A different kind of synthesis: artificial synthesis of insulin in socialist China

ABSTRACT

In the 1950s, the studies of proteins through their synthesis captured the attention of a number of biochemists. Among teams that set out to chemically synthesize the protein insulin, a large team in the People’s Republic of China achieved success in 1966, months before the Cultural Revolution. By focusing on the ideological refashioning, material arrangement, and organizational style of the project, this paper addresses the political and material dimensions of the project, especially how it was reconstructed as an engineering project in-between biology and chemistry for the young republic. This case was different from the design rationales demonstrated in both American and German cases, in which insulin synthesis was viewed as either a challenging problem for biochemistry or primary research toward making synthetic fibers. The process reveals a fluid topography of the material, social, and political space that a group of biochemists could work with in socialist China.

KEYWORDS:

• Biochemistry
• insulin synthesis
• socialist China
• chemical engineering

Acknowledgements

The authors would like to thank Angela Creager for her crucial academic mentorship and connecting the authors which has made the paper possible. The paper benefited from extensive comments from Karen Rader, Tiago Saraiva, and anonymous reviewers. Ling also would like to thank Shirley Tilghman, who advised the original thesis at Princeton University, and the scientists in the US and China who shared their personal accounts with her.

Disclosure statement

No potential conflict of interest was reported by the authors.

Notes

1. Xiong and Wang, Hecheng yige danbaizhi, 85–86. Throughout this paper, names in pinyin will be presented in the last name-first name format.

2. Dikötter, The Cultural Revolution.

3. The year 2015 marked the fiftieth anniversary for the initial achievement. It also happened to be a year in which the Chinese pharmaceutical chemist Tu Youyou shared the Nobel Prize for Physiology or Medicine for the identification and isolation of artemisinin, an essential part of the anti-malarial regimens currently in use. Unsurprisingly, a flurry of commemorations in the forms of memoirs and documentaries about the insulin synthesis work became circulated in Chinese media, many of which lamented a missed chance for Nobel Prize.

4. For a sweeping history of modern biology in China, see Schneider, Biology and Revolution.

5. Schmalzer, Red Revolution, Green Revolution; and Jiang, “The Socialist Origins.”

6. Creager, “A Chemical Reaction.”

7. Slaton, “Engineering Improvement.”

8. Johnson, Hitting the Brakes.

9. Chee and Clancey, “The Human Proteome”; and Fischer, “A Tale of Two Genome Institutes.”

10. Kohler, Lords of the Fly; Rheinberger, Toward a History of Epistemic Things; and Creager, The Life of a Virus.

11. The involvement of a larger number of people, including non-experts such as farmers, was a feature of some grand socialist projects. See, for example, Smith, Works in Progress.

12. Edgerton, The Shock of the Old.

13. Cao, “China’s ‘Nobel Prize complex’.” For an updated reflection on this issue, see Cao, “The Universal Values.” This article is not to address the question of why China’s work in insulin synthesis was not awarded a Nobel Prize. The question has been addressed elsewhere, see Xiong and Wang, Hecheng yige danbaizhi, 119–126.

14. Wolfe, Competing with the Soviets; and Galison and Hevly, Big Science.

15. Walker, Science and Ideology. Historian Nikolai Krementsov shows the ways different scientists and scientists of different disciplines undertake these accommodations in Soviet Russia were heterogeneous: while some scientists with connection to the capitalist West or to suppressed disciplines became victims under suppression and persecution, others learned to ride on various political and ideological tides to promote their own research directions. See Krementsov, Stalinist Science.

16. Schneider, Biology and Revolution; and Hu, China and Albert Einstein.

17. Tsui, “Revisiting the Insulin Project in China.” It is extensively cited in Xiong and Wang, 2005.

18. Xiong and Wang, Hecheng yige danbaizhi.

19. Dikötter, Mao’s Great Famine. An estimate of twenty million people died of starvation in the three-year period.

20. Selva, White, and Anfinsen, “Reductive Cleavage”; and Strasser, “A World in One Dimension.”

21. Chantrenne, “Newer Developments.”

22. Sifferd and du Vigneaud, “A New Synthesis of Carnosine.”

23. The year 1953, when du Vigneaud synthesized oxytocin, happened to be the same year Sanger solved the amino-acid sequence of insulin. du Vigneaud et al., “The Synthesis of Oxytocin.” Sanger and Thompson, “The amino-acid sequence.”

