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The Right Chemistry: The discovery of testosterone

Koch’s intent was to study substances the testes released into the bloodstream that produced effects elsewhere in the body. The term “hormone” for such chemical messengers had been coined back in 1902 by the English physiologists William Bayliss and Ernest Starling from the Greek for “stir into action.” This was prompted by their discovery of “secretin,” a substance that stimulates the flow of digestive juices from the pancreas after being released by the small intestine in response to the entry of food. A half-century earlier, Arnold Adolph Berthold had unknowingly laid the foundation to hormone research by demonstrating that a rooster’s comb withered upon castration and that re-implantation of a testicle into the body cavity caused the comb to flourish again.Most Popular Steroids Materials

In the 1880s, Harvard professor Charles-Édouard Brown-Séquard was intrigued enough by that observation to inject himself with an extract produced from the testes of dogs and guinea pigs with hopes of rejuvenating himself. There were some transient effects, but Brown-Séquard dropped this line of research in part due to being ridiculed by the scientific community. Long before Berthold and Brown-Séquard, ancient Greek athletes experimented with hormones. There are accounts of some athletes in the ancient Greek Olympiads consuming sheep testicles to improve their performance.

Professor Koch aimed at building on the work of his scientific predecessors, and although he had plenty of bovine testes to work with, he needed hands to do the tedious extraction. Luckily, university professors are blessed with a natural resource available to them, namely, students. Koch recruited a number of them to mash the testicles, extract them with a solvent, and separate the components by column chromatography. Eventually, from 40 pounds of testes the professor and his students managed to isolate 20 milligrams of a substance that when administered to castrated roosters, pigs and rats had the effect of re-masculinizing them.

Serious research on the identification of this substance had to wait until more significant amounts became available. That happened when pharmaceutical companies became interested in the therapeutic potential of such testicle extracts, with researchers at the Dutch company Organon finally managing to isolate a crystalline form of the hormone. They named the compound “testosterone,” paying homage to its origin and the fact that in terms of molecular structure it was in the “sterol” category. The exact structure of the molecule was worked out by Adolf Butenandt, then at the Schering pharmaceutical company. Once the structure was identified, Butenandt developed a chemical synthesis starting from cholesterol. A similar synthesis was carried out independently by Leopold Ruzicka at the Ciba company who went on to share the Nobel Prize for chemistry in 1939 with Butenandt. While Butenandt made stellar contributions to chemistry, including the discovery of bombykol, the pheromone of the silkworm moth, his legacy is tainted by his involvement with the Nazi party.
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