The Pill, Pygmy Chimps, and Degas’ Horse: The Autobiography of Carl Djerassi
The ‘Abortion Pill’
The world population now increases by 1.7 percent (90 million) per year, while production of cereals is increasing by only 0.9 percent per year. During the past twenty years there have been about 200 million hunger-related deaths; the growing food deficit may raise that number five-fold in the next twenty years. The population of some of the poorest countries is growing fastest. Bangladesh, with a land area smaller than that of Wisconsin, now has a population of 114 million, which is expected to outstrip the present population of the United States, 240 million, in about thirty years’ time. What will happen to these poor people? Even if by some miracle of science enough food could be produced to feed them, how could they find the gainful employment needed to buy it? These prospects are so grim to contemplate that both the Pope and the White House are reported to have forced the recent conference on the environment at Rio to ignore them.
Tragically, the population explosion is the result of the North’s least controversial contribution to the South, the prolongation of life by modern medicine and hygiene, or, as Viktor Weisskopf put it, the introduction of death control without birth control.
Carl Djerassi, the inventor of the contraceptive pill, and Etienne-Emile Baulieu, the inventor of the abortion pill, have provided the means to avert or at least mitigate the catastrophe. Both their autobiographies express bitterness that religious and political pressures are preventing the introduction of these pills into some of the countries that need them most.
Djerassi, who was brought up in Vienna, came to New York just before World War II with twenty dollars in his pocket, and thirty years later he had become a world-famous scientist and millionaire. Fortunately when he arrived at the age of sixteen he had a first-class high-school education and a good knowledge of English. He had the cheek to ask Eleanor Roosevelt to find him a college scholarship and, even more remarkably, she responded by forwarding his letter to the Institute for International Education, which found him a scholarship at Tarkio College, Missouri, a Presbyterian school of twenty teachers and 140 students. After a year he was offered a room, board, and tuition scholarship at the Episcopalian Kenyon College in Gambier, Ohio, where, during the next year, he obtained the bachelor’s degree in chemistry, needed in wartime, he tells us, in order to be drafted into the army as an officer rather than an enlisted man. However, a lame knee kept him out of the army, and he found a job with a pharmaceutical company in New Jersey instead. While working there he attended night classes in chemistry at New York University and the Brooklyn Polytechnic, helped to synthesize one of the first antihistamines and got his name on a patent, all in one year. The next step was an Alumni Research Foundation Scholarship at the University of Wisconsin at Madison, where Djerassi obtained his Ph.D. in chemistry in two years at the age of only twenty-two.
In view of complaints of anti-Semitism at American colleges by the physicist Richard Feynman and others, I found it heartening that a penniless Jewish immigrant from Vienna was launched on a brilliant career by scholarships at two Protestant colleges and one university in the heart of the allegedly xenophobic Midwest. To judge by the time it took him to finish his studies, he must have possessed a phenomenal combination of talent and drive.
Djerassi returned to the pharmaceutical firm to work on antihistamines, but became restless for a greater challenge. The anti-arthritic properties of cortisone had just been discovered, but it had to be extracted from the adrenal glands of animals at a cost of $200 a gram. Djerassi wanted to attempt to make cortisone synthetically. When his firm showed no interest in such a forbiddingly difficult project, he left and joined Syntex, a newly formed pharmaceutical company run in Mexico City by young immigrant chemists from Europe.
Everyone had warned him that serious chemical research could never be done in such a remote place, but by May 1951 Djerassi’s team had synthesized cortisone from a compound extracted from a Mexican yam. Their paper announcing that great feat arrived at the office of the editor of the American Chemical Society a few days ahead of papers by two famous chemists, R.B. Woodward and L.F. Fieser, who had achieved the same synthesis by different methods.
Nature makes its own contraceptive, progesterone, a steroid hormone that inhibits ovulation once pregnancy has begun. It can be administered to prevent pregnancy, but it is too weak when given by mouth: to work it must be injected. Djerassi set out to synthesize a contraceptive analogous to progesterone that would be active when administered orally. On October 15, 1951, Luis Miramontes, a Mexican chemistry student working under the direction of Djerassi and the young head of the laboratory, George Rosenkranz, synthesized a compound, called norethindrone, that had the required chemical structure. Djerassi writes: “Not in our wildest dreams did we imagine that this substance would eventually become the active progestational ingredient of nearly half the oral contraceptives used worldwide.” The team had accomplished this synthesis in less than six months, when Djerassi was twenty-eight years old. Eleven years later, after conducting a great many tests, the US Food and Drug Administration approved norethindrone for contraceptive use.
