Daniel Bovet

1907-1992

Swiss-French-Italian Pharmacologist

Daniel Bovet received the 1957 Nobel Prize in physiology or medicine for his discoveries of important chemotherapeutic agents, including the first antihistamine and various muscle relaxants. His research on structure-activity relationships made it possible to block the effect of biologically active amines with pharmacological agents. The naturally occurring biogenic amines—epinephrine (adrenaline), histamines, and acetylcholine—exert important effects on several organ systems, including the vascular system and the skeletal muscles. In addition to his work on the effects of biologically active amines, he made significant contributions to psychopharmacology and chemotherapy.

Bovet was born in Neuchâtel, located in the French-speaking region of Switzerland. He was the son of Pierre Bovet, a psychologist and professor of pedagogy at the University of Geneva, and his wife, Amy Babut. Bovet studied biology at the University of Geneva and graduated in 1927. He remained at the university for postgraduate work in physiology and zoology and wrote a thesis on the influence of the nervous system on organ regeneration. After obtaining his doctorate in 1929, he began working in pharmacology at the Pasteur Institute in Paris, where he was greatly influenced by Ernest Fourneau. In 1939 Bovet became head of the laboratory of therapeutic chemistry. He married Filomena Nitti, the sister of Bovet's colleague, the bacteriologist Federico Nitti. Filomena was closely and continuously associated with Bovet's research and publications. Their son Daniele became a professor of information science at the University of Rome.

In 1947 Domenico Marotta, director of the Superior Institute of Health in Rome, invited Bovet to organize a chemotherapeutics laboratory in Italy. In 1964 Bovet left the Superior Institute to become a professor of pharmacology at the University of Sassari Medical School in Sardinia. He was a visiting professor at the University of California in Lost Angeles in 1965. From 1969-1971 he was the head of the new psychobiology and psychopharmacology laboratory of the National Research Council in Rome. He also served as a professor of psychobiology at the University of Rome until he reached age 75, when the appointment was turned into an honorary professorship.

When Bovet began work at the Pasteur Institute, he joined Fourneau in the search for antimalarial drugs. This work led to Bovet's discovery of Prosympal, the first synthetic sympatholytic (or antiadrenergic) drug, and other antiadrenergic compounds. Although these drugs had little impact on clinical medicine, they did point the way to the eventual development of drugs for the treatment of hypertension. Moreover, Bovet realized that apparently unrelated compounds might reveal common structural requirements for specific physiological and pharmacological activities. Bovet and his associates at the Pasteur Institute studied the work of Gerhard Domagk (1895-1964) and proved that the antistreptococcal action of Prontosil was due to the sulfanilamide portion of the molecule.

Within 20 years of Henry H. Dale's (1875-1968) 1910 demonstration that histamine provoked anaphylactic shock, researchers had generally accepted the idea that histamine played a key role in the allergic response. Bovet reasoned that if ergot and synthetic antiadrenergic drugs could block the effects of epinephrine, it should be possible to discover drugs that could block the effect of histamine. In 1937 he began the search for antihistaminic compounds that could be used to treat urticaria, hay fever, edema, and other allergic diseases. No naturally occurring compounds with antihistaminic action were known. In 1942 Bovet discovered Antergan, a weak antiadrenergic and antihistaminic compound. Two years later, he discovered pyrilamine (mepyramine, or Neo-antergan), which effectively counteracted the histamine reaction and is still used in the treatment of allergies. By the 1950s hundreds of synthetic antihistamines had been synthesized and used in the treatment of allergies, motion sickness, nausea, and vomiting.

In 1947 a search for a synthetic substitute for curare led Bovet to the discovery that gallamine and various derivatives of succinsylcholine could mimic the effects of curare. Since 1942 curare, a South American arrow poison, had been used in conjunction with light anesthesia during surgery to induce muscle relaxation. Researchers knew that tubocurarine, the active agent in curare, antagonizes acetylcholine at the neuromuscular junction. Bovet's search for synthetic cholinergic and anticholinergic drugs produced diethazine, one of the first synthetic drugs for Parkinson's disease, and curare-like drugs, which produced fewer unwanted side effects than tubocurarine. Moreover, Bovet's sophisticated approach to structure-activity relationships helped guide further research in pharmacology.

LOIS N. MAGNER