Germline Modification and Policymaking: The Relationship between Mitochondrial Replacement and Gene Editing

Abstract

‘Mitochondrial replacement’ and ‘germline gene editing’ are relatively new techniques that represent a significant moral, technological, and legal threshold, as they would introduce permanent and heritable changes to the human gene pool. This article examines the close relationship between these two technologies over time, considering what regulatory lessons can be learned from the former as attention turns to the latter. It argues that the UK’s ‘mitochondrial replacement’ approval process should not be taken as a model for the wider regulation of germline gene editing, and that policy-making needs to contend with a comprehensive picture of the social and political meaning of these technologies in the world.

KEYWORDS:

• human germline modification
• germline gene editing
• mitochondrial replacement
• language
• biopolicy
• bioethics and biopolitics

Notes on contributors

Jessica Cussins is a consultant to the Center for Genetics and Society and a Research Fellow at the Center for Long-Term Cybersecurity, where she conducts research on the security implications of artificial intelligence and the governance of digital technologies. She received her MA in public policy from Harvard University and her BA in anthropology from the University of California, Berkeley with highest distinction honors.

Leah Lowthorp, PhD, is Program Manager and Mellon/ACLS Public Fellow at the Center for Genetics and Society. Her research focuses on international germline modification policy, the social and ethical implications of human reproductive and genetic technologies, and the ways in which biopolitical narratives circulate both online and face-to-face. Leah has taught at the University of Pennsylvania and Harvard University, and is a regular contributor to Biopolitical Times.

Notes

1 Also known as the Oviedo Convention, the Council of Europe's Convention on Human Rights and Biomedicine indicates in Article 13 that ‘an intervention seeking to modify the human genome may only be undertaken for preventive, diagnostic or therapeutic purposes and only if its aim is not to introduce any modification in the genome of any descendants’ (Council of Europe 1997). UNESCO's Universal Declaration on the Human Genome and Human Rights states that ‘germ-line interventions’ could be ‘contrary to human dignity’ (UNESCO 1997).

2 The UK has considered itself a leader in innovative reproductive technologies since the 1978 birth of the world's first child created via in vitro fertilization (IVF), Louise Brown, and some have posited that a drive to secure other ‘world firsts’ is behind these new policy deliberations, see Dickenson and Darnovsky 2014.

3 As Baylis (2017) notes, the technique is often described in the largely unquestioned terms of satisfying a ‘need’ for genetically-related children. She argues that this constitutes an ‘inappropriate overvaluing of genetic relatedness within families,’ and that genetic-relatedness does not constitute a need, but only a ‘desire’. Baylis further suggests that, as this technology responds to the wants of ‘an infinitesimally small number of people,’ it does not warrant the investment of public research funds that would be better spent ameliorating larger social and health inequities.

4 However, unlike germline gene editing, changes made via ‘mitochondrial replacement’ techniques are only heritable through the female line. Newson and Wrigley (2017) therefore propose the term ‘conditionally inheritable genomic modification’ for these techniques.

5 See also Baylis 2017; Gómez-Tatay et al. 2017; Jones 2015; Nisker 2015.

6 See also Baylis 2017.

7 González-Santos (2017) provided a recent compelling argument surrounding this controversy over terminology, https://doi.org/10.1093/jlb/lsx022.

8 See also Knoepfler 2015.

9 The United Mitochondrial Disease Foundation's 2015 Position Statement on Mitochondrial Replacement Therapy cites these misleading statistics as well, http://www.umdf.org/mitochondrial-replacement-therapy/.

10 This is reminiscent of a comment made by Richard Hynes, co-author of a 2017 National Academies of Sciences, Engineering, and Medicine report on human genome editing, at the report's press release in February 2017, suggesting that the only reason for previous opposition to germline editing in the past was because it was not safe or feasible. See Lowthorp 2017.

11 See Lowthorp 2016b.

12 See Johnson 2016 for more details.

13 See Gómez-Tatay et al. 2017; Muir et al. 2016; Dunham-Snary and Ballinger 2015.

14 Dieter Egli, a noted scientist from the Yamada et al. (2016) study, viewed this mtDNA carryover and reversion as serious enough to postpone any clinical applications of NGT (Knoepfler 2016b). Despite this, the HFEA's Fourth Review of NGT concluded that it was not a serious concern (Lowthorp 2016a), and, less than six months after the study was published, the HFEA approved the clinical application of the technology.

15 See Gómez-Tatay et al. 2017.

16 See Norsigian 2006; see also Ikemoto 2009; Schenker and Ezra 1994.

17 See Lowthorp 2018; Sample 2018.

18 John Zhang was widely quoted in the press as claiming that ‘there are no rules’ in Mexico concerning this technology. As Palacios-González and De Jesús Medina Arellano (2017) have noted, however, Zhang may well have violated both Mexican federal and Jalisco state law. As Chan et al. (2017) have recently pointed out as well, Zhang's unauthorized cross-border procedure is a type of scientific tourism that can have harmful effects on science in developing countries.

19 See Medscape 2016, https://www.pscp.tv/Medscape/1BRJjANLwVgGw.

20 See New Hope Fertility Center 2016 video at 3:05, https://www.youtube.com/watch?v=h9AK-76_1AE&feature=youtu.be.

21 See Gallagher 2016.

22 See Scutti 2017.

23 Eligible patients are described as ‘patients in whose germ line there are likely to be high levels of heteroplasmy or homoplasmy for the abnormal (pathogenic) mtDNA, and who are thus unlikely to have any suitable embryos for transfer. Pre-treatment assessment would need to take into account the particular mutation involved, the inheritance pattern in the family, the likely clinical manifestations of disease, the efficacy of any previous treatments such as PGD, and the patient's understanding of the risks and limitations of what is being offered.’

24 http://www.biopoliticaltimes.org/downloads/DKeefeMRconsiderations.pdf.

25 For an example of this discourse in relation to gene editing, see Eschner 2017, and for a critique, see Shanks 2018.

26 For an example of this discourse in relation to human cloning, see Shermer 2003.

27 https://www.congress.gov/bill/114th-congress/house-bill/2029.

28 For Canada, see CBC News 2017; for Australia, see Johnston 2016.

29 See Shanks 2015 and Lowthorp 2016c. The U.S. Congress does not permit the FDA to consider applications for the propose ofngenetically modifying human embryos.

30 The study also claimed to have no off-target effects or mosaicism. A number of prominent scientists have since raised doubts about the accuracy of the study's findings. See Egli et al. 2017; Servick 2017a.

31 See Mullin 2017b.

32 See also Hasson 2017.

33 For an allied argument, see Darnovsky 2013.

34 The British Fertility Society has called for Purdy, the world's first embryologist, to be recognized as IVF's third pioneer alongside Edwards and Steptoe on the 40th anniversary of IVF next year, see Photopoulos 2017. Edwards was awarded the Nobel Prize in Physiology or Medicine in 2010 for in vitro fertilization. Since the Nobel Prize is not awarded posthumously, Steptoe did not receive the recognition.