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Power play

The replacement of mitochondria does not signal ethical problems.

Galloping advances in genetic and stem-cell technologies raise the inviting prospect that some devastating diseases could be treated. Conditions caused by natural mutations might be avoided by judicious genome tinkering to set things right for the next generations. But ‘inviting’ does not always mean ‘advisable’.

The United Kingdom last week released new draft guidelines for one such treatment — mitochondrial replacement (see The guidelines are scheduled to come into force next month, when clinics in Britain will be allowed to offer the treatment. Not everybody agrees that this inviting idea is advisable. As such, it is timely to consider the ethical and technical matters at stake.

At issue is not the nuclear genome, which contains the blueprint of an entire organism, but the genomes in our mitochondria — the small, energy-generating organelles in most of our cells. The often-overlooked mitochondrial genome contains only a few dozen genes, but it deserves as much respect as its much larger room-mate, which contains some 20,000. The impacts of an unfortunate mitochondrial mutation range from an inability to exercise hard to very serious, albeit rare, diseases.

Mitochondrial replacement involves replacing diseased mitochondria with fresh, healthy ones. This requires involving a third person beyond the parents — a woman to donate an egg to the process that contains only healthy mitochondria (hence ‘three-person embryo’).

The procedure does not alter the mitochondrial genome. But on the basis of animal experiments, some biologists claim that foreign mitochondrial genes might interfere with the expression of the nuclear genome in unpredictable, and perhaps dangerous, ways (see page 444).

These concerns were brought up during the consultation process with scientists and the public carried out by the UK Human Fertilisation and Embryology Authority (HFEA) before the UK Parliament voted in February in favour of allowing the procedure. Far from being rushed, as some claim, the consultation was done over many years and was judged as a fair public-engagement exercise by independent experts who monitored the process.

The HFEA regulations should dispel fears of a slippery slope.

The HFEA believes that the problems seen in organisms such as flies and mice would not be repeated in humans — in the main because they have not shown up in children of mixed-race couples in which the mitochondrial DNA of the mother and the nuclear DNA of the father are likely to be the most distant. This point helps to address ethicists’ worries that unanticipated problems in children born following mitochondrial replacement could be passed on through the generations.

Other ethical concerns about the UK move can be summarized as anxiety over a possible slippery slope to full-scale germline manipulation to address a broader range of conditions. These concerns are heightened by advances in gene-editing techniques such as CRISPR/Cas9.

Last week’s release of the HFEA regulations should dispel fears of a slippery slope. Applications are narrow and oversight is strict. The agency decided to allow mitochondrial replacement only to avoid serious diseases, and not for the attempted treatment of infertility. (Some clinics in Canada have offered the procedure in the belief that a shot of fresh, young mitochondria may somehow invigorate eggs from older women, but there is little scientific evidence for this.)

The regulations explicitly exclude the editing of the nuclear or mitochondrial genome. Licences will be given only to centres whose competence has been approved, and even then, these centres will have to seek separate approval for each patient. Licensed centres will be obliged to put a process in place to monitor the clinical follow-up of children born following mitochondrial donation, providing that parents agree.

Scientists estimate that the number of women likely to be eligible for the procedure will be around 150 per year in Britain and about 800 in the United States, where the Institute of Medicine is carrying out a similar consultation for the US Food and Drug Agency, which will be responsible for licensing it. The United Kingdom has made an advisable step forward that serves as a useful invitation for all to follow.

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The hidden risks for ‘three-person’ babies 2015-Sep-23

World hails UK vote on three-person embryos 2015-Feb-10

Reproductive medicine: The power of three 2014-May-21

Regulators weigh benefits of ‘three-parent’ fertilization 2013-Oct-15

Related external links

HFEA draft regulations on mitochondrial donation (PDF)

HFEA scientific review of safety issues in mitochondrial donation (PDF)

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Power play. Nature 525, 425–426 (2015).

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