Inventor of Librium and Valium
Monday 03 October 2005
Leo Sternbach was one of history's most prolific drug designers. He invented modern tranquillisers including Librium and Valium, a sleeping pill called Mogadon, and drugs for epilepsy and muscle spasms. He synthesised radically new molecules. He also synthesised the vitamin biotin and developed a drug that reduced bleeding during brain surgery.
He was primarily a chemist, who used classic scientific procedures, combined with doggedness, teamwork, serendipity and intuition. He worked for the Roche drug company for 33 years. From 1965 to 1972, Valium was the most-prescribed drug in the United States, and it was in the UK's top five. (It is now number 189 in the US medicinal hit parade.)
Librium, the first tranquilliser, was welcomed because it was less sedating than the existing phenothiazine drugs. Valium, which followed, was so popular that the Rolling Stones wrote a song, "Mother's Little Helper", about it. Later, there was a backlash against it, but now, 45 years later, Valium and closely related drugs are regarded as an indispensable short-term treatment for acute anxiety - the treatment of choice for alcohol withdrawal symptoms - as well as being used for pre-operative sedation and to relieve muscle spasms, including that of back pain.
In 1981, sales plummeted after a report that Valium promoted cancer-cell growth in a test-tube. This finding was not confirmed (if it were true, there would have been a cancer epidemic) and Valium is safe for cancer patients. The safeness of tranquillisers has prevented many deaths by suicide. Valium is listed as an essential drug by the World Health organisation and is safe for everyone except babies under six months, and some glaucoma patients.
Sternbach's tranquillisers were in a chemical class called benzodiazepines, and he had helped synthesise them while he was a postdoctoral student in Poland, 20 years earlier. Their biological activity was unknown. He derived 40 compounds from them, all of which proved biologically inert. Finally, he treated one of the derivatives with a substance called methylamine, labelled the white, crystalline substance Ro-0690 and put it on a shelf. Eighteen months later, in 1957, it was rediscovered and he sent it for screening. It was found to have sedative and sleep-inducing properties in mice, and was a muscle-relaxant in cats. When tried in agitated elderly patients it caused relaxation but made them unsteady on their feet, with slurred speech. When tried on psychiatric outpatients with neuroses, it cured their anxiety states without clouding consciousness or causing intellectual dysfunction. It was also remarkably safe.
Working on the same basic molecule as Librium, Sternbach came up with Valium in 1963, which was more potent but as clean of side-effects. Two years later he produced Serax, used to treat acute alcoholism, convulsions and muscle tensions.
The drugs he invented made millions, and Roche became the world's largest pharmaceutical company. Sternbach, however, was interested only in chemistry, not economics, and in benefiting humanity.
Leo Sternbach was born in the fashionable coastal resort of Abbazia in the dying days, and territory, of the Austro-Hungarian Empire. The town, once favoured by Franz Joseph, the last Austrian emperor, is now called Opatijo and is in Croatia. (Both names mean "Abbey".) Sternbach's father was Polish and his mother Hungarian. His father, a pharmacist, moved back to Poland, and Leo went to high school in Bielsko, and then to Jagiellonian University, Krakow, where he gained a master's degree in pharmacy in 1929 and a PhD in organic chemistry in 1931. His main work was developing potential dyes.
He remained there until 1937, followed by a few months in Vienna. Because of mounting anti-Semitism, he moved to the Swiss Federal Institute of Technology in Zurich, working with some of the world's most distinguished chemists. In 1940 he joined Hoffmann-La Roche, and worked for them for the rest of his life. In 1941, with the possibility of a Nazi invasion, the company moved its entire Jewish staff to New Jersey, USA. He newly wed wife, Herta Kreutz, was Swiss but under Swiss law took on her husband's nationality. Roche arranged for him to have a Swiss passport, and they escaped to America via occupied France and Portugal. Herta was a Protestant and they had a civil wedding, followed by a church ceremony.
They settled in New Jersey in the summer of 1941, where Leo was group chief at the Roche research laboratory. He was subsequently promoted to senior group chief, section chief and, from 1966 to his official retirement in 1973, aged 65, director of medicinal chemistry. He continued to work in the office nearly every day until 2003, when he was 95 and moved to North Carolina to be near his son Daniel, who is a chemist with GlaxoSmithKlein.
As recently as 1964, drugs synthesised by him accounted for 28 per cent of the company's revenue. He held 230 patents, and earlier this year he was admitted to the US National Inventors Hall of Fame, run by the US Patent Office. He shared the inauguration ceremony with the inventors of colour film, photocopiers, genetic fingerprinting, gas masks, three-way traffic signals, the electric guitar, optical character recognition and plutonium.
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