Synthesis by microbes or chemists? Pharmaceutical research and manufacturing in the antibiotic era
2009; Routledge; Volume: 25; Issue: 3 Linguagem: Inglês
10.1080/07341510903083237
ISSN1477-2620
Autores Tópico(s)Biotechnology and Related Fields
ResumoAbstract This article presents a case study of the rise of Pfizer as a leading pharmaceutical company, with a focus on changing relationships between manufacturing technology and R&D between the mid 1940s and the mid 1960s. Pfizer first moved into pharmaceuticals through participation in the US government's penicillin effort during World War II. The company had expertise in deep tank, biological fermentation for the production of chemicals that it adapted to the manufacture of penicillin. Having greatly expanded its biological manufacturing capacity to meet state needs, Pfizer adopted an R&D program to find new microbial antibiotics suited to its manufacturing technology after the war ended. Pfizer's successes in this antibiotic era established the firm as a major pharmaceutical company. In looking to larger commercial markets for drugs, Pfizer, like its competitors, pursued medicines for chronic diseases rather than acute infections. For this pursuit, in the 1950s and 1960s, Pfizer transformed itself into a chemistry‐orientated pharmaceutical firm by reorienting its R&D toward chemistry. This led to a growing divergence between R&D and manufacturing and the eventual replacement of biological manufacturing with chemical manufacturing. The article explores the changing trajectories of R&D and manufacturing at Pfizer, their shifting positions within the firm, and the consequences of these changes and shifts for the firm's strategy and organization. Keywords: pharmaceutical manufacturingchemical synthesisfermentationPfizerantibioticspenicillintetracycline Acknowledgments I am grateful to the anonymous reviewer, David Brock, Christophe Lécuyer, Harry Marks, and Leo Slater for comments on previous versions of this paper. Notes 1. Lesch, First Miracle Drugs; Hobby, Penicillin; Mahoney, Merchants of Life. 2. Sturchio, Values and Visions, 65–81; Mahoney, Merchants of Life, 191–203; Vagelos and Galambos, Medicine, Science and Merck, 105–51. 3. Sheehan and Henery‐Logan, 'Total Synthesis,' 3089–94; Swann, 'Search for Synthetic Penicillin,' 154–90. 4. Selassie, 'History of Quantitative Structure,' 1–48. 5. Hounshell, 'Industrial Research,' 59–65; Walsh, 'Paradigms in the Evolution,' 189–219. 6. Sturchio, Values and Visions, 89–91. 7. Johnson, 'New Developments and Prospects.' 8. Bartmann, Zwischen Tradition und Fortschritt; Engel, Medicine Makers of Kalamazoo; Kahn, All in a Century; Kogan, Long White Line; Mines, Pfizer; Merck, Sharpe & Dohme, By Their Fruits. 9. Shapin, Scientific Life, 127–64. 10. Achilladelis, 'Innovation in the Pharmaceutical Industry,' 19. 11. Manufacturing does not appear in any of the economic studies of the pharmaceutical industry published since 2000; for a small sample, see: Granville, Economics of Essential Medicines; Mazzucato and Dosi, Knowledge Accumulation; Puig‐Junoy, Public Financing of Pharmaceuticals. 12. Daemmrich, Pharmacopolitics; Galambos and Sewell, Networks of Innovation; Liebenau, Medical Science; Rasmussen, 'Moral Economy,' 161–85; Swann, Academic Scientists. For a notable study that considers firm strategy in light of overall product portfolios, see: Chandler, Shaping the Industrial Century, 177–229. 13. Slinn, 'Development of the Pharmaceutical Industry,' 156; Quirke, 'From Alkaloids to Gene Therapy,' 177–90. 14. Bud, 'Antibiotics, Big Business,' 329–49; Bud, Penicillin, 23–53; Wainwright, Miracle Cure; Waksman, The Antibiotic Era. 15. Chandler, Visible Hand, 372–6, 484–500; Hounshell, 'Evolution of Industrial Research,' 13–85; Porter, Competitive Strategy, 156–88. 16. Mines, Pfizer, 1–4 17. Daemmrich and Bowden, 'Rising Drug Industry,' 28–42. 18. Pfizer, Pfizer Quality, 29. 19. Other commodities produced through fermentation during World War I included glycerol in Germany and isoprene in England; see Bud, Uses of Life, 35–45; Fruton, Fermentation, 93–112. 20. Richards, 'Production of Penicillin,' 441–5; Clarke et al., Chemistry of Penicillin. 21. Lax, Mold in Dr. Florey's Coat. 22. Pratt and Dufrenoy, Antibiotics; Urdang, 'Antibiotics and Pharmacy,' 388–405. 