 

  • Harris, H., & Watts, J. W. (1962). The relationship between nuclear and cytoplasmic ribonucleic acid. Proceedings of the Royal Society of London B, 156(962), 109–121.

    Article  Google Scholar 

  • Harrison, E. (1987). Whigs, prigs and historians of science. Nature, 329(6136), 213–214.

    Article  Google Scholar 

  • Hiatt, H. H. (1962). A rapidly labeled RNA in rat liver nuclei. Journal of Molecular Biology, 5(2), 217–229.

    Article  Google Scholar 

  • Hoagland, M. (2004). Enter transfer RNA. Nature, 431(7006), 249.

    Article  Google Scholar 

  • Hoppe-Seyler, F. (1871). Ueber die chemische zusammensetzung des eiters. Medizinische Chemische Untersuchungen, 4, 486–501.

    Google Scholar 

  • Houck, M. M. (2009). Science versus crime. New York: Facts On File.

    Google Scholar 

  • Hunter, G. K. (1999). Phoebus Levene and the tetranucleotide structure of nucleic acids. Ambix, 46(2), 73–103.

    Article  Google Scholar 

  • Jardine, N. (2003). Whigs and stories: Herbert Butterfield and the historiography of science. History of Science, 41(2), 125–140.

    Article  Google Scholar 

  • Jeffreys, A. J., & Flavell, R. A. (1977). The rabbit beta-globin gene contains a large large insert in the coding sequence. Cell, 12(4), 1097–1108.

    Article  Google Scholar 

  • Jelinek, W., Adesnik, M., Salditt, M., Sheiness, D., Wall, R., Molloy, G., et al. (1973). Further evidence on the nuclear origin and transfer to the cytoplasm of polyadenylic acid sequences in mammalian cell RNA. Journal of Molecular Biology, 75(3), 515–532.

    Article  Google Scholar 

  • Jones, M. E. (1953). Albrecht Kossel, a biographical sketch. Yale Journal of Biology and Medicine, 26(1), 80–97.

    Google Scholar 

  • Judson, H. F. (1996). The eighth day of creation (Expanded ed.). New York: Cold Spring Harbor Laboratory Press.

    Google Scholar 

  • Kalckar, H. M. (1941). The nature of energetic coupling in biological synthesis. Chemical Reviews, 28, 71–178.

    Article  Google Scholar 

  • Keller, E. G. (1951). Turnover of proteins of cell fractions of adult rat liver in vivo. Federation Proceedings, 10, 206.

    Google Scholar 

  • Keuth, H. (2005). The philosophy of Karl Popper. Cambridge: Cambridge University Press.

    Google Scholar 

  • Keyes, M. E. (1999). The prion challenge to the ‘central dogma’ of molecular biology, 1965–1991. Part I: Prelude to prions. Studies in the History and Philososophy of Biological and Biomedical Sciences, 30(2), 181–218.

    Article  Google Scholar 

  • Kossel, A. (1881). Untersuchungen über die Nucleine und ihre Spaltungsprodukte. Strassburg: K.J. Trübner.

    Google Scholar 

  • Kossel, A. (1883–1884). Ueber guanin Hoppe-Seyler’s Zeitschrift für Physiologische Chemie, 8, 404–410.

  • Kossel, A. (1885). Ueber das adenin. Berichte der Deutschen Chemischen Gesellschaft, 18, 1928–1930.

    Article  Google Scholar 

  • Kossel, A. (1887). Ueber das adenin. Berichte der Deutschen Chemischen Gesellschaft, 20, 3356–3358.

    Article  Google Scholar 

  • Kossel, A. (1888). Ueber das adenin. Hoppe-Seyler’s Zeitschrift für Physiologische Chemie, 12, 241–253.

    Google Scholar 

  • Kossel, A. (1893). Ueber das thymin, ein spaltungsproduct der nucleinsäure. Berichte der Deutschen Chemischen Gesellschaft, 26, 2753–2756.

    Article  Google Scholar 

  • Kossel, A. (1910). Albrecht Kossel–Nobel Lecture: The chemical composition of the cell nucleus. Nobelprize.org. Nobel Media AB 2013. http://www.nobelprize.org/nobel_prizes/medicine/laureates/1910/kossel-lecture.html.

  • Kossel, A. (1911–1912). In: Harvey lectures, the chemical composition of the cell (Vol. 7, pp. 33–51). Philadelphia: J. B. Lippincott.

