The ethics of human gene transfer


Almost 20 years since the first gene-transfer trial was carried out in humans, the field has made significant advances towards clinical application. Nevertheless, it continues to face numerous unresolved ethical challenges — among them are the question of when to initiate human testing, the acceptability of germline modification and whether the technique should be applied to the enhancement of traits. Although such issues have precedents in other medical contexts, they take on a different character in gene transfer, in part because of the scientific uncertainty and the social context of innovation.

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  1. 1

    Guo, J. & Xin, H. Chinese gene therapy. Splicing out the West? Science 314, 1232–1235 (2006).

    CAS  Article  PubMed  Google Scholar 

  2. 2

    Booth, C. et al. Management options for adenosine deaminase deficiency; proceedings of the EBMT satellite workshop (Hamburg, March 2006). Clin. Immunol. 123, 139–147 (2007).

    CAS  Article  PubMed  Google Scholar 

  3. 3

    Branca, M. A. Gene therapy: cursed or inching towards credibility? Nature Biotechnol. 23, 519–521 (2005).

    CAS  Article  Google Scholar 

  4. 4

    President's Commission for the Study of Ethical Problems in Medicine and Biomedical and Behavioral Research. Splicing Life: A Report on the Social and Ethical Issues of Genetic Engineering with Human Beings. (US Government Printing Office, Washington, 1982).

  5. 5

    Raper, S. E. et al. Fatal systemic inflammatory response syndrome in a ornithine transcarbamylase deficient patient following adenoviral gene transfer. Mol. Genet. Metab. 80, 148–158 (2003).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  6. 6

    Baum, C. What are the consequences of the fourth case? Mol. Ther. 15, 1401–1402 (2007).

    CAS  Article  PubMed  Google Scholar 

  7. 7

    Kaiser, J. Clinical research. Death prompts a review of gene therapy vector. Science 317, 580 (2007).

    CAS  Article  PubMed  Google Scholar 

  8. 8

    Horstmann, E. et al. Risks and benefits of Phase 1 oncology trials, 1991 through 2002. N. Engl. J. Med. 352, 895–904 (2005).

    CAS  Article  PubMed  Google Scholar 

  9. 9

    Kimmelman, J. Recent developments in gene transfer: risk and ethics. BMJ 330, 79–82 (2005).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  10. 10

    Dettweiler, U. & Simon, P. Points to consider for ethics committees in human gene therapy trials. Bioethics 15, 491–500 (2001).

    CAS  Article  PubMed  Google Scholar 

  11. 11

    Gaspar, H. B. et al. Gene therapy of X-linked severe combined immunodeficiency by use of a pseudotyped γ-retroviral vector. Lancet 364, 2181–2187 (2004).

    CAS  Article  PubMed  Google Scholar 

  12. 12

    Will, E. et al. Importance of murine study design for testing toxicity of retroviral vectors in support of Phase I trials. Mol. Ther. 15, 782–791 (2007).

    CAS  Article  Google Scholar 

  13. 13

    Manno, C. S. et al. Successful transduction of liver in hemophilia by AAV-Factor IX and limitations imposed by host immune response. Nature Med. 12, 342–347 (2006).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  14. 14

    Freedman, B. Equipoise and the ethics of clinical research. N. Engl. J. Med. 317, 141–145 (1987).

    CAS  Article  PubMed  Google Scholar 

  15. 15

    Orkin, S. H. & Motulsky, A. G. Report and Recommendations of the Panel to Assess the NIH Investment in Research on Gene Therapy. (National Institutes of Health, Bethesda, Maryland, 1995).

    Google Scholar 

  16. 16

    Kimmelman, J. Stable ethics: enrolling non-treatment-refractory volunteers in novel gene transfer trials. Mol. Ther. 15, 1904–1906 (2007).

    CAS  Article  PubMed  Google Scholar 

  17. 17

    Evans, J. H. Playing God: Human Genetic Engineering and the Rationalization of Public Debate. (University of Chicago Press, 2002).

    Google Scholar 

  18. 18

    King, N. M. RAC oversight of gene transfer research: a model worth extending? J. Law Med. Ethics 30, 381–389 (2002).

    Article  PubMed  Google Scholar 

  19. 19

    Ashcroft, R. E. Gene therapy in the clinic: whose risks? Trends Biotechnol. 22, 560–563 (2004).

