Mitochondrial replacement therapy (MRT), also called nuclear genome transfer and mitochondrial donation, is a new technique that can be used to prevent the transmission of mitochondrial DNA diseases. Apart from the United Kingdom, the first country to approve MRT in 2015, Australia became the second country with a clear regulatory path for the clinical applications of this technique in 2021. The rapidly evolving clinical landscape of MRT makes the elaboration and evaluation of the responsible use (...) of this technology a pressing matter. As jurisdictions with less strict or non-existent reproductive laws are continuing to use MRT in the clinical context, the need to address the underlying ethical issues surrounding MRT’s clinical translation is fundamental. (shrink)

This article argues that two forms of mitochondrial replacement therapy, maternal spindle transfer and pro-nuclear transfer, 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. (shrink)

A clinical trial on mitochondrial replacement therapy is currently being conducted and if this technique proves effective, National Health Service England will fund MRT through the highly specialised services funding stream. This paper considers whether MRT should be publicly funded by the NHS. Given the current financial pressure the NHS is experiencing, a comprehensive discussion is essential. There is yet to be a thorough discussion on MRT funding, perhaps because this is a small-scale issue and presumed to (...) be covered by the HSS budget. However, the source of funding has not been confirmed due to the trial’s incompletion. Upon its completion, reasoned decisions need to be made over the allocation of scarce NHS resources. It is therefore important to consider the following arguments in advance. Three arguments given against NHS funding of MRT will be evaluated. The first argument against NHS funding examines the HSS overspending its budget in an underfunded NHS, suggesting funding must be carefully reprioritised. Second, the ethical issue of allowing public access to a technique with insufficient evidence behind it will be explored. The final point considers the option of privately funding MRT and how this would affect the treatment’s development. After illustrating the weaknesses of such arguments, it will be concluded that MRT should be funded by the NHS. (shrink)

Mitochondrial replacement technology (MRT) is an emerging and complex bioethical issue. This treatment aims to eliminate maternal inherited mitochondrial DNA (mtDNA) disorders. For Muslims, its introduction affects every aspect of human life, especially the five essential interests of human beings—namely, religion, life, lineage, intellect, and property. Thus, this technology must be assessed using a comprehensive and holistic approach addressing these human essential interests. Consequently, this article analyses and assesses tri-parent baby technology from the perspective of Maqasidic bioethics—that (...) is, Islamic bioethics based on the framework of Maqasid al-Shariah. Using this analysis, this article suggests that tri-parent baby technology should not be permitted for Muslims due to the existence of third-party cell gametes which lead to lineage mixing and due to the uncertain safety of the therapy itself and because the major aim of the technology is to fulfil the affected couples interest to conceive their own genetically healthy child, not to treat and cure mtDNA disorders sufferers. (shrink)

Mitochondria, the powerhouses of our cells, are essential to life. Normal mitochondrial function is achieved through the cooperative interaction of the nuclear and mitochondrial genomes. New IVF approaches intended to circumvent devastating mitochondrial disease look set to change the ancient pattern of mtDNA inheritance and interaction with unknown consequences.

Mitochondrial replacement therapy (MRT) utilises nuclear transfer technology to replace defective mitochondria with healthy ones and thereby minimise the risk of a mitochondrial disease passing from a mother to her child. It promises much but comes with ethical controversy, significant risk of harm and many unknowns. Forming a position on MRT requires accurate information about the current state of knowledge, and an appreciation of the ethical issues at stake. Ethical deliberations will vary depending on the framework (...) used. There are in principle objections to MRT on the grounds of direct harm to human embryos and germline genetic modification. But even without these objections MRT can be weighed in terms of the balance between risks and benefits, alternatives and uncertainties. This paper explores the evidence and lays out the relevant issues to assist such a deliberation. (shrink)

Mitochondrial replacement techniques have the potential to allow prospective parents who are at risk of passing on debilitating or even life-threatening mitochondrial disorders to have healthy children to whom they are genetically related. Ethical concerns have however been raised about these techniques. This article focuses on one aspect of the ethical debate, the question of whether there is any moral difference between the two types of MRT proposed: Pronuclear Transfer and Maternal Spindle Transfer. It examines how questions (...) of identity impact on the ethical evaluation of each technique and argues that there is an important difference between the two. PNT, it is argued, is a form of therapy based on embryo modification while MST is, instead, an instance of selective reproduction. The article's main ethical conclusion is that, in some circumstances, there is a stronger obligation to use PNT than MST. (shrink)

