Russell Marker — Mexican Yams, Progesterone and the Birth of the Steroid Industry

In the 1930s progesterone, the hormone that prepares and sustains the lining of the womb, was one of the scarcest and most expensive substances in medicine. It could be made only in tiny amounts, from cholesterol or from compounds isolated out of animal urine. Between 1938 and 1940 a Pennsylvania State College chemist named Russell Earl Marker (1902–1995) found a way to make it from plants instead. He showed that the side chain of plant steroids called sapogenins could be broken open and trimmed down, in a few steps, to the side chain of progesterone. Chemists still call this sequence the Marker degradation. Then he went looking in the forests of Veracruz for a wild yam big and rich enough to supply it.

That yam, and the barbasco yam that replaced it, became the raw material of a Mexican hormone industry that, in the words of the American Chemical Society’s 1999 landmark booklet, by the 1950s produced more than half of the sex hormones sold in the United States. It led on to cheaper cortisone and to norethindrone, one of the first oral contraceptive progestins. This wing tells the story in four deep-dive articles: the man, the chemistry, the Mexican yams, and the industry that followed. The overview below gives the whole story on one page. It is history and science for curious readers, not guidance on the use of any hormone or herb.

Table of Contents

  1. Deep-Dive Articles
  2. 1. Who Russell Marker Was
  3. 2. The Discovery on One Page
  4. 3. The Natural Source: Mexican Wild Yams
  5. 4. Timeline at a Glance
  6. 5. Later Significance: Cortisone, the Pill and Beyond
  7. 6. The Wild Yam Question
  8. Key Research Papers
  9. Connections
  10. Featured Videos

Deep-Dive Articles

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Russell Marker: Life and Career (1902–1995)

A log-cabin farm childhood near Hagerstown, the doctorate he walked away from, the octane rating, the Rockefeller Institute and Penn State, two Mexican companies, and the chemist who left chemistry at 47.

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The Marker Degradation: Turning Plant Sapogenins into Progesterone

What a steroid is, why progesterone was so scarce, Marker’s new structure for sarsasapogenin, how the side chain is broken and trimmed, and the open, unpatented process that followed.

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Cabeza de Negro and Barbasco: The Mexican Wild Yams Behind the Hormone Industry

True yams of the genus Dioscorea, a picture in a botany book, the 1942 road to Orizaba, ten tons of root, the barbasco gatherers, how a yam makes diosgenin, and what wild yam cream trials measured.

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After Marker: Cortisone, the Pill and the Mexican Steroid Industry

The first kilo of progesterone in Mexico City, the 1949 cortisone sensation, cortisone from a yam, the mould that added an oxygen, norethindrone in 1951, and how steroid drugs are made today.

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1. Who Russell Marker Was

Russell Earl Marker was born on 12 March 1902 on a farm near Hagerstown, Maryland, in a one-room log cabin, the oldest of three children of a tenant farmer. His high school offered only commercial courses, so he reached the University of Maryland in 1919 without any chemistry or physics. He took a B.S. there in 1923 and an M.S. in 1924, and began doctoral research with Morris Kharasch on organometallic compounds. According to the ACS landmark booklet and Marker’s own 1987 oral history, Kharasch accepted the thesis, but Marker refused to take the physical chemistry courses the degree also required and left in 1925 without the Ph.D.

After a few months as an analytical chemist at the Naval Powder Factory at Indian Head, Maryland, he joined the Ethyl Gasoline Corporation laboratory in Yonkers, New York, in 1926. There he prepared very pure n-heptane, which knocked badly in an engine, and 2,2,4-trimethylpentane (“isooctane”), which did not. Blends of the two became the reference fuels for knock testing, and the Science History Institute and the chemist-historian Jeffrey Seeman describe him as having helped develop the octane rating. From 1928 until 1934 he worked with P. A. Levene at the Rockefeller Institute in New York on optical rotation and molecular configuration, writing about 32 papers with him.

