Mitochondrial Replacement Therapy, the Embryo, and Community

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Abstract

Mitochondrial replacement therapy (MRT), also known as mitochondrial donation (MD), is promoted as an option to prevent transmission of mitochondrial disorders to offspring. Since its first reported use in humans, MRT has raised numerous ethical and medical concerns. This article will explore the technology behind MRT and arguments in favor of and opposing it, concluding that a response through the lens of Scripture promotes flourishing of individuals and families affected by mitochondrial disorders without sacrificing others in the process.

Keywords: Mitochondrial Disorders, Mitochondrial Replacement Therapy, DNA, Embryo, Germ Line, Disability, Parenthood

Introduction

Leigh syndrome is one of a number of genetic disorders whose inheritance is through the mitochondrial DNA (mtDNA) passed on by the child’s mother. In its most severe form, it leads to muscle weakness in infancy, loss of peripheral sensation, and ultimately respiratory failure.[1] Mitochondrial replacement therapy (MRT), also known as mitochondrial donation (MD), is promoted as an option to prevent transmission of mitochondrial disorders like Leigh syndrome to offspring.[2] Since its first reported use in humans, MRT has raised numerous ethical and medical concerns.[3] This article will explore the technology behind MRT and arguments supporting and opposing it, concluding that a response through the lens of Christian Scripture promotes flourishing of individuals and families affected by mitochondrial disorders without sacrificing others in the process.[4]

The Disorders

Mitochondrial disease exists in approximately one in 5000 adults.[5] Presentation is variable, however, due to genetic influence from both nuclear and mitochondrial DNA, which in turn affect the biochemical process of mitochondrial oxidative phosphorylation involved in energy production within the cell.[6] In all, over two hundred genes within the nucleus and mitochondria are involved.[7] Variability makes diagnosis and treatment difficult, with defects in oxidative phosphorylation leading to alterations in organs requiring high energy loads.[8] In mild cases, ocular manifestations cause blindness or deafness; whereas severe forms lead to organ failure, seizures, and death.[9]

The Technology

MRT claims to cure disorders inherited through mtDNA of affected embryos and prevent inheritance in future generations.[10] Four technologies to relocate genetic material have been identified—pronuclear, maternal spindle, blastomere, and cytoplasmic transfer. Pronuclear transfer (PNT) involves the creation of two fertilized eggs, one from the intending mother who carries the defective mitochondria and her partner or sperm donor, and another from a fertilized egg created by a “donor” with healthy mitochondria which also contains sperm from the intending mother’s partner or a sperm donor.[11] This second fertilized egg is then enucleated and the pronucleus from the intending mother’s fertilized egg is transferred to this “donor” embryo.[12] Maternal spindle transfer (MST), on the other hand, involves the transfer of the intending mother’s nuclear DNA (nDNA) via her spindle from her affected egg to a “donor” egg that has had its own maternal spindle removed.[13] The modified egg is then fertilized and allowed to develop in vitro before transfer to the intending mother or her surrogate.[14] Although presented as mitochondrial donation by a third party, in essence both these procedures actually result in the intending mother donating her nuclear material to what is referred to as a “donor” egg.[15] In fact, Newman argues that the woman providing her enucleated egg with its mitochondria provides the majority of the genetic material needed for early development.[16] Therefore, she is closer to being the “biological mother” than is the intending mother.[17]

In blastomere nuclear transfer (NT), a fertilized egg is created using the intending mother’s egg and partner or donor sperm, but the egg is allowed to develop to the blastocyst stage, approximately five days after fertilization.[18] Cells are then harvested and the nuclei removed and injected into multiple enucleated “donor” eggs, in essence creating cloned embryos.[19] Here again, the “donor” egg is actually the recipient of the intending mother’s fertilized nuclear material. One or more of these new embryos is then transferred into the intending mother or her surrogate.[20] Finally, mitochondrial or cytoplasmic transfer (CT) involves the transfer of healthy mitochondria from a donor egg into the cytoplasm of an affected egg before fertilization to “dilute” the effect of abnormal mitochondria in the intending mother’s gene line.[21] Although this technique most closely represents true donation of mitochondrial material to the intended mother’s egg, it, along with the other techniques, results in the addition of close to 20,000 mitochondrial genes from the “donor” in the process.[22] Of the four procedures, PNT and MST will be the focus of this discussion, as NT has fallen out of favor due to its creation of multiple embryos with identical genes—in essence “cloning” an individual—whereas research involving CT has been largely discredited because of questionable benefits.[23]

Support for MRT

The United Kingdom’s Human Fertilisation and Embryology Authority (HFEA) was the first governmental entity to recommend approval of MRT following its legalization by Parliament.[24] This followed the Nuffield Council on Bioethics’ review that recommended in favor of cautiously proceeding with the technology, citing “health and social benefits to individuals and families of living free from mitochondrial disorders.”[25] Providing genetically related but disease-free offspring to mothers affected by mitochondrial disorders is the primary factor in calling for the approval of PNT and MST techniques.[26] Craven et al. point out that, outside of MRT, no options exist for a woman carrying defective mitochondrial DNA to have a healthy genetically related child.[27] Therefore, refusing a woman the option of MRT denies her autonomy to make her own reproductive choices.[28]

Pompei and Pompei go further, stating, a “ban on MRT is in direct violation of a woman’s constitutionally protected rights to privacy and reproductive autonomy, encompassing both positive [freedom to decide whether or not to have children] and negative [freedom to prevent the conception or birth of afflicted children] rights.”[29] They note women can abort unwanted children, but, by not allowing MRT technology to be offered more universally, these same women “are prohibited by the government’s mandate from assuring the health and wellbeing of their unborn and wanted children.”[30] Therefore, as a means to allow women to have genetically related children free from mitochondrial disorders, MRT should be embraced.

