Medical Milestones

The pill: emblem of liberation

BMJ 2007; 334 doi: (Published 04 January 2007) Cite this as: BMJ 2007;334:s15
  1. Carl Djerassi, professor of chemistry emeritus [email protected]
  1. 1Department of Chemistry, Stanford University, Stanford, CA 94305-5080, USA

    The pill is one of the few drugs to have remained essentially unchanged decades after its synthesis—testament to its enduring value

    “What sort of pill?” is a question that very few readers seeing the topic of this article would ask themselves. Surely, that already tells us something about the popularity of an oral contraceptive that I, an organic chemist, would call 19-nor-17α-ethynyltestosterone (norethindrone, or some other closely related progestogen) combined with 17α-ethynylestradiol. What single procedure or vaccine would be known by the equivalent labels of “the operation” or “the jab?” The answer is none. Yet does the persistent popularity of “the pill” warrant adding the invention of the oral contraceptive to the list of 15 greatest medical milestones since 1840? To justify my affirmative answer, I first need to define what in my view does not qualify as a medical milestone.

    Clean drinking water and effective sewage disposal are of enormous benefit to public health, but in my book they are not a medical milestone because only the consequence, and not the originator, is medical in nature. Lifestyle changes such as stopping smoking, with its fantastic health benefits—although more of a borderline case than the first example—still would not qualify for me. Also, basic research advances that are far from the actual medical application won't qualify, because then we would also have to include important chemical synthetic reactions and analytical methods that make possible many chemical syntheses of substances that eventually become drugs. Thus, even a monumental discovery such as the elucidation of the chemical nature of DNA may be a borderline case.

    Making waves around the world

    Nevertheless, there is such a mass of truly important, practical, and medically unambiguous milestones that have affected millions of people that selecting the 15 most important seems to me patently impossible. For instance, how would I compare the eradication of a global scourge such as smallpox or polio with the importance of oral contraceptives? Such disease eradication should win hands down, since other types of birth control always did and do exist. So why did I agree to make a case for the inclusion of the pill among the 15 exalted milestones? The primary reason is that no other milestone has had as many societal, “non-medical” consequences; the pill is a stone thrown into water that has produced ripples and waves way beyond any reasonable expectation, for the following reasons.

    • The pill and intrauterine devices raised the expectations for contraceptive effectiveness to an extraordinarily high level, which in turn has had enormous favourable consequences for millions of women.

    • The pill offers women the ability to decide on their own, in private, whether or when to become pregnant, thus undermining the historical dominance of men in all matters relating to sex and reproduction. The consequences range from cultural to economic, professional, and educational aspects, most of them positive.

    • The pill and intrauterine devices introduced reversible birth control that was independent of the sex act, completely changing the nature of sexual intercourse, which now ranges from unworried pleasure to undisciplined promiscuity.

    • The pill was the first potent drug to be consumed for years by millions of “healthy” people, thus raising questions of defining safety and the risk-benefit balance in the long term that were quite distinct from those for other drugs taken over long periods (such as cholesterol lowering drugs), where the “benefit” was the prevention of a medical condition. The more serious the disease, the higher the tolerance for side effects, cancer being a classic example. In the case of the pill the “disease” is an unwanted pregnancy, for which the level of tolerance of side effects is very low. The discipline of epidemiology has probably been improved in depth and sophistication more through the thousands of studies of the pill than of virtually any other drug. No other class of drug has been examined in such depth and for such a wide range of side effects, from blood clots and cancer to the production of ear wax.

    • No other drug has had such an enormous effect on religion. For instance, Catholic couples, faced with their church's opposition to contraception, often make family planning a higher priority than avoiding “mortal” sin.

    • The explosion of medical litigation in the most litigious of all countries, the United States, started in the 1960s with the pill, with consequences—beneficial and counterproductive—that greatly affected the regulatory process for many other drugs.

    If these examples are not convincing, adding more to the list—such as that the pill is the preferred method of reversible contraception in more than half the countries in the world, that more than 80% of women in the US have at one time used the pill, or that about 100 million women worldwide at any one time are on the pill—would probably be overkill.

    An enduring classic

    Considering this implied panegyric, you might think that current research into even better methods of birth control would be flourishing. Nothing could be further from the truth. Of the 20 largest drug firms in the world, only three are active in modest efforts to improve the pill, and none is working on fundamentally new approaches, such as a contraceptive vaccine, or addressing the field of male contraception. The very long development time (about 12-15 years, because of the need to study the side effects from long term use), the fear of litigation, and the current emphasis on blockbuster multibillion dollar drugs aimed primarily at elderly people make research in this field highly unpopular. In fact, desired demographic changes, whether in “paediatric” countries (those where population growth is undesirable) in Africa, Asia, and parts of Latin America or in the “geriatric” countries of Europe and Japan (where the opposite holds), now depend much less on changes in contraceptive “hardware”—the actual means of birth control—than on “software” considerations, the legal, economic, cultural, educational, and public health conditions in each country.1 As a result, the active ingredient of the pill (administered orally, by injection, or through implants, patches, or even vaginal rings), though seemingly sold under hundreds of labels worldwide, is still limited to about half a dozen slight chemical variants of the first oral progestogen, norethindrone, which was synthesised in a small Mexican company (Syntex) in 1951. The fact that the original norethindrone is still being consumed by millions of women is one of the relatively rare examples (aspirin being the most famous, then the antihistamine diphenhydramine (Benadryl) and the anticoagulant warfarin) where the original chemical is still being used in unmodified form decades after its original synthesis.


    • Publication of this online supplement is made possible by an educational grant from AstraZeneca

    • Competing interests: In 1951 CD was involved in the first synthesis of an oral contraceptive.


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