Hostname: page-component-cd9895bd7-jkksz Total loading time: 0 Render date: 2024-12-25T06:22:14.390Z Has data issue: false hasContentIssue false
  • English
  • Français

Interactions Among Theory, Experiment, and Technology in Molecular Biology

Published online by Cambridge University Press:  28 February 2022

Kenneth F. Schaffner
Kenneth F. Schaffner*
Affiliation:
George Washington University
Get access Rights & Permissions [Opens in a new window]

Extract

In this paper, I revisit a problem in immunology and molecular genetics that I had first tried to understand some philosophical implications of over twenty years ago. At that time, some immunologists such as Mel Cohn at the Salk Institute, referred to it as the GOD problem, which was the acronym for Generator Of Diversity (also see Cohn's more recent discussion in his 1994, 41-48). In the early 1970s there were three or four different theories that had been proposed to account for the way in which antibody diversity is generated and considerable argument among the proponents of the different approaches to the problem (see Cohn, 1994). In 1971-72 I attempted to assess the strengths and weaknesses of the competing theories of antibody diversity from the perspective of a “logic of comparative theory evaluation” that had seemed to work reasonably well in physics (Schaffner, 1970), and I drafted an essay that ultimately sided with one of those theories (somatic mutation).

Type
Part VI. Search Heuristics, Experimentation, and Technology in Molecular and Cell Biology
Information
PSA: Proceedings of the Biennial Meeting of the Philosophy of Science Association , Volume 1994 , Issue 2: Volume Two: Symposia and Invited Papers 1994 , 1994 , pp. 192 - 205
Copyright
Copyright © 1995 by the Philosophy of Science Association

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

Footnotes

1

I would like to express my gratitude to Drs. Philip Leder and Susumu Tonegawa for providing copies of their reprints. Partially supported by the National Science Foundation's Studies in Science, Technology, and Society Program. This paper is a short version of a much more detailed chapter in an in-progress book on theory structure and research strategies in molecular biology. Due to stringent space considerations, historical references have had to be kept to an absolute minimum, but a full bibliography is available from the author on request.