Beneficence toward future children and their descendants also prompts support for MRT.[31] Afflicted families testify to the devastating effects on their offspring. Often these children appear healthy at birth only to quickly deteriorate, suffering seizures, organ failure, and subsequent death.[32] For others, the disorder does not appear until well into adulthood, leading to infertility or early pregnancy loss, blindness, multi-organ failure, and early death.[33] In both cases, families acknowledge the physical and emotional suffering they and their loved ones experience.[34] Techniques that offer future generations a chance to avoid such deleterious effects, the Nuffield Council concluded, should be pursued.[35]

Briscoe approaches MRT more from the ethical perspective of reducing maleficence, in essence claiming MRT is the lesser of two evils. She argues that, in any case, many children who are conceived with a disability are later aborted; therefore “it is likely that most people would prefer to intervene during the conception of the child rather than merely prevent it from being born.”[36] For her, MRT “is arguably a more ethically justifiable method” of procreation and is therefore acceptable.[37] Briscoe’s belief that early manipulation of a human gamete or embryo is ethically more permissible than abortion is echoed by others as well. Shannon and Wolter, for example, speaking from a Catholic perspective, believe the embryo does not have the moral status of personhood until approximately the third week after fertilization.[38] Although arguing from the standpoint of justified early abortion, their logic would extend to those embracing MRT. They point to the lack of differentiation within early cells, including their totipotency and ability to twin.[39] Because of this lack of differentiation, the authors claim “neither the zygote nor the blastocyst is an ontological individual, even though it is genetically unique and distinct from the parents. . . . One can reasonably conclude, then, that if there is no single human entity, there is no person.”[40] Recognizing there is a unique life created after fertilization, the authors claim this life is not an individual person.[41] Arguing from this standpoint, then, early manipulation of an embryo to correct a mitochondrial deficiency would be permissible because that which is being manipulated does not have personhood.

Peterson argues also from a Christian viewpoint that permitting germ line modification, as long as it is done appropriately, is morally ethical because it avoids “errors of omission” that Christ cautions against in Matthew 25.[42] He believes we can “best serve our neighbors” by intervening early enough in a disease process to prevent transmission of severe mitochondrial disorders to future generations.[43] Peterson recognizes genetic intervention of any type as a possibility, providing it is “safe and reliable.”[44] As long as the risks are proportionate to the benefits, a technology should be considered. For Peterson, faithful stewardship as Christians compels us to do what is possible, including germ line therapy, to improve the lives of those suffering from genetic disorders, as long as the technology subscribes to his five standards.[45]

Still others see a much broader benefit of MRT. Shortly after his announcement of a successful birth of a baby boy via MST to a carrier of Leigh syndrome, Zhang formed a company, Darwin Life, to offer germ line therapy to women to treat age-related infertility.[46] A further step he planned was to “combine the technique with editing genes, so that parents can select hair or eye color, or maybe improve their children’s IQ.”[47] Human enhancement was clearly Zhang’s goal. For others, MRT is a way to expand biological parenthood for non-traditional families, including lesbian couples who each desire to share their genetic make-up with a child.[48] This technique is also of benefit for three individuals who want to share parentage of a genetically related child.[49] Reconsidering parenthood, it is argued, is what really is at stake in the MRT debate.[50]

Thus, it is argued by supporters that MRT is ethically moral because it considers the autonomy of a mother who desires children who are biologically related to her, while also practicing beneficence by making it less likely the child will suffer from a debilitating mitochondrial disorder. Manipulation of the embryo is appropriate because it lacks personhood. Since the resulting child’s mitochondria have been changed, further generations will be protected from mitochondrial disease, extending beneficence to them as well. In addition, with society’s changing views of parenthood, MRT levels the playing field for non-traditional parents to participate in the genetic make-up of a child, providing justice to certain members of the population.

Concerns with MRT

Whereas supporters of MRT express their arguments mainly as duties to intervene to aid a mother and her child, those opposed more likely cite concerns over the value and dignity of the egg “donor,” mother, embryo, and future child. First, there is concern for the woman who serves as the mitochondrial “donor.” In preparation for harvesting her eggs, she undergoes artificial hormonal manipulation of her reproductive cycle.[51] Eggs are then harvested surgically.[52] To date, there has been no long term follow-up of egg donors to determine the effects of this type of intervention on these women.[53] This practice, whether or not the woman is paid for her participation, commodifies “donors.”[54] As MRT technology gains traction, and especially if its use expands to treat infertility or produce “designer” babies as Zhang envisions, the demand for egg donors is expected to increase.[55]

The intending mother is commodified as well. She, too, is subjected to medical manipulation, including hormonal interventions and egg harvesting, but will also face painful decisions on which and how many fertilized eggs to implant. During the pregnancy, she will be offered prenatal diagnosis (PND) testing, since MRT procedures still carry the risk of transmitting low levels of diseased mitochondria.[56] If the developing fetus is found to have a defect, she will be counseled to abort a child with which she has bonded. Likewise, rather than providing an option for all women carrying a mitochondrial defect, MRT is likely to suffer from inequitable distribution by limiting its services to those with the financial resources to afford it.[57] Since only a few women will be considered eligible each year for MRT, it is likely to be offered at just a few specialized care centers, further raising costs for women who would be required to travel for treatment.[58]

