The Oxford Science Lecture Series
Professor Kay Davies
University of Oxford
“Therapy for Duchenne muscular dystrophy: time for optimism”
Dorothy Hodgkin Memorial Lecture 2016
University Museum, Oxford, 4th March 2016
The 2016 Dorothy Hodgkin Lecture was given by Professor Dame Kay Davies from the Department of Physiology, Anatomy & Genetics in Oxford. Professor Davies started by explaining that she wasn’t a structural biologist, as many of the previous Dorothy Hodgkin lecturers have been, but she did have a link with Dorothy as she was a fellow Somervillian and Dorothy had attended one of Kay’s lectures. Somerville had been tremendously supportive of Dorothy, even though she was married which was not encouraged at the time, and in her turn Dorothy had been very supportive of the women who had worked with her. Professor Davies went on to say that it is important to have an International Festival for Women (of which this lecture forms a part each year) to celebrate success and encourage girls into science.
Professor Davies began her scientific career by studying chemistry in Oxford in 1969, at which time there were about 200 males and 22 females reading chemistry. She did her Part II project, and then her DPhil, in the biochemistry department and then moved to Paris with her then husband. During this period, a break-through paper was published which described the possibility of following the inheritance of disease through DNA and so Professor Davies returned to London to work in genetics. She was interested in Duchenne muscular dystrophy (DMD) which is a disease only seen in boys (apart from a few rare occasions). DMD results from a genetic disorder which causes cells to lack dystrophin, a large protein that tethers the contractile machinery of a muscle cell to the cell membrane. This gives the membrane strength and prevents damage due to wear and tear.
The dystrophin gene is located on the X chromosome, so females (who have 2 X chromosomes) with a mutation in the dystrophin gene will normally have a second, healthy copy on the other X chromosome and will be able to make functional dystrophin. In males (who have one X and one Y chromosome), there is no second X chromosome to compensate and so if the dystrophin gene is mutated then their cells will fail to contain functional dystrophin. DMD occurs in about 1 in 5000 boys and leads to gradual muscle and cardiac damage so that the boys are restricted to a wheelchair by about the age of 12. There is no effective treatment and, at the time Professor Davies started researching the disease, there was no effective diagnosis.
This disease is so debilitating that, at that time, mothers with one DMD child might abort a second child rather than risk that child suffering the same disease. Professor Davies realised that if she studied the X chromosome of the very rare female patients with the disease this would give her valuable information as to where the gene was located and this enabled her to develop a test which could be used for pre-natal diagnosis. She told us that the first test took three weeks to produce the diagnosis, whereas now the results are back within hours.
In 1986, the gene that causes DMD was identified, and so for a time Professor Davies thought that meant there was no more to be done, until she realised that this was just the start of everything and that she should begin to look for a cure. This was not a trivial undertaking. Muscle forms 40% of our body mass, and an effective cure would need to target all the muscle in the body throughout life. She identified a protein called utrophin, which is very similar to dystrophin but is usually only found in the neuromuscular junction.