When Bob Ross (MDA senior vice president and executive director) invited me to write a small piece on the role MDA had played in my research, I was not short of things to say. I was merely overwhelmed by how much has been achieved over the last 15 years!

I first became an MDA grantee when I was working with Robert W. Williamson at the University of London. At that stage (1980), Bob and I intended to clone the cystic fibrosis gene. But, in order to prove principles of the new approaches in genetics, we needed to study a good model, that is, a disease for which we knew the chromosome location.

PINPOINTING THE GENE

Duchenne muscular dystrophy (DMD) fit this requirement. The precise gene had not yet been identified, but earlier MDA grantees had narrowed its location to a certain area of the X chromosome. Both the Muscular Dystrophy Group of Great Britain and Northern Ireland (MDG) and the American MDA encouraged us to tackle Duchenne. Their support was instrumental in our making the first human chromosome library (a collection of samples of DNA from the X chromosome). From this material, we developed the markers that were used for the first prenatal diagnosis of DMD in 1981.

With our clinical collaborator, Peter Harper at the University of Wales in Cardiff, we formally proved the localization of DMD in the Xp21 region of the chromosome. We also demonstrated that Becker muscular dystrophy is an allelic disease, that is, a mutation of the same gene.

In addition to funding our work, the support of MDA promoted the close collaboration of the main groups working in the area, particularly the groups of Louis M. Kunkel at Children's Hospital in Boston, Ronald G. Worton at Hospital for Sick Children in Toronto, and my own at John Radcliffe Hospital at the University of Oxford. Without this direct involvement, the exchange of resources and ideas would not have happened and the identification of the gene would have taken much longer.

Annual meetings, alternating between Europe and the United States, were an important part of the scientific progress. These events were exciting and tense as we all strived to get the gene first while maintaining a strong sense of co-operation.

COLLABORATING ON THE DANCE FLOOR

Scientific discussions were not confined to the formal program of the meetings. Much discussion went on in the bar after the meetings or on walks in the early evenings. I remember getting tangled up in the bramble bushes while debating the size of the deletion in patient BB with Uta Francke of Yale University before dinner one evening during a meeting in Baarn in Holland.

That was the memorable meeting when the Dutch served us pea and ham soup. We all thought it was the first course, failing to realize as we refused second helpings that it was the whole dinner in traditional Dutch style. There were many hungry geneticists getting extra carbohydrates from beer that evening! I also remember some very good dancers discussing the problems of DMD in the bar that night and trying to guess how long it would take to find the gene. Don Wood, the MDA representative, will remember how much energy we all had for science and dancing.

The meeting in 1986 was particularly exciting when Lou Kunkel presented the pERT87 cloning, a technique that was to mark a crucial step in the identification of the gene. My group rushed back to the laboratory anxious to test it out on patients. We worked from the early hours until late at night every day of the week. MDA provided extra resources to enable many groups to collaborate so that prenatal diagnosis and carrier detection could be provided to families who wanted it as rapidly as possible.

TAKING NEW PATHS

The DMD gene was found six years after MDA had first encouraged groups to compete and work together to find the gene. This collection of scientists was now ready for the next challenge: What did the gene do? How could we develop therapy?

My own group went down a rather unconventional route and began to study proteins related to dystrophin (the one missing in people with DMD). Again, through the MDA Task Force on Genetics, together with the MDG and the Medical Research Council, we were able to secure funding to explore ways of compensating for the lack of dystrophin in DMD patients. Today, we have made substantial progress toward that goal and demonstrated that the protein utrophin can compensate for dystrophin deficiency in the mouse. The challenge now is to find ways to upregulate (increase production of) utrophin as a means of therapy for DMD, a move that is being very much encouraged by MDA.

In 1980, I did not even know what DMD was and I had never seen a person with the disorder. Today I understand much about the disease, from both scientific and personal sides through the many affected families I have met. As scientists, we have worked together as a team, and the patients and their families and friends have kept us going with their invaluable support and encouragement.

