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Clinical Trials and the Reorganization of Medical Research in post-Second World War Britain

Published online by Cambridge University Press:  17 May 2012

Carsten Timmermann
Affiliation:
Helen Valier, PhD, The Honors College at the University of Houston, 212 M.D. Anderson Library, Houston, TX 77204–2001, USA; hkvalier@uh.edu Carsten Timmermann, PhD, Centre for the History of Science, Technology & Medicine, University of Manchester, Simon Building, Brunswick Street, Manchester M13 9PL, UK; carsten.timmermann@manchester.ac.uk
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Abstract

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Type
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Copyright
Copyright © The Author(s) 2008. Published by Cambridge University Press

References

1 Some important studies on the post-Second World War “biomedicalization” of health and illness in the United States include: Adele E Clarke, Janet K Shim, Lauro Mamo, Jennifer R Fosket, and Jennifer R Fishman, ‘Biomedicalization: technoscientific transformations of health, illness, and US biomedicine’, Am. Sociol. Rev., 2003, 68: 161–94; Jean-Paul Gaudillière, Inventer la biomédecine: la France, l'Amérique et la production des savoirs du vivant (1945–1965), Paris, La Découverte, 2002; and Peter Keating and Alberto Cambrosio, Biomedical platforms: realigning the normal and the pathological in late-twentieth-century medicine, Cambridge, MA, MIT Press, 2003. In this paper we are not dealing with the more recent, Foucaultian meanings associated with the term biomedicine: see Nikolas Rose, The politics of life itself: biomedicine, power, and subjectivity in the twenty-first century, Princeton University Press, 2007.

2 Peter Keating and Alberto Cambrosio, ‘From screening to clinical research: the cure of leukemia and the early development of the cooperative oncology groups, 1955–1966’, Bull. Hist. Med., 2002, 76: 299–334; Ilana Löwy, Between bench and bedside: science, healing, and interleukin-2 in a cancer ward, Cambridge, MA, Harvard University Press, 1996, ch. 1; Harry M Marks, The progress of experiment: science and therapeutic reform in the United States, 1900–1990, New York, Cambridge University Press, 1997.

3 On the meanings of the term “control” in this context, see Martin Edwards, Control and the therapeutic trial: rhetoric and experimentation in Britain, 1918–48, Amsterdam and New York, Rodopi, 2007.

4 Keating and Cambrosio, op. cit., note 1 above, p. 52. The authors note that the use of this term until the post-war period was sporadic and not common in the medical literature.

5 For an overview of the Medical Research Council's first forty years, see Joan Austoker and Linda Bryder (eds), Historical perspectives on the role of the MRC: essays in the history of the Medical Research Council of the United Kingdom and its predecessor, the Medical Research Committee, 1913–53, Oxford University Press, 1989.

6 Joan Austoker, ‘Walter Morley Fletcher and the origins of a basic biomedical research policy’, in Austoker and Bryder (eds), op. cit., note 5 above, pp. 23–33.

7 Joan Austoker and Linda Bryder, ‘Preface’, in Austoker and Bryder (eds), op. cit., note 5 above, pp. v–vii.

8 ‘Relations between the Ministry of Health and the Medical Research Council, 12 February, 1924’, UK National Archives (hereafter NA), MH 123/498. The 1924 concordat was reaffirmed by both parties in 1949 in response to the implementation of the National Health Service Act.

9 Austoker, op. cit., note 6 above. There were some notable exceptions, such as the (MRC funded) first full-time professor of medicine at UCL, Thomas Renton Elliott, a friend of Fletcher. Elliot trained as a physiologist at Cambridge before going on to medical school.

10 J Liebenau, ‘Industrial R & D in pharmaceutical firms in the early twentieth century’, Business History, 1984, 26: 329–34; John P Swann, Academic scientists and the pharmaceutical industry, Baltimore, Johns Hopkins University Press, 1988; M Weatherall, In search of a cure: a history of pharmaceutical discovery, Oxford University Press, 1990.

