Abstract
In a very real sense, molecular biology is all about sequences. First, it tries to reduce complex biochemical phenomena to interactions between defined sequences — either protein or polynucleotide, sometimes carbohydrates or lipids — then, it tries to provide physical pictures of how these sequences interact in space and time.1
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Notes
Gunnar von Heijne, Sequence Analysis in Molecular Biology: Treasure Trove or Trivial Pursuit. (San Diego Academic Press Inc., 1987), p. 151.
Harold J. Morowitz and Temple Smith, Report of the Matrix of Biological Knowledge Workshop. (Santa Fe, NM: Santa Fe Institute, July 13-August 14, 1987), pp. 1–2.
Excerpt from a letter of the president of Johns Hopkins, December 1991.
David B, Wake, “Comparative Terminology,” Science, 265, July 8 1994, 268.
Robert Pollack, Signs of Life: The Language and Meanings of DNA (Boston Houghton Mifflin Company, 1994), p. 159.
For histories of the Human Genome Initiative see Charles R. Cantor, “Orchestrating the Human Genome Project,” Science, 248, April 6 1990, pp 49–51; Robert M. Cook-Deegan, The Gene Wars: Science, Politics, and the Human Genome, (New York: W.W. Norton & Co., 1994); Michael Fortun, “Mapping and Making Genes and Histories: The Genomics Project in the United States, 1980-1990,” doctoral, History of Science Department, Harvard University, 1993; and Judson (1992); James D. Watson, “The Human Genome Project: Past, Present, and Future,” Science, 249, April 6 1990, pp. 44-49.
See quotes from other biologists at the beginning of this paper. There is an “old” theoretical biology, which has existed for some time, but which has not had the reputation of, say, theoretical physics. See von Heijne, Sequence Analysis in Molecular Biology. As historians of science have noted, this is not a novel move. The transformation of the body into an information system began in the 1940s, and has continued since that time, with the development of computers, cybernetics research, information theory, and military maneuvers to build command-and-control systems. The delineation of the structure of DNA was another step in this process of the informatizing of the body, but not the beginning of the process. See Donna J. Haraway, “The High Cost of Information in Post-World War II Evolutionary Biology: Ergonomics, Semiotics, and the Sociobiology of Communication Systems,” The Philosophical Forum, XIII, Winter-Spring 1981–1982, pp. 244-278; Evelyn Fox Keller, “The Body of a New Machine: Situating the Organism Between Telegraphs and Computers,” in Reflguring Life: Metaphors of Twentieth Century Biology (New York Columbia University Press, 1995); Lily Kay, “Who Wrote the Book of Life? Information and the Transformation of Molecular Biology, 1945-55,” in Experimentalsysteme in den Biologische-Medizinische Wissenschaften: Objekt, Differenzen, Konjunkturen, ed. Michael Hagner and Hans-Jorg Rheinberger (Berlin: Akademie Verlag, 1994); and Rich Doyle, “Mr. Schrodinger Inside Himself? The Rhetorical Origins of the Genetic Code,” Chapter 2 (Department of Rhetoric, University of California, Berkeley, doctoral dissertation, 1993).
Walter Gilbert, “Towards a Paradigm Shift in Biology,” Nature, 349, Jan 10 1991, 99.
Gilbert also argued that this paradigm shift from experimental biology to an information-based theoretical science will cure the “malaise” of technologization that has befallen biology. Many molecular biologists, as well as many graduate students in molecular biology, agree with Gilbert that molecular biology has become a series of cookbook techniques, complete with recipes and kits. Indeed, Gilbert’s own development of fast and relatively simple sequencing techniques contributed to the technologization of molecular biology. See Joan H. Fujimura, “The Molecular Biological Bandwagon in Cancer Research: Where Social Worlds Meet,” Social Problems, 35, (1988), pp. 261–283.
Gilbert, “Towards a Paradigm Shift in Biology,” p. 99.
Von Heijne, Sequence Analysis in Molecular Biology, p. 151.
