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The Locus of Corporate Entrepreneurship: Kirin Brewery's Diversification into Biopharmaceuticals

Published online by Cambridge University Press:  13 December 2011

Michael J. Lynskey
Michael J. Lynskey
Affiliation:
MICHAEL J. LYNSKEY is researcher at the Saïd Business School, University of Oxford.
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Abstract

The Kirin Brewery Company is a large, long-established, and successful firm in a traditional, “old economy” sector in Japan. Nevertheless, in the early 1980s it entered the “new economy” business of biopharmaceuticals, based on advances in scientific techniques at the time and prospects for the bio-technology industry in the future. This essay explains why Kirin entered this field and how it developed the necessary competences. The development of these new competences was in no small part owing to entrepreneurial alertness and opportunity recognition by individuals in various functions of the firm. As such, the case illustrates the presence in the large modern corporation of the individual entrepreneur, a figure whose existence and role is often downplayed or simply omitted in nominalist treatments of entrepreneurship, which depict innovation as a somewhat mechanistic endeavor, absent any element of entrepreneurial behavior.

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Articles
Information
Business History Review , Volume 80 , Issue 4 , Winter 2006 , pp. 689 - 723
Copyright
Copyright © The President and Fellows of Harvard College 2006

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References

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17 The government increased the alcohol tax by as much as 20 percent in 1984, with the result that overall alcohol consumption, including beer and wine, declined by 3.2 percent in the first year, and whiskey sales fell by 19.9 percent. See Richard Phalon, “Whiskey Rebellion – Japan's New Alcohol Tax and Changes in Bottling is Giving Distillers the Shakes,” Forbes, 1 July 1985.

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19 Jun Kojima, administrative manager, Kirin Pharmaceutical Division, quoted in Gary Schaefer, “Brewer Taps into Pharmaceuticals Market: Kirin Seeks Ways to Ease Reliance on Alcohol Sales,” San-Diego Union-Tribune, 22 Mar. 2000, C5.

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27 Ibid.

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35 Chemical companies were motivated also because of their falling rates of profit. See Itami, Hiroyuki, Why Is the Japanese Chemical Industry behind Other Industries? (Tokyo, 1991Google Scholar); Fransman, Martin, Visions of Innovation: The Firm and Japan (Oxford, 1999CrossRefGoogle Scholar).

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40 Tomoo Itoga was Kirin's senior vice president for technology. The company president during these discussions, and until April 1981, was Yasusaburo Sato, who became president in 1978. In April 1981, Shuji Konishi became president of Kirin, and he oversaw the operational diversification into the pharmaceutical industry. Another senior executive at the time, Koichiro Aramaki, became the president of Kirin Pharmaceutical Company, and eventually became president of the Kirin Group in March 2001, succeeding Yasuhiro Sato, who served as president from March 1996 to March 2001. Aramaki spearheaded Kirin's pharmaceutical business. He held a B.S. (Tokyo) in agricultural chemistry, majoring in fermentation, an M.S. (California, Davis) in food science and technology, majoring in dairy microbiology, and a Ph.D. (Niigata) in biological science.

41 Masaharu Ishikawa, product development manager, Kirin Pharmaceutical Division, quoted in Gary Schaefer, “Brewer Taps into Pharmaceuticals Market: Kirin Seeks Ways to Ease Reliance on Alcohol Sales,” San Diego Union-Tribune, 22 Mar. 2000, C5. This diversification is remarked upon elsewhere: “Kirin Brewery, a giant beer producer, spends the larger part of its research budget in gene-splicing research designed to create new beverages, drugs, and vegetables.” Leontiades, M., “The Japanese Art of Managing Diversity,” Journal of Business Strategy 12, no. 2 (1991): 32CrossRefGoogle Scholar.

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45 Alick Isaacs and Jean Lindemann discovered interferon in 1957. It was not until 1980, however, that it became widely known when it was one of the first proteins to be produced by recombinant gene technology, and at the time was seen as a wonder drug in the treatment of cancer.

