Constructing Failure: Leonard Hayflick, Biomedicine, and the Problems with Tissue Culture

SUMMARY

By examining the use of tissue culture in post-war American biomedicine, this paper investigates how scientists experience and manage failure. I study how Leonard Hayflick forged his new definition of failure and ways of managing it by refuting Alexis Carrel's definition of failure alongside his theory of the immortality of cultured cells. Unlike Carrel, Hayflick claimed that every vertebrate somatic cell should eventually die, unless it transformed into a tumour cell. This claim defined cell death, which had been a problem leading to a laboratory failure, as a normal phenomenon. On the other hand, permanent life, which had been considered a normal cellular characteristic, became a major factor causing scientific failure, since it implied malignant transformation that scientists hoped to control. Hayflick then asserted that his cell strains and method would partly enable scientists to manage this factor—especially that occurred through viral infection—alongside other causes of failure in routine tasks, including bacterial contamination. I argue that the growing biomedical enterprise fostered this work of Hayflick's, which had repercussions in both his career and the uses of cells in diverse investigations. His redefinition of failure in the age of biomedicine resulted in the broad dissemination of his cells, medium, and method as well as his long struggle with the National Institutes of Health (NIH), which caused his temporarily failed career.

KEYWORDS:

• Tissue culture
• failure
• biomedicine
• Leonard Hayflick
• NIH

Acknowledgements

I thank Hallam Stevens, Lisa Onaga, Harry Wu, Lyle Fearnley, Shirley Sun, Sulfikar Amir, and the anonymous referees for helpful suggestions on my paper. I also appreciate Sheila Dean for her careful editing of the manuscript, as well as Deasoo Kim, Junho Lee, and Lim Bing for detailed scientific comments on contemporary cell culture techniques. In addition, I am grateful for Michael Lynch and Joanna Radin for sending me their papers that contributed to improving my work. Finally, I have to express my gratitude to Leonard Hayflick, who provided me with the valuable materials and recollections regarding his early research. This work was supported by the Start‐Up Grant of Nanyang Technological University [grant number: M4081119.100] and the Academic Research Fund Tier 1 from Singapore's Ministry of Education [grant number: M4011313.100].

Notes

¹According to Hans-Jörg Rheinberger, a sound experimental system produces many unexpected results, or ‘novelties’, which are incorporated in constantly changing scientific research. See Hans-Jörg Rheinberger, Toward a History of Epistemic Things: Synthesizing Proteins in the Test Tube (Stanford, CA: Stanford University Press, 1997). But it is obvious that not all such results engender new lines of investigation.

²For a good example, see Daniel Kevles, The Baltimore Case: The Trial of Politics, Science, and Character (New York: Norton, 1998).

³Lorraine Daston, ‘Scientific Error and the Ethos of Belief’, Social Research, 72 (2005), 1–28; Giora Hon, ‘On Kepler's Awareness of the Problem of Experimental Error’, Annals of Science, 44 (1987), 545–91.

⁴Thomas S. Kuhn, The Structure of Scientific Revolutions (Chicago, IL: University of Chicago Press, 1975), pp. 74–6.

⁵There are numerous publications by these scholars who created the field of STS (Science Technology Studies or Science, Technology, and Society). For some classical books relevant to both social constructivism and this paper, see Harry Collins, Changing Order: Replication and Induction in Scientific Practice (Chicago, IL: University of Chicago Press, 1992); David Gooding, Trevor Pinch, and Simon Schaffer, eds. The Uses of Experiment: Studies in the Natural Sciences (Cambridge: Cambridge University Press, 1993); Bruno Latour and Steve Woolgar, Laboratory Life: The Social Construction of Scientific Facts (Princeton: Princeton University Press, 1979).

⁶Gerald Geison, The Private Science of Louis Pasteur (Princeton: Princeton University Press, 1995), pp. 110–42.

⁷Daniel Kevles, The Baltimore Case: The Trial of Politics, Science, and Character (New York: Norton, 1998).

⁸Giora Hon, ‘Towards a Typology of Experimental Errors: An Epistemological View’, Studies in History and Philosophy of Science, 20 (1989), 469–504; Giora Hon, ‘On Kepler's Awareness of the Problem of Experimental Error’, Annals of Science, 44 (1987), 545–91; Douglas Alchin, ‘Error Types’, Perspectives on Science, 9 (2001), 38–59

⁹Kathryn Olesko, ‘The Meaning of Precision: The Exact Sensibility in Early Nineteenth-Century Germany’, in The Values of Precision, ed. by M. Norton Wise (Princeton: Princeton University Press, 1995), 103–34; Antonio Cadeddu, ‘The Heuristic Function of ‘Error’ in the Scientific Methodology of Louis Pasteur’, History and Philosophy of the Life Sciences, 22 (2000), 3–28; Jutta Schickore, ‘‘Through Thousands of Errors We Reach the Truth’—But How? On the Epistemic Roles of Error in Scientific Practice’, Studies in History and Philosophy of Science, 36 (2005), 539–56.

¹⁰See, for example, the problem of ‘PCR (Polymerase Chain Reaction) hell’, in Kathleen Jordan and Michael Lynch, ‘The Mainstreaming of a Molecular Biological Tool: A Case Study of a New Technique’, in Technology in Working Order: Studies of Work, Interaction, and Technology, ed. by Graham Button (London: Routledge, 1993), pp. 170–4. As a result of this ‘hell’, the authors claim, scientists often produce diverse variations of the original protocol.

