STERNBACH, LEO Discovered Valium-Scientist

But for his stubborn streak, chemist Leo Sternbach might not have discovered Valium, the drug that 40 years ago revolutionized treatment of anxiety and became a household name.

A top researcher at drug maker Hoffmann-La Roche Inc., Sternbach had spent much of the 1950s trying to make a tranquilizer to compete with a rival's popular new drug, Miltown. He was tinkering with chemical compounds, attaching various atom groups and testing the new compounds on animals, when his boss ended the project. But Sternbach tested one last version anyway. In just a day, he got the results: The compound made animals relaxed and limp.

Sternbach, now 95, had created a better drug, Librium _ and an entire new class of tranquilizers named benzodiazepines. They were safer and more effective than previous treatments: barbiturates, opiates, alcohol and herbs. He soon simplified Librium's structure into one three times more potent, Valium. Approved in May 1963, it became a cultural icon _ the country's most prescribed drug from 1969 to 1982.

"It had no unpleasant side effects. It gave you a feeling of well-being," Sternbach said recently at Hoffmann-LaRoche's Nutley headquarters. "Only when the sales figures came in, then I realized how important it was."

The company sold nearly 2.3 billion pills stamped with the trademark "V" at its 1978 peak.

"Sternbach profoundly changed the nature of pharmacology because then the standard became that you have to be at least as safe as these drugs," said Dr. Norman Sussman, professor of psychiatry at New York University School of Medicine.

Unlike earlier drugs, Valium did not slow breathing, so patients couldn't use it to commit suicide. But it was overused, Sternbach said; some patients became addicted, so a doctor's visit was required for refills.

Still, benzodiazepines remain the most prescribed anxiety drugs, partly because they start working as fast as one hour, slowing brain activity. They also are used for treating panic and phobia disorders and insomnia, calming patients before surgery and relaxing muscles.

"They were the first weapons in our arsenal for fighting anxiety disorders," helping people to function, said Jerilyn Ross, president of the Anxiety Disorders Association of America. "It was a huge leap."

HLR still researches other uses for them, said Louis Renzetti, who heads its efforts to speed up discovery of new compounds.

Valium was the first blockbuster for corporate parent Roche, the Swiss drug maker, said George Abercrombie, president and chief executive officer of Hoffmann-La Roche.

"It put us on the map," he said, and funded development of other key drugs.

Sternbach, who says he "loved chemistry" from an early age, was born in Croatia. He began working at Roche's Basel headquarters in 1940 after earning a Ph.D. in organic chemistry at University of Krakow in Poland and working as a research assistant.

Fearing Nazis would occupy Switzerland, the company sent its Jewish scientists to the United States. Sternbach fled on June 22, 1941, with his new bride Herta, his landlady's daughter. "We came with only our clothes," she recalled. When they reached Nutley, Roche's U.S. headquarters had just one building. Sternbach helped organize its new chemical laboratory.

The couple soon bought a modest home in Upper Montclair, where they raised two sons and still live.

Sternbach's first big success was synthesizing biotin, a B vitamin that breaks down fatty acids and carbohydrates. Vitamins previously were made from plant extracts, but Sternbach found an efficient way to synthesize the complex molecule, said Jeff Tilley, who joined Sternbach's research group in 1972.

Sternbach officially retired in 1973, but worked most days until recently. He mentored young scientists, corresponded and consulted with others, and worked on his biography, due out this fall under the title, "Good Chemistry: The Life and Times of Valium Inventor Leo Sternbach."

His other breakthroughs include the sleeping pills Dalmane and Mogadon, Klonopin for epileptic seizures and Arfonad, for limiting bleeding during brain surgery.

Named one of the 25 most influential Americans of the 20th century by U.S. News & World Report, his credits include 241 patents, 122 publications, honorary degrees and other awards.

"Leo was a game changer, really. It's quite inspiring to be on a campus with someone with that impact," Renzetti said.

Until a decade ago, one-fourth of Roche's sales came from Sternbach discoveries. "He's an inventor's inventor," said CEO Abercrombie. "Within every

company, there is a person or two whose legacy becomes the hallmark of what the company is about, and for Roche, it is Dr. Sternbach."

John Kraljic

By LINDA A. JOHNSON

AP Business Writer

The following Associated Press article concerns Leo Sternbach, a

Croatian Jew who discovered Valium.

July 1, 2003, 2:25 PM EDT