It is the embryos and children themselves, however, who are most exploited in MRT. In PNT, for every one embryo created, two will be destroyed.[59] In both PNT and MST, only about half will survive to the blastocyst stage.[60] More will be discarded during preimplantation genetic testing.[61] Only the “healthiest” embryos will be transferred to the womb. Once transplanted, PND will identify others to abort.[62] Assisted reproduction technology (ART) alone, even for those not affected by a chromosomal defect, carries two times the risk of birth defects, increasing the chances that the developing child will be disabled or discarded.[63]

George and Tollefson, although writing prior to the inauguration of MRT, hold it is “morally impermissible to engage in any research, for any purpose, that involves the destruction of human beings at any stage of their lives,” regardless of their inabilities.[64] Due to the unique changes that occur at fertilization that differentiate humans from other developing animals, the authors advocate that even those in the earliest stages of development “are the subjects of rights and the objects of moral duties and responsibilities.”[65] Applying natural law, they point out that “basic human goods”—such as health and the preservation of life—must be “pursued for their own sake.”[66] Therefore, anything that takes away from these goods, like embryonic manipulation, violates the human rights of individual persons.[67]

MacKellar points to still another problem with MRT. He cites two types of identities individuals have: numerical and qualitative.[68] For numerical identity, the biological sense of being remains the same from conception to death and is situated “in the three dimensions of space and over time.”[69] Qualitatively, the “psychological or biographical perspective” of being one and the same also remains consistent throughout time even if qualitative changes, like a joint replacement, occur.[70] Alterations of a somatic genome maintain this numerical and qualitative identity of an individual, as the intervention affects only the existing individual.[71] The distinction between numerical and qualitative identities becomes important, however, when a germ line is edited because, as MacKellar and others point out, editing a germ line does not provide a therapy for an existing individual, but instead prevents that specific individual from existing.[72] A separate person, MacKellar explains, “is being brought into existence and the manner in which this happens is inherently part of who he or she is. . . . A new individual with his or her particular beginning and subsequent life trajectory would be created who would be different from the one who would otherwise have existed had the biological change not occurred.”[73] The individual brought into life is an entirely different person, with different numerical and qualitative identities and a different future than that which would have been born without intervention.[74]

MacKellar then goes further, pointing out that germ line modification is essentially eugenics, selecting which individuals should be born.[75] This is not therapy for an existing disability, but instead prioritizes the creation of an individual over that of one lacking the genetic makeup preferred by the intending parent(s).[76] Going further, UNESCO acknowledges the risk of moving from interventions to prevent a disease process toward ones designed to select for desired features in order to fulfill a “wish for a better, improved life,” however that may be defined.[77]

Once born, exploitation continues.[78] Research shows an inter-connection between the pronucleus and mitochondria that accounts for “subtle selective pressure” from nuclear genetic material on the mitochondria.[79] This raises a concern the child would develop unanticipated and unknown health issues later in life.[80] Any adverse effects could be passed down to future generations and may not be discovered until much later.[81] The President’s Council on Bioethics summed this up in 2004, stating, “There are today no safe and effective means of genetic modification of early embryos.”[82] Eleven years later, UNESCO echoed these same concerns.[83]

Adding to the ethical dilemma, these children are denied autonomy because they cannot give informed consent or refuse modification even though experimentation on them will affect themselves and their offspring.[84] To resolve part of this problem, it has been proposed that sex selection of embryos be prioritized, with only males allowed to mature, as they would be unable to pass their mitochondria on to future generations.[85] This proposal, however, raises concerns about distributive justice. First, it favors the treatment of males for mitochondrial disorders over females, even denying females life. Secondly, it discriminates against males by permitting unique experimentation only on their sex.[86] Minimizing the impact that these decisions have on the rights and autonomy of affected existing embryos and those created through MRT equates them to property rather than unique developing human beings worthy of dignity.

Sutton agrees, stating the embryo and eventual child are treated as a “mere commodity of only instrumental value to us,” but are no less a “participant in human nature and thus in the image of God” than the rest of us.[87] Embryos re-designed by MRT are, in fact, “assembled according to design as manufactured items.”[88] These embryos become artifacts, “things produced or crafted by human endeavor,” whose worth is decided by those who have designed their purpose.[89] She goes on to say:

The end product of the technique is a “collage” assembled from pieces of previously complete embryos. And in both cases the child-to-be is fabricated with a view to meeting a certain standard. These techniques pursue established parameters of health at the expense of nascent human life. This is not to accept the child-to-be as an intrinsically valuable gift and as it is, with inherent integrity. . . . Rather, both pursue health at the expense [of] depersonalizing the child. Nor does the use of maternal spindle transfer satisfy the principle. . . . Once again, the child-to-be is not treated as a neighbor and gift, and it is not given an unconditional welcome as such.[90]

The modification, selection, and implantation of an embryo by MRT defines the worth of a child undergoing the procedure, signifying conditional acceptance within her family and society. With the harvesting of selected embryos and the discarding of others, some lives are judged more valuable than others.[91]

Germ line therapy redefines what is considered an “acceptable birth.”[92] Parents who permit the conception and birth of a child who suffers from a mitochondrial disorder fear being stigmatized.[93] Others have gone so far as to claim it is immoral to bring a child into the world who is disabled, ignoring the intrinsic worth of the disabled person as deserving equal status alongside others.[94] For Sutton, “At issue are human attitudes and aspirations that undermine the welcome of the child as a gift and deny it the respect it deserves as another person whose life comes to us as a gift from God.”[95] The sense of belonging by a child, by virtue of being born unconditionally into a family, becomes qualified for those whose genome takes precedence over their humanity.

