The Comparative and the Exemplary: Revisiting the Early History of Molecular Biology

This narrative was at the core of William R. Coleman's and Garland E. Allen's seminal work; see Coleman William R. , Biology in the nineteenth century: Problems of form, function and transformation (Cambridge, 1971), and Allen Garland E. , Life science in the twentieth century (Cambridge and London, 1978). It has served as a model for later work, for example Magner Lois N. , A history of the life sciences, 3rd edn (New York, 2002); Bowler Peter J. Morus Iwan Rhys , Making modern science: A historical survey (Chicago, 2005). For a richer description of the practices of natural historians that complicates the neat contraposition between descriptive and experimental life sciences see for instance Hagen Joel B. , “Experimental taxonomy, 1920–1950: The impact of cytology, ecology, and genetics on the ideas of biological classification”, Ph.D. dissertation, Oregon State University, 1984; Nyhart Lynn K. , “Natural history and the ‘new’ biology”, in Jardine Nicholas Secord James A. Spary Emma C. (eds), Cultures of natural history (London, 1996), 426–43; Kohler Robert E. , Landscapes and labscapes: Exploring the lab—field border in biology (Chicago, 2002); Kingsland Sharon E. , The evolution of American ecology, 1890–2000 (Baltimore, 2005); Milam Erika Lorraine , “‘The experimental animal from the naturalist's point of view’: Behavior and evolution at the American Museum of Natural History, 1928–1954”, in Cain Joe Ruse Michael (eds), Descended from Darwin: Insights into the history of evolutionary studies, 1900–1970 (Philadelphia, 2009), 157–78; Terrall Mary , “Following insects around: Tools and techniques of eighteenth-century natural history”, The British journal for the history of science, xliii (2010), 2010–88; Terrall Mary , “Frogs on the mantelpiece: The practice of observation in daily life”, in Daston Lorraine Lunbeck Elizabeth (eds), Histories of scientific observation (Chicago, 2011), 185–205.

Kohler Robert E. , Partners in science: Foundations and natural scientists (Chicago, 1991); Kay Lily E. , The molecular vision of life: Caltech, the Rockefeller Foundation and the rise of the new biology (New York, 1993).

Kay Lily E. , “Life as technology, representing, intervening and molecularizing”, in Sarkar Sahotra (ed.), The philosophy and history of molecular biology: New perspectives (Dordrecht, 1996), 87–100; Creager Angela N. H. , The life of a virus: Tobacco mosaic virus as an experimental model, 1930–1965 (Chicago, 2002); Rasmussen Nicolas , Picture control: The electron microscope and the transformation of biology in America, 1940–1960 (Stanford, 1997); de Chadarevian Soraya , Designs for life: Molecular biology after World War II (Cambridge, 2002); Strasser Bruno J. , La fabrique d'une nouvelle science: La biologie moléculaire à l'âge atomique (1945–1964) (Florence, 2006).

On phage, Fischer Ernst P. Lipson Carol , Thinking about science: Max Delbrück and the origins of molecular biology (New York, 1988); on TMV, Creager , The life of a virus (ref. 3); on moulds, Berg Paul Singer Maxine , George Beadle, an uncommon farmer: The emergence of genetics in the 20th century (Cold Spring Harbor, NY, 2003); on flies, Kohler Robert E. , Lords of the fly: Drosophila genetics and the experimental life (Chicago, 1994); on worms, de Chadarevian Soraya , ” of worms and programmes: Caenorhabditis elegans and the study of development”, Studies in history and philosophy of biological and biomedical sciences, xxix (1998), 1998–105 and Ankeny Rachel A. , “The natural history of Caenorhabditis elegans research”, Nature reviews genetics, ii (2001), 2001–79; on mice, Rader Karen A. , Making mice: Standardizing animals for American biomedical research, 1900–1955 (Princeton, 2004); on plants, Leonelli Sabina , “Arabidopsis, the botanical Drosophila: From mouse cress to model organism”, Endeavour, xxxi (2007), 2007–8; and more generally on model organisms and systems, Creager Angela N. H. Lunbeck Elizabeth Wise M. Norton , Science without laws: Model systems, cases, exemplary narratives (Durham, 2007).