46 Interview with Jun Kojima, 27 May 2002. Toray, another Japanese “new entrant” firm, diversified into Pharmaceuticals from its core business in fibers and other synthetic materials in the 1970s and pioneered interferon in Japan. Suntory, another new entrant and Japan's largest whiskey maker, entered Pharmaceuticals in 1979 and developed gamma-interferon for therapeutic purposes.

47 June Kinoshita, “Is Japan a Boon or a Burden to U.S. Industry's Leadership? (Biotechnology Industry),” Science, 29 Jan. 1993, 596.

48 Dr. Masaharu Ishikawa, Product Development Manager, Kirin Pharmaceutical Division, quoted in Gary Schaefer, “Japanese Brewery Sees Future in Drugs,” Pittsburgh Post-Gazette, 23 Mar. 2000, F4.

49 Interview with Isao Ishida, 15 Feb. 2002. In 1973, the research of Takeji Miyake of Kumamoto University became known to the renowned American biochemist, Eugene Goldwasser, of the University of Chicago, who was searching for the causal agent in blood that signals bone marrow to replace red blood cells. Goldwasser arranged for Miyake to go to the United States under an NIH grant to work with him. In 1976, Miyake and his colleagues isolated and purified EPO from the urine of humans. EPO was the first hematopoietic growth factor to be identified. See Miyake, T., Kung, C. K.-H. and Goldwasser, Eugene, “Purification of Human Erythropoietin,” Journal of Biological Chemistry 252 (1977): 5558–64Google ScholarPubMed.

50 Collins, H. M., “Tacit Knowledge and Scientific Networks,” in Science in Context: Readings in the Sociology of Science, eds. Barnes, Barry and Edge, David (Cambridge, Mass., 1982Google Scholar).

51 Interview with Jun Kojima, 27 May 2002. Jun Kojima confirmed: “In other words, there was a tacit part and we were unable to produce EPO simply in accordance with the papers. We could not easily replicate Dr. Miyake's results.”

52 Arguably, Penrose's most important contribution to the theory of the firm is the notion of “productive opportunity.” See Penrose, The Theory of the Growth of the Firm, 31–32.

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55 Interview with Tadashi Sudo, 1 Mar. 2000.

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58 Interview with Jun-ichi Koumegawa, 16 Feb. 2000.

59 Interview with Akihiro Shimosaka, 15 July 2002.

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63 Interview with Isao Ishida, 15 Feb. 2002.

64 Interview with Jun-ichi Koumegawa, 16 Feb. 2000. For example, in its research on transchromosomic mice and human immunoglobulin genes, Kirin worked with Mitsuo Oshi-mura in the Faculty of Medicine, Tottori University. For its human antibody project, Kirin collaborated with Kazunori Hanaoka in the Laboratory of Molecular Embryology, Kitasato University. Kirin also collaborated with public research institutes, e.g., with Michio Oishi at the Helix DNA Research Institute in Chiba.

65 Interview with Tadashi Sudo, 1 Mar. 2000.

66 The Microbial Chemistry Research Foundation was founded by Hamao Umezawa, formerly of the National Institutes of Health. The foundation's research is funded by patent revenues and fees from research assignments. Hamao Umezawa (1914–86) developed a succession of new antibiotics, such as kanamycin (1957), pentamycin (1958), kasugamycin (1965) and bleomycin (1969), all of which were licensed to industry and used worldwide.

67 Interview with Akihiro Shimosaka, 15 July 2002. Fumimaro Takaku was an expert in hematopoietic growth factor and also belonged to the National Hospital Center in Tokyo.

68 In discussing the joint venture, I acknowledge that I am presenting events based primarily on the accounts of Kirin personnel only.

69 Badaracco, Joseph, The Knowledge Link: How Firms Compete Through Strategic Alliances (Boston, Mass., 1991Google Scholar).

70 Amgen was founded in April 1980 by two venture capitalists–Sam Wohlsteadter and William Bowes–with a UCLA molecular biologist, Winston Salser, and about $200,00 0 in seed money. They persuaded George Rathmann, a senior scientific executive at Abbott Laboratories, to join the company. In February 1981, they attracted additional capital by selling shares privately for $18.8 million, at the time one of the largest private placements ever for a biotechnology business.

