Year: 2017
Type: article
Abstract: If I can stop one heart from breaking, I shall not live in vain; If I can ease one life the aching, Or cool one pain, Or help one fainting robin Unto his nest again, I shall not live in vain. Emily Dickinson (1830–1886) The fine contribution by Palacios-Gonzalez and Medina-Arellano in this issue of the journal delineates the Mexican laws and regulations governing the conduct of Mitochondrial Replacement Therapy (MRT) for the prevention of mitochondrial DNA diseases.1 On the strength of this analysis, the authors conclude that a widely reported MRT procedure carried out in 2015 by a US-led team in Guadalajara for a Jordanian national likely violated federal Mexican regulations.1 It would thus appear that the legal landscape in Mexico is hardly MRT permissive and that the aforementioned US-led team may have, perhaps inadvertently and unknowingly, run afoul of Mexican law.1 Equally sobering is the realization that the cross-border MRT initiative in question would have never come to pass in the first place were it not for a statutory US moratorium on the conduct of MRT. The latter, a renewable appropriation rider, first enacted on December 18, 2015, is presently in force through September 30, 2017.2,3 Whether or not an Investigational New Drug Application with the FDA for the conduct of MRT would have been approved absent the moratorium cannot be ascertained. All told, this episode is a stark reminder that we live in a globalized world where, absent extraterritorial extension of law, prohibition in one country may lead to medical tourism in another. Viewed in the here and now there is no escaping the conclusion that the legal landscape in both the US and Mexico is ill disposed to the conduct of MRT. The precise rationale for this state of affairs is unknown in that the grounds for the prohibition of MRT have not been publicly explicated. Absent an explicit account of the why and wherefore of the legislative MRT moratoria in question, the relevant motivational roots can only be surmised. It is the objective of this peer commentary to explore the potential common roots behind the legislative opposition to MRT in both nations. Special emphasis will be placed on the possibility that the prohibition of MRT is attributable to fear of the unfamiliar, to safety concerns, to ethical considerations, and to doctrinal objections. Human history is littered with examples of fearful reactions to disruptive scientific breakthroughs which all too often are deemed contra naturum. One need look no further than the inquisitional trial of Galileo Galilei for championing the heliocentric view of the solar system in violation of the geocentric Christian dogma. This non-specific fear of the unknown, the uncharted, and the unfamiliar is all about the threat of revising the laws of nature, tampering with creation, altering a world order known to man for millennia, and in many cases, challenging the long-reigning precept of the traditional family. Resistant to cerebral and utilitarian arguments, this fear may all too often be aggravated by charged phrases such as ‘Slippery Slope’ ‘Playing God,’ or ‘Crossing a Line.’ This reality, thoroughly grasped by British author Philip Ball in ‘Unnatural reactions,’ has been articulated earlier by British scientist J.B.S. Haldane who stated that ‘…there is no great invention…which has not been hailed as an insult to some god. But if every physical and chemical invention is a blasphemy, every biological invention is a perversion’.4,5 This very same ill-defined fear likely prompted Nobel Laureate Sir Robert G. Edwards of in vitro fertilization fame to quote Professor Ian Donald (Regius Professor of Obstetrics and Gynaecology at Glasgow University) as saying ‘…a Frankenstein monster may not be too far away. The dangers are very real…scientists are not all saints’.6 Closer to home, it was Susan L. Solomon, Co-Founder and Chief Executive Officer of the New York Stem Cell Foundation, who remarked with MRT in mind ‘I don’t think [that] we should be motivated by a fear of the unknown’.7 Viewed in this light, the statutory prohibition of MRT in both the USA and Mexico may represent, at least in part, what has been dubbed by legal scholar Cass R. Sunstein a ‘Law of Fear’ which has been enacted largely—if not solely—in response to ‘risk panic’.8 Yet another possible motivation for a legislative ban of MRT may have drawn on safety concerns many of which have been the subject of extensive scientific scrutiny.9,10,11,12 The conduct of MRT in nonhuman primates has proven both safe and efficacious though longer-term follow-up of the resultant progeny is still in progress.13 A parallel body of work involving MRT-derived preimplantation human embryos proved equally reassuring.14 Residual—if uncertain—safety concerns now revolve around the prospect of harmful interactions between the mitochondria of the donor and the nucleus of the recipient (mitonuclear incompatibility).15,16,17,18,19,20 Whether or not mitonuclear incompatibility is applicable to outbred primate species including the human remains uncertain.21 Developing donor-independent versions of MRT might put this concern to rest. Yet another safety concern entails the possibility of delayed expansion of residual mutant (maternal) mitochondrial DNA in progeny born in the wake of MRT. Whether or not these concerns merely represent an observed in vitro phenomenon remains to be determined.22,23,24,25,26 In search of synthesis, the Human Fertilisation and Embryology Authority (HFEA) of the UK commissioned four independent scientific reviews of the safety and efficacy of MRT. It was the conclusion of the review committee that MRT may be ‘cautiously adopted in clinical practice where inheritance of the disease is likely to cause death or serious