Human germline modification offers promise and pitfalls

April 18, 2014

Late this winter, an advisory committee of the Food and Drug Administration held two days of public hearings on the topic of “oocyte modification in assisted reproduction for the prevention of transmission of mitochondrial disease.” The FDA is considering whether to approve human clinical trials of a germline modification therapy, which has so far been the subject of animal experimentation only. In monkeys, it has been shown to be scientifically feasible.

If oocyte modification does advance to human trials, that could be a step on the way toward the development of therapies that enable women whose ova have mitochondrial defects to give birth to children who will not be afflicted with genetic disease. Presumably, the therapeutic technique would begin with a donor egg with healthy mitochondria. Its nucleus would be replaced with that of the mother; and then the egg would be fertilized in vitro. (That is why human germline modification is sometimes referred to, perhaps a bit sensationally, as “three-parent IVF,” or the creation of “designer babies.”) In theory, the technique could work with a variety of genetic defects.

Many in the scientific community and in the general public as well, as a result of news coverage of the FDA hearings and a comprehensive article published in the New York Times on March 3, “A Powerful New Way to Edit DNA,” are excited about the potential that germline modification may have for eradicating some of humankind’s great genetic scourges. At the same time, many cautionary words have been said about the possibility of unintended bad effects of a manipulation of human genes that creates inheritable genetic changes. 

As the Los Angeles Times pointed out recently in an editorial “When tinkering with our DNA, researchers should take it slow,” the procedure would represent “the first time scientists were changing the genetic material of humans in a way that could be passed down through the generations.” Critics of germline modification ask whether genetic material might inadvertently be added to the gene pool that could later do harm. They point out that the test animals have not yet reproduced, so we don’t know if unanticipated problems may be manifest in their offspring.

Public advocacy organizations that are concerned with bioethical issues, such as the California-based Center for Genetics and Society (CGS), have come out strongly against clinical trials for human germline modification. The technique, CGS says, “carries a wide range of predictable and unpredictable risks for any resulting children and for future generations.” CGS also expressed concern that, prior to the public hearings, the FDA announced that those hearings would not address “ethical and social policy issues related to genetic modification of eggs and embryos,” saying that such issues were “outside the scope of the meeting.” Groups like CGS think that those issues need to be discussed from the start, by a variety of stakeholders, and they are right.

In the United States, scientific research never takes place outside of a social and ethical context—particularly in these times when science has unfortunately become enmeshed in so many proxy “culture wars” (e.g.,  regarding climate change). It cannot be isolated from the world of business either. According to the New York Times article, three biotechnology companies, two in the U.S. and one in England, are exploring the commercial possibilities of human germline modification.

No doubt, those entities are awaiting the FDA’s decision on clinical trials with interest. So are prospective parents and many others. The agency has announced no timetable. The conversation about manipulation of the human germline will continue, both among scientists and more generally. If and when clinical trials, and perhaps therapeutic applications, become realities, that conversation may become an increasingly heated one.