“The Pill”

An estimated 6 billion people live on our planet today. But in 1950, the world population was only half that. And it was fear of a population explosion that led to the search for the first oral contraceptive.

This is for May 15 — with a landmark in 20th century scientific research. In May of 1960, the U.S. Food & Drug Administration approved the first oral contraceptive.

The first effective birth control pill was called Enovid. The FDA had already approved it more than two years earlier for use in treating menstrual disorders. “The Pill”, as it became known, was developed by a team of researchers at the Worcester Foundation for Experimental Biology, headed by Dr. Gregory Pincus.

Most birth control pills contain synthetic versions of two hormones — progesterone and estrogen. These hormones occur naturally in a woman’s body — they control the menstrual cycle. By controlling the levels of these hormones, birth control pills make a woman’s body act in some ways as it does when she’s pregnant. She doesn’t ovulate — or release eggs. And the lining of her uterus changes to prevent sperm from even reaching the eggs.

That’s “the pill” — approved by the FDA 40 years ago this month. It’s given millions of women a reliable way to prevent unwanted pregnancy.

According to population experts, the world’s human population surpassed 6 billion in the Fall of last year 1999. In 1950, the world population was about 3 billion. It was this kind of population explosion that worried Margaret Sanger — an early crusader for birth control in the U.S. — and Katherine Dexter McCormick — a philanthropist who had already contributed money to scientific research on steroids. In early 1951, Margaret Sanger challenged Dr. Gregory Pincus of the Worcester Foundation for Experimental Biology to find an effective oral contraceptive. Over the next few years, Margaret’s friend Katherine McCormick donated a considerable amount of money to support the search. Dr. Pincus accepted the challenge — and the sorely needed research money that went with it. In less than 10 years, “The Pill” would be born.

Hormones Reproduction 1921-1950

Before the race to find an effective oral contraceptive began in earnest in 1951, there were several important developments in the 1920s, 30s and 40s that laid the foundations for success. During that period, researchers weren’t looking for an oral contraceptive at all. They were trying to understand steroid hormones. They were looking for cures to diseases such as rheumatoid arthritis.

Steroid hormones are substances produced by plants and animals. In animals, including humans, many of them play important roles in the reproductive system. These so called “sex hormones” come in three varieties: androgens masculine hormones, such as testosterone, estrogens feminine hormones, and progestogens. Androgens are responsible for development and function of male genital organs. They also promote masculine features and the sex drive. Estrogens prepare a woman’s womb for pregnancy and promote breast development. Progestogens include progesterone, also called the “pregnancy hormone.” It’s involved in pregnancy and in regulation of the menstrual cycle.

Other steroid hormones, such as cortisone, help the body maintain itself. Cortisone is effective in combating rheumatoid arthritis.

The first serious, modern suggestion of a hormone-based contraceptive came from Ludwig Haberlandt — an Austrian researcher — in 1921. The suggestion followed studies using reproductive organs transplanted from pregnant animals to non pregnant animals. It was found that when the ovary of a pregnant rat was placed in a non pregnant rat, the rat stopped ovulating. The hormones that made this “magic” trick possible weren’t identified at the time.

It was 30 years before researchers understood hormones well enough and had enough confidence to attempt a more impressive feat — to make a fertile woman sterile for any desired length of time, then just as easily, allow her body to become fertile again.

To study steroid hormones, researchers needed an inexpensive and abundant supply. It occurred to one visionary researcher to use steroids found naturally in plants instead of those found in animal tissues. Russell Marker, a researcher at Pennsylvania State University, knew that it was expensive and difficult to obtain steroids from animals. They were often derived from organs obtained at slaughterhouses. Plants such as cabeza de negro, barbasco, and Mexican yam contain useful steroids that can be modified and used in humans.

Marker formed Syntex, a company designed to make this technology available to researchers. Marker discovered a way to make progesterone from cabeza de negro. His novel approach would eventually make possible the synthesis of cortisone from plant material. Coritsone was in big demand for its effectiveness against rheumatoid arthritis. But Marker soon left Syntex due to disagreements with his partner, Emerik Somlo.

Syntex researcher Carl Djerassi picked up where Russell Marker left off. Carl Djerassi was born in Vienna, Austria on October 29, 1923. He was a refugee from the war in Europe. Djerassi joined Syntex in 1949, initially to synthesize cortisone. In 1950, he began a new search: develop a version of progesterone that is effective when taken orally. Before then, effective doses of the stuff were so high that they had to be injected. In November of 1951, he applied for a patent for the product of that search, and dubbed it “norestheisterone” or norethindrone. He holds a U.S. patent for this substance for use as an oral contraceptive Patent No. 2,744, 122.

In August of 1953, G.D. Searle, a pharmaceutical company, applied for a patent on “norethynodrel”, a version of progesterone similar to Djerassi’s. Searle researchers claimed no knowledge of the similar work at Syntex. Like Djerassi, Searle’s chief research chemist, Frank Colton, did not realize he was helping to create a birth control pill.

