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An RNA Phage Lab: MS2 in Walter Fiers’ Laboratory of Molecular Biology in Ghent, from Genetic Code to Gene and Genome, 1963–1976

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Abstract

The importance of viruses as model organisms is well-established in molecular biology and Max Delbrück’s phage group set standards in the DNA phage field. In this paper, I argue that RNA phages, discovered in the 1960s, were also instrumental in the making of molecular biology. As part of experimental systems, RNA phages stood for messenger RNA (mRNA), genes and genome. RNA was thought to mediate information transfers between DNA and proteins. Furthermore, RNA was more manageable at the bench than DNA due to the availability of specific RNases, enzymes used as chemical tools to analyse RNA. Finally, RNA phages provided scientists with a pure source of mRNA to investigate the genetic code, genes and even a genome sequence. This paper focuses on Walter Fiers’ laboratory at Ghent University (Belgium) and their work on the RNA phage MS2. When setting up his Laboratory of Molecular Biology, Fiers planned a comprehensive study of the virus with a strong emphasis on the issue of structure. In his lab, RNA sequencing, now a little-known technique, evolved gradually from a means to solve the genetic code, to a tool for completing the first genome sequence. Thus, I follow the research pathway of Fiers and his ‘RNA phage lab’ with their evolving experimental system from 1960 to the late 1970s. This study illuminates two decisive shifts in post-war biology: the emergence of molecular biology as a discipline in the 1960s in Europe and of genomics in the 1990s.

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References

  • Abir-Am, P.G. 1998. La mise en mémoire de la science. Pour une ethnographie historique des rites commémoratifs. Amsterdam: éditions des Archives contemporaines.

    Google Scholar 

  • Abir-Am, P.G. and Elliot, C.A. (eds.). 1999. “Commemorative Practices in Science: Historical Perspectives on the Politics of Collective Memory.” Osiris 14: 324–372.

  • Adams, J.M., Jeppesen, P.G.N., Sanger, F., and Barrell, B.G. 1969. “Nucleotide Sequences from Fragments of R17 Bacteriophage RNA.” Cold Spring Harbor Symposia on Quantitative Biology 34: 611–620.

    Google Scholar 

  • Anonymous. 1974. “FEBS Advanced Courses (Formerly Summer Schools).” FEBS Letters 40 supplement: S170–S171.

  • Arehart-Treichel, J. 1972. “Molecular Biology’s Flower Child.” Science News 103: 12–13.

    Article  Google Scholar 

  • Argetsinger Steitz, J. 1969. “Nucleotide Sequences of the Ribosomal Binding Sites of Bacteriophage R17 RNA.” Cold Spring Harbor Symposia on Quantitative Biology 34: 621–633.

    Google Scholar 

  • Billeter, M.A., Dahlberg, J.E., Goodman, H.M., Hindley, J., and Weissmann, C. 1969. “Nucleotide Sequence Analysis of an Enzymatically Synthesized RNA Corresponding to the 5′-Terminal Region of Qβ RNA.” Cold Spring Harbor Symposia on Quantitative Biology 34: 635–646.

    Google Scholar 

  • Bostanci, A. 2004. “Sequencing Human Genomes.” J.P. Gaudillière and H.J. Rheinberger (eds.), From Molecular Genetics to Genomics: The Mapping Cultures of Twentieth Century Genetics. London: Routledge.

    Google Scholar 

  • Brownlee, G.G., Sanger, F., and Barrell, B.G. 1968. “The Sequence of 5S Ribosomal Ribonucleic Acid.” Journal of Molecular Biology 34: 379–412.

    Article  Google Scholar 

  • Burian, R.M. 1997. “Exploratory Experimentation and the Role of Histochemical Techniques in the Work of Jean Brachet, 1938–1952.” History and Philosophy of the Life Sciences 19: 27–45.

    Google Scholar 

  • Cairns, J., Stent, G.S., and Watson, J.D. (eds.). 2007. Phage and the Origins of Molecular Biology: The Centennial Edition. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory Press.

    Google Scholar 

  • Chantrenne, H., Linderstrøm-Lang, K., and Vandendriessche, L. 1947. “Volume Change Accompanying the Splitting of Ribonucleic Acid by Ribonuclease.” Nature 159: 877–878.

    Article  Google Scholar 

  • Chiang, H.H. 2009. “The Laboratory Technology of Discrete Molecular Separation: The Historical Development of Gel Electrophoresis and the Material Epistemology of Biomolecular Science, 1945–1970.” Journal of the History of Biology 42: 495–527.