Marker wanted to make hormones from plant steroids. The Rockefeller Institute declined to back the project, and in 1934 he moved to Pennsylvania State College on an $1,800 fellowship arranged by Frank Whitmore, with research funding from the drug company Parke-Davis. Working with some 32 students and postdoctoral chemists, many of whom went on to industry, he published more than 160 papers in the steroid field. He resigned on 1 December 1943 and moved his work to Mexico, where in early 1944 he co-founded Syntex, S.A., in Mexico City with Emeric Somlo and Federico Lehmann. He left in May 1945 after what the ACS booklet calls “a rancorous dispute” over profits and their distribution, founded a second small company, Botanica-mex, and in 1949, aged 47, left chemistry altogether. He spent the following decades commissioning Mexican silversmiths to reproduce eighteenth-century European silver, and he died on 3 March 1995 in Wernersville, Pennsylvania. The full story is in Russell Marker: Life and Career.

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2. The Discovery on One Page

Every steroid shares the same skeleton of four fused carbon rings. What makes one steroid cholesterol, another progesterone and another diosgenin is mostly the small groups hung on that skeleton, above all the side chain on its last ring. Progesterone has a short two-carbon side chain. The plant steroids called sapogenins — the sugar-free halves of the soap-like saponins found in sarsaparilla root, beth root and yams — carry the same skeleton but a longer side chain folded into two extra rings. In the 1930s the leading chemists in the field regarded that side chain as chemically inert, which meant it could not be cut back to the progesterone shape.

In 1939 Marker and his co-worker E. Rohrmann proposed a new structure for sarsasapogenin, the sapogenin of sarsaparilla, in which the side chain is a spiroketal, a carbon bonded to two oxygens, and so open to attack. Heating the sapogenin with acetic anhydride at about 200 °C opened the side chain; an oxidation step and hydrolysis then cut it down. In the ACS booklet’s words, “What remained duplicated the side chain of progesterone.” In December 1939 Marker and Rohrmann reported sarsasapogenin converted to pregnanediol, and in 1940 Marker’s group took diosgenin — a sapogenin first described by the Japanese chemists Takeo Tsukamoto and Yosio Ueno from the yam Dioscorea tokoro — and trillin, its glycoside from beth root, through to progesterone. The same year he made testosterone and related compounds from the same plant starting materials.

Marker took out no patents on the process. Both the ACS booklet and his oral history report that when Parke-Davis had not filed patent applications by his deadline of 1 December 1943, he declined to assign the rights to anyone, and the chemistry was free for others to use. His group’s sapogenin work was gathered in a single 60-page paper, “Steroidal sapogenins”, in the Journal of the American Chemical Society in 1947. The chemistry is told step by step in The Marker Degradation.

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3. The Natural Source: Mexican Wild Yams

A process is only as useful as its raw material. Marker, his students and collaborating botanists examined more than 400 plant species, mainly in the south-western United States, and described about a dozen new sapogenins. Beth root (Trillium) contained diosgenin, but its roots were too small to gather in quantity. In November 1941, in Texas, Marker saw in an old botany book a picture of a large Dioscorea yam growing along a stream between Orizaba and Córdoba in Veracruz, with a root said to reach about 100 kilograms. Its local name was cabeza de negro, a period name taken from the dark, rough crown of the tuber that sits partly above the ground. The sources identify the species differently, as D. mexicana or D. macrostachya.

In January 1942 Marker travelled alone by bus to the Orizaba–Córdoba road and, at a country store owned by Alberto Moreno, obtained roots of the yam. Back at Penn State he extracted diosgenin from it. When Parke-Davis and other companies he approached declined to produce hormones in Mexico, he spent his own savings in the autumn of 1942 on about ten tons of sun-dried root, had it extracted to a syrup in Mexico City, and in a New York laboratory turned the syrup into about three kilograms of progesterone — “then the largest lot of progesterone ever produced”, according to the ACS booklet. From 1945 he switched to barbasco (Dioscorea composita), a yam the ACS booklet says held about five times as much diosgenin.