  • Kossel, A. (1912). The proteins. Bulletin of the Johns Hopkins Hospital, 23, 65–76.

    Google Scholar 

  • Kottler, M. J. (1974). From 48 to 46: Cytological technique, preconceptions, and the counting of human chromosomes. Bulletin of the History of Medicine, 48(4), 465–502.

    Google Scholar 

  • Kuhn, T. S. (1957). The copernican revolution—Planetary astronomy in the development of western thought. Cambridge, MA: Harvard University Press.

    Google Scholar 

  • Kuhn, T. S. (1970). The structure of scientific revolutions (2nd ed.). Chicago: The University of Chicago Press.

    Google Scholar 

  • Kuhn, T. S. (2000). The road since structure. Chicago: The University of Chicago Press.

    Google Scholar 

  • Lakatos, I. (1968). Criticism and methodology of scientific research programmes. Proceedings of the Aristotelian Society, 69(1), 149–186.

    Article  Google Scholar 

  • Lakatos, I. (1978). The methodology of scientific research programmes (Vol. 1, Lakatos Imre Philosophical Papers). Cambridge: Cambridge University Press.

  • Latham, H., & Darnell, J. E. (1965). Distribution of mRNA in the cytoplasmic polyribosomes of the HeLa cell. Journal of Molecular Biology, 14(1), 1–12.

    Article  Google Scholar 

  • Lee, S. Y., Mendecki, J., & Brawerman, G. (1971). A polynucleotide segment rich in adenylic acid in the rapidly-labeled polyribosomal RNA component of mouse sarcoma 180 ascites cells. Proceedings of the National Academy of Sciences of the USA, 68(6), 1331–1335.

    Article  Google Scholar 

  • Levene, P. A. (1909). Über die hefennucleinsäuren. Biochemische Zeitschrift, 17, 120–131.

    Google Scholar 

  • Levene, P. A. (1919). The structure of yeast nucleic acid: IV. Ammonia hydrolysis. The Journal of Biological Chemistry, 40(2), 415–424.

    Google Scholar 

  • Levene, P. A. (1921). On the structure of thymus nucleic acid and on its possible bearing on the structure of plant nucleic acid. The Journal of Biological Chemistry, 48(1), 119–125.

    Google Scholar 

  • Levene, P. A., & Bass, L. W. (1931). Nucleic acids. New York: The Chemical Catalog Company.

    Google Scholar 

  • Levene, P. A., & Jacobs, W. A. (1909a). Über die pentose in den nucleinsäuren [I}. Berichte der Deutschen Chemischen Gesellschaft, 42(2), 2102–2106.

    Article  Google Scholar 

  • Levene, P. A., & Jacobs, W. A. (1909b). Über die pentose in den nucleinsäuren [II]. Berichte der Deutschen Chemischen Gesellschaft, 42(3), 3247–3251.

    Article  Google Scholar 

  • Levene, P. A., & London, E. S. (1929). The structure of thymonucleic acid. The Journal of Biological Chemistry, 83(3), 793–802.

    Google Scholar 

  • Levene, P. A., & Mandel, J. A. (1908a). Über die darstellung und analyse einiger nucleinsäuren. XIII. Über ein verfahren zur gewinnung der purinbasen. Biochemische Zeitschrift, 10, 215–220.

    Google Scholar 

  • Levene, P. A., & Mandel, J. A. (1908b). Über die konstitution der thymo-nucleinsäure. Berichte der Deutschen Chemischen Gesellschaft, 41(2), 1905–1909.

    Article  Google Scholar 

  • Levene, P. A., & Simms, H. S. (1926). Nucleic acid structure as determined by electrometric titration data. The Journal of Biological Chemistry, 70(2), 327–341.

    Google Scholar 

  • Levene, P. A., & Tipson, R. S. (1935). The ring structure of thymidine. The Journal of Biological Chemistry, 109(2), 623–630.

    Google Scholar 

  • Lightman, A., & Gingerich, O. (1992). When do anomalies begin? Science, 255(5045), 690–695.

    Article  Google Scholar 

  • Lipmann, F. (1941). Metabolic generation and utilization of phosphate bond energy. Advances in Enzymology, 1, 99–162.

    Google Scholar 

  • Loftfield, R. B. (1947). Preparation of 14C-labeled hydrogen cyanide, alanine and glycine. Nucleonics, 1(3), 54–57.