    Article  Google Scholar 

  • Creager, A.N.H. 2002. The Life of a Virus: Tobacco Mosaic Virus as an Experimental Model, 1930–1965. Chicago: Chicago University Press.

    Google Scholar 

  • Creager, A.N.H. 2007. “Christian B. Anfinsen.” N. Koertge (ed.), New Dictionary of Scientific Biography. New York: Charles Scribner’s Sons.

    Google Scholar 

  • Creager, A.N.H. 2009. “Phosphorus-32 in the Phage Group: Radioisotopes as Historical Tracers of Molecular Biology.” Studies in History and Philosophy of Biological and Biomedical Sciences 40C: 29–42.

    Article  Google Scholar 

  • Creager, A.N.H. 2010. “The Paradox of the Phage Group: Essay Review.” Journal of the History of Biology 43: 183–193.

    Article  Google Scholar 

  • Creager, A.N.H and Morgan, G.J. 2008. “After the Double Helix. Rosalind Franklin’s Research on Tobacco Mosaic Virus.” Isis 99: 239–272.

    Article  Google Scholar 

  • Davis, J.E., Strauss Jr., J.H., and Sinsheimer, R.L. 1961. “Bacteriophage MS2: Another RNA Phage.” Science 134: 1427.

  • de Chadarevian, S. 2002. Design for Life: Molecular Biology After WWII. Cambridge: Cambridge University Press.

    Google Scholar 

  • de Chadarevian, S. and Strasser, B.J. 2002. “Introduction. Molecular Biology in Postwar Europe: Towards a ‘Glocal’ Picture.” Studies in History and Philosophy of Biological and Biomedical Sciences 33C: 361–365.

    Article  Google Scholar 

  • De Wachter, R. and Fiers, W. 1967. “Studies on the Bacteriophage MS2. IV. The 3′-OH Terminal Undecanucleotide Sequence of the Viral RNA Chain.” Journal of Molecular Biology 30: 507–527.

    Article  Google Scholar 

  • De Wachter, R. and Fiers, W. 1972. “Preparative Two-Dimensional Polyacrylamide Gel Electrophoresis of 32P-Labeled RNA.” Analytical Biochemistry 49: 184–197.

    Article  Google Scholar 

  • Derynck, R., Remaut, E., Saman, E., Stanssens, P., De Clercq, E., Content, J. and Fiers, W. 1980. “Expression of Human Fibroblast Interferon Gene in Escherichia coli.” Nature 287: 193–197.

    Article  Google Scholar 

  • Fiers, W. 1964. “The Primary Structure of Nucleic Acids.” Revue des Fermentations et des Industries Alimentaires 19: 36–51.

    Google Scholar 

  • Fiers, W. 1989. Curriculum Vitae. InBev-Baillet Latour Fund. www.inbevbailletlatour.com/media/misc_media/CV_Walter_Fiers.pdf. Accessed 13 April 2010.

  • Fiers, W. 1995. “Pioneering Work.” Science 269: 1805.

    Article  Google Scholar 

  • Fiers, W. 2007. Interview with Jérôme Pierrel. Ghent: VIB/Ghent University.

    Google Scholar 

  • Fiers, W., Contreras, R., Duerinck, F., Haegeman, G., Iserentant, D., Merregaert, J., Min Jou, W., Molemans, F., Raeymaekers, A., Van den Berghe, A., Volckaert, G., and Ysebaert, M. 1976. “Complete Nucleotide Sequence of Bacteriophage MS2 RNA: Primary and Secondary Structure of the Replicase Gene.” Nature 260: 500–507.

    Article  Google Scholar 

  • Fiers, W., Contreras, R., Haegeman, G., Rogiers, R., Van de Voorde, A., Van Heuverswyn, H., Van Herreweghe, J., Volckaert, G., and Ysebaert, M. 1978. “Complete Nucleotide Sequence of SV40 DNA.” Nature 273: 113–120.

    Article  Google Scholar 

  • Fiers, W., Lepoutre, L., and Vandendriessche, L. 1965. “Studies on the Bacteriophage MS2. I. Distribution of Purine Sequences in the Viral RNA and in Yeast RNA.” Journal of Molecular Biology 13: 432–450.

    Article  Google Scholar 

  • Fiers, W. and Sinsheimer, R.L. 1962a. “The Structure of the DNA of Bacteriophage Phi-X174. I. The Action of Exopolynucleotidases.” Journal of Molecular Biology 5: 408–419.

    Article  Google Scholar 

  • Fiers, W. and Sinsheimer, R.L. 1962b. “The Structure of the DNA of Bacteriophage Phi-X174. III. Ultracentrifugal Evidence for a Ring Structure.” Journal of Molecular Biology 5: 424–434.

