There are many ways to measure a scientist’s commitment to their work. Adolf Butenandt’s preferred measure was in liters.
Specifically, the fifteen thousand liters of urine he collected from young Berlin police officers to isolate fifteen milligrams of a compound called androsterone.
To put that in perspective: if you poured those fifteen thousand liters into a standard backyard swimming pool, you would fill roughly a third of it. The yield from that third of a pool of human urine was approximately the weight of three grains of rice.
This was considered a success.
The Starting Logic
Why urine?
In the early twentieth century, biochemists understood something important about how the body manages hormones: it produces them in glands, uses them systemically, and then excretes metabolic byproducts through the urine. The urine of people with unusually active endocrine states — pregnant women, for instance — contains elevated levels of hormone metabolites.
This made urine a detective’s goldmine for hormone research. You didn’t need to dissect glands or sacrifice animals. You needed a large, steady supply of human urine and enough patience to process it.
Butenandt’s approach to the male hormone was precisely this: collect enough urine from healthy males with presumably normal testosterone production, process it at industrial scale, and isolate whatever androgenic compounds were present in the metabolite pool.
The Berlin Policemen
The logistics of collecting fifteen thousand liters of urine from human volunteers in 1931 were, to put it gently, novel. Butenandt’s team worked with the Berlin police force, which provided a corps of young, healthy men whose occupation made them easy to organize and whose presumably vigorous health made them good donors.
The urine was collected, shipped to the laboratory, and processed through an elaborate sequence of chemical extraction steps. The hormone metabolites were extracted using organic solvents, concentrated, purified through crystallization, and characterized spectroscopically to identify their chemical structure.
Fifteen thousand liters in. Fifteen milligrams out.
The compound was androsterone — a weaker androgenic steroid that the body produces as a breakdown product of testosterone. It was not testosterone itself, but it was structurally related, and it had androgenic activity when tested in the standard bioassay of the era: the capon comb growth test, which measured whether the compound could restore comb growth in castrated roosters (completing a circle back to Berthold’s original roosters from 1849).
Androsterone worked. It was a real androgen. It just wasn’t the primary one.
The Structural Insight
What Butenandt understood, working with androsterone and the other sex hormones he’d isolated, was the significance of the molecular backbone.
All sex hormones — estrogens, androgens, progestogens — share the same basic four-ring carbon scaffold. This scaffold is identical to the structure of sterols, of which cholesterol is the most familiar example. The differences between testosterone, estrogen, and progesterone come down to relatively minor modifications: which functional groups are attached where, which bonds are present or absent, and subtle variations in three-dimensional shape.
This insight meant that these hormones weren’t exotic, unrelated compounds requiring completely different chemistry for each one. They were variations on a theme. And the theme’s base structure — that four-ring scaffold — was something chemistry already knew how to work with, because cholesterol was abundant and available.
The implication was profound: if you could start with cholesterol and modify it chemically in specific ways, you could synthesize sex hormones in the laboratory without needing to collect them from biological sources at all.
The Oestrone Work
Before tackling the male hormone, Butenandt had already made his name with the female side of the equation.
Working from pregnant women’s urine — where female sex hormones are present at dramatically elevated levels — he extracted, purified, and characterized oestrone, a form of estrogen. Edward Doisy in the United States accomplished the same isolation independently, but Butenandt additionally worked out the complete chemical structure, which was the more significant scientific contribution.
From pig ovaries, he then isolated and characterized progesterone — the hormone critical to the female reproductive cycle.
By the time Butenandt turned his attention to testosterone synthesis in 1935, he had already built a comprehensive picture of steroid hormone chemistry across both sexes. The 1939 Nobel Prize was recognition of this entire body of work, not just the testosterone synthesis.
The Synthesis That Ended the Urine Era
In 1935, working with the structural knowledge accumulated over years of isolation and characterization, Butenandt and his colleague G. Hanisch published the chemical synthesis of testosterone from cholesterol.
You no longer needed fifteen thousand liters of urine. You needed cholesterol — available from any animal fat source — and a sequence of specific chemical transformations to convert it into testosterone.
The yield from synthesis was dramatically higher. The process was scalable. The molecule was identical to what the body produced.
This was the transition from chemistry-as-extraction to chemistry-as-manufacturing. For testosterone, it meant that a clinically usable supply of the hormone became a realistic possibility for the first time.
The Man Behind the Science
Adolf Butenandt was not a colorful figure. He was methodical, systematic, and exceptionally patient — qualities that were necessary for the kind of industrial-scale chemistry his work required.
He was also, it must be said, complicated by his historical context. He worked in Nazi Germany throughout the war, leading the Kaiser Wilhelm Institute for Biochemistry. Questions about his political choices during that period — whether he did enough to resist or protect colleagues — have been debated by historians. He declined his 1939 Nobel Prize under Nazi pressure and accepted it after the war. He went on to a distinguished postwar career and lived until 1995, dying at the age of ninety-one.
The science was unambiguous in its importance. The man behind it was, like most scientists of his era, shaped by forces larger than the laboratory.
What’s Next
We’ll meet Leopold Ruzicka in the next post — the Croatian-Swiss chemist who approached sex hormones from a completely different theoretical direction, and who synthesized testosterone independently just weeks after Butenandt did.
Two men, two laboratories, one molecule, one year. The story of scientific convergence doesn’t get much cleaner than 1935.
