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Abstract
Recombinant DNA technology was invented in 1973. Within a few years, molecular biologists began developing practical applications and establishing private companies to exploit them commercially. In 1978, Harvard biologist Walter Gilbert, one of the leading figures in the field, joined the founding scientific advisory board of a Swiss biotech startup called Biogen. He later became the company’s CEO. His participation helped Biogen recruit top scientific talent in the United States and Europe and encouraged many of his professional colleagues to follow his example and go into business. In this way, Gilbert became a linchpin in the formation of the contemporary biotechnology industry. Because his adventures in business were shaped by circumstances unique to the late twentieth century, Gilbert’s case adds a distinctive point of reference to studies of academic entrepreneurship. It also points to internal contradictions and conceptual ambiguities in neo-institutional accounts of research privatization.
Notes
1. Sharp, “Oral History,” Life Sciences Foundation, 2.
2. Hughes, Genentech, 2011.
3. Adams, “Oral History,” Life Sciences Foundation, 11.
4. The Stanford University Office of Technology Licensing filed a patent application on the process with the US Patent and Trademark Office on November 4, 1974. The patent was granted on 2 December 1980. See Riemers, “Tiger by the Tail”; and Hughes, “Making Dollars Out of DNA.”
5. Weissmann, “The Cloning of Interferon,” 103.
6. Mach, “Oral History,” 8.
7. Murray, “Oral History,” 3.
8. Hofschneider, “Oral History,” 2.
9. Swanson, “Co-founder, CEO, and Chairman of Genentech,” 13.
10. Hughes, Genentech, chap. 3.
11. This account relies heavily on oral histories recorded by the authors for the Life Sciences Foundation and a series of oral histories conducted by Biogen Inc. for an internal company history project in 2000. The Chemical Heritage Foundation now holds both collections. For discussion of historiographic issues related to the use of interviews in contemporary history of science and technology, see de Chadarevian, “Using Interviews”; and Hoddeson, “The Conflicts of Memories and Documents.”
12. Beer, “Aspects of Professionalization”; Ben-David, “The Universities and the Growth of Science”; and Harwood, “Universities.”
13. On the commercialization of life science research in the nineteenth century, see Geison, The Private Science of Louis Pasteur; Gradmann, “Money and Microbes”; Liebenau, Medical Science and Medical Industry; Linton, Emil von Behring; and MacLeod, “Reluctant Entrepreneurs.” For an historical overview of applied microbiology, see Demain, “History of Industrial Biotechnology.”
14. For accounts of early twentieth century engagements of academic life scientists with government agencies and private sector entities in a variety of fields, see Bud, The Uses of Life; Gaudillière, “Professional or Industrial Order?”; Kimmelman, “The American Breeders Association”; Palladino, “Between Craft and Science”; Porter, The History of Public Health; Starr, The Social Transformation of American Medicine; and Swann, Academic Scientists and the Pharmaceutical Industry.
15. See Shapin, The Scientific Life, 97, 98, on the difficulties of contrasting ‘basic’ and ‘applied’ science. The distinction does not map neatly onto the institutional divide between the academy and the private sector. Shapin points out that ‘basic’ or ‘fundamental’ research has always been conducted in corporate laboratories in addition to and often as a necessary prerequisite for technology or product development. Similarly, inquiries into fundamental laws or mechanisms in academic settings often require technology development in order to advance – the process of technology development often yields insights into the basic workings of the natural world. This was certainly the case with the invention and refinement of recombinant DNA technology.
16. Kohler, Lords of the Fly, chap. 7.
17. The history molecular biology is well documented. See for example, de Chadarevian, Designs for Life; Judson, The Eighth Day; Morange; A History of Molecular Biology; and Olby, The Path to the Double Helix.
18. The persistence of these epistemological tensions surfaced in the context of biological theorizing in the writings of Erwin Schrödinger and Max Delbrück. See Schrödinger, What is Life?; cf. Delbrück, “A Physicist’s Renewed Look at Biology,” 1315. As Delbruck saw it, the regulation of the genome ‘is a highly complex affair, susceptible to perturbations in its details.’