Pickstone John V. , “Ways of knowing: Towards a historical sociology of science, technology and medicine”, The British journal for the history of science, xxvi (1993), 433–58; Pickstone John V. , “Museological science? The place of the analytical/comparative in nineteenth-century science, technology and medicine”, History of science, xxxii (1994), 1994–38; Pickstone John V. , Ways of knowing: A new history of science, technology and medicine (Manchester, 2000); Pickstone John V. , “Working knowledges before and after circa 1800: Practices and disciplines in the history of science, technology and medicine”, Isis, xcviii (2007), 2007–516.

For an early use of the expression, see Mitchison J. M. , The biology of the cell cycle (Cambridge, 1971), 6. We thank Rachel Ankeny for providing this reference.

See for example the naturalist E. O. Wilson's reaction to the attacks of molecular biologists such as Watson James D. Wilson Edward O. , Naturalist (Washington, DC, 1994), chap. 12; and Dietrich Michael R. , “Paradox and persuasion: Negotiating the place of molecular evolution within evolutionary biology”, Journal of the history of biology, xxxi (1998), 1998–111; Hagen Joel B. , “Naturalists, molecular biology, and the challenge of molecular evolution”, Journal of the history of biology, xxxii (1999), 1999–41; Milam Erika Lorraine , “The equally wonderful field: Ernst Mayr and organismic biology”, Historical studies in the natural sciences, xl (2010), 2010–317.

On other attempts to challenge this distinction, see Milam , “‘The experimental animal from the naturalist's point of view’” (ref. 1); Kohler , Landscapes and labscapes (ref. 1); Nyhart, “Natural history and the ‘new’ biology” (ref. 1); Bruno J. Strasser, “Laboratories, museums, and the comparative perspective: Alan A. Boyden's serological taxonomy, 1925–1962”, Historical studies in the natural sciences, xl (2010), 2010–82. On collecting as an essential practice in a wide spectrum of sciences, including genomics, see Pickstone , Ways of knowing (ref. 5); Bruno J. Strasser, “Collecting and experimenting: The moral economies of biological research, 1960s–1980s”, Preprints of the Max-Plack Institute for the History of Science, no. 310 (2006), 105–23; Robert E. Kohler, “Finders, keepers: Collecting sciences and collecting practice”, History of science, xlv (2007), 2007–54.

Pickstone , Ways of knowing (ref. 5), chap. 4.

Fleck Ludwik , Genesis and development of a scientific fact (Chicago, 1979); Kuhn Thomas S. , The structure of scientific revolutions, 2nd edn (Chicago, 1970); Foucault Michel Gordon Colin , Power/knowledge: Selected interviews and other writings, 1972–1977 (New York, 1980); Holton Gerald James , Thematic origins of scientific thought: Kepler to Einstein (Cambridge, MA, 1973); Crombie Alistair C. , Styles of scientific thinking in the European tradition: The history of argument and explanation especially in the mathematical and biomedical sciences and arts (London, 1994).

Hacking Ian , “‘Style’ for historians and philosophers”, Studies in history and philosophy of science, xxiii (1992), 1–20.

See also Hacking Ian , “The self-vindication of the laboratory sciences”, in Pickering Andrew (ed.), Science as practice and culture (Chicago, 1992), 29–64. For a critique of Hacking's notion of “style”, see Kusch Martin , “Hacking's historical epistemology: A critique of styles of reasoning”, Studies in history and philosophy of science, xli (2010), 2010–73.

Pickstone , “Museological science?” (ref. 5).

For a very useful exposition of exemplary cases in the clinic, see Löwy Ilana , “The experimental body”, in Cooter Roger Pickstone John (eds), Medicine in the twentieth century (Amsterdam, 2000), 435–49. On model organisms more generally, see ref. 5.

Strasser , “Laboratories, museums, and the comparative perspective” (ref. 8).

Monod Jacques Jacob François , “General conclusions: Teleonomic mechanisms in cellular metabolism, growth, and differentiation”, Cold Spring Harbor Symposia on Quantitative Biology, xxi (1961), 389–401. On the origins of this expression, see Friedmann Herbert C. , “From ‘Butyribacterium’ to ‘E. coli’: An essay on unity in biochemistry”, Perspectives in biology and medicine, xlvii (2004), 2004–66. In the earlier part of the twentieth century, knowledge derived from animal model organisms was believed to hold true only for animals, not plants and microbes, as would become the case in molecular biology starting in the late 1950s.