    Google Scholar 

  • Loftfield, R. B., Grover, J. W., & Stephenson, M. L. (1953). Possible role of proteolytic enzymes in protein synthesis. Nature, 171(4362), 1024–1025.

    Article  Google Scholar 

  • Losee, J. (2005). Theories on the scrap heap. Pittsburgh, PA: The University of Pittsburgh Press.

    Google Scholar 

  • Martin, A. (2004). Can’t anybody count? Counting as epistemic theme in the history of human chromosomes. Social Studies of Science, 34(6), 923–948.

    Article  Google Scholar 

  • Mayr, E. (1990). When is historiography Whiggish. Journal of the History of Ideas, 51(2), 301–309.

    Article  Google Scholar 

  • Melchior, J., & Tarver, H. (1947a). Studies on protein synthesis in vitro; on the uptake of labeled sulfur by the proteins of liver slices incubated with labeled methionine (S35). Archives of Biochemistry, 12(2), 309–315.

    Google Scholar 

  • Melchior, J. B., & Tarver, H. (1947b). Studies in protein synthesis in ro; on the synthesis of labeled cystine (S35) and its attempted use as a tool in the study of protein synthesis. Archives of Biochemistry, 12(2), 301–308.

    Google Scholar 

  • Miescher, F. (1871). Ueber die chemische zusammensetzung der eiterzellen. Medicinisch-Chemische Untersuchungen, 4, 441–460.

    Google Scholar 

  • Miura, K., Watanabe, K., & Sugiura, M. (1974a). 5′-Terminal nucleotide sequences of the double-stranded RNA of silkworm cytoplasmic polyhedrosis virus. Journal of Molecular Biology, 86(1), 31–48.

    Article  Google Scholar 

  • Miura, K., Watanabe, K., Sugiura, M., & Shatkin, A. J. (1974b). The 5′-terminal nucleotide sequences of the double-stranded RNA of human reovirus. Proceedings of the National Academy of Sciences of the USA, 71(10), 3979–3983.

    Article  Google Scholar 

  • Molloy, G. R., & Darnell, J. E. (1973). Characterization of the poly(adenylic acid) regions and the adjacent nucleotides in heterogeneous nuclear ribonucleic acid and messenger ribonucleic acid from HeLa cells. Biochemistry, 12(12), 2324–2330.

    Article  Google Scholar 

  • Mulder, C., Arrand, J. R., Delius, H., Keller, W., Pettersson, U., Roberts, R. J., et al. (1974). Cleavage maps of DNA from adenovirus types 2 and 5 by restriction endonucleases EcoRI and HpaI. Cold Spring Harbor Symposia on Quantitative Biology, 39, 397–400.

    Article  Google Scholar 

  • Ogston, A. G. (1945). On the numerical consequences of certain hypotheses of protein structure. Transaction of the Faraday Society, 41, 670–676.

    Article  Google Scholar 

  • Olby, R. (1974). DNA before Watson–Crick. Nature, 248(5451), 782–785.

    Article  Google Scholar 

  • Olby, R. (1994). The Path to the double helix: The discovery of DNA. New York: Dover.

    Google Scholar 

  • Osborne, T. B., & Harris, I. F. (1902a). Die nucleinsäure des weizenembryos. Hoppe-Seyler’s Zeitschrift für Physiologische Chemie, 36, 85–133.

    Article  Google Scholar 

  • Osborne, T. B., & Harris, I. F. (1902b). The nucleic acid of the embryo of wheat. Annual Report of the Connecticut Agricultural Experimental Station, 25, 365–430.

    Google Scholar 

  • Painter, T. S. (1923). Studies in mammalian spermatogenesis. II. The spermatogenesis of man. Journal of Experimental Zoology, 37(3), 291–336.

    Article  Google Scholar 

  • Penman, S., Scherrer, K., Becker, Y., & Darnell, J. E. (1963). Polyribosomes in normal and poliovirus-infected Hela cells and their relationship to messenger-RNA. Proceedings of the National Academy of Sciences of the USA, 49(5), 654–662.

    Article  Google Scholar 

  • Perry, R. P., & Kelley, D. E. (1974). Existence of methylated messenger RNA in mouse L cells. Cell, 1(1), 37–42.

    Article  Google Scholar 

  • Perry, R. P., & Kelley, D. E. (1975). Methylated constituents of heterogeneous nuclear RNA: Presence in blocked 5′ terminal structures. Cell, 6(1), 13–19.

