The Vaccine Race

by Meredith Wadman

  6. Centers for Disease Control, Morbidity and Mortality Weekly Report 34, nos. 2, 5, and 7 (1985), reprinted in Journal of the American Medical Association (March 15, 1985): 1540.

  7. Ibid.; Wiktor, Plotkin, and Koprowski, “Development and Clinical Trials,” 4.

  8. Mario V. Fernandes, Hilary Koprowski, and Tadeusz J. Wiktor, “Method of Producing Rabies Vaccine,” U.S. Patent 3,397,267, filed September 21, 1964, and issued August 13, 1968, www.google.com/patents/US3397267.

  9. Wiktor, Plotkin, and Koprowski, “Development and Clinical Trials,” 5; Tadeusz J. Wiktor, Stanley A. Plotkin, and Doris W. Grella, “Human Cell Culture Rabies Vaccine: Antibody Response in Man,” Journal of the American Medical Association 224, no. 8 (1973): 1170–71.

  10. Wiktor, Plotkin, and Grella, “Human Cell Culture Rabies Vaccine,” 1170–71.

  11. Wiktor, Plotkin, and Koprowski, “Development and Clinical Trials,” 5, 7.

  12. Bahmanyar et al., “Successful Protection of Humans,” 2754.

  13. Ibid.

  14. Ibid.

  15. Center for Disease Control, “Recommendation of the Immunization Practices Advisory Committee (ACIP): Rabies Prevention,” Morbidity and Mortality Weekly Report 29, no. 3 (1980): 266.

  16. Centers for Disease Control, “Rabies Postexposure Prophylaxis with Human Diploid Cell Rabies Vaccine: Lower Neutralizing Antibody Titers with Wyeth Vaccine,” Morbidity and Mortality Weekly Report 34, no. 7 (1985): 90–92.

  17. Ibid., 90–91.

  18. United Press International, “Wyeth Laboratories Tuesday Recalled Its Wyvac Rabies Vaccine,” February 19, 1985, http://www.upi.com/Archives/1985/02/19/Wyeth-Labora tories-Tuesday-recalled-its-Wyvac-rabies-vaccine-effective/5202477637200/.

  19. Jeffrey P. Koplan and Stephen R. Preblud, “A Benefit-Cost Analysis of Mumps Vaccine,” American Journal of Diseases of Children 136 (1982): 362; Kenneth B. Robbins, A. David Brandling-Bennett, and Alan R. Hinman, “Low Measles Incidence: Association with Enforcement of School Immunization Laws,” American Journal of Public Health 71, no. 3 (1981): 270.

  20. Michiaki Takahashi et al., “Live Vaccine Used to Prevent the Spread of Varicella in Children in Hospital,” Lancet 2, no. 7892 (1974): 1288–90.

  21. Michiaki Takahashi et al., “Development of Varicella Vaccine,” Journal of Infectious Diseases 197 (2008): S41–44. See also Robert E. Weibel et al., “Live Attenuated Varicella Virus: Efficacy Trial in Healthy Children,” New England Journal of Medicine 310, no. 22 (1984): 1409.

  22. Beverly J. Neff et al., “Clinical and Laboratory Studies of KMcC Strain Live Attenuated Varicella Virus,” Proceedings of the Society for Experimental Biology and Medicine 166, no. 3 (1981): 339–47.

  23. Alan Shaw, interview with the author, March 16, 2014; Louis Galambos with Jane Eliot Sewell, Networks of Innovation: Vaccine Development at Merck, Sharp & Dohme, and Mulford, 1985–1995 (Cambridge: Cambridge University Press, 1995), 231–32.

  24. Neff et al., “Clinical and Laboratory Studies,” 344.

  25. Nicholas Wade, “Hayflick’s Tragedy: The Rise and Fall of a Human Cell Line,” Science 194, no. 4235 (1976): 125.

  26. Philip Provost, interview with the author, December 18, 2012.

  27. Weibel et al., “Live Attenuated Varicella Virus,” 1409.

  28. Wade, “Hayflick’s Tragedy,” 127.

  29. E. L. Buescher, “Respiratory Disease and the Adenoviruses,” Medical Clinics of North America 51 (1967): 773–74.

  30. Centers for Disease Control, Morbidity and Mortality Weekly Report: Recommendations and Reports 39, no. RR-15 (1990): 1–18.