See Walter Gilbert, “Genes-in-Pieces Revisited,” Science, 228 (1985), pp. 823-824; J. Rogers, “Exon Shuffling and Intron Insertion in Serine Protease Genes,” Nature, 315 (1985), pp. 458-59; and W. Gilbert, M. Marchionni, and G. McKnight, “On the Antiquity of Introns,” Cell, 46 (1986), pp. 151-154.
Von Heijne, Sequence Analysis in Molecular Biology, p 40. For another example, see T.F. Smith, A. Srinivasan, G. Schochetman, M. Marcus, and G. Myers, “The Phylogenetic History of Immunodeficiency Viruses,” Nature, 333, June 1988, pp. 573-575. Hillis refers to exon shuffling as,“partial homology.,” David M. Hillis, “Homology in Molecular Biology,” in Homology: The Hierarchical Basis of Comparative Biology ed. Brian K. Hall. (New Yo Academic Press, 1944), pp. 339–368.
CMSHG Report of the Committee on Mapping and Sequencing the Human Genome, Board on Basic Biology, Commission on Life Sciences, National Research Council, 1988, p. 55.
Robert L. Dorit, Lloyd Schoenbach, and Walter Gilbert, “How Big Is the Universe of Exons?” Science, 250, Dec 7 1990, pp. 1377–1382. Critiques of the research of Dorit and his colleagues by molecular biologists ranged from arguments with the thesis of the paper to arguments about the detailed assumptions made in constructing the computer program that produced the final numbers.
Anthropologists would refer to this as an origin story.
More recently, several researchers have argued that so-called “junk DNA” plays critical roles in the organism’s activities. See Roy J. Britten, David B. Stout, and Eric H. Davidson, “The Current Source of Human Alu Retroposons Is a Conserved Gene Shared with Old World Monkey,” Proceedings of the National Academy of Sciences, USA, 86, May 1989, pp. 3718–3722; and Ben F. Koop and Leroy Hood, “Striking Sequence Similarity over Almost 100 Kilobases of Human and Mouse T-cell Receptor DNA,” Nature Genetics, 7, May 1994, pp. 48-53.
National Center for Human Genome Research. Annual Report I-FY 1990, Department of Health and Human Services, Public Health Service, National Institutes of Health, 1990, pp. 30–31.
I am studying this process in my larger ethnographic research project.
NCHGR, Annual Report I-FY 1990, p. 26. See also Michael S. Waterman, “Genomic Sequence Databases,” Genomics, 6 (1990), pp. 700–701.
See also Michael Fortun, “Time, Busy Bodies, and the Habit of Becoming Genetic,” (forthcoming) on “speeding,” as a more general phenomenon in the twentieth century.
Sequence databases are only one kind of database. Genetic map databases provide different kinds of information. Sequence databases are only one kind of database. Genetic map databases provide different kinds of information. Major efforts have also been directed at linking the various databases to provide means for linking protein, DNA, RNA, and genetic map information for each sequence of interest. There is great debate about how to construct the semantics of each database to provide the “best,” use of the diverse databases.
Not all laboratories have the funds for computer access, and if they do have access, their universities might not have funds available for the requisite computer infrastructure or personnel with the skills to deal with the intricacies of the databases.
All of these options require further work, access to new resources, and, therefore, work reorganization. For example, a graduate student sequenced a gene (RNA) of a protist and discovered to his chagrin that he then had to arrange to gain access to the single existing database of RNA sequences for this protist. The database was private — that is, it was developed by and is maintained by an academic researcher famous for his work on the protist. In order to gain access, the graduate student arranged to work as a postdoctoral fellow in the laboratory with his required database. He was not pleased about the arrangement, however. He felt that he had now become “a twig on the [scientist’s] tree,” in order to be able to make some meaning of his sequence.
These figures are for July 1988. See Rita R. Colwell, ed., Biomolecular Data: A Resource in Transition, (Oxford Oxford University Press, 1989), p. 124.
C. elegans was promoted by Schatz and Roberts as a model for the sequencing and database building of information on the human genome. Bruce R. Schatz, “Building an Electronic Scientific Community,” in Proceedings of the 24th Annual Hawaii International Conference on Systems Science, III., ed. Jay Nunmaker (Los Almaritos, CA: IEEE Society Press, 1991); Leslie Roberts, “The Worm Project,” Science, 248 June 15 1990, pp. 1310–1313.