Era of Discovery 1951-1960

The research team at the Worcester Foundation didn’t so much “invent” the Pill as give birth to it. The effects of progesterone on a woman’s reproductive system were already somewhat known. And techniques for synthesizing them from plants had been figured out by Marker. In a sense, Dr. Pincus’s team merely put the pieces together and boldly tested a new product that most pharmaceutical companies were afraid of testing and selling. You have to understand that it was not at all clear that the public would want an oral contraceptive. And opposition from religious groups was likely to be strong. Even the researchers that contributed most to synthesizing forms of progesterone — Russell Marker, Carl Djerassi, and Frank Colton — never intended to create an oral contraceptive.

Pharmaceutical companies, Syntex and G.D. Searle, both donated compounds to the Worcester Foundation for study — norestheisterone and norethynodrel, respectively. The Worcester Foundation evaluated the effectiveness of both versions of progesterone in 1953. It was found they they were both far superior to other progestational compounds when used in animals. Both were patented and eventually used as the basis for oral contraceptives.

Searle’s norethynodrel compound was chosen over Syntex’s version. For commercial purposes, it was given the more elegant name: Enovid. The first trials of Enovid were on three infertile women who nonetheless continued to ovulate. It was demonstrated that Enovid could be used to turn ovulation off and on at will. After this success, a full-scale human trial was mounted in Puerto Rico in 1956.

When the Worcester Foundation researchers chose Searle’s hormone for its human trials, Syntex — which had developed a viable oral contraceptive first — was left out in the cold. So Syntex began their own trials of norethisterone with the aid of Dr. Edward Tyler of the Los Angeles Planned Parenthood Federation and researchers at Parke-Davis, a U.S. pharmaceutical company.

In 1957, the U.S. Food and Drug Administration FDA approved the use of both norethisterone and norethynodrel in treating menstrual disorders. In May of 1960, G.D. Searle received approval from the FDA to sell their product — Enovid — as an oral contraceptive. In 1962, Syntex and their new licensees — the Ortho division of Johnson and Johnson — received the same approval for their product, “Ortho-Novum.”

Many people have been called the “father of the Pill.” Contenders include Carl Djerassi, Frank Colton, Gregory Pincus, and Russell Marker. But the undisputed “mother of the Pill” was Margaret Sanger. It was her vision. She brought together a source of money her friend Katherine McCormick and a researcher Gregory Pincus with the will and the background in hormones and reproduction to do it.

Margaret Sanger, who lived from September 14, 1879 to September 6, 1966, first coined the term “birth control.” She was the sixth of 11 children. She worked to make it legal to print contraceptive literature. In Brooklyn in 1916, she opened the first birth control center in the U.S. In 1927, she organized the first World Population Conference in Geneva, Switzerland. She also helped found the Planned Parenthood Federation of America in 1942.

Side Effects

When the first oral contraceptives became commercially available, some worrying side effects appeared. Risks ranged from nausea, breakthrough bleeding bleeding between menstrual periods, mood changes, weight gain, and breast tenderness to more serious problems such as strokes, blood clots, and heart attacks. In some rare cases, the use of the pills caused death. At first, these problems were largely ignored by a public hungry to try this powerful new drug. But by the late 1960s, consumers were wonder about side effects caused by oral contraceptives. Senate hearings on the safety of the pill were held in January of 1970.

There was a public debate on whether or not the risks outweighed the benefits of using the pill. But scientists had already discovered that the doses of hormones in the pills were higher than they needed to be. Pills with much lower hormone levels became available and side effects were greatly reduced. Eventually, public concerns faded and today birth control pills have become ubiquitous. There are, however, some lingering questions as to whether or not birth control pills impact a woman’s chances of developing certain kinds of cancer, such as those of the breasts and cervix.

“American women were quick to accept the pill. Within two years, approximately 1.2 million women were using it, within five years, 5 million, and by 1973, about 10 million. In the early ’80s, following reports of possible harmful side effects, use of the pill dropped to 8.4 million. Today in 1990, however, with safer, low-dose versions on the market, use is back up. Approximately 10.7 million American women now use the pill. It is the most popular method of non-surgical contraception.” “The Pill: 30 Years of Safety Concerns”, by Sharon Snider, December, 1990, FDA Online

The pill at 40

Today, in the year 2000, by some estimates, 100 million women use or have used birth control pills worldwide. The effectiveness of birth control pills is placed at 99.9 by experts — better than any other method, apart from abstinence or surgical sterilization. But the effectiveness depends on how faithfully it is used most regimens require taking one pill every day. The oral contraceptive was the first drug approved by the FDA with an express purpose other than to cure disease. It was also unique because it was a voluntary drug — not something you took because a doctor thought you needed it, but rather because you wanted to control your reproductive life.

According to Susan Scrimshaw, a researcher at the University of Illinois, the effects of the birth control pill are difficult to determine but it has made contraception in general more socially acceptable. It separated contraception from the sex act. Scrimshaw says, “We have smaller populations for the year 2000 than was predicted in the 1960s or even in earlier years. … Optimistic predictions were 7 billion people for the year 2000. Without modern contraception, world population might be higher.”

She added, “The pill also helped change women’s attitudes about their ability to control their fertility and, therefore, plan their lives in a new way. In the U.S., I believe, this led to more certainty in women’s careers and was part of women’s really growing in stature and influence in the professions. Internationally, I think, it also helped women with the sense of control over their lives and is still part of transformations in women’s independence and growth in education and leadership.”

What you have in your mind?