71 The U.S. biotechnology firms included Cetus (founded in 1971), Genentech (1976), Biogen (1977), Genex (1977), Molecular Genetics (1979), and the Genetics Institute (1980). It is only in recent years that biotechnology venture firms–and venture firms generally–have emerged in Japan because of the provision of venture capital and institutional change. See the following articles by Lynskey, Michael J.: “A Profile of Biotechnology and Information Technology Venture Firms in Japan: Firm-level and Managerial Characteristics,” International Journal of Biotechnology 5 (2003): 105–24CrossRefGoogle Scholar; “The Commercialisation of Biotechnology in Japan: Bio-ventures as a Mechanism of Knowledge Transfer from Universities,” International Journal of Biotechnology 6 (2004): 155–85CrossRefGoogle Scholar; “Determinants of Innovative Activity in Japanese Technology-based Start-up Firms,” International Small Business Journal 22 (2004): 159–96CrossRefGoogle Scholar; “Bioentrepreneurship in Japan: Institutional Transformation and the Growth of Bioventures,” Journal of Commercial Biotechnology 11 (2004): 9–37CrossRefGoogle Scholar; “Knowledge, Finance and Human Capital: The Role of Social Institutional Variables on Entrepreneurship in Japan,” Industry and Innovation 11 (2004): 373–405CrossRefGoogle Scholar; “Transformative Technology and Institutional Transformation: Coevolution of Biotechnology Venture Firms and the Institutional Framework in Japan,” Research Policy 35 (2006): 1389–422CrossRefGoogle Scholar.

72 Until the early 1980s, EPO was only produced artificially in infinitesimally small quantities, so that its use in therapy was impossible. However, owing to the work of Fu-Kuen Lin, who discovered the gene that codes for this hormone, EPO became a widely available therapeutic candidate. Lin's first patent was filed on 13 December 1983, and other patents on the process for producing recombinant EPO were filed shortly thereafter.

73 Interview with Akihiro Shimosaka, 15 July 2002.

74 Roberts, E. B., “New Ventures for Corporate Growth,” Harvard Business Review 58 (July/Aug. 1980): 134–42Google Scholar.

75 On Amgen's size, Jun-ichi Koumegawa said, “When we established the agreement with Amgen, it was a very small company; maybe the total number of employees was about 120.” Interview with Jun-ichi Koumegawa, 16 Feb. 2000. At the end of 1981, Amgen's staff numbered 42, expanding to 100 in 1982. See George Rathmann, B., “Biotechnology Startups,” in Biotechnology: The Science and the Business, eds. Moses, Vivian and Springham, D. G., 2nd ed. (Amsterdam, 1999), 47–58Google Scholar.

76 Interview with Akihiro Shimosaka, 15 July 2002. According to Kirzner, “Entrepreneurial profit opportunities exist where people do not know what they do not know, and do not know that they do not know it. The entrepreneurial function is to notice what people have overlooked.” Kirzner, Israel M., “The Theory of Entrepreneurship in Economic Growth,” in Encyclopedia of Entrepreneurship, eds. Kent, Calvin A., Sexton, Donald L., and Vesper, Karl H. (Englewood Cliffs, N.J., 1982), 273Google Scholar.

77 Interview with Jun Kojima, 27 May 2002.

78 Akihiro Shimosaka joined Kirin in 1969 and worked initially in quality control for beer and later whiskey production. A graduate of the University of Tokyo in agricultural chemistry, he later gained a doctorate in microbiology from the Institute of Applied Microbiology, University of Tokyo.

79 Interview with Akihiro Shimosaka, 15 July 2002.

80 Ibid.

81 Writing on U.S.-Japan strategic alliances in biotechnology, Prevezer and Toker state that these relationships take at least a year to negotiate and develop. Prevezer, M. and Toker, S., “The Degree of Integration in Strategic Alliances in Biotechnology,” Technology Analysis and Strategic Management 8 (1996): 117–33CrossRefGoogle Scholar.

82 Rathmann, quoted in Marilyn Chase, “Amgen, Japan Brewery Form Venture to Make Synthetic Hormone,” Wall Street Journal, 14 May 1984.

