SPECIAL ARTICLE The Story of Percy Lavon Julian Against All Odds James G. Ravin, MD, MS; Eve J. Higginbotham, MD The only thing that has enabled me to keep doing the creative work was the constant determination: Take heart! Go farther on. Percy Lavon Julian1 he persistent drive to attain a goal, no matter how difficult, has been essential for many discoveries. This straightforward concept is exemplified in the career of the black chem- ist Percy Lavon Julian, PhD (1899-1975) (Figure), whose discoveries had a significant effect on the treatment of persons with glaucoma and inflammatory diseases. Among other Tachievements, he was the first person to synthesize physostigmine (eserine), which was the first medi- cation that was effective in treating glaucoma, and he constructed a method to mass-produce cortisone. Physostigmine, which is a cholinesterase inhibitor, was first described in the oph- thalmology literature by Laqueur in 1876.2 Shortly afterward, pilocarpine was shown to be useful in treating persons with glau- coma.3 These 2 medications, which are bo- tanical in origin, were sometimes com- bined into a single eye drop formulation. Pilocarpine is derived from a South Ameri- can shrub and is readily available, but the natural source of physostigmine, the Cala- bar bean from tropical West Africa, is scarce. Julian’s chemical synthesis permit- ted production of the medication in a large quantity at a reduced cost. Physostig- mine and pilocarpine were the mainstays of the medical treatment of glaucoma for more than half a century. (Adrenergic ago- nists were introduced commercially dur- ing the middle of the 1900s. ␤-Adrenergic blockers, carbonic anhydrase inhibitors, and prostaglandin agonists were more re- cently developed.) In recounting his life story, Julian of- Figure. Percy Lavon Julian US postal stamp. ten told friends how he dealt with the ob- stacles in his path to becoming a re- spected scientist, inventor, business leader, gomery, Alabama, where his father worked and champion of human rights. Al- for the United States Postal Service; gov- though he was the grandson of slaves who ernment employment gave the family had been denied formal learning, his par- higher social status than most blacks had ents emphasized education as the best at the time. His father was a prodigious means to success. He was born in Mont- reader who enjoyed difficult material in mathematics and philosophy. The Julian Author Affiliations: Division of Ophthalmology, University of Toledo College of family was close knit; in his youth, Percy Medicine, Toledo, Ohio (Dr Ravin); and Department of Ophthalmology and Visual sometimes worked with relatives in his Science, Morehouse School of Medicine, Atlanta, Georgia (Dr Higginbotham). grandfather’s cotton fields. When the fam- (REPRINTED) ARCH OPHTHALMOL / VOL 127 (NO. 5), MAY 2009 WWW.ARCHOPHTHALMOL.COM 690 ©2009 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/28/2021 ily would sing spirituals, young Ju- 1929, he was awarded a Rockefeller tury and later led to Julian’s election lian wanted to understand the lyr- Foundation fellowship, which he used to the National Academy of Sciences ics. Once he asked his great- to earn a doctoral degree from the in 1973. This distinction is exemplary grandfather, Cabe, to explain a song University of Vienna, Vienna, Aus- on its own; however, when one con- about the prophet Jeremiah; he was tria. Professor Ernst Späth, his teacher siders that he was only the second told the lesson to be learned from there, said Julian was “an extraordi- black person to achieve this honor, that biblical figure is that there is al- nary student, his like I have not seen it takes on added importance. ways a way out of difficulty. The op- before in my career as a teacher.”5(p13) Julian spent 4 years as a re- timism he gained from his great- His doctoral thesis concerned a bo- search fellow at DePauw, but the grandfather and the strong sense of tanical alkaloid, and this work proved trustees of both DePauw and the family unity were always impor- very useful for his later focus on University of Minnesota, Minneapo- tant to him. Late in life he would tell physostigmine. lis, denied him higher appoint- audiences that the breakdown of Two years later he was back at De- ments to their faculties on racial black family life has removed the Pauw, working with physostig- grounds. Julian decided to leave aca- feeling of hope with which he was mine. His coworker Josef Pikl gave demia for industry. He accepted a re- reared, a problem that has no simple this description of him at that time: search position at the Institute of solution. However, his motto was “Percy generated ideas faster than half Paper Chemistry in