Cortisone Jackpot?

Scarce and expensive drugs are the potential jackpot payoffs of pharmaceutical chemistry. Right now one of the most valuable is the steroid hormone, cortisone, which sells at wholesale for $23 a gram. Reason: under present commercial methods, it takes the bile from 1,000 tons of cattle to make a month's supply of cortisone for a single arthritis patient.

In the great chemists' drive to synthesize cortisone, some researchers start at the beginning with simple ingredients (TIME, May 7), others are trying to make the magic drug out of complex vegetable substances, which contain the building blocks of cortisone.

Chemical Trick. Some hormones are not difficult to make in this way. Syntex Inc. of Mexico City, for example, has been making sex hormones (testosterone, progesterone, etc.) out of an inedible wild yam called cabeza de negro, which yields a substance containing the four-ringed steroid nucleus. But cortisone is tougher. For one thing, its molecule has an oxygen atom attached to one of its carbon atoms (No. 11), and to place that oxygen in the correct spot is a difficult chemical trick.

Last week Syntex announced that a group of its chemists headed by Dr. George Rosenkranz had at last accomplished the feat, starting with diosgenin from cabeza de negro. They transformed it by 18 chemical steps to "Reichstein's Compound D,* which had been found in minute quantities in the adrenal gland, but had never been synthesized. Only three more steps were needed to turn this compound into cortisone.

Within a year, says Syntex, it hopes to make as much yam cortisone as is now produced from cattle bile. In three years, when its new $2,000,000 plant is finished, it hopes to supply enough cortisone for the entire U.S. demand.*

New Code Words. If all this works out (there may be unforeseen difficulties), it is good news for those patients who are helped by cortisone. Perhaps even more promising is another aspect of the Syntex accomplishment. The steroid hormones are, in effect, "code words" which help to control the cells of the body. They are all very similar, built around the same nucleus, but the slightest difference (such as the shift of an oxygen atom from one carbon atom to another) changes their effect. Medical researchers would like to try hundreds of steroids to see what each can do to make the body work properly.

The Syntex process produces, along the line, whole classes of promising steroid compounds. Some of them have been found in adrenal glands, but in quantities too small for practical experimenting. Now, says Syntex, these "cortisone precursors" can be made in any amount desired. Some of them may prove more potent biologically than cortisone itself.

*Chemical name: Allopregnane-3 beta, 17 alpha, 21-triol-n, 20-dione. *Which is growing steadily. Newest use: Pediatrician Lawson Wilkins of Johns Hopkins reported last week in Seattle that girls who show marked outward signs of masculinity (pseudo-hermaphrodites) respond magically to small doses of the hormone. They shed facial hair, develop curves in right places, seem to become feminine in every way.

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