César Palacios-González

Mitochondrial replacement techniques: egg donation, genealogy and eugenics

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.

Mitochondrial Replacement Techniques and Mexico’s Rule of Law: On the Legality of the First Maternal Spindle Transfer Case

[This corrects the article DOI: 10.1093/jlb/lsw065.].

Author's Response to Peer Commentaries: Mexico's rule of law and MRTs

We would like to thank Rebecca Dimond and Atina Krajewska,1 Sandra GonzálezSantos,2 and Tetsuya Ishii3 for their thoughtful comments on our article.4 Here we will reply to their commentswhile at the same timeweprovide further clarificatory notes regarding what transpired inMexico, in relation to the use of mitochondrial replacement techniques (MRTs). WHAT’S IN A NAME? MRTs are new reproductive techniques where the nuclear DNA of an egg, or zygote, that was housed in a cell with deleteriously mutated mitochondria is transferred to a donated enucleated egg, or zygote, that possesses healthy mitochondria.5 The term MRTs has been used to refer to two techniques: pronuclear transfer andmaternal spindle transfer. In her commentary, from a science and technology studies perspective, González-Santos criticizes the use of this term. She argues that using it ‘helps silence each technique’s particular history, intended purpose, and technological and biological implications; it inaccurately suggests that what is being replaced is the mitochondria,

Ethics of Mitochondrial Replacement Techniques: A Habermasian Perspective

Abstract 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.

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.

Chimeras intended for human gamete production: an ethical alternative?

Human eggs for basic, fertility and stem-cell research are in short supply. Many experiments that require their use cannot be carried out at present, and, therefore, the benefits that could emerge from these are either delayed or never materialise. This state of affairs is problematic for scientists and patients worldwide, and it is a matter that needs our attention. Recent advances in chimera research have opened the possibility of creating human/non-human animal chimeras intended for human gamete production (chimeras-IHGP). In this paper, I examine four arguments against the creation of such chimeras and prove that all of them are found wanting. I conclude by showing that there is a strong moral reason for scientists to pursue this research avenue.

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

Abstract 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 mothers uterus. Zhangs teams 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.

Article Commentary: Mitochondrial Replacement Techniques: Genetic Relatedness, Gender Implications, and Justice

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.

Mitochondrial Replacement Techniques: Genetic Relatedness, Gender Implications, and Justice

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.

Resource Allocation, Treatment, Disclosure, and Mitochondrial Replacement Techniques

There has been a lively exchange in this journal between Inmaculada de MeloMartin and John Harris on the ethics of mitochondrial replacement techniques (MRTs). Initially, Harris advocated, here and elsewhere, for MRTs.1 He tried to show that the arguments against them are flawed and that MRT research and clinical practice should be supported because MRTs diminish suffering and increase well-being. In response, de Melo-Martin2 argued that Harris’s arguments defending MRTs are found wanting and that the scientific community should oppose them. She contended three things: that Harris only engaged with the weakest arguments that have been advanced against MRTs, that the resources that are used for MRT research and clinical practice should be repurposed for achieving worthier goals, and that MRTs are not necessary for women who have a mitochondrial DNA disease and want to have children genetically related to them, as they could have children through other means (e.g., adoption or egg donation). Harris then replied3 to de Melo-Martin and defended his arguments. First, he argued that in most instances both of them maintain the same position regarding de Melo-Martin’s objections to MRTs, and that where they do diverge, it is de Melo-Martin who is on the wrong side. Second, Harris contends that de MeloMartin’s main criticism is off target. He maintains that he was not making any claim about what priority we should give to MRT research and clinical practice, only that his sole aim was to assess if in principle MRTs, conceived solely as biotechnologies and abstracted from our social reality, are morally objectionable or not. This article constitutes a fourth act in this interplay of opinion. Here I will broaden the scope of the debate by presenting a richer account of the MRTs Responses and Dialogue