Carl Djerassi (1923–2014)

By Gavin @ 2022-11-29T20:36 (+36)

Carl Djerassi helped invent the synthetic hormone norethindrone, one of the 500 most important medicines (actually top 50 by prescription count). A large supply is a basic requirement of every health system in the world. 

Norethindrone is important for two reasons. First, it treats menstrual disorders and endometriosis, together 0.3% of the global burden of disease. More famously, it was a component of The Pill.^[1] People mix up the timelines, which is why he is sometimes called the 'Father of the Pill'. But "neither Djerassi nor the company he works for, Syntex, had any interest in testing it as a contraceptive" and it was only used for birth control 12 years after.

As usual in industrial chemistry, Djerassi got no royalties from the blockbuster medicine he helped develop - but, surprise ending! - he bought cheap shares in Syntex and got rich when it became one of the most important medicines in history for two reasons.

He also synthesized the third-ever practical antihistamine, and applied new instruments in 1,200 papers on the structure of many important steroids. He also worked on one of the first AI programs to do useful work in science.

Achievements

Epistemic status: little better than a guess.

Not many inventions are fully counterfactual; most simple, massively profitable things which get invented would have been invented by someone else a bit later. So the appropriate unit for lauding inventors is years saved. And if I put a number on that I'd just be making it up.

Here are the numbers I made up:

• About 4 million US users, so maybe up to 94 million world users at present. No sense of the endometriosis / contraception split. 
• Call it 600 million users, 10% endometriosis use case.
• For menstrual disorders: 
  • on the market 65 years and counting. 
  • Counterfactual: on the market 3 years before the next oral progestogen was.
  • It was the first practical oral progestogen, so we should compare to the injectable alternatives
    • About 1/6 of Americans hate needles so much that they refuse treatment.
    • Attrition and missed doses for needle treatments is higher than pill treatments.
  • Endometriosis is about 0.25 - 0.35 QALY loss. So if it's 30% effective, around  $30 / QALY, an amazing deal.
• For easy contraception: 
  • on the market 59 years and counting.
  • The big gains (besides autonomy) are averting unintended pregnancies, abortions, and pregnancy-related deaths.
  • Modern cost-effectiveness in Ethiopia is $96 / QALY.
  • There's probably some additive effect for endometriosis sufferers (who would want contraception anyway).
• A full account would guess the Pill's effect on the sexual revolution and cultural attitudes toward women. But I've reached my limit. (You might also consider the role of the Pill in the ongoing decline of church authority: "1980: In spite of the Pope's ruling against the Pill and birth control, almost 80% of American Catholic women use contraceptives, and only 29% of American priests believe it is intrinsically immoral.")
• How many years did he bring the invention forward? Call it 5.
• Then split the credit three ways with Luis Miramontes and George Rosenkranz.

So (largely made-up numbers) it looks like millions of QALYs for the treatment overall, and tens of thousands counterfactually for Djerassi.
 

Artist

After surviving cancer, he decided to become a writer. 

I was very depressed, and for the first time thought about mortality. Strangely enough I had not thought about death before... I realized that who knows how long I would live? In cancer they always talk about five years: if one can survive five years then presumably the cancer had been extirpated. And I thought: gee, had I known five years earlier that I would come down with cancer, would I have led a different life during these five last years? And my answer to myself was yes. I said, well, Carl Djerassi, now you know it... I decided I wanted to live another intellectual life: a very different one... So, by 1989, when I really started reducing the size of my research group on a substantial scale I wrote the first autobiography. I wrote my first novel...

It's extremely rare for any successful academic to shutter their lab. (They claw too long to build it.)

But suicide is a death that has a purpose, and the person who commits suicide usually sends out a message... the survivors ought to be able to figure out what had prompted this irrevocable step... So, this was my answer in the context of my daughter’s death and why I founded an artist’s colony in her memory... I wanted to create again something living out of death.

You can see one of his plays here. It's ok. 

Most of [Djerassi's] plays are directly scientific. When playwrights use science – he cites Michael Frayn and his old friend Tom Stoppard – they usually do so as metaphor, not, as Djerassi intends, as a subject in its own right.

(I would say when playwrights abuse science.)

1. ^{^}

   but owing to 12 years of delay the substance was actually the 'world's second-ever reversible birth control pill'