Equally concerning is proponents’ advocacy for using MRT to address issues beyond mitochondrial disorders. Zhang’s ambitions included creating enhanced children with traits picked by parents.[96] Other countries have claimed successful births using MRT to treat infertility, although their studies are questionable.[97] Likewise, none of this takes into account the changing understanding of biological parenthood when three adult germ lines are used to treat a disorder or further creative procreation.[98]

A Christian Response

An appropriate Christian response to MRT takes into account these complex issues in light of Scripture. First, we learn through the Creation story that God is the designer of all human life and calls all he makes “good” (Gen 1:31, ESV). Proclamations in the Bible confirm God’s active involvement in the creation of each person (Ps 139; Luke 1:13–25). Ramsey notes that, until a child is created, disability concerns or the need for germ line manipulation do not exist.[99] Should a child’s germ line be modified to prevent a disease, a “hypothetical” child is brought into existence from the original.[100] Instead of providing medical treatment to an already existing person, a new child is formed. From a Christian viewpoint, Ramsey recognizes that technologies like MRT shift the focus from God as Creator to humankind as creators, now able to manipulate cells to their design to fulfill their own desires. O’Donovan agrees, lamenting the anonymity of ART that changes the status of children from “begotten” to “made.”[101] This is not to negate the value of the “made” child, who shares the same intrinsic dignity as the “begotten” one, but points to how God’s providence fades into insignificance when humankind determines it knows better about a child and his ability to flourish than God does.

Additionally, although it is claimed these technologies are gifts from God to be used to overcome effects of the Fall, any technology that glorifies God cannot destroy embryos or reshape parenthood in the process. Science confirms the fertilized human egg is a unique human individual, and therefore a person.[102] In accepting this confirmation of humanity from science, the embryo bears a distinct individuality and commands “inherent human dignity.”[103] Because dignity is derived from our status as image-bearers of God, humanity should take seriously the commands to honor and respect others (Exod 20:10–17; Matt 22:39). The destruction of embryos to create new ones is morally unjust because it places greater value on the new embryo due to its genome than it does on those that preceded it. Ramsey points out we are more than our parts, or, in the case of MRT, our genes. We are “embodied soul[s],” sacred, and worthy of “the awesome respect required of men in their dealings with men.”[104] Whether begotten or made, the human embryo is of intrinsic worth to God and should be treated reverentially.

Living post-Fall, though, subjects us to disease and disability that cannot be ignored. Nonetheless, eugenic policies cannot be supported as part of a Christian response. MRT as it exists today is not the lesser of two evils, as Briscoe would claim, but is in and of itself evil due to its destruction of preexisting embryos in order to avoid disability.[105] Christians must acknowledge that the sanctity of the individual extends even into disability. Individuals with disabilities have much to teach families and the Church. Within disability, we learn the virtue of compassion without expecting anything in return. Other virtues, like patience, gentleness, and long-suffering, are also molded (Gal 5:22–23; Jas 1:2–15; Rom 1:2–4). The Church should be counter-cultural as it embraces those with broken bodies and minds as well as their families.[106] Rather than attempting to solve a genetic problem by denying life to those with disabilities, greater efforts should be placed on caring for those affected by mitochondrial disorders and advocating for safer techniques to treat them. The Church should be a place where the disabled and those who care for them experience hospitality and glimpse the New Creation promised to all who place faith in Christ. Community must be created, encouraging these families in their faith as they experience difficult trials (Rom 1:11–12).

However, we cannot deny the right or responsibility for humankind to steward Creation in such a way that disease and disability, both consequences of the Fall, are mitigated. Techniques that overcome the disabling effects of an inherited mitochondrial disorder should be sought out and developed as long as doing so does not endanger the life of another embryo or future generations.[107] Regardless, if mitochondrial disability cannot be surmounted without harming others, the positive impact of these affected children through all stages of development must be affirmed by the Church and society. O’Donovan notes that a reverential awe of God’s creation of “new human beings, including those whose humanity is ambiguous and uncertain to us” is mandatory in helping us learn how to love others.[108] God values all human life equally from conception to death. We are better able to understand Christ’s love for us and to love others when we embrace the creative design of God in humanity.

Finally, we must be reminded that Scripture teaches us that we are not individually autonomous creatures. A mother’s decisions argued upon autonomy affect that of those around her, including the child, the father, extended family, and future generations, even as she is situated under her vertical relationship with God. Christ has made us to be in community, positioned with and dependent upon each other. Decisions are not made in a void, but their consequences reflect the inter-relatedness God designed us for (Gen 2:18, 3). God’s Word roots us within our situated beings. Our true autonomy comes from recognizing God’s authority over Creation and our dependence on Christ’s sacrifice on our behalf as a payment for our sin—finding freedom, ultimately, in our knowledge that he has released us from the disabling effects of the Fall. It is through Christ’s resurrection that we recognize the power and grace available to us that allow us to face our fears, including the fear of passing on mitochondrial disorders to our children, and respond in ways that glorify him.

