The regulation of xenotransplantation in the United Kingdom after UKXIRA: Legal and ethical issues

Journal of Law and Society

Volumn 34, Issue 4, 2007, Pages 441-464

  Williamson, Laura ^a   Fox, Marie ^b   McLean, Sheila ^a  

^a UNIVERSITY OF GLASGOW   (United Kingdom)

^b KEELE UNIVERSITY   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

EID: 36549019964     PISSN: 0263323X     EISSN: 14676478     Source Type: Journal    
DOI: 10.1111/j.1467-6478.2007.00400.x     Document Type: Article

References (138)

1. I. Welsh and R. Evans, 'Xenotransplantation, risk, regulation and surveillance: social and technological dimensions of change' (1999) 18 New Genetics and Society 197-217;
2. E.R. Gold and W.A. Adams, 'Reconciling Private Benefit and Public Risk in Biotechnology: Xenotransplantation as a Case study in Consent' (2002) 10 Health Law J. 31-75, at 32.
3. Thus, the Human Reproductive Cloning Act 2001 was a response to new methods of human cloning; the Human Tissue Act 2004 established (in s. 13) a new Human Tissue Authority to oversee research involving human materials; in 1999 a non statutory body - the Human Genetics Commission (HGC) - was entrusted with analysing current and potential developments in human genetics and advising Ministers on their likely impact on human health and healthcare, and their social, ethical, legal, and economic implications; in 2006 a Government White Paper introduced proposals which would radically overhaul existing laws regulating reproductive technologies and embryology - Department of Health, Review of the Human Fertilisation and Embryology Act: Proposals for revised legislation (including establishment of the Regulatory Authority for Tissue and Embryos) (2006; Cm. 6989).
4. Nuffield Council on Bioethics, Animal-to-Human Transplants: The Ethics of Xenotransplantation (1996);
5. Advisory Group on the Ethics of Xenotransplantation, Animal Tissue into Humans (1996) (The Kennedy Report);
6. World Health Organzation (WHO), Report of the WHO Consultation on Xenotransplantation, Geneva, Switzerland 28-30 October 1997 (1998);
7. WHO, Xenotransplantation: Guidance on Infectious Disease Prevention and Management (1998);
8. OECD/WHO, Consultation on Xenotransplantation: Summary Report (2001).
9. K. Reemtsma et al., 'Heterotransplantation of the Kidneys: Two Clinical Experiences' (1964) 143 Science 700-2;
10. J.D. Hardy, 'Heart Transplantation in Man: Developmental Studies and Report of a Case' (1964) 188 J. of the Am. Medical Association 1132-40, at 1132;
11. L.L. Bailey et al., 'Baboon-to-human Cardiac Xenotransplantation in a Neonate' (1985) 254 J. of the Am. Medical Association 3321-9.
12. Human Tissue Act s. 1.
13. Information obtained from United Kingdom. Transplant at 〈http:// www.uktransplant.org.uk/ukt/default.jsp〉 (accessed on 26 March 2007).
14. S. Boseley, 'Chief medical officer urges organ donor opt-out to beat crisis' Guardian, 18 July 2007.
15. C. Freed et al., 'Survival of Implanted Fetal Dopamine Cells and Neurologic Improvement 12 to 24 Months after Transplantation for Parkinson's Disease' (1992) 327 New England J. of Medicine 1549-55;
16. C.G. Groth et al., 'Transplantation of Porcine Fetal Islet-Like Cell Clusters into Eight Diabetic Patients' (1993) 25 Transplantation Proceedings 970;
17. C.V. Borlongan and P.R. Sanberg, 'Neural Transplantation for Treatment of Parkinson's Disease' (2002) 7 Drug Discovery Today 674-82;
18. W.M. Rideout et al., 'Correction of a genetic defect by nuclear transplantation and combined cell and gene therapy' (2002) 109 Cell 17-27;
19. A.E. Rosser and S.B. Dunnett, 'Neural Transplantation in Patients with Huntington's Disease' (2003) 17 CNS Drugs 853-67.
20. S. Saadi and J.L. Platt, 'Mini Review: Immunology of Xenotransplantation' (1998) 62 Life Sciences 365-87;
21. D. Sachs, 'The Immunology of Xenotransplantation: Introduction,' in Xenotransplantation: Scientific Frontiers and Public Policy, eds. J. Fishman, D. Sachs, and R. Shaikh (1998) 1-4.