Appleton, Wis- “There is no such thing as can’t.”4 a dozen people could critically re- consin, only to learn that a statute In the early 1900s, public school- view and test them. He also did most in that city stated, “No Negro should ing for black children in Alabama of the writing, did practically all of be bedded or boarded in Appleton ended with the eighth grade. After 2 the analytical work...andhelped overnight.”5(p18) The Glidden Com- years of private education at the State with much of the dish-washing pany in Chicago, Illinois, hired him Normal School for Negroes in Mont- chores.”5(p15) Julian and Pikl pub- as director of research for one of its gomery, Julian was admitted to De- lished 3 articles that were leading to divisions. Under Julian, the divi- Pauw University, Greencastle, Indi- the final step in the synthesis of phy- sion increased its profits during his ana, as a subfreshman in 1916. Family sostigmine, only to find that a paper 18-year tenure, and he was respon- members who saw him off on the on the same subject had been pub- sible for filing more than 100 pat- northbound train included a grand- lished by a group at The University ents. One of the company’s most use- father who waved a hand that was of Oxford, Oxford, England, under ful products was closely related to missing 2 fingers, the punishment for the direction of a Nobel Prize win- his earlier research on physostig- learning to read, and a 99-year-old ner, Sir Robert Robinson. Julian was mine. He identified a sterol in the grandmother who had established a about to come in second in the race Calabar bean that led to the synthe- record by picking 350 pounds of cot- for his most important achieve- sis of progesterone from soybeans. ton in 1 day. Julian lived in the attic ment. He was convinced that his This made the hormone available in of a fraternity house at DePauw and method was correct and that the Brit- large quantities for the first time. was able to earn enough as a waiter ish group’s method was flawed. He Soon afterward, in 1948, cortisone to cover his tuition. Later, the entire added a statement to his next paper was shown to be useful in treating family followed him to Indiana. Percy declaring that Robinson’s group had persons with rheumatoid arthritis. was the eldest of 6 children, each of made an error. If Julian were to be Julian devised a practical method of whom graduated from DePauw; his shown wrong in his challenge of such synthesizing it and other corticoste- 2 younger brothers became physi- a prominent scientist’s work, his ca- roids. By developing a cost- cians. Despite weaknesses in his el- reer would be seriously jeopar- effective method to produce corti- ementary education, Julian was an ex- dized. Another professor wrote him, sone from soybean oil and, later, cellent student. He was elected to Phi “I know you realize that you must be from yams, the benefits of corti- Beta Kappa, obtained his bachelor’s right in this cordial polemic or else sone treatment could be provided to degree in 1920, and was valedicto- it might lead to grave doubts con- a greater number of patients. Also rian of his class. During the next 2 cerning the authenticity of your fu- while at Glidden, he devised a fire years, he was an instructor in chem- ture work.”5(p17) In his final paper on retardant, Aerofoam, which proved istry at Fisk University, Nashville, the subject, “Studies in the Indole Se- very useful for the military; this foam Tennessee. Then he was awarded a ries, V: the Complete Synthesis of effectively quenched gasoline fires fellowship in biophysics and or- Physostigmine (Eserine),”6 Julian and saved countless lives during ganic chemistry at Harvard Univer- held his ground. His synthesis was World War II. In addition, he de- sity, Cambridge, Massachusetts, confirmed and the scientific commu- veloped a soy protein that became where he obtained a master’s degree nity congratulated him. In 1999, the an important ingredient in latex in 1923. No faculty position was avail- American Chemical Society desig- house paint. able for a black man at that institu- nated his laboratory a National His- However, Glidden wanted Ju- tion at the time, nor could he obtain toric Chemical Landmark for the lian to continue to concentrate on a doctoral degree in his field of inter- “first total synthesis of the anti- paint-related products rather than est. Instead, he joined the faculty of glaucoma drug physostigmine.” This the botanical compounds that really West Virginia State College in Insti- accomplishment is considered one of interested him. They parted ways tute, an all-black institution at the the 25 most important achieve- and he established his own com- time, as a professor of chemistry.