The Man Who Made Testosterone Came From the Perfume Industry

Leopold Ruzicka shared the 1939 Nobel Prize in Chemistry "for his work on polymethylenes and higher terpenes."[1] Not for testosterone. Terpenes are the molecular family behind natural scent, and Ruzicka came to the male sex hormone from the chemistry of musk perfume.

He had been studying the structures of the active components of natural musk, and it was from that structural work that he proposed a connection between the terpene family and the sex hormones Adolf Butenandt was characterising.[1] The link between a fragrance molecule and a hormone was the insight.

Why perfume and hormones are the same problem

Both are built on rings of carbon. Musk compounds and steroids share a structural logic, and a chemist who has spent years working out how large carbon rings assemble is exactly the person who can work out how to build one deliberately.

Ruzicka's expertise was not in endocrinology. It was in making complicated ring structures on purpose. Testosterone is a complicated ring structure.

Isolation and synthesis, again

The distinction matters here more than anywhere. In 1935, Ernst Laqueur's Amsterdam group isolated testosterone; Butenandt in Gdansk and Ruzicka in Zürich synthesised it.[2]

Isolation gets you a sample. Synthesis gets you a supply. Without a synthetic route, testosterone would have remained a laboratory curiosity extracted in trace amounts from animal tissue — which is precisely what the failed organotherapy of the previous fifty years had been trying and failing to do.

What synthesis unlocked

Once the molecule could be made rather than harvested, everything downstream became possible: testosterone has been available for clinical use since 1935.[2]

It also immediately exposed the next problem. Given orally, testosterone is inactivated in the liver, so parenteral routes or modifications of the molecule had to be found.[2] Ruzicka's chemistry solved supply. It did not solve delivery, and that took another eighty-five years of slow improvement.[2]

Frequently asked questions

Did Ruzicka set out to make testosterone? His recognised work was on terpenes and polymethylenes.[1] The connection to sex hormones came from that structural chemistry rather than from a hormone-first research programme.

Who deserves credit for testosterone? It is genuinely shared. Laqueur isolated, Butenandt and Ruzicka synthesised, all in 1935.[2] Berthold established that the testes secreted something at all, in the previous century.[3]

Is synthetic testosterone different from natural testosterone? No — synthesis produces the same molecule. What differs between products is the ester or delivery vehicle attached to it, which changes how it behaves in the body, not what it is.

Next in this series

Butenandt's side of the work began somewhere less glamorous than a Zürich chemistry bench.

Continue with the man who collected the urine.

References

3 sources

1. The Nobel Foundation. The Nobel Prize in Chemistry 1939 — Adolf Butenandt "for his work on sex hormones" and Leopold Ruzicka "for his work on polymethylenes and higher terpenes". nobelprize.org
2. Nieschlag E, Nieschlag S. ENDOCRINE HISTORY: The history of discovery, synthesis and development of testosterone for clinical use. Eur J Endocrinol. 2019;180(6):R201–R212. doi:10.1530/EJE-19-0071 · PMID 30959485
3. Freeman ER, Bloom DA, McGuire EJ. A brief history of testosterone. J Urol. 2001;165(2):371–373. doi:10.1097/00005392-200102000-00004 · PMID 11176375