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Safety concerns over mitochondrial replacement (3-person IVF)

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A new paper in Science has raised safety concerns about mitochondrial replacement (MR).
Mitochondrial disease arising from mutations in extranuclear mitochondrial DNA can be largely (though not certainly) prevented if the nucleus of the mother’s egg cell is transplanted into a donor egg cell from which the nucleus has been removed, which is then fertilised by the father’s sperm. This technique is also called three-person IVF because the resulting embryos have DNA from three adults, although the contribution from the egg donor is very small.
Currently, legislative developments are setting the stage for the UK to become the first country in the world to permit the use of MR (see previous news). These moves have followed Human Fertilisation and Embryology Authority (HFEA) consultations into the safety and public acceptability of the technique.
However, a Science paper says that MR could potentially disrupt interactions between nuclear and mitochondrial DNA, causing ‘adverse health outcomes’, citing the observation that MR in fruit flies altered expression of around 10% of genes in male (but not female) offspring, with effects on fertility. They call for further checks prior to approval of MR for use in humans, pointing out that macaque studies have tracked the effects of MR only to the age of three, whereas studies in mice and other animals have suggested that harmful effects may not become apparent until adulthood. They suggest that the longer-term effects on health and fertility in macaques born from MR should be followed at least until their sexual maturity (another year).
They also call for studies into mtDNA haplotype matching between egg donors and recipients for MR to reduce the risk of problems. However, other experts have dismissed this risk as trivial. The HFEA has reiterated that their expert panel: ‘concluded that the evidence did not show cause for concern’ on this issue, although they also noted that any move from research into clinical practice involved ‘a degree of uncertainty’.

Comment: It is true that introducing new techniques into clinical practice is always a risk, and if no risks were ever taken then the progress of medicine would be very limited. However, although the potential problems from MR are considered very unlikely by many experts, they are also quite serious – especially since the whole purpose of the technique is to allow affected couples to have their own unaffected biological children (as opposed to, say, children conceived from the donor egg and father’s sperm). So maybe it would be worth watching those macaques for a bit longer. Indeed, the HFEA panel did originally say that it would be essential to perform MR ‘in a non-human primate model, with the demonstration that the offspring derived are normal’.  

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