Compact Disc Read Only Memory, or CD-ROM, contain digitally encoded information readable by computer. These discs are “read only,” that is, they cannot be modified by the user. However, “read and write,” CDs will soon be commercially available. It is unclear what impact “read and write,” CDs will have on the collective production and use of genome information. An addendum: Walter Gilbert has predicted that, as various human genome projects proceed, each individual will soon be able to have her or his own genome on a CD.
Von Heijne, Sequence Analysis in Molecular Biology, p. 123.
Russell F. Doolittle, Of Urfs and Orfs: A Primer on How to Analyze Drived Amino Acid Sequences. (Mill Valley, CA University Science Books, 1987), p. 25. For an early example, see below.
Ibid., p. 17.
David B. Wake, “Comparative Terminology,” p. 268.
Ibid.
Doolittle, Of Urfs and Orfs, pp. 35–36.
Von Heijne, Sequence Analysis in Molecular Biology, p. 123.
Hillis, “Homology in Molecular Biology,” pp. 340–341.
Colin Patterson, “Introduction,” in Molecules and Morphology in Evolution: Conflict or Compromise? ed. C. Patterson (Cambridge Cambridge University Press, 1987), p. 18.
Michael J. Donoghue, “Homology,” in Keywords in Evolutionary Biology, ed. Evelyn Fox Keller and Elizabeth A. Lloyd (Cambridge, MA Harvard University Press, 1992), p. 170.
Hillis, “Homology in Molecular Biology,” p. 340.
Donoghue, “Homology,” p. 171.
Donoghue With respect to the second point, differences in form between two animals or species were interpreted to mean that change or transformation had occurred, rather than that the two were unrelated.
I cannot do justice to the many complex debates about homology in this short paper. For a more extensive and nuanced view of these complexities, see Brian K. Hall, ed., Homology: The Hierarchical Basis of Comparative Biology (New York Academic Press, 1944).
For biologists who criticize this view, see, example. V. Louise Roth, “Within and Between Organisms: Replicators, Lineages, and Homologues,” in Homology: The Hierarchical Basis of Comparative Biology, ed., Brian K. Hall (New York Academic Press, 1944), especially pp. 311–312; Ruth Hubbard, The Politics of Women’s Biology (New Brunswick: Rutgers University Press, 1990); R. Hubbard and E. Wald. Exploding the Gene Myth (Boston: Beacon Press, 1993); and Richard C. Lewontin, Biology as Ideology: The Doctrine of DNA (New York: Harper Collins, 1991). For historians of science who criticize this view, see example, Donna J. Haraway, Simians, Cyborgs and Women: The Reinvention of Nature (New York: Routledge, 1991); Lily Kay, “Constructing Histories of Twentieth-Century Experimental Life Science: The Promise and Perils of Archives,” The Mendel Newsletter: Archival Resources for the History of Genetics and Allied Sciences, 2, November 1992; Evelyn Fox Keller, Reflections on Gender and Science (New Haven: Yale University Press, 1985); and Evelyn Fox Keller, Secrets of Life, Secrets of Death: Essays on Language, Gender and Science (New York: Routledge, 1992).
George V. Lauder, “Homology, Form, and function,”in Homology:The Hierarchical Basis of Comparative Biology, ed. Brian K. Hall, (New York Academic Press, 1944), pp. 162–163.
Neil H. Shubin “History, Ontogeny, and Evolution of the Archetype,” in Homology: The Hierarchical Basis of Comparative Biology, ed. Brian K. Hall, (New York Academic Press, 1944), p. 252.
Roth, “Within and Between Organisms,” p. 307.
Roth quoted in Lauder, “Homology, Form, and function,” p. 163.
Lauder, “Homology, Form, and function,” p. 163.
Ibid., p. 163.
Donoghue, “Homology,” p. 173.
If a protein sequence is not available, biologists translate the DNA sequences into sequences of amino acids before beginning a homology search. Since there are only four possible nucleotide bases to permute in DNA and RNA sequences, the probabilities of random matches are very high (25% on the average). The 20 amino acids that constitute proteins reduce the probabilities of random matches. For a discussion of other difficulties of determining homologies using DNA sequences, see Russell F. Doolittle, “Similar Amino Acid Sequences: Chance or Common Ancestry?” Science, 214, October 9 1981, p. 153.