References

Alberts, B. et al. (1994), Molecular Biology of the Cell. 3rd edit. New York: Garland.Google Scholar
Bechtel, W. and Richardson, R. (1993), Discovering Complexity: Decomposition and Localization as Strategies in Scientific Research. Princeton: Princeton University Press.Google Scholar
Brack, C. and Tonegawa, S. (1976), “Variable and Constant Parts of the Immunoglobulin Light Chain Gene of a Mouse Myeloma are 1250 Nontranslated Bases Apart,” Proceedings of the National Academy of Sciences USA, 73: 5652–5656.Google Scholar
Brenner, S. and Milstein, C. (1966), “Origin of Antibody Variation”, Nature 211: 242–243.CrossRefGoogle ScholarPubMed
Burnet, F.M. (1957), “A Modification of Jerne's Theory of Antibody Production Using the Concept of Clonal Selection”, The Australian Journal of Science 20: 67–69.Google Scholar
Burnet, F.M. (1959), The Clonal Selection Theory of Acquired Immunity. Nashville: Vanderbilt University Press.10.5962/bhl.title.8281CrossRefGoogle Scholar
Burnet, F.M. (1968), Changing Patterns. Melbourne: William Heinemann.Google Scholar
Cohn, M. (1970), “Selection under a Somatic Model”, Cellular Immunology 1: 461–467.CrossRefGoogle Scholar
Cohn, M. (1994), “The Wisdom of Hindsight”, Annual Review of Immunology 12: 1–62.CrossRefGoogle ScholarPubMed
Culp, S. (1994) “Defending Robustness: the Bacterial Mesosome as a Test Case,” in Hull, D., Forbes, M., and Burian, R. M. PSA 1994 vol 1. East Lansing: Philosophy of Science Association. Pp. 46–57.Google Scholar
Culp, S. and Kitcher, P. (1989), “Theory Structure and Theory Change in Contemporary Molecular Biology,” British Journal for the Philosophy of Science 40: 459–483.10.1093/bjps/40.4.459CrossRefGoogle Scholar
Darden, L. (1991), Theory Change:in Science: Strategies from Mendelian Genetics. New York: Oxford University Press.Google Scholar
Dreyer, W.J. and Bennett, J.C. (1965), “The Molecular Basis of Antibody Formation: A Paradox”, Proceedings of the National Academy of Sciences USA 54: 864–869.10.1073/pnas.54.3.864CrossRefGoogle ScholarPubMed
Duhem, P. (1914), Aim and Structure of Physical Theory. 2d ed. Translated by Wiener, P. P.. New York: Atheneum Publishers.Google Scholar
Edelman, G.M. and Gaily, J.A. (1967), “Somatic Recombination of Duplicated Genes: An Hypothesis on the Origin of Antibody Diversity”, Proceedings of the National Academy of Sciences USA 57: 353–358.CrossRefGoogle ScholarPubMed
Galison, P. (1987), How Experiments End. Chicago: University of Chicago Press.Google Scholar
Gally, J.A. and Edelman, G.M. (1970), “Somatic Translocation of Antibody Genes”, Nature 227: 341.10.1038/227341a0CrossRefGoogle ScholarPubMed
Honjo, T.; Packman, S.; Swan, D.; Nau, M.; and Leder, P. (1974), “Organization of Immunoglobulin Genes: Reiteration Frequency of Mouse k Chain Constant Region”, Proceedings of the National Academy of Sciences USA 71: 3659–3663.10.1073/pnas.71.9.3659CrossRefGoogle Scholar
Hood, L. and Talmage, D. (1970), “Mechanisms of Antibody Diversity: Germ Line Basis for Variability”, Science 168: 325–334.10.1126/science.168.3929.325CrossRefGoogle Scholar
Hozumi, N. and Tonegawa, S. (1976), “Evidence for Somatic Rearrangement of Immunoglobulin Genes Coding for Variable and Constant Regions,” Proceedings of the National Academy of Sciences USA 73: 3628–3632.CrossRefGoogle Scholar
Hunter, L. (ed.) (1993), Artificial Intelligence and Molecular Biology. Menlo Park, CA and Cambridge, MA: AAAI and MIT Press.Google Scholar
Jerne, N.K. (1955), “The Natural-Selection Theory of Antibody Formation”, Proceedings of the National Academy of Sciences USA 41: 849–857.10.1073/pnas.41.11.849CrossRefGoogle ScholarPubMed
Jerne, N.K. (1971), “The Somatic Generation of Immune Recognition”, European Journal of Immunology 1: 1–9.10.1002/eji.1830010102CrossRefGoogle ScholarPubMed
Kindt, T.J. and Capra, J. D. (1984), The Antibody Enigma. New York: Plenum Press.10.1007/978-1-4684-4676-0CrossRefGoogle Scholar
Kitcher, P. (1989), “Explanatory Unification and the Causal Structure of the World,” in Kitcher, P. and Salmon, W. (eds.) Scientific Explanation. Minneapolis: University of Minnesota Press, pp. 410–505.Google Scholar
Knorr-Cetina, K. (1981), The Manufacture of Knowledge. Oxford: Pergamon Press.Google Scholar
Landsteiner, K. (1945 [1933]), The Specificity of Serological Reactions. Rev. ed. Cambridge: Harvard University Press.Google Scholar