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 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. (shrink)

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 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. (shrink)

Mitochondrial replacement therapy 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, (...) 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. (shrink)

Abstract 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. (shrink)

Few discussions of the ethics of mitochondrial ‘replacement’ techniques have drawn significant ethical distinctions between the two approaches now legal in the U.K. However, Anthony Wrigley, Stephen Wilkinson and John Appleby have together argued that under some circumstances pronuclear transfer (PNT) may be in better ethical standing than maternal spindle transfer (MST). They base their conclusion on what they allege to be different implications of the techniques with respect to non‐identity considerations, which they ground on a version of (...) origin essentialism. I raise a series of problems for their argument, which have cautionary implications for invocations of origin essentialism that go beyond specialized debates regarding MST and PNT. I argue that (i) origin essentialism is a fragile foundation for non‐identity considerations; (ii) gametic essentialism, which Wrigley et al. believe licenses their claims, is more questionable than origin essentialism; (iii) gametic essentialism does not straightforwardly justify their conclusion; and (iv) their conclusion in fact relies on an especially dubious position that we can call chromosomal origin essentialism. No good reasons have yet been supplied to distinguish PNT from MST on ethical grounds, and one should be wary of basing claims with practical impact on fragile foundations relating to origin essentialism. (shrink)

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: how should we classify mitochondrial donation techniques?; and what ethical implications surround such a classification? First, we outline how methods of genetic intervention, such as germ-line gene (...) class='Hi'>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’. (shrink)

Der weltweit erste Mitochondrien-Transfer, auch als Erzeugung eines „Drei-Eltern-Kindes“ bezeichnet, hat 2016 eine intensive Debatte ausgelöst. Hinsichtlich des Verfahrens, das bisher nur in Großbritannien zugelassen ist, werden auch verschiedene ethische Aspekte angesprochen. Dazu gehören die Risikoabwägung, die reproduktive Selbstbestimmung und die psychosoziale Entwicklung eines Kindes, das von drei Individuen abstammt. Dabei fällt auf, dass zentrale konzeptuelle Fragen hinsichtlich des Mitochondrien-Transfers nicht geklärt sind. Ist der Mitochondrien-Transfer eine genetische Intervention in die Keimbahn? Handelt es sich bei dem Verfahren um eine medizinisch (...) indizierte Therapie oder um eine elektive Behandlung assistierter Reproduktion? Welche Konzepte von Identität und Elternschaft liegen der Auffassung eines „Drei-Eltern-Kindes“ zugrunde? Im Kontext dieser konzeptuellen Fragen muss eine ethische Analyse des Mitochondrien-Transfers durchgeführt werden. In den meisten Fällen zeigt sich allerdings, dass die ethische Analyse zu stark auf Einzelaspekte fokussiert ist, wodurch diese konzeptuellen Fragen aus dem Blick geraten. Daher verbinden wir in unserem Beitrag die ethische Analyse mit konzeptuellen Überlegungen. Dabei ist es von zentraler Bedeutung, auch die biomedizinischen Grundlagen des Verfahrens eingehend zu erörtern, um die konzeptuellen Aspekte angemessen einordnen zu können. In einem ersten Schritt erläutern wir die unterschiedlichen Verfahren des Mitochondrien-Transfers. In einem zweiten Schritt schlagen wir eine konzeptuelle Klärung der drei genannten Fragen vor. Diese konzeptuelle Klärung dient als Grundlage, um die ethischen Aspekte der reproduktiven Selbstbestimmung, Risikoabwägung sowie Elternschaft und Identitätskonzeption zu analysieren. In einem dritten Schritt fassen wir die Ergebnisse zusammen. (shrink)

We review a recent paper in Genome Research by Guantes et al. showing that nuclear gene expression is influenced by the bioenergetic status of the mitochondria. The amount of energy that mitochondria make available for gene expression varies considerably. It depends on: the energetic demands of the tissue; the mitochondrial DNA (mtDNA) mutant load; the number of mitochondria; stressors present in the cell. Hence, when failing mitochondria place the cell in energy crisis there are major effects on gene expression (...) affecting the risk of degenerative diseases, cancer and ageing. In 2015 the UK parliament approved a change in the regulation of IVF techniques, allowing “Mitochondrial replacement therapy” to become a reproductive choice for women at risk of transmitting mitochondrial disease to their children. This is the first time that this technique will be available. Therefore understanding the interaction between mitochondria and the nucleus has never been more important. (shrink)