19. See Kay, The Molecular Vision of Life, 39–57.
20. Powell et al., “Disciplinary Baptisms,” 11–13.
21. Kohler, Partners in Science, chap. 12, 13; and Abir-Am, ‘The Rockefeller Foundation.’
22. Delbrück, ‘A Physicist’s Renewed Look at Biology,’ 1312.
23. Henry Etzkowitz has suggested that contemporary academic science is distinctly entrepreneurial in form and character, especially in America. He maintains that principal investigators in competition for grants from governments, corporations, and private foundations run their university laboratories like small businesses. See Etzkowitz, ‘Research Groups as “Quasi-Firms.”’ See also, Abir-Am, ‘The Politics of Macromolecules.’
24. de Chadarevian, Designs for Life; and Strasser, “Institutionalizing Molecular Biology.”
25. Bush, Science: The Endless Frontier.
26. Allen, ‘Early Years of NIH Research Grants,’ 6.
27. Ginzberg and Dutka, The Financing of Biomedical Research, 12, 37–9.
28. Appel, Shaping Biology.
29. Bloom and Randolph, Funding Health Sciences Research, 218, 219. On the origins of recombinant DNA technology, see Boyer, “Recombinant DNA Research at UCSF”; Cohen, “Science, Biotechnology, and Recombinant DNA”; Jones, “The Invention of Recombinant DNA Technology”; and Yi, The Recombinant University.
30. On postwar funding and institutional support for molecular biology in the United States and Europe, see Abir-Am, “Molecular Biology”; de Chadarevian, Designs for Life; Strasser, “Institutionalizing Molecular Biology”; and Quirke and Gaudillière, “The Era of Biomedicine.”
31. Cohen, “Science, Biotechnology and Recombinant DNA,” 150–65; and Boyer, “Recombinant DNA Research at UCSF,” 115–119.
32. Reimers, “Tiger by the Tail,” 464, 465.
33. Nicolas Rasmussen has presented the case of Caltech biochemist James Bonner’s work on plant hormones in the 1930s to highlight continuities in academic-industry relations in American biology. See Rasmussen, “The Forgotten Promise of Thiamin.” He argued further that Bonner’s contract research ‘prefigured’ the emergence of the biotech industry forty years later, and shared certain distinctive features with it, including ‘… the intoxicating hype and the domination of basic research agendas by potential massive profit.’ We appreciate Rasmussen’s superb account of Bonner’s project and agree that academic biochemists and plant physiologists remained continuously in touch with industrial partners through the twentieth century, but we believe that the rise of molecular biology in the late 1930s was driven by the application of technical advances in physical chemistry to problems in microbial genetics and that this represented a radical discontinuity in terms of commercial engagement in the life sciences. We also believe that in character, scope, and scale, the phenomenon of biotech entrepreneurship in the 1970s and 1980s represented a clear departure from anything that came before.
34. One notable exception emerged from experimental work that Stanford biochemist and future Nobel laureate George Beadle performed with mutant strains of Neurospora, a mold, in the 1940s. Beadle developed a bioassay that proved useful in testing the content of vitamin and amino acid formulations. Research on the assay attracted funding from food and drug companies. See Kay, The Molecular Vision of Life, 199–210.
35. Sharp, “Oral History,” Life Sciences Foundation, 2.
36. Sharp, “Oral History,” Biogen, Inc., 2.
37. Walter Gilbert, ‘Interview,’ Nobel Prize.org, accessed 26 April 2017. http://www.nobelprize.org/mediaplayer/index.php?id=1482.