  31. “1 Mil. Merck-Hayflick Contract for WI-38 Cells Revealed by NIH: Researcher Denies Wrongdoing, Sues Govt. for Defaming Character,” Blue Sheet: Drug Research Reports 19, no. 13 (March 31, 1976): 3, investigations 9 (Human Diploid Cells Under Gvt. Ownership), file folder 1 (Jan–August 1976), Historical Files, Office of the Director, National Institutes of Health.

  32. U.S. Food and Drug Administration, “WI-38 Cells Pre-tested for Vaccine Manufacture (ATCC 7/19/96),” response to Freedom of Information Act Request from Leonard Hayflick, August 26, 1996. Courtesy of Leonard Hayflick.

  33. John E. Shannon and Marvin Macy, eds., The American Type Culture Collection Registry of Animal Cell Lines, 2nd ed. (Rockville, MD: American Type Culture Collection, 1972), 17.

  Chapter Twenty-four: Biology, Inc.

  1. William Rutter, “The Department of Biochemistry and the Molecular Approach to Biomedicine at the University of California, San Francisco,” oral history conducted in 1992 by Sally Smith Hughes, p. 58, Regional Oral History Office, Bancroft Library, University of California at Berkeley, 1998.

  2. Leonard Hayflick, interview with the author, March 5, 2013.

  3. Ronald E. Cape, oral history conducted in 2003 by Sally Smith Hughes, Regional Oral History Office, Bancroft Library, University of California at Berkeley, http://digitalassets.lib.berkeley.edu/roho/ucb/text/cape_ron.pdf.

  4. Robert Beyers, “Free Inquiry Must Be Rule in Research,” Campus Report 13, no. 7 (1980): 1, 18. Found in Sally Smith Hughes, “Making Dollars Out of DNA: The First Major Patent in Biotechnology and the Commercialization of Molecular Biology, 1974–1980,” Isis 92 (2001): p. 573.

  5. Brook Byers, “Brook Byers: Biotechnology Venture Capitalist, 1970–2006,” oral history conducted by Thomas D. Kiley, 2002–5, Regional Oral History Office, Bancroft Library, University of California, p. 19, http://digitalassets.lib.berkeley.edu/roho/ucb/text/byers_brook.pdf.

  6. Wendy H. Schacht, “The Bayh-Dole Act: Selected Issues in Patent Policy and the Commercialization of Technology,” Congressional Research Service, December 3, 2012, p. 2, https://www.fas.org/sgp/crs/misc/RL32076.pdf.

  7. Elizabeth Popp Berman, Creating the Market University: How Academic Science Became an Economic Engine (Princeton, NJ: Princeton University Press, 2012), 106.

  8. Ibid., 105. Readers interested in a more detailed history should read Berman’s excellent account.

  9. Ibid., 107–8.

  10. Patent and Trademark Law Amendments Act, Public Law 96-517, U.S. Statutes at Large 94 (1980): 3015.

  11. Berman, Creating the Market University, 108.

  12. Diamond v. Chakrabarty, 447 U.S. 303 (1980), https://supreme.justia.com/cases/federal/us/447/303/case.html.

  13. Ibid., 309.

  14. The 2015 figures were provided by the Biotechnology Innovation Organization in Washington, DC.

  15. Readers interested in close coverage of these converging forces should read Elizabeth Popp Berman’s account in Creating the Market University, 69–79.

  16. Berman, Creating the Market University, 83.

  17. Hughes, “Making Dollars Out of DNA,” : 569.

  18. Maryann Feldman, Alessandra Colaianni, and Kang Liu, “Commercializing Cohen-Boyer, 1980–1997,” Druid (Toronto: University of Toronto Rotman School of Management, 2005), 1.

  19. Floyd Grolle (former licensing officer of the Cohen-Boyer patents), personal communication to Sally Smith Hughes, cited in Hughes, “Making Dollars Out of DNA,” 570.