The historian Gabriela Soto Laveaga describes how the search for cheap steroids made barbasco the raw material of choice and gave an “erstwhile ‘weed’” a cash value. Gathering the wild root by hand transformed parts of rural Mexico, giving rise to peasant organisations and to government efforts to control barbasco production. Modern plant science has since traced how yams make diosgenin: a 2019 study in Nature Communications showed that plants build it from cholesterol using pairs of cytochrome P450 enzymes, an ability that arose independently in Paris polyphylla and in fenugreek, and called diosgenin “the single most important precursor for the world steroid hormone industry”. The yam story is told in Cabeza de Negro and Barbasco.

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4. Timeline at a Glance

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5. Later Significance: Cortisone, the Pill and Beyond

In 1949 Philip Hench, Edward Kendall and colleagues at the Mayo Clinic reported dramatic effects of compound E, soon called cortisone, in rheumatoid arthritis. The first industrial route, from deoxycholic acid in ox bile, took more than thirty steps. In 1951 George Rosenkranz, Carl Djerassi and colleagues at Syntex published a synthesis of cortisone that Djerassi later described as starting from diosgenin. In 1952 D. H. Peterson and H. C. Murray at Upjohn reported that a common mould, Rhizopus, could add an oxygen at carbon 11 of progesterone in a single step, making progesterone a practical starting point for cortisone. Writing in a Japanese journal of pharmacy history, M. Uchibayashi credits the affordable cortisone that followed to yam-derived progesterone together with that microbial step; his figures run from about $200 a gram of cortisone in 1949 to $3.50 by 1955. J. A. Hogg, writing a history of steroid work at Upjohn, records that the progesterone used in the mould work had been made from soybean stigmasterol — a reminder that soy sterols, the route associated with Percy Julian, ran in parallel with the yam.

On 15 October 1951 Luis Miramontes, working with Djerassi and Rosenkranz at Syntex, synthesised norethindrone, a progestin that is active when swallowed. A related compound, norethynodrel, made by Frank Colton, became the first oral contraceptive approved by the US Food and Drug Administration, in May 1960, and norethindrone and its relatives went on to become among the most widely used progestins. Today most steroid drugs are made by combining microbial conversion of plant sterols (phytosterols) with chemistry, a market that a 2018 review put at more than $10 billion a year, while diosgenin remains an industrial starting material for drugs including progesterone, testosterone, dexamethasone and norethindrone. The full legacy is in After Marker: Cortisone, the Pill and the Mexican Steroid Industry.

Carl Djerassi, quoted in the ACS booklet, wrote that the Mexican connection “stemmed from the work of one gutsy individualist, Russell E. Marker”. In 1987 the Penn State student newspaper headlined an interview with him “The Forgotten Man of Chemistry”. Twelve years later, plaques were placed at Pond Laboratory at Penn State and at the first Syntex site in Mexico City.

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6. The Wild Yam Question

Because progesterone was once made from yams, wild yam (Dioscorea villosa) creams are sometimes described as a natural source of progesterone. The research on that point is specific. In a 2001 double-blind, placebo-controlled crossover trial in 23 healthy menopausal women, a topical wild yam cream produced no change in any hormone measured, including serum and salivary progesterone, and no statistically significant difference from placebo in symptoms. The conversion of diosgenin into progesterone is a laboratory process — the chemistry Marker worked out with acetic anhydride, oxidation and hydrolysis. Separately, a 2008 study in rats found that a D. villosa extract given for 28 days raised markers of kidney fibrosis and liver inflammation, with no signs of acute toxicity. Both findings are described in Cabeza de Negro and Barbasco.