¹¹Giora Hon, Jutta Schickore and Friedrich Steinle, ‘Introduction: Mapping ‘Going Amiss’’, in Going Amiss in Experimental Research, ed. by Giora Hon, Jutta Schickore, and Friedrich Steinle (Dordrecht: Springer, 2009), pp. 1–7. I think that this book's perspective is broader than Hon's earlier scholarship on experimental errors. In particular, it successfully deals with ‘errors of nature’ and the problems of the Whiggish interpretation of history.

¹²Hannah Landecker, Culturing Life: How Cells Became Technologies (Cambridge, MA: Harvard University Press, 2007), pp. 107–39; Joan Fujimura, Crafting Science: A Sociohistory of the Quest for the Genetics of Cancer (Cambridge, MA: Harvard University Press), pp. 37–45.

¹³Leonard Hayflick and Paul S. Moorhead, ‘The Serial Cultivation of Human Diploid Cell Strains’, Experimental Cell Research, 25 (1961), 585–621; Frank Macfarlane Burnet, Intrinsic Mutagenesis: A Genetic Approach to Ageing (New York: Wiley, 1974), p. 60.

¹⁴Jan Witkowski, ‘Dr. Carrel's Immortal Cells’, Medical History, 24 (1980), 129–42.

¹⁵Jerry Shay and Woodring Wright, ‘Hayflick, His Limits, and Cellular Ageing’, Nature Reviews Molecular Cell Biology, 1 (2000), 72–6; Geoff Watts, ‘Leonard Hayflick and the Limits of Ageing’, Lancet, 377 (2011), 2075.

¹⁶This has been discussed by some scholars. See Lijing Jiang, ‘Causes of Aging Are Likely to Be Many: Robin Holliday and Changing Molecular Approaches to Cell Aging, 1963–1988’, Journal of the History of Biology, 47 (2014), 547–84 (pp. 555–6, 564–5); Tiago Moreira and Paolo Palladino, ‘Ageing between Gerontology and Biomedicine’, BioSocieties, 4 (2009), 349–65 (pp. 358–9); Tiago Moreira and Paolo Palladino, ‘Squaring the Curve: The Anatomo-Politics of Ageing, Life and Death’, Body and Society, 14 (2008), 21–47; Stephen Hall, Merchants of Immortality (Boston: Houghton Mifflin, 2003), pp. 14–41.

¹⁷Hannah Landecker, Culturing Life: How Cells Became Technologies (Cambridge, MA: Harvard University Press, 2007), pp. 68–106, 166–7.

¹⁸The birth and growth of biomedicine has been extensively studied. See, for example, Jean-Paul Gaudillière, Inventer la biomedicine: La france, l'amérique et la production des savoirs du vivant (1945–1965) (Paris: Découverte, 2002); Peter Keating and Alberto Cambrosio, Biomedical Platforms: Realigning the Normal and the Pathological in Late-Twentieth Century Medicine (Cambridge, MA: MIT Press, 2003); Adele Clarke, Janet Shim, Laura Mamo, Jennifer Fosket and Jennifer Fishman, ‘Biomedicalization: Technoscientific Transformations of U.S. Health, Illness, and U.S. Biomedicine’, American Sociological Review, 68 (2003), 161–94; Ilana Löwy, ‘Historiography of Biomedicine: ‘Bio’, ‘Medicine’, and in between’, Isis, 102 (2011), 116–22; Soraya De Chadarevian, and Harmke Kamminga, eds., Molecularizing Biology and Medicine: New Practices and Alliances 1910s-1970s (Amsterdam: Harwood, 1998); Christopher Lawrence and George Weisz, eds., Greater Than the Parts: Holism in Biomedicine, 1920–1950 (Oxford: Oxford University Press, 1998). Also see Kathleen Jordan and Michael Lynch, ‘The Dissemination, Standardization and Routinization of a Molecular Biological Technique’, Social Studies of Science, 28 (1998), 773–800. Some scholars have discussed these as late‐twentieth‐century phenomena. But Löwy's, Gaudillière's, and others’ accounts show that these phenomena of the late twentieth century had already started to emerge as early as the 1950s.

¹⁹Ross Harrison, ‘Observations on the Living Developing Nerve Fiber’, Proceedings of the Society for Experimental Biology and Medicine, 4 (1906), 140–3; Alexis Carrel, ‘Rejuvenation of Cultures of Tissues’, Journal of the American Medical Association, 57 (1911), 1611.

²⁰Hannah Landecker, Culturing Life: How Cells Became Technologies (Cambridge, MA: Harvard University Press, 2007), pp. 68–92; Shelly McKellar, ‘Innovation in Modern Surgery: Alexis Carrel and Blood Vessel Repair’, in Creating a Tradition of Biomedical Research, ed. by Darwin Stapleton (New York: Rockefeller University Press, 2004), pp. 135–50.

²¹Andrés Horacio Reggiani, God's Eugenicist: Alexis Carrel and the Sociobiology of Decline (New York: Berghahn, 2007), p. 11; David Hamilton, A History of Organ Transplantation (Pittsburgh: University of Pittsburgh Press, 2012), pp. 90–92.

²²Alexis Carrel, ‘A Method for the Physiological Study of Tissues In Vitro’, Journal of Experimental Medicine, 38 (1923), 407–18; Alexis Carrel and Montrose Burrows, ‘Cultivation of Adult Tissues and Organs Outside of the Body’, Journal of the American Medical Association, 55 (1910), 1379–81.

