The Quest for Cortisone
Publication Year: 2012
In 1948, when “Mrs. G.,” hospitalized with debilitating rheumatoid arthritis, became the first person to receive a mysterious new compound — cortisone — her physicians were awestruck by her transformation from enervated to energized. After eighteen years of biochemical research, the most intensively hunted biological agent of all time had finally been isolated, identified, synthesized, and put to the test. And it worked. But the discovery of a long-sought “magic bullet” came at an unanticipated cost in the form of strange side effects. This fascinating history recounts the discovery of cortisone and pulls the curtain back on the peculiar cast of characters responsible for its advent, including two enigmatic scientists, Edward Kendall and Philip Hench, who went on to receive the Nobel Prize. The book also explores the key role the Mayo Clinic played in fostering cortisone’s development, and looks at drugs that owe their heritage to the so-called “King of Steroids.”
Published by: Michigan State University Press
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Title Page, Copyright
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Nobody moves to Minnesota for the weather. This observation is as true today as it was on August 21, 1883. The weather in Rochester had been pleasant that morning, but over the course of the afternoon it turned oppressively hot, humid, and hazy. Dr. Will Mayo, twenty-two years old and recently graduated from medical school, had spent the day seeing patients. His eighteen-year-old brother, Charlie, was tagging along...
Chapter 1. Addison and His Disease
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At two o’clock the afternoon dinner bell rang. Dr. Thomas Addison was ambling through the well-manicured garden outside his home, accompanied as always by two watchful “companions.” Unfortunately, the thought of English cuisine again was more than his fragile psyche could handle today; he suddenly broke away from his attendants and hurled himself over a dwarf-wall, diving headfirst onto the stone pavement nine feet...
Chapter 2. Introducing Dr. Kendall
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Edward Kendall took a sample of his highly concentrated acid-insoluble thyroid extract and dissolved it in a small amount of ethanol.1 He placed the glass vessel holding the aromatic concoction into a steam bath and stared as the solution began to slowly boil away. It was mesmerizing. For most chemists, this procedure, commonly called “chemical extraction,” was as boring as a high school production of...
Chapter 3. Life After the Thyroid
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With his work on the thyroid unceremoniously usurped and finished by rivals, Kendall began contemplating a new adventure in alchemy. Unfortunately, the forty-year-old chemist was trapped in research limbo; a decade of thyroid study had forced him to focus his considerable expertise on an extremely narrow aspect of glandular biochemistry, and like the proverbial “top specialist in the field,” he’d learned “more and more about less...
Chapter 4. Introducing Dr. Hench
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There are a million jokes that begin with “A man walks into a . . .” We generally assume they are fictitious: the possibility that such an event actually took place sometime or somewhere seems ludicrous, and yet the following story, which has been repeated for decades in various forms as a joke, appears to have actually occurred. Reliable witnesses and independent sources swear this happened—more or less exactly as described.1 Even if it is not true, it should be....
Chapter 5. Nice Guys, Saints, Eccentrics, and Geniuses
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There are people connecting the dots between cortisone, the Mayo Clinic, and the Nobel Prize without whom this story cannot be told. These characters weave in and out of the tale in a manner that initially seems erratic and perhaps even superfluous, but they are ultimately as important to the outcome as any of the main players. Some of these “supporting actors,” like Percy Julian, Russell Marker, and Tadeus Reichstein,...
Chapter 6. 1929 and the Decision to Hunt for Cortisone
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The Great Depression kicked off with the stock market
crash on Black Tuesday, October 29, 1929, and as a result most of the civilized
world was soon feeling depressed.
But not Ernest Hemingway. Life in 1929 was going surprisingly well for the testosterone-stoked writer. “Demon Depression,” which typically followed him as surely as the darkness of night follows day, could only bide its...
Chapter 7. Another Kendall False Start, Another Great Announcement
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For Percy Julian, the 1930s brought nothing but good news. After graduating from DePauw University in 1920 as class valedictorian, Julian earned a master’s degree from Harvard in 1923 and then moved to Austria (with funding from the Rockefeller Foundation), where he obtained his PhD from the University of Vienna. His doctoral thesis focused on the medicinal chemistry of various plants. With his degree in hand, he returned to...
Chapter 8. Kendall Strikes Out Again
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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...
