Leo H Sternbach
Inventor of benzodiazepines. He was born on May 7, 1908, in Abbazia, formerly Austria (now Croatia), and died in Chapel Hill, NC, USA, on Sept 28, 2005, aged 97 years.
Leo Sternbach loved chemistry. He would become best known for his synthesis of diazepam (Valium) in 1963 and other benzodiazepines, which revolutionised the treatment of anxiety and played a large part in the commercial success of the drug company Hoffmann-LaRoche, for whom he worked. But it was his synthesis of biotin in the 1950s that most impressed his chemist colleagues. “He developed a commercially viable synthesis of a chiral natural product that took 50 years to replace”, said Jeff Tilley, a Roche colleague since 1972. “It was robust, practical chemistry that presaged a lot of interest in natural product synthesis that really emerged 30 years later. It was just a tour de force in chemistry using the crude tools that were available at the time.”
Sternbach earned a master of pharmacy and then a PhD in chemistry in 1937 from the University of Krakow, Poland. He then worked in Vienna on colloidal chemistry, and went to Zurich to work with Leopold Ruzicka at the Swiss Federal Institute of Technology. Throughout his childhood, Sternbach had faced discrimination because he was Jewish; this intensified as Hitler’s power rose, although his mentors and employers in chemistry always looked out for him. In 1940, he joined F Hoffmann-La Roche in Basel, Switzerland, but the plan was that he would be transferred to the USA to work in a new facility in Nutley, NJ. With the assistance of Roche, Sternbach and his wife, Herta, made the difficult journey to the USA, landing in Jersey City on June 22, 1941.
His first few years in the Roche laboratories at Nutley were disappointing, but in February, 1943, he began work on the synthesis of biotin. After his success with that compound, he developed trimetaphan camsilate (Arfonad), a ganglionic blocker used in bloodless surgery. The next 4 years were spent on the development of chlordiazepoxide (Librium) after executives at Roche became interested in creating a product to compete with the anti-anxiety drug meprobamate (Miltown), which had been brought to market in 1953. For that, Sternbach reached back to his student days in Krakow, according to Hans Maag, a Roche colleague. “At the time we were looking for new azo dyes or interesting dye stuff intermediates, and we came across some substances known as 4,5-benzo-[hept-1,2,6-oxdiazines] in the German literature”, Sternbach would later write. “From a chemical point of view, they were very interesting. They were formed in good yields and by interesting chemical reactions, but unfortunately did not lend themselves to transformation into usable dyes. With regret we dropped this group of compounds and turned to other things.”
Sternbach’s team in Nutley turned back to those compounds, but would have dropped them again because of poor results were it not for a chance event that occurred while they were cleaning the laboratory to make way for other projects. “During this procedure, Earl Reeder, my co-worker, drew my attention to a few hundred milligrams of two products, a nicely crystallized base and its hydrochloride”, Sternbach wrote. Those products, after testing by pharmacologist Lowell Randall, would become chlordiazepoxide. “He decided to re-examine the chemistry of his student period in Poland and resurrected the benzodiazepines into the most important series of drugs to combat anxiety, at that time a newly defined mental disorder”, former colleague Milan Uskokovic once said. “He became a grand master of modern medicinal chemistry.”
In addition to benzodiazepines such as diazepam and clonazepam (Klonopin), Sternbach would develop clidinium bromide (Quarzan), an anticholinergic, and hypnotics, including nitrazepam (Mogadon) and flunitrazepam (Rohypnol). He held 241 US patents. Speaking of diazepam in 2003 on the drug’s 40th birthday, he told the Associated Press: “It had no unpleasant side-effects. It gave you a feeling of well-being. Only when the sales figures came in, then I realised how important it was.” Sternbach would test many of the compounds on himself, Tilley said. He would serve as director of medicinal chemistry at Roche until his retirement in 1973, although he was a consultant at Roche until 2003, visiting nearly every day. As recently as 1994, products he patented accounted for 28% of the company’s worldwide pharmaceutical sales, Roche said.
Sternbach was recalled for his kindness. “He was proud of what he had done, but he wasn’t really arrogant about it”, Tilley said. He was always interested in the welfare of people who worked with him, said Maag. He is survived by his wife, Herta, and two sons, Michael and Daniel.