²³Alexis Carrel, ‘Rejuvenation of Cultures of Tissues’, Journal of the American Medical Association, 57 (1911), 1611.

²⁴Ibid.

²⁵Hannah Landecker, Culturing Life: How Cells Became Technologies (Cambridge, MA: Harvard University Press, 2007), pp. 92–106.

²⁶Hannah Landecker, ‘On Beginning and Ending with Apoptosis’, in Remaking Life & Death: Toward an Anthropology of the Biosciences, ed. by Sarah Franklin and Margaret Lock (Santa Fe: School of American Research Press, 2003), pp. 23–59 (p. 43).

²⁷Friedrich Hildebrand, ‘Die Lebensdauer und Vegetationsweise der Pflanzen, ihre Ursache and ihre Entwickelung’, Botanische Jahrbücher für Systematik, Pflanzengeschichte und Pflanzengeographie, 2 (1882), 51–134. Plant cells did not seem to have a strict distinction between soma and germ plasm, which applied to all animal cells, as the German zoologist August Weismann argued. See August Weismann, Essays upon Heredity and Kindred Biological Problems, ed. by Edward B. Poulton, Selmar Schönland and Arthur E. Shipley (Oxford: Clarendon, 1889), pp. 24–32.

²⁸Edwin Conklin, ‘The Size of Organisms and of Their Constituent Parts in Relation to Longevity, Senescence and Rejuvenescence’, in The Harvey Lectures (Philadelphia: Lippincott, 1913), series 8, 252–79; Charles Manning Child, Senescence and Rejuvenescence (Chicago: University of Chicago Press, 1915), p. 186. From today's standpoint, these phenomena could be called regeneration or heterogamy.

²⁹David Hamilton, The Monkey Gland Affair (London: Chatto and Windus, 1986), pp. 8–10.

³⁰Hyung Wook Park, ‘Refiguring Old Age: Shaping Scientific Research on Senescence, 1900–1960’ (PhD Thesis, University of Minnesota, 2009), pp. 38–51.

³¹Alexis Carrel and Montrose Burrows, ‘On the Physicochemical Regulation of the Growth of Tissues’, Journal of Experimental Medicine, 13 (1911), 562–70 (p. 564).

³²Alexis Carrel, ‘Tissue Culture and Cell Physiology’, Physiological Reviews, 4 (1924), 1–20 (p. 6).

³³Pearl Katz, ‘Ritual in the Operating Room’, Ethnology, 20 (1981), 335–50; Stefan Hirschauer argues that surgical sterility is to ‘be understood relative to the patient-body’, whose boundary must be respected, as we usually respect the boundary of other people's body in ‘everyday situation’. See Stefan Hirschauer, ‘The Manufacture of Bodies in Surgery’, Social Studies of Science, 21 (1991), 279–319 (pp. 306–7).

³⁴For example, see Kathleen Jordan and Michael Lynch, ‘The Sociology of a Genetic Engineering Technique: Ritual and Rationality in the Performance of the “Plasmid Prep”’, in The Right Tools for the Job, ed. by Adele Clarke and Joan Fujimura (Princeton: Princeton University Press, 1992), pp. 77–114 (pp. 96–101).

³⁵Pearl Katz, ‘Ritual in the Operating Room’, Ethnology, 20 (1981), 335–50 (pp. 335–6).

³⁶Albert Lansing, ed. Cowdry's Problems of Aging (Baltimore: Williams and Wilkins, 1952), chapters 2 and 3; Hannah Landecker, Culturing Life: How Cells Became Technologies (Cambridge, MA: Harvard University Press, 2007), chapter 2.

³⁷Hannah Landecker, Culturing Life: How Cells Became Technologies (Cambridge, MA: Harvard University Press, 2007), pp. 108–9.

³⁸Harry Collins, Changing Order: Replication and Induction in Scientific Practice (Chicago: University of Chicago Press, 1992), pp. 79–111.

³⁹Hannah Landecker, Culturing Life: How Cells Became Technologies (Cambridge, MA: Harvard University Press, 2007), p. 92.

⁴⁰David Hamilton, The Monkey Gland Affair (London: Chatto and Windus, 1986), pp. 120–42.

⁴¹Hyung Wook Park, ‘Edmund Vincent Cowdry and the Making of Gerontology as a Multidisciplinary Scientific Field in the United States’, Journal of the History of Biology, 41 (2008), 529–72 (pp. 538–40, 546, 551, 557–8); Club for Research on Ageing, Secretary's Report, p. 2, Box 30, Folder Club for Aging 1943 Feb, Nathan W. Shock Papers, Bentley Historical Library, Ann Arbor, Michigan (hereafter NWS).

⁴²Peter Brian Medawar, ‘The Growth, Growth Energy, and Ageing of the Chicken's Heart’, Proceedings of the Royal Society of London. B. Biological Sciences, 129 (1940), 332–55. For a detailed discussion of the significance of this finding in Medawar's research, including his evolution theory of aging, see Hyung Wook Park, ‘Refiguring Old Age: Shaping Scientific Research on Senescence, 1900–1960’ (PhD Thesis, University of Minnesota, 2009), pp. 128–77.

⁴³Peter Brian Medawar, ‘Discussion on Growth and New Growth’, Proceedings of the Royal Society of Medicine, 35 (1942), 590–4 (p. 593).

⁴⁴Peter Krohn, ‘The Nuffield Foundation: Nuffield Gerontological Research Fellowship, Proposals for Research’, pp. 3–6, Box NF AGE1, Folder Age 18 Nuffield Gerontological Research Fellowship, Nuffield Foundation Archive, London, England (hereafter NF). Accessed in September 2006.

