Research into Policy: A Brief History of Mitochondrial Donation

Mitochondrial DNA disorders are a group of common genetic diseases which affect both children and adults. They lead to progressive multisystem disease for which there is no curative treatment. Inherited mitochondrial DNA mutations are transmitted maternally, and preventing transmission of these diseases is a priority for families. An important new approach is a novel in vitro fertilisation (IVF) technique called mitochondrial donation using either maternal spindle transfer or pronuclear transfer [1]. The 4th March 2015 saw an historic event—the legislation was put in place to make mitochondrial donation legal in the UK. Critics of the technique have claimed that the new law was rushed through and that there had been insufficient time to debate the issues. Here we provide a brief account of the past 17 years to show that this is not the case. The complete human mitochondrial genome, made up of only 16,569 base pairs, was first sequenced in 1981 [2]. Around the same time, in an entirely unrelated area of research, the technique of nuclear transplantation between mouse embryos was described [3, 4]. The first human pathogenic mitochondrial DNA mutations were identified in 1988 [5, 6] and by 1995, the possibility of preventing the transmission of mitochondrial DNA disease by nuclear transplantation was already being considered [7]. Since then, although the name for the technique we now know as mitochondrial donation has changed several times, the scientific, ethical, and legal issues have been examined in detail by a number of independent groups and committees over many years. The need to regulate the use of human embryos in both fertility treatment and scientific research was recognized in the UK following the birth of the first IVF baby in 1978. This major breakthrough led to concerns about the social and legal implications of such advances in human assisted reproduction. To address these issues, the Government established the Committee of Inquiry into Human Fertilisation and Embryology chaired by the now Baroness Mary Warnock. The report [8], published in 1984, set out a blue-print for the regulation of both IVF and embryo research, and with admirable foresight, included a chapter describing possible future developments in embryo research. This report was followed by the White Paper “Human Fertilisation and Embryology: A Framework for Legislation” which was published in 1987 and formed the basis for the Human Fertilisation and Embryology Act 1990 (“the 1990 Act”) [9]. There were rapid and significant advances in non-human embryo research over subsequent years, including somatic cell nuclear transfer and the birth of Dolly the sheep in 1996 [10]. These developments generated much public interest and highlighted the need for a clarification of the legislation regarding the implications for human clinical embryology. A report by the Human Fertilisation and Embryology Authority (HFEA) and Human Genetics Advisory Commission (HGAC) [11], published in 1998, acknowledged that some of the scientific possibilities being discussed at this time had not been envisaged when the 1990 Act was drafted. Specifically, the Report recommended that the purposes for which human embryos could be used in research should be extended to allow the development of methods of therapy for mitochondrial diseases. Following this Report, the Government established an expert group chaired by the Chief Medical Officer (Professor Sir Liam Donaldson) to examine the potential benefits of a number of new areas of human embryo research, including methods to prevent mitochondrial disease. The report [12] made several recommendations Wellcome Trust Centre for Mitochondrial Research, Institute of Neuroscience, and Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom; Newcastle Fertility Centre, Newcastle Hospitals NHS Foundation Trust, Newcastle upon Tyne, United Kingdom; Hempsons, Hempsons House, Villiers Street, London, United Kingdom