    Article  Google Scholar 

  • Perry, R. P., & Kelley, D. E. (1976). Kinetics of formation of 5′ terminal caps in mRNA. Cell, 8(3), 433–442.

    Article  Google Scholar 

  • Perry, R. P., Kelley, D. E., Friderici, K., & Rottman, F. (1975). The methylated constituents of L cell messenger RNA: Evidence for an unusual cluster at the 5′ terminus. Cell, 4(4), 387–394.

    Article  Google Scholar 

  • Philipson, L., Pettersson, U., Lindberg, U., Tibbetts, C., Vennström, B., & Persson, T. (1974). RNA synthesis and processing in adenovirus-infected cells. Cold Spring Harbor Symposia on Quantitative Biology, 39, 447–456.

    Article  Google Scholar 

  • Philipson, L., Wall, R., Glickman, G., & Darnell, J. E. (1971). Addition of polyadenylate sequences to virus-specific RNA during adenovirus replication. Proceedings of the National Academy of Sciences of the USA, 68(11), 2806–2809.

    Article  Google Scholar 

  • Platt, J. R. (1964). Strong Inference: Certain systematic methods of scientific thinking may produce much more rapid progress than others. Science, 146(3642), 347–353.

    Article  Google Scholar 

  • Plósz, P. (1871). Ueber das chemische verhalten der kerne der vogel- und schlangenblutkörperchen. Medizinisch-chemische Untersuchungen, 4, 461–462.

    Google Scholar 

  • Popper, K. (1970). Normal science and its dangers. In I. Lakatos & A. Musgrave (Eds.), Criticism and the growth of knowledge (pp. 51–58). Cambridge: Cambridge University Press.

    Chapter  Google Scholar 

  • Popper, K. (2002). The logic of scientific discovery. London: Routledge Classics.

    Google Scholar 

  • Prusiner, S. B. (1982). Novel proteinaceous infectious particles cause scrapie. Science, 216(4542), 136–144.

    Article  Google Scholar 

  • Reddy, R., Ro-Choi, T. S., Henning, D., & Busch, H. (1974). Primary sequence of U-1 nuclear ribonucleic acid of Novikoff hepatoma ascites cells. The Journal of Biological Chemistry, 249(20), 6486–6494.

    Google Scholar 

  • Rheinberger, H. J. (1993). Experiment and orientation: Early systems of in vitro protein synthesis. Journal of the History of Biology, 26(3), 443–471.

    Article  Google Scholar 

  • Rheinberger, H. J. (1995). From microsomes to ribosomes: “strategies” of “representation”. [Historical Article]. Journal of the History of Biology, 28(1), 49–89.

    Article  Google Scholar 

  • Rheinberger H. J. (1997). Toward a history of epistemic things: Synthesizing proteins in the test tube (Vols. 32, 3): Palo Ato, CA: Stanford University Press.

  • Rheinberger, H. J. (2004). A history of protein biosynthesis and ribosome research. In K. H. Nierhaus & D. N. Wilson (Eds.), Protein synthesis and ribosome structure: Translating the genome. Weinheim: Wiley.

    Google Scholar 

  • Russel, C. A. (1971). History of valence. New York: Humanities Press.

    Google Scholar 

  • Salditt-Georgieff, M., Jelinek, W., Darnell, J. E., Furuichi, Y., Morgan, M., & Shatkin, A. (1976). Methyl labeling of HeLa cell hnRNA: A comparison with mRNA. Cell, 7(2), 227–237.

    Article  Google Scholar 

  • Sarabhai, A. S., Stretton, A. O., Brenner, S., & Bolle, A. (1964). Co-linearity of the gene with the polypeptide chain. Nature, 201(4914), 13–17.

    Article  Google Scholar 

  • Scheele, V. Q. (1776). Examen chemicum calculi urinari. Opuscula, 2, 73.

    Google Scholar 

  • Scherrer, K., & Darnell, J. E. (1962). Sedimentation characteristics of rapidly labelled RNA from HeLa cells. Biochemical and Biophysical Research Communications, 7(6), 486–490.

    Article  Google Scholar 

  • Scherrer, K., Latham, H., & Darnell, J. E. (1963). Demonstration of an unstable RNA and of a precursor to ribosomal RNA in HeLa cells. Proceedings of the National Academy of Sciences of the USA, 49(2), 240–248.

