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Discovery of Natural Progesterone

Who Discovered Progesterone Could be Made from a Plant Source?


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Russell Marker
March 12, 1902 - March 23, 1995

 

The Story of the
Mexican Wild Yam
(Dioscorea barbasco)
A natural source of progesterone

Introduction

During the 1920s progesterone was made from the ovaries of sows (pigs). During the 1930’s and 1940’s the source was switched to cholesterol or bile acids. However, the process was very long and difficult. For years chemists tried to find a better raw material than using cholesterol and bile acids. In 1936, Japanese researchers realized that diosgenin extracted from yams were similar to some of the adrenal hormones. Russell Marker, a chemist from the University of Pennsylvania, found that diosgenin could be converted into progesterone. Marker then went to Mexico to see if he could find the richest plant source containing diosgenin.

The search for the richest source of diosgenin

In 1935 Russell Marker left his gasoline projects to pursue the study of steroids. He knew that certain plant substances were used for birth control and to treat female problems throughout Central and South America and China. Therefore, he theorized that some wild yam plant species have hormonal properties.

Marker was best known for the “Marker Degradation.” This degradation involves 5 steps in which diosgenin is chemically converted to progesterone using high temperature and pressure. Marker experimented with many plant sources and finally when he tested samples from a Japanese plant Dioscorea japonica (diosgenin), he found the structures he needed for the production of progesterone.

At Penn State, his lab tested over 400 species of plants from southern U.S and Mexico. In 1943 he went to Mexico to look for the wild yam plants since he found that they contained the richest amount of diosgenin. Marker read that Dioscorea machrostachya grew several hundred pounds along the highways in Mexico. On the way to obtain the plant, he met a man named Alberto Moreno, who joined Marker to collect the plants for him. Marker then loaded the plants on a bus and headed back to the U.S and took them to his financial supporter, Parke-Davis & Co., a pharmaceutical company. They asked him to sign patent rites over to them for the process Marker used to convert the yam to the natural progesterone molecule, but Marker declined.

Making progesterone available

Marker refused to sign patent documents because he wanted to make the process of obtaining progesterone from the plant source open to everyone. He said he “wanted to leave the field open to anyone who wished to produce in competition, to force the price of the various hormones down to the point where they would be available for medical purposes at reasonable prices.”
It is Russell Marker who caused the price of pure progesterone to go from over $80.00 per gram in the early 1940s to 80 cents per gram.

Starting in 1944, Marker was beginning to start up hormone companies to produce progesterone. His first company was Syntex. After disputes over profits and salaries, Marker broke ties with Syntex and started another company called Botanica-Mex. The owner of Syntex threatened Marker with jail for “stealing Syntex processes,” thus, it forced Marker to close Botanica-Mex.


A new source of diosgenin

Even though Marker’s company was closed, he remained in Mexico and continued to collect new species of dioscorea. One of the plants he collected was Dioscorea barbasco. He found that barbasco contained 5 times as much diosgenin as the cabeza. This then led Marker to restart Botanica-Mex and eventually merged with Hormosynth in 1946. In 1949 the company went under ownership changes and today it is a European drug company known as Quimica Esteroidal, S.A.


Russell Marker Retired

In 1969 Marker wrote a letter that was published in December 1992 issue of Steroids. He said “after 5 years of production and research in Mexico, I felt I had accomplished what I had set out to do. I had found sources for the production of steroidal hormones in quantity at low prices, developed the process for manufacturer, and put them into production. I assisted in establishing many competitive companies in order to insure a fair price to the public without a patent protection or royalties from the procedure.”

Marker was given an award by the Mexican Chemical Society in 1969 and also honored in 1990 on the 50th anniversary of the discovery of the Mexican Wild Yam for his contribution to steroidal hormone research.

Source: Bennett, Michael, PhD, Wild Yam Nature’s Source of Phytohormones, 1997


Other Notes

Is diosgenin or “yam extract” the same natural substance as progesterone?

No, they may have a synergistic effect and biological activity, but they do not convert to the natural progesterone molecule without the lab process involving heat and pressure.

What about soy?

Soy has been another valuable starting material for certain hormones, but diosgenin was preferred for steroid hormone production.