Scientists use the term “mitochondrial replacement techniques” to describe the process of adding mitochondrial DNA from a donor to the eggs or fertilized eggs of a woman seeking to become pregnant. In the media and among the public, we often hear the result described as a “three parent embryo,” since three different people are contributing their genetic material to the subsequent baby – the intended mother, the father, and the donor.      

       Whatever we call it, this idea has been controversial ever since its emergence nearly two decades ago. The FDA halted its use here in the early 21st century. In Great Britain, where a ban was also in place, the British Parliament reversed course and approved research on mitochondrial transfer in February 2015, nearly a year to the day before a committee set up by the FDA to advise the agency on the subject made a similar recommendation. Earlier this month, on February 3, a special committee of the Institute of Medicine (IOM)* issued a report to the FDA on the ethics of using mitochondrial replacement techniques, or MRT, to prevent the transmission of mitochondrial diseases from mother to child.

       How does MRT work? The techniques replace the mitochondrial DNA (mtDNA) in the egg or fertilized egg of a woman who wants to become pregnant. The IOM considered using MRT only for women who are carriers for  mitochondrial disease, allowing them the opportunity to bear healthy children. Mitochondrial disease can be devastating, often causing severe physical or cognitive disabilities. It can appear at birth or develop later. It generally affects children but can develop in adults. It is progressive and incurable.

       What’s the FDA’s interest? It considers these techniques a form of gene therapy, which the FDA already regulates, because they modify human eggs (oocytes) or fertilized eggs (zygotes) in order to make sure that a disease in the mother’s mitochondria would not be passed on to her child. Genetic modification is the key here: these techniques would permanently change the mitochondrial DNA of the child. And if the child were a girl, she’d pass down those modifications to future generations.

       Why do it? Those who support such research want to make it possible for women who carry mitochondrial disease to bear their own biological children. Mitochondrial DNA is different from nuclear DNA. Nuclear DNA gives us most of our heritable features, such as hair and eye color, body type, even some behavioral characteristics. When we say, “He looks just like his mother,” or “she walks just like her father,” we’re talking about nuclear DNA, (nDNA), not Mitochondrial DNA (mtDNA). This is not to say mtDNA is insignificant. It exists in nearly every cell in the body and produces “energy for cells.” 

        What might be the problem with allowing such research? The idea is controversial for several reasons. First, the child to be born would have the genetic material of three people, which is where we get the term “three-parent embryo.” Some wonder what the long term generational consequences would be. Others believe that its use would devalue the lives of the disabled, and still others object to the fact that research would invariably destroy human embryos. Finally, some argue that if the technology proved successful, it would not be limited to those who are mitochondrial disease carriers.

        The committee did not ignore the objections but nevertheless concluded that MRT, under certain circumstances, was ethical. It recommended a number of restrictions to the use of the technique, including limiting any proposed embryo transfers to male embryos only until the long term effects could be understood. Why only boys? Because any changes to a male child’s mtDNA would not be transmitted to the next generation, since mtDNA is not present in sperm, but only in eggs.

       Does this mean that researchers can now get to work? Not so fast. I was glued to my computer for the webcast and thought the recommendation was a big deal, so I was surprised at how little public attention the announcement received. There was a story on NPR, a segment on the PBS Newshour, a smattering of articles in the press. After this little flurry, pretty much nothing, perhaps because almost before the media could react, the FDA poured cold water over any hope that research might begin in the near future. Why not? I don’t think we can fault the FDA. It looks as if Congress pre-emptively tied the agency’s hands. Last summer, the House of Representatives inserted language into its appropriations bill that explicitly forbid the FDA to use federal funds to approve such research. In December, the bill passed and was signed into law by the president. Within a few hours after the Institute of Medicine panel issued its recommendations, the FDA informed the media that such research “cannot be performed in the United States” at this time.

       What’s next? As I read the situation, it doesn’t look as if we’re going to see the use of mitochondrial replacement techniques anytime soon. Between the appropriations act and the now twenty-year old Dickey-Wicker amendment, which prohibits federal funds being used for any research in which a human embryo is either created for research purposes or destroyed as part of the research, it’s difficult to see a clear path forward.  The current law prevents the FDA from using federal funds to accept “investigational new drug applications” – called INDs – that would allow them to approve research into human MRTs. And even though Dickey-Wicker has no power to stop private research, the two laws together create a one-two punch. One, the FDA has said that MRT can’t go forward without its approval. But, then: Two, the 2016 federal law prohibits the FDA from reviewing proposals for research. Bottom line: It doesn’t matter whether the private sector would be funding the research, the FDA gets the final say over whether research can proceed. But since the FDA is not allowed to use federal money to approve any INDs, its hands appear to be tied. Unless Congress eliminates these provisions, hardly likely in this political climate, it looks like we are in a Catch-22.

       Is that the end of it? Hard to say. Right now, federal law, in the form of the 2016 Appropriations Act, stands in the way. But in the long run, the recommendation could make a real difference. If the FDA succeeds in actually being able to use its authority to regulate the development and use of these techniques, it may be able to extend its authority to other areas of research into other new reproductive technologies. And that might spark the development of an actual set of national policies regarding assisted reproduction, which is something nearly every developed country in the world – except the U.S. – already has. We’ll have to wait and see.

* 2023: The Institute of Medicine is now the National Academy of Medicine.