From “The Brass Tack”: http://www.brasstack.blogspot.com/A Medical History of the Contraceptive Pill
This article was first given on November 7, 2008 at the conference of the Center for Ethics & Culture, University of Notre Dame. A version also appeared on the MercatorNet website on January 15, 2010. A short time later, the well known Australian feminist Anne Summers quoted from it in her column in the Sydney Morning Herald.
Ernest Starling (1866-1927) was the British physiologist who in 1905, along with William Bayliss, established the existence of “hormones”, chemicals which were produced in one tissue of the body, delivered into the bloodstream and elicited a response from another distant tissue.
The term “hormone” was coined in 1905 by the British physiologist Ernest Starling, after the Greek word meaning “to incite to activity”. In the early 20th century, a variety of chemicals were found to have “hormonal” effects in humans: they were produced in one tissue, entered the bloodstream and incited a specific effect on another distant and unrelated tissue. Insulin, thyroxine, testosterone and cortisone were discovered at this time and were found to have remarkable restorative properties when given to patients with a number of common diseases. This enthusiasm for the therapeutic potential of “hormones” also extended to the area of human reproduction In the late 19th century, Professor Brown-Sequard, at the age of 72, injected himself with the extracts of guinea pig testicles and reported their rejuvenating effects.
Between 1910 and 1930, the hormones estrogen and progesterone were found to play important roles in the physiology of female mammalian reproduction, and so by around 1940, it became apparent that in human females, fertility depended upon the complex interactions of a hierarchy of hormones which affected the ovaries first, and then the uterus. The ovaries were found to be the source of a “female factor” in human development (the ova or egg): complementary to and just as necessary for human reproduction as the “male factor”. This picture — which seems so clear today — was in fact a dramatic insight, considering that even in the second half of the 19th century many scientists still believed that conception occurred when the male factor – a seed – was sown into the female womb– the soil. A woman’s contribution to conception was thought to be that off a passive receptacle offering a favorable environment for the germination of the seed.
The picture that now emerged meant that fertility in women was in the normal case orderly and cyclical, and therefore predictable. This new understanding of human reproduction seemed to lift the veil on an awesome event that, until then, had been shrouded in mystery. Science began to expose the mystery, to reveal the mechanics of how human beings came about, and made that event accessible and open to manipulation.
The notion that fertility in mammals could be controlled by the manipulation of reproductive hormones was first proposed by the Austrian physiologist Ludwig Haberlandt, who based his hypothesis on his own work with laboratory animals He and others observed that the ovarian follicle would not mature and ovulation would not occur during normal pregnancy, and that
If pregnancy does not occur during a normal menstrual cycle (above), the corpus luteum will stop producing progesterone, the endometrium will stop growing and menstrual bleeding will occur. If pregnancy occurs, the zygote produces human chorionic gonadotropin (HCG) which prevents the involution of the corpus luteum. Persistent progesterone production by the corpus luteum sustains the viability of the endometrium so that development of the embryo can continue.
So scientists like Haberlandt, who would seek to develop a birth control pill, focused their efforts on finding a chemical that would mimic the normal effects of progesterone. In effect, they sought a chemical that would induce a pseudo-pregnant state Haberlandt was probably the first to propose that “hormonal sterilization” — which he had successfully induced in several animal models — could and should be applied to humans. He even developed a progestin-based oral contraceptive which – a few decades after his death in 1932 – was studied and distributed as the contraceptive “Infecundin” in Eastern Europe by Marxist governments. His original observations on the contraceptive potential of progesterone in animals proved to be of use to others years later in planning strategies for control of human fertility.
Margaret Sanger (1879-1966) was an early and ardent supporter of birth control, founding the American Birth Control League in 1921. In 1942, the group was renamed Planned Parenthood Federation of America, today a major provider of contraception and abortion throughout the world.
While Sanger was primarily a political activist using the language and methods of class warfare to foster grassroots support for her movement, others sought to justify the need for birth control through geopolitical arguments. Generously funded by important private foundations, eugenicist academics like Frank Notestein and Kingsley Davis developed demographic models that were appealing by virtue of their simplicity and logic. They were also founded on a vision of the human person where self-interest was the driving force of every human action and a human being’s capacity for transcendence was a priori disallowed.