    CAS  Article  PubMed  Google Scholar 

  20. 20

    Danzon, P. & Towze, A. The economics of gene therapy and of pharmacogenetics. Value Health 5, 5–13 (2002).

    Article  PubMed  Google Scholar 

  21. 21

    Danzon, P. & Towze, A. The genomic revolution: is the real risk under-investment rather than bankrupt health care systems? J. Health Serv. Res. Policy 5, 253–255 (2000).

    CAS  Article  PubMed  Google Scholar 

  22. 22

    National Hemophilia Foundation. Financial and Insurance Issues. [online], (2006).

  23. 23

    Herper, M. Avigen Leads Gene Therapy Charge. Forbes [online], (2006).

    Google Scholar 

  24. 24

    Ja, H. & Kling, J. China offers alternative gateway for experimental drugs. Nature Biotechnol. 24, 117–118 (2006).

    Article  Google Scholar 

  25. 25

    Jia, H. Controversial Chinese gene-therapy drug entering unfamiliar territory. Nature Rev. Drug Discov. 5, 269–270 (2006).

    CAS  Article  Google Scholar 

  26. 26

    Jia, H. Gene therapy finds welcoming environment in China. Nature Med. 12, 263–264 (2006).

    CAS  Article  PubMed  Google Scholar 

  27. 27

    Marshall, E. Gene therapy. Panel reviews risks of germ line changes. Science 294, 2268–2269 (2001).

    PubMed  Google Scholar 

  28. 28

    Kazazian, H. H. An estimated frequency of endogenous insertional mutations in humans. Nature Genet. 22, 130 (1999).

    CAS  Article  PubMed  Google Scholar 

  29. 29

    Kaplan, J. & Roy., I. Accidental germ-line modifications through somatic cell gene therapies: Some ethical considerations. Am. J. Bioeth. 1, w13 (2001).

    CAS  PubMed  Google Scholar 

  30. 30

    King, N. M. Accident & desire. Inadvertent germline effects in clinical research. Hastings Cent. Rep. 33, 23–30 (2003).

    Article  PubMed  Google Scholar 

  31. 31

    Cohen, J., Scott, R., Schimmel, T., Levorn, J. & Wiladsen, S. Birth of infant after transfer of anucleate donor oocyte cytoplasm into recipient eggs. Lancet 350, 186–187 (1997).

    CAS  Article  PubMed  Google Scholar 

  32. 32

    Zoon, K. C. Letter to sponsors/researchers: human cells used in therapy involving the transfer of genetic material by means other than the union of gamete nuclei. FDA Center for Biologies Evaluation and Research. [online], (2001).

    Google Scholar 

  33. 33

    Firfer, H. How Far Will Couples Go To Conceive? CNN [online], (2004).

    Google Scholar 

  34. 34

    Robertson, J. A. Oocyte cytoplasm transfers and the ethics of germ-line intervention. J. Law Med. Ethics 26, 211–220 (1998).

    CAS  Article  PubMed  Google Scholar 

  35. 35

    Council of Europe. Convention for the Protection of Human Rights and Dignity of the Human Being with Regard to the Application of Biology and Medicine: Convention on Human Rights and Biomedicine. European Treaty Series 164 (4 Apr 1997).

  36. 36

    Hébert, M., Chenier, N. M. & Norris, S. Bill C-6 Assisted Human Reproduction Act. Statutes of Canada, chapter 2 (2004). Available at

    Google Scholar 

  37. 37

    Indian Council of Medical Research, New Delhi. Ethical guidelines for biomedical research on human participants. [online], (2006).

  38. 38

    Steinbock, B. in Designing Our Descendants: The Promises and Perils of Genetic Modifications. (eds Chapman, A. R. & Frankel, M. S.) 179–198 (Johns Hopkins University Press, Baltimore, 2003).

    Google Scholar 

  39. 39

    Genetics and Public Policy Center, Johns Hopkins University. Attitudes about Reproductive Genetics. [online], (2002)

  40. 40

    Garber, K. RAC urges changes to retinoblastoma plan. Science 284, 2066 (1999).

    CAS  Article  PubMed  Google Scholar 

  41. 41

    RAC Department of Health and Human Services National Institutes of Health Recombinant DNA Advisory Committee. Minutes of meeting, June 14 1999 [online], (1999).

  42. 42

    Melman, A., Bar-Chama, N., McCullough, A., Davies, K., Christ, G. hMaxi-K gene transfer in males with erectile dysfunction: results of the first human trial. Hum. Gene Ther. 17, 1165–1176 (2006).