  20. Michael Cleare (former executive director of Columbia’s Science and Technology Ventures Office), personal communication to Richard R. Nelson (Henry R. Luce professor of international political economy at Columbia University) and Bhaven Sampat (assistant professor of health policy and management, Mailman School of Public Health, Columbia University), August 29, 2006, cited in Alessandra Colaianni and Robert Cook-Deegan, “Columbia University’s Axel Patents: Technology Transfer and Implications for the Bayh-Dole Act,” Milibank Quarterly 87, no. 3 (2009): 700, 711.

  21. National Science Board, Science and Engineering Indicators: 1993 (Washington, DC: National Science Foundation, 1993), 430; Association of University Technology Managers, FY 2014 US Licensing Activity Survey (Oakbrook Terra
ce, IL: Association of University Technology Managers, 2014), 23.

  22. National Science Board, Science and Engineering Indicators 2014 (Arlington, VA: National Science Foundation 2014): 5–54.

  23. David Blumenthal et al., “University-Industry Research Relationships in Biotechnology: Implications for the University,” Science 232, no. 4756 (1986): 1364.

  24. Vincent B. Terlep Jr. to Thomas Malone, February 22, 1980, Directors’ Files, NIH, Office of the Director, investigations 9, folder 2.

  25. Richard J. Riseberg, note to Dr. Raub, July 24, 1989, investigations 9 (Human Diploid Cells Under Gvt. Ownership), file folder 2 (September 1976–July 1989), Historical Files, Office of the Director, National Institutes of Health. This letter reads in part: “[Hayflick is] not aware that a principal consideration in causing the government to settle had nothing to do with the merits but just the fact that Jim Schriver had retired and it was proving very expensive to use him as a consultant.” Riseberg was discussing the matter with William Raub, then the NIH’s acting director, because Hayflick had goaded Raub by sending the top NIH official a new paper that Hayflick had written, giving a one-sided account of his conflict with the NIH and describing how some biologists had profited from the legal and policy changes of the previous decade. Hayflick’s paper was titled “A New Technique for Transforming Purloined Human Cells into Acceptable Federal Policy.”

  26. Leonard Hayflick, Edmond C. Gregorian, Michael Hughes, and Vincent B. Terlep, “Settlement Agreement,” September 15, 1981, 1–8, investigations 9, folder 1, Directors’ Files, Office of the Director, National Institutes of Health.

  27. Ibid., 2.

  28. Bernard L. Strehler et al., “Hayflick-NIH Settlement,” Science 215 (1982): 240, 242.

  29. Leonard Hayflick, “Hayflick’s Reply,” Science 202 (1978): 128–36.

  Chapter Twenty-five: Hayflick’s Limit Explained

  1. Leonard Hayflick and Paul S. Moorhead, “The Serial Cultivation of Human Diploid Cell Strains,” Experimental Cell Research 25, no. 3 (1961): 585–621.

  2. Leonard Hayflick, “The Limited in Vitro Lifetime of Human Diploid Cell Strains,” Experimental Cell Research 37 (1965): 634.

  3. P. L. Krohn, “Aging,” Science 152 (1966): 392.

  4. Ibid.; Sir Macfarlane Burnet, Intrinsic Mutagenesis: A Genetic Approach to Ageing (Lancaster, UK: Medical and Technical, 1974): 62; L. M. Franks, “Cellular Aspects of Aging,” Experimental Gerontology 5 (1970): 281–89; R. L. Walford, The Immunologic Theory of Aging (Copenhagen: Munksgaard, 1969).

  5. Burnet, Intrinsic Mutagenesis, 62.

  6. Hayflick, “The Limited in Vitro Lifetime,” 625.

  7. Ibid.

  8. G. M. Martin, C. A. Sprague, and C. J. Epstein, “Replicative Life-span of Cultivated Human Cells: Effects of Donor’s Age, Tissue, and Genotype,” Laboratory Investigation: A Journal of Technical Methods and Pathology 23, no. 1 (1970): 86–92; Y. Le Guilly et al., “Long-term Culture of Human Adult Liver Cells: Morphological Changes Related to in Vitro Senescence and Effect of Donor’s Age on Growth Potential,” Gerontologia 19, no. 5 (1973): 303–13; E. L. Bierman, “The Effect of Donor Age on the in Vitro Life Span of Cultured Human Arterial Smooth-Muscle Cells,” In Vitro 14, no. 11 (1978): 951–55.

