World War II and the Genesis of Modern Psychopharmacology

In an earlier post, I told the stories of Ludwig Guttmann and Ernst Gutmann as examples of how refugees from Hitler’s Germany and its expansion into Eastern Europe played a major role in the development of modern neuroscience. The same can be said of the genesis of psychopharmacology. By way of illustration, let’s look at the lives of Frank Berger, who developed the first modern tranquilizer; Leo Sternbach, who made the first benzodiazepine; and Heinz Lehmann, who spurred the clinical development of chlorpromazine.

An abundance of pills

Source: PIxabay, in Wikimedia Commons/Public Domain

Frank Berger and Meprobamate

Frank Berger (1913-2008) was a young prize-winning physician working as a bacteriologist at the Czechoslovakia National Institute of Health when Hitler’s army entered his country on March 15, 1939. Berger and his pregnant wife left the same day; they entered Britain, where for the first few nights he had to sleep on a park bench, while his wife was put up at the Salvation Army. Eventually, the Czech Refugee Fund was able to find a hostel for them, and he initially took care of patients at an internment camp.

By 1943, he had found work in the British Drug Houses. While there in 1945, he was working on finding preservatives for penicillin, when he noticed that rats and mice given one possible preservative became very quiescent. Berger, who had always had an interest in anxiety, tried to convince his superiors to develop the compound as a drug that made people calmer, without avail. Around this time a competitor developed a better penicillin preservative, and his company moved on to other areas.

In 1947, Berger moved to the U.S., and by 1949 had returned to his earlier interest; along with a chemist colleague B.J. Ludwig, he developed meprobamate, which made animals quiescent. Once again he was unable to interest his bosses, who were skeptical that there was a market for a medicine to make people calmer.

Undeterred, Berger created a film showing the drug’s effects on rhesus monkeys, and showed it as part of a talk at a San Francisco medical meeting. There was great interest, in the face of which the management reconsidered—and by 1955, meprobamate was on the market under the name of Miltown. It was an immediate success, to the degree that by the end of the decade, it was one of the most widely prescribed drugs in the U.S.

Leo Sternbach and the Benzodiazepines

Leo Sternbach’s life (1908-2005) has already been described in a previous post, so we will just briefly summarize his early years here. He was born in an area now in Croatia; as a result of economic difficulties following World War I, the family moved around, ultimately settling in Krakow, where he assisted in his father’s pharmacy.

Sternbach chose to pursue chemistry as a career, and after receiving his Ph.D. at the University of Krakow, he stayed on as a lecturer until 1936, when his position was taken away in favor of a non-Jewish candidate. By 1940, he was working for the pharmaceutical house Hoffmann LaRoche in Basel, Switzerland.

With the German invasion of Greece and Yugoslavia in 1941, however, the situation became uncertain, and with the aid of papers prepared by Roche, he fled through France and Portugal, settling at their new headquarters in Nutley, New Jersey. There he discovered the first clinical benzodiazepine, chlordiazepoxide (Librium), which came onto the market in 1960, and was soon followed by others. By the mid-1970s, they represented one in ten prescriptions in the U.S., and were the most widely used tranquilizers worldwide.

Heinz Lehmann and the Clinical Development of Chlorpromazine

Heinz Lehmann (1911-1999) was born in Berlin, the son of a Jewish chest physician and a protestant mother. He had read Freud at the age of 13 and was drawn to psychiatry. In 1937, two years after obtaining his medical degree, the family helped him get Gestapo permission to leave Germany by obtaining a letter from a friend in Quebec, asking him to come for a ski vacation. He arrived with only his skis and possessions suitable for a two-week vacation.

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Lehman’s refugee status allowed him to obtain only a temporary medical license, and for many years he was required to check in regularly with the Royal Canadian Mounted Police (he was not granted a full license until age 52). He chose to work at the Verdun Protestant Hospital, a psychiatric facility for chronic patients in Montreal. He kept up with the European literature, and one Sunday in 1952, according to him while reading in a bathtub, he came across one of the papers on chlorpromazine by Pierre Deniker and Jean Delay from Saint Anne Hospital in Paris.

He was quick to obtain it and was struck by its effectiveness. The first paper describing the studies which he conducted with his colleague H.E. Hanrahan came out in 1954, and along the way, he invented the word "antipsychotic" to describe this new class of drugs. Ultimately the recognition grew, and it came onto the U.S. marketplace as Thorazine in 1955, initially as a drug for nausea and later as an antipsychotic. Chlorpromazine continued to transform the practice of psychiatry, in a way as revolutionary as the earlier development of penicillin for the consequences of syphilis on the nervous system (1).

Why These Medication Discoveries Matter Today

When looking retrospectively at some of the drugs described here, it is tempting to discount them in view of years of experience and the creation of newer generations of compounds. Meprobamate is now very rarely used due to its many drawbacks including toxicity in overdose and abuse potential, and the last decades have seen growing concern about the consequences of widespread use of the benzodiazepines, including difficulties in withdrawal and the marked toxicity when combined with opiates (1).

At the time they were created, however, these were remarkable steps; as we have described, meprobamate came about at a time when there was skepticism that there would be interest in a drug that helped anxiety. Chlorpromazine is used less in view of the development of newer generations of medicines, but in the 1950s it represented a revolutionary approach to treating psychoses.

And all of these developments came about because of the work of physicians and scientists who fled the rise of Naziism. We will never know about the possible contributions that might have been made by those who didn’t escape.

Portions of this article are excerpted from Trial by Fire: World War II and the Founders of Modern Neuroscience and Psychopharmacology.