Mitochondrial replacement therapy is a process whereby a child is created by combining the nuclear DNA of two people wishing to have a child with mitochondrial DNA donated by a third person. It poses a new question as to the extent of a person’s right to know the identity of those from whom their DNA is inherited. In commentary upon Turkmendag’s paper, I evaluate the consistency of UK regulation of this issue with the European Convention of (...) Human Rights. Under UK law, a person created using donated mtDNA is only entitled to information about the procedure which does not identify the donor. I argue that this approach is consistent with the previous European Court of Human Rights and UK judicial decisions on the rights of individuals to information about their identity and ancestry and with the deeper foundational principle which Kai Möller argues the Convention protects existential self-understanding. I conclude that, as mtDNA has not been proven to affect an individual’s life choices and outward characteristics to the extent that gamete donation does, it is acceptable to prioritize the interests that anonymous donation protects over the desire of the recipient to know the identity of their donor. (shrink)

With the recent report of a live birth after use of Mitochondrial replacement therapy, sometimes called ‘Three-parent IVF’, the clinical application of the technique is fast becoming a reality. While the United Kingdom allows the procedure under regulatory scrutiny, it remains effectively outlawed in many other countries. We argue that such prohibitions may violate individuals’ procreative rights, grounded in individuals’ interest in genetic affinity. The interest in genetic affinity was recently endorsed by Singapore’s highest court, reflecting an (...) emphasis on the importance of biological ties found across the globe. We apply that reasoning to make the case for a right to ‘Three-parent IVF’. (shrink)

It has recently been argued that reproductive genetic manipulation technologies like mitochondrial replacement and germline CRISPR modifications cannot be said to save anyone’s life because, counterfactually, no one would suffer more or die sooner absent the intervention. The present article argues that, on the contrary, reproductive genetic manipulations may be life-saving (and, from this, have therapeutic value) under an appropriate population health perspective. As such, popular reports of reproductive genetic manipulations potentially saving lives or preventing disease are not (...) necessarily mistaken, though such terminology still requires further empirical validation. (shrink)

Two genetic technologies capable of making heritable changes to the human genome have revived interest in, and in some quarters a very familiar panic concerning, so-called germline interventions. These technologies are: most recently the use of CRISPR/Cas9 to edit genes in non-viable IVF zygotes and Mitochondrial Replacement Therapy the use of which was approved in principle in a landmark vote earlier this year by the United Kingdom Parliament. The possibility of using either of these techniques in humans (...) has encountered the most violent hostility and suspicion. However it is important to be aware that much of this hostility dates back to the fears associated with In Vitro Fertilization and other reproductive technologies and by cloning; fears which were baseless at the time concerning both IVF and cloning the use of both of which have proved to be highly beneficial to humanity and which have been effectively regulated and controlled. This paper argues that CRISPR should by pursued through res.. (shrink)

Until recently, scientific consensus held firm that genetically manipulated embryos created through methods including Mitochondrial Replacement Therapy or human germline genome editing should not be used to initiate a pregnancy. In countries that have relevant laws pertaining to heritable human germline modifications, the vast majority prohibit or restrict this practice. In the last several years, scholars have observed a transformation of scientific and policy restrictions with insistent calls for creating a regulatory pathway. Multiple stakeholders highlight the role (...) of social consensus and public engagement for governance of heritable human germline modifications. However, in the drive to gain public acceptance and lift restrictions, some proponents provide distorted or misleading narratives designed to influence public perception and incrementally shift the consensus. This article describes eight discrete strategies that proponents employ to influence framing, sway public opinion, and revise policymaking of human germline modifications in a manner that undermines honest engagement. (shrink)

ZusammenfassungDer schnelle Fortschritt der Biomedizin fördert fortwährend neue bioethische Problemstellungen zutage und erfordert Anpassungen überlieferter Normbestände an neue Gegebenheiten. Für viele neue Verfahren stellen sich jedoch Fragen nicht nur der moralischen Bewertung, sondern auch der begrifflichen Einordnung. Diese besagt dann häufig etwas über das Gewicht, das einerseits sachlichen, andererseits normativen Kontinuitäten und Diskontinuitäten beigelegt wird. Der Beitrag illustriert die in diesem Zusammenhang auftretenden Konflikte am Beispiel des Gene editing bei Nutzpflanzen, der mitochondrial replacement therapy, des aktiven Behandlungsabbruchs (...) bei Schwerkranken und dem freiwilligen Verzicht auf Nahrung und Flüssigkeit zur Lebensbeendigung (Sterbefasten). Besonderes Augenmerk gilt den Dilemmata, die sich ergeben, wenn sich diese Konflikte angesichts verhärteter normativer Fronten diskursiv nicht auflösen lassen. (shrink)