⁴⁵‘Professor P. L. Krohn’, 11 October 1966, Box NF AGE1, Folder Age 18 Gerontological Fellowships, NF. On the problems in British research on ageing, see Tiago Moreira and Paolo Palladino, ‘Ageing between Gerontology and Biomedicine’, BioSocieties, 4 (2009), 349–65 (pp. 357–8); Moira Martin, ‘Medical Knowledge and Medical Practice: Geriatric Medicine in the 1950s’, Social History of Medicine, 8 (1995), 443–61.

⁴⁶Peter Krohn, ‘The Nuffield Foundation: Nuffield Gerontological Research Fellowship, Proposals for Research’, pp. 1–6, Box NF AGE1, Folder Age 18 Nuffield Gerontological Research Fellowship, NF.

⁴⁷According to Tiago Moreira and Paolo Palladino, gerontology forged a domain rather different from biomedicine. See Tiago Moreira and Paolo Palladino, ‘Ageing between Gerontology and Biomedicine’, BioSocieties, 4 (2009), 349–65.

⁴⁸Peter Keating and Alberto Cambrosio, ‘Does Biomedicine Entail the Successful Reduction of Pathology to Biology?’ Perspectives in Biology and Medicine, 47 (2004), 357–71.

⁴⁹The emergence of ‘laboratory medicine’ has been studied by several historians. See, for example, Andrew Cunningham and Perry Williams, eds. The Laboratory Revolution in Medicine (Cambridge: Cambridge University Press, 1992); Gerald Geison, The Private Science of Louis Pasteur (Princeton: Princeton University Press, 1995).

⁵⁰Timothy Lenoir and Marguerite Hays, ‘The Manhattan Project for Biomedicine’, in Controlling Our Destinies: Historical, Philosophical, Ethical, and Theological Perspectives on the Human Genome Project, ed. by Phillip Sloan (Notre Dame: University of Notre Dame Press, 2000), pp. 29–62.

⁵¹Jean-Paul Gaudillière, Inventer la biomedicine: La france, l'amérique et la production des savoirs du vivant (1945-1965) (Paris: Découverte, 2002); Adele Clarke, Janet Shim, Laura Mamo, Jennifer Fosket and Jennifer Fishman, ‘Biomedicalization: Technoscientific Transformations of U.S. Health, Illness, and U.S. Biomedicine’, American Sociological Review, 68 (2003), pp. 161–94; Ilana Löwy, ‘Historiography of Biomedicine: ‘Bio’, ‘Medicine’, and in between’, Isis, 102 (2011), pp. 116–22.

⁵²David Hamilton, A History of Organ Transplantation (Pittsburgh: University of Pittsburgh Press, 2012), 173–253; Thomas Schlich, The Origins of Organ Transplantation: Surgery and Laboratory Science 1880-1930 (Rochester: University of Rochester Press, 2010).

⁵³Hannah Landecker, Culturing Life: How Cells Became Technologies (Cambridge, MA: Harvard University Press, 2007), pp. 155–6; H. Moser, ‘Modern Approaches to the Study of Mammalian Cells in Culture’, Experientia, 16 (1960), pp. 385–98 (p. 393); Joanna Radin, ‘Latent Life: Concepts and Practices of Human Tissue Preservation in the International Biological Program’, Social Studies of Science, 43 (2013), 484–508.

⁵⁴Indeed, graduate training in the life sciences had been consistently expanding in America after the late nineteenth century. See Gerald Geison, ‘International Relations and Domestic Elites in American Physiology, 1900-1940’, in Physiology in American Context, 1850-1940, ed. by Gerald Geison (Bethesda: American Physiological Society, 1987), pp. 115–54 (pp. 136–47); Philip Pauly, Biologists and the Promise of American Life (Princeton: Princeton University Press, 2000), pp. 126–44; Jane Maienschein, ‘Whitman at Chicago: Establishing a Chicago Style of Biology?’ in The American Development of Biology, ed. by Ronald Rainger, Keith R. Benson and Jane Maienschein (New Brunswick: Rutgers University Press, 1988), pp. 151–82 (pp. 165–8).

⁵⁵William Scherer and Alicia Hoogasian, ‘Preservation at Subzero Temperatures of Mouse Fibroblasts (strain L) and Human Epithelial Cells (strain HeLa)’, Proceedings of the Society for Experimental Biology and Medicine, 87 (1954), 480–7.

⁵⁶Hannah Landecker, Culturing Life: How Cells Became Technologies (Cambridge, MA: Harvard University Press, 2007), pp. 133–4.

⁵⁷Alexis Carrel and Montrose Burrows, ‘Cultivation of Adult Tissues and Organs Outside of the Body’, Journal of the American Medical Association, 55 (1910), 1379–81 (p. 1381); Joan Fujimura, Crafting Science: A Sociohistory of the Quest for the Genetics of Cancer (Cambridge, MA: Harvard University Press), pp. 37–45.

⁵⁸Angela Creager and Jean-Paul Gaudillière, ‘Experimental Arrangements and Technologies of Visualization’, in Heredity and Infection: The History of Disease Transmission, ed. by Jean-Paul Gaudillière and Ilana Löwy (London: Routledge, 2001), pp. 203–41; Joan Fujimura, Crafting Science: A Sociohistory of the Quest for the Genetics of Cancer (Cambridge, MA: Harvard University Press), pp. 45–67.

