Professor C. David Marsden died suddenly on September 29, 1998, from an unsuspected congenital coronary anomaly. He was 60 years old.
The untimely death of this outstanding neurologist and—for me—close friend and colleague came as a shock to all of us in the neurologic and neuroscience community who admired his enormous accomplishments and anticipated that he would have many more productive years. Just a month ago, he arrived at the National Institutes of Health, in Bethesda, Md, from the National Hospital at Queen Square in London, England, to begin a year's sabbatical. He planned to conduct a detailed clinical study of apraxia and to have an active teaching schedule.
David was a pioneer and leader in the field of movement disorders as well as a superb general clinical neurologist and teacher. His interest in the basal ganglia started in medical school, where his thesis had been on the comparative anatomy of the substantia nigra in mammals. This phylogenetic study showed that the nigra is largest, most pigmented, and best developed in humans. It resulted in the publication of his first full scientific paper, in the Journal of Anatomy. At the time of his death he had authored or coauthored some 800 full papers, 200 book chapters and books, and more than 60 invited reviews. He was not only prolific, but also profound. He was the most frequently cited clinical neuroscientist, and among the 10 most cited biomedical scientists in the world.
David was born on April 14, 1938, the son of an English surgeon. After Cheltenham College, he went to medical school at St Thomas' Hospital at the University of London, graduating in 1963. Having published several other neuroanatomical papers, and while still in medical school, he started investigations in neurophysiology, beginning with measurements of parkinsonian tremor. This was the forerunner of his great passion for human neurophysiology, a field in which he was a world leader and had trained many outstanding motor control physiologists.
After winning a number of honors and awards during his medical school days, he went on to specialize in neurology, first at St Thomas' and then at the National Hospitals for Nervous Diseases at Maida Vale and Queen Square, completing his training there in 1970. By then he had published 30 full scientific papers, 3 invited reviews, and 2 book chapters. In 1972, at age 34 and just 2 years postresidency, he competed for and won the appointment of professor of neurology and head of the new University Department of Neurology then being established at the Institute of Psychiatry and King's College Hospital Medical School. While his new laboratories were being constructed, he traveled to the United States, visiting various Parkinson disease research centers. On that trip, he spent several days at the University of Pennsylvania, where I was then located. From that point on, we became good friends.
To join him in his new department at the Institute of Psychiatry, David recruited 2 junior scientists who remained his close collaborators until his death, and who became, in time, world leaders in their own right—pharmacologist Peter Jenner and neurophysiologist John Rothwell. Working with David and other associates and trainees, they produced a prodigious number of papers on the physiology, pharmacology, and biochemistry of Parkinson disease, tremor, dystonia, and myoclonus. With his colleagues, David described new movement disorder syndromes such as painful legs/moving toes, abdominal dyskinesias, jumpy stumps, reticular reflex myoclonus, cortical myoclonus, propriospinal myoclonus, and primary writing tremor. Through his insight, David brought together under the single heading of focal dystonias many disparate entities previously thought to be unrelated and not even considered dystonia at that time, such as blepharospasm, spasmodic dysphonia, torticollis, and writer's cramp. By doing so, he brought order into the spectrum of dystonia.
While at the Institute of Psychiatry, David attracted postdoctoral trainees in movement disorders from more than 20 countries, and many became leaders in the field. These include Mark Hallett from the United States, Tony Lang from Canada, Jose Obeso from Spain, Philip Thompson from Australia, and Niall Quinn from London.
In Parkinson disease, David analyzed the motor complications from levodopa, and worked on new drug development, testing them in the clinic. I don't think there is an anti-Parkinson drug that David and his team have not worked on. He established the UK Parkinson's Disease Society's Brain Bank, which ultimately provided the tissues for many pathological and biochemical investigations. In dystonia, myoclonus, and essential tremor, he pioneered studies on motor control physiology and investigated new treatments.
In the biochemistry of Parkinson disease, David and his associates discovered the mitochondrial defect in the substantia nigra, and showed it was specific to Parkinson disease and not present in other forms of parkinsonism. They demonstrated the presence of oxidative stress in the substantia nigra in postmortem parkinsonian brains. They developed the novel idea of studying brains of individuals with incidental Lewy bodies discovered at post mortem, identifying this condition as the preclinical state of Parkinson disease, and thereby detected the earliest biochemical change in the nigra—a decrease of the important antioxidant, reduced glutathione. David teamed with David Brooks, and they became leaders in fluorodopa positron emission tomographic scanning and used this methodology to demonstrate the growth of embryonic tissue transplants in patients with Parkinson disease.
In 1987, David moved from the Institute of Psychiatry to the Institute of Neurology at the National Hospital for Neurology and Neurosurgery at Queen Square as professor and head of the University Department of Clinical Neurology. He teamed up with Anita Harding and several younger colleagues to study genetics in dystonia, mitochondrial disorders, and Parkinson disease. In 1995, he was elected dean of the Institute of Neurology, University of London, with the plan to have Anita take over as head of the Department of Clinical Neurology. Anita's death from rapidly progressive cancer was traumatic for him. His tenure as dean came at a critical period, and David was effective in saving the National Hospital from being dismantled by National Health Service cost-cutters. He was happy to step down from the deanship, which he did on August 31, 1998, and then began his sabbatical leave at the National Institutes of Health.
For his outstanding research in neuroscience, David was elected a Fellow of the Royal Society in 1983, and in the following year was awarded the honorary doctor of science degree from the University of London. Honors in the United States included being named the Robert Wartenberg Lecturer of the American Academy of Neurology in 1982 and the F. E. Bennett Lecturer of the American Neurological Association in 1994. He won the Fred Springer Award of the American Parkinson's Disease Association in 1991 and the James Parkinson Medal from the Parkinson's Disease Foundation in 1997. He was honored with lectureships in many universities around the world and was elected an Honorary Member of the Sociedad Español de Neurologia, the Societé Français de Neurologie, the Italian Society of Neurology, and the American Neurological Association. He cofounded and served as second president of the Movement Disorder Society. He served 10 years as editor of both the Journal of Neurology, Neurosurgery and Psychiatry and the journal Movement Disorders. He has also served on the editorial boards of 21 other journals and on medical and scientific review boards for Parkinson disease, dystonia, and myoclonus foundations.
In addition to his scientific accomplishments, David was a fantastic teacher across the breadth of neurology. His store of knowledge was phenomenal, and he was able to sift through the clinical facts to come up with accurate diagnoses. It was always pure joy to watch him discuss obscure cases, which I was fortunate to observe in our 17-year joint running of the Unusual Movement Disorder Seminar at the American Academy of Neurology.
David excelled in just about everything he decided to engage himself in, including sports of all sorts. I recall his attending the annual picnic of neurology attendings and residents at the University of Pennsylvania, which took place at the time he was visiting us. He joined the softball game on the side of the faculty. The first time at bat, he backed away from the plate and swung cricket style, trying to hit the ball as if were next to the ground. We told him the ball is to come across the plate in the strike zone, from where he should hit it. The residents all laughed and moved in close. Well, on the next pitch, David tore into the ball, and it sailed over the outfielders' heads for a home run. Other pleasures were sailing, country dancing, and gardening; he specialized in the cultivation of fuchsias. Most recently he took up golf, to which he was fast becoming addicted.
His death leaves his family, friends, and colleagues with great sadness, and a major void in research and leadership in movement disorders. We trust that those he trained and with whom he worked will continue making progress, and that these accomplishments will extend his remarkable legacy. His death is simply a tremendous loss to our field, as well as a personal loss for many of us.
Thank you for giving me the opportunity to memorialize David Marsden, a giant among neurologists.