Additional material honoring Dr. Sternbach
Fifty years ago, when it came to treating acute anxiety and related disorders, the cure was often worse than the disease. Other than “the talking cure,” sufferer’s options were limited to a handful of toxic substances, such as barbiturates, which, in addition to causing significant impairment of cognitive and motor functions, were highly addictive and potentially lethal. All that changed suddenly in 1960, when the healthcare company Roche introduced Librium, the first of the benzodiazepine class of drugs. Offering the promise of a s fast-acting, effective and safer alternative, the benzodiazepines revolutionized the medical treatment of anxiety and convulsive disorders and ushered in a new era in psychopharmacology research.
The invention of the benzodiazepines is now viewed as one of the greatest accomplishments of 20th century pharmacology.. Now, for the first time, Good Chemistry tells the fascinating story of the benzodiazepines and the genius behind the invention.
Beginning in 1908, in the Adriatic resort town of Abazzia, now a part of Croatia, Good Chemistry traces the life and career of Leo Sternbach, the pharmacist’s son who, in the face of withering anti-Semitism and financial hardship, followed his passion for chemistry to become one of the most influential scientists of the 20th century, or as he was dubbed by U.S. News & World Report, one of the Twenty-five Shapers of the Modern Era. We learn about his early years as a student in Europe prior to joining Roche in Switzerland in 1940, and how the company aided his flight from Nazi persecution to a new home in the United States. It was there that, , in 1958, while working as a research chemist for Roche, he made his momentous discovery in a discarded test tube containing a few crystals from a long-forgotten experiment. And we learn of his no less impressive accomplishments in the years following, for which he holds an astonishing 230 patents.
The second half of Good Chemistry is a compelling medical and social history of Valium and its rise to near-iconic stature in our popular culture. The authors offer a lively account of Valium’s uses and abuses over the past forty years and explain how its evolution from “panacea” to “Mother’s Little Helpers” was based on a common misconception of Valium’s effects on the human nervous system. They also review exciting recent research into the psychopharmacology of benzodiazepines that has revealed how, unlike virtually ever other class of anxiolytic, sedative, and mood stabilizer, the benzodiazepines work in harmony with the body’s own natural system for inhibiting anxiety and managing stress.
Each day, tens of millions of people around the globe take some form of benzodiazepine to calm their fears, to help them sleep, to overcome life-threatening seizures, or to assist them through the trauma of surgery. Good Chemistry tells the captivating story of the development of these medications and of the remarkable man who introduced them to the world.
The fascinating story of one of the most important breakthroughs of 20th century pharmacology and the man behind the invention
The development by Roche of Valium and the benzodiazepine class of chemical compounds was among the greatest accomplishments of modern pharmacology. Good Chemistry combines a detailed account of that momentous development with an engaging biography of Leo Sternbach, the brilliant chemist who invented Valium and whose achievement heralded a new era in research and therapeutics.
A thought-provoking biographical history, Good Chemistry reveals the fascinating story of a gifted young man who, forbidden to follow his passion for chemistry because he was Jewish,, fled the persecution of his homeland for the United States, overcoming seemingly insurmountable odds to become one of the 20th century’s premier chemists. It also traces the surprising and often dramatic developments that led to the invention of Valium, and traces the grim history of previous drug therapies for anxiety that made the invention of the benzodiazepine group of drugs such a revolution in drug treatments. And it offers a fascinating cultural history of one of the most praised and maligned drugs of modern times and its impact on society.
LETTER Valium Saved My Life Published: October 5, 2012 To the Editor:
Re “Valium’s Contribution to Our New Normal,” by Robin Marantz Henig (Sunday Review, Sept. 30):
After serving in the Army in Vietnam and suffering from what is now called post-traumatic stress disorder, I found that Librium, and then Valium, definitely saved my life.
Whatever negatives there may be about the use and overuse of Valium, it has saved many lives and improved the quality of millions of lives.
Its positives dramatically outweigh its negatives, and right now, there is really no adequate substitute for the psychoactive drugs.
MICHAEL J. GORMAN
Whitestone, Queens, Sept. 30, 2012