Mitochondrial donation – birth of a policy

Mitochondrial donation (or mitochondrial replacement techniques, MRT) is a special form of in vitro fertilisa­ tion involving the mitochondrial DNA (mtDNA) of a third (donor) party. This technique eliminates the risk of severe mitochondrial pathologies, genetically inher­ ited from the mother, by replacing part of her mtDNA with healthy mtDNA from another woman, the donor. This implies that the future child will have DNA from both parents, as well as some DNA from a healthy fe­ male donor of mitochondrial contents. Mitochondria are small structures contained in the cy­ toplasm of human cells, including eggs. They generate the majority of a cell’s energy supply which powers every part of our body. The genetic contribution of mitochondria is small, both qualitatively and quantita­ tively. Qualitatively, because they do not transmit any of the traits that confer the usual family resemblances and distinctive personal features. Quantitatively, mito­ chondria constitute approximately 0.1% of the human genotype. Nevertheless, for any cell to function, the mi­ tochondrial genes need to work properly, so the impact when they fail to function is considerable. Mitochon­ dria with gene abnormalities can cause severe medical disorders known as mitochondrial diseases. Mitochon­ drial diseases affect parts of organs that use a lot of energy, causing problems such as loss of muscle co­ ordination, heart disease, liver disease, neurological problems, diabetes mellitus, deafness and dementia, leading to morbidity and in some cases to premature death. In fact, patients can be mildly, severely or fatally affected, depending on which organs are dysfunctional and to what extent. According to the Human Fertilisa­ tion and Embryology Authority (the UK regulator of the use of gametes and embryos in assisted reproduction and research), in the UK, one in 200 children is born with mitochondrial disease each year, with symptoms ranging from light to severe,1 whereas in the scientific literature it is estimated that one in 400 persons carries a disease­causing mitochondrial mutation [1]. How­ ever, the probability of a child being born with mito­ chondrial disease is difficult to evaluate [2]. It is esti­ mated that the number of women likely to be eligible for the procedure under consideration will be around 150 per year in Britain [3] and about 800 per year in the United States [4]. Both sexes can inherit a mitochondrial disease, but it is only women who are at risk of transmitting the disease to their children. The two most common techniques used for mitochondrial transfer are maternal spindle transfer (MST) and pronuclear transfer (PNT). In the first method, MST, a patient’s nuclear genetic material is removed from her eggs and transferred into donated eggs once their nuclear genetic material has been re­ moved. The eggs containing the patient’s nuclear ge­ netic material and the donor’s healthy mitochondria are fertilised with the intended father’s (or a donor’s) sperm to create embryos. In the second method, PNT, the patient’s eggs are fertilised with the intended father’s (or a donor’s) sperm in a laboratory to create embryos. The nuclear genetic material within each embryo is then transferred into embryos created using donated eggs and sperm from the sperm provider, once the nuclear genetic material has been removed. In both MST and PNT, the resulting embryos containing the female patient’s and her partner’s (or sperm donor’s) genetic material as well as the mitochondria donor’s healthy mitochondria are transferred to the patient’s womb and hopefully implant and develop into a foetus. There is a wide and traditional international consensus on prohibiting human germ­line modification,2 and in