Julian supervised the assembly of the plant at Glidden when he arrived in 1936. He then designed and supervised construction of the world’s first plant for the production of industrial-grade, isolated soy protein from oil-free soybean meal. Isolated soy protein could replace the more expensive milk casein in industrial applications such as coating and sizing of paper, glue for making Douglas fir plywood, and in the manufacture of water-based paints.
At the start of World War II, Glidden sent a sample of Julian’s isolated soy protein to National Foam System Inc. (today a unit of Kidde Fire Fighting), which used it to develop Aer-O-Foam, the U.S. Navy’s beloved fire-fighting “bean soup.” While it was not exactly Julian’s brainchild, his meticulous care in the preparation of the soy protein made the firefighting foam possible. When a hydrolyzate of isolated soy protein was fed into a water stream, the mixture was converted into a foam by means of an aerating nozzle. The soy protein foam was used to smother oil and gasoline fires aboard ships and was particularly useful on aircraft carriers. It saved the lives of thousands of sailors and airmen. Citing this achievement, in 1947 the NAACP awarded Julian the Spingarn Medal, its highest honor.
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 and patented.[2][26] At that time clinicians were discovering many uses for the newly discovered hormones. However, only minute quantities could be extracted from hundreds of pounds of the spinal cords of animals.
In 1940 Julian was able to produce 100 lb of mixed soy sterols daily, which had a value of $10,000 ($82,000 today) as sex hormones. Julian was soon ozonizing 100 pounds daily of mixed sterol dibromides. The soy stigmasterol was easily converted into commercial quantities of the female hormone progesterone, and the first round of progesterone he made, valued at $63,500 ($521,000 today), was shipped to the buyer, Upjohn, in an armored car. Production of other sex hormones soon followed.
His work made possible the production of these hormones on a larger 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 had prevented a significant reduction in wholesale and retail prices for clinical use of these hormones in the 1940s. He saved many lives with this discovery.
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, starting with deoxycholic acid from cattle bile acids. On September 30, 1949, Julian announced an improvement in the process of producing cortisone. This eliminated the need to use osmium tetroxide, which was a rare and expensive chemical. By 1950, Glidden could begin producing closely related compounds which might have partial cortisone activity. Julian also announced the synthesis, starting with the cheap and readily available pregnenolone (synthesized from the soybean oil sterol stigmasterol) of the steroid cortexolone (also known as Reichstein’s Substance S), a molecule that differed from cortisone by a single missing oxygen atom; and possibly 17α-hydroxyprogesterone and pregnenetriolone, which he hoped might also be effective in treating rheumatoid arthritis, but unfortunately they were not.
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 to concentrate on Substance S. Julian developed a 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 (equivalent to $460,000 in 2017) 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 acquired exclusive licenses of Glidden patents for the synthesis of Substance S. Pfizer had developed a fermentation process for microbial 11β-oxygenation of steroids in a single step that could convert Substance S directly to 11β-hydrocortisone (cortisol), with Syntex undertaking large-scale production of cortexolone at very low cost.
Circa 1950, Julian moved his family to the Chicago suburb of Oak Park, becoming the first African-American family to reside there. Although some residents welcomed them into the community, there was also opposition. Before they even moved in, on Thanksgiving Day, 1950, their home was fire-bombed. Later, after they moved in, the house was attacked with dynamite on June 12, 1951. The attacks galvanized the community, and a community group was formed to support the Julians. Julian’s son later recounted that during these times, he and his father often kept watch over the family’s property by sitting in a tree with a shotgun.
In 1953, Julian founded his own research firm, Julian Laboratories, Inc. He brought many of his best chemists, including African-Americans and women, from Glidden to his own company. Julian won a contract to provide Upjohn with $2 million worth of progesterone (equivalent to $16 million today). To compete against Syntex, he would have to use the same Mexican yam Mexican barbasco trade as his starting material. Julian used his own money and borrowed from friends to build a processing plant in Mexico, but he could not get a permit from the government to harvest the yams. Abraham Zlotnik, a former Jewish University of Vienna classmate whom Julian had helped escape from the Holocaust, led a search to find a new source of the yam in Guatemala for the company.
In 1964, Julian founded Julian Associates and Julian Research Institute, which he managed for the rest of his life.