On September 27, 2016 people across the world looked down at their buzzing phones to see the AP Alert: “Baby born with DNA from 3 people, first from new technique.” It was an announcement met with confusion by many, but one that polarized the scientific community almost instantly. Some celebrated the birth as an advancement that could help women with a family history of mitochondrial diseases prevent the transmission of the disease to future generations; others held it unethical, citing (...) medical tourism and consequences for the future of the therapy. The child in question was actually born a few months earlier on April 6, 2016, but the research was published a few months later in the October edition of Fertility and Sterility. The mother carries DNA that could have given the baby Leigh Syndrome, a severe neurological disorder characterized by psychomotor regression that typically results in death between ages two and three.[1] Also known as subacute necrotizing encephalomyelopathy, Leigh Syndrome is caused by genetic mutations in mitochondrial DNA, which causes defective oxidative phosphorylation. Because people with this condition cannot re-form ATP, “demyleniation, gliosis, necrosis, spongiosis, or capillary proliferation”[2] can occur, thereby producing bilateral lesions across the central nervous system. The 36-year-old mother previously had four miscarriages and successfully birthed two children, both of whom survived less than six years due to the syndrome. For religious reasons, the mother opted for Spindle Nuclear Transfer instead of Pronuclear Transfer,[3] which many religious organizations oppose because it entails the destruction of fertilized eggs.[4] In Pronuclear Transfer, both the parent and donor egg are fertilized. The parent’s nuclear material is then removed from the egg containing mutated mitochondria and inserted into the fertilized donor egg—from which the original nuclear material has been removed and destroyed. Spindle Nuclear Transfer, on the other hand, removes the mother’s nuclear material from the egg with unhealthy mitochondria, then implants it into a donor’s egg. The newly created egg is then fertilized with the father’s sperm. This Spindle Nuclear Transfer was performed in Mexico by a team of doctors led by Dr. John Zhang, the founder of the New Hope Fertility Center in New York City. In their report, the doctors outline that five oocytes were successfully reconstituted, four of which developed into blastocysts. Only one was euploid: containing 46 XY chromosomes. Researchers then biopsied that blastocyst and found that the transmission rate of maternal mtDNA was, “5.10 ± 1.11% and the heteroplasmy level for 8993T>G was 5.73%.”[5] This indicates that at the blastocyst stage, around five percent of the mitochondria are from the original maternal egg with the mutation for Leigh Syndrome. After birth, they biopsied different tissues and found that they had an average of less than 1.60 ± 0.92% of transmitted mtDNA from the original maternal egg. The baby is reportedly doing well and the team of doctors concluded that “[h]uman oocytes reconstituted by SNT are capable of producing a healthy live birth. SNT may provide a novel treatment option in minimizing pathogenic mtDNA transmission from mothers to their babies."[6] Even when considered theoretically, Spindle Nuclear Transfer is controversial. Many doctors believe that the risks at this stage of research are too great. Dr. Trevor Stammers, a bioethicist at St. Mary’s University in London, points out: “We do not yet have a clear picture of the interaction between nuclear DNA and mitochondria.”[7] Others hold that faulty mitochondrial DNA can still be transferred during the procedure. Still more argue this technology could create problems because of germline modification.[8] Dr. Paul Knoepfler, a cell biologist at the UC Davis School of Medicine, explains: “Since this is uncharted territory and the children born from this technology would have heritable genetic changes, there are also significant unknown risks to future generations.”