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.

Genome Modifying Reproductive Procedures and their Effects on Numerical Identity.

The advantages and risks of a number of new genome modifying procedures seeking to create healthy or enhanced individuals, such as Maternal Spindle Transfer, Pronuclear Transfer, Cytoplasmic Transfer and Genome Editing, are currently being assessed from an ethical perspective, by national and international policy organizations. One important aspect being examined concerns the effects of these procedures on different kinds of identity. In other words, whether or not a procedure only modifies the qualities or properties of an existing human being, meaning that merely the qualitative identity of this single individual is affected, or whether a procedure results in the creation of a new individual, meaning that a numerically distinct human being would have come into existence. In this article, the different identity arguments proposed, so far, are presented with respect to these novel reproductive procedures. An alternative view is then developed using the Origin Essentialism argument to indicate that any change in the creative conditions of an individual such as in his or her biology but also the moment in time, and the three dimensions of space, will have a numerical identity effect and bring into existence a new individual who would not, otherwise, have existed. Because of this, it is concluded that a form of selection may have taken place in which a preference was expressed for one new possible individual instead of another, based on some frame of reference. This may then mean that a selection between persons has occured  contravening the European Union Charter of Fundamental Rights which was ratified in 2000.

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.

The need for donor consent in mitochondrial replacement.

Mitochondrial replacement therapy (MRT) requires oocytes of women whose mitochondrial DNA will be transmitted to resultant children. These techniques are scientifically, ethically and socially controversial; it is likely that some women who donate their oocytes for general in vitro fertilisation usage would nevertheless oppose their genetic material being used in MRT. The possibility of oocytes being used in MRT is therefore relevant to oocyte donation and should be included in the consent process when applicable. In present circumstances (especially because MRT is still an emerging technique), specific consent should be obtained. However, once MRT becomes more routine, such consent could be incorporated into the general consent process for oocyte donation. The reported lack of proper consent for MRT from the oocyte donor in the first baby born via the technique is an ethical failing and should be corrected in any future practice of MRT.

Mitochondrial replacement therapy.

PURPOSE OF REVIEW: The present study briefly reviews the history of mitochondrial replacement therapy (MRT); however, the focus is on recent advancements and future directions of the field. Specifically addressing societal and legal concerns and advances in MRT. RECENT FINDINGS: There continue to be new ethical debates surrounding MRT. In addition, there have been advancements in MRT techniques which could improve potential outcomes. Furthermore, advances in genetics continue to provide alternative approaches to treatment of many diseases, including alternatives to MRT. SUMMARY: MRT may be beneficial to eradicate a severely debilitating and often fatal disease. Despite significant supporting safety and efficacy, there are still many social and legal barriers to instituting MRT to clinical practice.

Lesbian motherhood and mitochondrial replacement techniques: reproductive freedom and genetic kinship.

In this paper, we argue that lesbian couples who wish to have children who are genetically related to both of them should be allowed access to mitochondrial replacement techniques (MRTs). First, we provide a brief explanation of mitochondrial diseases and MRTs. We then present the reasons why MRTs are not, by nature, therapeutic. The upshot of the view that MRTs are non-therapeutic techniques is that their therapeutic potential cannot be invoked for restricting their use only to those cases where a mitochondrial DNA disease could be 'cured'. We then argue that a positive case for MRTs is justified by an appeal to reproductive freedom, and that the criteria to access these techniques should hence be extended to include lesbian couples who wish to share genetic parenthood. Finally, we consider a potential objection to our argument: that the desire to have genetically related kin is not a morally sufficient reason to allow lesbian couples to access MRTs.

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.

Should Mitochondrial Donation Be Anonymous?

Currently in the United Kingdom, anyone donating gametes has the status of an open-identity donor. This means that, at the age of 18, persons conceived with gametes donated since April 1, 2005 have a right to access certain pieces of identifying information about their donor. However, in early 2015, the UK Parliament approved new regulations that make mitochondrial donors anonymous. Both mitochondrial donation and gamete donation are similar in the basic sense that they involve the contribution of gamete materials to create future persons. Given this similarity, this paper presumes that both types of donor should be treated the same and made open-identity under the law, unless there is a convincing argument for treating them differently. I argue that none of the existing arguments that have been made so far in favor of mitochondrial donor anonymity are convincing and mitochondrial donors should therefore be treated as open-identity donors under UK law.

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.

Does egg donation for mitochondrial replacement techniques generate parental responsibilities?

Children created through mitochondrial replacement techniques (MRTs) are commonly presented as possessing 50% of their mother's nuclear DNA, 50% of their father's nuclear DNA and the mitochondrial DNA of an egg donor. This lab-engineered genetic composition has prompted two questions: Do children who are the product of an MRT procedure have three genetic parents? And, do MRT egg donors have parental responsibilities for the children created? In this paper, I address the second question and in doing so I also address the first one. First, I present a brief account of mitochondrial diseases and MRTs. Second, I examine how MRTs affect the numerical identity of eggs and zygotes. Third, I investigate two genetic accounts of parenthood and MRT egg donation. Fourth, I explore three causal accounts of parenthood and MRT egg donation. My conclusion is that, under the appropriate circumstances, MRT egg donors are parentally responsible for the children created under genetic accounts of parenthood and under causal accounts of parenthood.

Mitochondrial Replacement Techniques, Scientific Tourism, and the Global Politics of Science.

The United Kingdom is the first and so far only country to pass explicit legislation allowing for the licensed use of the new reproductive technology known as mitochondrial replacement therapy. The techniques used in this technology may prevent the transmission of mitochondrial DNA diseases, but they are controversial because they involve the manipulation of oocytes or embryos and the transfer of genetic material. Some commentators have even suggested that MRT constitutes germline genome modification. All eyes were on the United Kingdom as the most likely location for the first MRT birth, so it was a shock when, on September 27, 2016, an announcement went out that the first baby to result from use of the intervention had already been born. In New York City, United States-based scientist John Zhang used maternal spindle transfer (one of the recognized MRT methods) to generate five embryos for a woman carrying oocytes with deleterious mutations of the mitochondrial DNA. Zhang then shipped the only euploid embryo to Mexico, where it was transferred to the mother's uterus. Zhang's team's travel across international borders to carry out experimental procedures represents a form of scientific tourism that has not been properly ethically explored; it can, however, have seriously detrimental effects for developing countries.

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.