83 Philip J. Whitcome, director of strategic planning, Amgen, quoted in Victor F. Zonana, “Teaming Up: When it Comes to Forging Alliances, Japan Proves a More Willing Partner,” Los Angeles Times, 22 Feb. 1988.

84 Rathmann, quoted in Neil Henderson, “Biotech Firms Reach Overseas for Partners–Ties between U.S. Firms and Foreign Competitors,” Washington Post, 19 May 1985.

85 The original U.S. patent (no. 4,703,008) was issued to Kirin-Amgen, Inc., of Thousand Oaks, California, for DNA, vectors, and host cells in late October 1987, protecting its invention of “DNA Sequences Encoding Erythropoietin.” The patent text cited an estimate at the time “that the availability of erythropoietin in quantity would allow for treatment each year of anemias of 1,600,000 persons in the U.S.”

86 Kirin's second hematology product, G-CSF (granulocyte colony-stimulating factor), was a protein that stimulates the production of white blood cells used in the creation of antibodies to help prevent bacterial infections. G-CSF was used in the treatment of cancerrelated neutropenia (low white-blood-cell count) in chemotherapy, hematological disorders, such as HIV, and bone marrow transplants.

87 The core engineers in question were Ken Suzuki, vice president, pharmaceutical research laboratory, Kirin Brewery, Takahashi, Gunma; Hajime Ichihashi, plant manager, pharmaceutical production plant, Kirin Brewery, Takahashi, Gunma; and Atsuo Odagawa, production manager, pharmaceutical production plant, Kirin Brewery, Takahashi, Gunma.

88 See Kunitake, R., Suzuki, A., Ichihashi, H., Matsuda, S., Hirai, O. and Morimoto, K., “Fully-Automated Roller Bottle Handling System for Large Scale Culture of Mammalian Cells,” Journal of Biotechnology 52, no. 3 (1997): 289–94CrossRefGoogle ScholarPubMed.

89 See S. Oda, “Zouketsu Horumon Seizai de ‘Baioiyaku no Kirin’ e“ [Following Hematosis Hormone Products: A Shift towards Kirin Biopharmaceuticals] (in Japanese), Nikkei Biotechnology & Business (Sept. 2001): 106–9.

90 “Two Groups Seek EPO Approval,” Biotechnology Newswatch 9 (6 Feb. 1989): 4Google Scholar.

91 Chase, “Amgen, Japan Brewery Form Venture to Make Synthetic Hormone”; Lawrence Surtees, “Legal Prowess Plays Crucial Role in Amgen's Biotech Race,” Globe and Mail, 11 Apr. 1988.

92 “Amazing Amgen–Big Time Rx Firm or Shooting Star?: EPO … A Great Way to Start,” Genesis Report-Rx, 1 June 1992.

93 N. Miyadai, “Kirin Bīru: Beikoku Benchā Kigyō to no Gōben ni Yoru Iyakuhin Kenkyu Kaihatsu no Jissai“ [Kirin Beer: Realizing Pharmaceutical R&D through a Joint Venture with a U.S. Start-up] (in Japanese), Business Research (Mar. 1989): 25; “Can Amgen Follow Its Own Tough Act?” Business Week, 11 Mar. 1991, 95.

94 The Japanese market for EPO was divided approximately equally between two manufacturers: Kirin and Chugai Pharmaceutical Company.

95 “Kirin Brewery Expands Indications of Erythropoietin and G-CSF Preparations,” Pharma Japan, 3 June 1993, 16.

96 “Kirin Brewery to Launch Blood Boosting Drugs,” Biotechnology Newswatch, 2 Dec. 1991, 9; “Kirin Brewery–A Profile,” Applied Genetics News, 1 Mar. 1993.

97 David P. Hamilton, “Suds and Drugs: Japan's Kirin Brews Success in Biotechnology Venture,” Asian Wall Street Journal, 14 Jan. 1993, 1; Hamilton, “Kirin Brewery's Plunge into Biotechnology Pays Off–Ten Years Later, Japan Concern's Sales of Two Top Drugs Surpass Rivals,” Wall Street Journal, 25 Jan. 1993, B3.

