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Response to Human Fertilisation and Embryology Authority Consultation Medical Frontiers: Debating Mitochondria Replacement

7 December 2012
This policy document is a response submitted by the Progress Educational Trust (PET) to the Human Fertilisation and Embryology Authority (HFEA)'s Consultation Medical Frontiers: Debating Mitochondria Replacement.
Responses to this consultation were summarised and responded to by the HFEA (.pdf 389KB) in March 2013.
PET has also responded to public consultations on mitochondrial donation conducted by the Nuffield Council on Bioethics (NCoB) in February 2012 and by the Department of Health in May 2014, has responded to a survey on mitochondrial donation conducted by the HFEA in July 2015, and has drafted briefings for MPs and Peers on the science and ethics of mitochondrial donation.

1. What are your views on offering maternal spindle transfer and/or pronuclear transfer to people at risk of passing on mitochondrial disease to their child?
We believe that provided pronucelar transfer (PNT) and maternal spindle transfer (MST) can be shown to be adequately safe and effective, and provided these techniques become subject to suitable regulation by the HFEA (with up-to-date information and appropriate support made available to prospective patients), it would be ethical to offer either technique or both techniques as treatments to the appropriate patient groups.
It is ethically legitimate for prospective parents to aim to avoid the transmission of inherited mitochondrial DNA (mtDNA) disorders, particularly given the severity of the health and social consequences such disorders might have for their (genetically related) future children. Some people at risk of transmitting mtDNA disorders will prefer to try to conceive a child who is both genetically related to them and healthy, and this preference is legitimate and deserving of support.
Potential parents may believe that there are strong health and social benefits to themselves, to their existing children and to their wider family of having the opportunity to try to conceive a child who neither has, nor is likely to transmit, mtDNA disorders. Some prospective parents who are currently at risk of transmitting mtDNA disorders may feel unable to try for children, and/or may terminate any unplanned pregnancy because of concern about transmitting such disorders. Other prospective parents will seek to conceive naturally, but may suffer great anxiety about whether and how their pregnancy and their future child will be affected - not least because of the many uncertainties inherent in antenatal testing for mtDNA disorders, and the attendant issues involved in antenatal testing per se.
We believe that the above points are compelling reasons for researching the feasibility of techniques to prevent the transmission of mtDNA disorders - notwithstanding the fact that there may be a spectrum of severity in the symptoms of such disorders, and notwithstanding the fact that more work remains to be done to improve the accuracy of diagnosis of such disorders and prognosis in individual cases.
In our view, techniques involving the use of unfertilised eggs (MST) do not have any preferable or less problematic ethical status, compared with techniques involving the use of zygotes (PNT). Similarly, we cannot envisage having any particular objection to a hypothetical technique that involved nuclear transfer from a more developed embryo than is used in PNT.
If techniques to avoid the transmission of mtDNA disorders are found to be adequately safe and effective, we believe that these techniques should be offered to patients as a form of NHS-funded treatment. We are concerned that patients have already reported sometimes prohibitive difficulties in accessing NHS-funded preimplantation genetic diagnosis, and that these difficulties may in future affect novel techniques to avoid the transmission of genetic disorders.

2. Do you think there are social and ethical implications to changing the germline in the way the techniques do?
The proposed techniques are thought to change only the mitochondrial germline. In our view, a 'change' via these techniques - from mutated, potentially disease-causing maternal mitochondria to predominantly non-mutated, non-disease-causing mitochondria - would be of benefit to the future child, and would have positive implications for their family and for subsequent generations. To us, these are positive ethical reasons for seeking to change the mitochondrial germline.
It is also worth noting that the proposed techniques constitute a form of germline genetic modification in which DNA molecules are left completely intact. This precludes any risk that might be posed by intervening in the gene sequence within the molecule.

3. Considering the possible impact of mitochondria replacement on a person's sense of identity, do you think there are social and ethical implications?
Without a means of avoiding the transmission of mtDNA disorders, people seriously affected by such disorders (and their families) will certainly experience adverse impacts upon their sense of identity, given the health problems and consequent social difficulties that are entailed.
A person who inherits their mitochondria from a donor may subsequently become aware of the background context of a serious genetic disorder which may have affected their parents, siblings and wider maternal family, while expecting to remain free of mtDNA disorders themselves. Given the alternatives, this seems a preferable position for a future person to find themselves in, as regards the development of their identity.
The provenance of a person's mitochondria may be important to their sense of identity, for example if they view genetic links of any kind as indicative of the creation of parental social roles. However, we believe that in today's society, genetic links and parental roles are - for the most part - viewed quite differently.
We believe that a dispassionate view of genetic links is likely to extend to mitochondrial donation, in light of the fact that no physical resemblance or other personal or observable characteristics (with the sole exception of effectively functioning mitochondria) would be inherited from a mitochondrial donor. Also, no individually identifying genetic link is made between a child and their mitochondrial donor (or the rest of the donor's close maternal family), in the way that a donation of nuclear genes would bring about.

