Rheumatoid Arthritis Support

Julian's research at Glidden changed direction in 1940 when he began work on synthesizing progesterone, estrogen and testosterone from the plant sterols, stigmasterol and sitosterol, isolated from soybean oil by a foam technique he invented. At that time clinicians were discovering many uses for the newly discovered hormones. However, only minute quantities could be produced from the extraction of hundreds of pounds of spinal cords.

In 1940 Julian was able to produce 100& lb of mixed soy sterols daily, which had a value of $10,000, in sex hormones. Julian was soon ozonizing 100 pounds daily of mixed sterol dibromides. The result was the female hormone progesterone which was put on the American market in bulk for the first time. Production of other sex hormones soon followed.

His work made possible the production of these hormones on a larger (kilogram) industrial scale, with the potential of reducing the cost of treating hormonal deficiencies. Julian and his co-workers obtained patents for Glidden on key processes for the preparation of progesterone and testosterone from soybean plant sterols. Product patents held by a former cartel of European pharmaceutical companies prevented a significant reduction in wholesale and retail prices for clinical use of these hormones in the 1940s.

On April 13, 1949, rheumatologist Philip Hench at the Mayo Clinic announced the dramatic effectiveness of cortisone in treating rheumatoid arthritis. The cortisone was produced by Merck at great expense using a complex 36-step synthesis developed by chemist Lewis Sarett. It started with deoxycholic acid from cattle bile acids. On September 30, 1949, Julian announced an improvement in the process of producing cortisone from bile acids. This eliminated the need to use osmium tetroxide (a rare and expensive chemical). By 1950, Glidden could begin producing closely related compounds which may have partial cortisone activity. Julian also announced the synthesis, starting with pregnenolone from soybean oil sterols of the steroid cortexolone and possibly 17α-hydroxyprogesterone and pregnenetriolone, which he hoped might also be effective in treating rheumatoid arthritis .

On April 5, 1952, biochemist Durey Peterson and microbiologist Herbert Murray at Upjohn published the first report of a fermentation process for the microbial 11α-oxygenation of steroids in a single step (by common molds of the order Mucorales). Their fermentation process could produce 11α-hydroxyprogesterone or 11α-hydroxycortisone from progesterone or Compound S, respectively, which could then by further chemical steps be converted to cortisone or 11β-hydroxycortisone (cortisol).

After two years, Glidden abandoned production of cortisone from bile acids to concentrate on Compound S. Julian developed an excellent multistep process for conversion of pregnenolone, available in abundance from soybean oil sterols to cortexolone. In 1952, Glidden, which had been producing progesterone and other steroids from soybean oil, shut down its own production and began importing them from Mexico through an arrangement with Diosynth (a small Mexican company founded in 1947 by Russell Marker after leaving Syntex). Glidden's cost of production of cortexolone was relatively high, so Upjohn decided to use progesterone, available in large quantity at low cost from Syntex, to produce cortisone and hydrocortisone.

In 1953, Glidden decided to leave the steroid business which had been relatively unprofitable over the years despite Julian's innovative work.

On December 1, 1953, Julian left Glidden after 18 years, giving up a salary of nearly $50,000 a year, to found his own company, Julian Laboratories, Inc., taking over the small, concrete-block building of Suburban Chemical Company in Franklin Park, Illinois.

On December 2, 1953, Pfizer and Syntex acquired exclusive licenses of Glidden patents for the synthesis of Compound S. Pfizer had developed a fermentation process for microbial 11β-oxygenation of steroids in a single step that could convert Compound S directly to 11β-hydrocortisone (cortisol), with Syntex undertaking large-scale production of cortexolone at very low cost.


Adapted from the Wikipedia article Percy Lavon Julian, under the G. N. U. Free Documentation License. Please also see http://en.wikipedia.org/wiki