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Leo Sternbach, 97; Invented Valium, Many Other Drugs

October 01, 2005|Thomas H. Maugh II | Times Staff Writer

Leo Sternbach, the medicinal chemist who soothed the anxieties of a generation of Americans with the invention of Librium and Valium, died Wednesday at his home in Chapel Hill, N.C. He was 97.

Sternbach had 241 drug patents, and at one point his discoveries accounted for 40% of the Roche Group's worldwide sales. His discovery of the benzodiazepine class of anti-anxiety drugs, which included the famous "Mother's Little Helper" of the Rolling Stones' hit record, was noted by U.S. News & World Report, which named him one of the 25 most influential Americans of the 20th century.

The discovery was an impressive achievement for a project he was not even supposed to be working on.

The saga began in 1953 when Wallace Pharmaceuticals brought out an anti-anxiety drug called Miltown that was then thought -- wrongly, it was learned later -- to be free of the many adverse side effects that afflicted barbiturates, the most widely used drugs for anxiety at the time.

Sternbach's bosses at Roche in New Jersey ordered him to produce a "me too" version of Miltown by modifying the drug enough to bypass Wallace's patents. Sternbach, however, thought modifying another man's drug was boring.

Instead, he followed a hunch about some compounds he had studied as potential dyes years earlier in Poland. Their structures, he reasoned, could interact favorably with the human nervous system.

But two years of research proved fruitless, and his bosses told him to drop the project and switch to the development of antibiotics. Sternbach began working on the germ-killers, but he kept tinkering with the dyes. "I always did what I wanted to do," he later said.

Within two years, he and his colleagues -- especially chemist Earl Reeder -- had discovered the first benzodiazepine. As they did with other potential anti-anxiety drugs, they tested it on mice that were placed at the bottom of a steeply inclined screen. Normal mice climb the screen easily. Drugged mice relax and slide back down, where they mingle in a group torpor.

With the new drug, the mice also relaxed and slid back down. But even at the bottom, they were awake and alert, a remarkable thing.

Because he was not supposed to be working on anti-anxiety drugs, Sternbach sat on the discovery for six months. Finally, using the excuse of a periodic laboratory cleanup, he presented it to Lowell Randall, Roche's chief of pharmacology, as something they had stumbled across that should be tested.

A few days later, Randall called back to say the compound was "interesting" and asked for more. The drug was Librium, which went on the market in 1960.

Three years later, the company brought out Valium, also discovered by Sternbach, as the successor to Librium. Valium was the biggest-selling drug in the country from 1969 to 1980, but it lost some of its luster when it was found to be addictive.

Sternbach's total profit on each drug was $1, handed over for signing away the patent rights. He did, however, receive a $10,000 prize that was then offered by the company for the discovery of drugs that were significantly profitable. That award was dropped, he said, "after I won it three or four times."

Leo Henryk Sternbach was born May 7, 1908, in the seaside town of Abbazia, in what is now Croatia, the son of a lower-class Polish pharmacist who married an upper-class Hungarian Jew. He honed his skill in chemistry as a teenager by disassembling leftover artillery shells from World War I and using the powder to make fireworks.

He earned a doctorate in chemistry at the University of Krakow in Poland and worked there for six years before moving on to the Swiss Federal Institute of Technology in Zurich.

It was made clear to him that a Jew could not advance far at the institute, and in 1940 he joined what was known then as F. Hoffman-La Roche Ltd. in Basel.

When Roche moved all its Jewish employees to the United States, Sternbach and his wife, Herta, traveled through Nazi-occupied France to Portugal, where they caught a ship to safety. The key document in their travels was a Swiss passport, which the Swiss government issued to some non-citizens and which did not list nationalities or religions.

When he began working for Roche in Nutley, N.J., Sternbach felt largely isolated because of his religion. "There was a period when I was in the wilderness, so to speak, due to office politics," he said later.

But as his productivity grew, so did respect for him. By the mid-1960s, he was head of a team of more than 20 PhDs, plus junior chemists and clerks.

An old-school chemist, Sternbach was a member of the breed of "two-legged rats" who often tested drugs on themselves before they entered clinical trials. His lab notebooks meticulously record his reactions to a dose of Librium, noting that it didn't affect his appetite, but that by the end of the day he was very, very tired.

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