The Quest for Cortisone

The Quest for Cortisone

Thom Rooke
Copyright Date: 2012
Pages: 192
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  • Book Info
    The Quest for Cortisone
    Book Description:

    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."

    eISBN: 978-1-60917-326-5
    Subjects: Health Sciences, Biological Sciences

Table of Contents

  1. Front Matter
    (pp. [i]-[vi])
  2. Table of Contents
    (pp. [vii]-[viii])
  3. Introduction
    (pp. 1-8)

    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 trying to make himself useful. The siblings could feel energy building in the clouds overhead.¹

    At 6 P.M. the boys closed the office and prepared to run an errand—a trip to...

  4. CHAPTER 1 Addison and His Disease
    (pp. 9-16)

    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 below.¹ The impact shattered his forehead, driving jagged fragments of skull deep into the underlying gray matter. The brain damage was massive and irreparable. Dr. Addison never regained consciousness and, according to theBrighton Herald, died...

  5. CHAPTER 2 Introducing Dr. Kendall
    (pp. 17-26)

    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 ofInherit the Wind. But for young Dr. Kendall, working through the complex, multistep process for recovering the mysterious substance in this witch’s brew provided just about the most excitement any human could have without actually...

  6. CHAPTER 3 Life After the Thyroid
    (pp. 27-34)

    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 and less” for so long that it now felt as if he knew “everything about nothing.” Kendall’s research abilities, already considered suspect by some of his Mayo Clinic colleagues, now appeared less promising than...

  7. CHAPTER 4 Introducing Dr. Hench
    (pp. 35-42)

    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.

    “A man walks into an elevator . . .” In this case, he’s a big, powerful-looking man. The elevator...

  8. CHAPTER 5 Nice Guys, Saints, Eccentrics, and Geniuses
    (pp. 43-52)

    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, play obvious, high-profile roles. Others, like Leonard Rowntree, Albert Szent-Györgyi, and the Alvarez family, contributed to these stories in ways that were much more subtle but nonetheless important.

    The start...

  9. CHAPTER 6 1929 and the Decision to Hunt for Cortisone
    (pp. 53-58)

    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 time for now. The future Nobel Prize winner had just published an enormously successful novel,A Farewell to Arms.At the University of Chicago (just a few miles from Hemingway’s place of birth and boyhood home), an...

  10. CHAPTER 7 Another Kendall False Start, Another Great Announcement
    (pp. 59-66)

    The bad news—Adolf Hitler became chancellor of Germany in January 1933. The good news—Prohibition ended in the United States in December 1933. The world was getting ready to go to hell, but at least Americans could face it with a drink in their hand.

    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...

  11. CHAPTER 8 Kendall Strikes Out Again
    (pp. 67-74)

    By 1931 the Great Depression was finally easing, but now Hemingway was getting vexed. His latest manuscript, which would eventually be calledDeath 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 ofThe 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...

  12. CHAPTER 9 Kendall Presses On
    (pp. 75-80)

    Nineteen thirty-six was not looking like a good year for the ladies.

    Amelia Earhart was missing over the Pacific.

    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...

  13. CHAPTER 10 Score: Szent-Györgyi–1; Kendall–0
    (pp. 81-86)

    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, with special reference to vitamin C and the catalysis of fumaric acid,”¹ sent a wave of Hungarian pride across the nation. When the Nobel committee called to inform him of its decision, Mrs. Szent-Györgyi was at home and took the message. She made sure that most of the city of Szeged knew who...

  14. CHAPTER 11 Transitions and Travels
    (pp. 87-92)

    The end of the 1930s was a time of transition and travel.

    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 vigorously opposed Hungary’s increasingly sinuous alliance with the Axis powers, and he took public, often unpopular, stands on behalf of his beliefs. Anti-Semitism was growing in eastern Europe, where even liberal academic campuses like...

  15. CHAPTER 12 War Looms
    (pp. 93-98)

    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:

    We have no quarrel with the German people, except that they allow themselves to be governed by a Nazi government. As long as that government exists and pursues the methods it has so persistently followed during the last two years, there will be no peace in Europe. We shall merely pass...

  16. CHAPTER 13 Hench Meets Kendall
    (pp. 99-104)

    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 torture. By the time Luis sought medical help, the situation was becoming urgent. Tests confirmed that his gallbladder was the problem. It had to be removed. Luis was living in...

  17. CHAPTER 14 World War II and Military Steroid Reserch
    (pp. 105-112)

    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 adrenal glands and using it to help Luftwaffe pilots tolerate the stress of high-altitude flight. Similar rumors soon began circulating about Nazi interest in anabolic steroids.