On this point see also Pickstone , “Working knowledges before and after circa 1800” (ref. 5), 513–14.

Strasser Bruno J. , “A world in one dimension: Linus Pauling, Francis Crick and the central dogma of molecular biology”, History and philosophy of the life sciences, xxviii (2006), 491–512.

The general rule was interpreted less strictly when the idea of “allosteric” proteins was developed a few years later. Creager Angela N. H. Gaudillière Jean-Paul , “Meanings in search of experiments and vice-versa: The invention of allosteric regulation in Paris and Berkley, 1959–1968”, Historical studies in the physical and biological sciences, xxvii (1996), 1–89.

Crick Francis H. C. , “On protein synthesis”, Symposia of the Society for Experimental Biology, xii (1958), 138–63.

Schmitt Stéphane , “From physiology to classification: Comparative anatomy and Vicq d'Azyr's plan of reform for life sciences and medicine (1774–1794)”, Science in context, xxii (2009), 145–93; Outram Dorinda , Georges Cuvier: Vocation, science, and authority in post-revolutionary France (Manchester, 1984).

de Chadarevian Soraya , “Sequences, conformation, information: Biochemists and molecular biologists in the 1950s”, Journal of the history of biology, xxix (1996), 361–86; Garcia-Sancho Miguel , “A new insight into Sanger's development of sequencing: From proteins to DNA, 1943–1977”, Journal of the history of biology, xliii (2010), 2010–323.

Sanger Frederick , “Species differences in insulins”, Nature, clxiv (1949), 529; Brown H. Sanger Frederick Kitai Ruth , “The structure of pig and sheep insulins”, Biochemical journal, lx (1955), 1955–65; Harris J. Ieuan Naughton Michael A. Sanger Frederick , “Species differences in insulin”, Archives of biochemistry and biophysics, lxv (1956), 1956–38; de Chadarevian Soraya , “Protein sequencing and the making of molecular genetics”, Trends in biochemical sciences, xxiv (1999), 1999–6.

Harris Naughton Sanger , “Species differences in insulin” (ref. 23); Brown Sanger Kitai , “The structure of pig and sheep insulins” (ref. 23), 565.

Harris Naughton Sanger , “Species differences in insulin” (ref. 23), 437. Sequence comparisons did not necessarily regard sequences from other species. They could also concern enzyme families from the same species. This project was pursued for instance by Brian Hartley who later moved together with Sanger to the Laboratory of Molecular Biology in Cambridge. His comparative study of various pancreatic enzymes first served to study the catalytic mechanism of the enzymes, but soon led to comparative evolutionary studies; see de Chadarevian , Designs for life (ref. 3), 273.

de Chadarevian , “Sequences, conformation, information” (ref. 22).

Crick , “On protein synthesis” (ref. 20), 142.

Ibid.

Tuppy Hans Bodo Gerhard , “Cytochrom c. III: Zur Frage der Artspezifität von Säugetier-Cytochrom c”, Monatshefte für Chemie, lxxxv (1954), 1182–6.

Paléus Sven Tuppy Hans , “A hemopeptide from a tryptic hydrolysate of Rhodospirillum rubrum cytochrome-c”, Acta chemica scandinavica, xiii (1959), 641–6, p. 642.

Tuppy Hans , “Über die Artspezifität der Proteinstruktur”, in Neuberger Albert (ed), Symposium on protein structure (New York, 1958), 66–76.

Blombäck Birger Blombäck Margareta Grondahl Nils Jakob , “Studies on fibrinopeptides from mammals”, Acta chemica scandinavica, xix (1965), 1789–91, p. 1789.

Anfinsen C. B. Aqvist S. E. Cooke J. P. Jonsson B. , “A comparative study of the structures of bovine and ovine pancreatic ribonucleases”, Journal of biological chemistry, ccxxxiv (1959), 1118–23, p. 1118.

Ibid., 143.