[9] However, proponents counter these arguments. They say the benefits outweigh the risks, as “mitochondrial replacement techniques [like Spindle Nuclear Transfer] would eliminate maternal transmission of mitochondrial disease… allowing a woman with a family history of mitochondrial diseases to ensure her children would not be affected.”[10] Additionally, experts say that no symptoms will occur if less than 20% of the transferred mitochondrial DNA is faulty.[11] And while opponents see potential germline modification as a problem, advocates answer that this could stop a family history of mitochondrial disease, which they deem a more serious concern. In this case specifically, however, there are more issues at hand. While the team of doctors did eliminate the possibility of germline modification by selecting a male embryo, there are other ethical concerns. Some argue that this case could be described as “medical tourism.” While New Hope Medical Clinic does maintain a branch in Mexico, Dr. Zhang stated that Mexico has “no rules.”[12] It is a country with underdeveloped regulations, making it difficult to confirm that doctors adhere to widely-held medical and ethical standards. Furthermore, while it is highly unlikely that the child will develop Leigh’s Syndrome, Dr. Dietrich Egli of the New York Stem Cell Foundation says the 5% mitochondrial transfer rate indicates that the technique “was not carried out well.”[13] He points to studies of embryos where the rate of mtDNA transfer was almost ten times lower. Spindle Nuclear Transfer is currently legal in the UK,[14] and many are hoping to see it legalized in the US, although Congress currently prohibits the FDA from considering applications that would entail trials in people.[15] While Dr. Zhang’s work is arguably revolutionary, many wonder if the manner in which this study was performed—in Mexico and with a high mitochondrial transfer rate—will impact the technology’s future in the US. Last week, Dr. Zhang presented the report to scientists gathered in Salt Lake City, saying that while science isn’t a race, it is “in a sense, a race for the family to find a cure, to find hope.”[16] Only time will tell if this study set back other families racing and hoping for a cure. References 1. "Leigh Syndrome." Genetics Home Reference, US National Library of Medicine, 25 Oct. 2016. Accessed 26 Oct. 2016. 2. McKusick, Victor A., and Ada Hamosh. "LEIGH SYNDROME; LS." Online Mendelian Inheritance in Man, Johns Hopkins University, 20 Jan. 2016. Accessed 30 Oct. 2016. 3. Zhang, J, H Liu, S Luo, A Chavez-Badiola, and Z Liu. "First live birth using human oocytes reconstituted by spindle nuclear transfer for mitochondrial DNA mutation causing Leigh syndrome." Fertility and Sterility, vol. 106, no. 3, 2016, pp. e375-76. Accessed 30 Oct. 2016. 4. Sample, Ian. "‘Three-parent’ babies explained: what are the concerns and are they justified?" The Guardian, 2 Feb. 2015. Accessed 30 Oct. 2016. 5. Zhang, et al. 6. Ibid. 7. Knapton, Sarah. "Three-parent babies: the arguments for and against." The Telegraph, 3 Feb. 2015. 8. Ibid. 9. Ibid. 10. "Mitochondrial Replacement Therapy FAQs." New York Stem Cell Foundation Research Institute, New York Stem Cell Foundation. Accessed 30 Oct. 2016. 11. Reardon, Sara. "‘Three-parent baby’ claim raises hopes — and ethical concerns." Nature, 28 Sept. 2016. Accessed 30 Oct. 2016. 12. Hamzelou, Jessica. "Exclusive: World’s first baby born with new “3 parent” technique." New Scientist, 27 Sept. 2016. Accessed 30 Oct. 2016. 13. Reardon, Sara. "‘Three-parent baby’ claim raises hopes — and ethical concerns." Nature, 28 Sept. 2016. Accessed 30 Oct. 2016. 14. "3-Person IVF: A Resource Page." Center for Genetics and Society, 24 Oct. 2016. Accessed 30 Oct. 2016. 15. Ritter, Malcolm. "Baby born with DNA from 3 people, first from new technique." Associated Press, 27 Sept. 2016. Accessed 30 Oct. 2016. 16. Chen, Daphne. "Controversy swirls around first three-parent baby." Deseret News, 19 Oct. 2016. Accessed 30 Oct. 2016. Works consulted Swetlitz, Ike. "FDA urged to approve ‘three-parent embryos,’ a new frontier in reproduction." STAT, 3 Feb. 2016. Accessed 30 Oct. 2016. (shrink)