The demographic transition theory,first proposed in 1929 and developed further by Notestein, Davis and Coales, attempts to explain how economic growth can determine changes in human population. These early advocates of birth control argued that aggressive use of family planning could accelerate the achievement of low birth rates and low death rates (phase 4) in developing countries, a situation they believed to be optimal for social stability and human fulfillment.
Aided by their academic prestige and an abundance of financial resources, they argued the need for birth control as the most effective way of avoiding the otherwise inevitable depletion of the earth’ resources by a growing population of consumers. Both these groups skillfully influenced public opinion in the post-war period to soften opposition to the pill.
The scientific obstacles to development of the pill were substantial as well. Most experts had settled on progesterone as the preferred agent, but progesterone –like estrogen and most other steroid hormones — was digested, not absorbed, when taken by mouth. Chemists sought to alter the structure of the naturally occurring hormone so that it could be absorbed orally and still retain its natural effects. Raw progesterone was very expensive because it was very hard to come by. Until the 1940s, European pharmaceutical firms held a virtual monopoly on steroid hormone production, but their sources were limited to crude biological material from animal products: glands obtained from slaughterhouses, hormone derivatives obtained from the urine of pregnant animals. For example, the drug “Premarin”, commonly used as an estrogen supplement, is an acronym of the terms “pregnant mare urine”. These inefficient low-yield processes were inadequate to meet the high demand for hormones.
The challenge was to discover alternate sources of steroid molecules. This was possible because the hormones involved in human reproduction belonged to a large group of natural chemical compounds with a very similar structure. All the steroids have4 basic rings and their different effects in the body depend upon the addition or deletion of side chains to the rings.
Among those taking up the challenge was Russell Marker, a botanist and biochemist who sought and found an important source of steroid hormones in plants. Between 1939 and 1943, Marker and his team demonstrated that plant compounds called “sapogenins”, could be used as precursors of steroid synthesis. He devoted himself to identifying plants with high concentrations of sapogenins. In 1941, while on a search for plant sources in New Mexico he stumbled on a reference book describing a tuberous plant of the Dioscorea family: a common yam plant called “barbasco” by the natives of eastern Mexico (Veracruz) where it grew abundantly. He decided to analyze Dioscorea plants, obtained samples and confirmed very high levels of a sapogenin called diosgenin. The yam species Dioscorea villosa was particularly suited to his work.
The Mexican connection
Marker developed a simple, five-step method of converting diosgenin to progesterone, a process called the “Marker degradation”. He approached Parke-Davis, an American pharmaceutical firm that had supported his early research at Penn State, encouraging them to set up a production center in Mexico, but they declined. Being a pragmatic person, he sought local support by checking the Mexico City telephone book for chemistry labs that might be willing and able to work with steroid hormones. He found “Laboratorios Hormona”, a company founded by two eastern European émigrés, Emeric Somlo and Federico Lehmann. When they first met, Marker showed them a sample of his work: 80 grams of pure progesterone, representing almost one third of the world’s supply of the chemical. They agreed to form a new company, naming it Syntex Laboratories, from “synthesis” and “Mexico”. After a year of successful work, Marker and his partners disagreed over finances, and he left the company, taking the instructions for synthesizing progesterone from diosgenin along with him.
Gregory Pincus (1903-1967) performed studies in animals to confirm the contraceptive effects of norethinodrel. His data were used to justify human research using the same chemical. He collaborated closely with the obstetrician John Rock, and was supported financially and politically by Katherine Dexter McCormick, Margaret Sanger and other birth control activists.
The Worcester Foundation was intended to be a place for drug companies to send promising chemicals to test their pharmacological effects in animals. Their initial attempts, working primarily for GD Searle, were disasters and the Worcester Foundation almost went out of business several times. The change in his fortunes began in 1951 when he met Margaret Sanger at a dinner hosted by Abraham Stone, an executive of the Planned Parenthood Federation.
Sanger had been looking for a scientist with his skills, who would also be willing to take on a controversial project. Pincus’ collaboration with Sanger and Planned Parenthood started him down the path to the Pill, but their financial support was sporadic and limited. Real progress in identifying an orally active birth control pill did not occur until Katherine Dexter McCormick became involved, lending abundant financial support to the project. McCormick was the heiress by marriage to the International Harvester fortune. Born into a distinguished family of progressive Chicago attorneys, she was the second woman ever to graduate from MIT, the first with a degree in the sciences. She gave up plans to study medicine and reluctantly married Stanley McCormick, who within 18 months had to be institutionalized for schizophrenia. They had no children, and lived apart for most of their lives. She was an ardent supporter of women’s suffrage and birth control, having first crossed paths with Margaret Sanger in 1917.