disease and where there are no acceptable alternatives’.27 On the strength of these recommendations, the HFEA has recently ‘approved the first application by Newcastle Fertility at Life for the use of mitochondrial donation to treat patients’.28 Consideration must also be given to the possibility that the statutory prohibition of MRT has been driven by troubling ethical considerations. Ethical concerns of note are likely to include—but need not be limited—to the ‘tri-parental’ construct (‘three parent babies’), the parental status of the mitochondrial donor, the matter of non-consenting progeny, the question of a life worth living, and the matter of germline modification.29 Intent on facing up to the potential ethical dilemmas wrought by MRT, the independent Nuffield Council on Bioethics carried out a careful ethical review. It was the conclusion of the Council's working group that ‘the health and social benefits…of living free from mitochondrial disorders, and where potential parents express a preference to have genetically-related children…if these novel techniques are adequately proven to be acceptably safe and effective…it would be ethical for families to use them, if they wish to do so’…30 Similar conclusions have been reached by the Institute of Medicine of the National Academy of Sciences, which placed emphasis on risk-limiting studies inclusive of the transfer of ‘male embryos…to avoid introducing heritable genetic modification during initial clinical investigations’.31 Finally, consideration must also be given to the possibility that legislative banning of MRT may reflect deep-seated doctrinal concerns consonant with the catechism of western Christianity. One leading religious doctrinal concern is bound to entail the sanctity of life which is liable to be violated by the destruction of a human zygote in one form of MRT (ie Pronuclear Transfer).32,33 The embryo-sparing version of MRT (ie Maternal Spindle Transfer) might put this concern to rest.34 Another religious doctrinal concern is likely to focus on the dignity of procreation that is ‘begotten’ through conjugal marital love as opposed to ‘made’ as in ‘reproduction without sex’.35 Understandably, neither MRT let alone the attendant triparental construct are compatible with this ecclesiastical ideal. Yet, another sectarian concern is apt to target the attendant modification of the human germline which in the view of C.S. Lewis comported with the dystopic ‘abolition of man’.36,37,38,39According to this world view, the absence of limits on human finitude amounts to a display of hubris and to a usurpation of divine power.40 Taken together, these doctrinal concerns are consonant with several papal encyclicals which affirm the sanctity of life, the centrality of conjugal married love, and the illicit nature of genetic engineering.41,42,43,44 Encyclicals of special relevance include the Gaudium et spes and Humanae vitae by Pope Paul VI, the Donum Vitae by Pope John Paul II, and the Dignitas Personae by Pope Benedict XVI.45,46 In a departure from some of the aforementioned convictions, the Bishop of Carlisle of the Church of England (The Right Reverend James Newcome) came out in support of MRT in the course of the parliamentary debate in the UK House of Lords.47 The prohibitions on MRT in US and Mexican laws might be seen as in tension to the beneficence, widely recognized as the bedrock of medicine wherein it constitutes a key virtue of the virtuous health professional.48 More importantly, beneficence and altruism comprise the very essence of professionalism in medicine.49,50Apart and distinct from the preceding considerations, beneficence also comprises a central tenet of western Christianity.51 Christ remains the very embodiment of beneficence as are the lessons of the Parable of the Good Samaritan.52 Physicians pledge to ‘come for the benefit of the sick’ as well as to bring forth treatment ‘for the benefit of the sick’ in the name of altruism.53 Prohibiting MRT might be thought to pose a blow to beneficence: surely no well-intentioned legislator would wish to ignore the inevitable, that is, the birth of oxygen-starved wheel chair-bound children. Surely no well-meaning legislator would take pleasure at the sight of grief-stricken parents whose agony is indescribable. The strongest rejoinder is that the choice prohibiting MRT will not result in children with severe disabilities, but instead steer the would-be parents toward adoption or using donor gametes. Thus, in determining the justifiability of an MRT prohibition one would need to arrive at two determinations: the first question is empirical—how many people faced with a prohibition on MRT would choose to go forward and reproduce and produce children with mitochondrial disease or engage in medical tourism to get MRT elsewhere as opposed to using donor gametes or adoption? The second question is normative, if individuals are steered to donor gametes or adoption as an alternative, should we view that as normatively problematic? That is, has the person in question been unjustifiably forced to give up something enjoyed by many others without mitochondrial diseases—having a child with whom one has a genetic connection—or does the technology instead problematically emphasize the importance of genetic connection. Given that there are 1000 affected births per year in the USA alone, it is essential that we have a robust ethical debate about whether this technology should be permitted rather than the legislation without deliberation that has characterized the current ban in the USA.54
DOI: 10.1093/jlb/lsx023
Authors: Eli Y. Adashi, I. Glenn Cohen
Institutions: Brown University, Harvard University
Language: English
Subfield: Physiology
Field: Medicine
Domain: Health Sciences
Open Access status: diamond
OpenAlex ID: W2744440013