The Fifth Freedom

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.

The most spectacular new development has come from France, where Etienne-Emile Baulieu, the author of one of the books under review, invented an abortion pill called mifepristone, or RU 486. Like Djerassi’s contraceptive pill, it is an analogue of the hormone progesterone that prevents ovulation once a woman has become pregnant. While Djerassi’s pill mimics progesterone in its action, RU 486 blocks progesterone’s uterine receptors so that this hormone cannot act on them. The uterus responds by menstruating and ejecting the embryo.

In France RU 486 is now sold in 860 authorized family planning center pharmacies where every pill must be accounted for on a register, and doctors are supplied only with the exact amounts needed. Its use is allowed up to seven weeks after the last period, and only after a delay of seven days which is provided for the mother to reflect on whether she really wants to have the operation. She then takes three pills of RU 486 in the doctor’s presence, goes home and returns 36 to 48 hours later for the administration of a prostaglandin that promotes the expulsion of the embryo. After four hours’ rest she is allowed to go home. By 1991 over 80,000 Frenchwomen had used RU 486. Its use has also been approved by the British National Health Service and by the government of China.

In a trial of RU 486 combined with prostaglandin on 588 women in Britain, the treatment induced complete abortion in 553 women—94 percent. Only 35 women needed surgical abortion afterward. Many women complained of severe pains for two hours after administration of the prostaglandin, and 5 percent still suffered them two days afterward, but none by nine days. Sixteen percent suffered severe bleeding for one or two days after termination and two women suffered it for nine days. The report concludes, “This procedure needs to be clinic-based, and preferably hospital-based, in view of the small but definite risk of severe haemorrhage,” a condition that may restrict its wide use in developing countries.³

In Britain about 160,000 pregnancies are terminated legally and free under the National Health Service each year; yet the abortion rate is only two fifths that of the United States—a fact that American opponents of abortion might reflect on. The National Health Service welcomes RU 486 because, unlike surgical termination, it needs neither operating theaters nor anesthesia and therefore saves money and doctors’ time.

According to the traditional doctrine of the Catholic Church, making love is sinful except for the procreation of children; an unwanted child has therefore been conceived in sin. Abortion is held to be wrong not only because it kills a budding human life but also because it relieves the mother of the consequences of her sin and encourages sin in others. In Catholic Austria, for example, the law formerly included the notorious paragraph 144 that made abortion punishable by imprisonment for both the mother and whoever helped her. But, as Baulieu writes, such laws did not stop abortion, they only made it more dangerous to the mother, especially if she was poor.

As a medical man, Baulieu has no moral scruples about the abortion pill. He writes that more than 50 million abortions are performed in the world each year, about half of them illegally. In the former Soviet Union abortion was the main method of birth control; according to official figures 7 to 8 million were performed a year. In Poland abortion has been legal if approved by two doctors and a psychiatrist. Since these are hard to find in a poor country, about half a million of the 600,000 abortions a year are performed illegally and at great danger to the mother; recent legislation, moreover, threatens to make virtually all abortions illegal. In Japan, doctors have such a strong vested interest in abortion that they have prevented the introduction of contraceptives. In the United States 1.6 million abortions are performed annually, half of them on girls under twenty; the US has the highest rate of teen-age pregnancy in the developed world, four times that of the Netherlands. In Romania, Ceauçescu made abortion punishable by death, but this Draconian law made the birth rate rise only briefly. Instead of producing more babies, the law resulted in the highest rate of dead mothers in Europe. Opponents of abortion might well reflect on that experience and on the appalling mortality and morbidity of women caused by badly done abortions in all countries where the operation is illegal or medical help is unavailable.

Baulieu writes that 200,000 women throughout the world die each year from botched abortions. For every one who dies, twenty to thirty others suffer infections, perforations of the uterus, or lasting injuries that can lead to infertility. “Medicine’s mission is to help people,” he writes. “Why should 200,000 women die each year for lack of a better way? If science can make it otherwise, why must a woman’s decision to terminate an unintended pregnancy be accompanied by pain and punishment?” Baulieu tells of encountering poor women who injured themselves with a stick, and of brutal surgeons who tell their assistants not to bother with anesthesia when repairing the damage, in order “to teach them a lesson.” He set out early in his career to find a better and more humane way.

Anti-abortionists have branded RU 486 a death pill or a chemical time bomb, and Baulieu has been compared to “an amalgam of Joseph Stalin and Adolf Hitler,” and accused of plotting the death of several billion human beings. Like Djerassi, he is a doctor’s son, but unlike Djerassi he was never employed by industry and has spent his entire career in university clinics. He began research on sex hormones and their receptors with support from the Ford Foundation and the Population Council in New York in the 1960s, and it took him fifteen years to develop RU 486. He receives, as he emphasizes, no royalties from its sales. (Baulieu quotes an older colleague’s description of himself as “optimistic, enthusiastic, high-spirited, open-minded, cultured, serious, but always aware of the comedy, philosophic but never ponderous.” Yet he sounds rather solemn when he writes: “I have always been motivated by my scientific curiosity and, at the same time, I want to take part in advancing science to benefit society.”)

