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International contribution in the development of the pill


Synthesising orally active progesterone
Carl Djerassi Scientist
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So that was the end of any idea of using progesterone as a contraceptive, but the idea was well known and published. What progesterone was then used in medicine, however, was for some of its other uses, namely, it is produced by women during the menstrual cycle, but generally during the second part of the menstrual cycle, in preparation for... in case they got pregnant, in which case the secretion would then continue for nine months to inhibit further ovulation, and further fertilisation, and also to maintain the proper environment in the uterus for the development after implantation of the embryo and the blastocyst, and so on. So it’s used for menstrual disorders to this day, and it was used for infertility, which is ironic, but there are women who get pregnant without difficulty, but cannot maintain a pregnancy to term, because they do not produce enough progesterone, and therefore their uterine environment, let’s say, is not optimal, and they suffer spontaneous abortion, and that is... particularly at that time, was one of the treatments for habitual abortion... spontaneous habitual abortion in women. They were then given progesterone by injection, in order to offset it, and in a number of cases, of course it did so. And one man who did quite a bit of work in this field was a clinician named John Rock, at Harvard. So there you have Rock... And then... so that was that.

In 1951 we synthesised this compound norethindrone, because we wanted to develop new drugs, of course, for Syntex, and we thought this was an interesting one. Namely, Syntex was in the progesterone business, as a supplier of the raw material to pharmaceutical companies, but what if we could make a proprietary drug, which would be a much more remunerative thing, and one that would have a real function which progesterone did not fulfil, namely to be orally active, and that’s why we made this compound, and I indicated how, and it turned out to be orally active and the most potent progestational compound known at that time, much more potent than the natural hormone. We were then, even though we were a very small company that had no biology, or clinic, we then farmed it out to... sent it to many different biologists, and quite a number of them published then on our work, and we also sent it to Gregory Pincus, who at that time was in the Worcester Foundation, and was a recognised biologist in that area, and suggested he might be interested in this. He, in fact, was not the first one to publish on this, even though people think he was, but it was... or claim he was. No, not even claim, ignored the fact that he was not, but that’s sort of, beside the point. We sent it also to the National Cancer Institute, and that’s where it was first published, but what they all confirmed was the compound was active orally, and they then carried it through rabbits, guinea pigs, to monkeys, and the very first clinical experiment, the very first clinical experiment on the clinical efficacy of norethindrone was done by a man named Tyler, T-Y-L-E-R, who is now dead, but at that time was working for the... at UCLA, and he was Medical Director of Planned Parenthood. But he was interested in various applications of progesterone. Pincus was interested in really... I wouldn’t say rediscover, because of course he knew about it, but extending and improving the basic idea of Haberlandt, and that’s perfectly okay. In fact that’s what science is all about, you build on the predecessors. But I have never forgiven him is that this book of his that has 1600 references, and quite a number of them are totally unimportant, has not a mention of Haberlandt. If you look in the index, where there are hundreds and hundreds of names, not only doesn’t he have any chemists, and he might say, all right, he’s a biologist who doesn’t believe in chemistry, but here was a biologist, and he’s not there. And that bothers me, and therefore calling Pincus solely the father of the pill is inappropriate. Calling him a father is totally appropriate, but he was a key contributor, but not the only one, and something came way before, and that was Haberlandt, and then what came then was the chemists making the orally active compound, and then came me, and then the first clinician, and that was John Rock, interestingly enough. So he clearly would be the midwife, and I think it is appropriate to call Pincus a father, or maybe even the father, but he certainly didn’t play the maternal role, he needed that too, and that is the one that I have been describing, both here and in this book, and then the brutal details, and there are interesting patent details, because a year and a half... and we published our stuff right away, patented it right away. Four weeks, or five weeks after we published this, we published it... I mean completed it, on October 15, 1951, there's was a real birthday, and by November, something like 22, or so on, we’d already filed a patent application, and in March of the following year had already published it, the first report, and then a little bit later a very detailed one, in the Journal of the American Chemical Society. A year and a half later, after that, another chemist, Colton at GD Searle, which was a much larger pharmaceutical... well, a real pharmaceutical company, near Chicago, much larger than ours... he worked there... made a very close analog of it, so close that if you... some people would call it, like me, call it a pro-drug. That is... it is a compound that is different from the actual active compound, but if you put it into the body it gets transferred... transformed into the original compound, and that’s the active one, and in fact it is a compound that the double bond is only in a difference position, and when it’s exposed to acid, in other words the stomach acid, it gets transformed into our compound, but that, of course circumvented our patent. It’s perfectly legal this also, I’m not talking that there’s any shenanigans about it, I don’t mean that at all, but that was a year and a half later. But he worked for the company that supported much of Pincus’ work, and sent it off to Pincus, of course considerably after we did, and Pincus selected that for the first... for his work, and that was again perfectly appropriate. He had financial and other relations with them, and there was nothing inappropriate about it, that’s what you would pick.

Austrian-American Carl Djerassi (1923-2015) was best known for his work on the synthesis of the steroid cortisone and then of a progesterone derivative that was the basis of the first contraceptive pill. He wrote a number of books, plays and poems, in the process inventing a new genre, 'science-in-fiction', illustrated by the novel 'Cantor's Dilemma' which explores ethics in science.

Listeners: Tamara Tracz

Tamara Tracz is a writer and filmmaker based in London.

Tags: Syntex, Journal of the American Chemical Society, progesterone, contraceptive, Worcester Foundation for Biomedical Research, GD Searle, Gregory Goodwin Pincus, John Rock, Ludwig Haberlandt, Edward T Tyler, Frank Benjamin Colton

Duration: 7 minutes, 7 seconds

Date story recorded: September 2005

Date story went live: 24 January 2008