Summary

MRT lauds itself as a compassionate option for parents who risk passing on a mitochondrial disorder to their children, allowing these families a chance to have a biologically related child who is free from mitochondrial defects. However, this option is indifferent to the humanity of the embryo. Current MRT practices place the desires of parents over the uniqueness of their children, creating children to meet parents’ own design, while committing them to ongoing research. Sharing genetic information between three individuals, discarding multiple embryos, and harvesting multiple eggs from donors all are signs of commodification. Rather, we should, like Ramsey, recognize that “there may be some things that men should never do.”[109] Modifying the human genome through MRT that sacrifices some embryos for others is one such technology that we should refuse. Instead, a proper response is to advocate for research that does not place higher value over particular lives than it does that of the disabled embryo, or whose effects on future generations is unknown. Research should also support families in their current struggles, embracing the unique worth of all who are created in God’s image despite their disability, inviting them into refreshing fellowship within the household of Christ as we yearn for the restoration of broken bodies in God’s New Creation.

References

[1] “Leigh Syndrome,” MedlinePlus-U.S. National Library of Medicine, September 8, 2020, https://medlineplus.gov/genetics/condition/leigh-syndrome/.

[2] Sarah Fogleman et al., “CRISPR/Cas9 and Mitochondrial Gene Replacement Therapy: Promising Techniques and Ethical Considerations,” American Journal of Stem Cells 5, no. 2 (August 20, 2016): 39;  Agneta M. Sutton, “Mitochondria Replacement to Avoid Maternal Transmission of Mitochondrial Disease,” Dignitas 20, no. 3 (Fall 2013): 4, https://www.cbhd.org/dignitas-articles/mitochondria-replacement-to-avoid-maternal-transmission-of-mitochondrial-disease; Rebecca Briscoe, “Ethical Considerations, Safety Precautions and Parenthood in Legalising Mitochondrial Donation,” The New Bioethics 19, no. 1 (March 2013): 3–4, https://doi.org/10.1179/2050287713Z.00000000027.

[3] John Zhang et al., “Live Birth Derived from Oocyte Spindle Transfer to Prevent Mitochondrial Disease,” Reproductive Biomedicine Online 34, no. 4 (April 2017): 361–68, https://doi.org/10.1016/j.rbmo.2017.01.013.

[4] The term “mitochondrial replacement therapy” (MRT) will be used in this paper as it is widely recognized, although some have argued that the term “mitochondrial donation” (MD) may be more accurate. See Jessica Cussins and Leah Lowthorp, “Germline Modification and Policymaking: The Relationship between Mitochondrial Replacement and Gene Editing,” The New Bioethics 24, no. 1 (2018): 77, https://doi.org/10.1080/20502877.2018.1443409.

[5] Yi Shiau Ng and Doug M. Turnbull, “Mitochondrial Disease: Genetics and Management,” Journal of Neurology 263 (2016): 179, https://doi.org/10.1007/s00415-015-7884-3.

[6] Ng and Turnbull, “Mitochondrial Disease,” 179.

[7] Ng and Turnbull, “Mitochondrial Disease,” 179.

[8] Ng and Turnbull, “Mitochondrial Disease,” 180.

[9] Ng and Turnbull, “Mitochondrial Disease,” 180–87.

[10] Fogleman et al., “CRISPR/Cas9 and Mitochondrial Gene Replacement,” 39; “Novel Techniques for the Prevention of Mitochondrial DNA Disorders: An Ethical Review” (Nuffield Council on Bioethics, June 2012), 28, https://www.nuffieldbioethics.org/assets/pdfs/Novel_techniques_for_the_prevention_of_mitochondrial_DNA_disorders.pdf. An embryo will be defined as the individual in the first eight weeks of development following fertilization. See Rebecca Oliver and Hajira Basit, “Embryology, Fertilization,” in StatPearls (Treasure Island, FL: StatPearls Publishing, 2021),  http://www.ncbi.nlm.nih.gov/books/NBK542186/; and Robert George and Christopher Tollefsen, Embryo: A Defense of Human Life, 2nd ed. (Princeton, NJ: The Witherspoon Institute, 2011), 36–49.

[11] Sutton, “Mitochondria Replacement to Avoid Maternal Transmission,” 1. A more accurate name for “eggs” is oocytes, but for the purpose of this paper the term “egg” will be used. See George and Tollefsen, Embryo, 28.

[12] Sutton, “Mitochondria Replacement to Avoid Maternal Transmission,” 1. Pronucleus here is defined as “the membrane-bound nuclear genetic material derived from the oocyte or spermatozoa following fertilization.” See Anne Claiborne, Rebecca English, and Jeffrey Kahn, eds., Mitochondrial Replacement Techniques: Ethical, Social, and Policy Considerations (Washington, DC: National Academies Press, 2016), 28, https://doi.org/10.17226/21871.

[13] Nuffield Council on Bioethics, “Novel Techniques,” 34. The nDNA material is located to one side of the egg, giving the technique its name.

[14] Nuffield Council on Bioethics, “Novel Techniques,” 34.

[15] David Albert Jones, “The Other Woman: Evaluating the Language of ‘Three Parent’ Embryos,” Clinical Ethics 10, no. 4 (September 1, 2015): 3, https://doi.org/10.1177/1477750915599721.

[16] Stuart Newman, “FDA Asked to Approve Creation of Genetically Modified Children,” HuffPost, February 20, 2014, https://www.huffpost.com/entry/fda-asked-to-approve-crea_b_4809876.