The German pharmaceutical firm Hoechst owns a controlling interest in Roussel-Uclaf, the French manufacturers of RU 486. According to Baulieu, Wolfgang Hilber, the Catholic president of Hoechst, opposed the introduction of the pill, partly from conviction and also because he feared reprisal against Hoechst by opponents of abortion in the US. When RU 486 was first introduced in France, abortion opponents bombarded the French embassy in Washington with intimidating letters and threatened to boycott all Roussel-Uclaf’s goods. Faced with those threats and vociferous Catholic protests at home, the directors of Roussel-Uclaf decided in 1988 to suspend distribution of RU 486 just as Baulieu was departing for the World Congress of Gynaecology and Obstetrics in Rio to report on his new drug. He was shattered by the decision, but a few days after his arrival there he heard that Claude Evin, the French Minister of Health, had told Roussel-Uclaf that if they refused to produce RU 486, the rights would go to another company that would. Evin declared: “From the moment governmental approval for the drug was granted, RU 486 became the moral property of women, not just the property of a drug company.” His courageous decision reopened the way to the marketing of the drug in France.

Recently a social worker in California, Ms. Leona Benten, in collaboration with prochoice organizations, tried to bring the issue of the introduction of RU 486 into the United States to a head. She became pregnant, flew to London to purchase twelve pills of RU 486, and notified the Food and Drug Administration that she would import them at Kennedy Airport in order to use them on herself under her doctor’s supervision.

The Food and Drug Administration had ruled some years ago that a person is allowed to import untested drugs not approved by them if they are for personal use. Under political pressure the FDA officials later excepted RU 486 from that rule. When Ms. Benten arrived at Kennedy Airport, FDA officials were there to meet her and confiscate the pills of RU 486. Ms. Benten, her doctor, and lawyer then applied to the federal court for the Eastern District of New York for return of the drugs and also asked the court to enjoin the enforcement of a ban on the drug. Judge Charles Sifton ruled that the pills should be returned to Ms. Benten, commenting that she could “hardly be faulted for relying on her own physician, in her own state,” to perform the supervision necessary to ensure a safe and successful outcome. But he denied the broader application sought by the plaintiffs. A few days later, the 2nd Circuit Court of Appeals blocked his ruling. An emergency request to the Supreme Court to annul the Appeals Court’s decision was turned down on the grounds, The Washington Post reported, “that the petitioners had failed adequately to make their case that the FDA’s confiscation was illegal.”

If the opposition of the FDA and the Supreme Court to introducing RU 486 into the US derives in part from the fear that it would further increase the number of abortions, so far such an increase has not taken place in France where the abortion pill was introduced in 1988. By 1989 about one third of the total number of French abortions were performed with it. According to the statistics of the Institut National de la Santé et de la Recherche Médicale, the French equivalent of the National Institutes of Health in the US, the number of abortions since 1980 has varied from a peak of 182,862 in 1983 to a low point of 162,352 in 1987. The total was 163,090 in 1989 and 169,303 in 1990, well within the usual fluctuations. The number of abortions per hundred live births has remained steady since 1986 at just above twenty-one. The number of abortions per head of population performed annually in France is slightly larger than in Britain, despite the fact that France is predominantly Catholic and Britain predominantly Protestant.

In 1965 the great Scottish gynecologist Sir Dugald Baird gave a lecture with the title “A Fifth Freedom?” He began it by reminding his audience of a speech by Franklin D. Roosevelt on January 6, 1941, about the four freedoms for which World War II was being fought: freedom of speech and expression; of worship; and freedom from want and fear. Baird suggested that it was time to consider a fifth freedom, from the tyranny of civilized man’s excessive fertility.⁴ Unwanted pregnancies are a sad fact of life, and the decision whether an abortion is to be performed at all and whether by surgery or by hormone treatment should be a personal and medical decision rather than a judicial or political one.

Unfortunately, however, the anti-abortion position of the Bush administration, combined with the anti-abortionists’ terrorist tactics, gives little hope that RU 486 will be approved for sale in the US. Roussel-Uclaf now sells the drug only to industrialized countries with closely monitored pharmacy distribution and well-run modern clinics, which excludes many developing countries, probably because the firm fears the adverse publicity that might result from any accidents caused by its misuse. In theory, the World Health Organization would be able to supply RU 486 to any qualifying country that requests it, but in practice its officials fear the wrath of the American administration on which WHO depends for financial support. That fear extends into the poorest corners of the world. Baulieu writes that “in Bangladesh, some government hospitals refused to assist women who had attempted their own abortions, endangering their lives, for fear of losing American aid.”

Baulieu castigates the Indian bureaucracy for delaying the introduction of RU 486 to India, but he does not seem to consider that its cost may deter them. Roussel-Uclaf originally asked the French Health Service to pay $80 per dose; the Service offered $16, and they eventually compromised on $41. I wonder how many governments of developing countries could afford to buy it at that price; if it were sold to women wanting abortions, only the better-off would be able to pay for it, but they probably need it least, because they may well use contraceptives already. Nor will RU 486 help the huge number of women in developing countries who live too far from hospital clinics to use the pill under medical supervision.

I therefore believe that Carl Djerassi is right when he pleads for continued intensive research on better and cheaper contraceptives as the most effective and humane way not only of reducing the number of abortions but of helping to limit population growth, particularly in poor countries; such research and the contraceptives that result from it, however, will not have a wide impact if intelligent programs of sex education are not also provided for young people. The low rate of teen-age pregnancies in the Netherlands is said to be a direct outcome of the excellent education about sexual behavior that children receive at school. Indian medical authorities have repeatedly made it clear that educating women about sex, pregnancy, and contraception is essential for lowering the birth rate. I have little doubt that instead of legal sanctions against abortion, such education could also be the most effective way of reducing the number of unwanted teen-age pregnancies in the United States.