The right Pill at precisely the right time

September 28, 2001

If the creation of the oral contraceptive had been delayed, it would never have made it to the market, argues its inventor Carl Djerassi.

On October 15 1951, the first synthesis of a steroid oral contraceptive was completed in the laboratories of Syntex, a small pharmaceuticals company in Mexico City. That very substance, albeit in lower dosage, is still consumed today by millions of women.

In general, scientific breakthroughs occur only when enough background information has accumulated. For instance, someone else would probably have discovered the double-helix structure of DNA within months of the Watson-Crick announcement, but certainly not ten years earlier.

The same can be said about the synthesis of the first two steroids, norethindrone (1951) and norethynodrel (1953), which opened the door to orally effective contraceptives. Developments in steroid chemistry in the preceding dozen years in Germany, the US and the UK enabled our team at Syntex to conceive of the chemical structure of norethindrone and then to complete its synthesis in October 1951. Whether the subsequent production of the closely related norethynodrel in 1953 was done independently or based on our publication does not really matter, because the state of steroid chemistry was such that somebody could have made such discoveries about that time. Our group just happened to be first.

But if we had synthesised norethindrone 15 years later - in 1966 - oral contraceptives would very likely be a scientific curiosity rather than an important component of 20th-century social history. This is not the opinion of an arrogant chemist, however convinced he may be of the crucial role of his scientific discipline, but rather that of a pragmatist. Such a delay would not have prevented the eventual scientific demonstration that a steroid oral contraceptive was possible. If our chemical research had been completed in 1966, we still would have sent norethindrone to various biologists who would have demonstrated in animals that such synthetic steroids could be used for what the Austrian physiologist Ludwig Haberlandt had envisaged in the 1920s as oral "hormonal temporary sterilisation". And there is little doubt that, by the early 1970s, clinical researchers would have tested such steroids in humans. But then a wall would have been reached, because hardly any pharmaceuticals company with the muscle needed to bring oral contraceptives to the market would have been willing to carry on.

Why? In a word: thalidomide. By 1960, the use of thalidomide to treat prenatal nausea had revealed its tragic legacy of birth defects. The regulatory climate changed dramatically, especially when it came to the justified concerns about teratogenic side-effects. At the same time, the litigious nature of drug liability suits escalated qualitatively and quantitatively. A second horror scenario - this time in the birth-control field - involved the Dalkon Shield intrauterine device, which eventually drove the company marketing it into bankruptcy. It thus became clear that, in developing a systemic contraceptive used for long periods of time by healthy people who were not prepared to risk many side-effects, much of the 17-year life of a patent would be consumed by that development phase.

Although the much increased development costs for preventive drugs (such as contraceptives or vaccines) consumed by "healthy" people was one factor, a second and, in some respects, even more important one came into play in the late 1970s - precisely the date when clinical work for an oral contraceptive would have been completed if the basic chemical research behind it had only been delayed by 15 years.

In the last quarter of the 20th century, the international pharmaceuticals industry came to centre increasingly on blockbuster drugs, and this led the industry to consolidate via mega-mergers. The nature of the mix of drugs that came out under this new emphasis - psychopharmaceuticals, anti-inflammatory, cardiovascular drugs, anti-cancer chemotherapeutics and, most recently, palliatives in Alzheimer's disease - revealed the influence of another set of social, economic and political trends: the emphasis on diseases of an increasingly geriatric patient population, the only age group in the US to have achieved universal health insurance as well as the most rapidly growing age group in affluent Western Europe and Japan - consumers whose personal radar hardly encompassed birth control. Thus, it should come as no surprise that a 1988 survey of the international pharmaceuticals industry showed that new human fertility control methods were not even among their top 35 research priorities. Today, only one of the world's ten largest pharmaceuticals companies, ninth-ranking American Home Products, has a marketing and research commitment to the field of birth control.

If my hypothetical scenario had actually played out, in 2000 the status of a Pill for women would be identical to the current status of a Pill for men. Reproductive scientists have known for years how to create a systemic contraceptive for men - a combination of a steroid turning off sperm production and of a long-acting testosterone derivative to maintain libido - but none of the world's 20 largest pharmaceuticals companies is prepared to spend the necessary $300-$500 million for converting that scientific knowledge into a commercial product.

Given my Pill-less scenario, what would have happened to the sexual revolution of the 1960s, which is almost universally credited to or blamed on the Pill for women? While possibly delayed by a few years, we still would have had greatly increased sexual freedom because the recreational drug gurus, the Beatles and other rock-and-roll musicians, the hippies and the flower children - the social and cultural icons of the 1960s - would all have left their indelible marks. Simone de Beauvoir, Betty Friedan, Germaine Greer and the other flag-bearers of the woman's liberation movement had already been born. Pill or no Pill, they all would have written the words that launched the most important social revolution of the past few decades. But without the Pill - even with more extensive use of condoms, diaphragms and IUDs - western society would have faced a plethora of unwanted pregnancies. Some of them would have been hidden in the time-honoured palliative of the shotgun wedding, but I have no doubt that the number of back-alley abortions would have risen greatly and created even more pressure for the legalisation of abortion.

In the final analysis, it was the women's movement coupled with more effective birth control (and not the other way around) that unlocked the doors of the kitchens, nurseries and bedrooms so that women streamed into the working world with all the consequences that so many Pill critics bemoan and blame on the Pill. In 1900, 6 per cent of US married women worked outside the home, compared with 61 per cent now.

Does all this imply that the Pill played a negligible role in four decades of continued clinical use? If all these things would have happened anyway, why did millions of women in the developed world accept the Pill in the 1960s with totally unanticipated speed as their preferred choice of contraception? Why, as we enter the 21st century, is the Pill the top modern contraceptive method among married women in 78 out of 150 countries - countries such as Brazil, Bangladesh and Algeria, to pick just three outside North America and Europe? The Pill played an enormous role, partly causative, though mostly facilitative, by the simple fact that at precisely the right time in western social history, a convenient oral contraceptive became available that completely divorced contraception from sex. The fact that a woman could use it in privacy and that it was her decision alone was crucial.

That brings me to my final question: do technocrats and technophobes alike credit the means with more influence on the ends than is justified? Is it not equally likely that the 15-year window of opportunity for the development of oral contraceptives as a practical means of birth control was created by the confluence of two seemingly separate movements in the 1960s: the women's movement and the then geopolitically fashionable focus on the population explosion?

Forty years ago, somewhat naively, it was assumed by many government leaders that a technological fix through new methods of birth control was the sole answer. That feeling and women's desire to take more control of their own reproductive function created a climate that hardly exists now. Population issues have now receded from the consciousness of many rich countries, and women's reproductive control is now taken for granted. As a result, the 50-year-old Pill in one of its diverse forms is unlikely to have much competition in the foreseeable future.

Carl Djerassi is professor of chemistry at Stanford University and author of This Man's Pill: Reflections on the 50th Birthday of the Pill , which is published next week by Oxford University Press, £12.99. On October 12, he will present a Friday Evening Discourse at the Royal Institution on "A Revisionist History of the Pill".

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