38. Gilbert, “Oral History,” Life Sciences Foundation, 13.
39. Gros et al. ‘Unstable Ribonucleic Acid Revealed.’
40. Quoted in Hall, Invisible Frontiers, 29.
41. See Judson, The Eighth Day, 585–8.
42. Maxam and Gilbert. “A New Method for DNA Sequencing.”
43. Hall, Invisible Frontiers, chap. 10.
44. Rasmussen, Gene Jockeys, chap. 2.
45. Sharp, “Oral History,” Life Sciences Foundation, 11.
46. Gilbert, “Oral History,” Life Sciences Foundation, 15.
47. Sharp, “Oral History,” Biogen, Inc., 4.
48. Gilbert, “Protein Synthesis.”
49. Sharp, “Oral History,” Biogen, Inc., 4.
50. Hartley, “Oral History,” 4.
51. Hofschneider, “Oral History,” 2.
52. Weissmann, ‘Cloning Interferon,’ 103.
53. Schaller, “Oral History,” 14.
54. Gelfand, “Oral History,” 32.
55. Hartley, “Oral History,” 4.
56. Sharp, “Oral History,” Biogen, Inc., 6.
57. Alafi, “Biotech Pioneer and Entrepreneur,” 16.
58. Mach, “Oral History,” 9.
59. Gilbert, “Oral History,” Biogen, Inc., 3.
60. Hofschneider and Murray, “Combining Science and Business,” 43.
61. See Rasmussen, Gene Jockeys, chap. 4–6.
62. Quoted in Hall, Invisible Frontiers, 209.
63. Gilbert, “Oral History,” Biogen, Inc., 4.
64. Gilbert, “Oral History,” Life Sciences Foundation, 17.
65. Kenney, Understanding Silicon Valley; Lécuyer, Making Silicon Valley; and Rosegrant and Lampe, Route 128.
66. Sharp, “Oral History,” Biogen, Inc., 4.
67. Quoted in Hall, Invisible Frontiers, 195.
68. Hartley, “Oral History,” 4.
69. Sharp, “Oral History,” Biogen, Inc., 4.
70. Sharp, “Oral History,” Biogen, Inc., 7.
71. Murray, “Oral History,” 10.
72. Murray, “Oral History,” 10.
73. Murray, “Oral History,” 7.
74. Mach, “Oral History,” 11.
75. According to Weissmann, the required lead time for preparing patent applications was typically two to three months. See Weissmann “Oral History,” Biogen, Inc., 4; and Schaller, “Oral History,” 4.
76. Weissmann, “The End of the Road,” 2.
77. Hall, Invisible Frontiers, chap. 14.
78. Hofschneider and Murray, “Combining Science and Business,” 43–5.
79. See Biogen, “Memorandum of Private Placement.” Kourilsky dropped out of Biogen within a year, and soon founded a company called Transgène with colleague Pierre Chambon in Strasbourg, France. He was replaced at Biogen by Belgian molecular biologist Walter Fiers.
80. Biogen, “Memorandum of Private Placement,” 15, 16.
81. Biogen, “Memorandum of Private Placement.”
82. Hall, Invisible Frontiers, 210.
83. Zucker and Darby, “Start Scientists and Institutional Transformation.”
84. Bourne, Paths to Innovation, chap. 3–5.
85. De Chadarevian, Designs for Life, chaps. 7, 10; and Morange, Molecular Biology, chap. 15.
86. Donis-Keller, “Oral History,” 2.
87. Davies, “Gathering No Moss,” 22.
88. Fishlock, “Biogen Attracts Staff,” 1.
89. Rosen, “Oral History,” 1.
90. Kamen, “Oral History,” Life Sciences Foundation. Kamen went on to direct the development of Humira, a treatment for rheumatoid arthritis, which became the world’s best selling drug in 2014. Revenues from sales in 2016 exceeded $16 billion. See Grant, ‘What Can Stop the World’s Best-Selling Drug?’ 1.
91. Flavell, “Oral History,” Life Sciences Foundation, 2.
92. Donis-Keller, “Oral History,” 11.
93. Quoted in Hilts, ‘The Gold Rush,’ A1.
94. Shapin observes that ‘ivory tower’ talk about universities emerged only in the middle decades of the twentieth century and not as an empirical description, but rather as a resource for justifying or delegitimizing individual actions or administrative policies: It has been ‘invoked by some practitioners against others, and by universities of some types and tendencies against others.’ See Shapin, “‘The Ivory Tower,” 24.
