Percy Lavon Julian: Pioneer in Chemical Synthesis and Advocate for Equality

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 person to synthesize the natural product physostigmine and a pioneer in the industrial large-scale chemical synthesis of the human hormones progesterone and testosterone from plant sterols such as stigmasterol and sitosterol. His work helped to greatly reduce the cost of steroid intermediates to large multinational pharmaceutical companies. This significantly expanded the use of several important drugs, including synthetic cortisone. Julian was one of the first African Americans to be allowed to earn a doctorate in chemistry.

Early Life and Education

Percy Lavon Julian was born on April 11, 1899, in Montgomery, Alabama, the first of six children born to James Sumner Julian and Elizabeth Lena Adams Julian. Both of his parents were graduates of what was to be Alabama State University. At a time when access to an education beyond the eighth grade was extremely rare for African Americans, Julian's parents steered all of their children toward higher education.

Julian attended DePauw University in Greencastle, Indiana. The college accepted few African-American students. The segregated nature of the town subjected him to social humiliations. He was not allowed to live in a college dormitory and first stayed in an off-campus boarding home, which refused to serve him meals. It took him days before he found an establishment where he could eat. He later found work firing the furnace, waiting tables, and doing other odd jobs in a fraternity house; in return, he was allowed to sleep in the attic and eat at the house.

By 1930, his father had moved the family to Greencastle so that all his children could attend DePauw. He still worked as a railroad postal clerk. James owned his own home; his house, worth $3,000 in 1930, was worth about $58,000 in 2025.

After graduating from DePauw in 1920 Phi Beta Kappa and valedictorian, Julian wanted to obtain his doctorate in chemistry, but learned it would be difficult for an African American to do so. Instead, he obtained a position as a chemistry instructor at Fisk University. In 1923 he received an Austin Fellowship in Chemistry, which allowed him to attend Harvard University to obtain his M.S. However, worried that white students would resent being taught by an African American, Harvard withdrew Julian's teaching assistantship, making it impossible for him to complete his Ph.D.

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. Europe gave him freedom from the racial prejudices that had stifled him in the States. He freely participated in intellectual social gatherings, attended the opera, and found greater acceptance among his peers.

Academic Career and Research at DePauw

After returning from Vienna, Julian taught for one year at Howard University. At Howard, in part due to his position as a department head, Julian became caught up in university politics, setting off a chain of scandals. At university president Mordecai Wyatt Johnson's request, he goaded white professor of chemistry Jacob Shohan (Ph.D., Harvard), into resigning.

In late May 1932, Shohan retaliated by releasing to the local African-American newspaper the letters Julian had written to him from Vienna. Around this same time, Julian also became entangled in an interpersonal conflict with his laboratory assistant, Robert Thompson. Julian had recommended Thompson for dismissal in March 1932. Thompson sued Julian for "alienating the affections of his wife", Anna Roselle Thompson, stating he had seen them together in a sexual tryst. Julian counter-sued him for libel.

When Thompson was fired, he too gave the paper intimate and personal letters which Julian had written to him from Vienna. Julian's letters revealed "how he fooled the [Howard] president into accepting his plans for the chemistry building" and "how he bluffed his good friend into appointing" a professor of Julian's liking. Through the summer of 1932, the Baltimore Afro-American published all of Julian's letters. Eventually, the scandal and accompanying pressure forced Julian to resign.

At the lowest point in Julian's career, his former mentor, William Martin Blanchard, a professor of chemistry at DePauw, threw him a much-needed lifeline. Blanchard offered Julian a position to teach organic chemistry at DePauw in 1932. Julian then helped Josef Pikl, a fellow student at the University of Vienna, to come to the United States to work with him at DePauw.

Read also: More on Julien Alfred

Synthesis of Physostigmine

In 1935, Julian and Pikl completed the total synthesis of physostigmine and confirmed the structural formula assigned to it. Robert Robinson of Oxford University in the U.K. had been the first to publish a synthesis of physostigmine, but Julian noticed that the quoted melting point of Robinson's end product was incorrect, indicating that he had not created it. When Julian completed his synthesis, the melting point matched the correct one for natural physostigmine from the calabar bean. Julian published the first total synthesis of physostigmine, an important drug, and corrected errors of the then-reigning organic chemist Robert Robinson.

Physostigmine, the principal alkaloid of the Calabar bean, has long been used as a drug. The project, which took three years to complete, was reported in a series of papers in the Journal of the American Chemical Society. Julian's paper, entitled "Studies in the Indole Series V. The Complete Synthesis of Physostigmine (Eserine)," explained how Julian synthesized physostigmine. Glaucoma, a disorder in which the pressure in the eyeball increases when the aqueous humor does not drain normally, can cause damage to the optic nerve and a loss of vision. Physostigmine promotes drainage of this fluid by easing the constriction of outflow channels. Starting from phenacetin, Julian and Josef Pikl, who was working as an assistant in chemistry, assembled physostigmine in 11 synthetic steps.