Dorit, Schoenbach, and Gilbert, “How Big Is the Universe of Exons?” pp. 1377–1382.
Donoghue, “Homology,” p. 173.
Gerald R. Reeck, Christoph de Haen, David C. Teller, Russell F. Doolittle, Walter M. Fitch, Richard E. Dickerson, Pierre Chambon, Andrew D. McLachlan, Emanuel Margoliash, Thomas H. Jukes, and Emile Zuckerandl, “Homology” in Proteins and Nucleic Acids: A Terminology Muddle and a Way Out of It,” (Letter to the Editor), Cell, 50, August 28, 1987, p.667 (emphasis added).
Von Heijne, Sequence Analysis in Molecular Biology, p. 137.
Doolittle, “Similar Amino Acid Sequences,” p. 153.
S. Karlin and C. Matessi, “Kin Selection and Altruism,” Proceedings of the Royal Society of London B, 219 (1983), pp. 327–353.
I do not mean to elevate “wet lab” work in molecular biology above any other. I present it instead as an alternative.
RNA tumor viruses are retroviruses, which have genes constituted of RNA sequences rather than DNA. They replicate by producing a strand of DNA sequences through the activities of an enzyme called reverse transcriptase. Retroviruses have come to be common knowledge through the HIV or human immunodefiency virus that is believed to cause AIDS.
D. Stehelin, H.E. Varmus, J.M. Bishop, and P.K. Vogt, “DNA Related to the Transforming Gene(s) of Avian Sarcoma Viruses Is Present in Normal Avian DNA.” Nature, 260 (1976), pp. 170–173.
D.H. Spector, H.E. Varmus, and J.M. Bishop, “Nucleotide Sequences Related to the Transforming Gene of Avian Sarcoma Virus Are Present in the DNA of Uninfected Vertebrates,” Proceedings of the National Academy of Sciences U.S.A., 75 (1978), pp. 5023–5027.
Bishop interview (emphasis added).
Bishop interview.
I use quotations around the term, “evolutionary success,” to indicate the complexity of this term. Evolutionary biology is embroiled in many debates about the units, levels, and processes of selection. For example, does natural selection operate at the level of the gene, the entire genome, the individual organism, the “group,” or the population? Does it operate on DNA sequences, genes, or the structural proteins? What is selection? Are all selection pressures identical in their impact? What about engineering? “Evolutionary success,” then, is a highly contextualized set of discussions and debates rather than an explanatory mechanism. See, for example, Elisabeth A. Lloyd, “Unit of Selection,” in Keywords in Evolutionary Biology, ed. Evelyn Fox Keller and Elisabeth A. Lloyd (Cambridge, MA Harvard University Press, 1992); Elisabeth A. Lloyd, The Structure and Confirmation of Evolutionary Theory (Westport: Greenwood Press, 1988); and Robert N. Brandon, Adaptation and Environment (Princeton, NJ: Princeton University Press, 1990) for an overview analysis of “the units of selection” debates.
R.F Doolittle, M.W. Hunkapiller, L.E. Hood, S.G. DeVare, K.C. Robbins, et al., “Simian Sacroma Virus onc Gene, v-sis, Is Derived from the Gene (or Genes) Encoding a Platelet-Derived Growth factor,” Science, 221 (1983), pp. 275–76. M.D. Waterfield, G.T. Scrace, N. Whittle, P. Stroobant, A. Johnson, A. Wasteson, B. Westermark, J. Huang, T.F. Deuel, “Platelet-Derived Growth Factor is Structurally Related to the Putative Transforming Protein p28sis of Simian Sarcoma Virus,” Nature, 304 (1983), pp 35-39.
J. Michael Bishop, “Cellular Oncogenes and Retroviruses,” Annual Review of Biochemistry, 52 (1983), pp. 347–348.
This reminds me of Donna Haraway’s argument that new and unexpected kinds of solidarities are being constructed in this age of the domination of informatics; see “A manifesto for Cyborgs: Science, Technology, and Socialist Feminism in the 1980s,” in Haraway, Simians, Cyborgs, and Women, pp. 149–181.
