“Once you eliminate the impossible, whatever remains, no matter how improbable, must be the truth.” Sir Arthur Ignatius Conan Doyle [1859-1930]
Dr Philip Showalter Hench [1896-1965] was then Chief of the Medical Service and Director of the Rheumatism Center at the Army/Navy General Hospital in Hot Springs, Arkinsas. His interest was in arthritic diseases, a field then just emerging as a specialty.
Hench had served as the Mayo Clinic’s first rheumatologist and was appointed director of the Clinic’s new Division of Rheumatology in 1926. He saw that many of his patients with rheumatoid arthritis suffered chronic, unremitting pain with little hope of remission.
In 1923 he had recognized that two conditions—jaundice and pregnancy—were often associated with temporary but dramatic reduction in pain. He postulated that an unknown substance (“Substance X”) caused the decrease in intensity of symptoms.
These observations showed that rheumatoid arthritis was reversible and not caused by germs. In the late 1930s and early 1940s Hench and biochemist Edward Kendall conferred many times about the possible identity of “Substance X”.
Kendall was working with colleagues to isolate hormones from the human adrenal gland. Four of these compounds were of special interest by virtue of their physiologic activity, e.g. their influence on functions such as metabolism, resistance to toxicity and muscle response as demonstrated in trials on animals. These were identified simply as A, B, E and F.
In the search for Substance X, Hench and colleagues administered a number of substances to patients with rheumatoid arthritis:
- Blood transfusions from jaundiced or pregnant donors
- Female sex hormones
- Production of experimental increase in serum bilirubin
- Toluylene diamine to induce jaundice
- Serum from jaundiced patients
- Lactophenin (a sedative and antipyretic)
- Lecithin extract
None were effective.
By 1941 Kendall and Hench decided to see whether one of these adrenal hormones—in particular, Compound E—might in fact be the long sought-after “Substance X.”
Finally, in September 1948, Kendall worked through the necessary channels to obtain a small amount of Compound E for Hench and his associates to administer to a patient with rheumatoid arthritis.
Early results were nothing less than astounding. Within four days, Hench’s formerly wheelchair-bound patient walked out of the hospital. Over the next months, additional patients received the compound (now called cortisone) with similar good effect.
Hench had indeed found his “Substance X.” Although Hench, Kendall and their Mayo associates viewed the results as preliminary findings only, the New York Times broke the story of the promising new treatment.
In December 1950 Hench travelled to Sweden to receive his share of that year’s Nobel Prize in Physiology or Medicine. The award, he said, “belonged truly to all the men and women of the Mayo Clinic because it was the spirit of co-operative endeavour, the fundamental credo of the institution, which made possible the work that resulted in the trip to Stockholm.”
Hench retired from the Mayo Clinic in 1957 and died in 1965.
A multi-faceted man defined by more than his role in the story of cortisone, he was a compassionate physician of the highest calibre, a teacher, writer, medical historian and lifelong scholar.
As a sideline to his illustrious career in medicine, he was an active member of the “Baker Street Irregulars Society,” a group of dedicated devotees of Sherlock Holmes. His collection of first editions and related materials, now housed within the Special Collections and Rare Books at the University of Minnesota, has been described by curators as “one of the more remarkable Sherlockian libraries ever assembled.”
Not surprising, of course, that Philip Hench would be a man who liked his mysteries and backed his hunches.
Written by John Quintner, Physician in Pain Medicine & Rheumatology (retired)
References:
Cortone: A Handbook of Therapy. New York: Merck (North America) Inc., 1952.
Hench PS, Kendall EC, Slocumb CH, Polley HF. The effect of a hormone of the adrenal cortex (17-hydroxy-11-dehydrocorticosterone: Compound E) and of pituitary adenocorticotropic hormone on RA. Preliminary Report. Ann Rheum Dis 1949;8:97-104.
Neeck G. Fifty years of experience with cortisone therapy in the study and treatment of rheumatoid arthritis. Ann N Y Acad Sci 2002;96:28-38.
Shampo MA, Kyle RA. Stamp vignette on medical science: Philip S Hench – 1950 Nobel Laureate. Mayo Clin Proc 2001;76:1073.
