The Quest for Cortisone

Chapter 7. Another Kendall False Start, Another Great Announcement

59 Chapter 7 Another Kendall false start, Another Great Announcement Perhaps when a man has special knowledge and special powers like my own, it rather encourages him to seek a complex explanation when a simpler one is at hand. —sherLoCK hoLMes, THE ADVENTURE OF THE ABBEY GRANGE The bad news—Adolf hitler became chancellor of Germany in January 1933. The good news—Prohibition ended in the united states in December 1933. The world was getting ready to go to hell, but at least Americans could face it with a drink in their hand. for Percy Julian, the 1930s brought nothing but good news. After graduating from DePauw university in 1920 as class valedictorian, Julian earned a master’s degree from harvard in 1923 and then moved to Austria (with funding from the rockefeller foundation), where he obtained his PhD from the university of Vienna. his doctoral thesis focused on the medicinal chemistry of various plants. With his degree in hand, he returned to DePauw university in 1931 and embarked on a research career in chemistry .1 The first project Percy Julian undertook in indiana could not have been more challenging. Julian’s work in Vienna had involved the study of alkaloids—specifically, the identification of the soothing ingredient found in the Austrian shrub Corydalis cava.2 success with this project led him to envision a 60| Chapter 7 bigger endeavor—the synthesis of an alkaloid called physostigmine. Why physostigmine? ophthalmologists like Conan Doyle knew the answer— physostigmine was one of the few potential treatments for glaucoma. extracts of the Calabar bean had been used since 1855 to cause constriction of the pupil (which improves the drainage of intraocular fluid, thus reducing pressure within the eye), and in 1877 Ludwig Laqueur administered Calabar extract to reduce the elevated intraocular pressure caused by glaucoma .3 The active ingredient turned out to be physostigmine, a substance first isolated and identified in 1864 by Julius Jobst and oswald hesse. But extracting physostigmine from Calabar beans was an expensive, tedious process . A way was needed to synthesize physostigmine in a pure form, starting from simple, cheap precursors. But no one had ever synthesized a drug of this class—an alkaloid—before. it’s not that people weren’t trying.4 sir robert robinson, world-famous chemist and international leader in the field of organic synthesis, published a paper in the Journal of the Chemical Society in 1932 claiming to have synthesized the critical alkaloid-like ingredient needed to make physostigmine. he was quickly challenged by another blue ribbon organic chemist, Toshio hoshino of Japan, who in 1934 published an article in the Proceedings of the Imperial Academy of Japan claiming he was the first to produce the critical physostigmine substrate. The two international Goliaths were battling fiercely when Percy Julian stepped into the academic arena and claimed that he was the only one to have synthesized the precursor in question. Julian was at an immediate disadvantage. he lacked the reputation of an acknowledged authority like robinson, and his institution, DePauw, paled in the eyes of the chemistry community when compared to a place like oxford. nonetheless, Percy Julian felt confident enough to challenge the prevailing superstars with his claim that “he alone . . . had the correct synthesis ” for the crucial physostigmine precursor.5 Julian’s challenge resulted in a typical scientific pillow fight, but when the feathers cleared the man from DePauw was left standing. Percy Julian had indeed achieved the first complete synthesis of an indole alkaloid—in this case, physostigmine. his triumph was published in 1935.6 it was a spectacular achievement for any chemist, but not enough to earn Julian the chairmanship of DePauw’s Chemistry Department. racism was likely a factor in this disappointing outcome. Pursuing other avenues for advancement, Julian took a position with the Glidden Company in Appleton, Wisconsin.7 he became an expert in soybean products and developed pathways to synthesize numerous substances starting from soy-based ingredients.8 one of his soy-related developments would revolutionize the cortisone story. Another Kendall False Start, Another Great Announcement| 61 once physostigmine could be synthesized from chemical precursors, it was no longer necessary to extract it from other sources (like the Calabar bean). But obtaining naturally occurring pharmaceutical agents by extracting them from appropriate sources was still the rule. As noted earlier, estrogens derived from human or horse urine were commercial success stories. if Kendall was correct, extraction of...