Mitochondrial replacement techniques, 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 has claimed that MRTs affect only the qualitative identity of the resulting child, while the Working Group of the Nuffield Council on Bioethics 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. (shrink)

In a recent publication Tom Douglas and Katrien Devolder have proposed a new account of genetic parenthood, building on the work of Heidi Mertes. Douglas and Devolder’s account aims to solve, among other things, the question of who are the genetic parents of an individual created through somatic cell nuclear transfer (i.e. cloning): (a) the nuclear DNA provider or (b) the progenitors of the nuclear DNA provider. Such a question cannot be answered by simply appealing to the folk account of (...) genetic parenthood, according to which the genetic parents of an individual are those individuals who produced the egg and sperm, respectively, which fused to create the embryo. It cannot be so as in cloning there is no fertilization as such. In this article I critically examine Douglas and Devolder’s new account of genetic parenthood and demonstrate that it is vulnerable to counterexamples that exploit the lack of a condition specifying that genetic parents should cause a child’s coming into existence. (shrink)

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 and pronuclear transfer. 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. (shrink)

In February 2015 the UK became the first country to legalise high-profile mitochondrial replacement techniques, which involve the creation of offspring using genetic material from three individuals. The aim of these new cell reconstruction techniques is to prevent the transmission of maternally inherited mitochondrial disorders to biological offspring. During the UK debates, MRTs were often positioned as a straightforward and unique solution for the ‘eradication’ of mitochondrial disorders, enabling hundreds of women to have a healthy, biologically-related (...) child. However, many questions regarding future applications and potential users remain. Drawing on a current qualitative study on reproductive choices in the context of mitochondrial disorders, this article illustrates how the potential limitations of MRTs have been obscured in public debates by contrasting the claims made about the future beneficiaries with insights from families affected by mitochondrial disorders and medical experts. The analysis illuminates the complex choices with which families and individuals affected by mitochondrial disorders are faced, which have thus far remained invisible. An argument is presented for improved information for the public as well as an intensification of critical empirical research around the complex and specific needs of future beneficiaries of new reproductive biotechnologies. (shrink)

Mitochondrial replacement techniques (MRTs) usually aim to prevent the genetic transmission of maternally inherited mitochondrial diseases. Until now, only the UK and Australia have implemented specific legal regulations of MRTs. In both countries, clinical trials on these techniques are only permissible for cases with a high risk of severe mitochondrial disease in the offspring. However, these techniques can also be applied to treat infertility, especially for older women with impaired oocyte quality. In some countries without legal (...) regulation of these techniques, MRTs are already offered for this purpose. Yet, this application of MRTs has received insufficient attention in the bioethical literature so far.In this paper, I examine whether there are ethical reasons to prohibit trials on MRTs in the context of infertility when they are permitted for preventing mitochondrial disease. Allowing MRTs in one context but not the other might be justified either because their application in the context of mitochondrial disease (1) is supported by a more convincing evidence base, (2) has a higher potential benefit or (3) has a lower risk. I compare both applications of MRTs with respect to these three factors. I conclude that there is no convincing reason to prohibit clinical trials on MRTs for infertility when they are permitted in the context of mitochondrial disease. (shrink)

Mitochondrial replacement techniques 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 directly, through altering the genetic makeup and physical characteristics of (...) the child, or 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. (shrink)

Mitochondrial replacement techniques are designed to allow couples to have children without passing on mitochondrial diseases. Recently, Giulia Cavaliere and César Palacios-González argued that prospective parents have the right to use MRTs to pursue genetic relatedness, such that some same-sex couples and/or polygamous triads could use the process to impart genetic relatedness between a child and more of its caregivers. Although MRTs carry medical risks, Cavaliere and Palacios-González contend that because MRTs are identity-affecting, they do not cause (...) harm to an existing human being, and our intuitions otherwise arise from the non-identity problem. Here, I review several attempts to address the non-identity problem, and propose a solution to the problem. Furthermore, I argue that regardless of one’s stance on whether MRTs are identity-affecting, the use of MRTs to pursue genetic relatedness alone falls outside the scope of the medical profession, as they involve substantive medical risk for no medical benefit. (shrink)

Several objections against the morality of researching or employing mitochondrial replacement techniques have been advanced recently. In this paper, I examine three of these objections and show that they are found wanting. First I examine whether mitochondrial replacement techniques, research and clinical practice, should not be carried out because of possible harms to egg donors. Next I assess whether mitochondrial replacement techniques should be banned because they could affect the study of genealogical ancestry. Finally, (...) I examine the claim that mitochondrial replacement techniques are not transferring mitochondrial DNA but nuclear DNA, and that this should be prohibited on ethical grounds. (shrink)