  9. J. R. Smith and R. G. Whitney, “Intraclonal Variation in Proliferative Potential of Human Diploid Fibroblasts: Stochastic Mechanism for Cellular Aging,” Science 207 (1980): 82–84.

  10. Ibid., 82.

  11. W. E. Wright and L. Hayflick, “Formation of Anucleate and Multinucleate Cells in Normal and SV40 Transformed WI-38 by Cytochalasin B,” Experimental Cell Research 74 (1972): 187–94.

  12. W. E. Wright and L. Hayflick, “Nuclear Control of Cellular Aging Demonstrated by Hybridization of Anucleate and Whole Cultured Normal Human Fibroblasts,” Experimental Cell Research 96, no. 1 (1975): 113–21.

  13. Leonard Hayflick, “Mortality and Immortality at the Cellular Level: A Review,” Biochemistry (Moscow) 62 (1997): 1180–90.

  14. Hermann J. Muller, “The Remaking of Chromosomes,” Collecting Net 13 (1938): 181–98.

  15. Barbara McClintock, “The Stability of Broken Ends of Chromosomes in Zea mays,” Genetics 126 (1941): 234–82.

  16. Alexey M. Olovnikov, “Telomeres, Telomerase, and Aging: Origin of the Theory,” Experimental Gerontology 31, no. 4 (1996): 445.

  17. A. M. Olovnikov [“Principles of Marginotomy in Template Synthesis of Polynucleoetides”], Doklady Akademii Nauk SSSR 201, no. 6 (1971): 1496–99 (in Russian).

  18. A. M. Olovnikov, “A Theory of Marginotomy: The Incomplete Copying of Template Margin in Enzymic Synthesis of Polynucleotides and Biological Significance of the Phenomenon,” Journal of Theoretical Biology 41 (1973): 186.

  19. Ibid., 188.

  20. Ibid., 181–90.

  21. James D. Watson, “Origin of Concatameric T7 DNA,” Nature: New Biology 239 (1972): 197–201.

  22. Catherine Brady, Elizabeth Blackburn and the Story of Telomeres: Deciphering the Ends of DNA (Cambridge, MA, and London: MIT Press, 2007), 3.

  23. Elizabeth H. Blackburn and Joseph G. Gall, “A Tandemly Repeated Sequence at the Termini of the Extrachromosomal Ribosomal RNA Genes in Tetrahymena,” Journal of Molecular Biology (1978): 33–53.

  24. Elizabeth H. Blackburn, Carol W. Greider, and Jack W. Szostak, “Telomeres and Telomerase: The Path from Maize, Tetrahymena and Yeast to Human Cancer and Aging,” Nature Medicine 12, no. 10 (2006): 1134; Jack W. Szostak, “Biographical,” Nobelprize.org, www.nobelprize.org/nobel_prizes/medicine/laureates/2009/szostak-bio.html.

  25. Jack W. Szostak and Elizabeth H. Blackburn, “Cloning Yeast Telomeres on Linear Plasmid Vectors,” Cell 29, no. 1 (1982): 245–55.

  26. Janis Shampay, Jack W. Szostak, and Elizabeth H. Blackburn, “DNA Sequences of Telomeres Maintained in Yeast,” Nature 310, no. 5973 (1984): 154–57.

  27. Carol W. Greider, e-mail to the author, May 15, 2016.

  28. Carol W. Greider and Elizabeth H. Blackburn, “Identification of a Specific Telomere Terminal Transferase Activity in Tetrahymena Extracts,” Cell 43, no. 2, part 1 (1985): 405–13.

  29. Guo-Liang Yu et al., “In Vivo Alteration of Telomere Sequences and Senescence Caused by Mutated Tetrahymena Telomerase RNAs,” Nature 344 (1990): 126–32.

  30. Carol W. Greider and Elizabeth H. Blackburn, “A Telomeric Sequence in the RNA of Tetrahymena Telomerase Required for Telomere Repeat Synthesis,” Nature 337 (1989): 331–37.

