The UK today became the first country to formally allow children to be genetically altered to ensure they do not inherit disorders caused by mutations in mitochondria – a momentous decision that could eventually lead to other kinds of reproductive genetic engineering.
The country’s Human Fertilisation and Embryo Authority has given a cautious go-ahead to the use of mitochondrial replacement therapy to prevent mitochondrial disorders, which can be fatal. Clinics that wish to carry out the procedure now have to convince the HFEA that they are competent. After that, the HFEA will approve applications on a case by case basis.
Earlier this year, a healthy boy was born after the first-ever use of mitochondrial replacement therapy to prevent inherited diseases. The head of the clinic in Mexico, where the procedure was carried out in 2015, told New Scientist last week that he aims to establish another 20 pregnancies in the first half of 2017.
However, while the clinic had ethical approval and followed all relevant laws, Mexican law-makers have not voted on whether to allow mitochondrial replacement. On the contrary, they are currently considering a proposal on embryo research and assisted reproduction that would outlaw it.
The UK parliament, by contrast, voted to allow mitochondrial replacement in 2015. That vote gave the HFEA the power to approve the therapy. It has now done just that after a scientific report recommended cautious approval.
Clinicians estimate that only around 3000 women in the UK are at risk of passing on serious mitochondrial diseases, but many couples from other countries are likely to seek treatment in the UK if it is not available elsewhere.
Genetic engineering
Mitochondrial replacement therapy is a form of germline genetic engineering. Mitochondria are energy-producing structures found in the fluid inside cells, each of which has a tiny genome of its own containing just 37 genes.
If a high proportion of the mitochondria inside each cell have harmful mutations, cells can’t make enough energy.
Mitochondrial replacement involves removing the nucleus containing the main genome from an egg or fertilised embryo, and placing it in a donor egg or embryo whose nucleus has been removed.
The idea is to ensure that a child has healthy mitochondria, but this also means 37 of the child’s genes come from the woman who donated the egg (the “third parent”).
Proponents say mitochondrial genes do not affect children’s appearance or personality, so this does not matter. But most of the 23,000 genes in the main genome could also be altered without altering children’s appearance or personality, too.
Allowing mitochondrial replacement takes us a step towards making other kinds of germline genetic changes – a prospect welcomed by some and opposed by others.Changes on demand
Until recently, this was a theoretical debate – we didn’t have the technology to safely alter the main genome in human embryos even if we wanted to. But the revolutionary new gene-editing method called CRISPR could soon make it possible.
Much could depend, therefore, on whether mitochondrial replacement proves to be safe. The biggest risk is that it fails to prevent the disorders it is meant to.
A few of the mother’s mitochondria always get transferred along with the nucleus. Lab experiments suggest that in about 1 in 20 cases they replicate faster than the donor mitochondria, meaning a child could still fall ill.
The HFEA had previously approved the use of preimplantation genetic diagnosis (PGD) for preventing mitochondrial diseases. The idea is to make embryos by normal IVF and implant only ones with a low proportion of abnormal mitochondria. But often none of a woman’s eggs have low enough levels – and even when they do there is still a risk of children ending up with higher levels of abnormal mitochondria.
The risk should be lower after mitochondrial replacement therapy than with PGD, the recent scientific report concluded, so its use should be allowed.
(New Scientist)
