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The power of partnerships: the Liverpool school of butterfly and medical genetics

Published online by Cambridge University Press:  29 April 2014

Department of Science and Technology in Society, Virginia Polytechnic Institute and State University, Blacksburg, VA, USA. Email:


From the 1950s to the 1970s, a group of physician–researchers forming the ‘Liverpool school’ made groundbreaking contributions in such diverse areas as the genetics of Lepidoptera and human medical genetics. The success of this group can be attributed to the several different, but interconnected, research partnerships that Liverpool physician Cyril Clarke established with Philip Sheppard, Victor McKusick at Johns Hopkins University, the Nuffield Foundation, and his wife Féo. Despite its notable successes, among them the discovery of the method to prevent Rhesus haemolytic disease of the newborn, the Liverpool School began to lose prominence in the mid-1970s, just as the field of medical genetics that it had helped pioneer began to grow. This paper explores the role of partnerships in making possible the Liverpool school's scientific and medical achievements, and also in contributing to its decline.

Research Article
Copyright © British Society for the History of Science 2014 

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1 Mollison, P.L. and Walker, W., ‘Controlled trials of the treatment of haemolytic disease of the newborn’, The Lancet (1952) 259, pp. 429433Google Scholar; and Reali, Giorgio, ‘Forty years of anti-D immunoprophylaxis’, Blood Transfusion (2007) 5, pp. 36Google Scholar.

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17 Clarke to Sheppard, 1 June 1953, APS, Ms. Coll. No 65, Series I, Box 4, folder: Clarke, Cyril A, #2.

18 Over the years that followed, similar studies sought possible relationships between blood-group markers and other disorders such as gastric ulcer and mitral stenosis. APS, Ms. Coll. No 65, Series I, Box 18, folder: The Nuffield Foundation #1 , 1954–61.

19 Clarke to Sheppard, 1 June 1954, APS, Ms. Coll. No 65, Series I, Box 5, folder: Clarke, Cyril A. #1.

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25 C.A. Clarke, draft of a history of the University of Liverpool Department of Medicine, 1958–1972, ULA, Cyril Astley Clarke papers, D36/B.21.

26 Some examples are Clarke, C.A., ‘Prevention of Rh-haemolytic disease’, British Medical Journal (1967) 4, pp. 712CrossRefGoogle ScholarPubMed; and Clarke, Cyril A. and Finn, Ronald, ‘Prevention of Rh-hemolytic disease: background of the Liverpool work’, American Journal of Obstetrics and Gynecology (1977) 127, pp. 538539CrossRefGoogle ScholarPubMed.

27 For example, some Rh-negative mothers who are also blood type O will not develop antibodies against an Rh-positive foetus if that foetus is blood group A or B but will when the foetus is blood group O like themselves. Levine, Philip, ‘Serological factors as possible causes in spontaneous abortions’, Journal of Heredity (1943) 34, pp. 7180Google Scholar; Nevanlinna, H.R. and Vainio, T., ‘The influence of mother–child ABO incompatibility on Rh immunisation’, Vox Sanguinis (1956) 1, pp. 2634Google Scholar.

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30 Sheppard to the Nuffield Foundation, 12 February 1959, APS, Ms. Coll. No 65, Series I, Box 18, folder: The Nuffield Foundation #1, 1954–61.

31 These include Zimmerman, David R., Rh: The Intimate History of a Disease and Its Conquest, New York: Macmillan, 1973Google Scholar; and Weatherall, David, ‘Cyril Clarke and the prevention of Rhesus haemolytic disease of the newborn’, British Journal of Haematology (2012) 157, pp. 4146Google Scholar.

32 Another group – Vincent Freda, John Gorman and William Pollack – working in the New York City area, used the same anti-D intervention but based it on a theoretical premise, different from that of the Liverpool group, that large doses of antibody, passively administered, could depress the ability of a woman's immune system to detect and respond to the presence of Rh antigen. They achieved the same successful clinical result shortly after that of the Liverpool group.

33 ‘Top of the decade’, Time (26 December 1969) 94, p. 31. The prevention of Rh disease was included with such advances as the birth-control pill, the polio vaccine, kidney transplantation and dialysis, and human heart transplantation.

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37 The Moore clinic was a direct descendent of a clinic that originally was dedicated to the study and treatment of venereal disease, particularly syphilis. Once penicillin was found to be a successful treatment for syphilis, the clinic enlarged its focus to include an emphasis on other types of chronic disease and, under McKusick's direction, included the genetic components of such diseases. When he took over the clinic, McKusick renamed it in honor of his predecessor, Moore, Joseph Earle. Harvey, A. McGehee, McKusick, Victor A. and Stobo, John D., Osler's Legacy: The Department of Medicine at Johns Hopkins 1889–1989, Baltimore, MD: Department of Medicine, The Johns Hopkins University, 1990, pp. 8385Google Scholar.

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39 Richard B. McConnell, interview by author, 6 May 1998.

40 McKusick to McConnell, 6 October 1957, Victor McKusick Collection, Alan Mason Chesney Medical Archives, Johns Hopkins Medical Institutions (subsequently CMA), Box 110B5-6 – Victor McKusick Papers: Old Moore Clinic Fellows, A-G-1960s, folder: Evans, David Alan Price.

