A Cautious Approach to Mitochondrial Replacement

Françoise Baylis comments on the US Institute of Medicine’s report on Mitochondrial Replacement.

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Today the Institute of Medicine (IOM) released a report, “Mitochondrial Replacement Techniques: Ethical, Social and Policy Considerations.” With this report, written at the request of the Food and Drug Administration, the United States is poised to proceed with research involving mitochondrial replacement.

Mitochondrial replacement research involves the transfer of nuclear DNA from an unfertilized or a fertilized egg (zygote) with dysfunctional mitochondrial DNA into a fertilized or unfertilized egg that has healthy mitochondrial DNA, and has had its nuclear DNA removed. Children born of this technology will have three genetic parents, insofar as they will have genetic material from a male sperm provider and two female egg providers.

This report, authored by the Committee on the Ethical and Social Policy Considerations of Novel Techniques for Prevention of Maternal Transmission of Mitochondrial DNA Diseases, makes a number of important contributions to the ethics and policy debates.

National Academies of Sciences, Engineering, and Medicine. 2016. Mitochondrial replacement techniques: Ethical, social, and policy considerations. Washington, DC: The National Academies Press.

National Academies of Sciences, Engineering, and Medicine. 2016. Mitochondrial replacement techniques: Ethical, social, and policy considerations. Washington, DC: The National Academies Press.

The Committee’s approach to mitochondrial replacement technology is notably more cautious than that adopted in the United Kingdom. The Committee recommends limiting research to the intrauterine transfer of genetically modified male embryos, so as to avoid heritable genetic modification. Mitochondria are maternally inherited; fathers do not pass on their mitochondria to their children. In the UK there is no such limit. The US approach aims to avoid potentially harmful, irreversible, intergenerational effects (assuming that harmful consequences would relate to the mitochondria). What is unclear with this approach is whether the ‘excess’ genetically modified female embryos should routinely be destroyed, used for other research purposes, or stored indefinitely for some future reproductive or research use.

The Committee is to be commended for accurately describing the pursuit of this research as a response to a ‘desire’ on the part of some women to have genetically-related children without mitochondrial disease. Too often the ‘desire’ of prospective parents for genetic relatedness is inappropriately described as a ‘need,’ placing focus on reproductive rights instead of parental responsibilities. It is important not to overvalue genetic relatedness within families.

In my view, a stronger (and possibly more honest) justification, especially given the time, talent and money to be spent on this research, would have focused on the advancement of knowledge around mitochondrial disease in the hope that this might yield insights relevant to other (more common) genetic diseases. Here it is worth remembering that a majority of mitochondrial disease is caused by nuclear DNA mutations, not dysfunctional mitochondrial DNA.

In the report, the proposed guiding principles for the oversight of research involving mitochondrial replacement are generally sound. These include “transparency, public engagement, partnership, maximizing data quality, circumscribed use, and long-term follow-up.” They are, however, incomplete in their failure to include a principle of “care and concern for egg providers.” Egg providers assume the risk of potential harm for no potential benefit (other than perhaps financial compensation which, for some, exposes them to the harms of commodification or exploitation).

Finally, it is unfortunate that the Committee elected to describe the technology as “mitochondrial replacement technology,” instead of “nuclear genome transfer technology” or “nuclear genome transplantation.” Arguably, these other terms more accurately reflect the fact that the technology involves the transfer of nuclear DNA from one cell to another cell. The Committee Chair defended the use of the term “mitochondrial replacement technology” during the public briefing of the IOM report. In his view, such alternative terms might erroneously have people thinking about cloning, which mitochondrial replacement is not.

While it is true that the motivation with mitochondrial replacement is distinct from cloning, it is important to note that the transfer technology is the same. The difference is in the source of the nuclear DNA – with cloning the source is a somatic cell, with mitochondrial replacement the source is a germ cell. To be clear, the micromanipulations with each of these technologies are the same. For this reason, it has been suggested that mitochondrial replacement can legitimately be seen as a “quiet way station” in which to refine the micromanipulations techniques essential for other genetic interventions (including cloning).

 

Françoise Baylis was an external reviewer for this report and provided comments on an earlier draft in October 2015.

A portion of this commentary is available on GENeS.

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Françoise Baylis is Professor and Canada Research Chair in Bioethics and Philosophy at Dalhousie University @FrancoiseBaylis