Chapter 9. Kendall Presses On
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Geraldine Smithwick, a senior at the University of Chicago, thought she was having a good year, but it turned out she was wrong—she just didn’t know it yet. She’d recently married Luis Alvarez; the young physicist from Rochester had passed his oral exams and received his PhD a few days earlier. In a month they would be heading off to his new job in Berkeley, California. But soon the war would separate the beautiful socialite from the scientist; they’d grow apart and eventually get a divorce....
Chapter 10. Score: Szent-Györgyi–1; Kendall–0
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Winning the Nobel Prize triggers an emotional, visceral response, and for Albert Szent-Györgyi, the October 1937 announcement that Sweden’s Karolinska Institute was bestowing the Nobel Prize for Physiology or Medicine on him was truly overwhelming. The award, honoring “his discoveries in connection with the biological combustion processes...
Chapter 11. Transitions and Travels
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Albert Szent-Györgyi was immersed in transition and travel—all of it distinctly unwanted. He spent the early part of the decade on the faculty of Szeged University in Hungary, where he probed the fascinating mystery of muscle metabolism. But as the 1940s approached, the scientist became dangerously outspoken in his anti-Nazi, antifascist politics. Szent-Györgyi...
Chapter 12. War Looms
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The world was learning just how “unmusical” German could be. World War II began with the invasion of Poland on September 1, 1939. British prime minister Neville Chamberlain, in an address later that day, summed up the sense of hopelessness much of the world was feeling at the moment:...
Chapter 13. Hench Meets Kendall
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The Japanese attacked Pearl Harbor on December 7, 1941.
The United States was now knee deep in a war on two fronts.
Luis Alvarez was doing his part at MIT, developing the radar systems that would prove critical to the war’s outcome. But as the spring of 1941 approached, all he could develop was abdominal pain.1 Mild and intermittent at first, the pain slowly worsened. Meals, especially fatty ones, became...
Chapter 14. World War II and Military Steroid Research
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World War II was stimulating research in steroids. Unfortunately,
it was often the ugliest research imaginable, and as the 1930s came
to a close the cortin story was taking a short, unpleasant digression down
the wrong path.
Rumors continued to buzz about Nazi interest in cortin and the possibility that the Nazis were isolating the substance from Argentinean beef...
Chapter 15. Plants, Politicians, and More Pessimism
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Percy Julian was becoming to the soybean what George Washington Carver was to the peanut. Julian had recently discovered a protein in soybeans that could be used to coat paper and make it less flammable. His superiors at the Glidden Company passed some of this soy protein along to a Pennsylvania laboratory; the lab used it to create a fire-retardant product...
Chapter 16. Good-bye Marker, Hello Sarett
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The world was still at war in early 1945. But not for long.
On July 16, 1945, Luis Alvarez witnessed his latest contribution to the war effort from the seat of a B-29.1 At an altitude of 30,000 feet and a distance of approximately fifteen miles, he watched as the detonator he had designed triggered the first nuclear explosion at the Trinity Site in Alamogordo, New Mexico. Alvarez could not find words to describe the
Chapter 17. Hench Returns to Mayo
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World War II was over; life was beginning to return to normal; and, just like his idol Sherlock Holmes, Philip Hench was beginning to care once again for the little things. Colonel Hench left the army in 1946, although he remained a consultant to the army surgeon general for matters relating to rheumatology.1 Now it was time to get back to his real work and interests. Compound E was still unavailable, so Hench pursued the yellow...
Chapter 18. Push On? Give Up?
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The years 1946 to 1948 were quite possibly the worst in
Edward Kendall’s entire life. Personally, he’d suffered the tragic loss of two
grown sons. Professionally, his research on cortin was going down in flames.
The “war committee” of the National Research Council (NRC) had made adrenal cortical research its number one priority, and, as noted previously,...
Chapter 19. The Decision to Test Compound E on Rheumatoid Arthritis
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Charles Slocumb had become the Mayo Clinic’s second rheumatologist in 1931; Howard Polley joined up as the third in 1942.1 The two junior men had faithfully supported Phil Hench’s research into new ways to treat rheumatoid arthritis. The latest effort involved the use of lactophenin, the liver toxin from Sweden that caused jaundice in many patients and relieved arthritis symptoms in some.2 These reports had stimulated Hench’s...
Chapter 20. The Amazing Mrs. G.
