Daniel Bovet. Courtesy National Library of Medicine, Images from the History of Medicine (IHM) collection. Contributor: Istituto Superiore di Sanità (ISS), Rome.
Daniel Bovet (1907–1992) was awarded the Nobel Prize in physiology or medicine in 1957 for his work on synthesizing compounds that inhibit the action of certain body substances, especially substances that act on the vascular system and muscles, such as adrenaline, histamine, and acetylcholine. His work helped scientists understand how to return the body’s own chemical systems to normal when they become overactive or underactive.
Bovet was born in 1907 in Neuchâtel, in the French-speaking part of Switzerland. His father was a psychologist and a cofounder of the child study institute at the University of Geneva, later directed by Jean Piaget. He was educated in Neuchâtel and at the University of Geneva, where he majored in the natural sciences. He then pursued graduate work in physiology and zoology at the university, earning his doctorate in 1929.
In the same year he joined the Pasteur Institute’s Laboratory of Therapeutic Chemistry in Paris, at the request of its director, with the charge of setting up a pharmacological unit there. Among Bovet’s colleagues was the bacteriologist Federico Nitti, son of a former prime minister of Italy, who was living in exile in France during the Fascist era. In 1938 Bovet married Federico’s sister Filomena Nitti, a scientist who collaborated closely with her husband throughout his career.
Much of Bovet’s early work at the Pasteur Institute related to drugs that fight infectious disease. In reacting to Gerhard Domagk’s announcement of the antibacterial sulfa drug Prontosil in 1935, Bovet and his colleagues prepared and experimented with various compounds related to Prontosil. They observed that a number of compounds whose physical and chemical characteristics differed greatly from Prontosil had the same effect on streptococcal infections in mice and rabbits. They deduced that a number of changes to the molecules must have occurred within the living organism, leaving the common constituent of sulfanilamide. They started experimenting with it and discovered that this relatively simple colorless substance was the source of Prontosil’s therapeutic powers. Bovet’s preliminary experiments with the Prontosil-like molecules not only supported the development of other sulfa drugs, but also gave a better understanding of the relation between molecular structure and function in this class of drugs. Bovet’s early accomplishments at the institute also included Rhodoquine, a synthetic antimalarial drug to replace quinine, the natural antimalarial extracted from the bark of cinchona trees.
A by-product of Bovet’s work on Rhodoquine was his synthesis of the first synthetic substance to inhibit the activity of adrenaline in the body, Prosympal (1933). Adrenaline, also known as epinephrine, is a substance naturally produced by the body in high-stress or physically exhilarating situations; it stimulates the heart-rate, dilates blood vessels and air passages, and has a number of more minor effects. Though Bovet’s synthetic antagonist for adrenaline found only temporary use in contemporary medicine, in testing substances in other chemical series Bovet gained a valuable working understanding of how a molecule must be structured to act like adrenaline in the body or to oppose its activity.
Bovet soon set out with his colleague Anne Marie Staub to find a synthetic antagonist for histamine, a substance released by the body’s immune system in response to pathogens and causing inflammation. Their search for an antihistamine was rewarded in 1937 by thymoxyethyldiethylamine. Though it was too toxic to be used as a drug, it did irrefutably show that histamine is most responsible for allergic reactions, including the serious medical condition of anaphylactic shock—a connection that was uncertain up to that time. The antihistamines used today to combat allergic symptoms are derived from this research.
Bovet also worked on antagonists for acetylcholine, a transmitter substance at many nerve endings, including the junctions between nerves and muscles. Bovet and his associates developed a synthetic form of curare, a poison used on darts by some South American Indian hunters to paralyze their prey. Curare worked (unknown to the Indians) by blocking or inhibiting the action of acetylcholine. The scientists introduced their synthetic curare and other similar agents into surgical practice to relax the body’s muscles.
In the era before nerve receptors were even discovered, let alone their molecular structures determined, Bovet and his wife systematized the knowledge gained from all the experimentation sketched above into a bible of molecules discovered to have effects on the autonomic (involuntary) nervous system: Structure et activité pharmacodynamique des médicaments du système nerveux végétative (1948). This book was commonly consulted by a generation of researchers to find the biological activities of various chemical structures on the autonomic nervous system.
In 1947 Bovet accepted an invitation to take charge of a new pharmacological laboratory at the Istituto Superiore di Sanità in Rome. There his new research team continued the work on curare and on a vast range of substances that affect the central nervous system (brain and spinal cord), which he noticed was affected by many of the substances that worked on the autonomic nervous system. In Paul Charpentier’s hands this research led a few years later to chlorpromazine, one of the first of the modern drugs used to relieve serious psychological disorders.
In the 1960s, during a period of troubles at the Istituto Superiore di Sanità, Bovet left to take positions at the University of Sassari in Sardinia and at the University of California in Los Angeles. He was particularly happy to come to the United States because of the availability there of inbred strains of mice he could use to pursue his new interest in the genetic basis of learning and memory and the drugs that interfere with memory consolidation.
In 1969 Bovet returned to Rome to become director of a new laboratory of psychobiology and psychopharmacology at the National Research Council, while simultaneously holding a professorship at the University of Rome.