Editorial: “Don’t fear babies made with genes from three parents“
Three-parent babies could soon become a fact of life. The UK’s Human Fertilisation and Embryology Authority (HFEA) advised the government today that it should legalise controversial new IVF techniques designed to prevent mitochondrial disease. If the government follows the advice, it will eventually lead to the birth of children with genes from three parents.
The new techniques have been developed to prevent devastating mitochondrial diseases, which affect thousands of people. Around 5000 adults in the UK have some type of mitochondrial disease. Mitochondria are the cells’ energy generators, and have their own DNA, mutations in which can cause mental impairment, blindness, seizures, dementia and death – although it is possible to have a low level of faulty mitochondria without disease.
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Faulty mitochondrial DNA gets passed down from mother to child, dispersed in the cytoplasm of the egg. Currently, the only option for women with such faulty DNA is to go through IVF to measure the amount of mutated DNA in her eggs, a technique called pre-implantation genetic diagnosis (PDG). This measurement allows parents to estimate how likely it is that a future child will develop mitochondrial disease.
Donor mitochondria
But there are ways to guarantee that a child is disease-free. One is being pioneered by at the Oregon National Primate Research Center in Beaverton. His method involves inserting the nucleus from an egg with faulty mitochondria into a donor egg that has had its nucleus removed. A second method spearheaded by a team at Newcastle University in the UK involves transferring the nucleus of a fertilised egg into an empty donor egg.
Neither technique is currently approved for use in humans in the UK or the US: a similar technique tested in women with fertility problems led to a ban in the late 1990s.
The HFEA’s advice to government today followed an update of a it carried out in 2011 and a recent (see “What do you think?“).
“Broadly speaking, the public were in favour of these new techniques being translated into treatments,” says Neva Haites from the University of Aberdeen, UK, who chaired the panel that oversaw the consultation.
The HFEA has advised the government to legalise the treatment, but only in licensed clinics. It also recommended that follow-up research takes place on children born using the new techniques, and that the donor should be thought of in the same way as a tissue donor, meaning they would have no rights over the child.
Human trials
So far, Mitalipov’s group has bred five macaques from healthy mothers using their technique. Last year, his team announced that they had taken the first steps to doing the same in people, extracting the nucleus from 65 human eggs and replacing each one with the nucleus from a donor egg. A few days after fertilisation, 48 per cent of the successfully fertilised embryos had developed into healthy blastocysts – balls of around 100 cells. In 2010, the Newcastle team demonstrated their technique in embryos that were discarded from other IVF treatments.
The techniques need to be optimised to increase the number of healthy blastocysts that develop. Currently, both have a success rate lower than the 40 to 50 per cent deemed acceptable for other types of IVF.
Mitalipov feels that he has done everything he can do to test the procedure in animals. The remaining questions can only be answered fully with human trials, he says.
Aside from efficacy, several other concerns have been raised. One technical worry was that some of the mother’s faulty DNA could cling to the egg’s nucleus as it is being transferred. In both methods, total mitochondrial DNA transferred from the mother has been measured at less than 2 per cent. Around 60 per cent of mitochondria need to be faulty to cause disease. However, any that do get transferred could become amplified over future generations – something the HFEA would like more research on.
Three parents?
So what of the idea that the techniques mean children have three parents? It is “misleading, inappropriate and unhelpful”, says Hugh Whittall, director of the Nuffield Council on Bioethics in London, which last year reviewed the procedures from an ethical standpoint. This is because the donor’s mitochondria would contribute just 37 genes to the child, compared with more than 20,000 from the parents. That’s a negligible amount, and far less than you would gain from a blood transfusion or organ transplant.
What’s more, although there is evidence that mitochondria do more than simply power our cells, “the features that give us our personality, our appearance, everything that makes us us, is all carried in the nuclear DNA”, says Whittall.
Other issues raised include the unknown ways in which the techniques might affect future generations. They are germ-line therapies – those that not only change the DNA of the person, but that of all their descendants. But Whittall says unintended consequences are likely to be minimal because of the limited function of mitochondria. “The germ-line effect here is a beneficial one. It removes the risk of disease,” he says.
Genetic engineering
Some people have expressed concern that acceptance of mitochondrial germ-line therapies might pave the way for nuclear germ-line therapies – where genes in the nucleus are altered.
Certainly it could be tempting to try to circumvent diseases that are passed on in nuclear DNA, such as cystic fibrosis, but its enormous complexity makes the risks of tinkering with it far larger. The issue also raises the spectre of designer babies: once you’ve fixed a disease, could you improve other features while you’re at it?
For both Whittall and the HFEA, this issue of nuclear germline therapies is separate to the issues of mitochondrial transfer. “It would involve a different technique for completely different purposes,” says Whittall.
Regardless of whether the UK government agrees to the use of mitochondrial transfer in humans, the techniques will probably be used somewhere soon. Everyone wants to be the first to create the next Louise Brown, says Mitalipov, referring to the first person conceived through IVF, in 1977. “What governments need to understand is that there’s no way we can hang on to this,” he says, adding that if the US and UK don’t do it, other countries with less oversight will. “We need to do it now,” he says.
What do you think?
Views from a UK consultation on mitochondrial replacement
“If, by introducing these techniques, we can wipe out mitochondrial diseases and the suffering that goes with them, then it can only be a good thing.”
Individual personally affected
“One cannot underestimate the amount of emotional and psychological damage inflicted on parents knowing they have passed on these diseases to their children.”
Acquaintance of someone affected
“I would liken this to replacing faulty spark plugs in a car, it will look and perform the same but the engine will run smoothly!”
Anonymous individual
“I worry that each new step, even if taken for noble reasons, will only stir up a chorus of voices demanding more frivolous treatments, such as sex selection.”
Anonymous individual
“I don’t see any implications for identity, and I say this as a donor-conceived person who believes that [donors’] genes help to make us who we are.”
Individual conceived using a donor
“My only concern about alterations in the germ line is that it reifies genetic ‘normality’ and creates an anti-disability narrative that will encourage people to be viewed as ‘abnormal’.”
Individual researcher