22. J.M. Dobson and J.H. Dark, The Physiology of Xenotransplantation (2002).
23. D.A. Muir and G.E. Griffin, Infection Risks in Xenotransplantation (2001).
24. L.E. Chapman et al., 'Xenotransplantation: The Potential for Xenogeneic Infections' (1999) 31 Transplantation Proceedings 909-10;
25. J.S. Allen, 'Xenograft Transplantation and the Infectious Disease Conundrum' (1995) 37 ILAR J. 37-48.
26. Advisory Group, op. cit., n. 3, pp. 141-6.
27. id.
28. Welsh and Evans, op. cit., n. 1 at p. 208. A non departmental public body (NDPB) has been, defined as 'A body which has a role in the processes of national government, but is not a government department, or part of one, and which accordingly operates to a greater or lesser extent at arm's length from ministers. However, although they are expected to function independently, ministers are ultimately responsible to Parliament for a NDPB's independence, effectiveness and efficiency' - see Civil Service, Public Bodies: A. Guide for Departments ch. 2 (available from 〈http://www.civilservice.gov.uk/ other/agencies/guidance_for_departments/ pb_guidance/index.asp〉 (accessed on 19 July 2007).
29. Gold and Adams, op. cit., n. 1, at p. 72
30. note that such models bring advantages, such as expertise, easy administration, promotion of dialogue between public and private interests, and an ability to feed into the government's decision-making process. However, concern has been expressed over the ad hoc nature of this incrementalist tendency and the difficulty it creates for imposing an effective system of scrutiny and accountability - M. Fox and J. McHale, 'Xenotransplantation: the Ethical and Legal Ramifications' (1998) 6 Medical Law Rev. 42-61, at 54-6.
31. UKXIRA, First Annual Report May 1997 - August 1998 (1998) 24.
32. UKXIRA, Guidance on Making Proposals to Conduct Xenotransplantation (1998).
33. Before a clinical trial is undertaken, it is standard procedure for the trial to be referred to a research ethics committee for approval. Such committees may be local (LRECs) or multi-centre (MRECs). For more detail see J. McHale and M. Fox, Health Care Law: Text and Materials (2007, 2nd edn.) at 670 ff.
34. GTAC was established as a national research ethics committee on gene therapy upon the recommendation of the Clothier Committee - Department of Health, Report of the Committee on the Ethics of Gene Therapy (1992; Cm. 1788).
35. id., pp. 8 ff.
36. See, for example, S.A.M. McLean and L. Williamson, Xenotransplantation: Law and Ethics (2005).
37. id; S. Fovargue, 'Consenting to Bio-risk: Xenotransplantation and the Law' (2005) 25 Legal Studies 404-30, at 406.
38. 〈http://www.advisorybodies.doh.gov.uk/ukxira〉 (accessed on 18 December 2006).
39. id.
40. 〈http://www.dh.gov.uk/PublicationsAndStatistics/Publications/ Publications PolicyAndGuidance/PublicationsPolicyAndGuidanceArticle/fs/en? CONTENT_ID= 4141213&chk=8QenyR〉 (accessed on 18 December 2006).
41. Written Statements, Tuesday 12 December 2006. Hansard Column WS177, WS182.
42. Commission Directive 2003/83/EC of 25 June 2003 amending Directive 2001/83/ EC of the European Parliament and of the Council on the Community Code Relating to medicinal products for human use; Directive 2001/20/EC of the European Parliament and of the Council of 4 April 2001 on the approximation of the laws, regulations and administrative provisions of the member states relating to the implementation of good clinical practice in the conduct of clinical trials on medicinal products for human use.
43. Kennedy Report, op. cit., n. 3, pp. 131 ff.
44. Medicines for Human Use (Clinical Trials) Regulations 2004, reg. 2(1).
45. Under Article 1, Directive 2001/83/EC, this was defined to mean 'any substance or combination of substances presented for preventing disease in human beings' or 'any substance or combination of substances which may be administered to human beings either with a view to restoring, correcting or modifying physiological functions by exerting a pharmacological, immunological or metabolic action, or to making a medical diagnosis.'
