Novel Techniques for the Prevention of Mitochondrial DNA Disorders: an Ethical Review
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Novel techniques for the prevention of mitochondrial DNA disorders: an ethical review Nuffield Council on Bioethics Professor Jonathan Montgomery (Chair) Professor Thomas Baldwin* Professor Steve Brown FMedSci Dr Amanda Burls Professor Robin Gill Professor Sian Harding FAHA FESC Professor Ray Hill FMedSci Professor Søren Holm Dr Rhona Knight FRCGP** Professor Graeme Laurie FRSE Dr Tim Lewens Professor Ottoline Leyser CBE FRS Professor Anneke Lucassen Professor Michael Moran FBA*** Professor Alison Murdoch FRCOG Dr Bronwyn Parry Professor Nikolas Rose Dr Geoff Watts FMedSci Professor Jonathan Wolff * co-opted member of the Council while chairing the Working Party Novel neurotechnologies: intervening in the brain ** co-opted member of the Council while chairing the Working Party on Donor conception: ethical aspects of information disclosure *** co-opted member of the Council while chairing the Working Party on Emerging biotechnologies iii Secretariat Hugh Whittall (Director) Kate Harvey Katharine Wright Tom Finnegan Dr Peter Mills Varsha Jagadesham Laura Riley Ranveig Svenning Berg Catherine Joynson Johanna White Sarah Walker-Robson Carol Perkins The terms of reference of the Council are: 1. to identify and define ethical questions raised by recent advances in biological and medical research in order to respond to, and to anticipate, public concerns; 2. to make arrangements for examining and reporting on such questions with a view to promoting public understanding and discussion; this may lead, where needed, to the formulation of new guidelines by the appropriate regulatory or other boy; 3. in the light of the outcome of its work, to publish reports; and to make representations, as the Council may judge appropriate. The Nuffield Council on Bioethics is funded jointly by the Medical Research Council, the Nuffield Foundation, and the Wellcome Trust iv Acknowledgments The Working Group would like to thank the following individuals who contributed presentations to project fact-finding meetings: ■ Professor Brenda Almond, Emeritus Professor of Moral and Social Philosophy, University of Hull ■ Professor Arthur L Caplan, University of Pennsylvania at Philadelphia ■ Professor Farzin Farzaneh, King’s College London ■ Professor Sarah Franklin, University of Cambridge ■ Professor Susan Golombok, University of Cambridge ■ Dr Caroline Jones, University of Southampton ■ Dr Calum MacKellar, Scottish Council on Human Bioethics* ■ Dr Shoukrat Mitalipov, Oregon Health and Science University ■ Dr Jackie Leach Scully, University of Newcastle ■ Dr Tom Shakespeare, World Health Organization ■ Professor Hubert Smeets, University of Maastricht ■ Professor Guido de Wert, University of Maastricht The Working Group are also indebted to all those who responded to the project’s public call for evidence. These thoughtful contributions from a range of perspectives greatly informed the Working Group’s considerations. Special thanks go to Professor Hubert Smeets and Dr Caroline Jones, who presented to the Working Group during the development of the project and also gave comments at drafting stage. Professor Peter Braude of the Working Group advised on diagrams, with some additional comments from Professor Doug Turnbull at Newcastle University. The illustrations in this report were drawn by Rebecca Kent. The Nuffield Council on Bioethics membership discussed the project and report in plenary at various stages with Dr Rhona Knight, Professor Søren Holm, Professor Robin Gill and Professor Steve Brown forming the project’s consultative subgroup of Council members. The Working Group would like to thank the subgroup for their comments, particularly at drafting stage. The Working Group would also like to thank Kate Harvey, Varsha Jagadesham and Tom Finnegan of the Nuffield Council on Bioethics secretariat for their assistance with copyediting and print production. Finally, the Working Group would particularly like to thank Laura Riley of the Nuffield Council on Bioethics secretariat who, as project leader, researched and managed the project and prepared this report. * Dr MacKellar presented his views to the Working Group in a personal capacity, due to the limited timeframe of the Working Group’s project and the longer frame required for the Council of the Scottish Council on Human Bioethics to submit an agreed opinion to the Working Group. v Foreword Inherited mitochondrial disorders are progressive and often cause severely debilitating and disabling health problems. There is no cure for these conditions, and they can result in the death of babies, children and young people. Mitochondria are tiny structures inside our cells which provide the energy for cells to function. Their failure