Esta historia también está disponible en español.
On a hot summer day in 2009, María A. Fernández-Herrera wobbled behind her guide down the steep hill of the tropical forest of Puebla, Mexico. She and her colleagues were searching for barbasco, a plant with a subterranean stem, or rhizome, that resembles a tortoise shell and has heart-shaped leaves. “[Our guide] helped us unearth a giant rhizome,” says an excited Fernández-Herrera. “There were yellow [ones] and white ones.” She took a few samples of the massive rhizome back to her lab in Puebla City and used it to perform a classic — but rarely used nowadays — chemical procedure used to extract diosgenin to witness the process herself.
Diosgenin is a plant steroid found in rhizomes of plants of the genus Dioscorea and was key to developing the contraceptive pill in Mexico in 1951. Fernández-Herrera, now at the Centre for Research and Advanced Studies of the National Polytechnic Institute (CINVESTAV), Mérida, is expert on the study of steroid sapogenins, a type of natural detergents found in plants made up of a steroid structure and a sugar molecule. Chemists like her can now synthesize the sapogenin diosgenin, or purchase it from a company, but in the 1940s, at the height of the study of steroids, diosgenin was one of the most valuable molecules for steroid researchers and was mostly extracted from plants.
The story of the contraceptive pill started with an American chemist visiting the tropical forests of Mexico and befriending a Mexican shop-owner. The pill triggered a social revolution for women around the world and catapulted Mexico to the scientific “big leagues” of the world. Yet, the story about the plant behind the multi-million discovery, Dioscorea composita or barbasco, remains poorly known.
Even when botanists Michael Joseph François Scheidweiler had described D. mexicana in Brussels in 1837, and William Botting Hemsley D. composita in London in 1884, both from plants obtained in Mexico, the chemical properties of Dioscorea plants were only known among locals who used them for and fishing, as it is toxic for fish, but not for mammals.
During the 1930s, dubbed the Decade of Sex Hormones, chemists determined the structure of progesterone and started using it as medical treatment for menstrual complications. But they soon realized that sourcing it from animal glands, as they used to do in those times, was not an option when the demand rose dramatically.
The alternative, turns out, was in plants. In 1944, Russell Marker, an American chemist studying steroids at Pennsylvania State University, flew to Mexico City and then took a bus to Veracruz, Mexico. In Fortín de las Flores, a small town west of Veracruz City, in the middle of the lush tropical forest, he met Alberto Moreno, a kind and well-connected shop-owner. They did not speak each other’s language, but Marker managed to ask Moreno for his help finding a species of Dioscorea. Legend goes Marker had seen a picture of D. mexicana in a botany textbook. He was aware of the Asian species D. tokoro, from which diosgenin had been isolated in 1936, and was exploring for alternative sources in the U.S. and Mexico. Marker followed Moreno into the tropical forest to a wild population of a species of Dioscorea known by locals as cabeza de negro (D. mexicana). He and Moreno collected, fermented and dried 10 tonnes of the rhizome. Afterwards, they extracted diosgenin and transformed it into 3 kilos of progesterone, worth $240,000 USD at the time, using a chemical process that would later become known as Marker’s degradation. The reaction removes the side chain of diosgenin through hydrolysis in acidic conditions to produce progesterone. Using this same process, diosgenin can also be converted into testosterone and estrone, a female sex hormone.
Seeing the potential of the plants, in 1944, Marker and two lab partners founded their own laboratory in Mexico City under the name Syntex but, because of personal disagreements, Marker left the partnership to start his own laboratory in the same city a year later. In 1949, Marker learned of a close relative of D. mexicana: D. composita, known as barbasco among locals in Veracruz. The plant soon became the industry’s favourite source of diosgenin because it had five times more substance than D. mexicana. That same year, physicians at the Mayo Clinic in the U.S. found that cortisone, another steroid that could be derived from diosgenin, helped ease rheumatoid arthritis pain. This discovery meant even more demand for diosgenin.
Around that time, scientists had found that progesterone was able to prevent spontaneous abortions. Synthetic progesterone is almost inactive due to its poor solubility in water, so chemists at Syntex were looking for a new molecule that could mimic progesterone. On October 15, 1951, Luis Miramontes and Carl Djerassi managed to synthesize norethindrone. Similar in function to progesterone, norethindrone not only avoided spontaneous abortions, but also stopped ovulation — and pregnancy — when administered regularly, something that women rights advocates in the U.S. had long sought. The contraceptive pill was born.
“Without Marker’s degradation, Luis Miramontes wouldn’t have been able to synthesize the contraceptive pill,” says Fernández-Herrera.
The discovery of the chemical properties of the plant led to the development of what The Economist would consider in 1999 “the invention that defined the 20th century” and “the most important contribution of the Mexican organic chemistry to the world,” according to Fernández-Herrera.
In the 1960s, the U.S. Food and Drug Administration approved the contraceptive pill, and with increasing access, women gained control over their lives — especially regarding their sexuality and professional development. Between 80% and 90% of the world’s production of steroid hormones came from Mexico. All this thanks to barbasco.
According to Gabriela Soto Laveaga, science historian at Harvard University, by 1959, only fifteen years after Marker’s rediscovery of barbasco, almost 30 million Dioscorea plants were collected in a single year. At the time, people believed that “barbasco was almost inexhaustible in Mexico.”
