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Moving Beyond ‘Therapy’ and ‘Enhancement’ in the Ethics of Gene Editing

Published online by Cambridge University Press:  17 September 2019

BRYAN CWIK
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Abstract:

Since the advent of recombinant DNA technology, expectations (and trepidations) about the potential for altering genes and controlling our biology at the fundamental level have been sky high. These expectations have gone largely unfulfilled. But though the dream (or nightmare) of being able to control our biology is still far off, gene editing research has made enormous strides toward potential clinical use. This paper argues that when it comes to determining permissible uses of gene editing in one important medical context—germline intervention in reproductive medicine—issues about enhancement and eugenics are, for the foreseeable future, a red herring. Current translational goals for gene editing research involve a different kind of editing than would be required to achieve manipulation of complex traits such as intelligence, and there are more pressing (and unresolved) questions that need attention if clinical use of gene editing in reproductive medicine ever becomes a possibility.

Keywords

gene editingenhancementreproductive medicineresearch ethicsgeneticstranslational research
Type
Article
Information
Cambridge Quarterly of Healthcare Ethics , Volume 28 , Special Issue 4: Clinical Neuroethics , October 2019 , pp. 695 - 707
Copyright
Copyright © Cambridge University Press 2019 

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Footnotes

Acknowledgments: Thanks to Monica Aufrecht, Nicolae Morar, Mark Bedau, Jay Odenbaugh, and Jesse Cwik for their comments on a draft of this paper. I also benefited greatly from conversations with Amy Koski during and after a seminar on gene editing we co-taught at Reed College in April 2018; thanks to Mark Bedau for inviting us to take over his class for a night. Versions of this paper were given at the International Bioethics Retreat in Paris, France, in June 2019; Lewis and Clark College in April 2019; the Center for Modeling Complex Interactions at the University of Idaho in April 2019; and the Northwest Philosophy Conference at Bellevue College in October 2018. Special thanks are due to Tomi Kushner, the editor of Cambridge Quarterly of Healthcare Ethics, for helpful comments and editorial support. Work on this paper was supported by the National Human Genome Research Institute of the National Institutes of Health under Award Number R03HG010417. The content is solely the responsibility of the author and does not necessarily represent the official views of the National Institutes of Health.

References

Notes

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11. Arguably, the most dramatic and high profile (but not the most solid or responsible) research result was the creation of a pregnancy from edited embryos, which resulted in the birth of twin girls, by He Jiankui, a researcher (formerly) of Southern University of Science and Technology in Shenzhen, China (He was subsequently fired). His announcement in November 2018 that he had used CRISPR to delete the CCR5 gene in the girls, to prevent horizontal transmission of HIV during conception via IVF (for which there is already a very low baseline probability if, as in this case, the father is HIV positive but the mother is not) and confer limited immunity to HIV infection, grabbed headlines and garnered a great deal of notoriety. However, as of the writing of this paper, the case has not been confirmed and is still under investigation, and many scientists believe the research was shoddy (in addition to being irresponsible and ethically unacceptable). See Cyranoski, D, Ledford, H. Genome-Edited Baby Claim Provokes International Outrage. Nature 26 Nov 2018; available at https://www.nature.com/articles/d41586-018-07545-0 (last accessed 12 Feb 2019).CrossRefGoogle Scholar

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14. “CRISPR” stands for Clustered Regularly Interspaced Short Palindromic Repeats. It is a gene editing technique based on an archaic bacterial immune system.

15. Homology directed repair is one of the mechanisms cells use to repair DNA lesions. The ‘wild type’ is the phenotype that results from having a ‘normal,’ nonmutated allele of a gene. In this case, the ‘wild type’ of MYBPC3 is healthy cardiac muscle.

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17. The mutation is a deletion of a GAGT base pair sequence in exon 16; the signifier for the mutated gene is MYBPC3 ΔGAGT. See note 12, Ma et al. 2017, at 414.

18. For explanation, see note 12, Ma et al. 2017, at 414–5.

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21. A similar point is made by note 4, Daley GQ, Lovell-Badge R, Steffan J 2019.

22. For discussion of beliefs about ‘magic switch’ genes for cognitive traits, see Reich, D, Who We Are and How We Got Here: Ancient DNA and the New Science of the Human Past. New York: Pantheon; 2018.Google Scholar

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25. The value of basic research involving GGE for understanding human development is argued for forcefully by Greenfield; see note 10, Greenfield 2018, at 24–6.