Sanger Frederick , “Sequences, sequences, and sequences”, Annual review of biochemistry, lvii (1988), 1–28, p. 3.

Baldwin Ernest , An introduction to comparative biochemistry (Cambridge, 1937; 2nd edn, Cambridge, 1966).

Baldwin was a student of Hopkins. On Hopkins, see Kohler Robert E. , From medical chemistry to biochemistry: The making of a biomedical discipline (Cambridge, 1982).

Baldwin , An introduction to comparative biochemistry (ref. 36), p. xiv.

de Chadarevian , Designs for life (ref. 3), 89.

Florkin Marcel , L'évolution biochimique (Paris, 1944; Engl. transl., New York, 1949).

Florkin , L'évolution biochimique (ref. 40), 11, translation ours.

Abir-Am Pnina , “The politics of macromolecules: Molecular biologists, biochemists, and rhetoric”, Osiris, vii (1992), 164–91.

Moore Stanford Spackman Darrel H. Stein William H. , “Automatic recording apparatus for use in the chromatography of amino acids”, Federation proceedings, lvii (1958), 1107–15. Commercial versions only became available in the 1960s.

Strasser , “Laboratories, museums, and the comparative perspective” (ref. 8).

Strasser Bruno J. , “Collecting, comparing, and computing sequences: The making of Margaret O. Dayhoff's Atlas of Protein Sequences and Structure, 1954–1965”, Journal of the history of biology, xliii (2010), 623–60.

Lederberg J. Dayhoff M. O. , 12 March 1964, National Biomedical Research Foundation Archives, Georgetown, MD.

de Chadarevian , Designs for life (ref. 3); Ferry Georgina , Max Perutz and the secret of life (New York, 2007).

Perutz Max F. , I wish I'd made you angry earlier: Essays on science, scientists, and humanity (Plainview, NY, 1998).

de Chadarevian Soraya , “Following molecules: Haemoglobin between the clinic and the laboratory”, in de Chadarevian Soraya Kamminga Harmke (eds), Molecularizing biology and medicine: New practices and alliances, 1910s–1970s (Amsterdam, 1998), 171–201.

Lehmann Hermann , Man's haemoglobins: Including the haemoglobinopathies and their investigation (Amsterdam, 1966).

Perutz Max F. Lehmann Hermann , “Molecular pathology of human haemoglobin”, Nature, ccxix (1968), 902–9; Morimoto Hermann Lehmann H. Perutz Max F. , “Molecular pathology of human haemoglobin: Stereochemical interpretation of abnormal oxygen affinities”, Nature, ccxxxii (1971), 1971–13. Significantly, clinical symptoms included observations obtained at the bedside (e.g. cyanosis, splenomegaly) as well as classifications based on laboratory data (e.g. inclusion body anemia, haemolytic anemia). Even before paper electrophoresis of abnormal haemoglobins became a standard procedure in hematology, hematologists relied heavily on microscopic observation and laboratory tests for the description and classification of diseases.

Morange Michel , A history of molecular biology (Cambridge, 2000), chap. 12; Kay Lily E. , Who wrote the book of life?: A history of the genetic code (Stanford, 2000).

Gamow George , “Possible relation between desoxyribonucleic acid and protein structure”, Nature, clxxiii (1954), 318; Gamow George Metropolis Nicholas , “Numerology of polypeptide chains”, Science, cxx (1954), 1954–80; Crick Francis H. C. , What mad pursuit (New York, 1990), 94.

Kay , Who wrote the book of life? (ref. 52).

Strasser , “Collecting, comparing, and computing sequences” (ref. 45).

See de Chadarevian , “Protein sequencing and the making of molecular genetics” (ref. 23).

For examples of this approach, see Gamow George Rich Alexander Yčas Martynas , “The problem of information transfer from the nucleic acids to proteins”, Advances in biological and medical physics, iv (1956), 23–68; Ycas Martynas , “The protein text”, in Yockey Hubert P. (ed.), Symposium on information theory in biology (New York, 1958), 70–102; Ycas Martynas , “Replacement of amino acids in proteins”, Journal of theoretical biology, i (1961), 1961–57. On the genesis of Gamow's review, see Kay , Who wrote the book of life? (ref. 52), 148. On the impossibility of overlapping codes, see Brenner Sydney , “On the impossibility of all overlapping triplet codes in information transfer from nucleic acid to proteins”, Proceedings of the National Academy of Sciences of the United States of America, xliii (1957), 1957–94. In fact, Brenner only showed that codes overlapping by 2 nucleotides out of 3 were impossible.

