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Scientists warn of potential mitochondrial replacement IVF health risks

23 September 2013
Appeared in BioNews 723

A group of scientists has expressed concerns that it may be too soon to bring mitochondrial replacement (MR) techniques, which are still under development, to the clinic. This follows the recent news that the UK Government will support the introduction of mitochondrial replacement therapy, with the relevant legislation due to be debated in Parliament next year (reported in BioNews 711).

In an article published in the journal Science, three biologists argued that while the availability of MR-assisted therapies is an 'exciting prospect', more time is needed to better understand the techniques in animals before moving on to clinical trials. They explain that there are extensive interactions between mitochondrial DNA and nuclear DNA, and that using donor mitochondria may have long-term consequences that are not yet understood.

'We draw attention to theory and experimental findings that appear to have been overlooked in the scientific and public forums of this debate', the authors wrote in the paper. 'Studies on model organisms, ranging from mice to fruit flies, indicate that MR can profoundly change the expression profiles of nuclear genes and affect a range of important traits such as individual development, cognitive behaviour, and key health parameters'.

MR-assisted IVF has successfully given rise to live offspring in macaque monkeys, but these offspring have not yet reached adulthood. The authors suggest further monitoring the health and fertility of these monkeys.

Klaus Reinhardt of the University of Tuebingen, Germany, lead author of the article, said: 'It is not at all our intention to be a roadblock, we think it is fantastic that for women affected there could be a cure. We are sure that the Human Fertilisation and Embryology Authority (HFEA) will decide [whether to allow the therapy] on a case-by-case basis and will have safeguards. But couples that have mild mitochondrial disease might choose to wait two years until the macaques are a bit more mature'.

MR involves taking the nuclear material out of a prospective mother's egg (thereby leaving behind the faulty mitochondria) and placing this nuclear material into a donor egg which has healthy mitochondria. MR could be used to treat mothers at risk of passing on faulty mitochondria to their children, as this can lead to complex and sometimes fatal mitochondrial disease.

The HFEA, which ran a public consultation in 2012 gathering evidence on the techniques and advised the Government on the evidence surrounding mitochondrial replacement therapy, has said that there is at present no reason to believe the techniques are unsafe.

In a statement, the HFEA said: 'The panel of experts convened by the HFEA to examine the safety and efficacy of mitochondria replacement carefully considered the interaction between nuclear and mitochondrial DNA and concluded that the evidence did not show cause for concern'.

Professor Doug Turnbull, from the mitochondrial research group at Newcastle University shares the HFEA's position. 'One of our prime interests is about the safety of these techniques,' he said. 'Mismatch between the mitochondrial and nuclear genome is a potential risk, but I don't think it's personally as big a risk as they're saying'.

David Thornburn, head of mitochondrial research at Murdoch Childrens Research Institute in Melbourne, Australia said in the New Scientist: 'In a black and white, risk-averse, litigation-averse world it's tempting to say let's wait and first do no harm'.

'To me, that ignores the daily lives and desires of these families', he added.

Mitochondrial Replacement, Evolution, and the Clinic
Science |  19 September 2013
New Controversy Over Experimental IVF Method
ScienceInsider |  19 September 2013
Warning of three-person IVF 'risks'
BBC News |  19 September 2013
Warning sounded over three-parent IVF safety
New Scientist |  19 September 2013
22 February 2016 - by Ryan Ross 
The use of IVF technologies could be storing up future health problems for children born through the technique, according to an evolutionary biologist...
9 June 2014 - by Alice Plein 
Two experimental IVF techniques that could prevent certain types of incurable genetic disease are 'not unsafe', a report from the UK's Human Fertilisation and Embryology Authority has found....
3 March 2014 - by Chee Hoe Low 
The USA's Food and Drug Administration (FDA) is considering whether to allow human clinical trials of mitochondrial replacement, an IVF technique that uses gametes from three people...
6 January 2014 - by Dr Calum MacKellar 
Mitochondrial replacement techniques are not a form of therapy in which a person is being treated or cured for a disorder, but instead make sure that that certain persons are not brought into existence. This is a crucial difference since it then questions the equality in value and worth of every possible future person...
2 December 2013 - by Dr John Appleby, Professor Rosamund Scott and Professor Stephen Wilkinson 
A group of European parliamentarians from the Council of Europe recently issued a declaration objecting to the HFEA's policy advice on experimental mitochondrial replacement therapy claiming that MRT is eugenic and inconsistent with human dignity. These are substantial moral claims, ones that deserve closer scrutiny, and it is an interesting and important exercise to consider how successful such arguments are...
1 July 2013 - by Dr Rosie Morley 
The UK Government is to support the introduction of mitochondrial replacement therapy. The IVF-based procedure could allow women with mitochondrial disease the opportunity to have healthy children, by replacing their own, faulty, mitochondria with healthy mitochondria from a donor....
21 March 2013 - by Sandy Starr 
Mitochondrial replacement therapy, where a small amount of a mother's genetic material is swapped with material from a donor during IVF to avoid passing on heritable illnesses, enjoys the 'general support' of the public, the UK's fertility regulator says...
29 October 2012 - by Joseph Jebelli 
Scientists have successfully created human embryos containing donated mitochondrial DNA in an effort to stop children inheriting life-threatening diseases...
22 October 2012 - by Dr Rebecca Dimond 
Techniques for the prevention of mitochondrial disease have attracted intense speculation, controversy and excitement...
Comment ( - 23/09/2013)
I think you will find that family's with a severe, potentially fatal variant of mitochondrial disease, would consider the risk worth taking. After all what is the alternative. For the milder variants, to wait may be the best option. This technique will not be forced on anyone. They will have a choice. My son died from MELAS at the age of 40 and I wouldn't wish his suffering on anyone. If their had been a way to save him from the cruelty of this disease, I would have taken it, regardless of the risk.
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