    Article  Google Scholar 

  • Schmidt, G. (1928). Über fermentative desaminierung im muskel. Hoppe-Seyler’s Zeitschrift für Physiologische Chemie, 179, 243–269.

    Article  Google Scholar 

  • Schmidt, G., & Levene, P. A. (1938). The effect of nucleophosphatase on “native” and depolymerized thymonucleic Acid. Science, 88(2277), 172–173.

    Article  Google Scholar 

  • Sharp, P. A., Gallimore, P. H., & Flint, S. J. (1974). Mapping of adenovirus 2 RNA sequences in lytically infected cells and transformed cell lines. Cold Spring Harbor Symposia on Quantitative Biology, 39, 457–474.

    Article  Google Scholar 

  • Siekevitz, P. (1952). Uptake of radioactive alanine in vitro into the proteins of rat liver fractions. The Journal of Biological Chemistry, 195(2), 549–565.

    Google Scholar 

  • Siekevitz, P., & Zamecnik, P. C. (1951). In vitro incorporation of 1-C14-DL-alanine into proteins of rat liver granular fractions. Federation Proceedings, 10, 246–247.

    Google Scholar 

  • Signer, R., Caspersson, T., & Hammersten, E. (1938). Molecular shape and size of thymonucleic acid. Nature, 141(3559), 122.

    Article  Google Scholar 

  • Sober, E. (2008). Evidence and evolution: The logic behind the science. Cambridge: Cambridge University Press.

    Book  Google Scholar 

  • Soeiro, R., Birnboim, H. C., & Darnell, J. E. (1966). Rapidly labeled HeLa cell nuclear RNA. II. Base composition and cellular localization of a heterogeneous RNA fraction. Journal of Molecular Biology, 19(2), 362–372.

    Article  Google Scholar 

  • Takahashi, H. (1932). Über fermentative dephosphorierung der nucleinsäure. Journal of Biochemistry (Japan), 16(2), 463–482.

    Article  Google Scholar 

  • Thomas, M., White, R. L., & Davis, R. W. (1976). Hybridization of RNA to double-stranded DNA: Formation of R-loops. Proceedings of the National Academy of Sciences of the USA, 73(7), 2294–2298.

    Article  Google Scholar 

  • Tibbetts, C., & Pettersson, U. (1974). Complementary strand-specific sequences from unique fragments of adenovirus type 2 DNA for hybridization-mapping experiments. Journal of Molecular Biology, 88(4), 767–784.

    Article  Google Scholar 

  • Tjio, J. H., & Levan, A. (1956). The chromosome number in man. Hereditas, 42(1–2), 1–6.

    Google Scholar 

  • Unger, B. (1846). Das guanin und seine verbindungen. Justus Liebigs Annalen der Chemie, 59, 58–68.

    Article  Google Scholar 

  • Unger, L., & Blystone, R. V. (1996). Paradigm lost: The human chromosome story. Bioscene, 22(2), 3–9.

    Google Scholar 

  • Van Slyke, D. D., & Jacobs, W. A. (1943). Phoebus Aaron Theodor Levene 1869–1943. Biographical Memoirs National Academy of Sciences, 23, 73–126.

    Google Scholar 

  • Vischer, E., & Chargaff, E. (1947). The separation and characterization of purines in minute amounts of nucleic acid hydrolysates. The Journal of Biological Chemistry, 168(2), 781.

    Google Scholar 

  • Vischer, E., & Chargaff, E. (1948a). The composition of the pentose nucleic acids of yeast and pancreas. The Journal of Biological Chemistry, 176(2), 715–734.

    Google Scholar 

  • Vischer, E., & Chargaff, E. (1948b). The separation and quantitative estimation of purines and pyrimidines in minute amounts. The Journal of Biological Chemistry, 176(2), 703–714.

    Google Scholar 

  • Vischer, E., Zamenhof, S., & Chargaff, E. (1949). Microbial nucleic acids; the desoxypentose nucleic acids of avian tubercle bacilli and yeast. The Journal of Biological Chemistry, 177(1), 429–438.

    Google Scholar 

  • Voegtlin, C., Maver, M. E., & Johnson, J. M. (1933). The influence of the oxygen tension on the reversal of proteolysis (protein synthesis) in certain malignant tumors and normal tissues. Journal of Pharmacology and Experimental Therapeutics, 48(2), 241–265.

