Percy Lavon Julian (April 11, 1899 – April 19, 1975) was a U.S. research
chemist and a pioneer in the
chemical synthesis of medicinal
drugs from plants.
[1] He was the first 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 laid the foundation for the
steroid drug industry's production of
cortisone, other
corticosteroids, and
birth control pills.
[2][3][4][5]
He later started his own company to synthesize steroid intermediates from the Mexican
wild yam. His work helped greatly reduce the cost of steroid intermediates to large multinational pharmaceutical companies, helping to significantly expand the use of several important drugs.
[6][7]
Julian received more than 130 chemical patents. He was 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 (behind
David Blackwell) from any field.
[6]
Percy Julian was born in
Montgomery, Alabama as the first child of six born to James Sumner Julian and Elizabeth Lena Julian, née Adams. Both of his parents were graduates of what was to be
Alabama State University. His father, James, whose own father had been a
slave, was employed as a clerk in the Railway Service of the
United States Post Office, while his mother, Elizabeth, worked as a schoolteacher.
[8][9][10] Percy Julian grew up in the time of racist
Jim Crow culture and legal regime in the southern United States. Among his childhood memories was finding a
lynched man hanged from a tree while walking in the woods near his home. 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 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 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. Julian graduated from DePauw in 1920
Phi Beta Kappa and
valedictorian.
[11] By 1930 Julian's father would move the entire family to
Greencastle so that all his children could attend college at DePauw. The father was still working as a railroad postal clerk.
[8]
After graduating from DePauw, Julian wanted to obtain his doctorate in chemistry, but learned it would be difficult for an African-American. 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 American 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. 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.
[12][13] Julian was one of the first African-Americans to receive a Ph.D. in chemistry, after
St. Elmo Brady and Edward M. A. Chandler.
[6][14]
After returning from
Vienna, Julian taught for one year at
Howard University, 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. (August 31, 1940 – February 24, 2008), who became a prestigious civil rights lawyer in
Madison, Wisconsin;
[15] and Faith Roselle Julian (1944– ), who still resides in their Oak Park home and often makes inspirational speeches about her father and his contributions to science.
[11]
At Howard, Julian became involved in university politics, setting off an embarrassing chain of events. At the university president's request, 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. Then Julian's laboratory assistant, Robert Thompson, charged he had discovered his wife together with Julian in a sexual tryst. When Thompson was fired for filing a lawsuit against the University, he too 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. Eventually, the scandal and accompanying pressure forced Julian to resign. He lost his position and everything he had worked for.
[6]
At the lowest point in Julian's career, his former mentor, William Blanchard, threw him a much-needed lifeline. Blanchard offered Julian a position to teach
organic chemistry at DePauw University 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. 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 melting point of Robinson's end product was wrong, 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.
[6]
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, in 1934, Butenandt and Fernholz, in Germany,
[16][17] had shown that stigmasterol, isolated from soybean oil, could be converted to
progesterone by synthetic organic chemistry.
Private sector work: Glidden[edit]
In 1936 Julian was denied a professorship at DePauw for racial reasons. DePauw had offered a job to fellow chemist Josef Pikl but declined to hire Julian, despite his superlative qualifications as an organic chemist, apologizing that they were "unaware he was a Negro".
[18] Julian next applied for a job at the Institute of Paper Chemistry (IPC) in Wisconsin. However, the Wisconsin city of Appleton, where the institute was located, was a
sundown town, forbidding African-Americans from staying overnight, stating directly "No Negro should be bed or boarded overnight in Appleton."
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 suffering from
infertility).
[3] After receiving the request, W.J. O'Brien, a vice-president at Glidden, made a telephone call to Julian, offering him the position of director of research at Glidden's Soya Products Division in Chicago. He was very likely offered the job by O'Brien because he was fluent in German, and Glidden had just purchased a modern continuous countercurrent solvent extraction plant from Germany for the extraction of vegetable oil from soybeans for paints and other uses.
[6]
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,
[19][20] 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
fire fighting 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.
[20] Citing this achievement, in 1947 the
NAACP awarded Julian the
Spingarn Medal, its highest honor.
Steroids[edit]
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][3][21] 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 in 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 pound of progesterone he made, valued at $63,500, was shipped to the buyer in an armored car.
[5] Production of other sex hormones soon followed.
[22]
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.
[23][24][25]
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.
[26][27][28][29] This eliminated the need to use
osmium tetroxide, which was a rare and expensive chemical.
[26] 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,
[26][27][28][29][30] but unfortunately they were not.
[29]
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).
[31]
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.
[29]
In 1953, Glidden decided to leave the steroid business, which had been relatively unprofitable over the years despite Julian's innovative work.