Katherine Dexter McMormick (1875-1967) used her immense fortune to support the clinical development of the oral contraceptive pill. Historians acknowledge that her active assistance was critical to the success of the scientific work.
The next step along the path to approval of the Pill would require studying these compounds in women, and so they turned to a physician – John Rock – who was an obstetrician-gynecologist. Harvard-trained, a pioneer in the treatment of human infertility and Irish-Catholic, Rock -– from the perspective of politically astute birth control activists — was the perfect man for the job. When he was approached by advocates of birth control, Rock had already devoted decades to the study of human reproduction and embryology, and was renowned for being the first -– along with his Harvard colleague Arthur Hertig -– to successfully fertilize a human egg in vitro.
The first human trials of norethinodrel were designed to measure ovulation rates and other effects on the reproductive system. It was first tested in Brookline, Massachusetts, on 50 women who were patients of Rock’s infertility clinic. None of them showed evidence of ovulation while taking the pill. The second group tested included 23 female medical students from the University of Puerto Rico. Within a few months of the trial, half of the women withdrew from the study — despite veiled threats of adverse academic repercussions by some of the investigators — citing side effects and cumbersome data collection requirements. A third group –patients at the local psychiatric hospital in Worcester – was also given norethinodrel and provided data that eventually led to the approval of large-scale trials to monitor its contraceptive effects specifically
The first large-scale study of norethinodrel’s contraceptive effect was conducted in Puerto Rico, a site not chosen randomly. Comstock laws were never in force there; it was an island with very high population density; and the local government was very cooperative, having established a network of family planning clinics with the assistance of Planned Parenthood years before In addition, Pincus noted that the US press would be less likely to interfere if studies were conducted away from the mainland. The study began in April, 1956 under the supervision of Edris Rice-Wray, an American-trained physician with ties to the medical school, the public health department of Puerto Rico. She had run a family planning clinic there, and trained health care workers in contraceptive use. Norethinodrel proved to be a highly effective contraceptive, despite the side effects that began to emerge.
Pincus, Rock and Searle executives were soon satisfied that the contraceptive efficacy of norethinodrel had been adequately demonstrated. In 1957, G.D. Searle marketed norethinodrel as Enovid — not for contraception but for “menstrual problems”. The package insert prominently noted as a “warning” that the drug could induce temporary infertility as a side effect. This was in effect Searle’s trial balloon. They quickly learned that prescriptions for the Pill far exceeded the number of women who had previously complained of menstrual problems.
The half century defined by the emergence of the science of human reproduction around 1910 and the approval of the first hormonal contraceptive pill in 1960 was a period of dramatic scientific and social change. Science demystified human reproduction, breaking down the process into its basic components and making it accessible to manipulation.
These new scientific insights offered some people – a relatively small group of influential individuals persuaded by a materialist worldview and eugenicist principles – an opportunity to advance their ideology of social engineering on a global scale. They were radical political activists working together with brilliant, ambitious scientists and academics, and wealthy agnostics, who eventually succeeded in presenting birth control as a moral imperative for modern societies. An analysis of the effects of the hormonal contraceptive on individuals and societies over the ensuing 50 years should provide important opportunities to value the mystery of the generation of new human life more fully.
+ The Fertility Doctor by Margaret Marsh and Wanda Ronner is a recent account of the tragic life of John Rock written by two sisters, one a historian the other a gynecologist. They were given access to personal papers by the family of Dr. Rock.
+ Birth Control in America: The Career of Margaret Sanger by David Kennedy steers a course between hagiography and hostility.
+ Katherine Dexter McCormick: Pioneer for Women’s Rights takes a benevolent view of its subject, but does not skate over her troubled life.
+ The scholarly book Sexual Chemistry by Lara Marks is an excellent detailed account of the history of the Pill. A scholarly article by Marks and Suzanne White may be found online here.
+ For a less detailed history see “On the Pill: A social history of oral contraceptives, 1950 -1970” by Elizabeth Siegel Watkins.
+ Carl Djerassi – self-proclaimed father of the birth control pill — has written two entertaining books about his own role, “This Man’s Pill” and “The Pill, Pygmy Chimps and Degas’ Horse”.