Britain is about to become the only country in the world to explicitly allow the inheritable genetic modification of humans. With a vote Feb. 3 in the House of Commons, the country has paved the way for "three-person in vitro fertilization," which combines genetic material from two women and a man.
Creating high-tech procedures like this to help women have healthy babies seems worthy of unquestioning support. But it's not so simple — and promises to soon get more complicated.
The techniques at immediate issue are relatively crude. They work by removing the nucleus from the egg (or embryo) of an intended mother, and inserting it into one provided by a second woman. Any resulting child would inherit its nuclear DNA from the intended mother and father and its mitochondrial DNA from the second woman.
Mitochondria exist inside cells, but outside the nucleus, and are passed from mother to child. The aim of the procedure is to prevent the transmission of defective mitochondrial genes that cause diseases.
There are a wide variety of mitochondrial diseases, and most also involve genetic mutations in the nucleus. About 15% of cases stem from solely defective mitochondria, and only these women — estimated to be fewer than 15 per year in Britain — would be candidates for three-person in vitro fertilization.
Later this month, the House of Lords will get the final say on the regulations. If the bill is approved, it will carve out an exception to British law against the inheritable genetic modification of humans and put the country at odds with laws in 45 countries and provisions in several international treaties.
Crossing this threshold raises a profound societal question that until now has been hypothetical: As biotechnologies improve and enable us to make more specific genetic changes in our offspring, how far will we go? Will "mission creep" expand the genetic manipulations performed on future generations?
Genetic-engineering techniques now being developed, including "precision gene editing," soon may enable specific changes to nuclear DNA in embryos that would directly influence specific inherited traits. How do we ensure that we don't sleepwalk into a world of biotechnological eugenics in which genetic alterations or "enhancements," driven by parental preference or fertility industry marketing, exacerbate existing social inequalities?
Women affected by devastating mitochondrial diseases understandably would want to give cutting-edge methods a try — if they were safe, and if there were no better alternatives. But neither of these caveats holds in this case. In February 2014, an expert committee convened by the U.S. Food and Drug Administration reviewed the same evidence available in Britain and concluded that three-person in vitro fertilization wasn't even ready for clinical trial. Yet Britain is barreling ahead to offer it in approved fertility clinics, outside a research context. Even more concerning, there is no required follow-up to study the health of any resulting children.
The FDA's experts and other scientists point to a range of complications that could seriously harm children conceived this way. Among their concerns: While mitochondria contain only a few dozen genes (compared with tens of thousands in the nucleus), there are hundreds or thousands of mitochondria in the cells of different human tissues. In fact, mitochondrial DNA and nuclear DNA are constantly interacting, and swapping different people's nuclei and mitochondria could disrupt that cellular communication.
Then there's the problem that if even tiny amounts of defective mitochondria wind up in the embryo, they could be preferentially replicated throughout a child's cells, causing or aggravating the very disease the procedure is meant to prevent. In addition, serious cellular harm can be caused by the nuclear transfer process itself.
There are safer family-building alternatives for women at risk of passing on mitochondrial disease. Egg donation and adoption are the obvious ones. Another is the embryo genetic-screening technology that can be used with conventional in vitro fertilization. Nearly all women affected by mitochondrial mutations produce some eggs with sufficient "good" mitochondria to produce a healthy child, and embryos created with these eggs can be selected and implanted. The resulting child would be fully genetically related to its parents.
Technological advances are exciting, but that should not blind us to the scientific evidence — nor the social and policy consequences. Like other powerful emerging technologies, inheritable genetic engineering calls for caution, cross-disciplinary engagement and informed public deliberation.
Will Britain's decision put pressure on U.S. regulatory authorities to greenlight such techniques? At the FDA's request, the Institute of Medicine recently began a 19-month review of their social policy and ethical implications. We are hopeful that this will be a venue for thoughtful deliberation of the entangled social, policy and safety questions at hand. Britain may soon be an international outlier, but the U.S. need not blindly follow suit.
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