    Article  Google Scholar 

  • Finch, J. 2008. A Nobel Fellow on Every Floor: A History of LMB. Cambridge: Medical Research Council Laboratory of Molecular Biology.

    Google Scholar 

  • Fox Keller, E. 2000. The Century of the Gene. Cambridge: Harvard University Press.

    Google Scholar 

  • Garcia-Sancho, M. 2008. Sequencing as a Way of Work: A History of Its Emergence and Mechanisation – From Proteins to DNA, 1945–2000. PhD Thesis, Centre for the History of Science, Imperial College, London.

  • Garcia-Sancho, M. 2010. “A New Insight into Sanger’s Development of Sequencing: From Proteins to DNA, 1943–1977.” Journal of the History of Biology 43: 265–323.

    Article  Google Scholar 

  • Gaudillière, J.-P. 1996. “Molecular Biologists, Biochemists, and Messenger RNA: The Birth of a Scientific Network.” Journal of the History of Biology 29: 417–445.

    Article  Google Scholar 

  • Gaudillière, J.-P. 2002a. Inventer la Biomédecine: la France, l’Amérique et la production des savoirs du vivant (1945–1965). Paris: La Découverte.

    Google Scholar 

  • Gaudillière, J.-P. 2002b. “Paris–New York Roundtrip: Transatlantic Crossings and the Reconstruction of the Biological Sciences in Post-War France.” Studies in History and Philosophy of Biological and Biomedical Sciences 33C: 389–417.

    Article  Google Scholar 

  • Gingras, Y. 2010. “Revisiting the “Quiet Debut” of the Double Helix: A Bibliometric and Methodological Note on the “Impact” of Scientific Publications.” Journal of the History of Biology 43: 159–181.

    Article  Google Scholar 

  • Holley, R.W., Apgar, J., Everett, G.A., Madison, J.T., Marquisee, M., Merrill, S.H., Penswick, J.R., and Zamir, A. 1965. “Structure of a Ribonucleic Acid.” Science 147: 1462–1465.

    Article  Google Scholar 

  • Kay, L. 2000. Who Wrote the Book of Life? A History of the Genetic Code. Stanford: Stanford University Press.

    Google Scholar 

  • Kendrew, J.C. 1967. “How Molecular Biology Started.” Scientific American 216: 141–144.

    Google Scholar 

  • Khorana, H.G. 1968. “Nucleic Acid Synthesis in the Study of the Genetic Code.” Nobel Lecture. http://nobelprize.org/nobel_prizes/medicine/laureates/1968/khorana-lecture.html.

  • Kohler, R.E. 1994. Lords of the Fly: Drosophila Genetics and the Experimental Life. Chicago: University of Chicago Press.

    Google Scholar 

  • Lai, M.M.C. 1992. “RNA Recombination in Animal and Plant Viruses.” Microbiological Reviews 56: 61–79.

    Google Scholar 

  • Lewis, J. 2004. “From Virus Research to Molecular Biology: Tobacco Mosaic Virus in Germany, 1936–1956.” Journal of the History of Biology 37: 259–301.

    Article  Google Scholar 

  • Loeb, T. and Zinder N. 1961. “A Bacteriophage Containing RNA.” Proceedings of the National Academy of Sciences of the United States of America 47: 282–289.

  • McElheny, V.K. 2010. Drawing the Map of Life: Inside the Human Genome Project. New York, NY: Basic Books.

    Google Scholar 

  • Min Jou, W., Haegeman, G., and Fiers, W. 1971. “Studies on the Bacteriophage MS2. Nucleotide Fragments from the Coat Protein Cistron.” FEBS Letters 13: 105–109.

    Article  Google Scholar 

  • Min Jou, W., Haegeman, G., Ysebaert, M., and Fiers, W. 1972. “Nucleotide Sequence of the Gene Coding for the Bacteriophage MS2 Coat Protein.” Nature 237: 82–88.

    Article  Google Scholar 

  • Morange, M. (ed.). 1991. L’Institut Pasteur: contribution à son histoire. Paris: La Découverte.

    Google Scholar 

  • Morange, M. 2000. A History of Molecular Biology. Cambridge: Harvard University Press.

    Google Scholar 

  • Morange, M. 2007. “Robert William Holley.” N. Koertge (ed.), New Dictionary of Scientific Biography, Vol. 3. New York: Charles Scribner’s Sons.

  • Mullins, N.C. 1972. “The Development of a Scientific Specialty: The Phage Group and the Origins of Molecular Biology.” Minerva 10: 51–82.

