MEXICAN YAMS--CORTISONE, STEROIDS, AND ORAL CONTRACEPTIVES

Yam (Dioscorea spp.)

DIOSCOREACEAE, Yam Family

Plants have had a major impact on modern medicine in providing important steroids. Cortisone is one of the most famous of the steroids that was desperately needed by the medical community in this country. Cortisone is manufactured in the cortex of the adrenal glands, located above the kidneys. Cortisone raises the blood sugar level by increasing the conversion of amino acids to carbohydrates. This compound can be used to treat such diseases as rheumatical arthritis, asthma, bursitis, gout, hepatitis, Addison's disease, leukemia, rheumatoid heart diseases, and skin diseases, such as poison oak (Toxicodendron). However, cortisone originally had to be obtained from animals. For example, in 1935 chemists were isolating the compound from bile acids in the urine of oxen. Elaborate chemical procedures, involving 38 steps, were then required to make important human steroids. In 1938, a gram of natural cortisone was worth $100 (1938 dollars!).

For many years ethnobotanists had known that certain plants had been used by primitive peoples as fish poisons, soaps, and shampoos. These plants produce foam in water and are called saponins, which are steroids. As a fish poison, saponin destroys red blood cells on contact, which causes the fish to be stunned and then float to the surface. Nonetheless, these fish are not poisonous to humans when eaten. Some of these saponin-bearing plants were also used by societies as oral contraceptives. For example, in Mexico and Central America, several plants were taken to stop female ovulation, and the Matto Grosso Indian women in Brazil took plant products daily to prevent pregnancy.

One person who was keenly aware of plant saponins was Russell Marker, a maverick biochemist. In 1939 he published a study on sarsasapogenin, the saponin in Smilax used to make sarsaparilla. The next year he published studies on diosgenin, a saponin isolated from a Mexican yam species of the genus Dioscorea. From diosgenin he was able to synthesize the human hormone testosterone in eight steps and progesterone in just five steps. Marker made plans to use yams for mass production of human steroids, but proposals were rejected by the pharmaceutical companies, who saw no need for the venture. So in mid-1942, Marker got an indefinite separation from his wife and went to live in Mexico. In Mexico he set up a laboratory in his room to make steroids from yams. Marker worked round-the-clock for several weeks to make progesterone. Then he offered the progesterone for sale to a businessman in Mexico City, who offered him $80 per gram. However, the businessman was in shock when Marker handed him two kilograms of the stuff ($160,000), which he had produced in such a short time.

A company called Syntex was then organized to make steroids from Mexican yams, using the syntheses invented by Marker. After a while, the maverick Marker left the company, but he left also with the secret of a crucial step in the process. Shortly after, Syntex hired Dr. George Rosenkranz, who went to Mexico and figured out the missing step. Rosenkranz took yams and was able to make progesterone, then testosterone, and finally the female hormone esterone. Rosenkranz is credited with the saying, "Adam goes into the test tube and Eve comes out."

All of this work in Mexico occurred while major pharmaceutical companies in the United States were trying to make hydrocortisone from the adrenal glands of 2,200,000 hogs. This was a high priority treatment for arthritis. Once again, Marker made another important discovery; he identified a yam saponin called botogenin. This compound has an oxygen located at the carbon-12 position. Upjohn chemists used microorganisms to convert this compound into a useful form, because they could easily move the oxygen to the C-11 position. This procedure opened the door for advanced cortical steroids. About 66 pounds of fresh yams (two or three yam tubers) could yield one pound of diosgenin and, eventually, through botogenin about two ounces of cortisone. Another species was soon found to have three to four times the level of diosgenin. In the 1960s, a gram of cortisone cost two dollars to produce; at this cheap price the industry could produce cortisones, human sex hormones, and human steroids inexpensively and also produces huge profits. Inexpensive steroids made it possible to produce inexpensive oral contraceptives, fertility drugs, and a wide assortment of cortisone drugs, which can now be purchased often without prescription.

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