Cell injection - artificial insemination
Breakthrough: damaged mitochondrial DNA can be swapped for that of a healthy donor © Getty

From his clinic in Newcastle, north-east England, Doug Turnbull is preparing for the probable launch in the coming months of a pioneering medical intervention with substantial benefits — and considerable ethical repercussions.

His approach to replacing damaged mitochondrial DNA in human cells — leading the way to what has popularly been dubbed “three parent children” — is expected to gain regulatory approval and start to be offered to couples during 2016. It offers hope to dozens of parents each year in the UK seeking to have children without the risk of passing on a range of health disorders.

“I have to say, I enjoyed my Christmas break because I’ll need it,” he jokes, as he expresses continued caution about the steps his team must still successfully complete before they can start using the process with patients at his in vitro fertilisation centre.

“I’ve spent 30 years looking after patients with mitochondrial disease. I’m going to be more rigorous than anybody else to ensure we have got everything in a row before anything happens,” says Prof Turnbull.

Britain is being closely watched around the world as the first country set to introduce mitochondrial transfer. UK experts are also exploring still more radical interventions including genome editing to reduce the risk of other diseases being passed on to children.

Mitochondria are the “batteries” that provide energy to cells. Damaged mitochondrial DNA — inherited from the mother — can lead to rare diseases with few treatment options, including neuropathy, ataxia, and retinitis pigmentosa and Leigh syndrome. Estimates suggest that 2,500 women of childbearing age in the UK are at risk of passing a serious mitochondrial disease to their children.

Prof Turnbull’s team at Newcastle University and the Newcastle upon Tyne Hospitals NHS Foundation Trust has developed the “pro-nuclear transfer” technique. This removes the nuclear material of the parents’ fertilised egg, containing damaged mitochondria, and implants it into a donor’s healthy egg from which the nuclear material has been removed.

An alternative process called maternal spindle transfer technique, developed by US researchers, uses the same approach but fertilisation takes place only after the parents’ material is implanted into a healthy egg.

Mitochondrial DNA contains just 37 genes, compared with the 23,000 in the nuclear genome. That means using the healthy equivalent from a donor’s egg has scant impact on the characteristics of the child. The anonymous donor has no rights over the baby.

No team has yet applied for approval from the Human Fertilisation and Embryology Authority (HFEA), which will regulate the process. However, Robin Lovell-Badge, head of the division of stem cell biology and developmental genetics at the Francis Crick Institute, and a member of the HFEA oversight committee on mitochondria, says either technique could be considered.

Catholics have been among the critics of the techniques, particularly pro-nuclear transfer because it destroys a fertilised egg.

“If someone has a religious objection, they should declare that rather than saying it is not scientifically safe without evidence,” says Mr Lovell-Badge. “I respect that view, although I personally disagree. I would value a child more than an early human embryo.”

His views are reflected both in the UK’s decision to create the HFEA in 2008 and legislation passed last year specifically to permit mitochondrial transfer.

Prof Turnbull argues that the UK’s leading position has been helped by a combination of substantial medical research, patient support and advocacy, and charitable funding.

He also singles out the role of the state-supported National Health Service. “It allows us to look after more patients than anyone else. Sometimes we’re great at mocking the UK, but we don’t realise how lucky we are.”

The remaining steps before Prof Turnbull’s technique can be offered to couples include peer review of final studies to demonstrate safety and efficacy; the receipt of a licence from the HFEA; and agreement with the NHS on whether — and how — mitochondrial transfer would be funded. Subject to parental consent, there will also be efforts to follow children’s progress after their birth.

As work continues on mitochondrial transfer, earlier stage research is also proceeding on genome editing, which has the potential to alter genetic sequences to tackle many other diseases — both in treatment and to remove inherited conditions. That is still a long way off, and will raise still tougher scientific challenges and ethical debates.

But for now, mitochondrial transfer is coming close to reality. “Other countries are watching the UK very closely, including the US, Australia, Scandinavia, Belgium, the Netherlands and China,” says Mr Lovell-Badge. “It will take off.”

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