    Article  Google Scholar 

  • Pierrel, J. 2009. La pratique du séquençage ARN à Cambridge, Strasbourg et Gand, 1960–1980. PhD Thesis, Institut de Recherches Interdisciplinaires sur les Sciences et la Technologie, Strasbourg University.

  • Rheinberger, H.-J. 1997. Toward a History of Epistemic Things: Synthesizing Proteins in the Test Tube. Stanford: Stanford University Press.

    Google Scholar 

  • Sanger, F. 1971. “Nucleotide Sequences in Bacteriophage Ribonucleic Acid.” Biochemical Journal 124: 833–843.

    Google Scholar 

  • Sanger, F. 1988. “Sequences, Sequences, and Sequences.” Annual Review of Biochemistry 57: 1–28.

    Article  Google Scholar 

  • Sanger, F., Brownlee, G.G., and Barrell, B.G. 1965. “A Two-Dimensional Fractionation Procedure for Radioactive Nucleotides.” Journal of Molecular Biology 13: 373–398.

    Article  Google Scholar 

  • Sanger, F. and Dowding, M. (eds.). 1996. Selected Papers of Frederick Sanger (with Commentaries). London: World Scientific.

    Google Scholar 

  • Santesmases, M.J. 2006. “Peace Propaganda and Biomedical Experimentation: Influential Uses of Radioisotopes in Endocrinology and Molecular Genetics in Spain (1947–1971).” Journal of the History of Biology 39: 765–794.

    Article  Google Scholar 

  • Sinsheimer, R.L. 1994. The Strands of a Life: The Science of DNA and the Art of Education. Berkeley: University of California Press.

    Google Scholar 

  • Strasser, B.J. 2002. “Institutionalizing Molecular Biology in Post-War Europe: A Comparative Study.” Studies in History and Philosophy of Biological and Biomedical Sciences 33C: 533–564.

    Google Scholar 

  • Strasser, B.J. 2006a. La fabrique d’une nouvelle science : La biologie moléculaire à l’âge atomique, 1945–1964. Florence: Olschki.

    Google Scholar 

  • Strasser, B.J. 2006b. “Collecting and Experimenting: The Moral Economies of Biological Research, 1960s–1980s.” Preprints of the Max-Planck Institute for the History of Science 310: 105–123.

    Google Scholar 

  • Summers, W.C. 1999. Felix d’Herelle and the Origins of Molecular Biology. New Haven: Yale University Press.

    Google Scholar 

  • Thieffry, D. 1997. “Contributions of the ‘Rouge-Cloître Group’ to the Notion of ‘Messenger RNA’.” History and Philosophy of the Life Sciences 19: 89–111.

    Google Scholar 

  • Van de Voorde, A. 2007. Interview with Jérôme Pierrel. Ghent: Innogenetics.

    Google Scholar 

  • Van Montagu, M. 1968. “Studies with Amber and UGA Mutants of the RNA Phage MS-2.” Archives Internationales de Physiologie et de Biochimie 76: 393–394.

    Google Scholar 

  • Van Montagu, M. 2000. “The Early Years.” The Plant Journal 23: 1–2.

    Article  Google Scholar 

  • Weissmann, C., Simon, L., and Ochoa, S. 1963. “Induction by an RNA Phage of an Enzyme Catalyzing Incorporation of Ribonucleotides into Ribonucleic acid.” Proceedings of the National Academy of Sciences of the United States of America 49: 407–414.

  • Yi, D. 2008. “Cancer, Viruses, and Mass Migration: Paul Berg’s Venture into Eukaryotic Biology and the Advent of Recombinant DNA Research and Technology, 1967–1980.” Journal of the History of Biology 41: 589–636.

    Article  Google Scholar 

  • Zinder, N.D. 1988. “RNA Phage.” F. Fenner and A. Gibbs (eds.), Portraits of Viruses: A History of Virology. Basel: S. Karger AG.

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  1. Laboratoire Épistémê (EA 2971), Bordeaux University, 40 rue Lamartine, 33405, Talence, France

    Jérôme Pierrel

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  1. Jérôme Pierrel
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Correspondence to Jérôme Pierrel.

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This research was conducted as part of my PhD at IRIST (EA3424), LESVS team, Strasbourg University, France. See Pierrel, 2009.

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Pierrel, J. An RNA Phage Lab: MS2 in Walter Fiers’ Laboratory of Molecular Biology in Ghent, from Genetic Code to Gene and Genome, 1963–1976. J Hist Biol 45, 109–138 (2012). https://doi.org/10.1007/s10739-010-9267-z

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