https://orcid.org/0000-0002-5570-3403
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Abstract
The distinction between germline and somatic gene editing is fundamental to the ethics of human gene editing. Multiple conferences of scientists, ethicists, and policymakers, and multiple professional bodies, have called for moratoria on germline gene editing, and editing of human germline cells is considered to be an ethical “red line” that either never should be crossed, or should only be crossed with great caution and care. However, as research on germline gene editing has progressed, it has become clear that not all germline interventions are alike, and that these differences make a significant moral difference, when it comes to ethical questions about research, regulation, clinical application, and medical justification. In this paper, I argue that, rather than lumping all germline interventions together, we should distinguish between revising, correcting, and transferring genes, and I assess the consequences of this move for the ethics of gene editing.
ACKNOWLEDGMENTS
The idea for this paper came out of an attempt to answer an objection raised during a talk I gave at the Center for Modeling Complex Interactions at the University of Idaho in April 2019. Thanks to Aleta Quinn, for raising the objection and for extended discussion of it during that visit, and to Graham Hubbs, for inviting me to speak at Idaho. Ideas in the paper were floated in presentations at the 2019 International Bioethics Retreat in Paris, France; the 2019 American Society for Bioethics and Humanities Meeting in Pittsburgh, PA; and California State University, Northridge. Thanks to Tomi Kushner for inviting me to speak in Paris, and to Sarah Hansen and Kristina Meshelski, for inviting me to speak at Northridge. The complete paper got a full hearing in a presentation at the Institute for Practical Ethics at the University of California, San Diego. The bulk of the paper was written while the author was a visiting scholar at the UCSD Institute for Practical Ethics; thanks to John Evans and Craig Callender for their hospitality and for facilitating the visit. Thanks also to John and to Reuven Brandt for discussion of the ideas in the paper. 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.
DISCLOSURE STATEMENT
Dr. Shoukhrat Mitalipov, director of the Oregon Health and Science University Center for Embryonic Cell and Gene Therapy, and Principal Investigator and coauthor of two studies on germline gene editing cited in this paper, is on the advisory committee for the grant that funded work on this paper. Dr. Cwik reports grants from the National Human Genome Research Institute during the conduct of the study; and the author is a member of the external advisory board for the Oregon Health and Science University Center for Embryonic Cell and Gene Therapy. Members of this center were involved in public research discussed in this paper.
Notes
1 This paper is the second of two essays on these distinctions; on the therapy/enhancement distinction, see Cwik (Citation2019). For a good overview of the ethics of gene editing that gives pride of place to the role of the therapy/enhancement distinction, see Gyngell et al. (Citation2017).
2 Thus the concept of a gene implicit in the ethics of gene editing roughly corresponds to what Griffiths and Stotz (Citation2006) call the “postgenomic” gene, which “embodies the continuing project of understanding how genome structure supports genome function, but with a deflationary picture of the gene as a structural unit” (515). The way different concepts of the gene operate in bioethical discussion about gene editing, precision medicine, and biotechnology is an interesting and significant subject in its own right, one that is the focus of ongoing research by Reuven Brandt.
3 “CRISPR” stands for Clustered Regularly Interspaced Short Palindromic Repeats. It is a gene editing technique in which a guide RNA directs a CRISPR-associated (or “Cas”) nuclease to a target.
4 This distinction between inducing uncommon and correcting common mutations and an argument for its relevance is made in Cwik (Citation2019).
5 There is significant disagreement about whether it is appropriate to put MRT in the same ethical category as germline gene editing. Baylis (Citation2017), for instance, argues that it should be, Parens and Juengst (Citation2001) argue that it is more complicated. The statements and position papers discussed in section 1 do not include MRT in the category “germline gene editing”. For purposes of this paper, this debate does not matter. If the reader is committed to the idea that MRT is in a different ethical category from editing of nuclear DNA at the germline, then the reader should take MRT as a stand in for future editing procedures that involve transfer of nuclear DNA, which is at least hypothetically possible in humans, and would be necessary for many of the kinds of exotic gene editing (for enhancement, for example) that generate so much bioethical controversy. In such cases transfer of DNA would result in an individual with a genome that they could not have via non gene editing-involved reproduction from their two progenitors (that is, they would have a genome that is not just different from what they would have had, but includes novel material than they could not have had, given the possible combinations from their male and female progenitors), and this would raise many of the same questions as outlined here in the discussion of MRT (for instance, questions about risks and about genetic identity and parentage). How these would relate to those discussed here about MRT is a topic for a different paper. The point here is that, whether it is mitochondrial or nuclear DNA, the mechanics of the procedure—transfer of genetic material—raises different questions that are not subsumed by those generated by other germline interventions.
6 Thanks to an anonymous referee for raising this point.
7 “Gene correction” as a description for this sort of procedure has been used before (see, for instance, Koch Citation2016; Lander et al. Citation2019; Wolf et al. Citation2019). Lander and others (Citation2019) make a distinction between correction and enhancement, which is a narrower distinction than the one I am making here between correction and revision. Revising genes can include enhancement (as discussed below and in section 5), but not all revision is enhancement, as revision can also be used for therapeutic aims, as it was in the He Jiankui case (however misguided).
8 The utility of making fine grained distinctions for this purpose is discussed in Cwik (Citation2019).
9 Some would undoubtedly argue that it is too strict; the point here is not that we should adopt this rule, the point is that we can formulate a rule that permits some forms of germline gene editing without inevitably leading us down the slippery slope.
10 As alleged, for example, by Pinker (Citation2015).