24. Gutte and Merrifield, “The Synthesis of Ribonuclease A.” The pressures for “engineerability” of biomolecules and life in general became more pronounced in the emerging scientific field of synthetic biology. See Calvert, “Synthetic Biology.”

25. Bliss, The Discovery of Insulin. Also mentioned by Don Steiner in his interview by Ling, at University of Chicago, 27 December 1993.

26. Ling, Steiner Interview, 27 December 1993.

27. Shen and Xia, “The Great Leap Forward.”

28. Reardon-Anderson, The Study of Change, 332.

29. Wang, “The Chinese developmental state”; and Wang, “Theory Attached to Practice,” 228–247.

30. Anonymous, “An outline of 1956–1967.”

31. Schneider, “Michurinist Biology.”

32. Jiang, “Crafting Socialist Embryology”.

33. Tsou, “Comprehensive Biology,” 357.

34. Engels, Dialectics of Nature.

35. Cao, “Yidaosu rengong hecheng.” However, there were conflicting testimonies as to whether the Marxist association was an afterthought to justify the project or the ideological driving force of its genesis.

36. Ling’s interview of Li Chung-hsi, 31 July 1993, Beijing. Compare this with the impression of the yellow uranium sample in a meeting in 1955, as told in Wang, “Theory Attached to Practice,” 235.

37. Ling interview of Wang You, Shanghai, 15 July 1993.

38. See note 7 above.

39. Wang, “Saving China through Science.”

40. Reardon-Anderson, The Study of Change. Due to the late-coming of biochemistry, it is not surprising that Reardon-Anderson’s book covers the work in translation, research, and education of inorganic and organic chemistry and chemical industry, and speaks little about biochemistry.

41. Anonymous, “Niu Jingyi.”

42. Ling interview.

43. de Chadarevian, Designs for Life, esp. 98–135.

44. Tsou, “Cytochrome c Modified”; and Tsou, “Exogenous and Endogenous Cytochrome C.”

45. Zou, “Kexue Yanjiu Wushinian.”

46. Wang, “Transnational Science.”

47. Ibid.

48. Xiong and Zou, Zou Chenglu zhuan, 11–15.

49. Israel, Lianda.

50. Needham and Needham, Science Outpost.

51. Su, Science and Technology in China, 158, 172.

52. Ibid., 309.

53. Xiong and Wang, 2005, 22.

54. Cao Tianqin (also Tsao T. C.) obtained his Ph.D. in chemistry from Cambridge University and was a good friend of Joseph Needham. According to Needham, Cao was one of the three close friends by whom he was inspired to study Chinese science. He may have learnt Chinese from Cao at some stage. Needham, Science and Civilization in China, vol. 1. Cao later on wrote a defense in response to Wang You’s challenge to the significance of insulin synthesis pertaining to the synthesis of life.

55. Chen, “Choujian Dongfeng.”

56. Hu et al, “Quanhecheng yidaosu.”

57. Ling interview of Wang Ziya, Shanghai, 19 July 1993.

58. Ibid. Dong feng, its meaning in Chinese being “East Wind” bears with it the direct challenge to beat the “West Wind” of the capitalist west.

59. Zhang, “In Memory of Prof Tianqin Cao,” 507–509.

60. This direction was initially to gain experience in peptide synthetic techniques. Later, it grew to become an industrial production of oxytocin for domestic consumption and export.

61. Yu and Wang, “Wang Yinglai Suozhang.”

62. Xiong and Wang, 2005, 25–27.

63. From archival internal reports of the Institute of Biochemistry, Xiong and Wang, 2005, 27.

64. Xiong and Wang 2005, 28. Anfinsen et al., “The kinetics of formation.”

65. du Vigneaud et al., “The Synthesis of Oxytocin.”

