Mitochondria have a curious history. They are thought to be descendants of bacteria that colonised other bacteria over two billion years ago to help the larger bacteria produce energy. This knowledge is significant, as an important remnant of this process remains with us – mitochondria still contain their own DNA.
Wellcome Trust Centre for Mitochondrial Research’s Professor of Neurology Doug Turnbull describes the importance of preserving the health of the human ‘powerhouse’…
Professor Doug Turnbull
Just like the Duracell rabbit in the adverts, humans are all powered by ‘batteries’. Called mitochondria, these batteries are present in every tissue within our bodies and are essential for our daily activities. Unsurprisingly, when they malfunction, they can lead to severe, often life-threatening, diseases that are incredibly difficult to treat. A new technique being developed at the Wellcome Trust Centre for Mitochondrial Research, however, offers the hope of preventing them from occurring in the first place.
Mitochondria, hailed as the ‘powerhouse’ of the cell in thousands of textbooks, are essential for human life. They are a vital part of aerobic respiration – how cells use oxygen to transfer the energy from food into a form that the body can use. Understanding the way that mitochondria work has been the focus of intense scientific endeavour for many years in the UK, with three Nobel Prize winners leading the scientific effort (Fred Sanger, Peter Mitchell and John Walker).
Mitochondria have a curious history. They are thought to be descendants of bacteria that colonised other bacteria over two billion years ago to help the larger bacteria produce energy. This knowledge is significant, as an important remnant of this process remains with us – mitochondria still contain their own DNA. This mitochondrial DNA was the first human genome to be sequenced, by Professor Fred Sanger and colleagues in 1981.
Mitochondrial DNA also has a surprising pattern of inheritance. We are all used to hearing about how our mothers and fathers make an equal contribution to our genetic makeup, but this is not true for mitochondrial DNA. We get all of our mitochondria and mitochondrial DNA from our mothers. This happens because eggs contain hundreds of thousands of copies of mitochondrial DNA, whereas the sperm has only a few copies that are subsequently actively degraded after fertilisation. This strict maternal inheritance has been used by scientists mapping the evolution of species for many years, and analysing mitochondrial DNA has been crucial in proposing that modern humans are all descended from a single woman from Africa about 200,000 years ago – Mitochondrial Eve.
More recently, mitochondrial DNA has been recognised as an important cause of genetic disease. This stems back to the 1988 discovery by Anita Harding and colleagues in London of mitochondrial DNA abnormalities in patients with a particular form of muscle disease. Since then, there has been a plethora of reports of mitochondrial DNA involvement in a range of different diseases affecting predominantly tissues that are highly dependent on energy metabolism such as heart, muscle and brain. These mitochondrial DNA abnormalities may even play a role in ageing and some common degenerative diseases, such as Parkinson’s disease.
All these advances in understanding disease are of little help to the patients and families that carry these mitochondrial DNA mutations. New treatments for such disease are extremely challenging because of the complexities of mitochondria and energy metabolism. So if these diseases cannot be treated, could they instead be prevented?
One option, already available for some mothers with mitochondrial DNA mutations, is a technique called pre-implantation genetic diagnosis. This involves a couple undergoing IVF and then selection of an embryo that is least likely to be affected by mitochondrial disease. This approach is helpful for some – but not all – families.
However, a more radical solution is also being developed. Mitochondria, and their DNA, are entirely separate from nuclear DNA, which is responsible for 99.9 per cent of our genetic makeup – all the characteristics that make us who we are. We propose generating embryos that have the nuclear DNA from both parents but the healthy mitochondria from another woman, and then, implanting them into the mother’s womb. Recent experiments in both animal models and abnormally fertilised human eggs suggest that this is possible. Work is now being carried out to show that such techniques would be as safe and efficient as possible.
At the moment, the Human Fertilisation and Embryology (HFE) Act 2008 permits such research to be carried out in the laboratory, but prohibits an embryo that has undergone these manipulations from being implanted into a woman. However, if an acceptably safe and effective technique does become possible, then the HFE Act enables secondary legislation to be passed by Parliament to permit its use. The Human Fertilisation and Embryology Authority has asked the Wellcome Trust Centre for Mitochondrial Research to conduct a number of essential follow-up investigations and is conducting a public consultation to seek opinion on the research. It is expected to report its findings to parliament in March 2013. Recently, the Nuffield Council on Bioethics, an influential independent body that examines and reports on ethical issues in biology and medicine, issued a report examining whether such techniques would be ethical. Its report, entitled ‘Novel techniques for the prevention of mitochondrial DNA disorders’, concludes: "Due to the health and social benefits to individuals and families of living free from mitochondrial disorders, and where potential parents express a preference to have genetically related children, on balance we believe that if these novel techniques are adequately proven to be acceptably safe and effective as treatments, it would be ethical for families to use them, if they wish to do so and have been offered an appropriate level of information and support."
It is remarkable how science continues to raise challenging questions for society and how lucky we are to live in a society that will allow active debate. Whilst one cannot predict the outcome, due to the major investment of the Wellcome Trust in mitochondrial DNA research, there is at least hope for families suffering from these currently incurable genetic diseases.
Professor Turnbull's article will be published in the seventh issue of Public Service Review: UK Science and Technology.