Latour, B. (1987), Science in Action. Cambridge: Harvard University Press.Google Scholar
Latour, B. and Woolgar, S. (1979/1986), Laboratory Life: The Construction of Scientific Facts. Princeton: Princeton University Press (2nd edit. publ. 1986).Google Scholar
Leder, P.; Honjo, T.; Packman, S.; and Swan, D. (1974), “The Organization and Diversity of Immunoglobulin Genes”, Proceedings of the National Academy of Sciences USA 71: 5109–5115.10.1073/pnas.71.12.5109CrossRefGoogle ScholarPubMed
Leder, P. (1982), “The Genetics of Antibody Diversity”, Scientific American 246: 102–115. (Page references are to the reprint.)CrossRefGoogle ScholarPubMed
Leder, P. (1994), “The Genetic Basis of Antibody Diversity,” in Leder, P., Clayton, D., and Rubenstein, E. (eds.) Scientific American Introduction to Molecular Medicine. New York: Scientific American, Inc., pp. 83–102.Google Scholar
Lederberg, J. (1959), “Genes and Antibodies”, Science 129: 1649–1653.CrossRefGoogle ScholarPubMed
Mazumdar, P.M. (1994), Species and Specificity. New York: Cambridge University Press.Google Scholar
Nagel, E. (1961), The Structure of Science. New York: Harcourt, Brace & Co.10.1119/1.1937571CrossRefGoogle Scholar
Paul, W.E. (ed.) (1993), Fundamental Immunology. 3rd edit. New York: Raven Press.Google Scholar
Rheinberger, H-J. (1992), “Experiment, Difference and Writing: I.: Tracing Protein Synthesis; II.: The Laboratory Production of Transfer RNA,” Studies in History and Philosophy of Science, 23: 305–333 and 389-422.CrossRefGoogle Scholar
Schaffner, K.F. (1970), “Outlines of a Logic of Comparative Theory Evaluation with Special Attention to Pre-and Post-Relativistic Electrodynamics”, in Stuewer, R., (ed.) Historical and Philosophical Perspectives of Science. Minnesota Studies in the Philosophy of Science, vol. 5. Minneapolis: University of Minnesota Press, pp. 311–364.Google Scholar
Schaffner, K.F. (1992), “Theory Change in Immunology: The Clonal Selection Theory -- Part I: Theory Change and Scientific Progress; Part II: The Clonal Selection Theory” Theoretical Medicine, 13, No. 2 (June): 191–216.10.1007/BF02163628CrossRefGoogle Scholar
Schaffner, K.F. (1993), Discovery and Explanation in Biology and Medicine. Chicago: University of Chicago Press.Google Scholar
Shapere, D. (1982), “The Concept of Observation in Science and Philosophy,” Philosophy of Science 49: 485–525.CrossRefGoogle Scholar
Silverstein, A.M. (1989), A History of Immunology. San Diego: Academic Press.Google Scholar
Smith, G.P. (1977), The Signficance of Hybridization Kinetic Experiments for Theories of Antibody Diversity”, Cold Spring Harbor Symposia on Quantitative Biology 41: 863–875.10.1101/SQB.1977.041.01.096CrossRefGoogle Scholar
Smithies, O. (1963), “Gamma-Globulin Variability: A Genetic Hypothesis”, Nature 199: 1231–1236.10.1038/1991231a0CrossRefGoogle ScholarPubMed
Talmage, D.W. (1957), “Allergy and Immunology”, Annual Review of Medicine 8: 239–256.10.1146/annurev.me.08.020157.001323CrossRefGoogle ScholarPubMed
Talmage, D.W. (1972), “Immunological Factors”, Report in Nature 236: 203–204.Google Scholar
Tauber, A.I. (1994), The Immune Self: Theory or Metaphor? Cambridge, UK: Cambridge University Press.10.1017/CBO9780511624957CrossRefGoogle ScholarPubMed
Tonegawa, S.; Steinberg, C; Dube, S.; and Bernardini, A. (1974), “Evidence for Somatic Generation of Antibody Diversity”, Proceedings of the National Academy of Sciences USA 71: 4027–4031.10.1073/pnas.71.10.4027CrossRefGoogle ScholarPubMed
Tonegawa, S.; Hozumi, N.; Matthyssens, G.; and Schuller, R. (1976), “Somatic Changes in the Content and Context of Immunoglobulin Genes”, Cold Spring Harbor Symposia on Quantitative Biology 41: 877–889.CrossRefGoogle Scholar
Tonegawa, S.; Brack, C. Hozumi, N. and Schuller, R. (1977), “Cloning of an Immunoglobulin Variable Region Gene from Mouse Embryo,” Proceedings of the National Academy of Sciences USA 74: 3518–3522.10.1073/pnas.74.8.3518CrossRefGoogle Scholar
Tonegawa, S.; Maxam, A.M.; Tizard, R.; Bernard, O.; and Gilbert, W. (1978), “Sequence of a Mouse Germ-Line Gene for a Variable Region of an Immunoglobulin Light Chain”, Proceedings of the National Academy of Sciences USA 75: 1485–1489.10.1073/pnas.75.3.1485CrossRefGoogle ScholarPubMed
Weigert, M., Cesari, I, Yonkovich, S. and Cohn, M. (1970), “Variability in the Lambda Light Chain Sequences of Mouse Antibody.” Nature 228: 1045–1047.10.1038/2281045a0CrossRefGoogle ScholarPubMed