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Historic Decision Makes Controversial Fertility Treatment Legal in U.K.

A controversial assisted reproduction technique became legal in the first country in the world on February 24 following a vote by both houses of the U.K.’s parliament. While the decision affects only the U.K. for now, it has international implications. The technique, called mitochondrial DNA replacement, could prevent transmission of certain rare diseases and perhaps address some causes of infertility. It is sometimes called “three-person IVF” because it uses genetic material from three people.

What is it? The technology aims to prevent the transmission of inherited diseases caused by defects in the DNA (genetic material) of mitochondria—structures within cells that convert the energy from food into a form that the cells can use. These defects, which are inherited from mother to child, can cause loss of muscle coordination, visual and/or hearing problems, mental retardation, and other problems mainly of the brain, heart, at muscles. Each year, an estimated 1,000 to 4,000 babies are born with mitochondrial disease in the U.S., according to the United Mitochondrial Disease Foundation. Mitochondrial disease has several causes, with only some cases caused by defects in mitochondrial DNA. The hope for the technology is that it will be used to prevent mitochondrial disease in some babies who would otherwise be affected.

Mitochondrial DNA replacement is a technique that involves in vitro fertilization. An egg is taken from the mother and sperm from the father, but unlike in conventional IVF, the technique also uses mitochondrial DNA from the egg of a donor without mitochondrial defects. In one version of mitochondrial DNA replacement, the nucleus from the donor’s eggs is replaced with the nucleus of the egg from the prospective mother. The nucleus contains most of the egg’s genetic information. This egg is then fertilized with sperm from the prospective father. Another method begins by fertilizing the mother’s egg and the donor’s egg with the father’s sperm, and then replaces the nucleus of the donor’s fertilized egg with that of the mother’s. Either way, the resulting embryo has nuclear DNA from the prospective mother and father and mitochondrial DNA from the egg donor.

Why is it controversial? There are lingering questions about the safety of the technology, mainly for the resulting children. Among the questions is whether the technology itself might cause problematic genetic or epigenetic changes in the embryo or otherwise damage it, and that the DNA from the three parties might be incompatible.

These safety questions also contain ethical dilemmas. How do we balance trade-offs between different values– in this case, for example, the benefit of enabling women with defects in their mitochondrial DNA to have a genetically related child against the possible risk  that a child created this way might be harmed by the technology itself?

However, most of the ethical debate is outside the realm of safety and focuses instead on what some see as a fundamental line that is crossed. Unlike other human assisted reproduction technologies, mitochondrial DNA replacement would alter the germline of the embryo, meaning that the donor‘s mitochondrial DNA would be passed on from the child to subsequent generations. Some people are opposed to this kind of genetic alteration, believing that it oversteps the proper role of humans in procreation and, indeed, evolution. Critics are also concerned that this technology could lead to producing “designer babies” in the future—children who are not simply free of severe genetic diseases, but whose genes have been altered in pursuit of desired traits such as a particular eye color or high intelligence, however that might be defined. Others consider these concerns overblown. After all, the donor’s mitochondria contribute just 37 genes to the child, whereas the parents contribute more than 20,000.

What’s next? The U.K.’s historic decision is bound to have implications for other countries that have been considering legalizing mitochondrial DNA replacement, including the United States. The question is whether and how closely other countries will follow the U.K.’s lead. Since 1990, U.K. law has required all persons intending to manipulate eggs, sperm, and embryos to be licensed by a statutory authority. Now, that authority will be empowered to issue licenses to researchers who are developing these techniques and who now wish to begin clinical trials to assess their safety and effectiveness. The technique will not immediately be available outside of the research context in the U.K.

A similar process is underway in the U.S., where the Food and Drug Administration is considering an application from a researcher to begin clinical trials of the technique. The FDA held a public hearing in response to this application a year ago, and requested a report on the ethical and policy considerations of the technology from the Institute of Medicine, which held its first meeting in January of this year. The next meeting of the IOM meeting will take place in March.

“The U.K. regulations appear reasonable,” says Josephine Johnston, director of research at The Hastings Center who studies ethical considerations with assisted reproduction. “The U.K. has a highly developed process for regulating and overseeing the development and conduct of reproductive technologies, which includes public consultation. The parliamentary vote on the proposed regulations is the final step in a process that began seven years ago. The U.S. could learn a lot from its deliberate, open, and careful process in this area.

“Whether permitting the manipulation of an embryo’s genetics in this case opens the door to other requests to alter the characteristics of future children remains to be seen,” Johnston adds. “Rather than assuming that all attempts to manipulate an embryo’s genes are problematic, my hope is that we continue to carefully and critically assess each development in reproductive technology, engaging in a public conversation about its implications for children and families, as well as for the widely held values of freedom and equality.” Johnston expanded on her views in an interview in Frontline Medical News.