This article was inspired by my reading of The Emperor of All Maladies: A Biography of Cancer, by Sid-dhartha Mukherjee, M.D. (1) and in particular, by reading two reviews of the book by scientists whom I admire (2, 3). These reviewers were transfixed, as was I, by accounts in the early chapters of Sidney Farber and his use of folic acid analogs, beginning in 1947, in the experimental treatment of acute lymphocytic leukemia in desperately ill children. However, both reviewers and I were struck by how little information was presented about mechanisms of action of the early antimetabo-lites, including the folate analogs used by Farber, and at how many of those early antimetabolites were mentioned only briefly, if at all. Gertrude Elion and George Hitchings at Burroughs-Wellcome rate a page for their synthesis of 6-mercaptopurine (6-MP) and other purine analogs, but Charles Heidelberger, who synthesized 5-fluorouracil (FU) and 5-fluorodeoxyuridine (FUdR), receives no mention at all.
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