We all know the story of the ‘birds and the bees’ or more accurately ‘sperm meets egg’. This tale is complicated by the insidious exploits of infertility, which has led to the development of in vitro fertilisation (IVF) technology. IVF takes the ‘sperm meets egg’ story, sets it in a lab and with the helping hands of fertility specialists ensures that sperm does indeed meet egg. Recent research at the Institute of Ageing and Health, Newcastle takes IVF one step further in a bid to also help fertile couples facing the prospect of conceiving unhealthy offspring, due to mutations in the DNA of the intended mother.
Mutations in a special type of DNA, called mitochondrial DNA, lead to a host of debilitating diseases that cause blindness, deafness, heart disease and can even be fatal. A recent advancement in IVF called pro-nuclear transfer (PNT) may prevent these diseases, which affect one in every 6,500 children in the UK, from being inherited. PNT picks up where the ‘sperm meets egg’ story concludes and introduces yet another egg to the mix - specifically a donor egg that provides the potentially life-saving DNA.
Most of our DNA is stored in the command centre of the cell called the nucleus. ‘Nuclear DNA’ is a mix of the DNA we inherited from our parents; half from our father and half from our mother. Some DNA is however stored outside the nucleus, in hundreds of tiny structures called mitochondria. Mitochondria are the cell’s powerhouses, churning out the energy needed to keep our cells alive. ‘Mitochondrial DNA’ is unique, as it is not a mix of DNA inherited from both our parents, but comes entirely from our mother. Consequently, if a woman carries a disease-causing mutation in her mitochondrial DNA all her offspring will inherit it. PNT may be able to circumvent this problem by picking up where IVF leaves off.
IVF involves fertilising one egg with one sperm to form an embryo. If the egg used contains healthy nuclear DNA but unhealthy mitochondrial DNA, the resulting embryo will also contain unhealthy mitochondrial DNA. PNT involves transplanting the nucleus (and so nuclear DNA) of this embryo into a donor egg. The donor egg has already had its own nucleus removed and is left with only its healthy mitochondrial DNA. The embryo resulting from PNT contains the healthy nuclear DNA of the intended father and mother and the healthy mitochondrial DNA of the donor egg from another woman. When put into practice, PNT may prevent the transmission of mitochondrial disease from a mother with mutant mitochondrial DNA and still allow a large part of her genetic heritage to pass onto her offspring. The offspring however would carry the genetic identity inherited from three individuals, raising questions over the ethics of such procedures.
The UK’s Nuffield Council on Bioethics points out that children created from this process would not have three parents, as the mitochondrial DNA donor would remain anonymous. In a report released in June this year, the Nuffield Council found that more research is needed into the safety and effectiveness of such treatments, but acknowledge the potential benefits for the future offspring of women carrying defective mitochondrial DNA. Making genetic alterations to human eggs or embryos before implantation into a woman is currently illegal in the UK. Much hinges on how this ethical debate is resolved, both for the women in question and for current UK laws on fertility treatment. The debate continues and shall be brought to public consultation this September by the Human Fertilisation and Embryology Authority.
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Tachibana M, Sparman M, Sritanaudomchai H, Ma H, Clepper L, Woodward J, Li Y, Ramsey C, Kolotushkina O, Mitalipov S. Mitochondrial gene replacement in primate offspring and embryonic stem cells. Nature. 2009 Sep 17;461(7262):367-72. PMID: 19710649
Nuffield Council on Bioethics Novel techniques for the prevention of mitochondrial DNA disorders: an ethical review. 15 June 2012.