Tuesday, November 27, 2001

MEXICO CITY At a start-up Mexican chemical company 50 years ago, two doctors and a graduate student made a discovery that changed women’s lives around the world: a synthetic hormone that went on to become the key ingredient in the birth-control pill.

This year, Mexican academics and health officials were honoring the researchers who made the discovery, based on a wild Mexican yam.

In 1942, American chemist Russell Marker found large quantities of diosgenin, a steroid that can be transformed into the female sex hormone progesterone, in the inedible root growing in the mountains of Veracruz. He created the Mexican chemical company Syntex with two owners of a small Mexico City pharmaceutical concern who had backed his work with the yams.

When he left the company in 1945, his partners recruited Dr. George Rosenkranz, a Hungarian immigrant who had fled to Cuba from Europe during World War II, to be the new scientific director. Dr. Rosenkranz in turn hired Dr. Carl Djerassi.

The two went on to use the yam’s steroid to make a synthetic form of the highly sought arthritis treatment cortisone, a feat that stunned competing U.S. pharmaceutical companies with much bigger budgets. It propelled Syntex onto the international stage.

Their work laid the foundation for the discovery of the birth-control pill ingredient, the “super-hormone” norethindrone. This synthetic hormone has many times the biological activity of progesterone, a natural female hormone.

The discovery of norethindrone was made in the Syntex labs on Oct. 15, 1951, by Luis Miramontes, then a graduate student working under the guidance of Drs. Rosenkranz and Djerassi.

Dr. Rosenkranz, now 85, was quick to point out that the idea of using progesterone as a contraceptive did not originate in his labs.

“Contrary to popular belief, this scientific event was not the result of chance, but the culmination of a long chain of events,” he said at a recent ceremony in his honor.

Dr. Rosenkranz credits Austrian endrocrinologist Ludwig Haberlandt with spotting progesterone’s contraceptive potential in the 1920s.

“He asked a very simple question: Why doesn’t a pregnant woman get pregnant again during her pregnancy? That is because of the role of the female hormone progesterone, which later as it turned out inhibits ovulation and all those processes,” Dr. Rosenkranz said in an interview with the Associated Press. “So that was a start.”

Still, Syntex’s research in 1951 was driven less by a search for contraceptives than by the need to produce a new form of progesterone, which at the time was used to treat menstrual disorders and infertility.

It wasn’t until five years later that research scientist Gregory Pincus in Massachusetts began testing birth-control pills using a nearly identical substance manufactured in 1953 by a competing company.

And it wasn’t until 1960 nearly 10 years after the discovery that the U.S. Food and Drug Administration approved “the pill” for public use.

Although norethindrone was discovered first, it was the competing substance, norethynodrel, made by G.D. Searle & Co., that won first approval for public use. Norethindrone followed with FDA approval in 1962.

The pill had numerous obstacles to overcome before it won general acceptance: the U.S. government’s concerns about potential bad side effects, religious opposition and widespread cultural values, Dr. Rosenkranz said.

“In certain cultures, you had the machismo, where a large family was a symbol of a virile man,” he said. “In other poor cultures, the large family was really life insurance for survival.”

The pill has survived many medical challenges current studies show it can help regulate the menstrual cycle, prevent anemia and help to prevent ovarian and endometrial cancers.

A report on oral contraceptives published last year by the School of Public Health at Johns Hopkins University said that in 44 of 68 developing countries with available contraception data, “more married women have used the pill than any other modern family-planning method.”

The study said that “among developing regions, the pill has been most widely used in Latin America, where 55 percent of all married women have used the pill at some time.”

In Mexico, one of the typically macho societies to which Dr. Rosenkranz referred, “the pill has been, since the beginning of family planning the most widely known contraceptive method,” says the National Population Council.

As a result of family-planning programs, Mexico’s fertility rate has dropped from an average of at least seven children per woman in the mid-1960s to 2.4 children in 2000, the council says.

Although use of the pill has diminished in Mexico and other countries in comparison with sterilization and the intrauterine device (IUD), “it was the advent of the pill that turned family-planning programs into effective and accessible programs for people worldwide,” said Dr. Paul Blumenthal, a contraceptive researcher and medical adviser to Planned Parenthood in the United States.

As the first contraceptive to truly free women from the burdens of unwanted pregnancy, the pill also became the catalyst for other freedoms, specialists say.

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