[17] Jones, “The Other Woman,” 7–8.

[18] Sutton, “Mitochondria Replacement to Avoid Maternal Transmission,” 4; Nuffield Council on Bioethics, “Novel Techniques,” 40.

[19] Sutton, “Mitochondria Replacement to Avoid Maternal Transmission,” 4.

[20] Nuffield Council on Bioethics, “Novel Techniques,” 40.

[21] Sutton, “Mitochondria Replacement to Avoid Maternal Transmission,” 4.

[22] Newman, “FDA Asked to Approve Creation of Genetically Modified Children.”

[23] Nuffield Council on Bioethics, “Novel Techniques,” 38–40; Sutton, “Mitochondria Replacement to Avoid Maternal Transmission,” 4.

[24] Annabel Slater, “UK Approves Mitochondrial Donation Babies,” BioNews, December 19, 2016, https://www.bionews.org.uk/page_95828.

[25] Nuffield Council on Bioethics, “Novel Techniques,” xvi.

[26] Marybeth Pompei and Francesco Pompei, “Overcoming Bioethical, Legal, and Hereditary Barriers to Mitochondrial Replacement Therapy in the USA,” Journal of Assisted Reproduction and Genetics 36, no. 3 (December 15, 2018): 388, https://doi.org/10.1007/s10815-018-1370-7; Robert Klitzman, Mark Toynbee, and Mark Sauer, “Controversies Concerning Mitochondrial Replacement Therapy,” Fertility and Sterility 103 (December 20, 2014): 345, https://doi.org/10.1016/j.fertnstert.2014.10.028;  Hitika Sharma et al., “Development of Mitochondrial Replacement Therapy: A Review,” Heliyon 6, no. 9 (September 14, 2020): 1, https://doi.org/10.1016/j.heliyon.2020.e04643.

[27] Lyndsey Craven et al., “Scientific and Ethical Issues in Mitochondrial Donation,” The New Bioethics 24, no. 1 (April 2018): 59, https://doi.org/10.1080/20502877.2018.1440725.

[28] Craven et al., 59; Klitzman, Toynbee, and Sauer, “Controversies Concerning MRT,” 345.

[29] Pompei and Pompei, “Overcoming Barriers,” 387.

[30] Pompei and Pompei, “Overcoming Barriers,” 388 (italics added).

[31] Alexa Woodword, “An Assessment of Mitochondrial Replacement Therapy,” Voices in Bioethics 3 (April 19, 2017): 3, https://doi.org/10.7916/vib.v3i.6009; Klitzman, Toynbee, and Sauer, “Controversies Concerning MRT,” 345.

[32] Jeffery Sauer, “Mitochondrial Replacement Therapy: How a Government for the People, Failed the People,” University of Miami Law Review 73, no. 1 (October 30, 2018): 302, https://repository.law.miami.edu/umlr/vol73/iss1/8; Magdalena Kegel, “Charlie Gard Case Captures Vast Need for Mitochondrial Disease Research, Groups Say,” Mitochondrial Disease News (blog), July 13, 2017, https://mitochondrialdiseasenews.com/2017/07/13/charlie-gard-case-captures-vast-need-for-mitochondrial-disease-research-treatments-groups-say/.

[33] Nuffield Council on Bioethics, “Novel Techniques,” 21–22.

[34] Forough Noohi, Miranda Li, and Yann Joly, “Clinical Translation of Mitochondrial Replacement Therapy in Canada: A Qualitative Study of Stakeholders’ Attitudes,” ed. Imogen Coe, FACETS 6, no. 1 (January 1, 2021): 456, https://doi.org/10.1139/facets-2020-0062.

[35] Nuffield Council on Bioethics, “Novel Techniques,” 88.

[36] Briscoe, “Ethical Considerations, Safety Precautions,” 5.

[37] Briscoe, “Ethical Considerations, Safety Precautions,” 5.

[38] Thomas Shannon and Allan Wolter, “Reflections on the Moral Status of the Pre-Embryo,” in On Moral Medicine: Theological Perspective in Medical Ethics, ed. M. Therese Lysaught et al., 3rd ed. (Grand Rapids, MI: Eerdmans, 2012), 343, 350.

[39] Totipotent cells have the ability to “develop into an embryo with all the specialized cells that make up a living being, as well as into the placental support structure necessary for fetal development,” including the umbilical cord and membranes. See Shoukhrat Mitalipov and Don Wolf, “Totipotency, Pluripotency and Nuclear Reprogramming,” Advances in Biochemical Engineering/Biotechnology 114 (2009): 185, https://doi.org/10.1007/10_2008_45.

[40] Shannon and Wolter, “Reflections on the Moral Status of the Pre-Embryo,” 346.

[41] Shannon and Wolter, “Reflections on the Moral Status of the Pre-Embryo,” 350.

[42] James Peterson, “Ethical Standards for Genetic Intervention,” in On Moral Medicine: Theological Perspectives in Medical Ethics, ed. M. Therese Lysaught et al., 3rd ed. (Grand Rapids, MI: Eerdmans, 2012), 969–70.

[43] Peterson, “Ethical Standards for Genetic Intervention,” 970.

[44] Peterson, “Ethical Standards for Genetic Intervention,” 970–72.