Since mitochondrial replacement techniques were developed and clinically introduced in the United Kingdom, there has been much discussion of whether these lead to children borne of three parents. In the UK, the regulation of MRT has dealt with this by stipulating that egg donors for the purposes of MRT are not genetic parents even though they contribute mitochondrial DNA to offspring. In this paper, I examine the way that the Human Fertilisation and Embryology Act in the UK (...) manages the question of parentage. I argue that the Act breaks the link typically made between genetic causation and genetic parenthood by redefining genetic causation solely in terms of nuclear genetics. Along with this, mtDNA is construed as a kind of supplement to the nuclear family. Drawing on the account of the supplement developed by Jacques Derrida, I argue that mtDNA and the women who donate it are seen as both essential to establishing the nuclear family but also exterior to and insignificant for it. (shrink)

News about the first baby born after a mitochondrial replacement technique (MRT; specifically maternal spindle transfer) broke on September 27, 2016 and, in a matter of hours, went global. Of special interest was the fact that the mitochondrial replacement procedure happened in Mexico. One of the scientists behind this world first was quoted as having said that he and his team went to Mexico to carry out the procedure because, in Mexico, there are no rules. In (...) this paper, we explore Mexico's rule of law in relation to mitochondrial replacement techniques and show that, in fact, certain instances of MRTs are prohibited at the federal level and others are prohibited at the state level. According to our interpretation of the law, the scientists behind this first successful MRT procedure broke federal regulations regarding assisted fertilization research. (shrink)

In this article, I draw on research carried out in Europe, primarily in Germany, on patients’ and scientists’ perspectives on mitochondrial replacement techniques 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. (shrink)

In order to avoid the implication that ‘mitochondrial replacement techniques’ (MRT) would produce ‘three parent babies’, discourses around these techniques typically dismiss the contribution of the mitochondria to genetic parenthood and personal identity. According to many participants in debates about MRT, ‘real parenthood’ is a matter of contributing nuclear DNA, which in turn implies that men and women make the same contribution to the embryo. Even when the importance of the mitochondria is acknowledged, an emphasis on mitochondrial (...) DNA still has the effect of valorizing the role of DNA (and thus the paternal contribution to conception) at the expense of the role played by the cytoplasm of the oocyte in the development of the embryo and placenta, and that of the mother’s body in gestation. In this way, discourses around MRT falsely imply that what men and women contribute to reproduction and parenthood is the same—nuclear DNA—and thus erase the distinctive contribution that women make to conception. The potential of MRT to reconfigure relationships between the sexes in the service of patriarchal norms is perhaps one of the most significant things about it and should, we argue, be counted in the discussion of the ethical and policy implications of legitimating these procedures. (shrink)

Gene replacement therapy holds great promise in the treatment of many genetic CNS disorders. This commentary discusses the feasibility of gene replacement therapy in the unique context of the retina, with regard to: (1) the genetics of retinal neoplasia and degeneration, (2) available gene transfer technology, and (3) potential gene delivery vehicles.

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. (shrink)

In 2015 the United Kingdom (UK) became the first nation to legalize egg and zygotic nuclear transfer procedures using mitochondrial replacement techniques (MRTs) to prevent the maternal transmission of serious mitochondrial DNA diseases to offspring. These techniques are a form of human germline genetic modification and can happen intentionally if female embryos are selected during the MRT clinical process, either through sperm selection or preimplantation genetic diagnosis (PGD). In the same year, an MRT was performed by a (...) United States (U.S.)-based physician team. This experiment involved a cross-border effort: the MRT procedure per se was carried out in the US, and the embryo transfer in Mexico. The authors examine the ethics of MRTs from the standpoint of genetic relatedness and gender implications, in places that lack adequate laws and regulation regarding assisted reproduction. Then, we briefly examine whether MRTs can be justified as a reproductive option in the US and Mexico, after reassessing their legalization in the UK. We contend that morally inadequate and ineffective regulations regarding egg donation, PGD, and germline genetic modifications jeopardize the ethical acceptability of the implementation of MRTs, suggesting that MRTs are currently difficult to justify in the US and Mexico. In addition to relevant regulation, the initiation and appropriate use of MRTs in a country require a child-centered follow-up policy and more evidence for its safety. (shrink)

Florence Ashley has argued that requiring patients with gender dysphoria to undergo an assessment and referral from a mental health professional before undergoing hormone replacement therapy is unethical and may represent an unconscious hostility towards transgender people. We respond, first, by showing that Ashley has conflated the self-reporting of symptoms with self-diagnosis, and that this is not consistent with the standard model of informed consent to medical treatment. Second, we note that the model of informed consent involved in (...) cosmetic surgery resembles the model Ashley defends, and that psychological assessment and referral is recognised as an important aspect of such a model. Third, we suggest that the increased prevalence of psychiatric morbidity in the transgender population arguably supports the requirement of assessment and referral from a mental health professional prior to undergoing HRT. (shrink)

