1. Prof. Donna Dickenson University of London
The burning question in the UK: ‘mitochondrial replacement’ research and public policy
Prof. Donna Dickenson
University of London

2. A new and crucial development
New target for ART: not infertile couples
‘Mitochondrial replacement’ (MR) would allow fertile women with mitochondrial disease to have genetically related children who would not be at risk (since disease passes through maternal line)
Fact that it requires large quantities of eggs ignored by many commentators (‘sliver of DNA’)
Egg donation issue not being framed in terms of either altruism or commercialisation, but simply avoided altogether

3. Chronology
October 2012: Oregon scientists (Mitalipov et al.) publish key Nature paper on MR in 5 macaques, followed by UK research (Herbert et al.)
June 2013: UK government proposes regulatory changes to allow MR, although HFEA consultation finds majority of public opposed. Expert panel says no evidence techniques unsafe.
February 2014: US FDA hearings, however, conclude that ‘the full spectrum of risks has yet to be identified’ and that both basic and clinical science not far enough advanced to legalise MR

4. Chronology continued
March 2014: MPs of both parties speak against proposals. Government repeats that it intends to allow MR and will only allow debate on how trials will be regulated, but later has to modify position to allow conscience vote in Parliament. Another poll undermines official claim that public in favour. HFEA opens final scientific evidence call on safety but allows only two weeks for submissions.
May 21, 2014: Final consultation on draft regulations ends. What next?

5. What is ‘mitochondrial replacement’?
Term is actually inaccurate, masking contribution of egg donor and egg’s role in programming DNA
What is being transferred is not the 37 genes in mitochondria, but somatic cell (with some 20,000 genes) from a woman affected with mitochondrial disease to another woman’s healthy egg, from which nucleus has been removed; really ‘nuclear transplantation’
Preliminary research (Mitalipov et al.) used 106 eggs from 7 women, one of whom donated 28 eggs, indicating possible ovarian hyperstimulation

7. More on mitochondrial disease
Mithochondria sometimes described as the energy ‘batteries’ (piles) of the cell
One in 200 babies born with some mitochondrial disorder, but majority are healthy. Better estimate for severe disease is about one in 6500.
Can cause muscle weakness, heart, kidney and liver disease, and neurological disorders
Expected number of treatments: only 10 cases p.a., depending on cost (probably around £80,000)

8. So why this controversy over such a small number of cases?
UK proposals fly in face of international agreement against germline genetic modification (e.g. Oviedo Convention)
The fact that the US regulator has come out against the technology hasn’t been publicised in UK (cf my New Scientist article)
Opponents are being portrayed as either pro-Catholic, anti-science, or both, although many scientists are sceptical
Democratic consultative process has been flawed

9. Scientific evidence base
FDA: Apart from risks to egg donor and recipient, possible mutations from incompatibility between DNA of somatic cell donor and egg donor
Because only one study to date has used human eggs or embryos containing abnormal mitochondria, too early to judge effectiveness. Other studies showed abnormalities in human zygotes not found in monkeys.
Although UK Chief Medical Officer calls it ‘life-saving treatment’, technique cannot cure any existing sufferers; unclear whether‘bad’ mitochondria might reappear in later generations

10. Ethical concerns: 1. Altering DNA of future generations
Consultation document acknowledges that ‘the treatment techniques are akin to germline therapy to the extent that mitochondrial donation may have implications not only for the children born as a result of the procedure but for their descendants’
Although this might seem a change for the better, too little is known about long-term risks
Slippery slope towards other forms of alteration?

11. 2. Risks for recipients
US professor David Keefe has written to HFEA in these terms: ‘Displays of technical virtuosity should not blind us to potential hazards…Our own group moved away from this research because PGD (preimplantation genetic diagnosis, DPI) provides a relatively safe alternative to MR for the majority of patients and because vexing concerns linger about the safety of MR.’
In any case, women with severe mitochondrial disease might be too ill to endure pregnancy (FDA patient witnesses)

12. 3. For donors: parentage, consent and exploitation
Three or even four parents, if surrogate required because recipient too ill: questions downplayed in UK as sensationalistic, but although technique would probably not be permitted in France, where questions about projet parental are legitimate
Donor’s contribution of labour and risk-taking is being ignored. ‘Lady vanishes’: common phenomenon in stem cell research as well
Is altruism of donors being exploited? Can’t give truly informed consent in absence of long-term information about risks of technique

13. Country comparisons
Neo-liberal, science-led approval process for trials now being pushed through in UK contrasts not only with principled conservatism of French regulation but even with cautious findings of US FDA hearings
Consultation only concerns ‘the detail of the regulations that would put into effect the Government’s intention to allow it’ (s. 2.4 of document). Fait accompli?
Actually UK government being very dirigiste despite UK’s libertarian reputation abroad

14. Mobilisation of patient groups
Mehl identifies this as crucial difference between 1994 and 2011 French debates, but scepticism about how genuine Etats-generaux de bioethique really were
In US patient representatives did testify, but against new technique

15. En somme…
Consultation document, annex C: ‘The intended effects of the proposal are:
A. To enable safe and effective treatment for mitochondrial disease
But neither safety nor efficacy is yet established, and this is not treatment: at most prevention.

16. B. Second aim
B. ‘To ensure that only those mothers with a significant risk of having children with severe mitochondrial disease would be eligible for treatment’
But these might well be the very severely affected women for whom the risks of pregnancy would be too great

17. C. The heart of the matter
‘To signal the UK’s desire to be at the forefront of cutting edge of medical techniques’
But as any aficionado of spaghetti westerns knows, the frontier can be a lonely and dangerous place