To keep the supply of diosgenin going, an army of more than 100,000 local peasants or campesinos, known as barbasqueros, picked the plants from the wild. Local knowledge became vital to find the right species and to identify plants holding enough amounts of diosgenin.
Barbasco also grows in the tropical forests of other states in southern Mexico, like Oaxaca. Barbasco picking sustained whole families in this Mexican state in the time between harvests, says José Sarukhán Kermez, current coordinator for Mexico’s National Commission for Knowledge and Use of Biodiversity (CONABIO), who, during the early 1960s, studied the habitat of Dioscorea for his undergraduate dissertation.
Sarukhán Kermez’s mentor and botanist, Arturo Gómez Pompa, who many consider as one of the founding fathers of modern Mexican ecology, remembers in his memoirs: “It became evident the great importance of the work done by local field guides, who in reality, were the ones bearing the biggest burden, having to identify all the plants we collected.”
The emerging diosgenin industry not only resulted in enormous revenues for drug companies, but also in a wealth of knowledge that would cement the fields of botany and ecology in Mexico. Gómez Pompa and Sarukhán Kermez referred to one of their local guides, Agapito Hernández, as “their most important teacher.” Hernández would be responsible for revealing the secrets of the tropical forests of Oaxaca to the scientists.
“If it wasn’t for the knowledge [of the local guides], we wouldn’t have been able to get any work done,” writes Gómez Pompa.
Depending on the species, Dioscorea rhizomes need between three and seven years to harbour enough diosgenin for industrial purposes, so the demand for older plants left behind only small, less potent ones. The need for diosgenin — and the rhizomes that contain it — grew to a point that it became necessary to cultivate Dioscorea.
At the same time, the plant’s distribution remained largely unknown. Meanwhile, people in the Mexican government began to worry that barbasco was not, in fact, inexhaustible. To produce one kilo of diosgenin, for example, chemists required 25 kilos of dried Dioscorea. Such level of extraction, coupled with the clearing of land for cattle and agriculture, made plants scarcer. Therefore, at the end of the 1950s, the Mexican Secretariat of Agriculture formed the Commission for the Study of the Ecology of Dioscorea, led by Gómez Pompa. Its mission was to study the ecology of the Mexican tropical forests to provide management suggestions for Dioscorea.
Dioscorea propelled scientific research in Mexico fueled by pharmaceutical firms. “[F]or every tonne that was extracted of Dioscorea, [the pharmaceutical companies] would have to make an economic contribution to the recently created National Institute of Forest Investigations (INIF), for the study of the Mexican Dioscoreas and to evaluate the [ecological] impact of the extraction of the rhizomes,” writes Gomez Pompa.
Money from the companies funded research of some scientists working in the Dioscorea Commission who would later become scientific trailblazers in Mexico — Sarukhán Kermez is a clear example.
“To work on an undergraduate dissertation with funding was unheard of [in 1961],” Sarukhán Kermez tells me. “It was like a free trip to the moon.”
Sarukhán Kermez became director of the Dioscorea Commission in 1965 and made his first-ever plane trip to Puerto Rico. He was on an in incognito mission visiting the experimental Dioscorea fields in search for clues to cultivate the plant in Mexico. At the time, foreign pharmaceutical firms were attempting to grow Dioscorea in Guatemala, Costa Rica and Puerto Rico after the Mexican government imposed prohibitive taxes for the exportation of barbasco and diosgenin in the early 1950s. Efforts to cultivate plants with enough diosgenin to be useful for industrial production were unsuccessful because scientists were still unfamiliar with basic aspects of the plant.
“Not only were the physiology and biochemistry of the plant unknown, but the developmental morphology, and even the taxonomy, were poorly understood,” reports Ray F. Dawson, former botanist from Columbia University.
Eventually, scientists from the U.S. found other intermediates to produce steroids out of soy oils and sisal waste. Whatever knowledge scientists acquired about the barbasco never crystallized into management plans for the plant nor for the protection of its habitat. INIF reported that there had been 7.6 million hectares where barbasco had once been exploited, but by the 1970s, 80% of those had been converted to agricultural and grazing lands.
The loss of international buyers imminently pushed the Dioscorea Commission in Mexico to dissolve. Despite further efforts of the Mexican government to regulate barbasco during the 1970s, it soon became a thing of the past.
The saga of Marker and Dioscorea is now told as a tale to students at the National Autonomous University of Mexico’s Faculty of Sciences almost as a curiosity: The plants have become a memento of the once glorious botanical industry in Mexico.
The global market of hormonal contraceptives produced synthetically in 2018 was valued at $13.36 billion and is expected to grow by 15.2% through 2022. For some chemists like Fernández-Herrera, though, plants and traditional knowledge are still relevant to the steroid industry today. Even when she has heard some chemists say that research around steroids “was over” in the 1940s, she believes there are compounds in plants still awaiting to be discovered. One of those plants might be the next barbasco.
Gómez Pompa might agree. In his memoirs, he writes: “If all this great steroid industry was born from a wild plant, how many others might be out there which have simply not been studied.”
Edited by Rodrigo Pérez Ortega and Alun Salt
Wonderful analysis; I really enjoyed reading it!
Fantastic article, thank you 🙂
Thank you, Ernesto! Glad to hear you found it interesting.