Abel, Takamine, and the isolation of epinephrine.

In the second half of the 19th century, medical researchers paid increasing attention to the so-called ductless (endocrine) glands. In 1848, German physiologist Arnold Berthold provided the first evidence that one of these glands could secrete a physiologically active substance directly into the bloodstream. A castrated rooster normally exhibited a shrinking of its comb, but Berthold showed that this shrinking did not occur if the excised testes were transplanted into the abdominal cavity. He suggested that the testes must be secreting some substance into the blood that affected the comb. Shortly thereafter, the research of other investigators, such as Charles-Edouard Brown Sequard in France, suggested that other ductless glands, such as the adrenal glands, might also secrete physiologically active substances into the bloodstream. Toward the end of the century, a number of glandular secretions were introduced into medicine as a form of ‘‘organotherapy.’’ Brown-Sequard believed that he had developed a testicular extract from animals that was capable of rejuvenating elderly men, although it was soon shown that his conclusions were erroneous. In the 1890s, Eugen Baumann in Germany had some success in the treatment of goiter with thyroid extract. In 1894, George Oliver and Edward Schäfer of the University of London reported that they had produced an extract of the adrenal gland that had a strong action on the blood vessels, the heart, and the skeletal muscles. Several investigators set out to try to isolate the active principle of the adrenal extract in a pure form. The successful isolation of this substance, epinephrine (or adrenaline), the first hormone to be isolated in a pure state, involved a certain amount of controversy over priority. Before discussing this complex history, however, it will be useful to provide some biographic background on the 2 main protagonists, John J. Abel and Jokichi Takamine.