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- 5 December 2013 11:26 am , Vol. 342 , #6163
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Charity Funding Boosts Controversial Therapy for Mitochondrial Disease
19 January 2012 3:42 pm
LONDON—Wellcome Trust, the United Kingdom's largest biomedical research charity, today announced more than £4 million in support for a pioneering, and potentially controversial, IVF treatment that could prevent some forms of muscular dystrophy and other diseases caused by defective mitochondria, the energy-generating organelle in cells. Several research groups, primarily one based at Newcastle University in the United Kingdom, are developing ways to eliminate a child's chance of inheriting diseased mitochondria present in its mother's egg by transferring nuclear DNA from that egg into an egg donated by a third party. Those groups have been hoping that the U.K. government will soon give its approval for clinical trials of strategy, but there have been some questions of safety and ethics since the approach arguably could create a child with three genetic parents—the donor egg is stripped of its own nuclear DNA but retains its mitochondria, which have DNA themselves. The Wellcome Trust, however, has now decided to throw its considerable weight behind the IVF research, providing a £4.4 million grant to Newcastle University researchers to start a new Centre for Mitochondrial Research. The university is bolstering the grant with another £1.4 million.
Last year, the U.K. Parliament discussed the mitochondrial transfer studies being led by Douglass Turnbull and Mary Herbert of Newcastle, and the Human Fertility and Embryology Authority (HFEA), a U.K. body in the Department of Health, issued a report that said there was no scientific evidence to suggest that the technology is unsafe. But HFEA said that before the Department of Health made the technique legal in the United Kingdom, there should be further safety experiments, including work in primates, before approval could be given. That work has not yet been done and the Newcastle group says they have no immediate plans to do it themselves.
Today, accompanying the Wellcome Trust funding news, HFEA announced the launch of a consultation to gather the public's thoughts and concerns on the potential use of the IVF technique. The authority will present the results of this consultation, in addition to their scientific recommendations from last April, to the secretary of health. Their report will be complemented by an independent report from the Nuffield Council on Bioethics regarding the controversial ethical issues.
"We reckon one in 5000 people in the U.K. have mitochondrial disease," and that half of those are inherited, Newcastle's Turnbull noted at a press conference here today. Currently, researchers are developing two types of IVF treatments designed to prevent such conditions. The one pioneered by the Newcastle researchers involves transferring the fertilized nucleus from the mother's egg into a donated egg with normal mitochondria but stripped of its nucleus. Thus far, the Newcastle team has worked with abnormally fertilized human eggs that will not develop into viable embryos; the new money will allow them to use normal, leftover eggs from IVF therapy. Another technique, known as maternal spindle transfer, is being developed by Shoukhrat Mitalipov's group at Oregon Health & Science University and involves moving the spindle, a molecular complex of chromosomes and proteins, from the mother's unfertilized egg into an unfertilized egg from a donor. This group has successfully raised baby monkeys who were conceived using the technique.
For their part, the researchers believe that once they sort out the technical issues of getting an egg subjected to these IVF procedures to develop into a normal, viable embryo, the benefits of allowing a couple to have a healthy child far outweigh other risks or ethical concerns. "This isn't shades of gray, this is black versus white," Turnbull says. "If this technology is as safe and effective as IVF, as preliminary studies suggest, it could totally prevent transmission" of inherited mitochondrial diseases. Peter Braude, who was on the HFEA's scientific review panel that issued a report on the IVF technique last year, was at the Wellcome Trust briefing. "There comes a point where you have to jump. There comes a point where you have to ask how much information do we need to know something is safe," he says. Newcastle's Herbert told ScienceInsider that once the United Kingdom green-lights clinical trials, they hope to enroll 30 to 40 patients per year—her group has already had more than enough interest from affected couples to make that a reality. With that level of need, "would it be ethical not to pursue it?" she asks.
A new ethical concern specific to these IVF techniques is that rather than just affecting the single offspring, any damage to the transferred DNA would be passed on through the sperm or egg into a future generation. "Whatever mistakes the gene transfer might make would be perpetuated to the next generation and beyond," says Geoffrey Watts, chair of the Nuffield Council of Bioethics' working group on the topic. And the donated egg's mitochondria, which could in theory have unknown defects or affect the nuclear DNA in some way yet unknown to science, would also be passed onto subsequent generations. Nuffield has just sent out its request for public comment on these and other issues, and although Watts says it's still in a very early stage, they hope to have a report ready for the Department of Health by early summer. Watts also expects his group will wrestle with whether the mitochondrial donor—the much-touted "third parent"—should have any legal rights to the child or be treated as an organ donor, and whether mitochondrial genes affect a person's "identity" in ways that are yet unknown to science.
Speaking at today's press conference, Wellcome Trust director Mark Walport discounted the "three-parents" angle, likening mitochondria, the powerhouses of a cell, to batteries. "You don't define a camera by whatever batteries it happens to have. We're talking about a tiny, tiny amount of genetic material." Still, he and the researchers concede, the concerns are valid and will be brought up by the public in the Nuffield consultation.