Having been responsible for two spectacular inventions, Djerrasi resigned from Syntex to become associate professor of chemistry at Wayne State University in Detroit. His real interest lay in fundamental rather than applied research, and he wanted to explore the chemistry of the giant cacti that grow in Mexico.
His next original contribution was the development of an optical method for determining the chemical structure of asymmetric compounds. This won him a prize from the American Chemical Society and a chair as a professor of chemistry at Stanford University, where he has remained ever since, and where, while keeping up his connection with Syntex, he has brought new ideas to research and teaching. Having given a course of lectures on steroid chemistry, he asked each student to formulate examination questions, promising to distribute the questions randomly among the class. When he returned the questions, one student after another protested that he had been given his own question back by mistake. Gradually they realized this had been Djerassi’s intention all along. Having tried to demonstrate their virtuosity by the complexity of their questions, each student was now faced with the grim task of answering them himself.
Despite Djerassi’s fame and wealth his autobiography ends on a note of bitterness. In the United States, the development of contraceptives has become so expensive that most pharmaceutical firms, including Syntex, have abandoned manufacturing them just when the world needs them most. A cheap, safe pill that can be taken once a month would ease contraception throughout the world, because many women, especially if they are uneducated, apparently find it hard to take the pill regularly every day at the correct interval after each period. Besides, many women cannot afford it One factor that makes the extensive research needed for development of such a pill uneconomic in the United States is a widespread public misunderstanding of the effects of the prolonged use of any drug on a large population. Genetic diversity insures that there will always be some people in whom even the safest drug produces adverse effects. If the percentage of such people is substantial, then the adverse effects show up in clinical trials carried out on several hundred people before the drug is released on the market; but if the adverse effects manifest themselves in only, say, one person out of 10,000, then the probability of their showing up in clinical trials is negligible. When the drug is later used by millions, and affected persons sue the manufacturers for negligence, then litigation and damages may cost that firm many millions of dollars. These costs and the accompanying adverse publicity are some of the factors that have discouraged further development of contraceptives.
The other factors derive from the safety regulations imposed by the Food and Drug Administration, which, in reports of damage suits in the press, has sometimes been blamed for being careless in approving drugs. The FDA has responded by demanding extensive and prolonged animal trials before any contraceptive could be approved for human use, including two-year toxicity studies of rats, dogs, and monkeys, followed by seven-year toxicity studies at two, ten, and twenty-five times the human equivalent in monkeys. Djerassi points out that these rules make the development of new contraceptives excessively expensive; yet they could never ensure complete safety, because reproductive cycles and responses to steroids differ too widely among different animals and even among different primates to produce results that are meaningful in human beings. There is no way of introducing better contraceptives or indeed any new drugs without risk to some people, and if the press, Congress, and the courts refuse to accept this, efforts to develop new contraceptives will move elsewhere.
This in fact is what has happened. Chemists at the Central Drug Research Institute in Lucknow, India, have developed an oral contraceptive, Centchroman, that does not use steroids and can be taken weekly.1 It inhibits the preparation of the uterus for “nidation” of the fertilized egg and also speeds its movement along the fallopian tube so that it arrives at the uterus too soon. Nearly 2,000 women of reproductive age have used it for an average of ten months without side effects and most of the 1,600 women who have used it for an average of twelve months have been protected from pregnancy. In those cases when the drug failed to protect the women, the babies born were normal. Normal fertility returned when the contraceptive was discontinued. This contraceptive was developed during the 1970s. The Indian literature I have read fails to explain why it is not being widely used. Judging by its complex chemical constitution, I suspect that it may be too expensive.
Scientists at the National Institute of Immunology in New Delhi have developed a vaccine against human chorionic gonadotrophin, a nonsteroidal hormone secreted by the corpus luteum (yellow body), a mass of cells that forms in the ovary after the egg has been expelled. Gonadotrophin normally enters the bloodstream and stimulates the secretion of progesterone, the steroid hormone that is needed to maintain pregnancy. By inactivating gonadotrophin the vaccine achieves the same results as the pill, and its effects can last for years.2 The first tests have shown that it works, but to be suitable for mass administration it must be cheap and produce a lasting effect after a single injection. The scientists are now making the vaccine by genetic engineering in a harmless vaccinia virus which can be cultured on a wide scale. A single injection of this engineered product has already protected monkeys from pregnancy for two years.
V.P. Kamboy, S. Ray, and B.N. Dhawan, "Centchroman," Drugs of Today, Vol. 28 (1992), pp. 226–231.↩
G.P. Talwar and others, "Phase I clinical trials with three formulations of anti-human chorionic gonadotropin vaccine," Contraception, Vol. 41 (1990), p. 301.↩