[45] Peterson, “Ethical Standards for Genetic Intervention,” 971–73. Peterson’s standards include: incremental implementation in order to understand the effects of processes along the way; allowing only “interventions that enhance a person’s options by freeing that individual from what is clearly destructive or by increasing the person’s capability,” as opposed to interventions that would limit an individual’s capabilities; placing decision-making for these interventions into the hands of the individual affected or his parents; creating societal standards of the “limits of intervention”; and insuring the risks associated with these procedures are proportionate to their benefits. Note that Peterson argues not just for correction of a disability, but for enhancement as well.  

[46] Emily Mullin, “The Fertility Doctor Trying to Commercialize Three-Parent Babies,” MIT Technology Review, June 13, 2017, https://www.technologyreview.com/2017/06/13/151273/the-fertility-doctor-trying-to-commercialize-three-parent-babies/.

[47] Mullin, “The Fertility Doctor Trying to Commercialize Three-Parent Babies.”

[48] Sharma et al., “Development of MRT,” 5.

[49] Briscoe, “Ethical Considerations, Safety Precautions,” 14–15.

[50] Mirko Daniel Garasic and Daniel Sperling, “Mitochondrial Replacement Therapy and Parenthood,” Global Bioethics 26, no. 3–4 (October 2, 2015): 198, https://doi.org/10.1080/11287462.2015.1066082.

[51] Donna L. Dickenson, “The Commercialization of Human Eggs in Mitochondrial Replacement Research,” The New Bioethics 19, no. 1 (March 2013): 22, https://doi.org/10.1179/2050287713Z.00000000018.

[52] City Fertility, Egg Collection: An Insight into the Procedure, YouTube, June 12, 2018, https://www.youtube.com/watch?v=tmy3Z-TfZ5I.

[53] Molly Woodriff, Mark V. Sauer, and Robert Klitzman, “Advocating for Longitudinal Follow-up of the Health and Welfare of Egg Donors,” Fertility and Sterility 102, no. 3 (September 2014): 662–66, https://doi.org/10.1016/j.fertnstert.2014.05.037; Emily Woodruff, “‘We Simply Don’t Know’: Egg Donors Face Uncertain Long-Term Risks,” STAT (blog), January 28, 2017, https://www.statnews.com/2017/01/28/egg-donors-risks/.

[54] Dickenson, “Commercialization of Human Eggs,” 26.

[55] Nuffield Council on Bioethics, “Novel Techniques,” 83.

[56] Craven et al., “Scientific and Ethical Issues,” 66.

[57] Noohi, Li, and Joly, “Clinical Translation of Mitochondrial Replacement Therapy in Canada,” 458.

[58] Noohi, Li, and Joly, “Clinical Translation of Mitochondrial Replacement Therapy in Canada,” 458.

[59] Nuffield Council on Bioethics, “Novel Techniques,” 32.

[60] Briscoe, “Ethical Considerations, Safety Precautions,” 8.

[61] Nuffield Council on Bioethics, “Novel Techniques,” 26–27.

[62] Nuffield Council on Bioethics, “Novel Techniques,” 26–29.

[63] President’s Council on Bioethics, Reproduction and Responsibility: The Regulation of New Biotechnologies (Washington, DC: President’s Council on Bioethics, March 2004), 38–39, https://bioethicsarchive.georgetown.edu/pcbe/reports/reproductionandresponsibility/.

[64] George and Tollefsen, Embryo, 24.

[65] George and Tollefsen, Embryo, 106.

[66] George and Tollefsen, Embryo, 98.

[67] George and Tollefsen, Embryo, 104.

[68] Calum MacKellar, Christianity and the New Eugenics (London: InterVarsity Press, 2020), 160–61.

[69] MacKellar, Christianity and the New Eugenics, 160.

[70] MacKellar, Christianity and the New Eugenics, 161.

[71] MacKellar, Christianity and the New Eugenics, 161–62.

[72] MacKellar, Christianity and the New Eugenics, 163–64; James Davison, “Gene Editing: A View through the Prism of Inherited Metabolic Disorders,” The New Bioethics 24, no. 1 (April 2018): 7, https://doi.org/10.1080/20502877.2018.1443563.

[73] MacKellar, Christianity and the New Eugenics, 165–66.

[74] Nuffield Council on Bioethics, “Novel Techniques,” 54.

[75] MacKellar, Christianity and the New Eugenics, 163, 168.

[76] MacKellar, Christianity and the New Eugenics, 171.

[77] Internal Bioethics Committee, “Report of the IBC on Updating Its Reflection on the Human Genome and Human Rights” (UNESCO, October 2, 2015), 26, https://unesdoc.unesco.org/ark:/48223/pf0000233258?posInSet=1&queryId=478099c2-5227-411a-b9af-fa4feadf942d (italics original).

[78] Sutton, “Mitochondria Replacement to Avoid Maternal Transmission,” 4.

[79] Wei Wei et al., “Germline Selection Shapes Human Mitochondrial DNA Diversity,” Science 364, no. 6442 (May 24, 2019): 9, https://doi.org/10.1126/science.aau6520.

[80] Jenny Sharpe, “DNA Study May Have Implications for Mitochondrial Donation,” BioNews, June 3, 2019, https://www.bionews.org.uk/page_143066; Calum MacKellar, GM Babies with 3 or 4 Parents (The Christian Institute, 2013), 17, https://www.christian.org.uk/wp-content/uploads/3-parents.pdf.

[81] Nuffield Council on Bioethics, “Novel Techniques,” 57. Research also indicates any gains made in the correction of mtDNA may be lost over subsequent divisions due to influence from maternal nDNA. See Mitsutoshi Yamada et al., “Genetic Drift Can Compromise Mitochondrial Replacement by Nuclear Transfer in Human Oocytes,” Cell Stem Cell 18 (June 2, 2016): 749, https://doi.org/10.1016/j.stem.2016.04.001.