    CAS  Article  PubMed  Google Scholar 

  43. 43

    RAC Department of Health and Human Services National Institutes of Health Recombinant DNA Advisory Committee. Minutes of meeting, March 10 2004 [online], (2004).

  44. 44

    Baoutina, A., Alexander, I. E., Rasko, J. E. & Emslie, K. R. Potential use of gene transfer in athletic performance enhancement. Mol. Ther. 15:, 1751–1766 (2007).

  45. 45

    Parens, E. Is better always good? The enhancement project. Hastings Cent. Rep. 28, S1–S17 (1998)

    CAS  Article  PubMed  Google Scholar 

  46. 46

    Sandel, M. J. The Case Against Perfection: Ethics in the Age of Genetic Engineering. (Harvard University Press, Cambridge, 2007)

    Google Scholar 

  47. 47

    Buchanan, A., Brock, D. W., Daniels, N. & Wikler, D. From Chance to Choice: Genetics and Justice. (Cambridge University Press, New York, 2001).

    Google Scholar 

  48. 48

    Mehlman, M. J. Genetic enhancement: plan now to act later. Kennedy Inst. Ethics J. 15, 77–82 (2005).

    Article  PubMed  Google Scholar 

  49. 49

    Mehlman, M. J. & Rabe, K. M. Any DNA to declare? Regulating offshore access to genetic enhancement. Am. J. Law Med. 28, 179–213 (2002).

    PubMed  Google Scholar 

  50. 50

    Parens, E. Should we hold the (germ) line? J. Law Med. Ethics 23, 173–176 (1995).

    CAS  Article  PubMed  Google Scholar 

  51. 51

    Imperiale, M J. Gene therapy and biosecurity. Mol. Ther. 15, 648–649 (2007).

    CAS  Article  PubMed  Google Scholar 

  52. 52

    Billings, P. R. In utero gene therapy: the case against. Nature Med. 5, 255–256 (1999).

    CAS  Article  PubMed  Google Scholar 

  53. 53

    Waddington, S. N. et al. In utero gene therapy: current challenges and perspectives. Mol. Ther. 11, 661–676 (2005).

    CAS  Article  PubMed  Google Scholar 

  54. 54

    Dresser, R. Genetic modification of preimplantation embryos: toward adequate human research policies. Milbank Q. 82, 195–214 (2004).

    Article  PubMed  PubMed Central  Google Scholar 

  55. 55

    Dennis, M. B. Welfare issues of genetically modified animals. ILAR J. 43, 100–108 (2002).

    CAS  Article  PubMed  Google Scholar 

  56. 56

    Massiello, S. A. Warning letter to James M. Wilson, Institute for Human Gene Therapy. FDA Freedom of Information [online], (2000).

    Google Scholar 

  57. 57

    Munson, R. in Outcome Uncertain: Cases and Contexts in Bioethics. (Munson, R. ed) (Wadsworth, Toronto, 2003).

    Google Scholar 

  58. 58

    Cornetta, K. & Smith, F. O. Regulatory issues for clinical gene therapy trials. Hum. Gene Ther. 13, 1143–1149 (2002).

    CAS  Article  PubMed  Google Scholar 

  59. 59

    Spink J. & Geddes, D. Gene therapy progress and prospects: bringing gene therapy into medical practice: the evolution of international ethics and the regulatory environment. Gene Ther. 11, 1611–1616 (2004).

    CAS  Article  PubMed  Google Scholar 

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I regret that, owing to the brevity of this Perspective, many important contributions to the literature on gene-transfer ethics went unmentioned. The work of the author is funded by a Canadian Institutes of Health Research Maud Menten New Principal Investigator Award.

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chronic granulomatous disease

cystic fibrosis

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ornithine transcarbamylase deficiency



Jonathan Kimmelman's homepage

Database of gene-transfer clinical trials in the United States

Genetic Modification Clinical Research Information System (GeMCRIS) database

Guidance on informed consent for gene-transfer trials from the National Institutes of Health

Information on the status of human gene transfer

Information on the regulation and status of human gene transfer in Europe and elsewhere

Journal of Gene Medicine database

Overview of ethical issues and literature surrounding human gene transfer

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Kimmelman, J. The ethics of human gene transfer. Nat Rev Genet 9, 239–244 (2008).

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