⁵⁹Angela Creager and Jean-Paul Gaudillière, ‘Experimental Arrangements and Technologies of Visualization’, in Heredity and Infection: The History of Disease Transmission, ed. by Jean-Paul Gaudillière and Ilana Löwy (London: Routledge, 2001), pp. 203–41 (pp. 224–9).

⁶⁰Jean-Paul Gaudillière, ‘The Molecularization of Cancer Etiology in the Postwar United States’, in Molecularizing Biology and Medicine, ed. by Soraya de Chadarevian and Harmke Kamminga (Amsterdam: Harwood, 1998), pp. 139–70.

⁶¹Hannah Landecker, Culturing Life: How Cells Became Technologies (Cambridge, MA: Harvard University Press, 2007), pp. 159–62; Rebecca Skloot, The Immortal Life of Henrietta Lacks (New York: Broadway, 2011).

⁶²Joan Fujimura, Crafting Science: A Sociohistory of the Quest for the Genetics of Cancer (Cambridge, MA: Harvard University Press), pp. 41–5.

⁶³Joe Hin Tjio and Albert Levan, ‘The Chromosome Number of Man’, Hereditas, 42 (1956), 1–6.

⁶⁴Raymond Parker, LaRoy Castor and Ernest McCulloch, ‘Altered Cell Strains in Continuous Culture’, Special Publications of the New York Academy of Sciences, 5 (1957), 303–13 (p. 305).

⁶⁵Jerome Syverton, ‘Comparative Studies of Normal and Malignant Human Cells in Continuous Culture’, Special Publications of the New York Academy of Sciences, 5 (1957), 333–40 (p. 339).

⁶⁶Joe Hin Tjio and Theodore Puck, ‘Genetics of Somatic Mammalian Cells. II. Chromosomal Constitution of Cells in Tissue Culture’, Journal of Experimental Medicine, 108 (1958), 259–68.

⁶⁷Theodore Puck, Steven Cieciura and Arthur Robinson, ‘Genetics of Somatic Mammalian Cells III. Long-Term Cultivation of Euploid Cells from Human and Animal Subjects’, Journal of Experimental Medicine, 108 (1958), 945–56 (p. 952).

⁶⁸H. Moser, ‘Modern Approaches to the Study of Mammalian Cells in Culture’, Experientia, 16 (1960), 385–98 (p. 392).

⁶⁹C. Pomerat, L. Hayflick, M. Fernandes and S. Kent, ‘Irradiation of Cells in Tissue Culture III. Measurement of Injury by pH Changes and Cytopathology in Test Tube Cultures’, Zeitschrift für Zellforchung, 47 (1958), 245–50.

⁷⁰Leonard Hayflick and Warren Stinebring, ‘Intracellular Growth of Pleuropneumonialike Organisms (PPLO) in Tissue Culture and In Ovo’, Annals of the New York Academy of Sciences, 79 (1960), 433–49.

⁷¹Leonard Hayflick, ‘Decontaminating Tissue Cultures Infected with Pleuropneumonia-like Organisms’, Nature, 185 (1960), 783–4.

⁷²Leonard Hayflick and Paul S. Moorhead, ‘The Serial Cultivation of Human Diploid Cell Strains’, Experimental Cell Research, 25 (1961), pp. 585–621 (p. 585).

⁷³GSA's official record shows that Hayflick joined the society in 1964. For gerontological literature in the 1950s and the 1960s discussing immortality and rejuvenation, see, for example, Albert Lansing, ed., Cowdry's Problems of Aging (Baltimore: Williams and Wilkins, 1952), esp. chapter 3; Bernard Strehler, Time, Cells, and Aging (New York: Academic Press, 1962), pp. 33–40.

⁷⁴See Tiago Moreira and Paolo Palladino, ‘Ageing between Gerontology and Biomedicine’, BioSocieties, 4 (2009), 349–65 (pp. 358–9). Hayflick stated, ‘I did not consider myself a biogerontologist when I published my paper in 1961. I am not certain but I think that it was in about 1964 that I joined the GSA [Gerontological Society of America]. In the early 1960s researchers on aging were not considered to be serious scientists. The scientific mainstream was not interested in aging and ridiculed those who were. For a young scientist like me at that time to admit to be doing research on aging was equivalent to committing academic suicide’. Leonard Hayflick, email message to author, February 5, 2014. Published with Dr. Hayflick's kind permission.

⁷⁵Leonard Hayflick and Paul S. Moorhead, ‘The Serial Cultivation of Human Diploid Cell Strains’, Experimental Cell Research, 25 (1961), 585–621 (p. 619).

⁷⁶Ibid., p. 598.

⁷⁷Ibid., p. 598.

⁷⁸Ibid., p. 613.

⁷⁹Ibid., p. 616.

⁸⁰For the experimental rats produced in the Wistar Institute, see Bonnie Tocher Clause, ‘The Wistar Rat as a Right Choice’, Journal of the History of Biology, 26 (1993), 329–49.

⁸¹Leonard Hayflick, ‘The Limited In Vitro Lifetime of Human Diploid Cell Strains’, Experimental Cell Research, 37 (1965), 614–36 (p. 616).

⁸²Leonard Hayflick, and Paul S. Moorhead, ‘The Serial Cultivation of Human Diploid Cell Strains’, Experimental Cell Research, 25 (1961): 585–621 (p. 598).

⁸³Ibid., p. 612.

⁸⁴Leonard Hayflick, ‘Hayflick's Reply’, Science, 202 (1978), 128–36 (p. 131).