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Key Research Papers

  1. Seeman JI. Russell Earl Marker and the Beginning of the Steroidal Pharmaceutical Industry. Chem Rec. 2023;23(4):e202300048. PubMed PMID: 36995067
  2. Lehmann PA, Bolivar A, Quintero R. Russell E. Marker. Pioneer of the Mexican steroid industry. J Chem Educ. 1973;50(3):195-9. PubMed PMID: 4569922
  3. Marker RE, Rohrmann E. Sterols. LIII. The Structure of the Side Chain of Sarsasapogenin. J Am Chem Soc. 1939;61(4):846-851. DOI: 10.1021/ja01873a020
  4. Marker RE, Rohrmann E. Sterols. LXXXI. Conversion of Sarsasapogenin to Pregnanediol-3(α),20(α). J Am Chem Soc. 1939;61(12):3592-3593. DOI: 10.1021/ja01267a513
  5. Marker RE, Tsukamoto T, Turner DL. Sterols. C. Diosgenin. J Am Chem Soc. 1940;62(9):2525-2532. DOI: 10.1021/ja01866a072
  6. Marker RE, Krueger J. Sterols. CXII. Sapogenins. XLI. The Preparation of Trillin and its Conversion to Progesterone. J Am Chem Soc. 1940;62(12):3349-3350. DOI: 10.1021/ja01869a023
  7. Marker RE, Wagner RB, Ulshafer PR, Wittbecker EL, Goldsmith DPJ, Ruof CH. Steroidal sapogenins. J Am Chem Soc. 1947;69(9):2167-2230. PubMed PMID: 20262743
  8. Laveaga GS. Uncommon trajectories: steroid hormones, Mexican peasants, and the search for a wild yam. Stud Hist Philos Biol Biomed Sci. 2005;36(4):743-60. PubMed PMID: 16337559
  9. Christ B, Xu C, Xu M, Li FS, Wada N, Mitchell AJ, Han XL, Wen ML, Fujita M, Weng JK. Repeated evolution of cytochrome P450-mediated spiroketal steroid biosynthesis in plants. Nat Commun. 2019;10(1):3206. PubMed PMID: 31324795
  10. Hench PS, Kendall EC, Slocumb CH, Polley HF. The effect of a hormone of the adrenal cortex (17-hydroxy-11-dehydrocorticosterone: compound E) and of pituitary adrenocortical hormone in arthritis: preliminary report. Ann Rheum Dis. 1949;8(2):97-104. PubMed PMID: 18623812
  11. Peterson DH, Murray HC. Microbiological oxygenation of steroids at carbon 11. J Am Chem Soc. 1952;74(7):1871-1872. DOI: 10.1021/ja01127a531
  12. Hogg JA. Steroids, the steroid community, and Upjohn in perspective: a profile of innovation. Steroids. 1992;57(12):593-616. PubMed PMID: 1481225
  13. Uchibayashi M. [Forgotten episodes of the birth of cortisone]. Yakushigaku Zasshi. 2001;36(1):70-5. PubMed PMID: 11777000
  14. Djerassi C. Steroid research at Syntex: “the pill” and cortisone. Steroids. 1992;57(12):631-41. PubMed PMID: 1481227
  15. Larrea F, Morales-Esponda M, Chirinos M, Díaz-Sánchez V. The origins of oral contraception: The role of Mexican scientists in developing the first synthetic oral contraceptive progestin. Rev Invest Clin. 2025;77(6):100028. PubMed PMID: 41330040
  16. Fernández-Cabezón L, Galán B, García JL. New Insights on Steroid Biotechnology. Front Microbiol. 2018;9:958. PubMed PMID: 29867863
  17. Pathak N, Negi AS. Plant based steroidal and triterpenoid sapogenins: Chemistry on diosgenin and biological aspects. Eur J Med Chem. 2024;279:116915. PubMed PMID: 39366126
  18. Komesaroff PA, Black CV, Cable V, Sudhir K. Effects of wild yam extract on menopausal symptoms, lipids and sex hormones in healthy menopausal women. Climacteric. 2001;4(2):144-50. PubMed PMID: 11428178
  19. Wojcikowski K, Wohlmuth H, Johnson DW, Gobe G. Dioscorea villosa (wild yam) induces chronic kidney injury via pro-fibrotic pathways. Food Chem Toxicol. 2008;46(9):3122-31. PubMed PMID: 18662738

PubMed Topic Searches

  1. PubMed: diosgenin progesterone history
  2. PubMed: Dioscorea diosgenin
  3. PubMed: barbasco Mexico
  4. PubMed: norethindrone history
  5. PubMed: cortisone history synthesis

Further Reading

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Connections

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