Commentary: Landmark Articles on Copper in the Field of Human Health

In deciding on an appropriate paper for this topic, we had to first choose between copper deficiency and copper toxicity. Copper deficiency is a common problem in some animals species, but is rare in the human. It occasionally occurs on a dietary basis, bowel surgery basis, or overtreatment with anticopper drugs. It is also a major clinical problem in the rare inherited condition, Menke’s disease. Progress has been made in the understanding of Menke’s disease, particularly with the cloning of the gene responsible, known as ATP7A [1–3]. Thus, a landmark article could have reasonably been selected from the Menke’s disease area. Copper toxicity is also a common problem in some animals species (e.g. sheep), and is, again, rare in the human. It is a major clinical problem in the relatively rare inherited condition, Wilson’s disease. As in Menke’s disease, the gene responsible, known as ATP7B, has been cloned [4–6], and this knowledge is leading to a better understanding of the mechanism of the disease process. In choosing between the two diseases, we took into consideration that a major difference exists between Menke’s disease and Wilson’s disease, in that the latter is so effectively treated, while the former is not. In thinking about “impact on human health,” we felt it important to not only consider intellectual understanding of the disease process, but whether understanding has led to better treatment. This is clearly the case with Wilson’s disease but not with Menke’s disease. Therefore, we decided to choose a paper from the Wilson’s disease area, and to look at the entire scope of discovery so far, in choosing the paper most deserving of this reward. In deciding which contribution in Wilson’s disease to honor, we had many choices. We will briefly go through the major historical highlights for background purposes. Wilson himself, for whom the disease is named, obviously deserves enormous credit for bringing diverse neurological and hepatic observations together into the “hepatolenticular degeneration” syndrome [7]. But he had no hint that the disease was due to copper, so in our opinion, his work doesn’t qualify for this particular landmark, which deals with the impact of copper-related discoveries on human health. Kayser [8] and Fleischer [9] early observed the corneal abnormalities that bear their names (KayserFleischer rings) which have been very useful in diagnosis. Fleischer [10] even detected an increase of copper in these rings in a patient. However, there was no suggestion at this point that the disease was caused by copper. The key etiological role of copper was missed early and often, as investigators