⁸⁵I do not argue that Hayflick prevented ‘experimenters’ regress’. But Hayflick certainly lessened the problem as he circulated his cells and method in the tissue culture community. As STS scholars have shown, the regress can be managed through scientists’ interactions within their community. See Steven Shapin and Simon Shaffer, Leviathan and the Air-Pump: Hobbes, Boyle, and the Experimental Life (Princeton: Princeton University Press, 1985), pp. 225–82.

⁸⁶Leonard Hayflick and Paul S. Moorhead, ‘The Serial Cultivation of Human Diploid Cell Strains’, Experimental Cell Research, 25 (1961), 585–621 (p. 619).

⁸⁷Leonard Hayflick, ‘Hayflick's Reply’, Science, 202 (1978), 128–36 (p. 131).

⁸⁸Leonard Hayflick, ‘Decontaminating Tissue Cultures Infected with Pleuropneumonia-like Organisms’, Nature, 185 (1960), 783–4.

⁸⁹G. T. M. Cummins and J. D. Ross, ‘Colonial Study of Cells from the Human Female Genitourinary Tract’, Cancer Research, 23 (1963), 1581–92 (p. 1589).

⁹⁰Nelly Auersperg, ‘Long-Term Cultivation of Hypodiploid Human Tumor Cells’, Journal of the National Cancer Institute, 32 (1964), 135–63 (p. 147).

⁹¹Jean Ferguson and Ann Wansbrough, ‘Isolation and Long-term Culture of Diploid Mammalian Cell Lines’, Cancer Research, 22 (1962), 556–62; Frank Ruddle, ‘Chromosome Variation in Cell Populations Derived from Pig Kidney’, Cancer Research, 21 (1961), 885–99.

⁹²Robert Krooth, Margery Shaw and Barbara Campbell, ‘A Persistent Strain of Diploid Fibroblasts’, Journal of the National Cancer Institute, 32 (1964), 1031–44.

⁹³Robert Krooth, ‘The Future of Mammalian Cell Genetics’, New Directions in Human Genetics: A Symposium. Birth Defects Original Article Series, 1 (1965), 21–56 (p. 26). Krooth's view was partially correct, because some tumour cells in vitro did stop growing and die naturally. See Joan Fujimura, Crafting Science: A Sociohistory of the Quest for the Genetics of Cancer (Cambridge, MA: Harvard University Press), pp. 23, 41, 246–7.

⁹⁴Leonard Hayflick, ‘The Limited In Vitro Lifetime of Human Diploid Cell Strains’, Experimental Cell Research, 37 (1965), 614–36 (p. 628). This belief became stronger over time. See Leonard Hayflick, ‘Immortality’, Science, 225 (1984), 268.

⁹⁵Leonard Hayflick, ‘Discussion’, National Cancer Institute Monograph, 7 (1961), 63–7 (p. 64).

⁹⁶For historical literature on model organisms for experimental research, see Robert Kohler, Lords of the Fly: Drosophila Genetics and Experimental Life (Chicago: University of Chicago Press, 1994); Karen Rader, Making Mice: Standardizing Animals for American Biomedical Research (Princeton: Princeton University Press, 2004); Angela Creager, The Life of a Virus: Tobacco Mosaic Virus as an Experimental Model, 1930–1965 (Chicago: University of Chicago Press, 2002); Rachel Ankeny, ‘Wormy Logic: Model Organisms as Case-Based Reasoning’, in Science without Laws: Model Systems, Cases, and Exemplary Narratives, ed. by Angela Creager, Elizabeth Lunbeck and M. Norton Wise (Durham: Duke University Press, 2007), 46–58.

⁹⁷Leonard Hayflick and Paul S. Moorhead, ‘The Serial Cultivation of Human Diploid Cell Strains’, Experimental Cell Research, 25 (1961), 585–621 (p. 613).

⁹⁸Angela Creager, The Life of a Virus: Tobacco Mosaic Virus as an Experimental Model, 1930–1965 (Chicago: University of Chicago Press, 2002), p. 5; Rachel Ankeny, ‘Wormy Logic: Model Organisms as Case-Based Reasoning’, in Science without Laws: Model Systems, Cases, and Exemplary Narratives, ed. by Angela Creager, Elizabeth Lunbeck and M. Norton Wise (Durham: Duke University Press, 2007), 46–58 (pp. 46–47).

⁹⁹From 1961 to 1965, seven among the 164 papers citing Hayflick raised a question on his claim.

¹⁰⁰Robert Kohler, Lords of the Fly: Drosophila Genetics and Experimental Life (Chicago: University of Chicago Press, 1994); Karen Rader, Making Mice: Standardizing Animals for American Biomedical Research (Princeton: Princeton University Press, 2004).

¹⁰¹Karen Rader, Making Mice: Standardizing Animals for American Biomedical Research (Princeton: Princeton University Press, 2004), pp. 135–60. Hayflick did not seem to create a moral economy of researchers as Morgan did. Hayflick's work was similar to Little's, but the two are not the same. In addition to what I discuss in the next section, the two were quite different, especially with regard to bioethical problems. Little's mice provoked no controversy on bioethics, while Hayflick's cells did. Whereas antivivisectionists did not care much about the mice which were regarded as a pest, Hayflick's cells, due to their origin from aborted human foetuses, became a subject of concern among anti-abortionists and the Catholics. See Meredith Wadman, ‘Cell Division’, Nature, 498 (2013), 422–6 (p. 425).

