- Historic Sites
The Story Of The Pill
How a Crash Program Developed an Efficient Oral Contraceptive in Less Than a Decade
August/September 1978 | Volume 29, Issue 5
During the immediately following years, as World War II began and raged—and for a number of years after the Foundation for Experimental Biology was established—Pincus’ attention was largely diverted from reproduction and allied phenomena to war-related research. For this, he and Hoagland made a well-balanced team. Their superficially widely separate specialties were at base quite closely complementary. Internal message communication, the exchange of information among component elements, is of the essence in any functioning organization, including the human body. There are two very different ways in which vital messages are transmitted from one part of the body to another. Pincus as endocrinologist was concerned with one of these—the chemical messages (hormones) flowing in blood through the circulatory system. Hoagland as neurophysiologist was concerned with the other, namely, messages sent as electrical impulses along the nervous system. So the two men could and did collaborate for several years in investigations of the relationship of hormones to stress and combat fatigue, in addition to studies of adrenal cortical function in schizophrenic patients.
After war’s end, the Hoagland-Pincus research collaboration waned, ceasing altogether in the late 1940’s, as Hoagland’s time and energy were increasingly absorbed into the financing and administration of the foundation, where he demonstrated a major talent for organization and executive direction. Pincus, meanwhile, had gathered around him, first at Clark and then at the foundation, a group of brilliant young investigators, most of whom were as devoted to him personally as they were dedicated to their work, for he had a rare ability to inspire a personal devotion fused with scientific dedication in those closely associated with him. The foundation swiftly grew. In a dozen years its scientific personnel (originally fifteen) increased tenfold and its annual budget (originally $100,000) fortyfold, fed by private donations and governmental grants-in-aid, and by research grants from individuals, private foundations, the federal government, and pharmaceutical companies. One of the latter, G. D. Searle of Chicago, played an especially important role in the earliest history of the foundation and subsequently, with great profit to itself, in the development and marketing of the Pill. A grant from Searle financed Pincus’ first research (on the pituitary) at Clark; shortly thereafter he was hired by Searle as a scientific consultant, a post he retained for many years.
The chief among Pincus’ recruits was a man enticed from Cambridge University, with which institution both Hoagland and Pincus retained close ties. This recruit was a tall, slender, ironically humorous young Chinese named MinChueh Chang. He had come to Cambridge from his native land just as World War II began and, while Britain endured the rumble and terror of war, had earned not only a doctoral degree but also a justified reputation as a phenomenally skilled laboratory technician whose skill was guided by an acute and profoundly informed scientific intelligence. He arrived at Worcester in 1945, when the foundation was less than a year old. Soon thereafter he was immersed in an exceedingly difficult but highly successful study (using rabbits) of the role played by the seminal plasma, which is ejaculated with the sperm, in rendering sperm capable of fertilizing the egg.
And it was with rabbits that Chang made the first of the long series of experiments and tests that led directly, by specific prior design, to production of a mass-marketable oral contraceptive. The experiment, as has been indicated, was a repetition at Pincus’ behest of the 1937 experiment by Makepeace and others at the University of Pennsylvania. It began on April 21,1951 (Chang made careful note of the date, as if he sensed it might become historic), not long after Pincus’ meeting with Sanger and McCormick.
By then it was known that estrogen is an effective inhibitor of ovulation in women; the fact had been abundantly documented in the clinical reports of the use of estrogen as a medicine for dysmenorrhea. Indeed, Harvard professor Fuller Albright had been led by this to suggest, in 1945, the use of estrogen as an oral contraceptive: a daily pill of one of the then just-developed synthetic estrogens could accomplish “birth control by hormone therapy,” he said. But it was also known from animal tests, to which Albright in his paper did not refer, that estrogen posed certain risks which progesterone, evidently, did not ; which is why Pincus and Chang focused at the outset on progesterone. And when repetition of the Makepeace et al experiment confirmed its conclusion—progesterone was indeed an effective inhibitor of ovulation in rabbits—Chang went on to make what Pincus called the “logical extension” of this observation, namely, “a more intensive study of the nature of the progesterone action as well as the action of certain derivatives and putative metabolites [substances acted upon in metabolism].” The results of this extension were published in 1952, by which time Chang was experimenting with progesterone on rats—animals that are more like humans than rabbits in their reproductive physiology, since the female rat regularly ovulâtes, whether mated or not. Masses of information as to the dosage required to be effective were accumulated, and it was found (as was to be expected) that a much larger dose was needed when taken by mouth than when injected beneath the skin.