11 For problems facing early co-operative trial groups, see Harry M Marks, ‘Notes from the underground: the social organization of therapeutic research’, in Russell C Maulitz and Diana E Long (eds), Grand rounds: one hundred years of internal medicine, Philadelphia, University of Pennsylvania Press, 1988, pp. 297–336; and on the influence of Pearson and Greenwood, Eileen Magnello, ‘The introduction of mathematical statistics into medical research: the roles of Karl Pearson, Major Greenwood and Austin Bradford Hill’, in Eileen Magnello and Anne Hardy (eds), The road to medical statistics, Amsterdam and New York, Rodopi, 2002, pp. 94–124.

12 Apart from the conspicuous successes of the Rockefeller-funded University College Hospital (London) unit established under Thomas Lewis, the inter-war professorial unit system generally proved to be an inadequate basis on which to produce a strong British tradition in academic clinical research. Over the years, despite much discussion and attempts to ignite wider interest in the unit system, the units themselves remained mostly clustered in London teaching hospitals, becoming progressively more over-burdened with teaching duties. See Christopher C Booth, ‘Clinical research since 1945’, in Ghislaine Lawrence (ed.), Technologies of modern medicine, London, Science Museum, 1993, pp. 148–50; and Christopher C Booth, ‘Clinical research’, in W F Bynum and Roy Porter (eds), Companion encyclopedia to the history of medicine, London and New York, Routledge, 1993, pp. 205–29; D Fisher, ‘The Rockefeller Foundation and the development of scientific medicine in Great Britain’, Minerva, 1978, 16: 20–41; H K Valier, ‘The politics of scientific medicine in Manchester, c.1900–1960’, PhD thesis, University of Manchester, 2002.

13 For an overview of the origins and development of the NHS, see Charles Webster, The National Health Service: a political history, Oxford University Press, 1998; Rudolph Klein, The new politics of the NHS, 3rd ed., London, Longman, 1995; Geoffrey Rivett, From cradle to grave: fifty years of the NHS, London, King's Fund, 1998.

14 See comments in ‘Medical research at hospitals in the National Health Service: Transfer of major schemes to Medical Research Council, 1949–1953’, NA, MH 123/498.

15 On the founding of the Emergency Medical Service, see C L Dunn, The emergency medical services, London, HMSO, 1952–1953, vol. 1.

16 A Landsborough Thomson, Half a century of medical research. Volume 2: The programme of the Medical Research Council (UK), London, HMSO, 1975, p. 255.

17 Linda Bryder, ‘Public health research and the MRC’, in Austoker and Bryder (eds), op. cit., note 5 above, pp. 59–81.

18 At least those of England, Wales and Northern Ireland did—Scottish hospitals came under the jurisdiction of the Scottish Secretary of State for Health, a separate body but accountable to the British Ministry of Health.

19 A Landsborough Thomson to J E Pater, 27 May 1949, NA, MH 123/498.

20 Ibid.

21 Francis R Fraser, ‘The challenge to the medical profession’, Br. med. J., 1960, ii: 1822–6.

22 Ministry of Health and Department of Health for Scotland, Report of the inter-departmental committee on medical schools, London, HMSO, 1944.

23 Clinical research in relation to the National Health Service, London, HMSO, 1953, p. 7.

24 NA, MH 123/499 contains examples of such returns.

25 Meeting between the MRC, Treasury and Ministry, ‘Transfer of Clinical Research’, 10 Oct. 1956, NA, FD 7/241.

26 Rivett, op. cit., note 13 above, ch. 2.

27 26 Nov. 1955, NA, MH 123/498.

28 Marks, op. cit., note 11 above; Edwards, op. cit., note 3 above.

29 The trials of “liver-extract” for pernicious anaemia in the 1920s and 1930s, and patulin for the common cold in the early 1940s were early attempts by the MRC to co-ordinate rigorous trials. The “liver extract” trials collapsed partly due to suspicions on the part of senior Council figures that certain clinical researchers were using the scheme for personal benefit (Valier, op. cit., note 12 above, ch. 3). The patulin trials, on the other hand, were significantly more successful in terms of organization, but they did not show the drug to be efficacious. Iain Chalmers and Mike Clarke have argued that it was this lack of efficacy that caused the trial to be virtually ignored as the immediate model for the subsequent, much celebrated, trials of streptomycin for tuberculosis. See Iain Chalmers and Mike Clarke, ‘The 1944 patulin trial: the first properly conducted multicentre trial conducted under the aegis of the British Medical Research Council’, Inter. J. Epidemiol., 2004, 33: 253–60.