41 McConnell to McKusick, 31 October 1957 (copy provided to the author by McConnell). The original letter is archived in CMA, Box 110B5-6 – Victor McKusick Papers: Old Moore Clinic Fellows, A-G-1960s, folder: Evans, David Alan Price.

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50 Clarke, op. cit. (25).

51 News and Notes, ‘Medical genetics at Liverpool’, The Lancet (1963) 282 (originally volume 2), p. 1074.

52 Other contributors to the building were the North West Cancer Research Fund (which supported a cytogenetics unit and an immunochemistry unit) and the university itself, which provided funds for a facility housing animals for research and for a Department of Radiodiagnosis.

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56 Nuffield Grant, ULA, Cyril Astley Clarke papers, D36/D.18 and D.19.

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58 See, for example, Pycior, Helena M., Slack, Nancy G. and Abir-Am, Pnina G. (eds.), Creative Couples in the Sciences, New Brunswick: Rutgers University Press, 1996Google Scholar; and Lykknes, Annette, Opitz, Donald L. and Van Tiggelen, Brigitte (eds), For Better or For Worse? Collaborative Couples in the Sciences, Basel: Birkhäuser, 2012Google Scholar.

59 Because she disliked her childhood nickname, Peggy, she and her mother selected another nickname, Féo, found in a novel. It became the name she used from her teen years throughout the rest of her life.

60 Weatherall, op. cit. (29), p. 75.

61 Miles Clarke, Stephen Clarke and Charles Clarke, interviews by the author, 16 September 2010.

62 McConnell, op. cit. (39).

63 Zallen, D.T., Christie, D.A. and Tansey, E.M. (eds.), The Rhesus Factor and Disease Prevention, Wellcome Witnesses to Twentieth Century Medicine, vol. 22, London: The Wellcome Trust Centre for the History of Medicine, 2004, p. 36Google Scholar.

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65 His findings, that the proportion of the three forms had not changed over the intervening years, were at odds with what had been observed in the Cothill colony near Oxford. Clarke, C.A., Clarke, F.M.M. and Owen, D.F., ‘Gene frequencies in an artificial Wirral colony of the scarlet tiger moth (Panaxia dominula L.) in the four years after its rediscovery, 1989–1992’, The Linnean (1993) 9, pp. 1820Google Scholar.

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69 F.M.M. Clarke, ‘Some elementary statistics for the entomologist’, a series of six articles in The Entomologist on the meaning of statistical significance (April 1963) 96, pp. 73–76; the chi-square test (September 1963) 96, pp. 218–223; simple tests for genetic linkage (May 1964) 97, pp. 113–120; the Hardy–Weinberg law (January 1965) 98, pp. 7–9; the normal distribution (May 1967) 100, pp. 128–131; and the analysis of variance (July 1967) 100, pp. 181–183. The first of these papers appeared after the publication of Clarke's Genetics for the Clinician book, op. cit. (57), in which all of these topics are discussed. It appears likely that Féo Clarke worked with her husband on that book and then took the opportunity, from the knowledge she gained about statistics, to explain the relevant concepts to entomologists.

70 Clarke, C.A., Clarke, F.M.M. and Sheppard, P.M., ‘Mimicry and Papilio memnon: some breeding results from England’, Malayan Nature Journal (1968) 21, pp. 201219Google Scholar; Clarke, F.M.M., ‘Papilio memnon: a tailed “butlerianus” in the Malay Peninsula’, Malayan Nature Journal (1978) 30, pp. 551553Google Scholar.

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73 Laurence Cook, Sally Thompson and Angela Urion, personal communications with the author.

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76 C.A. Clarke to David Zimmerman, 11 September 1973. A copy of this letter is inserted into Zimmerman's book, op. cit. (31), held by the library of the Royal College of Physicians in London. In that letter, Clarke states that an independent confirmation of Féo's role appeared in a book which was already in press before the Scientific American article came out: Jewkes, J., Sawers, D. and Stillerman, R., The Sources of Invention, 2nd edn, New York: W.W. Norton & Company, 1969, pp. 348351Google Scholar. However, it appears from the acknowledgements in that book that the information came to those authors from Philip Sheppard, who had heard about the incident directly from Cyril Clarke.

77 Zallen, Christie and Tansey, op. cit. (63), pp. 40–41.

78 David Weatherall, ‘Past Masters’ column, ‘David Weatherall pays tribute to the man who asked him to eat asparagus in the name of research’, Times Higher Educational Supplement, 4 November 1994, p. 17.

79 Weatherall, op. cit. (29), p. 80.

80 Clarke, op. cit. (25).

81 P.A. Coventry and John Pickstone, ‘From what and why did genetics emerge as a medical specialism in the 1970s in the UK? A case-history of research, policy and services in the Manchester region of the NHS’, Social Science and Medicine (1999) 49, pp. 1227–1238.

82 Among these alumni are David Weatherall (Oxford), Rodney Harris (Manchester), Marcus Pembrey (London) and Peter Harper (Cardiff).