¹⁰²Leonard Hayflick, ‘Discussion’, National Cancer Institute Monograph, 7 (1961), 63–7 (p. 63); Leonard Hayflick, Frank Perkins and Robert Stevenson, ‘Characterization and Uses of Human Diploid Cell Strains’, Nature, 200 (1963), 1161; Frank Perkins and Leonard Hayflick, ‘Cell Cultures’, Science, 155 (1967), 723–4.

¹⁰³Nicholas Wade, ‘Hayflick's Tragedy’, Science, 192 (1976), 125–7 (p. 125). The earliest paper mentioning the purchase of Hayflick's cells is Maurice Mufson, William Ludwig, Harvey James, Lloyd Gauld, Judith Rourke, Jacob Holper and Robert Chanock, ‘Effect of Neutralizing Antibody on Experimental Rhinovirus Infection’, Journal of the American Medical Association, 186 (1963), 578–84 (p. 580).

¹⁰⁴Hayflick's second paper on cellular lifespan, ‘The limited in vitro lifetime of human diploid cell strains’ (1965) was cited more than 4500 times. Data from Google Scholar, accessed in September 2014.

¹⁰⁵Henry Bloom, Ben Forsyth, Camp Lejeune, Karl Johnson and Robert Chanock, ‘Relationship of Rhinovirus Infection to Mild Upper Respiratory Disease’, Journal of the American Medical Association, 186 (1963), 38–45 (p. 38).

¹⁰⁶John Pearson, James Duff, Naomi Gearinger and Mary Robbins, ‘Growth Characteristics of Three Agents of the Psittacosis Group in Human Diploid Cell Cultures’, Journal of Infectious Diseases, 115 (1965), 49–58 (p. 49).

¹⁰⁷See, for example, H. Chandra and D. Hungerford, ‘An Aberrant Autosome (13-15) in a Human Female and Her Father, Both Apparently Normal’, Cytogenetics, 2 (1963), 34–41.

¹⁰⁸See, for example, J. R. E. Fraser and J. McCall, ‘Culture of Synovial Cells In Vitro’, Annals of the Rheumatic Diseases, 24 (1965), 351–9 (p. 358); Ernest Chu, ‘Chromosomal Stabilization of Cell Strains’, National Cancer Institute Monograph, 7 (1961), 55–62 (p. 58); William Mellman, ‘The Chromosome Analysis of Cultured Human Cells’, Proceedings of the Royal Society of Medicine, 56 (1963), 1064–6. In these years, only five articles cited Hayflick and Moorhead's 1961 paper with regard to research on ageing. Among them, only two were original research papers. See Virginia Childs and Marvin Legator, ‘Lactic Dehydrogenase Isozymes in Diploid and Heteroploid Cells’, Life Sciences, 4 (1965), 1643–50; M. Soukupová, E. Holečková and O. Cinnerová, ‘Behaviour of Explanted Kidney Cells from Young, Adult and Old Rats’, Gerontologia, 11 (1965), 141–52. Hayflick's idea was considered useful for gerontologists only after the publication of his 1965 paper.

¹⁰⁹Hilary Koprowski, ‘Live Poliomyelitis Virus Vaccines: Present Status and the Problems for the Future’, Journal of the American Medical Association, 178 (1961), 1151–5 (p. 1154).

¹¹⁰John Foley and Byron Aftonomos, ‘Growth of Human Breast Neoplasm in Cell Culture’, Journal of the National Cancer Institute, 34 (1965), 217–29 (p. 217).

¹¹¹Juan Embil and Ruth Faulkner, ‘Human Diploid Cell Strains and Their Susceptibility to Viruses’, Canadian Journal of Public Health, 55 (1964), 111–6 (p. 111).

¹¹²William Mellman, ‘The Chromosome Analysis of Cultured Human Cells’, Proceedings of the Royal Society of Medicine, 56 (1963), 1064–6 (p. 1065).

¹¹³M. R. S. Iyengar, ‘Cell Systems for Production of Viral Vaccines’, in Tissue Culture: Proceedings of the Seminar Held in Baroda, ed. by C. V. Ramakrishnan (The Hague: Junk, 1965), 217–24 (p. 218).

¹¹⁴Robert Krooth, ‘The Future of Mammalian Cell Genetics’, New Directions in Human Genetics: A Symposium. Birth Defects Original Article Series, 1 (1965), 21–56 (p. 25).

¹¹⁵Giora Hon, ‘On Kepler's Awareness of the Problem of Experimental Error’, Annals of Science, 44 (1987), 545–91; Kathryn Olesko, ‘The Meaning of Precision: The Exact Sensibility in Early Nineteenth-Century Germany’, in The Values of Precision, ed. by M. Norton Wise (Princeton: Princeton University Press, 1995), 103–34; Jerome Ravetz, Scientific Knowledge and Its Social Problems (Oxford: Clarendon Press, 1971), 94–101.

¹¹⁶Jerome Ravetz, Scientific Knowledge and Its Social Problems (Oxford: Clarendon Press, 1971), 94–101.

¹¹⁷Leonard Hayflick, Pat Jacobs and Frank Perkins, ‘A Procedure for the Standardization of Tissue Culture Media’, Nature, 204 (1964), 146–7.

¹¹⁸For a paper stressing plating efficiency and permanent cultivability as the reasons for choosing heteroploid lines, see L. De Carli, J. Maio, F. Nuzzo and A. Benerecetti, ‘Cytogenetic Studies with Alkaline Phosphate in Human Heteroploid Cells’, Cold Spring Harbor Symposia on Quantitative Biology, 29 (1964), 223–31. From 1961 to 1965, there were only two such papers.