26. On the basic science benefits of gene editing research, see Bedau, MA. The intrinsic scientific value of reprogramming life. Hastings Center Report 2011;41:29–31.CrossRefGoogle ScholarPubMed

27. This is discussed further in Cwik B. Revising, correcting, and transferring genes. In preparation.

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30. As one scientist involved in the research put it, “The simplest explanation is that those mutations will probably have an impact on cognitive function in the twins.” Quoted in Regalado, A. China’s CRISPR Twins Might Have Had Their Brains Inadvertently Enhanced. MIT Technology Review 22 Feb 2019; available at https://www.technologyreview.com/s/612997/the-crispr-twins-had-their-brains-altered/ (last accessed 22 Feb 2019).

31. On the germline as an ethical ‘red line,’ see note 5, Baltimore et al. 2015.

32. Perhaps the most infamous example is President’s council on bioethics. Human Cloning and Human Dignity: The Report of the President’s Council on Bioethics. NY: PublicAffairs; 2002.Google Scholar

33. See note 5.

34. For examples, see Juengst, ET. Can enhancement be distinguished from prevention in genetic medicine? Journal of Medicine and Philosophy 1997;22:125–42;CrossRefGoogle ScholarPubMed Miller, FG, Brody, H, Chung, KC. Cosmetic surgery and the internal morality of medicine. Cambridge Quarterly of Healthcare Ethics 2000;9:353–64; andCrossRefGoogle Scholar Mehlman, MJ, Berg, JW, Juengst, ET, Kodish, E. Ethical and Legal Issues in Enhancement Research on Human Subjects. Cambridge Quarterly of Healthcare Ethics 2011;20:30–45.CrossRefGoogle ScholarPubMed

35. Beta thalassemia is a family of inherited disorders in which individuals underproduce hemoglobin, resulting in a variety of conditions such as severe anemia. It is caused by a mutation of the HBB gene; this mutation was the target of the first experiment using CRISPR on human embryos. See note 16, Liang et al. 2015.

36. Biffi, A. Gene therapy as a curative option for β-thallesemia. New England Journal of Medicine 2018;378:1551–2.CrossRefGoogle Scholar

37. This question is considered with respect to GGE and preimplantation genetic diagnosis in Cavaliere, G. Genome editing and assisted reproduction: Curing embryos, society or prospective parents?. Medicine, Health Care and Philosophy 2018;21:215–25.CrossRefGoogle ScholarPubMed

38. See references in note 5.

39. This raises some interesting adjacent, but ultimately off-topic, issues in population ethics about these sorts of reproductive decisions, which I will not address here.

40. Holm, S. Let us assume that gene editing is safe – the role of safety arguments in the gene editing debate. Cambridge Quarterly of Healthcare Ethics 2019;28:100–11.CrossRefGoogle ScholarPubMed The arguments given by Holm differ from those here, and Holm brings in some metaphysical discussion about personhood and time (the infamous “nonidentity problem”). Despite this, the respective arguments end up at the same conclusion.

41. Depending on how one comes down on a host of questions about when personhood begins, and whether the application of GGE in the OHSU experiment involved existing persons, or—because the editing was done simultaneously with fertilization via ICSI—future, potential persons. Given the mechanics of the process discussed in section 2, I have assumed the latter, but this is something that is debatable. See note 37, Cavaliere 2018, at 220, for discussion of GGE and identity.

42. Note 40, Holm 2019, at 106.

43. As argued by Lanphier, E, Urnov, F, Haecker, SE, Werner, M, Smolenski, J. Don’t edit the human germ line. Nature 2015;519:410–1.CrossRefGoogle ScholarPubMed

44. I borrow the phrase here (and in the title of section 2), and the overall metaphor, from Cohen, GA. Where the action is: On the site of distributive justice. Philosophy & Public Affairs 1997;26:3–30.CrossRefGoogle Scholar

45. James Hughes makes a similar point, in his contribution to a special issue of this journal on gene editing. Hughes, JJ. A defense of limited regulation of human genetic therapies. Cambridge Quarterly of Healthcare Ethics 2019;28:112–20.CrossRefGoogle ScholarPubMed

46. Nicholas Agar notes as well the connection between these questions about gene editing and issues in the philosophy of medicine about health, disease, and illness, in his contribution to a special issue of this journal on gene editing. Agar, N. Why we should defend gene editing as eugenics. Cambridge Quarterly of Healthcare Ethics 2019;28:9–19.CrossRefGoogle ScholarPubMed