The Regulation of Mitochondrial Replacement Techniques Around the World.

Mitochondrial replacement techniques (MRTs, also referred to as mitochondrial replacement therapies) have given hope to many women who wish to have genetically related children but have mitochondrial DNA mutations in their eggs. MRTs have also spurred deep ethical disagreements and led to different regulatory approaches worldwide. In this review, we discuss the current regulation of MRTs across several countries. After discussing the basics of the science, we describe the current law and policy directions in seven countries: the United Kingdom, the United States, Canada, Australia, Germany, Israel, and Singapore. We also discuss the emerging phenomenon of medical tourism (also called medical travel) for MRTs to places like Greece, Spain, Mexico, and Ukraine. We then pull out some key findings regarding similarities and differences in regulatory approaches around the world.

Should Long-Term Follow-up Post-Mitochondrial Replacement be Left up to Physicians, Parents, or Offspring?

UK law permits parents to use mitochondrial replacement (MR) to have genetically-related children without serious mitochondrial disease. However, long-term follow-up is required for each case. Whether this follow-up should be left to physicians, parents, or offspring has not been established. Due to the experimental status of MR, physicians must inform parents of the risks and the importance of follow-up tailored to a specific mitochondrial disease. Given that the use of MR is a responsible exercise of reproductive freedom, parents should ensure that the follow-up is performed properly and in the best interests of their offspring. On becoming legally competent, the resulting children should be entitled to refuse follow-up provided that the prevention of mitochondrial disease with no adverse effects has been evident till then. This offspring-centred long-term follow-up approach might also be applied to the use of MR for infertility treatment, even though the primary endpoint is healthy live births.

Public attitudes towards novel reproductive technologies: a citizens' jury on mitochondrial donation.

STUDY QUESTION: Does an informed group of citizens endorse the clinical use of mitochondrial donation in a country where this is not currently permitted? SUMMARY ANSWER: After hearing balanced expert evidence and having opportunity for deliberation, a majority (11/14) of participants in a citizens' jury believed that children should be able to be born using mitochondrial donation. WHAT IS KNOWN ALREADY: Research suggests that patients, oocyte donors and health professionals support mitochondrial donation to prevent transmission of mitochondrial disease. Less is known about public acceptability of this novel reproductive technology, especially from evidence using deliberative methods. STUDY DESIGN, SIZE, DURATION: This study comprised a citizens' jury, an established method for determining the views of a well-informed group of community members. The jury had 14 participants, and ran over one and a half days in 2017. PARTICIPANTS/MATERIALS, SETTING, METHODS: Jurors were members of the public with no experience of mitochondrial disease. They heard and engaged with relevant evidence and were asked to answer the question: 'Should Australia allow children to be born following mitochondrial donation?' MAIN RESULTS AND THE ROLE OF CHANCE: Eleven jurors decided that Australia should allow children to be born following mitochondrial donation; 7 of whom added conditions such as the need to limit who can access the intervention. Three jurors decided that children should not (or not yet) be born using this intervention. All jurors were particularly interested in the reliability of evidence, licensing/regulatory mechanisms and the rights of children to access information about their oocyte donors. LIMITATIONS, REASONS FOR CAUTION: Jurors' views were well informed and reflected critical deliberation and discussion, but are not intended to be representative of the whole population. WIDER IMPLICATIONS OF THE FINDINGS: When presented with high quality evidence, combined with opportunities to undertake structured deliberation of novel reproductive technologies, members of the public are able to engage in detailed discussions. This is the first study to use an established deliberative method to gauge public views towards mitochondrial donation. STUDY FUNDING/COMPETING INTEREST(S): This study was funded by a University of Sydney Industry and Community Collaboration Seed Award (2017), which was awarded contingent on additional funding from the Mito Foundation. Additional funding was provided by the Mito Foundation. The Foundation was not involved in jury facilitation or deliberation, nor analysis of research data. TRIAL REGISTRATION NUMBER: Not applicable.

Overcoming bioethical, legal, and hereditary barriers to mitochondrial replacement therapy in the USA.

The purpose of the paper is to explore novel means to overcome the controversial ban in the USA against mitochondrial replacement therapy, a form of IVF, with the added step of replacing a woman's diseased mutated mitochondria with a donor's healthy mitochondria to prevent debilitating and often fatal mitochondrial diseases. Long proven effective in non-human species, MRT recently performed in Mexico resulted in the birth of a healthy baby boy. We explore the ethics of the ban, the concerns over hereditability of mitochondrial disease and its mathematical basis, the overlooked role of Mitochondrial Eve, the financial burden of mitochondrial diseases for taxpayers, and a woman's reproductive rights. We examine applicable court cases, particularly protection of autonomy within the reproductive rights assured by Roe v Wade. We examine the consequences of misinterpreting MRT as genetic engineering in the congressional funding prohibitions causing the MRT ban by the FDA. Allowing MRT to take place in the USA would ensure a high standard of reproductive medicine and safety for afflicted women wishing to have genetically related children, concurrently alleviating the significant financial burden of mitochondrial diseases on its taxpayers. Since MRT does not modify any genome, it falls outside the "heritable genetic modification" terminology of concern to Congress and the FDA. Correcting this terminology, the IOM's conclusion that MRT is ethical, the continuing normalcy of the first MRT recipient, and increasing public awareness of the promising benefits might be all that is required to modify the FDA's position on MRT.

Mexico and mitochondrial replacement techniques: what a mess.