¹¹⁹David White, ed., A Postgraduate Course in Cell Culture (Parkville, Victoria, Australia: The Cell Culture Society of Victoria, 1963), Experiment 11.

¹²⁰David White, ‘Principles of Cell Culture’, in A Postgraduate Course in Cell Culture, ed. by David White (Parkville, Victoria, Australia: The Cell Culture Society of Victoria, 1963), pp. 171–81 (p. 171).

¹²¹Ibid., p. 175.

¹²²Ernest Chu, ‘Chromosomal Stabilization of Cell Strains’, National Cancer Institute Monograph, 7 (1961), 55–62 (pp. 59–60).

¹²³J. P. Jacobs, C. Jones and J. Baille, ‘Characteristics of a Human Diploid Cell Designated MRC-5’, Nature, 227 (1970), 168–70.

¹²⁴Hannah Landecker, ‘On Beginning and Ending with Apoptosis’, in Remaking Life & Death: Toward an Anthropology of the Biosciences, ed. by Sarah Franklin and Margaret Lock (Santa Fe: School of American Research Press, 2003), pp. 23–59 (pp. 46–52).

¹²⁵See Box 8, Folder Correspondence Hayflick, NWS. Compare Bernard Strehler, Time, Cells, and Aging (New York: Academic Press, 1962) with Bernard Strehler, Time, Cells, and Aging. 2nd edn (New York: Academic Press, 1977), pp. 37–55.

¹²⁶Andrés Horacio Reggiani, God's Eugenicist: Alexis Carrel and the Sociobiology of Decline (New York: Berghahn, 2007); Jan Witkowski, ‘Dr. Carrel's Immortal Cells’, Medical History, 24 (1980), 129–42.

¹²⁷J. W. Schriver, ‘Investigation of activities relating to the storage, distribution, and sale of human diploid cell strains, WI-38 and WI-26. Working papers’ (Division of Management Survey and Review, National Institutes of Health, Bethesda, MD, 1976). I have tried to acquire this document from the National Archives and Records Administration and the NIH Library. But neither of them was able to locate the document in their collection.

¹²⁸Nicholas Wade, ‘Hayflick's Tragedy’, Science, 192 (1976), 125–7 (p. 125).

¹²⁹In Hayflick's methodology, the passage number of a cell approximately equals its total number of divisions after its removal from the foetus.

¹³⁰Leonard Hayflick, ‘Hayflick's Reply’, Science, 202 (1978), 128–36 (p. 129).

¹³¹Ibid., p. 131.

¹³²Constance Holden, ‘Hayflick Case Settled’, Science, 215 (1982), 271.

¹³³Philip M. Boffey, ‘The Fall and Rise of Leonard Hayflick, Biologist Whose Fight with U.S. Seems Over’, The New York Times, 19 January 1982.

¹³⁴Bernard Strehler, et al., ‘Hayflick-NIH Settlement’, Science, 215 (1982), 240, 242.

¹³⁵For a review of the politico-economic problems and ownership issue in bio-industry, see Arnold Thackray, ed., Private Science: Biotechnology and the Rise of the Molecular Sciences (Philadelphia: University of Pennsylvania Press, 1998). For the rise of the biogerontology business, see Stephen Hall, Merchants of Immortality (Boston: Houghton Mifflin, 2003).

¹³⁶Zhores Medvedev, ‘Hayflick's Tragedy’, Science, 192 (1976), 1182-4 (p. 1182); Meredith Wadman, ‘Cell Division’, Nature, 498 (2013), 422-6 (p. 423).

¹³⁷Daniel Kevles, The Baltimore Case: The Trial of Politics, Science, and Character (New York: Norton, 1998), pp. 96–117. While Kevles dealt with the problems in the 1980s, these problems or their precursors already existed in the 1960s and the 1970s.

¹³⁸I examined Medical Cytogenetics and Cell Culture (1977), Animal Cell Culture Methods (1970), Animal Tissue Culture (1972), Methods in Enzymology, Volume LVIII: Cell Culture (1979), and Cell and Tissue Culture (1975).

¹³⁹Jean Priest, Medical Cytogenetics and Cell Culture (Philadelphia: Lea and Febiger, 1977), p. 274.

¹⁴⁰G. D. Wasley and John May, Animal Cell Culture Methods (Oxford: Blackwell, 1970), pp. 92, 97.

¹⁴¹Kathleen Jordan and Michael Lynch, ‘The Sociology of a Genetic Engineering Technique: Ritual and Rationality in the Performance of the “Plasmid Prep”’, in The Right Tools for the Job, ed. by Adele Clarke and Joan Fujimura (Princeton: Princeton University Press, 1992), pp. 77–114 (pp. 96–101); Harry Collins, Tacit and Explicit Knowledge (Chicago: University of Chicago Press, 2010).

¹⁴²Cyrus Mody, ‘A Little Dirt Never Hurt Anyone: Knowledge-Making and Contamination in Materials Science’, Social Studies of Science, 31 (2001), 7–36.

¹⁴³Barbara Rawlings, ‘Coming Clean: The Symbolic Use of Clinical Hygiene in a Hospital Sterilizing Unit’, Sociology of Health and Illness, 11 (1989), 279–93 (pp. 289, 292).

¹⁴⁴Adele Clarke and Joan Fujimura, eds., The Right Tools for the Job: At Work in Twentieth-Century Life Sciences (Princeton: Princeton University Press, 1992).