46. This service replaced the Central Office for Research Ethics (COREC) from 1 April 2007.
47. Department of Health, Xenotransplantation Guidance (2006) 2.
48. Kennedy Report, op. cit., n. 3, paras. 4.44, 4.58, 4.63, 9.3.
49. For details, see McLean, and Williamson, op. cit., n. 21, at pp. 98-104.
50. Dobson and Dark, op. cit., n. 10; Muir and Griffin, op cit., n. 11.
51. Caulfield has stressed the importance of governments identifying and communicating information accurately in order to begin to formulate an effective regulatory response to a 'genetic revolution', which he defines so as to include xenotransplantation. T. Caulfield, 'Underwhelmed: Hyberbole, Regulatory Policy and the Genetic Revolution' (2000) 45 McGill Law J. 437-60, at 441.
52. MHRA, Business Plan for 2006-2007 at 11.
53. The Declaration was drawn up by the World Medical. Association in 1964; the latest amendment was in 2000 (with revisions in 2002 and 2004). However, the Clinical Trials Directive requires conformity with the 1996 version of the Declaration. Fovargue has queried whether the Declaration, offers adequate protection to participants in a xenotransplant trial: S. Fovargue, 'A Leap of Faith? Sanctioning Xenotransplant Clinical Trials' (2005) 26 Liverpool Law Rev. 125-48.
54. At a more general level, Annas has criticized the Helsinki Declaration for being overly permissive, particularly in relation to research on the terminally ill: G.J. Annas, 'The Changing Landscape of Human Experimentation: Nuremberg, Helsinki and Beyond' (1992) 2 Health Matrix 119-40.
55. E. Angell et al., 'Consistency in Decision making by Research Ethics Committees: A Controlled Comparison' (2006) 32 J. of Medical Ethics 662-4;
56. M. Hotopf et al., 'Are Ethics Committees Reliable?'(1995) 88 J. of the Royal Society of Medicine 31-3.
57. Gold and Adams, op. cit., n. 1, at p. 60.
58. See, for instance, NHS Executive West Midlands Regional Office, Report of a Review of the Research Framework in North Staffordshire NHS Trust (The Griffiths Review) (2000).
59. P. Mc Neil, The Ethics and Politics of Human Experimentation (1993).
60. COREC (Central Office for Research Ethics Committees), Governance Arrangements for Research Ethics Committees (2001) para. 4.10; paras 7.25-7 (hereafter GAfREC guidance)
61. E. Jackson, Medical Law: Text, Cases and Materials (2006) 483.
62. Kennedy Report, op. cit., n. 3, at p. 144.
63. UKXIRA, op. cit., n. 17, p. 6.
64. S. Kerrison and A.M. Pollock, 'The reform of United Kingdom research ethics committees: throwing the baby out with the bath water?' (2005) 31 J. of Medical Ethics 487-9.
65. 'Blair pledges to make "big push" to improve conditions for biotech,' report on ResearchResearch.com 5 March 2007. See, also, Department of Health, Science and Innovation Strategy (2001);
66. A. Harrison and B. New, Public Interest, Private Decisions: Health-Related Research in the United Kingdom (2002).
67. E. Cave and S. Holm, 'New governance arrangements for research ethics committees: is facilitating research achieved at the cost of participants' interest' (2002) 28 J. of Medical Ethics 318-21. An important related concern is that the bureaucracy involved, and the resultant increased workload on RECS means that independent academic research is becoming impossible without the backing of commercial drug companies:
68. see A. Hemmminki and P.L. Kellokumpu-Lehtinen, 'Harmful impact of EC clinical trials directive: Academic clinical research in cancer seems to have no future in Europe' (2006) 332 Brit. Medical J. 501-2.
69. S.D. Pattinson, Medical Law and Ethics (2006) at 359.
70. Guidance, op. cit., n. 32, at p. 2.
71. Similarly, Directive 98/44/EC of the European Parliament and of the Council of 6 July 1998 on the legal protection of biotechnological inventions aimed to promote biotechnological research by removing legal obstacles attributable to differences in patentability standards across member states: see A. Plomer et al., Stem Cell Patents: European Patent Law and Ethics Report (2006).
72. Department of Health, Report of the Ad Hoc Advisory Group on the Operation of NHS Research Ethics Committees (2005) [hereafter Ad Hoc Advisory Group report]. Available at 〈http://www.dh.gov.uk/en/ Publicationsandstatistics/ Publications/PublicationsPolicyAndGuidance/ DH_4112416〉, accessed 10 April 2007.
