The success of the folic acid antagonists proved that it was possible to block the growth of cancer cells, and antagonists were subsequently developed to inhibit the action of other cell nutrients such as the purines. Scientists call this the "antimetabolite" approach.
The substantial improvement in survival for some of the rarer forms of cancer, especially childhood leukemia and Hodgkin's disease, again depends on clinical research. Treatment depends on using a combination of agents which, together, have an improved effect over individual drugs. In his book Principles of Cancer Treatment (1982), Dr Steven Carter describes how many effective drug combinations emerged by trial and error in human studies and not because they were predicted to work by animal tests. It could hardly have been otherwise, because, as Carter explains, "while much work has been done testing drug combinations in rodent tumors, no system with established predictability has been illuminated."
Clinical research has also played a key role in developing heart drugs. The use of digitalis as a heart stimulant has a long history and derives from folklore reports that the foxglove plant could cure "dropsy." In 1775, the English physician William Withering commenced a long series of trials using digitalis extracted from the plant.(21) He believed the only way to test the efficacy of herbs was to administer them to the sick. Withering proved the value of digitalis in treating dropsy, which was later shown to be a symptom of heart failure. In 1905 further clinical studies showed that digitalis could also be used to treat atrial fibrillation,(22) a condition in which the heart beats in an irregular and chaotic fashion. Nowadays, doctors rely on digitoxin and digoxin, pure substances extracted from digitalis but which perform the same function. They are still regarded as amongst the most valuable drugs for heart failure.
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