Mitochondrial replacement techniques (MRTs) have made headlines as some countries have passed legislation permitting the creation of “three-parent embryos” and because of the recent revelation that a child has already been born following the use of these techniques. MRTs assist women with severe mitochondrial disease to have children who are free from mitochondrial disease. Essentially, the mitochondrial DNA of an ovum or embryo is removed and replaced with the mtDNA of a donor. The purpose of (...) this paper is to argue that MRTs are ethically impermissible but greater regulation is needed. There are five parts to this paper: (1) a brief history of mitochondrial manipulation, (2) a description of the MRT process, (3) ethical arguments in opposition to MRTs, (4) relevant counterarguments, and (5) a proposal for increased regulation. (shrink)

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 threegeneticparents? 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. (shrink)

For focal neurodegenerative diseases or brain tumors, localized delivery of protein or genetic vectors may be sufficient to alleviate symptoms, halt disease progression, or even cure the disease. One may circumvent the limitation imposed by the blood-brain barrier by transplantation of genetically altered cell grafts or focal inoculation of virus or protein. However, permanent gene replacement therapy for diseases affecting the entire brain will require global delivery of genetic vectors. The neurotoxicity of currently available viral vectors and the (...) transient nature of transgene expression invivomust be overcome before their use in human gene therapy becomes clinically applicable. (shrink)

Although informed consent models for prescribing hormone replacement therapy are becoming increasingly prevalent, many physicians continue to require an assessment and referral letter from a mental health professional prior to prescription. Drawing on personal and communal experience, the author argues that assessment and referral requirements are dehumanising and unethical, foregrounding the ways in which these requirements evidence a mistrust of trans people, suppress the diversity of their experiences and sustain an unjustified double standard in contrast to other forms (...) of clinical care. Physicians should abandon this unethical requirement in favour of an informed consent approach to transgender care. (shrink)

Mitochondrial replacement techniques (MRTs) are a new group of biotechnologies that aim to aid women whose eggs have disease-causing deleteriously mutated mitochondria to have genetically related healthy children. These techniques have also been used to aid women with poor oocyte quality and poor embryonic development, to have genetically related children. Remarkably, MRTs create humans with DNA from three sources: nuclear DNA from the intending mother and father, and mitochondrial DNA from the egg donor. In a recent publication (...) Françoise Baylis argued that MRTs are detrimental for genealogical research via mitochondrial DNA because they would obscure the lines of individual descent. In this paper, I argue that MRTs do not obscure genealogical research, but rather that MRT-conceived children can have two mitochondrial lineages. I argue for this position by showing that MRTs are reproductive in nature and, thus, they create genealogy. (shrink)

In a recent paper – Lesbian motherhood and mitochondrial replacement techniques: reproductive freedom and genetic kinship – we argued that lesbian couples who wish to have children who are genetically related to both of them should be allowed access to mitochondrial replacement techniques. Françoise Baylis wrote a reply to our paper –‘No’ to lesbian motherhood using human nuclear genome transfer– where she challenges our arguments on the use of MRTs by lesbian couples, and on MRTs more (...) generally. In this reply we respond to her claims and further clarify our position. (shrink)

Advances in genomic technologies such as CRISPR‐Cas9, mitochondrial replacement techniques, and in vitro gametogenesis may soon give us more precise and efficient tools to have children with certain traits such as beauty, intelligence, and athleticism. In this paper, I propose a new approach to the ethics of reproductive genetic engineering, a human rights approach. This approach relies on two claims that have certain, independent plausibility: (a) human beings have equal moral status, and (b) human beings have human rights (...) to the fundamental conditions for pursuing a good life. I first argue that the human rights approach gives us a lower bound of when reproductive genetic engineering would be permissible. I then compare this approach with other approaches such as the libertarian, perfectionist, and life worth living approaches. Against these approaches, I argue that the human rights approach offers a novel, and more plausible, way of assessing the ethics of reproductive genetic engineering. (shrink)

UK law permits parents to use mitochondrial replacement to have genetically-related children without serious mitochondrial disease. However, long-term follow-up is required for each case. Whet...