[82] President’s Council on Bioethics, Reproduction and Responsibility, 108.

[83] Internal Bioethics Committee, “Report of the IBC,” 3.

[84] Nuffield Council on Bioethics, “Novel Techniques,” 59. Until 2023, no children were known to have been born in the UK as a result of MRT technology, despite widespread approval of the research. This changed May 9, 2023, when it was announced that “’less than five’” children have been born using MRT. The UK’s Human Fertilisation and Embryology Authority has announced it will be purposely vague in information shared with the public to protect the families involved in this research. See Trevor Stammers, “Promises, Promises, Promises,” MercatorNet (blog), February 9, 2021, https://mercatornet.com/promises-promises-promises/70070/; and Ian Sample, “First UK Baby with DNA from Three People Born after New IVF Procedure,” The Guardian, May 9, 2023, sec. Science, https://www.theguardian.com/science/2023/may/09/first-uk-baby-with-dna-from-three-people-born-after-new-ivf-procedure.

[85] Nuffield Council on Bioethics, “Novel Techniques,” 80; Julian Koplin, “How Should Mitochondrial Donation Operate in Australia?” BioNews, April 12, 2021, https://www.bionews.org.uk/page_155799.

[86] Nuffield Council on Bioethics, “Novel Techniques,” 80; Woodword, “An Assessment,” 3.

[87] Sutton, “Mitochondria Replacement to Avoid Maternal Transmission,” 4.

[88] Sutton, “Mitochondria Replacement to Avoid Maternal Transmission,” 4.

[89] Sutton, “Mitochondria Replacement to Avoid Maternal Transmission,” 4.

[90] Sutton, “Mitochondria Replacement to Avoid Maternal Transmission,” 5.

[91] Michael J. Sleasman and Paige Comstock Cunningham, “Editing Human Beings,” Everyday Bioethics, July 6, 2015, https://www.cbhd.org/cbhd-resources/editing-human-beings.

[92] Sutton, “Mitochondria Replacement to Avoid Maternal Transmission,” 5; President’s Council on Bioethics, Reproduction and Responsibility, 98.

[93] Briscoe, “Ethical Considerations, Safety Precautions,” 5.

[94] Briscoe, “Ethical Considerations, Safety Precautions,” 5; Agneta Sutton, “Germ-Line Gene Therapy Could Prove a Two-Edged Tool,” Christian Bioethics 18, no. 2 (August 2012): 146, https://doi.org/10.1093/cb/cbs012.

[95] Sutton, “Germ-Line Gene Therapy Could Prove a Two-Edged Tool,” 149.

[96] Mullin, “The Fertility Doctor.”

[97] Ayala Ochert, “Mitochondrial Donation Technique Used in Ukraine, Doctors Claim,” BioNews, October 17, 2016, https://www.bionews.org.uk/page_95736. Sharma et al., “Development of MRT,” 2–4.

[98] Garasic and Sperling, “Parenthood,” 198–204;  Sarah Knapton, “Three Parent Babies Banned from Knowing ‘Second Mothers,’” The Telegraph, July 23, 2014, https://www.telegraph.co.uk/news/science/science-news/10984068/Three-parent-babies-banned-from-knowing-second-mothers.html; Jones, “The Other Woman,” 11–12, 17.

[99] Paul Ramsey, Fabricated Man: The Ethics of Genetic Control (London: Yale University Press, 1970), 119.

[100] Ramsey, Fabricated Man, 119.

[101] Oliver O’Donovan, Begotten or Made? (Oxford: Clarendon Press, 1984), 32–35.

[102] George and Tollefsen, Embryo, 218–20.

[103] Michael Panicola, “Three Views on the Preimplantation Embryo,” in On Moral Medicine: Theological Perspective in Medical Ethics, ed. M. Therese Lysaught et al., 3rd ed. (Grand Rapids, MI: Eerdmans, 2012), 352, 364; Calum MacKellar, “Questions Relating to ‘Mitochondrial Replacement,’” BioNews, February 10, 2014, https://www.bionews.org.uk/page_94479. See also Genesis 1:27.

[104] Paul Ramsey, The Patient as Person: Explorations in Medical Ethics, 2nd ed. (London: Yale University Press, 2002), xlvi.

[105] Briscoe, “Ethical Considerations, Safety Precautions,” 5.

[106] Brett Webb-Mitchell, “Welcoming Unexpected Guests to the Banquet,” in On Moral Medicine: Theological Perspectives in Medical Ethics, ed. M. Therese Lysaught et al., 3rd ed. (Grand Rapids, MI: Eerdmans, 2012), 614–15.

[107] For instance, researchers in Israel have developed a technique to transfer healthy mitochondria from a mother to her child suffering from one of two congenital mitochondrial defects using hematopoietic stem cells, showing promising results a year after the procedure. Although this research is still in its early stages and is not directed toward inheritable defects, it is an example of research that avoids human embryo destruction. See Mitch Leslie, “Moms’ Mitochondria May Refresh Cells in Sick Kids,” Science, December 21, 2022, https://www.science.org/content/article/moms-mitochondria-may-refresh-cells-sick-kids.

[108] O’Donovan, Begotten or Made? 66.

[109] Ramsey, Fabricated Man, 123.

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