The Quest for Cortisone

Chapter 8. Kendall Strikes Out Again

67 Chapter 8 Kendall strikes out Again It is a capital mistake to theorize before one has data. Insensibly one begins to twist facts to suit theories, instead of theories to suit facts. —sherLoCK hoLMes, “A sCAnDAL in BoheMiA” By 1931 the Great Depression was finally easing, but now hemingway was getting vexed. his latest manuscript, which would eventually be called Death in the Afternoon, was coming along well enough. But his friendship with f. scott fitzgerald was not. ernest hemingway and f. scott fitzgerald had met for the first time at the Dingo Bar in Paris in April 1925, shortly after the publication of The Great Gatsby. They initially became friends—drinking, exchanging advice, and offering support for each other’s careers. Their friendship later turned uncomfortable.1 fitzgerald’s wife, Zelda, disliked hemingway immediately, describing him in very negative terms and suggesting that his macho quality was “as phony as a rubber check.”2 she became delusionally convinced that hemingway and her husband were having an affair, which if true would have certainly been the antithesis of their testosterone-driven images. Zelda fitzgerald and ernest hemingway turned out to have more in common than the handsome Mr. fitzgerald—they would ultimately share mental illness, repeated institutionalizations, and various forms of antipsychotic convulsive therapy.3 By1931severalkeyscientificplayersintheunfoldingcortinsaga—russell Marker, Philip hench, edward Kendall, and Albert szent-Györgyi—were, 68| Chapter 8 like ernest and Zelda, moving along separate paths that would eventually converge in unpredictable ways. russell Marker, now established at Pennsylvania state university, was just beginning his work on steroids. he was particularly interested in progesterone , which was not only an important hormone in its own right but also a key ingredient in the manufacture of many other steroids. Parke-Davis (which provided the adrenal glands for Kendall’s work) was helping Marker in his efforts by supplying him with the necessary precursors of progesterone , most of which involved derivatives made from horse urine. Philip hench was in hot pursuit of new treatments for rheumatoid arthritis. he monitored reports of every novel therapy purported to offer a chance of helping the disease: fever therapy (typically produced by typhoid vaccine or bee stings); radiotherapy; injections of gold, olive oil, or histamine; dietary changes; vitamin therapy; bone marrow stimulation; and even tonsillectomy. one treatment in particular caught the Mayo rheumatologist ’s interest: the use of a liver toxin called cinchophen.4 its administration seemed to help some patients, but not others. The mechanism of action was not known, but it produced jaundice in many patients. Philip hench couldn’t stop thinking about the relationship he had observed in the past between jaundice and the relief of rheumatoid arthritis. he continued to collect and report on additional patients with jaundice-induced remission of rheumatoid arthritis. edward Kendall was busy building the required laboratory infrastructure for this type of research. his most pressing problem? if he wanted to make a serious foray into the search for cortin, Kendall realized he needed the capacity to measure cortin’s biological activity. This was an area of physiological expertise he did not possess, and for once the chemist seemed to understand that he was only as good as the people with whom he worked. he solved his problem by hiring Dwight ingle in 1934. According to Kendall , ingle was “endowed with an insatiable urge to find out why certain things are so. one of these things was . . . the endocrine glands.”5 ingle had been trained in psychology at the university of idaho, and later at the university of Minnesota, but he aggressively pursued studies in physiology after becoming convinced that psychological diseases were really manifestations of Kendall Strikes Out Again| 69 physiological problems. in an attempt to better understand the actions of certain newly discovered hormones, ingle developed his own unique techniques and devices for assessing the physiological activity of these compounds. one apparatus ingle invented required the use of an anesthetized rat; the rat’s leg muscles were electrically stimulated, causing them to twitch, and the strength of the twitch was measured. With this device the ability of various drugs to affect muscle function could be tested.6 Previous work had shown that removal of the rat’s adrenal glands caused the electrically stimulated muscles to cease twitching in less than twenty-four hours.7 But when cortin-containing solutions, such as those produced by Pfiffner and swingle, were given to the...