4 (a). In your view, how does the donation of mitochondria compare to existing types of donation? Please specify what you think this means for the status of a mitochondria donor.
Mitochondrial donation is, in our view, more akin to tissue or organ donation than it is to gamete or embryo donation (notwithstanding the fact that it involves the same egg retrieval process as is used in egg donation). The mitochondrial donor therefore does not need to be mandatorily identifiable to recipients, nor made subject to the same restrictions as reproductive donors, except where these relate to protecting of the health and wellbeing of the donor or recipient.

4 (b). Thinking about your response to Q4a, what information about the mitochondria donor do you think a child should have?
A person who inherits mitochondria from a donor should be able to obtain only medical information about that donor. Personal information about donors need not be held centrally. Voluntary groups may take on the role of fostering links between identifiable donors and recipients, if and when these are mutually desired.

5. If the law changed to allow mitochondria replacement to take place in a specialist clinic regulated by the HFEA, how should decisions be made on who can access this treatment?
The regulator should decide on the basis of recommendations from families and clinicians which symptoms (not 'mitochondrial diseases', as these are not easily categorised and have not all been named) are sufficiently serious to warrant mitochondrial replacement. Clinics and patients should then decide when it is appropriate to use the treatments in individual cases. This would avoid patients having to wait to receive a named diagnosis, and would enable the regulator to monitor the appropriateness of the patient groups to whom the treatment has been offered.
For example, we do not think MST should be used by clinics as a means of surreptitiously offering the 'rejuvenation' of healthy older women's eggs (a purpose for which cytoplasmic transfer has been offered outside the UK) until more is known about the likely effectiveness of doing this (not that there is anything ethically wrong with the aim of such 'rejuvenation'). Similarly, until more is known about the safety of PNT and MST techniques, they should not be offered for purely social reasons - for example, solely to bring about a mitochondrial genetic link to a social parent (although in principle there is nothing ethically wrong with this aim either).

6. In Q1, we asked for your views on the mitochondria replacement techniques maternal spindle transfer and pronuclear transfer. Please could you now tell us if you think the law should be changed to allow (one or both of) these techniques to be made available to people who are at risk of passing on mitochondrial disease to their child?
Yes, the law should be changed to permit the use of PNT and MST in a clinical trial and subsequently in treatment. The Secretary of State for Health should promptly bring forward the relevant draft regulations for Parliament to vote on.
We believe it would be ethical and beneficial to families, to permit either technique or both techniques to be evaluated in a clinical trial and to be used in clinical treatment thereafter. In order to make this possible, the relevant draft regulations need to be brought forward now.
That said, any change in the law should (continue to) be phrased in terms of avoiding the transmission of mtDNA disorders, not in terms of specifying techniques to achieve this aim. The overly specific phrasing employed in the question above - which describes the law being 'changed to allow (one or both of) these techniques to be made available' - is not 'future-proof', and may present undue impediments to future research.

7. Are there any other considerations you think decisionmakers should take into account when deciding whether or not to permit mitochondria replacement?
Throughout June and July this year, we ran a poll on the website of our BioNews publication, asking readers 'Should Government allow variations of IVF using genetic material from three people to prevent people from inheriting mitochondrial diseases?'. 793 people responded, of whom 542 (68%) said 'Yes' and 251 (32%) said 'No'. This suggests that the balance of opinion among our readers (who come from diverse lay and professional backgrounds) is in favour of the techniques being made legal, but that a significant minority is opposed.
Notwithstanding our interest in the wider public's views of this issue, we are of the firm opinion that the patients, researchers and practitioners who are familiar with the issues inherent in mtDNA disorders should be central to further advising decisionmakers. Given the complexity and diversity of mtDNA disorders and their symptoms, and given how counterintuitive these disorders can be in relation to the popular understanding of disease and heredity, this is an area in which we hope expert opinion will be given considerable credence and weight.
It is important that any future regulation in this area does not specify what research or treatment techniques, or what locus of origin of the disorder (for example, nuclear or mitochondrial DNA), are intended to be dealt with. It seems best to retain the current statutory wording, in order to allow researchers to come up with new solutions in future, and in order not to foreclose avenues of research or treatment. Failure to do this will mean that new treatments may not be permitted, and that specific patient groups may be disadvantaged.
In common with NCoB's recent report Novel Techniques for the Prevention of Mitochondrial DNA Disorders: An Ethical Review (.pdf 1.13MB), we believe that a wider policy debate could benefit from a fuller discussion of the ethics of the different kinds of prospective and theoretical germline therapies. This would include potential therapies that would act on the cell nucleus with heritable effects, and therapies which might involve nuclear transfer in its various forms.
We would also like any new regulations in this area to provide for the creation of a centrally funded long-term register of any such procedures performed in the UK. This register should be made accessible to researchers.