Background: The first live birth following the use of a new reproductive technique, maternal spindle transfer (MST), which is a mitochondrial replacement technique (MRT), was accomplished by dividing the execution of the MST procedure between two countries, the USA and Mexico. This was done in order to avoid US legal restrictions on this technique. Sources of data: Academic articles, news articles, documents obtained through freedom of information requests, laws, regulations and national reports. Areas of agreement: MRTs are new reproductive techniques that present novel ethical and legal challenges, since genetic material from three people is employed to create a child. Areas of controversy: Could the first MST procedure that culminated in a live birth negatively impact reproductive medicine in Mexico? Growing points: The USA and Mexico need specific and clear legislation on MRTs, in order for such techniques not to be governed by prior existing legislation on assisted reproduction that is inadequate for dealing with the new challenges that these techniques present. Areas timely for developing research: There is a pressing need for work to be done on the international governance of new reproductive techniques.

Mitochondrial Replacement Techniques : Examining Collective Representation in Emerging Technologies Governance.

In this article, I draw on research carried out in Europe, primarily in Germany, on patients' and scientists' perspectives on mitochondrial replacement techniques (MRTs) in order to explore some of the complexities related to collective representation in health governance, which includes the translation of emerging technologies into clinical use. Focusing on observations, document analyses, and interviews with eight mitochondrial disease patient organization leaders, this contribution extends our understanding of the logic and meanings behind the ways in which patient participation and collective representation in health governance initiatives take shape. My findings highlight the ways in which a commitment to a global mitochondrial disease patient community and a sense of patient solidarity influence expressions of support with regard to legalizing mitochondrial replacement techniques. My analyses illustrate how normative practices and expectations of participatory governance potentially foreclose opportunities for sustained collective patient engagement with the complex ethical, social, and political dimensions of emerging technologies and may silence diverse and potentially dissenting embodied and lived responses to the prospects of particular technological developments.

Gene Editing: A View Through the Prism of Inherited Metabolic Disorders.

Novel technological developments mean that gene editing - making deliberately targeted alterations in specific genes - is now a clinical reality. The inherited metabolic disorders, a group of clinically significant, monogenic disorders, provide a useful paradigm to explore some of the many ethical issues that arise from this technological capability. Fundamental questions about the significance of the genome, and of manipulating it by selection or editing, are reviewed, and a particular focus on the legislative process that has permitted the development of mitochondrial donation techniques is considered. Ultimately, decisions about what we should do with gene editing must be determined by reference to other non-genomic texts that determine what it is to be human - rather than simply to undertake gene editing because it can be done.

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

'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.

Preventing Mitochondrial Disease: A Path Forward.

In a possible first, the heritable transmission of a fatal mitochondrial DNA disease (Leigh syndrome) may have been prevented by replacing the mutation-bearing mitochondria of oocytes with donated mutation-free counterparts. The procedure, carried out by a U.S.-led team, took place in Mexico in circumvention of a statutory U.S. moratorium on mitochondrial replacement. This development calls into question the regulatory utility of a national moratorium in a globalized world wherein cross-border care is increasingly prevalent. This development also calls to account the moral defensibility of a moratorium that acquiesces in the birth of gravely ill children whose afflictions could have been prevented. In this Current Commentary, we outline a potential path forward by analyzing the dual imprint of the moratorium, examining its legislative shortcomings, exploring its motivational roots, considering its national effect, and proposing its unlinking from the related yet distinct ban on editing the genome of the human embryo.

Three persons, three genetic contributors, three parents: Mitochondrial donation, genetic parenting and the immutable grammar of the 'three x x'.

In 2015, two novel in vitro fertilisation techniques intended to prevent the inheritance of mitochondrial disease were legalised in the United Kingdom, following an intense period of inquiry including scientific reviews, public consultations, government guidance and debates within the Houses of Parliament. The techniques were controversial because (1) they introduced a third genetic contributor into the reproductive process and (2) they are germline, meaning this genetic change could then be passed down to subsequent generations. Drawing on the social worlds framework with a focus on implicated actors and discursive strategies, this article explores key features of the UK mitochondrial debates as they played out in real time through policy documents and public debate. First, it situates the technology within a repertoire of metaphors, emotional terminology and their politics. It then explores the immutable grammar of 'three x x' that formed a key component of the political debate, by focusing on how institutional reviews discursively negotiated uncertainty around genetic parentage and how beneficiaries were implicated and rendered distant. Following the 2016 announcement of the first baby born through mitochondrial donation (in Mexico) and several pregnancies (in the Ukraine), we close with a discussion about the specific nature of UK regulation within a global economy. Overall, this article contributes to a much needed sociological discussion about mitochondrial donation, emerging reproductive technologies and the cultural significance of genetic material and genetic relatedness.

Mitochondrial donation, patient engagement and narratives of hope.

This article develops the sociology of hope and patient engagement by exploring how patients' perceptions and actions are shaped by narratives of hope surrounding the clinical introduction of novel reproductive techniques. In 2015, after extensive public debates, the UK became the first country to legalise a mitochondrial donation technique aimed at preventing the transmission of inherited disorders. The article draws on the accounts of twenty-two women of reproductive age who are at risk of having a child with mitochondrial disease and would be the potential target of the technique. We explore the extent to which our participants engaged with the public debates and how they accounted for their support of mitochondrial donation. We show that while the majority of our participants were in favour of legalisation, they did not necessarily wish to use the technique themselves. We found that hope was multi-faceted, involving hope for self, hope for family and hope for society. We conclude by considering the implications of hope narratives for patients and families and the important but potentially limited role that patients can play as advocates for technology.

Mitochondrial Replacement Techniques: Remaining Ethical Challenges.

Recent developments in the field of mitochondrial replacement technique (MRT) research and clinical practice have raised ethical concerns worldwide. We argue that the future use of MRTs requires a concerted effort among the global research and clinical community to implement and enforce responsible innovation and governance.