In 1939, the Nobel Committee in Stockholm did something remarkable: they awarded the Nobel Prize in Chemistry to two scientists who had just cracked the molecular code of human sexuality.
Not to physicists splitting atoms. Not to medical researchers fighting infectious disease. To two chemists who figured out the structure of sex hormones and showed the world how to synthesize them from cholesterol.
Then World War II started. The Nazis pressured Butenandt to decline his prize. And somehow, a discovery that should have been remembered as one of the defining moments in medical history got buried under seventy years of other headlines.
You almost certainly have never heard of this Nobel Prize. You should have.
The Problem They Were Solving
By the early 1930s, the scientific world knew that sex differences in humans — and in most mammals — were controlled by chemical messengers produced in the gonads. The phenomenon was understood empirically for millennia. What nobody understood was the chemistry.
What exactly were these substances? What was their molecular structure? How were they made by the body? And could they be synthesized in a laboratory — making them available for medicine rather than requiring extraction from thousands of liters of urine or hundreds of kilograms of animal organs?
These were the questions that Butenandt and Ruzicka, working independently, were racing to answer.
The stakes were not abstract. Understanding sex hormone chemistry meant understanding reproduction, aging, the physiology of masculinity and femininity, the biology of puberty and menopause, and — eventually — the treatment of the conditions that arise when hormone production goes wrong.
Butenandt: The Man Who Processed 15,000 Liters of Urine
Adolf Butenandt was a German biochemist with extraordinary patience for scale.
His first major achievement was isolating oestrone — a form of estrogen — from pregnant women’s urine. This required processing thousands of liters of urine to yield milligrams of pure crystals. He worked out the chemical structure of oestrone. Then, separately, he isolated androsterone — a weaker androgenic compound — from the urine of men. For that project, his team processed fifteen thousand liters of urine collected from young Berlin policemen. The yield was fifteen milligrams.
He was not deterred. He then isolated progesterone from pig ovaries.
Butenandt was building a systematic picture of how sex hormones were structured chemically, what they had in common, and how they related to each other. By analyzing these isolated hormones, he recognized that they shared similar chemical structures — structures that bore a striking resemblance to sterols and steroids, a family of compounds of which cholesterol is the most abundant member.
This structural recognition was the conceptual breakthrough. If sex hormones were structurally related to cholesterol — a compound abundant in all animal tissue and cheap to obtain — then perhaps they could be synthesized from cholesterol rather than laboriously extracted from biological sources.
Ruzicka: The Man Who Thought in Molecules
Leopold Ruzicka came to the sex hormone problem from a completely different direction.
Ruzicka was a Croatian-Swiss chemist working at the ETH in Zurich and then at the Ciba pharmaceutical company in Basel. He had made his reputation studying the chemical structures of terpenes — the large family of compounds that includes rubber, natural fragrances like camphor and menthol, and, at the large end of the family, steroids and cholesterol.
His contribution was theoretical as well as experimental. He proposed that all terpenes — including cholesterol, which sits at the large end of the terpene family — were built from a common five-carbon building block called isoprene. This insight gave chemists a framework for understanding how living organisms built complex molecules from simpler precursors.
Applied to sex hormone chemistry, this meant that cholesterol — which living organisms build readily from simple precursors — could serve as the synthetic starting material for testosterone and other steroids. The structural backbone was already there. You just had to modify it in specific ways.
Ruzicka synthesized androsterone from cholesterol in 1934. The following year, both Butenandt’s group in Göttingen and Ruzicka’s group in Basel independently synthesized testosterone from cholesterol — publishing their results in the same year, independently, within weeks of each other.
The Convergence of 1935
The simultaneous synthesis of testosterone by two independent laboratories is one of the great convergence events in the history of chemistry.
Laqueur’s group in Amsterdam had just isolated testosterone from bull testes for the first time. Butenandt and Ruzicka, working from structural knowledge of the molecule, independently worked out how to build it synthetically. All three breakthroughs — isolation and two independent syntheses — happened within the same twelve months.
The significance was immediate. You no longer needed to process hundreds of kilograms of animal organs to get milligrams of hormone. You could synthesize testosterone in a chemistry laboratory, in quantity, from cholesterol.
Clinical medicine had just been given a usable supply of the molecule that governs male physiology.
The Nobel Prize, the War, and the Silence
In 1939, the Nobel Committee awarded the Chemistry Prize jointly to Butenandt and Ruzicka “for their work on sex hormones.” The prize covered the entire framework of discovery — the isolation, structural characterization, and synthesis of testosterone, estrogen, and progesterone.
The timing was almost impossibly bad.
Germany invaded Poland in September 1939 — the same month the Nobel Prizes were announced. Under pressure from the Nazi government, which had banned Germans from accepting Nobel Prizes since Carl von Ossietzky (a political prisoner) had received the Peace Prize in 1935, Butenandt was initially forced to decline his prize. He accepted it after the war ended.
Ruzicka accepted his prize immediately.
The wartime context buried the story. A Nobel Prize announced amid the opening weeks of World War II, declined by its German co-recipient under political pressure, was not the cultural moment it should have been. The discovery got folded into the chaos of the era rather than celebrated as the landmark it was.
What This Discovery Actually Enabled
It is worth stating plainly what the 1935 synthesis of testosterone — and the 1939 Nobel Prize recognizing it — actually unlocked:
- The entire field of anabolic steroid pharmacology
- The development of oral contraceptives (which use synthetic progestogens derived from the same steroid chemistry)
- The clinical treatment of male hypogonadism
- The pharmacological basis for managing conditions related to sex hormone imbalance in both men and women
- Eventually, testosterone replacement therapy as we practice it today
The 1939 Chemistry Nobel Prize is not famous. It doesn’t have the cultural footprint of the 1953 discovery of DNA structure, or the penicillin Nobel, or the insulin work. But in terms of practical medical consequence — in terms of the number of people whose health it has affected — it belongs in the conversation.
What’s Next
Now that we have the molecule, the obvious question is: what did medicine do with it?
The answer, for the next fifty years, was: inject it. And the story of what injections actually looked like — the rollercoaster of supraphysiological peaks and symptomatic crashes — is a story of doing the right thing in the worst possible way.