95. Etzkowitz, “Entrepreneurial Science,” 22.
96. Berman, Creating the Market University, 79, 85, 202.
97. Zucker and Darby, ‘Star Scientists and Institutional Transformation.’
98. Cawthorn, “Oral History,” 4.
99. For decades, the standard in the United States has been one day per week for consulting and other contracted services. The ‘one-fifth rule’ originated at MIT. See Etzkowitz, MIT and the Rise of Entrepreneurial Science, chap. 3.
100. Weissmann, “Oral History,” Life Sciences Foundation, 18.
101. Weissmann, “Oral History,” Biogen, Inc.
102. Mach, “Oral History,” 11.
103. Sharp, “Oral History,” Biogen, Inc., 18.
104. See Kenney, Biotechnology: The University-Industrial Complex, chap. 6.
105. Haseltine, “Oral History,” 34.
106. Murray, “Oral History,” 9.
107. Slaughter and Leslie, Academic Capitalism.
108. Maniatis, “Oral History,” 11.
109. See Bauer, “The Ptashne Fiasco”; and Kenney, Biotechnology, chap. 3.
110. Kenney, Biotechnology, 78.
111. Maniatis, “Oral History,” 11.
112. Knight, “Harvard Rules Out Role,” A1.
113. Maniatis, “Oral History,” 13. Bok wrote on relationships between universities and the private sector in Beyond the Ivory Tower. Presumably, the ‘Ptashne Fiasco’ shaped his views.
114. Skaletsky, “Oral History,” 5.
115. Cawthorn, “Oral History,” 26.
116. Sharp, “Oral History,” Biogen, Inc., 22.
117. Weissmann, “Oral History,” Biogen, Inc., 21.
118. Gilbert, “Oral History,” Life Sciences Foundation, 32.
119. Gilbert, “Oral History,” Life Sciences Foundation, 33.
120. Gilbert, “Oral History,” Life Sciences Foundation, 33.
121. Gilbert, “Oral History,” Life Sciences Foundation, 36.
122. Alafi, “Biotech Pioneer and Entrepreneur,” 55.
123. Sharp, “Oral History,” Chemical Heritage Foundation, 66.
124. Flavell, “Oral History,” Biogen, Inc., 38.
125. Weissmann, “Oral History,” Biogen, Inc., 37.
126. Quoted in Fisher, ‘The Rocky Road, 58.’
127. Flavell, “Oral History,” Biogen, Inc., 44.
128. Guagnini, “Ivory Towers?”
129. Mercelis, “Commercializing Academic Knowledge.”
130. König, “Engineering Professors as Entrepreneurs.”
131. See Reiner, “The Transformation of Venture Capital.”
132. See for example, Kenney, Biotechnology; Krimsky, Ennis, and Weissman, ‘Academic-Corporate Ties’; Mirowski and Sent, ‘The Commercialization of Science’; and Slaughter and Leslie, Academic Capitalism.
133. Berman, Creating the Market University.
134. Etzkowitz, “The Norms”; and Etzkowitz, The Triple Helix.
135. Mirowski, Science Mart.
136. See Shapin, The Scientific Life, chap. 5.
137. Historian of science Doogab Yi has written a fascinating and wonderfully detailed account of how Stanford University scientists and administrators responded to the appearance of commercial opportunities in biotechnology following the invention of recombinant DNA technology. Unfortunately, in our view, he wraps the historical analysis in a neo-institutional thesis that erases cultural complexities and conflates motives with justifications. He proposes that ‘scientist-entrepreneurs’ pursuit of profit, a by-product of their zeal to spur medical innovations for public benefit, became a moral calling for a scientific vocation in the age of commercial biotechnology.’ See Yi, The Recombinant University, 228.