Lasker~Koshland
Special Achievement Award in Medical Science

Award Presentation by Lucy Shapiro

Sir David Weatherall is the most respected clinical scientist of his generation. He has been knighted, his portrait hangs in the UK National Portrait Gallery, and there is an institute at Oxford that carries his name. Behind these accolades is a gentle, wry man with a deep passion for understanding the molecular basis of disease and its application to the health of his patients. Along the way, he has changed the training of physician scientists and medical practice in the developing world.

David was raised and educated in Liverpool. Upon completing his medical degree in the late 1950's, he was asked where he'd like to do his obligatory National Service. Being petrified of flying, fighting, and snakes, he opted for service in London. The British Army promptly sent him to Singapore where he first did a 6 month stint in surgery, after which his surgical boss told him that on no account should he be let loose as a surgeon. When he next moved on to spend 6 months on a medical service, he carefully explained to the powers that be that his only experience was in adult medicine. He was promptly put in charge of a children's ward. This turned out to be a seminal event not only in David's life and career, but an event that ultimately has had a significant impact on world health.

A critically ill young daughter of a Ghurka soldier appeared in David's ward with an undiagnosed illness that required regular blood transfusions. David diagnosed the illness as a specific genetic error in the child's hemoglobin, no mean feat at the time. He published the data that led to this diagnosis of this genetic defect and was nearly court- martialed for revealing that someone in the Gurkha regiment might have 'bad genes'. Upon being ordered not to do that again, David knew that his career was launched. David's lifelong passion has been to understand (and, yes, publish), diagnose, treat and manage thalassemias, diseases caused by aberrant hemoglobin.

David's quest to understand inherited blood diseases led him to Johns Hopkins University, where he began his remarkable work, along with John Clegg, to separate and identify the different forms of hemoglobin chains in patients suffering from thalassemias. This led to the surprising discovery, in those early days of research into the molecular basis of genetically inherited diseases, that some thalassemias result from unbalanced globin chain production. His continued work on patients with this disease at the University of Liverpool led to an important breakthroughÑthe correlation of a given genetic mutation with a disease. In 1971, David was contacted by a physician from Kingston, Jamaica whose patients were a family affected by α-thalassemias. David made the surprising discovery that the α-globin chain in this family was extended beyond the normal stop codonÑthe first report of a chain termination mutant. David also found that in some thalassemias, no α-chains chains are made—these still-born babies had a complete deletion of the gene encoding the α-chain: this was the first demonstration of a gene deletion in a human disease.

In 1974 he moved to Oxford as the Nuffield Professor of Clinical Medicine. The offer of the Chair was made and accepted by telephone and then he didn't hear a word for several weeks. Afraid that he had perhaps been hallucinating, he got his secretary to phone the appropriate dignitary at Oxford and was told "It was announced in the Times! What more does he want?"

Although a founding father of molecular hematology, David was never far removed from patients, and he transferred his fundamental laboratory discoveries to practical clinical applications that are now in world-wide use. These included the first DNA-based tests for pre-natal and post-natal diagnosis of globin abnormalities, the design of a technique to control iron overload in thalassemic patients, and a novel mode of treatment for children with thalassemias using transient transfusions through periods of maximum bone marrow expansion.

Throughout his career, David has been committed to the development of international health, working to develop partnerships between Oxford and Sri Lanka, Singapore, Vietnam, China, Thailand, Malaysia, and Kenya. With funding from the Welcome Trust, he trained people to deal with their local health problems, and not simply having scientists from developed nations swoop in, do some research, and go home to write glossy papers in high-profile journals. Rather, David envisioned and successfully implemented an economically feasible way of helping developing countries deal with endemic diseases. Notably, when he designed prenatal tests for the thalassemias, he established programs in third world nations to easily and effectively use this simple DNA technology, while always being mindful of the cultures of each country. When David retired as Governor of the Welcome Trust in 2000, instead of a grand farewell event, he chose to use the money towards equipping a new hospital in Sri Lanka.

In addition to being a compassionate clinician, a scholar, a scientist, and a devoted public servant, there is a completely different side to David—he is a committed and effective academic leader. As senior editor of the Oxford Textbook of Medicine, he helped set the standard for good clinical medicine. Then, during the 1980's, David began the work of putting together an institute at Oxford for early translational research—the first of its kind. This vision, of course, stemmed directly from his own lifetime of successful service as both a basic research scientist and clinician. During the necessary fund-raising efforts, he came up against Syndey Brenner who came to Oxford to review David's plans. Brenner is alleged to have opined that he was "skeptical of doctors mucking about in the laboratory." (Sydney has since come around on the issue). Nevertheless, in 1989, the Oxford University's Institute of Molecular Medicine was established, to "foster basic research in molecular and cell biology with direct application to the study of human disease". This Institute, renamed the Weatherall Institute of Molecular Medicine, focusing on areas of medicine from AIDS to malaria to cancer, has had, and continues to have, a major impact on the application of the molecular analysis of disease syndromes to the practice of medicine.

In 1992, David Weatherall was appointed Regius Professor of Medicine at Oxford University, the most prestigious honor in UK medicine. David has managed to lead an over-sized life with humility and kindness, and to provide a unique form of leadership that has inspired and empowered scientists, physicians, and health care providers around the globe.