Percy Lavon Julian (April 11, 1899 – April 19, 1975) was an American research chemist and a pioneer in the chemical synthesis of medicinal drugs from plants. He was the first to synthesize the natural product physostigmine; and was an American pioneer in the industrial large-scale chemical synthesis of the human hormones, steroids, progesterone, and testosterone, from plant sterols such as stigmasterol and sitosterol. His work would lay the foundation for the steroid drug industry's production of cortisone, other corticosteroids, and birth control pills. He later started his own company to synthesize steroid intermediates from the Mexican wild yam. His work helped reduce the cost of steroid intermediates to large multinational pharmaceutical companies.
During his lifetime he received more than 130 chemical patents. Julian was the one of the first African Americans to receive a doctorate in chemistry. He was the first African-American chemist inducted into the National Academy of Sciences, and the second African-American scientist inducted from any field.
Julian attended DePauw University in Greencastle, Indiana. The college accepted few African-American students. The segregated nature of the town forced social humiliations. Julian was not allowed to live in the college dormitories and first stayed in an off-campus boarding home, which refused to serve him meals. It took him days before Julian found an establishment where he could eat. He worked firing the furnace and doing other odd jobs in a fraternity house. In return, he was allowed to sleep in the basement and eat at the house. Julian graduated from DePauw in 1920 Phi Beta Kappa and valedictorian. By 1930 Julian's father had moved the entire family to Greencastle, Indiana so that all his children could attend college at DePauw. The father was still working as a railroad postal clerk.
Julian wanted to obtain his doctorate in chemistry, but learned it would be difficult for an African American. After graduating from DePauw, Julian became a chemistry instructor at Fisk University. He then received an Austin Fellowship in Chemistry and went to Harvard University in 1923 for his M.S. Worried that white students would resent being taught by an African American, Harvard withdrew Julian's teaching assistantship. He was unable to complete his Ph.D. at Harvard.
In 1929, while an instructor at Howard University, Julian received a Rockefeller Foundation fellowship to continue his graduate work at the University of Vienna, where he earned his Ph.D. in 1931. He studied under Ernst Späth and was considered an impressive student. In Europe, he found freedom from the racial prejudices that had nearly stifled him in the States. He freely participated in intellectual social gatherings, went to the opera and found greater acceptance among his peers. Julian was one of the first African Americans to receive a Ph.D. in chemistry, after St. Elmo Brady and Edward M. A. Chandler. During Julian's lifetime he earned more than 130 chemical patents for his work. Percy Julian was the second African American to get a masters degree in chemistry. He was the first African-American chemist inducted into the National Academy of Sciences, and the second African-American scientist inducted from any field.
After returning from Vienna, Julian taught at Howard University for one year, where he met his future wife, Anna Roselle Johnson (Ph.D. in Sociology, 1937, University of Pennsylvania). They married on December 24, 1935 and had two children: Percy Lavon Julian, Jr. (1940-February 24, 2008), who became a prestigious civil rights lawyer in Madison, Wisconsin; and Faith Roselle Julian (1944- ), who still resides in their Oak Park home and often makes moving speeches about her father and his contributions to science.
At Howard, Julian got involved in university politics and set off an embarrassing chain of events. After he goaded a white chemist named Jacob Shohan into resigning, Shohan retaliated by releasing to the local African-American newspaper the letters Julian had written to him from Vienna. The letters contained accounts of Julian's sex life, and criticism of individual Howard faculty members. Julian's laboratory assistant, Robert Thompson, also charged he had found his wife and Julian together in a sexual tryst. When Thompson was fired for filing a lawsuit against the University, he also gave the paper racy letters which Julian had written to him from Vienna. Through the summer of 1932, the Baltimore Afro-American published all of Julian's letters.
William Blanchard then offered Julian a position to teach organic chemistry at DePauw University in 1932. Julian helped Josef Pikl, a fellow student at the University of Vienna, to come to the United States to work with him at Depauw. In 1935 Julian and Pikl completed the total synthesis of physostigmine, and confirmed the structural formula assigned to it. Robert Robinson of Oxford University was the first to publish a synthesis of physostigmine, but Julian noticed that the melting point was wrong for Robinson's end product. When Julian completed his synthesis, the melting point matched the correct one for natural physostigmine from the calabar bean.
Julian also extracted stigmasterol, which took its name from Physostigma venenosum, the west African calabar bean that he hoped could serve as raw material for synthesis of human steroidal hormones. At about this time, 1934, Butenandt , and Fernholz ,in Germany, had shown that stigmasterol, isolated from soybean oil, could be converted to progesterone by synthetic organic chemistry.
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.
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. To compete against Syntex, he would have to use the same Mexican yam as his starting material. Julian borrowed and used his own money to build a processing plant in Mexico, but he could not get a permit from the government to harvest the yams. Abraham Zlotnik found a new source of the yam in Guatemala for the company.
In July 1956, Julian and executives of two other American companies trying to enter the Mexican steroid intermediates market appeared before a U.S. Senate subcommittee. They testified that Syntex was using undue influence to monopolize access to the Mexican yam. The hearings resulted in Syntex signing a consent decree with the U.S. Justice Department. While it did not admit to restraining trade, it promised not to do so in the future. Within five years, large American multinational pharmaceutical companies had acquired all six producers of steroid intermediates in Mexico. Four had been Mexican-owned. Syntex reduced the cost of bulk progesterone as an intermediate more than 250-fold over twelve years, from $80 per gram in 1943 to $0.31 per gram in 1955. Competition from Upjohn and General Mills, who had together made very substantial improvements in the production of progesterone from stigmasterol, forced the price of Mexican progesterone down to less than $0.15 per gram in 1957. The price continued to fall, bottoming out at $0.08 per gram in 1968. In 1958, Upjohn purchased 6,900 kg of progesterone from Syntex at $.135 per gram, 6,201 kg of progesterone from Searle (who had acquired Pesa) at $0.143 per gram, 5,150 kg of progesterone from Julian Laboratories at $0.14 per gram, and 1,925 kg of progesterone from General Mills (who had acquired Protex) at $0.142 per gram. Despite continually falling bulk prices of steroid intermediates, an oligopoly of large American multinational pharmaceutical companies kept the wholesale prices of corticosteroid drugs fixed and unchanged into the 1960s. Cortisone was fixed at $5.48 per gram from 1954, hydrocortisone fixed at $7.99 per gram from 1954, and prednisone fixed at $35.80 per gram from 1956. Merck and Roussel Uclaf concentrated on improving the production of corticosteroids from cattle bile acids. In 1960 Roussel produced almost one-third of the world's corticosteroids from bile acids.
One year Julian Laboratories chemists found a way to quadruple the yield on a product on which they were barely breaking even. Julian reduced their price for the product from $4,000 per kg down to $400 per kg. He sold the company in 1961, for $2.3 million dollars. The U.S. and Mexico facilities were purchased by Smith Kline and Julian's chemical plant in Guatemala was purchased by morgan michelle Upjohn.
In 1964, Julian founded Julian Associates and Julian Research Institute, which he managed for the rest of his life.
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