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From Poison Gases. Chemotherapy, broadly defined, got its biggest boost in 1941, when Chicago's Dr. Charles B. Huggins reported that prostate-cancer victims did better and lived longer after castration. The important thing was not the surgery, but the chemistry—removal of the main source of male sex hormones. Similar but less marked benefits resulted from "chemical castration" by administration of a female hormone. In women, some recurrent breast cancers were retarded by female hormones and others by male hormones. But these treatments relied on natural body chemicals, not synthetic magic.
The transition came in World War. II with nitrogen mustard—synthesized for use as a poison gas. Cancer researchers began testing it. found that it killed cells in rough proportion to their rate of reproduction. Though it killed the cancer cells faster than the normal, it was still highly poisonous, could be given (by intravenous injection) only in small doses. And eventually the cancer cells became resistant to it. History has sadly repeated itself with scores of chemicals of this class (technically "alkylating agents") developed since. About 20 are credited with definite but limited usefulness.
More ingenious than simply poisoning the cancer cell was the idea that it might be fooled into accepting, instead of a normal food substance (metabolite), an analogue (close chemical kin) to fill the metabolite's place but yield no nourishment. First to use antimetabolites this way was Dr. Sidney Farber of Boston Children's Hospital and the Children's Cancer Research Foundation. Knowing that leukemic cells are avid for the vitamin folic acid, he began in 1947 to treat child victims of acute leukemia with analogues of folic acid. Lederle Laboratories sent Dr. Farber two, aminopterin and amethopterin. which soon brought about improvement in most of the children. But after weeks or months, their disease became resistant.
In quick succession came the hormones ACTH and cortisone, which also produced brief remissions in acute leukemia (as in some other cancers of the blood and lymphatic system). Then came another antimetabolite. pioneered by Dr. Joseph H. Burchenal of Memorial Center: 6-mercaptopurine, which interferes with cell nutrition by supplying a counterfeit purine. Physicians treating acute leukemia now ring the changes on these, using one until it loses its effect, then switching to another, sometimes back to the first. No child victims of acute leukemia have yet been saved, but Dr. Farber can report a heartening gain. A dozen years ago, young leukemia patients lived an average of only three or four months, mostly in misery, after their disease was diagnosed. Now the average is at least a year; some live two or three years, and a few still longer. During their remissions the children appear healthy, spend most of their time at home playing happily.