98 Interestingly, Kirin's income was higher than that of the traditional Japanese pharmaceutical companies, such as Sankyo (32nd position), Takeda (42nd position), and Yamanouchi (45th position) in 1992.

99 “Kirin Founds U.S. Biotechnology Center, Provides Funds for 10 Years,” Biotechnology Newswatch, 21 Nov. 1988, 1.

100 Toshiaki Kawakami, principal investigator, La Jolla Institute for Allergy and Immunology, quoted in Ann Gibbons, “In Biotechnology, Japanese Yen for American Expertise,” Science, 27 Nov. 1992, 1431.

101 NESP is a hematopoietic factor that increases the production of red blood cells. See Rhonda L. Rundle, “Amgen Net Income Rises 30%, Beating Analysts Estimates,” Wall Street Journal, 19 July 1996 B3; Charles Craig, “Amgen Posts 30 Percent Income Jump for 2nd Quarter,” Bioworld Today, 22 July 1996.

102 See Jones, K. K. and Shill, W. E., “Japan: Allying for Advantage,” in Collaborating to Compete: Using Strategic Alliances and Acquisitions in the Global Marketplace, eds. Bleeke, Joel and Ernst, David (New York, 1993), 115–44Google Scholar.

103 Shigero Mishima, Pharmaceuticals analyst, S. G. Warburg (Japan), quoted in Hamilton, “Kirin Brewery's Plunge into Biotechnology Pays Off.”

104 Lowell Sears, senior vice president, Amgen, quoted in Gibbons, “In Biotechnology, Japanese Yen for American Expertise.”

105 Science and Technology Agency (STA), White Paper on Science and Technology (Tokyo, 1997Google Scholar).

106 Koichiro Aramaki, vice president, Kirin Pharmaceutical Division, quoted in Gibbons, “In Biotechnology, Japanese Yen for American Expertise.”

107 Rathmann quoted in Henderson, “Biotech Firms Reach Overseas for Partners.”

108 Hidemaru Yamaguchi, biotechnology research analyst, Nomura Research Institute, Tokyo, quoted in Stuart Dambrot, “Strength in Fine Chemicals: Japan Moves toward International Biotech Market,” Chemical Week, 8 Apr. 1992, 44.

109 Torres, A., “Unlocking the Value of Intellectual Assets,” McKinsey Quarterly 4 (1999): 28–37Google Scholar.

110 V. Griffith, “Amgen, TKT Patent Dispute Continues,” Financial Times, 10 Apr. 2000.

111 Amgen's annual turnover was larger than the entire British biotechnology industry in 2003. See “Financial Times Global 500 List of the World's Largest Companies,” Financial Times, 10 May 2002; Rosie Murray-West, “Evans Warns Biotech is No ‘British Success Story,’“ Daily Telegraph, 25 Nov. 2003.

112 In 2005, Kirin's pharmaceutical sales increased 7.8 percent to 67.6 billion yen and operating income increased 17.3 percent to 14.2 billion yen, representing 13 percent of a record consolidated operating income of 111.7 billion yen.

113 Interview with Jun-ichi Koumegawa, 16 Feb. 2000.

114 Interview with Isao Ishida, 15 Feb. 2002.

115 Ken Yamazumi, director of planning, Kirin Pharmaceutical Division, quoted in M. Hashimoto, “Kirin Biiru Iyaku Jigyo. Sanyu 20 Nen me Ookina Kake ni Deta: Saibo Iryo to Koutai Iyaku de Shoubu” [Kirin Beer Pharmaceutical Business: A Big Bet 20 Years On: Fight with Cell Therapy and Antibodies] (in Japanese), Nikkei Biotechnology & Business (Feb. 2002): 40–6.

116 The others were the U.S. biotechnology firms Amgen, Genentech in San Francisco, and ZymoGenetics in Seattle.

117 See “Four-way Fight Brews over Long-sought Platelet Factor,” Biotechnology Newswatch, 21 July 1994.

118 See D. Metcalf, “Thrombopoietin–At Last,” Nature, 16 June 1994, 519-20.

119 Kevin W. Sharer, president of Amgen, quoted in Larry Armstrong, “Amgen Could Use a Little Growth Factor: Can it Keep Profits Up While Awaiting the Next Breakthrough?” Business Week, 31 Oct. 1994, 122; Gordon Binder, CEO of Amgen, quoted in “CEO Interview–Amgen Inc.,” Wall Street Transcript, 20 Feb. 1995.