to work properly can have devastating effects. Mitochondrial disorders can be caused by either problems in the genes in the nucleus affecting mitochondrial function, or by problems in genes within the mitochondria themselves. Recent years have seen increasing attention paid to two techniques both currently at the research stage: pronuclear transfer (PNT) and maternal spindle transfer (MST). These two IVF-based techniques seem to have the potential to prevent transmission of maternally- inherited mitochondrial disorders caused by mutations in the genes of mitochondria. PNT involves using very early (one day old) embryos. MST uses unfertilised eggs. Both techniques would create embryos in which the nuclear genetic material of the intended parents is re-housed along with healthy mitochondria from a donated egg. This could come from either an unrelated donor or a maternal relative with healthy mitochondrial DNA. A maternal relative’s healthy donated mitochondria would be identical to any healthy mitochondria the intended mother had, effectively permitting her to pass on what she may regard as ‘her family’s’ mitochondrial DNA to her child. There are important questions still to be clarified about the safety and efficacy of these two techniques. However, if they were successfully brought into clinical use they would allow women who would otherwise pass on mutated mitochondria through their eggs to their children to give birth to healthy children whilst using their own nuclear genetic material. Techniques such as these are currently unlawful for treatment use in the UK, because they would involve making changes to a human egg or embryo before transfer to a woman’s body. Patient groups and medical research funders are pressing the Government to offer Parliament the opportunity to vote to approve the use of regulation-making powers already in place which would allow such techniques for use in preventing the transmission of mitochondrial DNA disorders in the UK, at such time as they can be considered acceptably safe and effective. The granting of a licence by the Human Fertilisation and Embryology Authority (HFEA), the UK’s fertility treatment and associated research regulator, to carry out research investigating PNT using human embryos to the Newcastle Fertility Centre at LIFE in 2005, and the promising results found there, have fuelled this pressure. In January 2012, the Wellcome Trust announced funding of £4.4 million for a new Wellcome Centre for Mitochondrial Research located at the University of Newcastle, with additional university funding. The centre will undertake research intended to establish the safety and efficacy of PNT and MST as part of its work, while adding to knowledge about the techniques already gained from research in the UK and US. The Newcastle team estimate that, depending on the supply of donated eggs available to them, they will know in two or three years’ time whether these techniques could become treatments. On the same day as the Wellcome Trust’s funding announcement, the Secretaries of State for Health, and for Business, Innovation and Skills tasked the Human Fertilisation and Embryology Authority and Sciencewise-ERC with seeking “public views on emerging IVF techniques designed to prevent the transmission of mitochondrial disease.”1 Together with previous requests for scientific information from the Secretary of State for Health to the HFEA, this makes it foreseeable that in the relatively near future Parliament could debate the approval of regulation-making powers in the Human Fertilisation and Embryology Act 1990 (as amended) to enable the techniques to be offered as treatments. 1 Human Fertilisation and Embryology Authority (19 January 2012) HFEA to consult on ethics of ‘mitochondria transfer’, available at: http://www.hfea.gov.uk/6898.html‘’. vii Ethical considerations will be key to arriving at a robust and sustainable decision on whether the techniques should be offered as treatments. As an independent body, the Nuffield Council on Bioethics has sought to identify the novel ethical issues raised, while also looking deeper into the issues which have already featured in the public debate about these techniques. Cell reconstruction techniques such as PNT and MST have attracted considerable interest partly because they would create children born with a genetic connection to three people. The new techniques also raise the question of whether seeking to rectify problems caused by mitochondrial genes is ethically different from seeking to rectify problems caused by genes in the nucleus, as mutations in either genome can be the cause of mitochondrial disorders. Cell reconstruction techniques also raise familiar ethical questions common to many assisted reproduction treatments, such as determining the acceptable level of risk when using a new treatment in order