[Forgotten episodes of the birth of cortisone]

Abstract

During World War II, a rumor reached the United States and the United Kingdom that the Germans were successfully using an adrenal hormone product to protect Luftwaffe pilots from the adverse effects of high altitudes. The product was said to be obtained from adrenal glands collected in a huge amount in Argentina and transported by U-boats to Germany. The U. S. and the U. K. exerted their war efforts by setting up urgent research projects to produce similar products. The war ended in 1945, however, before the goal was achieved. The German rumor turned out to be groundless. Cortisone acquired fame in 1949 as "a miracle drug" for the relief of rheumatic pain. Its therapeutic discovery was an outcome of the untenable assumption that rheumatoid arthritis patients must have suffered from adrenal insufficiency and hormone deficiency. The war efforts have led to successful syntheses of cortisone after the war, and its industrial production has reduced its cost drastically from $200.00 per gram in 1949 to $10.00 in 1951. To overcome the cumbersome synthetic routes for cortisone, natural product sources were sought as possible starting materials, but without much success. A microbiological transformation of steroidal compounds was developed in 1952 to introduce an oxygen function into the molecular position 11 by a microorganism found at a window of a laboratory. The fermentation process required progesterone which found its timely supply in Mexico. The cost of progesterone went down from $2.00 per gram to $0.15 and that of cortisone further from $10.00 to $3.50 in 1955. An ample supply of cortisone at an affordable price was admirably achieved by the combination of progesterone derived from diosgenin of the Mexican yam and a microbiological oxidation process developed by a chance discovery of suitable organisms. The former is attributed to R. E. Marker and the latter to D. H. Peterson.