Cortisone and the "Pill"
One research program led by Djerassi focused on the conversion of diosgenin to cortisone. Early in 1949, Philip
Hench and Edward Kendall at the Mayo Clinic had reported spectacular results from the treatment of rheumatoid
arthritis with cortisone. Newspapers featured stories of crippled arthritics dancing in the streets after therapy.
The medical community soon recognized the value of cortisone (and cortisol) in the treatment of other inflammatory
conditions, but it was too expensive for widespread use. At that time, cortisone could only be made by a laborious
36-step Merck & Co. process that started with desoxycholic acid isolated from ox bile. Syntex completed its synthesis
of cortisone from diosgenin; however, this achievement immediately was overtaken by another scientific breakthrough.
In 1951, scientists at the Upjohn Co. introduced a microbiological process, which specifically oxidized progesterone to a
product that was easily converted to cortisone. As Rosenkranz later recalled, " . . . in July 1951, I received a phone
call from Upjohn asking me whether we would be able to accept an order for 10 tons of progesterone at 48 cents per gram.
The going price at the time was in the $2 range and the quantity was unheard of." Soon, most cortisone was manufactured by
Upjohn's process using Syntex progesterone, although the Merck route was improved enough to remain competitive.
Syntex also competed with other drug companies in the hunt for an effective oral contraceptive. Because progesterone prevents
ovulation during pregnancy, research focused on the discovery of an orally active progesterone mimic. Using expertise obtained
in the conversion of testosterone to estradiol and estrone, along with two important leads from the chemical literature, Djerassi's
group designed and, in 1951, synthesized norethindrone, the active ingredient in the first practical oral contraceptive. For many
reasons, the first "pill" to be marketed was G. D. Searle and Co.'s norethynodrel, but norethindrone accounted for more than half
of the oral contraceptive market in the 1970s.
By the 1950s, Syntex and its competitors in Mexico* were producing more than half the sex hormones sold in the United States.
Syntex's economic success was matched by its scientific reputation, which was boosted by a very liberal publication policy.
Contributions made by Syntex accounted for more than 30% of all industrial citations in the Fiesers' definitive 1959
monograph, Steroids. In 1951, Fortune magazine headlined: "Syntex makes the biggest technological boom ever
heard south of the border." Considering the impact the Mexican steroid industry would have on world health and culture,
Fortune greatly underestimated the power of the explosion.
* Besides Diosynth and others, these competitors included Glidden and, later, Laboratories Julian, the independent
institute of Percy L. Julian (link), Glidden's former research director. Julian's starting material was stigmasterol,
a steroid isolated from soybean oil.