During the project, while the two chemists were working toward the synthesis of d,l-eserethole (a key intermediate compound two steps removed from physostigmine), a group of chemists, also working to synthesize physostigmine, under the direction of Sir Robert Robinson at Oxford University in England, reported their synthesis of d,l-eserethole. Unlike today, when chemists can rely on modern analytical methods such as nuclear magnetic resonance spectroscopy, mass spectrometry, and X-ray crystallography to determine unequivocally the composition and structure of a compound, chemists in the 1930s relied on simpler, indirect, physicochemical methods for their analysis. As it happened in the case of d,l-eserethole, the physicochemical parameters of Robinson's d,l-eserethole were not in agreement with those of Julian and Pikl.

Following the total synthesis of physostigmine and the separation of physostigmine into its optical isomers, Julian was to make another discovery at DePauw that not only would enhance his stature as a chemist but also greatly improve the lives of many. It was in the course of isolating geneserin, a companion alkaloid of physostigmine from the Calabar bean, that Julian discovered small crystals of the hydrate of stigmasterol in the acid-washed oil extracted from the beans.

Stigmasterol and Career Obstacles

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 the synthesis of human steroidal hormones. In 1956 Julian was denied a professorship at DePauw for racial reasons. DuPont offered a job to Pikl, but declined to hire Julian, despite his superlative qualifications as an organic chemist, apologizing that they were "unaware he was black".

Julian next applied for a job at the Institute of Paper Chemistry in Appleton, Wisconsin. However, Appleton was a sundown town, forbidding African Americans from staying overnight, explicitly stating "No Negro should be a bed or boarded overnight in Appleton."

Career at Glidden

Meanwhile, Julian had written to the Glidden Company, a supplier of soybean oil products, to request a five-gallon sample of the oil to use as his starting point for the synthesis of human steroidal sex hormones (in part because his wife was experiencing infertility). After receiving the request, W. J. O'Brien, a vice-president at Glidden, telephoned Julian, offering him the position of director of research at Glidden's Soya Products Division in Chicago. Julian was the first black scientist hired for such a position.

Julian supervised the assembly of the plant at Glidden when he arrived in 1936. He then designed and supervised the 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.

"Bean Soup" and Steroid Synthesis

Julian's meticulous care in the preparation of the soy protein made the Navy's firefighting "bean soup" possible. 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 has saved the lives of thousands of sailors and airmen. Citing this achievement, in 1947 the NAACP awarded Julian the Spingarn Medal, its highest honor.

Percy'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. 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 animal spinal cords. In 1940, Julian was able to produce 100 pounds (45 kg) of mixed soy sterols daily, which had a value of $10,000 ($108,000 today) as sex hormones. Julian was soon ozonizing 100 pounds (45 kg) daily of mixed sterol dibromides.

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.

Cortisone Synthesis

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 improved process for producing cortisone. This eliminated the use of osmium tetroxide, which was rare and expensive. By 1950, Glidden could begin producing closely related compounds which might have partial cortisone activity. 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-hydrocortisone from progesterone or Compound S, respectively, which could then by further chemical steps be converted to cortisone or 11β-hydrocortisone (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.

Julian Laboratories and Later Career

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).

Around 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, there was also opposition. Before they moved in, on Thanksgiving Day, 1950, their home was firebombed. Later, after they moved in, the house was attacked with dynamite on June 12, 1951.

He won a contract to provide Upjohn with $2 million worth of progesterone (equivalent to $22 million today). To compete against Syntex, he would have to use the same Mexican yam, obtained from the 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.

Within five years, large American multinational pharmaceutical companies had acquired all six producers of steroid intermediates in Mexico, four of which had been Mexican-owned. Syntex reduced the cost of steroid intermediates 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, which 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.

In 1958, Upjohn purchased 6,900 kg of progesterone from Syntex at $0.135 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 at $7.99 per gram from 1954, and prednisone 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.

In 1954, Julian left the Glidden Company to establish Julian Laboratories which specialized in producing his synthetic cortisone. He developed farms in Mexico and Guatemala and a laboratory in Mexico to produce botanical materials for steroid production. By 1961, Julian Laboratories had become so successful that the pharmaceutical giant Smith, Kline & French purchased the company for more than $2.2 million (approximately $22 million today).

Julian Laboratories chemists found a way to quadruple the yield on a product on which they were barely breaking even. In 1964, Julian founded Julian Associates and Julian Research Institute, which he managed for the rest of his life.

Personal Life and Legacy

On December 24, 1935, he married Anna Roselle (Ph.D. in sociology, 1937, University of Pennsylvania). They had two children: Percy Lavon Julian Jr.

As his business and fame grew, Julian became a major philanthropist, supporting academic institutions and Black and White charities. He led a National Association for the Advancement of Colored People Legal Defense and Educational Fund campaign to fight against discrimination in jobs and housing. In 1973, Julian was inducted into the National Academy of Sciences, as only the second African American to achieve this honor.

He received countless awards and honors including the prestigious Spingarn Medal from the NAACP and was asked to serve on numerous commissions and advisory boards. He received fifteen honorary degrees as well as authoring and co-authoring more than 160 publications. He was trustee of five universities, including DePauw.

Percy L. Julian died from liver cancer on April 19, 1975.

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