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Mrs. G. received her first injection of compound E in the early evening on September 21, 1948. Dr. Slocumb provided the 50 milligram injection; he was in charge of Dr. Hench’s hospital service, and would be overseeing the day-to-day care of Mrs. G. and the other patients hospitalized with rheumatological disorders.1...
Chapter 21. A Promising Start
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Dr. and Mrs. Hench departed for their ten-week trip to England on September 28, 1948, just seven days after Mrs. G.’s first dose of compound E. Although Hench’s trip had been set in stone for months, the events of the previous week mandated a slight change of plans. He made a short side trip to New York City en route to London, and there he met with two important corporate people: Dr. James Carlisle and Dr. Augustus Gibson.1...
Chapter 22. The Bad and the Ugly
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The apparent success of cortisone immediately created problems, and honoring Hench’s instructions to keep the trial a secret from the public—and his professional colleagues—was among the most pressing of these. A simple error in logistics was threatening to unveil their clandestine activities. What error? Hospital room assignment. Mrs. G. had been given the wrong hospital accommodations for an experiment of this type....
Chapter 23. Progress and Setbacks
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In mid-December 1948 Philip Hench returned to Rochester from his highly successful lecture series in England. Patient number five, the “make or break” subject upon whom the board of governors wanted to conduct a double-blind placebo-controlled study, had just been admitted to the Metabolic Study Unit at Saint Marys Hospital. This would be Hench’s first opportunity to follow a patient through a cycle of treatment with compound...
Chapter 24. Convincing the Skeptics
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As the trial progressed, more patients with rheumatoid arthritis in Rochester received treatment with compound E. And the results continued to be spectacular. Maybe too spectacular? As the number of patients successfully treated with compound E began to approach twenty, Merck & Company became nervous. As Dr. Polley noted: “In March, 1949, Merck & Company insisted on trials of compound E in patients in other parts of the country prior to any announcement of our preliminary results....
Chapter 25. Announcement
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Despite the best of efforts to keep it secret, rumors that the Mayo Clinic had made a breakthrough in the treatment of arthritis were beginning to circulate nationally. The preliminary compound E results had to be announced to the public soon or the story was certain to leak on its own. Hench arranged to make a presentation at the Association of American Physicians on May 3, 1949; this would serve to notify the scientific community of the results. But clinic protocol dictated that the Mayo staff...
Chapter 26. The Prize
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In 2006 a historical vignette about Walter Alvarez was published in the Mayo Clinic Proceedings; it mentions that John F. Kennedy spent one month at Mayo undergoing an evaluation for Addison’s disease—and that he “had lunch” with Dr. Alvarez.1 If so, Kennedy must have been among the last patients that Alvarez saw as a Mayo physician. The renaissance gastroenterologist retired from the clinic at about this time and moved...
Chapter 27. Stockholm
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On October 26, 1950, it was announced that Edward Kendall and Philip Hench, along with Tadeus Reichstein, had won the Nobel Prize. Three days later, on October 29, King Gustav V—who would have normally bestowed the award on the new recipients—died. At ninety-two years of age, his death was not unexpected. He was immediately succeeded by his son, fifty-eight-year-old Gustav (VI) Adolf. The old king’s death was...
Chapter 28. Aftermath
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The afterglow of the Nobel Prize does not last forever. The Mayo Clinic, and especially Drs. Hench and Kendall, had been basking in its glory for nearly a year, but by the start of 1952 things were beginning to return to normal in Rochester. The Mayo Clinic’s leadership was in a period of transition, and the new captains running the world-famous medical facility were steering it on a conservative downwind course. Perhaps the nautical...
Chapter 29. Twilight
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Buried inside the June 15, 1957, edition of the Rochester Post-Bulletin was an article noting that “two long-time members of the staff of the Mayo Clinic, Drs. Philip S. Hench and Claude F. Dickson, have requested early retirement from the staff and have been granted the request by the Board of Governors, it was announced today.” Hench was only sixty-one years old, still four years away from the mandatory retirement age that...
Chapter 30. The End of the Show
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Ernest Hemingway wasn’t out of the hospital for long. Depression still squeezed him in its serrated jaws. In the spring of 1961, just as Percy Julian was selling his steroid-manufacturing company, Julian Laboratories, to Smith, Kline, and French for more than $2 million,1 Hemingway attempted suicide again and wound up rehospitalized in Saint Marys Hospital. His subsequent treatment reportedly involved more...
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Page Count: 192
Publication Year: 2012