30 Christopher C Booth, ‘Clinical research’, in Austoker and Bryder (eds), op. cit., note 5 above, pp. 205–41, p. 205. By the 1930s the academic clinical research base sponsored by the MRC included university hospitals and clinics in London, Sheffield, Edinburgh and St Andrews, and the Surgical Unit at The Welsh National School of Medicine, Cardiff, but elsewhere MRC money was scarce.

31 On the increase in funding of military-related scientific research in Britain during the Second World War, see, for example, Brian Balmer, Britain and biological warfare: expert advice and science policy, 1930–1965, Basingstoke, Palgrave, 2001; David Edgerton, Warfare state: Britain, 1920–1970, Cambridge University Press, 2006; and Bryder, op. cit., note 17 above.

32 Medical Research Council, ‘Streptomycin treatment of pulmonary tuberculosis’, Br. med. J., 1948, 2: 769–82. For discussion of the MRC's early trial, see Lise Wilkinson, ‘Sir Austin Bradford Hill: medical statistics and the quantitative approach to disease’, Addiction, 1997, 92: 657–66; and A Yoshioka, ‘Use of randomisation in the Medical Research Council's clinical trial of streptomycin in pulmonary tuberculosis in the 1940s’, Br. med. J., 1998, 317: 1220–3. Yoshioka questions the extent to which the trial should be considered as truly novel in this regard, and considers the wider social and political context of centrally controlled randomization. On the wider significance of tuberculosis in post-Second World War Britain, see Anne Hardy, ‘Reframing disease: changing perceptions of tuberculosis in England and Wales, 1938–70’, Hist. Res., 2003, 76 (194): 535–56.

33 As described in the summary reports of current literature for the period carried by the British Medical Annual: A Yearbook of Treatment and Practitioner's Index.

34 Medical Research Council, op. cit., note 32 above, p. 770.

35 Ibid., pp. 780–1.

36 Ibid., pp. 769–70. Despite the various toxicity scares surrounding streptomycin, and the hype and “anti-hype” accompanying its testing phase (for details see Yoshioka, op. cit., note 32 above), the trial, none the less, recruited well and progressed smoothly.

37 This notion of “linking” trials is discussed by J G Scadding, ‘Clinical aspects of controlled trials in pulmonary tuberculosis’, in Controlled clinical trials, Oxford, Blackwell, 1960, pp. 52–6.

38 Sunil Amrith, ‘In search of a “magic bullet” for tuberculosis: South India and beyond, 1955–1965’, Soc. Hist. Med., 2004, 17: 113–30; H Valier, ‘At home in the colonies: the WHO–MRC trials at the Madras Chemotherapy Centre in the 1950s and 1960s’, in M Worboys and F Condrau (eds), Tuberculosis then and now: interdisciplinary perspectives on a post-modern plague, Montreal, McGill-Queens University Press, forthcoming.

39 A 1961 report by the British Tuberculosis Association recommended long term supervision, possibly life-long supervision, of all patients treated with chemotherapy for their tuberculosis. See ‘Relapse in pulmonary tuberculosis: an analysis of the fate of patients notified in 1947, 1951 and 1954. Report from the Association's Research Committee’, Tubercle, 1961, 42, 178–86.

40 James L Livingstone, ‘Observations on the treatment of pulmonary tuberculosis at the present time’, Br. med. J., 1955, i: 243–50.

41 D T Kay, ‘The treatment of pulmonary tuberculosis at work: a controlled trial. An interim report by the Research Committee of the Tuberculosis Society of Scotland’, Tubercle, 1957, 38: 375–81; Report from the Research Committee of the Tuberculosis Society of Scotland, ‘The treatment of pulmonary tuberculosis at work: a controlled trial’, Tubercle, 1960, 41: 161–70.

42 Here we are using “co-produced” in the sense outlined by Sheila Jasanoff in the introductory essay to Sheila Jasanoff (ed.), States of knowledge: the co-production of science and social order, London, Routledge, 2004, especially p. 6.