66. Ling, “Revisiting the Insulin Project in China,” 39.

67. It was especially the case during and after the 1960 CAS annual meeting in Shanghai. See Xiong and Wang 2005, 36–38.

68. The Fudan group was led by its president, a famous mathematician, Su Buqing, whose name in Mandarin sounds like “uncountable.” Because the relative junior status of biochemists in Fudan, the news had initially bruised the ego of more senior scientists working at the IBC and probably had convinced some that scientists of the younger generations could indeed contribute in surprising ways. Ling’s interview with Wang Zhiya, Shanghai, 19 July 1993. Also see Xiong and Wang, 2005, 39.

69. Ling’s interview with Wang You, Shanghai, 15 July 1993.

70. Xiong and Wang 2005, p. 55.

71. Ling’s interview with Wang Zhiya, July 1993. Shanghai.

72. See note 61 above.

73. Xiong and Wang, 2005, 40.

74. Ling’s interview with Wang Zhiya, July, 1993. Shanghai.

75. Ibid.

76. Ibid.

77. Xiong and Wang 2005, 31–33. Ling interview with Li Chongxi and Ye Yunhua, 31 July 1993, Beijing.

78. Ling’s interview with Wang Zhiya, 19 July 1993 Shanghai.

79. Ling’s interview with Ye Yunhua, Department of Chemistry, Peking University, Beijing, 31 July 1993.

80. Xiong and Wang 2005, 46.

81. Manning and Wemheuer, Eating Bitterness, 1, 22.

82. Ling’s interview with Wang You, 15 July 1993, Shanghai.

83. See note 78 above.

84. Researchers seized the opportunity also to communicate about previously confused information about each other during the ‘synthesis craze.’ It was also during the Qingdao Conference that the Peking University and the IOC teams realized they were working on insulin molecules of different species–Peking University had chosen sheep insulin and the IOC had picked bovine insulin. They eventually decided to continue the work on insulin of bovine origin, as the Peking University team had only synthesized A6-A10 of sheep insulin so far.

85. Ye Yunhua’s daughter was barely one year old when she left for Shanghai, and Li Chongxi’s daughter was also an infant. Both girls were sent to day care during the years when their parents were away in Shanghai. Ling’s interview with Ye Yunhua, Beijing, 31 July 1993.

86. Galison, Image and Logic, 781–844.

87. Ling’s interview with Gong Yeting, 19 July 1993, and with Du Yucang, 17 July 1993, both in Beijing.

88. Xiong and Wang 2005, 77.

89. Kung et al., “Total Synthesis.”

90. Tsou, “Comprehensive Biology,” 367.

91. Aiming to remove Mao Zedong’s enemies and consolidate his power in the wake of the Lin Biao incident, the Gang of Four took full rein to attack all areas of society. With the slogan, “get rid of the four olds” (chu si jiu’) – old customs, old habits, old culture, and old thinking, it lashed out on anything and anyone deemed not in complete alignment with the Party’s ideology.

92. Ling’s interview with Du, 17 July 1993, and with Niu, 17 July 1993. Both in Shanghai.

93. Xiong and Wang 2005, 87.

94. Ling’s interview with Niu, Shanghai, 17 July 1993.

95. Tsou, Current Biochemistry Research in China.

96. Ling’s interview with Wang Zhiya, Shanghai, 19 July 1993.

97. Niu and Zou earned the most votes. Wang You was opposed to this decision approach and abstained from voting.

98. Katsoyannis, “The Synthesis of the Insulin Chains.”

99. Ling, Steiner Interview, 27 December 1993, University of Chicago.

100. Zahn, “My Journey.”

101. Zhang, “Structure-Function Studies of Insulin.”

102. Zhao, “Cong Shengming Fenzi.”

103. How the chemical protein synthesis itself voiced into the arrangement of science in socialist China was not too different from the housing designs that maintained shanty towns for the urban poor in Rio de Janeiro – both as modifications of recent technologies transmitted from developed world, both redesigned as ‘creole technologies,’ to maintain established local hierarchies and social conditions. Edgerton, The Shock of the Old.

104. See “Making DNA and its becoming an experimental commodity,” in this issue.