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.

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 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.

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.

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.

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.

Ethics of Mitochondrial Replacement Techniques: A Habermasian Perspective.

Jürgen Habermas is regarded as a central bioconservative commentator in the debate on the ethics of human prenatal genetic manipulations. While his main work on this topic, The Future of Human Nature, has been widely examined in regard to his position on prenatal genetic enhancement, his arguments regarding prenatal genetic therapeutic interventions have for the most part been overlooked. In this work I do two things. First, I present the three necessary conditions that Habermas establishes for a prenatal genetic manipulation to be regarded as morally permissible. Second, I examine if mitochondrial replacement techniques meet these necessary conditions. I investigate, specifically, the moral permissibility of employing pronuclear transfer and maternal spindle transfer. I conclude that, according to a Habermasian perspective on prenatal genetic manipulation, maternal spindle transfer (without using a preselected sperm and egg) and pronuclear transfer are morally impermissible. Maternal spindle transfer is, in principle, morally permissible, but only when we have beforehand preselected a sperm and an egg for our reproductive purpose. These findings are relevant for bioconservatives, both for those who hold a Habermasian stance and for those who hold something akin to a Habermasian stance, because they answer the question: what should bioconservatives do regarding mitochondrial replacement techniques? In fact, the answer to this question does not only normatively prescribe what bioconservatives should do in terms of their personal morality, but it also points towards what kind of legislation regulating mitochondrial replacement techniques they should aim at.

Is Mitochondrial Donation Germ-Line Gene Therapy? Classifications and Ethical Implications.

The classification of techniques used in mitochondrial donation, including their role as purported germ-line gene therapies, is far from clear. These techniques exhibit characteristics typical of a variety of classifications that have been used in both scientific and bioethics scholarship. This raises two connected questions, which we address in this paper: (i) how should we classify mitochondrial donation techniques?; and (ii) what ethical implications surround such a classification? First, we outline how methods of genetic intervention, such as germ-line gene therapy, are typically defined or classified. We then consider whether techniques of mitochondrial donation fit into these, whether they might do so with some refinement of these categories, or whether they require some other approach to classification. To answer the second question, we discuss the relationship between classification and several key ethical issues arising from mitochondrial donation. We conclude that the properties characteristic of mitochondrial inheritance mean that most mitochondrial donation techniques belong to a new sub-class of genetic modification, which we call 'conditionally inheritable genomic modification' (CIGM).

Do Mitochondrial Replacement Techniques Affect Qualitative or Numerical Identity?

Mitochondrial replacement techniques (MRTs), known in the popular media as 'three-parent' or 'three-person' IVFs, have the potential to enable women with mitochondrial diseases to have children who are genetically related to them but without such diseases. In the debate regarding whether MRTs should be made available, an issue that has garnered considerable attention is whether MRTs affect the characteristics of an existing individual or whether they result in the creation of a new individual, given that MRTs involve the genetic manipulation of the germline. In other words, do MRTs affect the qualitative identity or the numerical identity of the resulting child? For instance, a group of panelists on behalf of the UK Human Fertilisation and Embryology Authority (HFEA) has claimed that MRTs affect only the qualitative identity of the resulting child, while the Working Group of the Nuffield Council on Bioethics (NCOB) has argued that MRTs would create a numerically distinct individual. In this article, I shall argue that MRTs do create a new and numerically distinct individual. Since my explanation is different from the NCOB's explanation, I shall also offer reasons why my explanation is preferable to the NCOB's explanation.

A Mitochondrial Story: Mitochondrial Replacement, Identity and Narrative.