120 Dr. Bruce Carter, corporate executive vice president and chief scientific officer, Novo Nordisk, quoted in “Novo Nordisk Signs License Agreement with Amgen and Kirin on Thrombopoietin,” Business Wire, 15 Aug. 1995.

121 Mitsuo Ohmi, senior analyst, Smith Barney, Tokyo, quoted in “Japan's Kirin/Denmark's Novo: Builds on Strong Area,” Dow Jones International News, 18 Aug. 1995.

122 Stem cells are expected to play an important role in clinical applications as their use in transplantation and gene therapy widens. The worldwide market is forecast to almost triple from $24.6 billion in 2005 to $68.9 billion in 2010.

123 Quoted in “Diabetes to Benefit from Tissue Engineering,” Kyodo News, 8 Dec. 2000.

124 Katsuhiko Asano, quoted in Hashimoto, “Kirin Biiru Iyaku Jigyo. Sanyu 20 Nen me Ookina Kake ni Deta: Saibo Iryo to Koutai Iyaku de Shoubu” [Kirin Beer Pharmaceutical Business: A Big Bet 20 Years On: Fight with Cell Therapy and Antibiotics].

125 Interview with Yasunori Yamaguchi, 1 Mar. 2000.

126 For example, Yasunori Yamaguchi spent two years, from 1992 to 1994, doing postdoctoral research with Ralph Steinmann, the discoverer of dendritic cells, at Rockefeller University.

127 Koichiro Aramaki, president, Kirin Pharmaceutical Division, quoted in “Dendreon and Kirin to Develop and Commercialize Dendritic Cell Therapies,” Business Wire, 10 Dec. 1998.

128 Christopher Henney, CEO of Dendreon, quoted in Ibid.

129 “Dendreon and Kirin Sign Research Agreement,” Business Wire, 4 May 1999; “Dendreon and Kirin Expand Their Collaboration,” Business Wire, 10 Aug. 2001; Marni Leff, “Kirin Drug Division, Dendreon Close Deal,” Seattle Post-Intelligencer, 11 Aug. 2001; “Kirin and Dendreon to Seek Cancer Vaccines,” Strategic Outsourcing Report, 1 Sept. 2001; “Kirin to Promote Cytotherapy Study, Targeting Cancer Treatment,” Japan Chemical Week, 11 Oct. 2001.

130 A monoclonal antibody (MAB) is an exact copy of a single antibody that binds to a specific antigen–a molecule on, say, a bacterium, virus, or cancer cell. It then triggers a response in the immune system that destroys or neutralizes the interloper. The market for MABs is projected to triple in value from $10.3 billion in 2004 to $30.3 billion in 2010.

131 Human immune systems tend to recognize pure mouse antibodies as foreign and destroy them with–ironically–antibodies. The reaction, known as human antimouse antibody response, not only prevented mouse antibodies from hitting their targets but also produced side effects that were sometimes lethal. Progress was made to engineer antibodies acceptable to humans: from chimera antibodies, to humanized antibodies, and human-type antibodies. Critical mouse characteristics, however, remained and hindered effectiveness, until Kirin developed the world's first genetically engineered mouse that could produce human antibodies.

132 Interview with Isao Ishida, 15 Feb. 2002.

133 In October 1997, a specialist antibody company called Medarex (Annandale, N.J.) acquired GenPharm (San Francisco). Cell Genesys (Foster City, Calif.) spun off its mouse technology into a separate company called Abgenix (Fremont, Calif.). See G. Stix, “Innovations: The Mouse That Warred,” Scientific American, June 2001, 34–5.