Kay points out that this information was used to confirm the code, but she does not raise the point that it was produced with the coding problem in mind; see Kay , Who wrote the book of life? (ref. 52), 187–9. However, Angela Creager makes this point; see Creager , The life of a virus (ref. 3), 303–11.

For example, if UUU coded for the amino acid phenylalanine, as Nirenberg and Matthaei had established, and phenylalanine were replaced by another amino acid in a mutant, scientists could deduce that this amino acid was coded by one of only nine different codons (all including two Us), thus excluding forty-four other possible combinations.

Speyer Joseph F. , “Synthetic polynucleotides and the amino acid code. II”, Proceedings of the National Academy of Sciences of the United States of America, xlviii (1962), 63–8; Lengyel Peter , “Synthetic polynucleotides and the amino acid code. III”, Proceedings of the National Academy of Sciences of the United States of America, xlviii (1962), 1962–4; Speyer J. F. , “Synthetic polynucleotides and the amino acid code. IV”, Proceedings of the National Academy of Sciences of the United States of America, xlviii (1962), 1962–8; Basilio Carlos , “Synthetic polynucleotides and the amino acid code. V”, Proceedings of the National Academy of Sciences of the United States of America, xlviii (1962), 1962–16.

Creager , The life of a virus (ref. 3), 303–11; Kay , Who wrote the book of life? (ref. 52), 179–92; Brandt Christina , Metapher und Experiment: Von der Virusforschung zum genetischen Code (Göttingen, 2004), chap. 6.

Smith Emil L. , “Nucleotide base coding and amino acid replacements in proteins”, Proceedings of the National Academy of Sciences of the United States of America, xlviii (1962), 677–84; Smith Emil L. , “Nucleotide base coding and amino acid replacements in proteins. II”, Proceedings of the National Academy of Sciences of the United States of America, xlviii (1962), 1962–64; Jukes Thomas H. , “Beta lactoglobulins and amino acid code”, Biochemical and biophysical research communications, vii (1962), 1962–3; Jukes Thomas H. , “Possible base sequences in amino acid code”, Biochemical and biophysical research communications, vii (1962), 1962–502; Jukes Thomas H. , “Relations between mutations and base sequences in amino acid code”, Proceedings of the National Academy of Sciences of the United States of America, xlviii (1962), 1962–15, Woese Carl R. , “Nature of the biological code”, Nature, cxciv (1962), 1962–15; Fitch Walter M. , “The probable sequence of nucleotides in some codons”, Proceedings of the National Academy of Sciences of the United States of America, cxxii (1964), 1964–305; Fitch Walter M. , “The relation between frequencies of amino acids and ordered trinucleotides”, Journal of molecular biology, xvi (1966), 1966–8. For a review of the contributions from the comparative approach, see Ochoa Severo , “Chemical basis of heredity, the genetic code”, Experientia, xx (1964), 1964–68; Crick Francis H. C. , “On the genetic code”, Science, cxxxix (1963), 1963–4.

Smith , “Nucleotide base coding and amino acid replacements in proteins” (ref. 62); Jukes Thomas H. , “The genetic code”, American scientist, li (1963), 227–45; Beale D. Lehmann H. , “Abnormal haemoglobins and the genetic code”, Nature, ccvii (1965), 1965–61.

Strasser Bruno J. , “The experimenter's museum: GenBank, natural history, and the moral economies of biomedicine”, Isis, cii (2011), 60–96.

Strasser , “Collecting, comparing, and computing sequences” (ref. 45). As Pickstone pointed out, forms of comparative analysis in the nineteenth century also spanned the natural and the human sciences; Pickstone , Ways of knowing (ref. 5), chap. 4.

For a history of early comparative approaches in morphology, see Russell Edward Stuart , Form and function: A contribution to the history of animal morphology (London, 1916).