U.K. to debate allowing germ-line gene therapy

LONDON – Deniz Safak was 5 years old when he first displayed symptoms of the disease that would later take his life. “He started being sick and had intense, stroke-like seizures,” his mother, Ruth, recalled.

Doctors were baffled by the boy’s condition, and it took months before a diagnosis was made. Ruth and her husband, Erdhal, were told that Deniz was suffering from mitochondrial disease, an incurable condition that is passed from mother to child and can often be fatal.

Deniz’s condition continued to worsen.

By the time he died last year at the age of 23, he had become deaf, suffered intense migraines and was confined to a wheelchair. “That is how he spent his life at the end,” said Ruth, who lives in Sunderland, northeastern England. “He was very bright, and he knew what he was missing from life.”

There is no cure for mitochondrial disease and, although its symptoms vary in their severity, the condition is often fatal. Health officials estimate that there are several thousand people in Britain affected by the condition, which is caused by mutations in the DNA in the mitochondria.

“Mitochondria are the little power packs that provide our cells with energy, and they have their own DNA,” said professor Douglas Turnbull, director of the Wellcome Trust Center for Mitochondrial Research at Newcastle University in northeast England. “The disease particularly affects cells that use a lot of energy, including those involved in hearing, pumping blood and firing nerves. About a third to a half of those who have the condition face an early death.”

It is a grim scenario. However, hopes of tackling mitochondrial disease will be raised in a few weeks when the government announces regulations that will permit the use of an in vitro fertilization technique that should rid affected families of the disorder. If these plans are approved by parliament, Britain will become the first nation to permit germ-line gene therapy, which will change the DNA of future generations in order to eradicate the condition.

The technique involves taking an egg with healthy mitochondria from a donor female. Its main set of nuclear genes is then scooped out and replaced with those of a woman affected by mitochondrial disease.

The egg is then fertilized using her partner’s sperm. In this way, an embryo is created that has the central genes of the two parents but no longer carries the mother’s mutated mitochondrial DNA. The technique is known as mitochondrial replacement. It has never been tried on humans but has worked in animal studies.

Most scientists and doctors, particularly those who work with families touched by mitochondrial disease, support the introduction of the technique. However, some groups vociferously oppose its use. “The social benefits for a relatively small number of women . . . do not come near to justifying the potential health risks from these techniques to the child and the risks to global society that stem from human genetic engineering,” said the campaign group Human Genetics Alert.

Anti-abortion groups also oppose mitochondrial replacement, while some tabloid newspapers have described the creation of embryos using the nuclear DNA of two parents and the mitochondrial DNA of a third-party donor as “three-parent babies” and have claimed that this represents a slippery slope to a “Frankenstein future.”

This last claim particularly infuriates researchers. “It is wrong to say this produces three-parent babies,” said Turnbull. “More than 99.9 percent of DNA is nuclear DNA, and that will not be affected. Mitochondrial DNA accounts for around 0.1 percent of our total DNA. We are changing only mitochondrial DNA. We are not changing a person’s hair or height or eye color.”

The disease is passed through the maternal line because men’s sperm do not have mitochondria.

Last year the Human Fertilization and Embryology Authority (HFEA) completed an extensive public consultation on mitochondrial replacement and found widespread support for it. Now the proposed regulations that will allow it to be carried out, under license from the HFEA, are to be published. Interested parties will give their views on these regulations before they are debated by parliament, probably on a free vote, later this year.

Alison Murdoch, professor of reproductive medicine at Newcastle University, hopes that parliament will approve the new regulations — though she is only cautiously hopeful. “This is controversial in some people’s eyes, and there will be attempts to block the regulations. My fear is that the government could still get cold feet and delay the vote, which would not be good news given we will have a general election next year.

“The trouble is that the people who oppose this work are much better organized and proactive than the people that actually need the treatment,” Murdoch said. “They claim that around 30 percent of the population is against this kind of medical intervention. But when you actually sit down with a group of people and explain what you want to do, they all say the same thing: ‘Why not?’ “

Ruth Safak will also be watching the forthcoming battle over the implementation of mitochondrial replacement therapy.

She is passionately in favor of the procedure: “If this treatment had become available for me when I was beginning my family, I could have had Deniz and he would still be with me now.”