In 1941, with the Second World War well underway, the Allies captured a German submarine that was returning from Argentina with an unusual cargo — a meaty mass that resembled adrenal glands, the two grape-sized organs that sit on top of kidneys and that produce the hormones adrenaline and cortisol, among others.
A rumor quickly spread around American military circles that the Nazis were injecting their pilots with an adrenal extract to make them resistant to stress and capable of zooming around at altitudes above 40,000 feet, unaffected by low oxygen levels.
By October, the buzz was so loud that the army requested a conference with leading scientists to discuss the potential development of similar hormones of the adrenal cortex. The American government made it their third research priority, after penicillin and antimalarials.
Edward Kendall, a chemist at the Mayo Foundation in Rochester, Minnesota, and a self-described "hormone hunter," turned his attention to extracting a "crystalline organic substance" from the adrenal cortex, which he named cortin. Kendall famously spent every single day in his lab, Christmas included. His workaholism was no doubt due in part to his competition with a Polish-Swiss chemist, Tadeusz Reichstein, who was attempting to purify the hormones of the adrenal cortex in his Zurich lab. Both men announced success at nearly the same time. In 1935, Kendall isolated five compounds from bovine adrenal glands, including compound E (cortisone) and compound F (cortisol). In 1936, Reichstein isolated seven compounds, also including cortisol and cortisone (it would later be discovered that cortisone was actually a metabolite of cortisol).
The Confounding Road to Compounds E and F
Accelerated wartime efforts to synthesize compound E finally met success in 1944. In what was called "the world's most complex chemical synthesis," a scientist working for Merck & Company obtained cortisone from cattle bile in 36 chemical steps. By 1948, Merck had spent over $13 million on the development of compound E but had no disease to use it on, leading Kendall to mark the year as a "low point."
In the late 1930s, Hench would occasionally meet with Kendall and would discuss his search for substance X. In January 1941, when Kendall mentioned that his cortin, or compound E, made some animals more resistant to post-typhoid vaccine reactions, Hench scribbled in his notebook to try it on arthritic patients. It took 7 more years, however, until he conducted the experiment. He discovered that his mysterious substance X and Kendall's elusive cortin might be the same thing.'
The First Patient
Mrs Gardner, a 29-year-old from Kokomo, Indiana, was so badly affected by rheumatoid arthritis that on most days the pain wouldn't allow her to walk or even get out of bed. She was staying at Saint Mary's Hospital in Rochester, Minnesota. She demanded to be treated with every experimental drug possible and refused to be discharged until she got better. On September 21, 1948, she received initial injections of large doses of compound E, even though one of her doctors called it an "absurd idea." Hench didn't expect it to work, either.
At first, nothing seemed to happen, yet after 4 days of treatment, Mrs Gardner's pain was completely gone. When Kendall visited her room, he found her exercising, lifting her hands up over her head — a feat she had been previously incapable of.
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