A panel of scientists and ethicists have said the US should allow clinical research into preventing genetic diseases by mitochondrial replacement, a technique which involves substituting the faulty mitochondria in a mother’s eggs with healthy mitochondria from a donor. In a report from the National Academy of Sciences, Engineering and Medicine, the panel said it would be ethically okay for women to be implanted with embryos whose mitochondria had been replaced, thereby having DNA from three people, as long as certain conditions were met. The technique, dubbed by the media as ‘3-person IVF’, was given legal approval in the UK last year.
Dr. Françoise Baylis, Professor and Canada Research Chair in Bioethics and Philosophy, Dalhousie University (webpage):
Expertise: bioethical aspects of women’s health, human embryo research, and novel genetic technologies.
“With the Institute of Medicine report, the US is poised to proceed with research involving mitochondrial replacement.
“The committee’s approach is notably more cautious than that adopted in the UK, recommending the limitation of research to the intrauterine transfer of genetically modified male embryos. 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” 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.
“Finally, 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” who assume the risk of potential harm for no potential benefit other than perhaps financial compensation which, for some, exposes them to the harms of either commodification or exploitation.”
Lori P. Knowles, Assistant Professor, Adjunct, School of Public Health, University of Alberta, Canada:
Expertise: ethical and social issues arrising from biotechnology, reproductive technology, international law and biotechnology policy.
“The Institute of Medicine (IOM) report recommends moving forward with restrictions and limitations in place as a means of managing the ethical, social and policy issues of mitochondrial DNA (mtDNA) transfer. This stance represents a natural next step following more than a decade of restricted use on mtDNA for clinical application.”
“While other countries like the UK may be moving forward at a faster pace, the report takes a cautious but progressive approach to combatting serious diseases, while minimizing risks to future children. Striking the balance between caution and progress inevitably exasperates those who with to go faster and those hoping to stop all movement. However, the IOM recommendations succeed in balancing both the American desire for progress and cures with widely held concerns about research on human embryos.”
“Restricting mtDNA transfer to male embryos will sanction the creation of children with three genetic ‘parents’ or donors. While noteworthy, it is in line with existing restrictions that seek to address serious genetic diseases and avoid the transmission of genetic changes to future generations. What is new is leaving the door open to the future use in female embryos, thereby effectively allowing a glimpse at a future in which genetic modifications could be passed to future offspring. The report is clear that evidence, experience, surveillance and oversight need to be in place well before that happens.”
“Perhaps what’s most noteworthy about this report is what isn’t in the headlines. This report provides the most up to date, careful and thoughtful compilation of ethical and policy thinking on embryo research, use of oocytes, issues of kinship and inheritable genetic modifications. As such it provides a blueprint for analyzing any of the myriad of new reproductive techniques that will be surely coming in the near future.”
Dr. Debra Mathews, Assistant Director of Science Programs, Johns Hopkins Berman Institute of Bioethics (webpage):
Expertise: Bioethics and policy issues related emerging biotechnologies.
“The Institute of Medicine Committee has, importantly, framed their conclusions around the ethical permissibility of clinical investigations of mitochondrial replacement techniques (MRT), rather than MRT itself. This is an important distinction, and sets the stage for a series of reasonable restrictions on such investigations, including limiting who may conduct the necessary trials, which conditions may be included, and the sex of the embryos ultimately transferred, all in an effort to minimize risks while improving our understanding of the techniques, their benefits and harms. Also key to their recommendations are their calls for transparency, public engagement and data pooling, to maximize the utility of the data resulting from trials, speed our understanding of these techniques, and rapidly identify any problems that may arise. That said, many details remain to be worked out, and what these restrictions, transparency and public engagement, for example, look like in practice will be vitally important.”
Dr. Bruce Cohen, Director, NeuroDevelopmental Science Center & Pediatric Neurology, Akron Children’s Hospital (webpage):
Expertise: Dr. Cohen specializes in researching and treating mitochondrial diseases and other neurological ailments.
“From the perspective of a clinician who takes care of people with mitochondrial disease, I think this report is positive and I’m very pleased with its thoroughness and content. The committee has taken a pragmatic approach, considering the science along with moral and ethical constructs to put together a set of recommendations that will allow the science to move forward towards developing new therapies.
“This potential therapy is designed to allow a women with a mitochondrial DNA mutation to have a child without (i) the risk of having the mutation, (ii) the disease associated with the mutation or (iii) the risk, if female, of passing on the mutation to her offspring. It does not address options for people with mutations in the nuclear DNA that cause mitochondrial disease. The limitation of transferring only male embryos creates a bit of a hurdle in some regards but it actually may quicken the process of developing therapies because it obviates the medical and possibly legislative issue around the question of what happens if the replacement doesn’t fully work or has pathogenic mitochondria that in the case of a female embryo will be passed on to the next generation. This is not in any way an attempt by the FDA or anyone else at gender selection and anyone who thinks that is misinformed.
“The report also emphasizes safeguards for conducting clinical research into mitochondrial replacement, many of which are already in place. I’m not directly involved in mitochondrial replacement therapy research but I suspect that the groups doing that are huddling down right now going through the recommendations carefully. My hope is that we will have clinical trial protocols up for review in a few months.
“I think we need to take a multi pronged approach to treat mitochondrial disease with mitochondrial replacement being one, medications being another and genetic modification like CRISPR being yet another option for treatment.”
Glenn Cohen, Professor of Law, Faculty Director, Petrie-Flom Center for Health Law Policy, Biotechnology & Bioethics, Harvard University (webpage):
Expertise: the intersection of bioethics and the law, health law in reproductive technology. Glenn Cohen co-wrote an article in Science with Dr. Eli Adashi, Professor of Medical Science and Former Dean of Medicine and Biological Sciences at Brown University on the regulation of mitochondrial replacement therapy in the United States.
“I’m very happy that the expert committee reached this conclusion on the ethical permissibility of mitochondrial replacement techniques. Overall I think this is an excellent report that is comprehensive and balanced. I think they could have done more to explain why they have not gone quite so far as the United Kingdom but it seems like a sensible first step.
“The limitation of use of mitochondrial replacement to males was surprising and clever twist on their part that makes a lot of sense. It allows them to hive off the germ-line issues that I think cause the most consternation. But notice that it creates a distinction from the UK approval process which allows transfer of either kinds of embryos. Moreover it means that there will be fertilized embryos created that will not be used (I.e., female ones) that some may find objectionable.
“The recommended FDA approval process set out towards the end of the paper are a more cumbersome process than the one envisaged under the UK system, but that has more to do with a difference in regulatory structure of the two countries (the Human Fertilisation and Embryology authority, the UK regulator grants clinical licenses while FDA needs to approve this through its pathways).
“The report itself is just a report. It makes recommendations but they have no force. The next step will likely be consideration by FDA and Congress. FDA has rule making and administrative adjudicative authority to implement this kind of system if it wanted to, but Congress can always try to implement a different system by legislation. I predict little to no action on this until after the election is over and what happens next may depend on who is elected. Even a favorable desire by FDA to implement will require many steps so I would not expect it to get to the clinic in the near future, but we may see a clinical trial application soon and FDA will have to decide how to deal with it.”
Declared interests (see GENeS register of interests policy):
Dr. Françoise Baylis: I was an external reviewer for this report and provided comments on an earlier draft in October 2015.
No further interests declared.
‘Mitochondrial Replacement Techniques: Ethical, Social, and Policy Considerations‘ by the National Academies of Sciences, Engineering and Medicine published on Wednesday 3 February 2016