134 Interview with Isao Ishida, 18 Sept. 2001.

135 Interview with Isao Ishida, 15 Feb. 2002.

136 Ibid. Ishida said that such abnormality is “similar to Down's syndrome in humans, caused by trisomy 21.” Down's syndrome is caused by one cell having two 21st chromosomes instead of one, so a resulting fertilized egg has three 21st chromosomes. Hence the scientific name, trisomy 21

137 Ibid.

138 Ibid.

139 Whereas the existing technology at the time allowed scientists to insert about 0.5 to 2 million base pairs of DNA into cells and into mice, the chromosome that Ishida and colleagues at Kirin could insert represented about 20 million base pairs of DNA.

140 See Tomizuka, K. et al. , “Functional Expression and Germline Transmission of a Human Chromosome Fragment in Chimeaeric Mice,” Nature Genetics 16 (1997): 133–43CrossRefGoogle ScholarPubMed.

141 Interview with Isao Ishida, 15 Feb. 2002.

142 Roger Reeves, associate professor of physiology, Center for Medical Genetics, Johns Hopkins University School of Medicine, Baltimore, on Talk of the Nation, National Public Radio (6 June 1997Google Scholar).

143 Interview with Dr. Kazuma Tomizuka, 1 Mar. 2000.

144 Donald Drakeman, president and CEO, Medarex, quoted in “Medarex Announces Strategic Alliance with Kirin,” PR Newswire, 10 Jan. 2000.

145 Michael Appelbaum, executive vice president of finance and administration, Medarex, quoted in Lisa Seachrist, “Medarex and Kirin Brewery Enter $12m Antibody Alliance,” Bio-World Today, June 2000.

146 Donald Drakeman, president and CEO, Medarex, quoted in “Squawk Box–Medarex Incorporated–CEO Interview,” CNBC/Dow Jones Business Video, 12 Jan. 2000.

147 “Kirin to Step Up Protein Production to Underpin Antibody Pharma Operations,” Japan Chemical Week, 18 Oct. 2001; “Antibody Drugs May Thrive before Genetics Drugs Appear,” Japan Chemical Week, 13 Dec. 2001.

148 Schumpeter, Capitalism, Socialism and Democracy, 133.

149 Nonaka, Ikujiro, and Takeuchi, Hirotaka, The Knowledge-Creating Company: How Japanese Companies Create the Dynamics of Innovation (Oxford, 1995), 135–40Google Scholar.

150 Schumpeter, The Theory of Economic Development.

151 Murray, J. A., “Marketing is Home for the Entrepreneurial Process,” Industrial Marketing Management 10, no. 2 (1981): 93–9CrossRefGoogle Scholar.

152 Cole, Arthur H., Business Enterprise in its Social Setting (Cambridge, Mass., 1959Google Scholar); Alford, B. W. E., “The Chandler Thesis: Some General Observations,” in Management Strategy and Business Development, ed. Hannah, Leslie (London, 1976Google Scholar); Minkes, A. L. and Foxhall, G. R., “Entrepreneurship, Strategy, and Organization: Individual and Organization in the Behavior of the Firm,” Strategic Management Journal 1, no. 4 (1980): 295–301CrossRefGoogle Scholar; Minkes, A. L., The Entrepreneurial Manager: Decisions, Goals and Business Ideas (Harmondsworth, U.K., 1987Google Scholar).

153 Foxhall, G. R. and Minkes, A. L., “Beyond Marketing: The Diffusion of Entrepreneurship in the Modern Corporation,” Journal of Strategic Marketing 4 (1996): 71–93CrossRefGoogle Scholar.

154 Alfred Marshall viewed the entrepreneur as an employer, a manager, and a coordinator. According to Schumpeter, however, “the Marshallian definition of the entrepreneur, which simply treats the entrepreneurial function as ‘management’ in the widest meaning, will naturally appeal to most of us. We do not accept it, simply because it does not bring out what we consider to be the salient point and the only one which specifically distinguishes entrepreneurial from other activities.” See Marshall, Principles of Economics; Schumpeter, The Theory of Economic Development, 77.

155 Weber saw the “rational-legal” type of organization, or “bureaucracy,” as the dominant institution of modern society, and described it as being like a machine. Weber, Max, The Theory of Social and Economic Organization (Oxford, 1947Google Scholar).

156 Minkes, The Entrepreneurial Manager.