Strangely Mixed Signal in Report on Germline Mitochondrial Manipulations

The U.S. National Academy of Medicine (NAM) today released a report requested by the Food and Drug Administration (FDA) on the “Ethical and Social Policy Considerations of Novel Techniques for Prevention of Maternal Transmission of Mitochondrial DNA Diseases.”

“Many passages of the National Academy of Medicine report adopt a welcome tone of caution, and it recommends putting a number of conditions on clinical investigations,” said Marcy Darnovsky, PhD, Executive Director of the Center for Genetics and Society. “But the report’s conclusion – that no ethical or policy considerations stand in the way of clinical investigations going forward – seems at odds with the many cautions, risks and concerns that it raises. It’s unclear why the report weighs those cautions as being less significant than the one potential benefit it identifies, which is the possibility of providing a very small number of women the possibility of having a genetically related child.”

Most people affected by mitochondrial disease – some 85% – have involvement of nuclear DNA and so would not be candidates for the techniques in question; of the remaining 15%, all would be able to have unaffected children by using third-party eggs, and some would be able to have unaffected and genetically related children by using pre-implantation genetic diagnosis. A spokesman for the UK fertility authority estimated that there would be 5-10 candidates per year in that country for the techniques.

The NAM report does not draw conclusions about the safety or efficacy of germline mitochondrial techniques; as it notes, such determinations are the purview of the FDA. In February 2014, an FDA committee heard two days of testimony about these techniques, after which the chair described the “sense of the committee” as being that “there is not enough data either in animals or in vitro to move on to humans, and that these concerns involved both the preclinical data and the basic science.”

“Though they are described as 'mitochondrial transfer,' these techniques involve the transfer of a nucleus from one embryo or egg to another,” Darnovsky said. “The procedure is very similar to cloning techniques, and carries some of the same risks.”

One of the report’s conclusions is that “federal regulation would be needed…to prevent slippage into applications that raise other serious and unresolved ethical issues.” The report mentions age-related infertility as a “likely candidate” for such applications, although evidence for that association is slim.

“It’s important to realize that if the FDA were to approve these techniques, it would have few mechanisms for preventing what would essentially be 'off label uses,'” Darnovsky said. “One US proponent of these techniques has already made it publicly clear that he would like to expand their use widely to fertility clinics. Their use could easily spin out of control.”

After the December summit on human gene editing, the organizing committee concluded that it would be irresponsible to proceed with germline modification unless and until a broad societal consensus had been reached. The NAM report recommends proceeding with a technique that is, as it acknowledges, a form of human germline modification.

Darnovsky commented, “The UK’s approval of these techniques is already being used by some as an argument for allowing all kinds of human germline alteration. Without US federal legislation prohibiting heritable modification of nuclear DNA – already adopted as law in dozens of countries – it is reckless to proceed with this form of germline modification.”

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The Center for Genetics and Society is a non-profit public affairs and policy advocacy organization working to encourage responsible uses and effective societal governance of human genetic and reproductive biotechnologies.

Contact:
Marcy Darnovsky
510-625-0819, ext 305
darnovsky[AT]geneticsandsociety[DOT]org