    Google Scholar 

  • Wall, R., Philipson, L., & Darnell, J. E. (1972). Processing of adenovirus specific nuclear RNA during virus replication. Virology, 50(1), 27–34.

    Article  Google Scholar 

  • Warner, J. R., Knopf, P. M., & Rich, A. (1963a). A multiple ribosomal structure in protein synthesis. Proceedings of the National Academy of Sciences of the USA, 49(1), 122–129.

    Article  Google Scholar 

  • Warner, J. R., Madden, M. J., & Darnell, J. E. (1963b). The interaction of poliovirus RNA with Escherichia coli ribosomes. Virology, 19(3), 393–399.

    Article  Google Scholar 

  • Warner, J. R., Soeiro, R., Birnboim, H. C., Girard, M., & Darnell, J. E. (1966). Rapidly labeled HeLa cell nuclear RNA. I. Identification by zone sedimentation of a heterogeneous fraction separate from ribosomal precursor RNA. Journal of Molecular Biology, 19(2), 349–361.

    Article  Google Scholar 

  • Wasteneys, H., & Borsook, H. (1930). The enzymatic synthesis of protein. Physiological Reviews, 10(1), 110–145.

    Google Scholar 

  • Watson, J. D., & Crick, F. H. (1953a). Genetical implications of the structure of deoxyribonucleic acid. Nature, 171(4361), 964–967.

    Article  Google Scholar 

  • Watson, J. D., & Crick, F. H. (1953b). Molecular structure of nucleic acids; a structure for deoxyribose nucleic acid. Nature, 171(4356), 737–738.

    Article  Google Scholar 

  • Watts, J. W., & Harris, H. (1959). Turnover of nucleic acids in a non-multiplying animal cell. Biochemical Journal, 72(1), 147–153.

    Article  Google Scholar 

  • Wei, C. M., & Moss, B. (1975). Methylated nucleotides block 5′-terminus of vaccinia virus messenger RNA. Proceedings of the National Academy of Sciences of the USA, 72(1), 318–322.

    Article  Google Scholar 

  • Werner, A. (1902). Ueber haupt- und nebenvalenzen und die constitution der ammoniumverbindungen. Justus Liebigs Annalen der Chemie, 322(3), 261–296.

    Article  Google Scholar 

  • White, R. L., & Hogness, D. S. (1977). R loop mapping of the 18S and 28S sequences in the long and short repeating units of Drosophila melanogaster rDNA. Cell, 10(2), 177–192.

    Article  Google Scholar 

  • Winnick, T., Friedberg, F., & Greenberg, D. M. (1947). Incorporation of C14-labeled glycine into intestinal tissue and its inhibition by azide. Archives of Biochemistry, 15(1), 160.

    Google Scholar 

  • Winnick, T., Friedberg, F., & Greenberg, D. M. (1948). The utilization of labeled glycine in the process of amino acid incorporation by the protein of liver homogenate. The Journal of Biological Chemistry, 175(1), 117–126.

    Google Scholar 

  • Yanofsky, C., Carlton, B. C., Guest, J. R., Helinski, D. R., & Henning, U. (1964). On the colinearity of gene structure and protein structure. Proceedings of the National Academy of Sciences of the USA, 51(2), 266–272.

    Article  Google Scholar 

  • Yanofsky, C., Drapeau, G. R., Guest, J. R., & Carlton, B. C. (1967). The complete amino acid sequence of the tryptophan synthase A protein (alpha subunit) and its colinar relationship with the genetic map of the A gene. Proceedings of the National Academy of Sciences of the USA, 57(2), 296–298.

    Article  Google Scholar 

  • Zamecnik, P. C., & Keller, E. B. (1954). Relation between phosphate energy donors and incorporation of labeled amino acids into proteins. The Journal of Biological Chemistry, 209(1), 337–354.

    Google Scholar 

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Acknowledgments

I am indebted to Drs. Iris Fry and Avram Hershko for their critical reading of this manuscript and to the two anonymous reviewers for their insightful comments and suggestions.

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  1. Department of Biochemistry, Rappaport Faculty of Medicine, Technion - Israel Institute of Technology, POB 9649, 31096, Haifa, Israel

    Michael Fry

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Fry, M. Dissolution of hypotheses in biochemistry: three case studies. HPLS 38, 17 (2016). https://doi.org/10.1007/s40656-016-0118-x

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