[32] On December 1, 1953, Julian left Glidden after 18 years, giving up a salary of nearly $50,000 a year (approximately $400,000 in 2014 dollars), to found his own company, Julian Laboratories, Inc., taking over the small, concrete-block building of Suburban Chemical Company in
Franklin Park, Illinois.
[33][34]
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.
[29]
Oak Park and Julian Laboratories[edit]
In about 1950 Julian moved his family to the
Chicago suburb of
Oak Park, where the Julians were the first African-American family.
[35] 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.
[36] 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.
[6]
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 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 Nazi European holocaust, led a search to find 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.
[25][37] 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.
[25] 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.
[25]
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.
[25][37] 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 to less than $0.15 per gram in 1957. The price continued to fall, bottoming out at $0.08 per gram in 1968.
[25][29]
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.
[38]
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.
[25][38] 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.
[29]
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 to $400 per kg.
[6] He sold the company in 1961 for $2.3 million.
[39] The U.S. and Mexico facilities were purchased by
Smith Kline, and Julian's chemical plant in Guatemala was purchased by
Upjohn.
In 1964, Julian founded Julian Associates and Julian Research Institute, which he managed for the rest of his life.
[40]
National Academy of Sciences[edit]
He was elected to the
National Academy of Sciences in 1973 in recognition of his scientific achievements.
[6] He became the second African-American to be inducted, after
David Blackwell.
Julian died of liver cancer on April 19, 1975 in St. Therese Hospital in
Waukegan, Illinois and was buried in Elm Lawn Cemetery in
Elmhurst, Illinois.
[9][41][42]
Legacy and honors[edit]
- In 1950, the Chicago Sun-Times named Percy Julian the Chicagoan of the Year.[11]
- Since 1975, the National Organization for the Professional Advancement of Black Chemists and Chemical Engineers has presented the Percy L. Julian Award for Pure and Applied Research in Science and Engineering.[43]
- In 1975, Percy L. Julian High School was opened on the south side of Chicago, Illinois as a Chicago public high school.
- In 1985, Hawthorne School in Oak Park, Chicago, was renamed Percy Julian Middle School.[44]
- In 1980, the science and mathematics building on the DePauw University campus was rededicated as the Percy L. Julian Mathematics and Science Center. In Greencastle, Indiana, where DePauw is located, a street was named after Julian.
- Illinois State University, where Julian served on the board of trustees, named a hall after him.[45]
- A structure at Coppin State University is named the Percy Julian Science Building.
- In 1990, he was inducted into the National Inventors Hall of Fame.[46]
- In 1993 Julian was honored on a stamp issued by the United States Postal Service.[47]
- In 1999, the American Chemical Society recognized Julian's synthesis of physostigmine as a National Historic Chemical Landmark.[48]
- In 2002, scholar Molefi Kete Asante listed Percy Lavon Julian on his list of 100 Greatest African-Americans.[49]
- In 2011, the qualifying exam preparation committee at the Albert Einstein College of Medicine was named for Percy Julian.
- In 2014, Google honored him with a Doodle.
Nova documentary[edit]
Ruben Santiago-Hudson portrayed Percy Julian in the
Public Broadcasting Service Nova documentary about his life, called Forgotten Genius. It was presented on the PBS network on February 6, 2007, with initial sponsorship by the
Camille and Henry Dreyfus Foundation and further funding by the
National Endowment for the Humanities. Approximately sixty of Julian's family members, friends, and work associates were interviewed for the docudrama.
[6][50]
Production on the biopic began at
DePauw University's Greencastle campus in May 2002 and included video of Julian's bust on display in the atrium of the university's Percy Lavon Julian Science and Mathematics Center. Completion and broadcasting of the documentary program was delayed in order for Nova to commission and publish a matching book on Julian's life.
[51]
According to
University of Illinois historian James Anderson in the film, "His story is a story of great accomplishment, of heroic efforts and overcoming tremendous odds...a story about who we are and what we stand for and the challenges that have been there and the challenges that are still with us."
[50]
Archive[edit]
The Percy Lavon Julian family papers are archived at
DePauw University.
[52]
Patents[edit]
- U.S. Patent 2,218,971, October 22, 1940, Recovery of sterols
- U.S. Patent 2,373,686, July 15, 1942, Phosphatide product and method of making
- U.S. Patent 2,752,339, June 26, 1956, Preparation of cortisone
- U.S. Patent 3,149,132, September 15, 1964, 16-aminomenthyl-17-alkyltestosterone derivatives
- U.S. Patent 3,274,178, September 20, 1966, Method for preparing 16(alpha)-hydroxypregnenes and intermediates obtained therein
- U.S. Patent 3,761,469, September 25, 1973, Process for the manufacture of steroid chlorohydrins; with Arnold Lippert Hirsch
Publications[edit]