CONTINUING THE DREAM

This is a wonderful age in which to be a geneticist. The science is changing and progressing so fast from gene to clinic, that it is a real pleasure to be part of it. I have also been fortunate in having worked with so many good colleagues, many of whom have groups of their own and stay in touch.

I have had to reorganize my life to fit everything in over the last 15 years, but I have enjoyed every minute of it. I cannot work continuously from 7 a.m. until 7 p.m. any more because of the needs of my 9-year-old son, Nicholas, but we are a very organized family, which means not a single hour in the day is wasted.

My dream is to find that compound that upregulates utrophin so that a drug can be used for effective therapy of DMD. Not only will we have helped many DMD families, but I will finally have a good reason to collaborate with my husband, Steve Davies, a chemist working in novel drug synthesis!

My husband and I had the pleasure of watching Jerry Lewis in "Damn Yankees" on stage in London in June, thanks to a kind invitation from Bob Ross and Jerry Weinberg (MDA director of field organization). It was a truly inspiring performance, a result of much talent and devoted hard work. I shall certainly continue to take pleasure in giving the same dedication to MDA-supported research in the future.

Utrophin Researcher To Receive MDA Science Award

MDA-funded researcher Kay Davies is professor of genetics at Oxford University in England and one of the major figures in muscular dystrophy research since the 1980s.

On the heels of the announcement last November that her MDA-funded research team had made a significant advance involving a protein called utrophin, Davies has been named to receive MDA's first annual S. Mouchly Small, M.D., Scientific Achievement Award.

Davies, who grew up in the western English town of Stourbridge, recalls being fascinated by biology from a very early age. "I used to go around looking at the types of plants and insects and that sort of thing," she remembers. "It really captured my imagination."

As a young biomedical researcher, in the early 1980s she became part of the international coalition of MDA-funded scientists who shared information in an effort to speed the discovery of the Duchenne gene. (The gene was discovered by an MDA-funded team at Children's Hospital in Boston in 1986.)

In 1989, her research team identified a protein called utrophin. In early human life, Davies says, utrophin serves as a kind of infantile form of dystrophin, the crucial protein missing or deficient in the muscle cells of boys with Duchenne and Becker muscular dystrophies.

However, as the organism reaches adulthood, the utrophin protein serves its own distinct function. "We think it's a stabilizing protein at the neuromuscular junction," Davies says.

Subsequent research by Davies and others suggested that utrophin might have the potential to serve as a "substitute" for dystrophin, thus providing an alternative to the gene therapy approach for treating muscular dystrophy which requires a sophisticated delivery system to get thousands of copies of the dystrophin gene into muscle cells.

"We were thinking about the difficulty of targeting all muscles by delivering dystrophin," she says. "We thought perhaps we can upregulate [increase the amount of] a compensatory molecule."

In a study that was published last Thanksgiving in the journal Nature, Davies showed that mice receiving extra utrophin don't develop certain signs of muscular dystrophy, even if they don't have the normal protein, dystrophin.

Donald S. Wood, MDA director of science technology, said: "By showing how a protein made in muscles of people with muscular dystrophy can successfully stand in for missing dystrophin, these MDA investigators have pioneered an exciting new avenue for therapy."

Since that announcement, Davies' team has been working on the notion that a chemical compound -- a drug -- might be developed that will cause the cells to produce more utrophin.

"Getting the body to make more of something it already produces is a significantly easier feat than introducing something new," Wood said.

In addition, there is a possibility that additional utrophin genes could be delivered into the cells via gene therapy. Unlike dystrophin, utrophin is already made by the cells so chances of interference by the immune system are minimized.

This year, MDA created the S. Mouchly Small, M.D., Scientific Achievement Award in honor of the noted psychiatrist and educator who was MDA president emeritus and whose service to the Association goes back to its beginnings in the early 1950s. Small died last December.

In addition to conferring recognition for scientific achievement, the award provides the recipient with a $10,000 grant to expedite research.

Davies will appear on the 1997 Jerry Lewis MDA Labor Day Telethon to receive the award and provide up-to-the-minute information on utrophin.