W. Bruce Fye Center For the History of Medicine: Discovery of Cortisone

Drs. Charles H. Slocumb, Philip S. Hench, Edward C. Kendall and Howard F. Polley in 1950.

Starting his research in the 1930s, Dr. Edward C. Kendall isolated several hormones from the adrenal gland, one of which later became known as cortisone. Doctor Philip S. Hench and his colleagues, Drs. Charles H. Slocumb and Howard F. Polley, initiated the clinical trials of cortisone for the treatment of rheumatoid arthritis in 1948.

Dr. Hench was Mayo Clinic’s first rheumatologist. He joined the Clinic in 1926 and saw numerous patients suffering from rheumatoid arthritis. He noticed that some patients’ arthritis improved under certain conditions and hypothesized that something must have prompted the secretion of a natural anti-rheumatic that he called “substance X.” 

Hench asked Kendall for help in discovering “substance X” and they decided that it was most likely an adrenal hormone, possibly compound E.

Letter from Dr. Hench to Merck and Company requesting more compound E to test effectiveness of the compound on a patient with rheumatoid arthritis, 1948 September 4.

In the late 1930s, Dr. Tadeus Reichstein sent Dr. Kendall vials containing various adrenal “substanzen” for comparison with compounds isolated from adrenal glands by the Mayo Clinic team. Kendall noted in his autobiography, Cortisone, that each of the main laboratories researching the adrenal cortex named their compounds alphabetically -- “the first crystalline compound to be isolated was designated A, the second B and so on”. Experiments showed that Reichstein’s subst. A was quite different from Mayo’s compound A, while his subst. Fa proved to be the same as Mayo’s compound E. The difference in nomenclature led to some early confusion in papers describing potential research advances.

Shown here are three of the vials sent by Reichstein to Kendall. They are (L. to R.): subst. A, subst. Fa, and desoxycorticosteron. Each sample label is initialed T. R., indicating that it was prepared by Dr. Reichstein.

Dr. Kendall's Nobel Prize certificate, 1950.

Dr. Kendall's diary of his trip to Sweden for the Nobel Prize ceremony, 1950.

“Dec. 10 was a day which will always remain apart from all others. The day is now the latest chapter in a long historical record which is characterized throughout by sincerity and simplicity. To have done work worthy of a Nobel Prize and to receive one are two facts which are far apart. Fortune is also involved but to be numbered among those who have received the prize is a source of great satisfaction.” -- diary entry dated December 11, 1950.

Sister Mary Pantaleon was the nursing supervisor in the arthritis wing at Saint Marys Hospital.

Letter to Sr. Pantaleon from Drs. Hench, Slocumb and Polley, 1950 November.

Drs. Hench, Slocumb, and Polley gave a portion of their Nobel Prize money to Sister Pantaleon in thanks for her devotion to the arthritic patients. They hoped she could use the money for a trip to Rome. In 1952, she traveled to Rome with Sister Mary Brigh and had an audience with Pope Pius XII.

Dr. Kendall joined Mayo Clinic in 1914 as its first scientist dedicated to research in biochemistry. In the 1930s, Dr. Kendall isolated 6 hormones from the adrenal gland. He named them compounds A through F in the order in which they were isolated. 

Page 60 of Edward Kendall laboratory notebook, dated 1945 October 9.

This page in one of Dr. Kendall’s lab notebooks -- dated October 9, 1945 -- shows his description of an experiment with compound A. The note at mid-page, “Vol. & amts taken from Reich—”, indicates that he might have been testing an experiment done by Dr. Tadeus Reichstein in Switzerland. In his memoir, Cortisone, Kendall discusses the respectful competition maintained between the two labs in the race to identify the adrenal hormones and their functions. 

Photograph of Dr. Tadeus Reichstein inscribed to Dr. Hench, 1950.

Dr. Tadeus Reichstein, a chemist from Switzerland, had simultaneously isolated hormones of the adrenal cortex. He was honored with the Nobel Prize for his work, along with Drs. Kendall and Hench. The inscription on this photograph reads,

“To Dr. Ph. Hench, with many thanks for having won me a Nobel prize. Dec. 1950. T. Reichstein.”

In 1943, Dr. Lewis Sarett, a chemist at Merck & Co., worked for 3 months in Dr. Kendall’s laboratory. Back at Merck, he was able to synthesize compound E. It was the most complicated compound ever made for medical use. By 1948, enough compound E had been synthesized to begin clinical testing.

A bottle of cortisone tablets and a vial of cortisone, undated.

Telegram sent to Dr. Hench on October 26, 1950, informing him of his Nobel Prize win.

Front and back of the Nobel Prize Medallion awarded to Dr. Hench, 1950.

Dr. Chuck Mayo congratulating Drs. Hench and Kendall on their Nobel Prize win, October 1950.

Drs. Charles Slocumb and Howard Polley were the 2nd and 3rd rheumatologists hired at Mayo Clinic and were important members of the cortisone clinical team. Dr. Slocumb was in charge of the arthritic service at Saint Marys Hospital and Dr. Polley administered most of the daily injections of compound E to the patients in the clinical trial. In recognition of their contributions to the research effort, Hench split his ~$10,000 Nobel Prize money with Slocumb and Polley. Dr. Kendall shared his Prize money with Dr. Vernon R. Mattox, a biochemist at Mayo Clinic who helped Kendall with research that ended up tripling the yield of cortisone.

Checks for $3,524.32 made out to Drs. Polley and Slocumb, February 1951.

Finding Substance X: The Team That Created Cortisone

The 2022 Heritage Days film is titled Finding Substance X: The Team that Discovered Cortisone. This film tells the intriguing story of the search for a mysterious hormone that ultimately led to new hope for patients, an important new class of medications and the Nobel Prize. You can view it internally on Mayo Clinic's video exchange or externally on Mayo Clinic’s History and Heritage website.