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The adrenal gland was first described by Eustachio in 1564, but its physiologic role remained unknown for three centuries. In the late 1890’s, many researchers had directed their attention to the isolation of adrenal extracts, but all failed until the successful efforts of biochemists Jokichi Takamine and Keizo Uenaka. Takamine’s patents on Adrenalin were the first ever awarded for a hormone and he used his royalties to improve international relations between America and Japan. There is considerable controversy, however, in how adrenaline was first crystalized, where the work was done, and to whom the credit for its discovery is given. Sources and Methods: Published contemporary medical literature, newspaper archives, and publicly accessible research archives in Japan, Sweden, and the United States Results: Takamine was a multilingual businessman with a background in western and eastern medicine, a successful biochemist, and importer/exporter before he took on the project of isolating adrenaline. His successful patents and savvy business acumen allowed him to support innovative research in physiology. He hired Keizo Uenaka, who had experience with isolating ephedrine, to develop the critical methods required to crystallize adrenal extracts where other contemporaries, including Takamine, had failed. Takamine applied for and was awarded five immediate US patents for the discovery although he did not include Uenaka in that effort. Takamine co-founded the Nippon Club and the Japanese Society of New York, both of which ultimately survived the anti-Japanese fervor of the 1940s and, in 1912, worked to bring the gift of 3,000 Japanese Cherry Trees to Washington DC. The Japanese Patent Office honored Takamine as one of Japan’s 10 Great Inventors but it was only after Uenaka’s death in 1960, and the discovery of his laboratory manuals, was Uenaka’s full role in the discovery of adrenaline made known. Conclusions: Jokichi Takamine was an international benefactor and biochemist extraordinaire who, with Keizo Uenaka, was the first to crystallize adrenal medullary catechols. Takamine’s efforts saved lives and did much to engender a spirit of Japanese-American goodwill that persisted for decades.

Adrenaline Rush: the race for the crystallization of adrenal extracts by Takamine and Uenaka