    Substances like androsterone and testosterone, both steroids, produce so-called anabolic effects—development of muscles, emergence...

  18. CHAPTER 15 Plants, Politicians, and More Pessimism
    (pp. 113-118)

    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 called Aero-Foam. The foam, which could be packaged in canisters and sprayed like shaving cream over oil or gas fires, was effective in extinguishing otherwise uncontrollable blazes, especially those occurring on ships at sea. Estimates of the number of...

  19. CHAPTER 16 Good-bye Marker, Hello Sarett
    (pp. 119-122)

    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 scene as the first atomic bomb went off. Instead, he sketched what he saw. His illustration of a mushroom cloud, drawn as he circled the...

  20. CHAPTER 17 Hench Returns to Mayo
    (pp. 123-128)

    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 fever story, political issues, and his ongoing rheumatology research.

    Most of the activity involving yellow fever centered on Hench’s copious correspondence. He was trying...

  21. CHAPTER 18 Push On? Give Up?
    (pp. 129-134)

    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, the project hadn’t exactly gone according to plan.¹ They were trying to produce compound A in the belief that it would be easier to make this substance than its biochemical big brother, compound E. But even making compound A wasn’t easy. Working with...

  22. CHAPTER 19 The Decision to Test Compound E on Rheumatoid Arthritis
    (pp. 135-142)

    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 interest, and the three investigators were now attempting to confirm and repeat the Scandinavian observations at the Mayo Clinic.

    Many patients came to Rochester hoping to get rid of jaundice. But in July...

  23. CHAPTER 20 The Amazing Mrs. G.
    (pp. 143-146)

    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

    Where was Hench? As usual, he was preparing for a trip. He’d be leaving in seven days for London, where he would give the prestigious Heberden Lecture.² Coincidentally, Hench’s upcoming talk was titled “The Potential Reversibility of Rheumatoid Arthritis.” As the date of departure approached, Hench shifted into hyperkinetic...

  24. CHAPTER 21 A Promising Start
    (pp. 147-154)

    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 Dr. Carlisle was the medical director of Merck, and now had primary responsibility for the compound E project and the huge ($14...

  25. CHAPTER 22 The Bad and the Ugly
    (pp. 155-162)

    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. The team had not anticipated that the effect of compound E would be so dramatic. Naively, they had put her in with a roommate. And now this roommate had witnessed everything.

    Mrs. G.’s roommate had been...

  26. CHAPTER 23 Progress and Setbacks
    (pp. 163-168)

    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 E. Dr. Polley, referring to his boss’s reluctance to visit Mrs. G. prior to his trip, quipped that this time, “I had lots less trouble getting Dr. Hench to come to Saint Marys...

  27. CHAPTER 24 Convincing the Skeptics
    (pp. 169-174)

    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. Although it was never verbalized, as far as we knew, it was quite evident that there was concern about the ‘Mayo mystique.’ ....

  28. CHAPTER 25 Announcement
    (pp. 175-182)

    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 should be “privately” notified prior to any public statement.¹ Early in April it was...

  29. CHAPTER 26 The Prize
    (pp. 183-188)

    In 2006 a historical vignette about Walter Alvarez was published in theMayo 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 to Chicago, where he signed on as a medical columnist for the Chicago Tribune Syndicate.

    Soon known as “America’s family doctor,” Alvarez became famous; his newspaper column was read by...

  30. CHAPTER 27 Stockholm
    (pp. 189-196)

    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 an unfortunate beginning to the biggest event of which Kendall or Hench would ever be a part.

    The Kendalls’ trek to Sweden for the December awards ceremony began well. The chemist...

  31. CHAPTER 28 Aftermath
    (pp. 197-204)

    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 analogy is not such a bad one: the Mayo Foundation board now included the chairman of Northwestern Mutual Life Insurance Company as one of its new...

  32. CHAPTER 29 Twilight
    (pp. 205-212)

    Buried inside the June 15, 1957, edition of theRochester Post-Bulletinwas 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 had sent Dr. Kendall to Princeton six years earlier. The article went on to state that Hench made the request because of the “steadily increasing commitments” he faced...

  33. CHAPTER 30 The End of the Show
    (pp. 213-218)

    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 electroconvulsive therapy.²

    Hemingway’s seemingly premature release from this hospitalization has provided endless fodder for conspiracy buffs. Why did his doctors let him out when they did? Had he feigned just enough psychiatric improvement to get himself dismissed?³ Did he...

  34. Notes
    (pp. 219-276)
  35. Back Matter
    (pp. 277-277)