THE STORY OF CORTISONE

I am once again back with another story that I heard from my senior colleague Prof. Hirji Adenwalla of Trichi in Kerala. As you will appreciate, while reading this blog, he is a treasure trove of knowledge and his story telling ability will keep you enthralled. He is the Head of Charles Pinto Centre of Cleft Lip, Palate and Cranio-facial Anomalies, and in his eighties he remains one of the senior most plastic surgeons of our country.

The story of the discovery of cortisone began in 1928 nearly 20 years before it was really discovered. A 65 years old doctor suffering from severe rheumatoid arthritis was admitted to the Mayo clinic under Dr. Philip Hench with an acute attack of jaundice. The doctor in passing, as an aside mentioned to Hench that his rheumatoid condition had almost disappeared with the onset of jaundice. He could now walk a mile without pain when before the jaundice he could walk only a few steps. Any other doctor would have put this aside  as mere coincidence. But not Hench he noticed the same phenomena in other patient with the same problem. In 1933 Hench who himself was suffering from a  wide unrepaired cleft palate wrote a paper which was published in the proceedings of the Mayo Clinic that there must be some substance that was produced by the jaundiced patient that caused the crippling symptoms of rheumatoid arthritis to abait. He accepted his ignorance and called this substance substance X.

Hench in desperation started hitting in the dark. He started feeding his rheumatoid arthritis patients with bile salts, liver extracts and he even injected blood taken from jaundiced patients but to no avail. He published his failures in the British medical Journal of 1938. Hench was a dogged clinician and would not let go he observed that it was not only jaundice which caused this remission but it also happened in pregnancy and he noted that it did not only cause remission in the rheumatoid condition but also in asthma, myasthenia gravis and in other autoimmune diseases. These were masterly observations. But here Hench met with a brick wall. What was this substance X?

He got Professor Edward Kendall professor of physiological chemistry at the Mayo clinic to try and identify this substance X. Kendall was already well known for his isolation of thyroxin which was curing    Myxoedema. As luck would have it Kendall was working on the hormonal secretions of the adrenal glands. Everyone knew of the clinical condition called Addison’s disease caused by destruction of the adrenals by tuberculosis. These patients with Addison’s disease died within 6 months. Patients with Addison’s disease were treated with extracts made from cat’s adrenals Kendall set out to identify this hormone. In 1932 Kendall isolated several compounds from the adrenal glands and called these compounds A, B, E, and F. Hench and Kendall working in the same institution became friends. They wondered if Hench’s substance X could be either A, B, E or F.

Then came the Second World War, and as often happens wars act as a catalyst for great medical and surgical advances, US intelligence reported that Nazi Germany was purchasing large quantities of adrenal glands from cattle in Argentina and extracts of these glands were injected into Germen pilots who as a result could fly high attitudes without distress. This was of course not true but it motivated a strong research programme in the United States which culminated in 1948 with the synthesis of a few grams of compound E which was identified as Hench’s substance X. This compound E was named cortisone. This break through took place at the Merck laboratory Dr. Lewis Sarett was responsible for it. Dr. Lewis Sarett was working in the Merck laboratory.

           

Now the scene shifts back to the rheumatology ward of Dr. Philip Hench. On the 26th of July 1948 a Mrs. Gardner suffering from severe rheumatoid arthritis was admitted under his care, she was confined to a wheel chair and was in severe pain. Hench, spoke to Kendall and Kendall requested Merck to send him some compound E now called cortisone for trial. Injections of 100 mg every day were started, four days later Mrs. Gardner who could hardly hobble a few steps went shopping. Dr. Hench treated 13 more cases with cortisone which was really the substance X that Hench had been talking about for years. The results were dramatic. He presented these cases at a clinical meeting at the Mayo clinic in April 1949. I quote from Albert Marel’s book “The Hormone Quest” “The lights were turned down and a color film began flickering on the screen. First came the before treatment pictures in which patients struggled to take a few steps.” Suddenly an electrifying gasp, swept through the audience as the after treatment scenes appeared and the doctors saw the very same patients jauntily climbing steps, swinging their arms and legs and even doing a little jig as if they had never been crippled. Even before the film ended, the watching physicians had filled the hall with wave after wave of resounding applause. When the lights went up Dr. Hench approached the lectern, he was greeted with a standing ovation”. No man deserved it more for his insight and his perseverance. It took 21 years for Philip Hench to prove what was first just a suspicion. A year later Hench and Kendall were awarded the Nobel Prize. Hench donated a part of his prize money to serve Sr. Pentaleon the nun in-charge of his rheumatology ward, so that she could fulfill her wish to travel to Rome and meet the Pope. But alas, Dr. Lewis Sarett who made the end possible was forgotten.

           

Like Penicillin cortisone did not fulfill its full expectations and was certainly not the answer to rheumatoid arthritis. But cortisone is today used to ameliorate the symptoms of a legion of diseases. “It generally does not ever cure but when correctly used, relieves, alleviates and controls several disease processes” and often saves lives. James Le Fanu in his book the Rise and fall of Modern medicine says “Hench got it right but for the wrong reasons”.