  31. Carol Greider, e-mail to the author.

  32. Robert K. Moyzis et al., “A Highly Conserved Repetitive DNA Sequence (TTAGGG)n, Present at the Telomeres of Human Chromosomes,” Proceedings of the National Academy of Sciences 85 (1988): 6622–26; Robin C. Allshire et al., “Telomeric Repeats from T. thermophila Cross Hybridize with Human Telomeres,” Nature 332 (1988): 656–59.

  33. Calvin B. Harley, A. Bruce Futcher, and Carol W. Greider, “Telomeres Shorten During Ageing of Human Fibroblasts,” Nature 345 (1990): 459.

  34. Stephen S. Hall, Merchants of Immortality: Chasing the Dream of Human Life Extension (Boston and New York: Houghton Mifflin, 2003), 58.

  35. Andrea G. Bodnar et al., “Extension of Life-span by Introduction of Telomerase into Normal Human Cells,” Science 279 (1998): 349–52.

  36. Nicholas Wade, “Cells’ Life Stretched in Lab,” New York Times, January 14, 1998, p. A1, www.nytimes.com/1998/01/14/us/cells-life-stretched-in-lab.html; Nicholas Wade, “Cells Unlocked, Longevity’s New Lease on Life,” Week in Review, New York Times, January 18, 1998, www.nytimes.com/1998/01/18/weekinreview/ideas-trends-cells-unlocked-longevity-s-new-lease-on-life.html; Nicholas Wade, “Cell Rejuvenation May Yield Rush of Medical Advances,” Science Times, New York Times, January 20, 1998, www.nytimes.com/1998/01/20/science/cell-rejuvenation-may-yield-rush-of-medical-advances.html.

 
37. Carl T. Hall, “Non-aging Human Cells Created in Lab; Bay Firm’s Stock Soars on Hopes of Medical Advances,” San Francisco Chronicle, January 14, 1998, p. 1.

  38. David Stipp, “The Hunt for the Youth Pill: From Cell-Immortalizing Drugs to Cloned Organs, Biotech Finds New Ways to Fight Against Time’s Toll,” Fortune, October 11, 1999, 199, http://archive.fortune.com/magazines/fortune/fortune_archive/1999/10/11/267014/index.htm.

  39. Mary Armanios and Elizabeth H. Blackburn, “The Telomere Syndromes,” Nature Reviews Genetics 13 (2012): 693–704; Susan E. Stanley and Mary Armanios, “The Short and Long Telomere Syndromes: Paired Paradigms for Molecular Medicine,” Current Opinion in Genetics & Development 33 (2015): 2–3.

  40. Mary Armanios, “Telomeres and Age-Related Disease: How Telomere Biology Informs Clinical Paradigms,” Journal of Clinical Investigation 123, no. 3 (2013): 996–1002.

  41. Gil Atzmon et al., “Genetic Variation in Human Telomerase Is Associated with Telomere Length in Ashkenazi Centenarians,” Proceedings of the National Academy of Sciences 107, supp. 1 (2010): 1710–17.

  42. Nam W. Kim et al., “Specific Association of Human Telomerase Activity with Immortal Cells and Cancer,” Science 266 (1994): 2011–15.

  43. Blackburn, Greider, and Szostak, “Telomeres and Telomerase,” 1137.

  44. Stanley and Armanios, “Short and Long Telomere Syndromes,” 3–6.

  Chapter Twenty-six: Boot-Camp Bugs and Vatican Entreaties

  1. Meredith Wadman, “Cell Division,” Nature 498 (2013): 425.

  2. Debi Vinnedge, telephone interview with the author, May 23, 2013.

  3. Y. Takeuchi et al., [“Field Trial of Combined Measles and Rubella Live Attenuated Vaccine”], Kansenshogaku Zasshi [Japanese Journal of Infectious Diseases] 76, no. 1 (2002): 56–62.

  4. The Japanese hepatitis A vaccine, Aimmugen, is made by the firm Kaketsuken using a line of cells from one African green monkey called GL37 cells. See David E. Anderson, “Compositions and Methods for Treating Viral Infections,” U.S. Patent 20,140,356,399 A1, filed January 11, 2013, and issued December 4, 2014, section 0032.