Reproductive medicine: The power of three

Illlustration by Vasava

Douglass Turnbull spends much of his time seeing patients who have untreatable, often fatal, diseases. But the neurologist has rarely felt more helpless than when he met Sharon Bernardi and her young son Edward.

Bernardi had lost three children within hours of birth, owing to a mysterious build-up of acid in their blood. So it was a huge relief when Edward seemed to develop normally. He did all his milestones: he sat up, he crawled and started to walk at 14 months, Bernardi recalls. But when he was about two years old, he began to fall over after taking a few steps; he eventually started having seizures. In 1994, when Edward was four, he was diagnosed with Leigh's disease, a condition that affects the central nervous system. Doctors told Sharon that her son would be lucky to reach his fifth birthday.

Turnbull, who works at Newcastle University, UK, remembers despairing that whatever we do, we're never going to be able to help families like that. His frustration sparked a quest to develop assisted-reproduction techniques to prevent disorders such as Leigh's disease, which are caused when children inherit devastating mutations in their mitochondria, the cell's energy-making structures.

The procedures sometimes called three-person in vitro fertilization (IVF) involve transferring nuclear genetic material from the egg of a woman with mutant mitochondria into another woman's healthy egg. Turnbull and others have tested the techniques in mice, monkeys and human egg cells in culture; now, they say, it is time to try them in people. The UK Parliament is set to vote on the issue later this year; if legislation passes, the country would be the first to allow this kind of genetic modification of unborn children.

Ewen Callaway talks to researchers and a patient about the techniques that replace faulty DNA in egg cells

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But some scientists have raised concerns over the safety of the procedures, and an increasingly vocal coalition of activists, ethicists and politicians argues that a 'yes' vote will lead down a slippery slope to designer babies. US regulators and scientists are closely watching the debate as they consider allowing similar procedures. I admire what they've done in Britain, says Dieter Egli, a stem-cell scientist at the New York Stem Cell Foundation, a non-profit research institute. I think they are far ahead in discussion of this, compared to the US.

The mitochondrion, according to one popular theory, was once a free-living bacterium that became trapped in a host cell, where it boosted the cell's capacity to generate the energy-carrying molecule ATP. As a result, each mitochondrion has its own genome but it no longer has all the genes it needs to function independently (the human mitochondrial genome, for example, has a paltry 37 genes).

Unlike the genome in the cell nucleus, which includes chromosomes from both parents, all of a person's mitochondria derive from the thousands contained in the mother's egg. For reasons still being studied, the mitochondrial genome is much less stable than the nuclear genome, accruing random DNA mutations about 1,000 times faster. As many as 1 in 5,000 children are born with diseases caused by these mutations, which affect power-hungry cells such as those in the brain and muscles. The severity of the conditions depends on the proportion of diseased mitochondria a mother passes on to her children.

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Reproductive medicine: The power of three