43 Joan Austoker, A history of the Imperial Cancer Research Fund, 1902–1986, Oxford University Press, 1988, pp. 73–6.

44 Austoker provides an excellent summary of these complex and shifting relationships, ibid., pp. 139–204. She argues that even in the early years of Fletcher's secretaryship, he had been determined to see all medical research in the UK come under the jurisdiction of the MRC. He therefore objected both to the (clinician-led) British Empire Cancer Campaign's refusal to co-operate in the administration of funds for cancer research, and the Ministry of Health's own planned programme of research. Arguments over the Ministry's cancer research initiative were a significant aspect of the drawing up of the 1924 concordat, in order that Fletcher and the Chief Medical Officer of Health, George Newman, might clarify their specific, respective fields of influence.

45 See D A Christie and E M Tansey (eds), Short-course chemotherapy for tuberculosis, London, Wellcome Trust Centre for the History of Medicine at UCL, 2005.

46 ‘The value of supervoltage therapy in the one to ten MeV range’, NA, FD 7/698; ‘Informal Conference on the Evaluation of Different Methods of Cancer Therapy’, invitation, ibid.

47 ‘Evaluation of different methods of cancer therapy: recommendations of the Council's steering committee’, NA, FD 7/327. The other participants, besides Windeyer were: P Armitage, D Baird, J Bruce, S Cade, Lord Cohen, D A G Galton (representing A Haddow), G Hadfield, A Bradford Hill, G Jefferson, R McWhirter, P R Peacock, R Platt, R Paterson, R W Scarff and L J Witts, as well as F J C Herrald and M Gorrill from MRC Headquarters. Invited but unable to attend were C Dodds, A Haddow, J S Mitchell, F G Spear and D W Smithers.

48 ‘Evaluation of dfferent methods of cancer therapy: recommendations of the Council's steering committee’, NA, FD 7/327.

49 ‘The value of supervoltage therapy in the one to ten MeV range’, NA, FD 7/698.

50 E Toon, ‘Does bigger mean better? British perspectives on American cancer treatment and research, 1948’, J. Clin. Oncol., 2007, 25: 5831–34.

51 For the history of radiotherapy in Britain, see C C S Murphy, ‘A history of radiotherapy to 1950: cancer and radiotherapy in Britain 1850–1950’, PhD dissertation, University of Manchester, 1986. See also David Cantor, ‘The MRC's support for experimental radiology during the inter-war years’, in Austoker and Bryder (eds), op. cit., note 5 above, pp. 181–204.

52 ‘Alexander Haddow’, Biog. Mem. Fellows R. Soc., 1977, 23: 133–91, especially pp. 153–60.

53 The members of the steering committee were: B W Windeyer (chairman), J S Mitchell, R B Hunter, R E Scarff, A L d'Abreu, J Gough, A Bradford Hill and L J Witts.

54 ‘Evaluation of different methods of cancer therapy: recommendations of the Council's steering committee’, NA, FD 7/327.

55 ‘Evaluation of different methods of Cancer Therapy Committee’, NA, FD 7/340.

56 Peter Keating and Alberto Cambrosio, ‘Cancer clinical trials: the emergence and development of a new style of practice’, Bull. Hist. Med., 2007, 81: 197–223, on p. 199.

57 ‘Evaluation of different methods of cancer therapy: recommendations of the Council's steering committee’, NA, FD 7/327.

58 For a more detailed account of these discussions and the trials, see Carsten Timmermann, ‘As depressing as it was predictable? Lung cancer, clinical trials, and the Medical Research Council in postwar Britain’, Bull. Hist Med., 2007, 81: 312–34.

59 Minutes of the steering committee meeting on 13 Jan.1958, NA, FD 7/327; Minutes of the meeting of the Lung Cancer Working Party on 24 June 1958, ibid.

60 Ibid.

61 Ibid.

62 Memorandum, 8 Oct. 1959, NA, FD 7/327.

63 D'Arcy Hart to Gorrill, 15 March 1960, NA, FD 23/1163.

64 Ibid. and Draft Memorandum, n.d., NA, FD 7/327.

65 Ibid.

66 Minutes of a Special Meeting with Consultant Surgeons and Radiotherapists, 25 July 1961, NA, FD 7/327

67 Ibid.

68 Another option considered and later apparently dropped was a trial in the fractionization of doses. See ibid. and Draft Memorandum, n.d., NA, FD 7/327.