For a good overview, see Michael Lynch and Steve Woolgar, “Introduction: Sociological Orientations to Representational Practice in Science” in Representation in Scientific Practice, ed. Lynch and Woolgar (Cambridge: The MIT Press, 1990), pp. 1-18.
See Harry M. Collins, Changing Order: Replication and Induction in Scientific Practice (Beverly Hills, CA Sage, 1985 ); J. H. Fujimura, “Constructing Doable Problems in Cancer Research: Articulating Alignment,” Social Studies of Science, 17, May 1987, pp. 257-293; Karin Knorr-Cetina, The Manufacture of Knowledge (Oxford: Pergamon Press, 1981); Bruno Latour and Steve Woolgar, Laboratory Life: The Social Construction of Scientific Facts (Beverly Hills: Sage, 1986 [1979]); Michael Lynch,Art and Artefact in Laboratory Science (London: Routledge and Kegan Paul, 1985); Susan Leigh Star, “Simplification in Scientific Work: An Example from Neuroscience Research,” Social Studies of Science, 13 (1983), pp. 205-28; and L. Suchman, Plans and Situated Action: The Problem of Human-Machine Communication (Cambridge: Cambridge University Press, 1987
See Michael Lynch, “Representation Is Overrated,” Configurations, 2, Winter 1994, pp. 137–149; Michael Lynch, Scientific Practice and Ordinary Action: Ethnomethodology and Social Studies of Science (New York: Cambridge University Press, 1993); and Lynch and Woolgar, “Introduction: Sociological Orientations.”
Steve Woolgar, “Time and Documents in Researcher Interaction: Some Ways of Making Out What is Happening in Experimental Science,” in ed. Michael Lynch and Steve Woolgar, Representation in Scientific Practice (Cambridge, MA Th MIT Press, 1990). Note that Lynch criticizes Woolgar in this quote and collaborates with him in the publication of the volume on representation. The “methodological horrors“ issue is a point of tension in much SSK work and fuels collective discussions.
Lynch, Scientific Practice and Ordinary Action, p. 194.
Lynch and Woolgar, “Introduction: Sociological Orientations, p. 13.
Lucy A. Suchman, “Representing Practice in Cognitive Science,” in Representation in Scientific Practice, ed. Michael Lynch and Steve Woolgar, p. 318.
I use this definition of a string of letters signifying “a standard understanding of that molecule” as my example because, as Lynch himself argues, while “the problem of correlating ‘text’ and ‘context’ may have no empirical or methodological solution[,] this does not mean that whenever we talk we perform an unrecognizable activity, or that language is always and inherently ambiguous. Nor does it mean that we can ‘construct’ the world in which we live any way we like” (Lynch, “Representation Is Overrated,” p. 146). Instead, Lynch would believe that molecular biologists would generally agree that a string of G, A, T, C represent molecules of deoxyribonucleic acids, and that a string of A, L, T, N, etc., represent molecules called amino acids.
In another line of science studies writings, Collins has similarly argued that the reproduction of “the same” scientific activities is never replicative in the manner that scientific textbooks define replication. This does not mean that there is no similarity. Instead, Collins and his colleagues problematize the construction of similarity (Collins, Changing Order).
See footnote 42 above.
Biologist Richard Lewontin states this argument more baldly: First, DNA is not self-reproducing. Second, it makes nothing. And third, organisms are not determined by it. See “The Dream of the Human Genome” in Lewontin, Biology as Ideology.
See Donna J. Haraway, “Universal Donors in a Vampire Culture: It’s All in the Family. Biological Kinship Categories in the Twentieth-Century United States,” in Reinventing Nature, ed. William Cronon, (New York Norton, 1995); Bruno Latour, “Give Me a Laboratory and I Will Raise the World,” in Science Observed, ed. Karin Knorr-Cetina and Michael Mulkay (Beverly Hills: Sage, 1983); Bruno Latour, The Pasteurization of France (Cambridge: Harvard University Press, 1988), and Michel Callon, “Some Elements of a Sociology of Translation: Domestication of the Scallops and the Fishermen of St. Brieuc Bay” in Power, Action and Belief, Sociological Review Monograph, ed. John Law (Boston: Routledge and Kegan Paul, 1986).