73. See, also, COREC, Building on improvement: Implementing the Recommendations of the Report of the Ad hoc Advisory Group on the Operation of NHS Ethics Committees (2006).
74. See Directive 2003/63/EC, Annex I, part IV.4, Specific Statement on Xenotransplantation.
75. D. Beyleveld, T. Finnegan, S. Pattinson, 'The Regulation of Hybrids and Chimeras in the United Kingdom' (2007) at 5 (report produced for CHIMRIDS (Chimera and Hybrids in comparative European, and International Research), copy on file with authors).
76. Compare Fovargue, op. cit., n. 22, at pp. 410-11.
77. A v. National Blood Authority (2001) 60 BMLR 1;
78. Directive 2002/98/EC of the European Parliament and of the Council, of 27 January 2003 setting standards of quality and safety for the collection, testing, processing, storage, and distribution of human blood and blood components and amending Directive 2001/83/EC.
79. Concerns have surfaced in particular due to the performance of the MHRA following its role in permitting the Phase 1 clinical trial of TGN1412 - a monoclonal antibody being developed to treat multiple sclerosis, leukaemia, and rheumatoid arthritis - at Northwick Park Hospital, London, which in 2006 resulted in six healthy volunteers becoming seriously ill as a result of organ failure: editorial, 'Urgent Changes Needed for Authorisation of Phase I Trials' (2006) 367 The Lancet 1214.
80. The MHRA's misreporting of a consultation exercise concerning the availability of the counterstatin Zocor Heart-pro has also been criticized: S. Mayor, 'Drug Regulator Criticised for Error in Reporting Consultation Results' (2005) 300 Brit. Medical J. 1410.
81. J.K. Mason and G.T. Laurie, Mason and McCall Smith's Law and Medial Ethics (2006, 7th edn.) at 651, para. 18.5.
82. UKXIRA, op. cit., n. 32, at p. 3.
83. Annas, op. cit., n. 38, at p. 126.
84. McLean, and Williamson, op. cit., n. 21, ch. 2.
85. Simms v. Simms [2003] 1 All E.R. 669.
86. In this context meaning that a responsible body of medical opinion would positively endorse the use of experimental treatment.
87. Simms, op. cit., n. 62, at p. 672, emphasis added.
88. J.A. Harrington, 'Deciding Best Interests: Medical Progress, Clinical Judgment and the "Good Family'" (2003) Web J. of Current Legal Issues.
89. UKXIRA, Fourth Annual Report December 2000 - December 2001 (2002) at v.
90. See P. Curtis, 'Ethicists Fear Free-for-all in Animal-Human Transplants' Guardian, 13 January 2007.
91. E. Cozzir et al, 'Xenotransplantation - Current Status and Future Prospects' (2006) 75-76 Brit. Medical Bull. 99-114;
92. A. d'Apice, 'Is Xenotransplantation of Vascularized Organs Just Too hard?' (2006) 13 Xenotransplantation 182-5.
93. For instance, Anderson has suggested that xenotechnologies are gradually emerging as a viable allotransplantation alternative, and notes that 'rapid progress in clinical xenotransplantation [is allowing] companies to quickly reallocate front end investment in research.' He also cites several surveys which indicate growing public approval rates for xenotransplantation across a range of jurisdcitions: M. Anderson, 'Xenotransplantation: a bioethical evaluation' (2006) 32 J. of Medical Ethics 205-8.
94. Annas, op. cit., n. 38, at p. 19.
95. N. Brown and M. Michael, 'Risky Creatures: institutional species boundary change in biotechnology regulation' (2004) 6 Health, Risk and Society 207-22, at 208.
96. id., at p. 213.
97. Ironically, the need for continuity of regulation and to minimize the overlap between sectors has been a key consideration in the government's proposal to establish the Regulatory Authority for Tissue and Embryos - see Department of Heath, op. cit., n.2, para. 3.2:
98. RATE will be able to ensure that in these closely linked areas common principles and standards are applied wherever that is appropriate ... and that there is continuity at the interface between related areas, for examples between embryo research and cell therapies.
