Dr Doug Turnbull
This profile is taken from the MRC Annual Review 10/11, Perspectives, which tells the stories of MRC scientists who made some of the most compelling research discoveries of 2010/11 by thinking about research problems from a new angle.
Professor of neurology at the University of Newcastle and director of the Lifelong health and Wellbeing Centre for Brain Ageing and Vitality.
Doug and his colleagues have pioneered a technique to transfer DNA between two human eggs, which could ultimately be used to stop mitochondrial diseases in their tracks.
Doug is a busy man. As well as directing the Centre for Brain Ageing and Vitality - co-funded by a group of research councils including the MRC – he runs a clinic for patients with mitochondrial disease from all over the country.
“The people in my lab either work on understanding mitochondrial diseases, trying to find new ways of treating or preventing them, or looking at mitochondria in other diseases such as neurodegeneration and the basic mechanisms of ageing,” he explains.
“For me, the motivation of our work is that there’s not a lot we can do for patients with these diseases at the moment – we can help them, but we can’t cure them – and prevention’s going to be better than cure.”
Microscopic generators
Mitochondria are tiny structures inside our cells which are essential for generating energy. When they are faulty, mitochondrial diseases occur. The more complicated the cell is, or the more energy it needs, the more likely it is to be affected when mitochondria don’t work properly.
Cells which need the most energy include those of the brain, muscle, heart and ears – so faulty mitochondria in these cells can cause conditions like severe muscle weakness, heart problems and deafness. Very severe defects mean that a baby born with the disease will not survive beyond the first few hours of life, but milder defects produce symptoms which only appear in childhood or later life.
“Mitochondria are unique because they have their own DNA, which is inherited only from the maternal side of a person’s family and which is entirely separate from DNA in the cell’s nucleus,” explains Doug. “Unlike the DNA in the nucleus, which contains the 23,000 genes needed to make up a person, mitochondrial DNA is a tiny piece of DNA comprising 37 genes, 13 of which are involved in actually making the mitochondria.”
With MRC funding, one area of the team’s research is concentrating on ways of preventing diseases caused by these 13 genes, and in 2010 they made a major breakthrough.
Changing the batteries
The reason why these diseases can’t presently be cured, explains Doug, is that trying to alter the genetic make-up of the cell is very difficult, and getting inside the mitochondria is even more tricky. But there is a way around this. He describes mitochondria as being like the batteries in a laptop computer. Without them, the computer (or cell) won’t work, but the batteries can be removed and swapped for new ones without having any detrimental effect.
Doug explains: “What we have been working on, with our colleagues Mary Herbert and Alison Murdoch at the Newcastle Fertility Centre, is using very early stage human embryos which are not suitable for IVF treatments which have been abnormally fertilised.
“In normal fertilisation, you get a female pronucleus from the mother’s egg cell and a male pronucleus from the father’s sperm cell. We've been using abnormal embryos with one or three pronuclei, so they can’t be used for IVF, and we’ve been able to successfully transfer pronuclei from one embryo to another without taking any mitochondria with them.”
The technique is a major leap forward for preventing mitochondrial diseases, because it means that the pronuclei from an embryo with faulty mitochondrial DNA can be removed and put into an ‘empty’ donor embryo which has had its pronuclei removed. The embryo would then have the donor cell’s normal mitochondrial DNA and grow up to be completely free of the disease.
Ending inherited diseases
In practice, the technique could be used to help women going through IVF treatment who have a known risk of passing on mutations which cause mitochondrial disease.
“The technique is for women who have high levels of mutations and have really limited reproductive options. For example, I’ve seen one lady who has had ten pregnancies and she’s lost five children in the first 24 hours of life. Her only surviving child recently died aged 21 from a severe type of degenerative brain disease called Leigh’s syndrome. These are the sort of people we want to be able to help. And of course if you take the disease out at this stage then the child won’t pass it on to her children either.”
More research is needed and ethical, legal and practical issues associated with the research need to be addressed before it can go forward. The next steps will be to assess the safety and effectiveness of the technique in normal human embryos, and scientists in this field of research are working with the government to try to change regulations in this area to bring it closer to benefiting patients.
Watch a video of Doug talking about his work
Published October 2011