The hidden risks for ‘three-person’ babies

Garry Hamilton in Nature:

MitoIn February, the UK government approved mitochondrial replacement therapy, a technique that would allow a woman with a mitochondrial disorder to give birth to healthy children by pairing her nuclear DNA with the healthy mitochondria from a donor's egg. The approval came after a 3.5-year effort to review the safety and ethics of creating individuals with DNA from three people (what some refer to as three-parent babies). And although many scientists lauded the decision, some worry that it is premature. “They're not looking at the bigger picture,” says Ted Morrow, an evolutionary biologist at the University of Sussex in Brighton, UK, who is arguing for more-rigorous safety testing. “The standards for a shampoo seem to be harsher.” A common refrain in favour of the therapy is that the genetic contribution from mitochondria is very small. And against the 3 billion base pairs of DNA and 20,000 genes found in the human nucleus, the mitochondrial genome can seem pretty insignificant (see 'A complicated relationship'). Inherited solely through a mother's egg, it comprises fewer than 17,000 base pairs and just 37 genes. But one cell can have thousands of copies of the mitochondrial genome, compared with just two of the nuclear genome — one from mum and one from dad. Mitochondrial DNA also accumulates mutations incredibly fast, at about ten times the rate of nuclear DNA — and geneticists can use the resulting variation as a sort of molecular clock.

…One way to examine whether mitochondria in one population work differently from those in another is to swap them. Such experiments would be unethical in people and impractical in many other animals, so Rand turned to fruit flies. He cross-bred two fly strains with different mitochondria and then repeatedly back-crossed them until the mitochondria from one were neatly paired with the nucleus of the other. He then put fruit flies with similar nuclear genomes but different mitochondria together in a cage, and found that flies with specific mitochondrial genomes would quickly come to dominate the population2. Something in the mitochondria was giving them a survival advantage. Subsequent work by Rand, Dowling and others has shown that it is not just the mitochondrial genome, but rather its interaction with the nuclear one that seems to be affecting a range of traits, including lifespan, reproductive success, rate of development, ageing, growth, movement, morphology and behaviour.

More here.