Mitochondrial replacement techniques (MRT) are intended to avoid the transmission of mitochondrial diseases from mother to child. MRT represent a potentially powerful new biomedical technology with ethical, policy, economic and social implications. Among other ethical questions raised are concerns about the possible effects on the identity of children born from MRT, their families, and the providers or donors of mitochondria. It has been suggested that MRT can influence identity (i) directly, through altering the genetic makeup and physical characteristics of the child, or (ii) indirectly through changing the child's experience of disease, and by generating novel intrafamilial relationships that shape the sense of self. In this article I consider the plausibility and ethical implications of these proposed identity effects, but I focus instead on a third way in which identity may be affected, through the mediating influence of the wider social world on MRT effects on identity. By taking a narrative approach, and examining the nature and availability of identity narratives, I conclude that while neither direct genetic nor indirect experiential effects can be excluded, social responses to MRT are more likely to have a significant and potentially damaging influence on the generation of MRT children's narratives of identity. This conclusion carries some implications for the collective moral responsibility we hold to ensure that MRT, if implemented, are practised in ethically justifiable ways.

The Mitochondrial Replacement 'Therapy' Myth.

This article argues that two forms of mitochondrial replacement therapy, maternal spindle transfer (MST) and pro-nuclear transfer (PNT), are not therapies at all because they do not treat children who are coming into existence. Rather, these technologies merely create healthy children where none was inevitable. Even if creating healthy lives has some value, it is not to be confused with the medical value of a cure or therapy. The article addresses a recent Bioethics article, 'Mitochondrial Replacement: Ethics and Identity,' by Wrigley, Wilkinson, and Appleby, who argue that PNT is morally favorable to MST due to the Non-Identity Problem. Wrigley et al. claim that PNT, since it occurs post-conception, preserves the identity of the resulting child, whereas MST, since it occurs pre-conception, is an identity-altering technique. As such, a child born with mitochondrial disease could complain that her parents failed to use PNT, but not MST. The present article argues that the authors are mistaken: both MST and PNT are identity-affecting techniques. But this is of little matter, for we should be cautious in drawing any moral conclusions from the application of the Non-Identity Problem to cases. The article then argues that the authors are mistaken in inferring that PNT is a type of embryonic cure or therapy for children with mitochondrial disease. The article cautions against the mistaken life-saving rhetoric that is common in bioethics discussions of MRTs.

Are there moral differences between maternal spindle transfer and pronuclear transfer?

This paper examines whether there are moral differences between the mitochondrial replacement techniques that have been recently developed in order to help women afflicted by mitochondrial DNA diseases to have genetically related children absent such conditions: maternal spindle transfer (MST) and pronuclear transfer (PNT). Firstly, it examines whether there is a moral difference between MST and PNT in terms of the divide between somatic interventions and germline interventions. Secondly, it considers whether PNT and MST are morally distinct under a therapy/creation optic. Finally, it investigates whether there is a moral difference between MST and PNT from a human embryo destruction point of view. I conclude, contra recent arguments, that regarding the first two points there is no moral differences between PNT and MST; and that regarding the third one MST is morally preferable to PNT, but only if we hold a gradualist account of the moral value of human embryos where zygotes have slight moral value.

Mitochondrial donation and 'the right to know'.

In this paper, I examine two key arguments advanced by the Human Fertilization and Embryology Authority (HFEA) and the Nuffield Council justifying anonymous mitochondrial donation, even though the 'right to know' is recognised in standard gamete donation. I argue that the two arguments they offer, what I call the argument from genetic connection and the argument from personal characteristics, are unsuccessful. However, I provide additional reasons for why recognising the right to know in gamete donation but not in mitochondrial donation may be justified. I further argue that the status quo in the UK, which is to not recognise a right to know in mitochondrial donation, is provisionally acceptable.

Having a child together in lesbian families: combining gestation and genetics.

The increasing acceptance of lesbian couples in medically assisted reproduction has led to new, unusual requests. This paper discusses the request for egg transfer from one partner to the other. In the first part, different analogies (egg donation, embryo donation, surrogacy and mitochondrial replacement) are made in order to find out whether one of these can help us determine whether this procedure is acceptable. It is shown that there are major difficulties with all analogies. In the second part, two balances are developed between the medical risks and costs of in vitro fertilisation (IVF) and intrauterine insemination on the one hand and the medical risks of IVF and the psychosocial benefits on the other hand. The final conclusion is that the disadvantages of the procedure can be compensated by the psychosocial advantages and thus can be accepted.