Denny-Brown and British Anti-Lewisite
(BAL, [2,3-Dimercaptopropanol]): The first curative treatment for Wilson's
Disease (Hepatolenticular Degeneration)
Joel A. VILENSKY1, Wendy M. ROBERTSON2, and
Wilson's disease is a neurological disorder characterized by tremors, ataxia, rigidity, ballistic movements, dystonia, drooling and speech defects, and is now known to result from insufficient bilary copper excretion. Copper accumulates preferentially in several body structures, particularly the liver, brain and cornea. Cumings (1948) first demonstrated copper accumulation in Wilson's disease, and he stated, based on a study by Mandelbrote et al. (1948) of BAL (a chelating agent developed as an antidote to arsenic poisoning after WWI) that BAL might be useful in treating Wilson?s disease.
Derek Denny-Brown (1901-1981) was Director of the Neurological Unit of the Boston City Hospital (affiliated with Harvard University) at this time and had many Wilson's disease patients. After Cumings' report Denny-Brown, with the assistance of Huntington Porter (a research fellow), conducted the first clinical trial using BAL to treat five patients with Wilson's disease. The results of the trial were presented at the American Neurological Association's Meeting in 1951 and described in an article that appeared that year in the New England Journal of Medicine (NEJM). Denny-Brown also filmed these patients and showed sequences of them before and after treatment at the meeting (these films are currently in our possession and sequences from the films will be depicted with our presentation).
It is clear from the NEJM article that Denny-Brown was very unsure of dosages and frequency of BAL applications, which were injected intramuscularly. Nevertheless, the results were striking. The tremors and rigidity disappeared and previously mute patients could speak.
Unfortunately, BAL alleviated symptoms only temporarily. The injections had to be repeated every few months, and they were expensive and painful, and lost their effectiveness over time. Nevertheless, BAL continued to be used in Boston and at other major medical centers (e.g., New York) until 1956 when Walshe introduced a safer and more effective chelating agent, Penicillamine.
Although relatively short-lived in its application, Denny-Brown's demonstration of the effectiveness of BAL constituted a major innovation in the treatment of movement disorders, as it was first curative (rather than palliative) treatment devised for such a disease.
Session VII -- Famous People and Disease
Los Angeles, California, USA