99. This proposal for a new body which would merge the Human Fertilisation and Embryology Authority and Human Tissue Authority has now been dropped. See Dept. of Health, Government's Response to the Report from the Joint Committee on the Human Tissue and Embryos (draft) Bill (2007; Cm. 7209).
100. UKXIRA, op. cit., n. 25, at p. 2.
101. id.
102. McLean and Williamson, op. cit., n. 21, pp. 113 ff.
103. id., pp. 115 ff;
104. Fovargue, op. cit., n. 22, at p. 406.
105. Fox and McHale, op. cit., n. 15; M. Fox, 'Reconfiguring the Animal/Human Boundary: The Impact of Xeno technologies' (2005) 26 Liverpool Law Rev. 149-67.
106. Now available as: S. McLean and L. Williamson, Xenotransplantation: Law and Ethics (2005).
107. UKXIRA, Fifth Annual Report January 2002-September 2003 (2004) 9
108. British Union for the Abolition of Vivisection (BUAV), Insight into xenotransplantation (2005).
109. Brown and Michael, op. cit., n. 71, at p. 214.
110. Department of Health, Governance Arrangements for NHS Research Ethics Committees (2001) para. 2.1.
111. id., para. 2.2.
112. R.R. Faden and T.L. Beauchamp, A History and Theory of Informed Consent (1986).
113. McLean and Williamson, op. cit., n. 21; Fovargue, op. cit., n. 22, at pp. 410 ff.
114. J. Hughes, 'Justice and Third-Party Risk: The Ethics of Xenotransplantation' (2007) 24 J. of Applied Philosophy 151-168.
115. Fovargue, op. cit., n. 22, pp. 421 ff.
116. T.A. Caulfield and G.B. Robertson, 'Xenotransplantation: Consent, Public Health and Charter Issues' (2001) 5 Medical Law International 81-99, at 90.
117. For a suggestion that a single consent mechanism may be inappropriate in the case of this technology, and an attempt at formulating a more complex scheme involving different levels of consent, see Gold and Adams, op. cit., n. 1.
118. Medicines for Human Use (Clinical Trials) Regulations 2004, schedule 1, part 3.
119. Kennedy Report, op. cit., n. 3, p. 112, paras. 7.6, 7.7;
120. Nuffield Council, op. cit., n. 3, p. 90 ff. paras. 7.23, 7.25.
121. Regulations 2004, op. cit., n. 91, schedule 1, part 5.
122. id., reg. 2.
123. McHale and Fox, op. cit., n. 18, at pp. 692-702.
124. See McNeil, op. cit., n. 42.
125. See, for instance, R.M. Martin, 'The Exercise of Public Health Powers in Cases of Infectious Disease: Human Rights Implications' (2006) 14 Medical Law Rev. 132-43;
126. Special supplement to Public Health, 'A collaboration between different disciplines to promote public health' (2006) available at 〈http:// www.nuffieldtrust.org.uk/research/index.asp?id=37〉; (last accessed 9 April 2007).
127. See note 26 above.
128. UKXIRA, Draft Report of the Infection Surveillance Steering Group of the UKXIRA (1999) at 31 ff.
129. Xenotransplantation Guidance at p. 2.
130. See Parts VI and V of the Regulations.
131. S. McLean and L. Williamson, 'The Demise of UKXIRA and the Regulation of Solid Organ Xenotransplantation in the United Kingdom.' (2007) 33 J. of Medical Ethics 373-5.
132. Brown and Michael, op. cit., n. 71, at p. 208.
133. HFEA, Hybrids and Chimeras: A Consultation on the ethical and social implications of creating human/animal embryos in research (2007) para. 1.5.
134. M. Brazier, A. Campbell, and S. Golombok, Surrogacy: A Review for Health Ministers of Current Arrangements for Payment and Regulation (1998).
135. J.V. McHale, 'The Human Tissue Act 2004: Innovative Legislation, Missed Opportunity or Fundamentally Flawed' (2005) 26 Liverpool Law Rev. 169.
136. Department of Health, Review of the Human Fertilisation and Embryology Act Consultation (2005).
137. C. Thomson, Making Parents: the Ontological Choreography of Reproductive Technologies (2005) ch. 3.
138. T. Woods, 'Have a Heart: Xenotransplantation, Nonhuman Death and Human Distress' (1998) 6 Society & Animals 47-65, at 49.