Journal of the History of Biology

, Volume 47, Issue 4, pp 547–584 | Cite as

Causes of Aging Are Likely to be Many: Robin Holliday and Changing Molecular Approaches to Cell Aging, 1963–1988

  • Lijing Jiang


Causal complexities involved in biological phenomena often generate ambiguous experimental results that may create epistemic niches for new approaches and interpretations. The exploration for new approaches may foment momentum of larger epistemological shifts, and thereby introduce the possibilities of adopting new technologies. This paper describes British molecular biologist Robin Holliday’s cell aging research from 1963 to the 1980s that transformed from simple hypothesis testing to working on various alternative and integrative approaches designed to deal with complex data. In the 1960s, hoping to use biochemical investigations of cells to settle a debate about whether DNA mutations or protein errors caused aging, Holliday carried out a series of experiments with fruit flies, fungi, and human fibroblast cells. The results seemed to demonstrate that cytoplasmic protein errors caused cell aging. However, other scientists obtained contradictory results and raised issues about potential flaws in Holliday’s experiments. In the 1970s, working as the director of the Genetics Division of the National Institute for Medical Research in Mill Hill, United Kingdom, Holliday relied on available talents of his associates, including computational expertise, to explore alternative hypotheses and approaches. By the early 1980s, they had worked out an epigenetic explanation and had established integrative, evolutionary models of cell aging that incorporated both DNA mutations and protein errors as critical factors. By delineating Holliday’s research path from simply testing hypotheses to integrating multiple factors involved in aging, this paper offers an account of the difficulties in targeting molecular cause in cell aging around the 1970s, whose failures nevertheless opened up an epistemic niche for integration.


Cell aging Cell culture Epigenetics Somatic mutation hypothesis of aging Error catastrophe hypothesis of aging Systems biology 


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This paper benefited tremendously from many discussions with Jane Maienschein and Manfred Laubichler and their comments on the earlier drafts. Early drafts have also benefited from comments at the History of Biogerontology Workshop at Arizona State University in 2011 and the 47th Joint Atlantic Seminar on History of Biology hosted by University of Pennsylvania in 2012. Among others, I would like to especially thank Michael Dietrich, Hannah Landecker, Michel Morange, Hyung Wook Park, Bill Summers, Nathan Comfort, Ben Hurlbut, Susan Lindee, Angela Creager, Crispin Barker, Maria Strecht Almeida, and two anonymous reviewers. Acknowledgements also go to the Embryo Project, the National Science Foundation Dissertation Improvement Grant, and the Chemical Heritage Foundation for their financial support for research, writing, and the 2011 workshop.


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© Springer Science+Business Media Dordrecht 2014

Authors and Affiliations

  1. 1.Department of East Asian Studies & History of Science ProgramPrinceton UniversityPrincetonUSA

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