Safety concerns remain over three-person IVF

http://www.theguardian.com/science/2014/jul/22/three-person-ivf-mitochondria-dna

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Later this year, parliament is expected to debate a change to the law that would allow a reproductive therapy called mitochondrial replacement (MR) into fertility clinics. A recent review of evidence by the UK fertility regulator, the Human Fertilisation and Embryology Authority, stated that this experimental technique is "not unsafe". But while the aim of the procedure is noble – to eliminate human mitochondrial diseases, which affect around 1 in 4,000 people – a number of important safety concerns remain unresolved.

Evolutionary theory predicts a mismatch between the DNA in the donor's mitochondria and the mother's nuclear DNA, with potentially serious and unpredictable consequences for any embryo created using MR, an issue my colleagues and I wrote about last year. When MR is carried out experimentally, it has been shown to alter the metabolism and cognitive ability of mice. In other species it results in male sterility, reduced survival, accelerated ageing and changes the expression of many hundreds of genes. But there is a lack of data from species more closely related to humans – a gap in our knowledge that we felt would be wise to fill before proceeding to clinical trials.

The problem of mismatching arises because of the peculiar way mitochondrial DNA (mtDNA) is inherited through mothers only, giving an opportunity every generation for the mtDNA and some of her nuclear DNA to be passed on together. This allows natural selection, nature's quality control mechanism, to weed out combinations of interacting mitochondrial and nuclear DNA that are not compatible with one another. Over long evolutionary timescales within populations, the two genomes will become matched or "coadapted" to one another. MR breaks these coadapted genomes apart, giving rise to a range of damaging effects. The particular design of the experiments needed to detect mismatching is especially important. They usually involve manipulating several distinct mitochondrial types and making observations in many individuals. Without these features the ability to detect mismatching is poor. So while demonstrations that MR is technically feasible (with the production of four macaques in 2009), it is not sufficient to rule out the possibility that the kinds of effects seen in other species will not be found in primates or humans.

The HFEA appear unconvinced that the coevolutionary process for which there is evidence is real, considering "such hypothetical problems to be very unlikely".

The report, passed to the Department of Health on the 2 June 2014, discusses several other technical issues related to the safety of the technique, and even outlines a number of areas for which more data is required. But for the issue of mismatching, they do not recommend any further research. This is concerning, as it appears a reasonable safety concern is being ignored.

From my perspective as an evolutionary biologist, a common thread in the debate so far is that humans are somehow special cases, despite the fact that the same set of mitochondrial genes are found from yeast to humans, and that the evolutionary theory is a general one, applying even to plants. This suggests to me that greater exposure to and integration of current evolutionary ideas in the training of biomedical scientists would be beneficial. This is not a new suggestion; a whole discipline called Darwinian medicine is slowly gaining traction, with the aim of giving medical professionals the ability to better predict disease risk.

It also seems that if evolutionary biologists were included earlier in the consultation process, there may have been more cautious conclusions about the safety of MR. The inertia behind the regulatory process, together with the resistance from biomedical researchers to consider evolutionary arguments, is substantial. I suggest that in the future policy makers would do well to cast a broader net when looking for expertise and evolutionary biologists themselves should engage more with policy makers.

Scientists are frequently urged to become more involved in developing evidence-based policy, and so it is somewhat perplexing to see that when theory and evidence are presented they are roundly dismissed as irrelevant or trivial. Evolutionary biology can offer a great deal of understanding about the world around us, including ourselves. We should make use of that knowledge.

• Ted Morrow is an evolutionary biologist at the University of Sussex