Suchman, “Representing Practice in Cognitive Science,” p. 318. See also Suchman, “Do Categories Have Politics: The Language/Action Perspective Reconsidered,” Computer Supported Cooperative Work, 2 (1994), pp. 177-190.
One of the first institutes to develop research colonies for the study of mammalian genetics was the Jackson Laboratory in Bar Harbor, Maine, founded by Clarence C. Little in 1929. See also Joan H. Fujimura, “Tools of the Trade: A Brief History of Standardized Experimental Systems in Classical Genetic and Virological Cancer Research, ca. 1920-1978,” History and Philosophy of the Life Sciences, 18 (Sept 1996): pp. 3–54.
At the turn of the twentieth century, biology was transformed into an experimental and analytic science. Growing commitments across scientific and medical disciplines to the ideals of positivist empiricism translated into ideals of quantifiable and reproducible experimentation in biology. Although naturalist and ecological inquiries continued in a more taxonomic vein, many new fields of biology began to pursue analytic methods of inquiry. Experimentation and analysis became the hallmarks of “science.”
For work on the relationship between language and molecular genetics, see “The Biopolitics of Postmodern Bodies: Constitutions of Self in Immune Systems Discourse,” in Haraway, Simians, Cyborgs and Women; Keller, Secrets of Life, Secrets of Death.
Haraway, “Universal Donors.”
See chapter 8 of Joan H. Fujimura, Crafting Science and Transforming Biology: The Case of Oncogene Research (Cambridge Harvard University Press, 1996).
“Authority” is itself an historical and contingent outcome. I do not propose an ahistorical, theoretical explanation for the “best” tools for producing “factness.”
For a molecular biologist’s view of language in molecular genetics, see Robert Pollack, Signs of Life: The Language and Meanings of DNA (Boston Houghton Mifflin Company, 1994).
Evelyn Fox Keller, Refiguring Life.
Joan H. Fujimura and Danny Chou, “Dissent in Science: Styles of Scientific Practice and the Controversy Over the Cause of AIDS,” Social Science and Medicine, 38 April 1994, pp. 1017–1036.
According to Hacking, each style of reasoning is historically created. “Every style comes into being by little microsocial interactions and negotiations. It is a contingent matter.… Each style has become what we think of as a rather timeless canon of objectivity, a standard or model of what it is to be reasonable about this or that type of subject matter. We do not check to see whether mathematical proof or laboratory investigation or statistical’ studies’' are the right way to reason: they have become (after fierce struggles) what it is to reason rightly, to be reasonable in this or that domain.” Ian Hacking, “The Self-Vindication of the Laboratory Sciences,” in Science as Practice and Culture, ed. Andrew Pickering. (Chicago University of Chicago Press, 1992), p. 10 (emphasis added).
Donoghue, “Homology,” p. 178.
Ibid. p. 179.
This is just a little play on the human genome project’s production of a “consensus genome.”
Donna J. Haraway, “A Manifesto for Cyborgs,” p. 161.
Haraway, “The Biopolitics of Postmodern Bodies,” p. 212.
Michel Foucault, The History of Sexuality, 1 (New York Pantheon, 1978); Discipline and Punish (New York: Vintage Press, 1975); The Order of Things: An Archaeology of the Human Sciences, a translation of Les Mots et Les Choses (New York: Random House, 1970); and The Birth of the Clinic: An Archaeology of Medical Perception (New York: Vintage Books, 1975[1963]).
Foucault, History of Sexuality, p. 93.
Ibid., p. 102.
Haraway, “The Biopolitics of Postmodern Bodies,” p. 208.
Ibid., p. 214.
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Fujimura, J.H. (1999). The Practices of Producing Meaning in Bioinformatics. In: Fortun, M., Mendelsohn, E. (eds) The Practices of Human Genetics. Sociology of the Sciences, vol 21. Springer, Dordrecht. https://doi.org/10.1007/978-94-011-4718-7_3
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