Frank Berger: Inventor of the first tranquilliser
Tuesday 10 June 2008
Frank Berger spawned a billion-pound industry when he invented meprobamate, the first tranquilliser. Until then the nearest drugs were barbiturates, which sedated rather than calmed and were often used by suicides. There was a huge need for a sedating drug that remained safe in overdose, and for a decade mebrobamate filled that gap. It was sold in the UK as Equanil and – combined with a painkiller – as Equagesic.
But it nearly didn't happen. Shortly after the Second World War, Berger was working in London for British Drug Houses (BDH), then one of Britain's leading pharmaceutical companies. BDH had been charged to produce penicillin in quantity, but in liquid suspension it was often destroyed by penicillinase, produced by contaminating bacteria.
Berger was set the task of overcoming this difficulty and sought a non-toxic compound that blocked penicillinase. The most promising substance was called mephenesin, and to test its toxicity Berger injected it into rodents. He found that when he laid them on their backs, they stayed there, looking stupidly happy, instead of righting themselves. Most importantly, their heart and respiration were unaffected. He was unable to convince BDH that this was a potentially important discovery, but in 1946 he described mephenesin's action, which he termed "tranquillising", in a now-classic paper in the British Journal of Pharmacology. In the meantime, American scientists found better ways of preserving penicillin, and BDH lost interest.
In 1947, Berger moved to America as assistant professor of paediatrics at the University of Rochester, in Minnesota. There, he performed clinical trials of mephenesin in his patients, and published the results in the Journal of the American Medical Association in 1948. Two years later, he joined Wallace Laboratories, part of Carter Products, as research director and synthesised meprobamate, a longer-acting, close relative of mephenesin, with a chemist named Bernard Ludwig. A trial at Mississippi state mental hospital showed that the drug cured 3 per cent of patients of their symptoms, and improved those of a further 80 per cent. His employers were not persuaded, but after Berger and colleagues made a short film documenting meprobamate's effects on rhesus monkeys and showed it at a medical conference in San Francisco, news travelled fast, and the drug became a huge success. Meprobamate earned the company £40m in its first year on the market.
It was called Miltown in the US, after a village near the research lab's headquarters. For a while America was in the grip of Miltown fever, and 5 per cent of Americans took it; it was also widely used in the UK. It was common for drugstores to have notices outside saying "Sold out of Miltown" or "Miltown available tomorrow." It brought immediate, though short-lived relief to thousands of people. Dr Andrea Tone, a medical historian at McGill University, said it was the first psychiatric drug to have a wide cultural impact: "This was a period when Americans were working hard and felt entitled to something that could get them through the day . . . For many people it was an emotional aspirin, a peace pill."
But for others it also brought dependency and gradually its sales fell off, until it was overtaken by Valium and Librium, which had fewer adverse effects. However, it remains a prescribable drug in Britain and the US, and in 1960 the US government forced Carter Wallace, as the company was by then called, to make its patent available.
Berger continued to work in drug development for Carter Wallace, rising to become president of the company. He developed the antispasmodic drug carisoprodol, which is related to meprobamate, and the epilepsy drug felbamate. He was affiliated with Harvard and Rutgers universities, and in 1974 moved to Louisville University as professor of psychiatry. He remained there until he retired in 1990.
Berger was born in Pilsen, Bohemia (now part of the Czech Republic), to parents who worked as cloth wholesalers. He went to Tilesen Gymnasium, Prague and studied medicine at Charles University, Prague, qualifying in 1937 and working at the Czechoslovak National Institute of Health. He left Czechoslovakia on 15 March 1939, the day Hitler annexed his country. He was refused a visa to America as the quotas were full, but he and his wife were permitted to enter Britain, where he spent his first few nights sleeping on a park bench while his pregnant wife was given a bed by the Salvation Army. They were given hostel accommodation in Bloomsbury by the Czech Refugee Fund and later he worked as a doctor in an internment camp.
Berger said he had always been intrigued by anxiety, which many people suffered from and which came and went for no apparent reason. "These people are not insane; they are simply over-excitable and irritable, and create crisis situations over things that are unimportant. What is the physiological basis of this?"
Frank Milan Berger, biomedical researcher: born Pilsen, West Bohemia 25 June 1913; chief pharmacologist, British Drug Houses 1945-47; Assistant Professor of Paediatrics, Rochester University 1947-49; Director of Research, Carter Wallace 1949-55, Vice-President 1955-58, President 1958-73; married 1939 Bozena Jahodova (died 1972; two sons), 1975 Christine Spadi (one stepson); died New York 18 March 2008.
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