23. Abraham et al., 'Further Observations on Penicillin,' 177–88; Keefer et al., 'Penicillin in the Treatment of Infections,' 1217–24. 24. Pratt, Pfizer, 9. 25. Lyons, 'Deep Tank Fermentation,' 33. 26. Rodengen, Legend of Pfizer, 59–64. 27. Bud, Penicillin, 44. 28. Rodengen, Legend of Pfizer, 77. 29. Industry was well in advance of academic curricula; the first biochemical engineering programs were established in 1947. See: Gaden, 'Microbiological Process Discussion,' 123. 30. Hobby, Penicillin, 190; Sturchio, Values and Visions, 112–15. 31. Hobby, Penicillin, 185; see also Mahoney, Merchants of Life, 240. 32. Lyons, 'Deep Tank Fermentation.' 33. Mahoney, Merchants of Life, 241. 34. 'Pfizer's Self‐Prescribed Tonic,' 154. 35. Pfizer, Pfizer Quality, 46. 36. Mines, Pfizer, 113–14. 37. Finlay et al., 'Terramycin,' 85. 38. For more on the clinical testing and FDA review of Terramycin, see: Daemmrich, Pharmacopolitics, 54–60. 39. Marks, The Progress of Experiment, 197–228; Matthews, Quantification and the Quest, 131–40. 40. Bauer et al., 'Clinical and Experimental Observations,' 395–406; Blake et al., 'Clinical Observations on Terramycin,' 495–507. 41. Reeves, 'Terramycin,' 145–7. 42. McFadyen, 'FDA's Regulation,' 159–69. 43. King to Pfizer, 23 March 1950, FDA Files, AF 12‐118, vol. 4. 44. McKeen, 'What Other Departments.' 45. McKeen, 'What Other Departments,' 11. 46. Mahoney, Merchants of Life, 243. 47. Mines, Pfizer, 117–120. 48. Bedingfield, 'Antibiotics Prove Boon,' F4. 49. Reeves, 'Terramycin'; Prescott and Dunn, Industrial Microbiology. 50. Dominick Attanasio, personal communication to the author. 51. Pratt, Pfizer: Bringing Science to Life, 9. 52. Federal Trade Commission, Economic Report, 74–5. 53. Bedingfield, 'Antibiotics Prove Boon,' F1. 54. Chemical & Engineering News, 'Pfizer Installs,' 4359; Chemical & Engineering News, 'Wall Street of Chemistry,' 240. 55. Pfizer Annual Reports, various years; Sturchio, Values and Visions, 185. 56. Argote and Ingram, 'Knowledge Transfer, 150–69; Clark, 'What Strategy can do for Technology,' 61–8; Nonaka, 'Knowledge Creating Company,' 96–104. 57. Moore, 'Medicinal Chemistry,' 582; Tischler, 'Production and Isolation,' 32–54. 58. US Patent 2,156,080; Sneader, Drug Discovery, 303–5. 59. Marks, 'Cortisone.' 60. Pfizer's R&D spending, like other pharmaceutical firms, grew to over 10% of sales in 1990; in 2007 it was over 17%. 61. Slater, 'Woodward, Robinson, and Strychnine,' 162–3. 62. Davenport, Letter to Woodward, 19 February 1952. Harvard University Archives, HUGFP 68.10, Box 28, Folder: Pfizer. 63. Lazier, Letter to Woodward, 24 July 1952. Harvard University Archives, HUGFP 68.6, Box 7, Folder: Pfizer and Co., Inc.; Kane, Letter to Woodward, 24 December 1953. Harvard University Archives, HUGFP 68.6, Box 7, Folder: Pfizer and Co., Inc.; Davenport, Letter to Woodward, 31 January 1955, Harvard University Archives, HUGFP 68.6, Box 7, Folder: Pfizer and Co., Inc. 64. Regna, 'Isolation and General Properties,' 4211; Hochstein et al., 'Structure of Terramycin,' 5455. 65. Lazier, Letter to Williams (Lederle Laboratories), 22 August 1952. Harvard University Archives, HUGFP 68.8, Box 35, Folder: Terramycin. 66. McKeen, 'President's Appraisal of Research,' 7. 67. McKeen, 'President's Appraisal of Research,' 7. 68. 'Science Notes,' New York Times, September 2, 1962; Conover and Woodward's work is described in: US Patent 2,699,054 and Conover, 'Terramycin XI,' 4622–3. 69. Conover, 'Discovering Tetracycline,' 20. 70. Brunnings, 'Trip Report,' HUGFP 68.10, Box 47, Folder: Terramycin 1958. 71. Mines, Pfizer, 120–1. 72. Brunings, 'Chemotherapeutic Research Planning,' Harvard University Archives, HUGFP 68.10, Box 26, Folder: Pfizer. 73. Conover, 'Tetracycline Total Synthesis, Progress and Plans,' Harvard University Archives, HUGFP 68.10, Box 26, Folder: Pfizer. 74. Laubach, 'Pfizer Worldwide Medicinal Product Research,' June 1966, Harvard University Archives, HUGFP 68.10, Box 26, Folder: Pfizer. 75. Mines, Pfizer, 213–14. 76. Rodengen, Legend of Pfizer, 101–2; Mines, Pfizer, 227–9. 77. Woodward, 'Acid Degradation Studies on Terramycin,' 1 March 1951, Harvard University Archives, HUGFP 68.8, Box 35, Folder: Terramycin. 78. Galdston, Impact of the Antibiotics, 88. 79. Pfizer Annual Report, 1985. 80. Raber, 'Pfizer's Penicillin Landmark,' 46.
Referência(s)