Wednesday, March 19, 2014

Mitochondrial Donation: Why the Controversy?

By: Michelle Bayefsky

Late last month, the Cellular, Tissue, and Gene Therapies Advisory Committee of the Food and Drug Administration (FDA) met to consider whether research on mitochondrial donation, which could be used to prevent women from passing on mitochondrial disease to their children, was ready to begin testing in humans.  Instead of excitement at the prospect of eradicating mitochondrial disease, which can cause blindness, dementia, epilepsy, and many other conditions, much of the public reaction was characterized by fear, confusion, and hostility.  Headlines from “Genetically Modified Babies” to “Tinkering with Frankenstein: Obama Admin Considers Three-Parent Embryos” flooded the internet, and scientists and bioethicists struggled to refocus attention on the medical feat that is close to being achieved.[1]

Mitochondrial donation involves either transferring healthy mitochondria from a donor into the egg of an affected woman, or inserting the pronuclei of two prospective parents into an enucleated donor egg.[2]  Since mitochondria carry their own DNA and are maternally inherited, children born after mitochondrial donation will technically have DNA from three people – hence the nickname “three-parent IVF” given to the procedure by the press.  This nickname is misleading, however.  The degree to which genetic parentage should be considered synonymous with parentage has already been questioned in debates regarding egg and sperm donation, surrogacy, and adoption.  “Three-parent IVF” suggests a complicated family situation which would be not at all necessary; if social and legal norms have been successfully established for donating gametes containing nuclear DNA to couples with infertility, surely the same could be accomplished with donating mitochondrial DNA.  Furthermore, it seems highly unlikely that we would come to view the donor of mitochondria, an organelle about which most members of the public have little knowledge, as a parent on equal footing with the parents who contribute nuclear DNA and/or intend to raise the resulting child.

Aside from the question of parentage, the major source of controversy surrounding mitochondrial donation is the fact that the technique constitutes a germline modification; the donated mitochondrial DNA would be passed down from generation to generation.  Previously, a line has been drawn (in law, in some countries) between gene therapies that treat problems in somatic cells, like muscular disorders, and modifications that are heritable.  Though mitochondrial donation is aimed at preventing disease, some worry that it will open the door to other types of germline modifications and the creation of ‘designer babies.’  These concerns are misplaced for two reasons.

First, it is unclear why the somatic-germ cell distinction in gene therapy should be our primary criterion rather than a distinction between healing and enhancing.  If our problem with the creation of designer babies – which, given the current state of reproductive medicine, embryology, and genetics is a very long way off – has something to do with satisfying petty parental preferences, we should focus our efforts on preventing the use of powerful reproductive procedures for insufficiently serious purposes.  We should debate what counts as the prevention of a serious genetic condition and what counts as enhancement, not ban germline modifications that are aimed at eradicating disease and reducing suffering.

A second reason that the emphasis on germline modification is misplaced is that technology is already available to select, if not modify, embryo’s genes.  Pre-implantation genetic diagnosis (PGD) is a technique that is used to test embryo’s genes during in vitro fertilization, before deciding which embryos to transfer into the woman’s uterus.  PGD can be used to select against serious heritable diseases, but it can also be used to select for sex, milder disabilities such as deafness or dwarfism, and children who can serve as tissue donors for sick siblings.  The US has no laws or regulations on the acceptable usage of PGD, and elective sex selection is relatively common.[3]  It seems inconsistent to object to the use of mitochondrial donation to prevent serious diseases when a technique that uses selection, rather than modification, to choose non-medical characteristics of future generations is currently unregulated and in use.

Finally, if we decide that the germline criterion must continue to be respected, even when using genetic modification to prevent disease, we could require that mitochondrial donation only be used to create male embryos.  We could use sperm sorting to select male sperm which would be combined with a female pronuclei and an enucleated egg with healthy mitochondria.  Since mitochondria are inherited maternally, if only males are created, the mitochondrial DNA would not be passed on to the next generation.  Though many people find sex selection objectionable, there is precedent for performing sex selection for medical purposes.  For example, PGD is sometimes used to select female embryos to avoid passing on X-linked disorders.

It is understandable that new developments at the intersection of reproductive medicine and genetic technology raise concerns about our attitudes towards future generations, especially given the history of eugenics.  However, we should regard mitochondrial donation for what it is – a tool designed to allow mothers suffering from mitochondrial disorders to have children to whom they are genetically related – rather than focusing on potential future abuses in the general area of genetics and fertility.  Though it is important to exercise caution in the modification of heritable genes, the distinction between healing and enhancing should be our primary criterion for deciding what techniques are ethical and permissible.

Michelle Bayefsky is a senior at Yale University, where she was elected to Phi Beta Kappa and founded and serves as Editor-in-Chief of the Yale Bioethics Journal.  After working as a research assistant at the Yale Interdisciplinary Center for Bioethics for over two years, she will graduate in May with a B.A. in Ethics, Politics and Economics.

[1] Last week, the UK’s Human Fertilisation and Embryology Authority, the governmental body responsible for regulating reproductive medical care, released draft guidelines that would permit mitochondrial donation in humans. Children of mitochondrial donation could be born in the UK as early as next year. See Telegraph article here.
[2] Lewis, Ricki. "FDA Considers Mitochondrial DNA Replacement." Medscape Medical News. Medscape, 26 Feb. 2014. Web. 09 Mar. 2014. <>.
[3] Ginsburg, Elizabeth S., Valerie L. Baker, Catherine Racowsky, Ethan Wantman, James Goldfarb, and Judy E. Stern. "Use of Preimplantation Genetic Diagnosis and Preimplantation Genetic Screening in the United States: A Society for Assisted Reproductive Technology Writing Group Paper." Fertility and Sterility 96.4 (2011): 865-68.

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