69 J G Scadding, J R Bignall, L G Blair, W P Cleland, et al., ‘Comparative trial of surgery and radiotherapy for the primary treatment of small- celled or oat-celled carcinoma of the bronchus: first report to the Medical Research Council by the Working-Party on the Evaluation of Different Methods of Therapy in Carcinoma of the Bronchus’, Lancet, 1966, ii: 979–86, on p. 984.

70 A B Miller, Wallace Fox, and Ruth Tall, ‘Five-year follow-up of the Medical Research Council Comparative Trial of Surgery and Radiotherapy for the Primary Treatment of Small-Celled or Oat-Celled Carcinoma of the Bronchus. A report to the Medical Research Council Working Party on the Evaluation of Different Methods of Therapy in Carcinoma of the Bronchus’, Lancet, 1969, ii: 501–5; Wallace Fox and J G Scadding, ‘Medical Research Council comparative trial of surgery and radiotherapy for primary treatment of small-celled or oat-celled carcinoma of bronchus: ten-year follow-up’, Lancet, 1973, ii: 63–5.

71 Note by J R H [Herrald], 22 August 1966, NA, FD 7/1151.

72 See, for example, R Abbey Smith, ‘Treatment of bronchial carcinoma’, Lancet, 1966, ii: 1134–5, and J R Belcher, ‘Treatment of bronchial carcinoma’, Lancet, 1966, ii: 1190–1.

73 NA, FD 7/327; FD 23/1163.

74 For critical remarks on studies undertaken with chemotherapy in lung cancer from France, the US and Denmark, see L Israel, ‘Chemotherapy in inoperable bronchial carcinoma’, Lancet, 1971, i: 971–2; Franco M Muggia, Heine H Hansen, and Per Dombernowsky, ‘Treatment of small-cell carcinoma of bronchus’, Lancet, 1975, 1: 692.

75 MRC Working Party, ‘Study of cytotoxic chemotherapy as an adjuvant to surgery in carcinoma of the bronchus’, Br. med. J., 1971, 2: 421–8; H Stott, R J Stephens, W Fox, and D C Roy, ‘5-year follow-up of cytotoxic chemotherapy as an adjuvant to surgery in carcinoma of the bronchus’, Br. J. Cancer, 1976, 34: 167–73.

76 MRC Working Party, op. cit., note 75 above, p. 427.

77 Ray Donnelly, Cinderella cancer: a personal history of the Roy Castle Lung Cancer Foundation, Liverpool, Bluecoat Press, 2006.

78 For a celebration of this success, see James Le Fanu, The rise and fall of modern medicine, London, Little, Brown, 1999, pp. 138–56.

79 G M Krueger, ‘“A cure is near”: children, families, and cancer in America, 1945–1980’, PhD dissertation, Yale University, 2003.

80 Timmermann, op. cit., note 58 above.

81 Valier, op. cit., note 38 above.

82 One of the main promoters of the German national centre for cancer research in Heidelberg, Karl Heinrich Bauer, for example, in 1958 argued against the term “cancer research” in the name of the new centre as this would give potential patients the idea that they might be experimented upon. See Gustav Wagner and Andrea Mauerberger, Krebsforschung in Deutschland: Vorgeschichte und Geschichte des Deutschen Krebsforschungszentrums, Berlin, Springer, 1989, p. 74.

83 See, for example, Claudia I Henschke and Peggy McCarthy, Lung cancer: myths, facts, choices, New York, Norton, 2002.

84 Donnelly, op. cit., note 77 above. See also http://www.roycastle.org/ research/index.htm, accessed on 18 April 2008.

85 ‘CTU History’, http://www.ctu.mrc.ac.uk/History.asp, accessed on 18 April 2008.

86 Sir Richard Doll, for example, was one of the speakers at an event held in the premises of the Royal College of Physicians in 2004 to celebrate sixty years of MRC clinical research, where, with Richard Peto, he presented the results of fifty years follow-up in the ‘Doctors Study’: Richard Doll and A Bradford Hill, ‘The mortality of doctors in relation to their smoking habits: a preliminary report’, Br. med. J., 1954, i: 1451–5.