ABSTRACT
Wilson’s definitive clinical and pathologic description of the disease was in 1912 [1]. The pathognomonic corneal ring was separately described by Kayser [2] and Fleischer [3] in 1902 and 1903, and it is likely that a number of earlier descriptions of progressive neurologic and hepatic disease represented the same syndrome; but Wilson’s 211-page monograph was not only a landmark, it also predicted that the causative agent was a toxin. A year later the increased content of copper in the liver was reported by Rumpel [4]. This critical element was rediscovered between 1929 and 1945 [5-7] and led to an important series of observations and hypotheses that made this disease so amenable to precise early diagnosis and effective treatment today. Bennetts and Chapman [8] observed that deficiency of copper in lambs produced a fatal demyelinating disease. This led to the demonstration by Mandelbrotte and colleagues [9] that there was an increased urinary excretion of copper in Wilson disease. Cumings reported on the increased content of copper in brain, as well as liver [10], and proposed that 2,3-dimercaptopropanol (British Anti-Lewisite, BAL) might be therapeutic by chelation of accumulated copper. This was effective in removing copper, but not practical for the
long-term therapy necessary. This problem was solved by the introduction of penicillamine therapy by Walshe in 1956 [11].
