Henri Laborit

Family and early years

Laborit was born in Hanoi, French Indochina, in 1914. His father was a physician and colonial officer who died in 1920 from tetanus. Laborit contracted tuberculosis at age 12. In Paris, he earned a baccalaureate. He spent two years in Indochina on a hospital ship. He passed the examinations at the Naval Health Service in Bordeaux, and became a navy physician. He was sent to Sidi Abdallah Bizerte. Feeling that his options for recognition would be better, he switched to become a surgeon. During World War II he was stationed on the torpedo boat Sirocco, where he witnessed the evacuation of the Dunkerque, and then was sunk by the Germans. He was saved by an English sloop that picked him up. He received the French Military Cross with distinction. He was later stationed in Dakar. By about 1949 he was appointed to Val-de-Grâce hospital in Paris.

Chlorpromazine

Laborit was the first to recognize the potential psychiatric uses of chlorpromazine. The science of anesthesiology was new since the 1930s. Surgeons were sometimes responsible for anesthetics and as a French navy surgeon, Laborit had seen patients die as a result of or after their operations. He became a researcher in anesthesiology. Laborit's ideas on anesthesia included potentiated anaesthesia, lowering basal metabolism and lowering body temperature (so-called artificial hibernation). He advocated the use of procaine, synthetic antihistamines, Diparcol (diethazine), tetraethylammonium bromide and vitamin B1. He did not like to use morphine.

With Pierre Huguenard, Laborit invented the lytic cocktail, a combination of drugs that could be given to patients to reduce the shock and stress they experienced during and after surgery. Huguenard had success with a combination of promethazine and pethidine, at the time under the trade names Diparcol and Dolossal, and told Laborit of his finding. Laborit thought that putting patients into a state of artificial hibernation would prevent some aspects of stress reactions. These drugs made bodies stop their reactions to cooling.

Laborit suggested to Rhône-Poulenc (a pharmaceutical company that became Sanofi) that they create antihistamines that optimized stabilization of the central nervous system. There, chemist Paul Charpentier headed a group trying to improve on the existing drug diphenhydramine (Benadryl, Dramamine, Sominex). So Charpentier created a new series of phenothiazines, one of them by adding a chlorine atom. Simone Courvoisier tested the series on laboratory rats and discovered that RP 4560 (chlorinated promazine, later known as chlorpromazine) could reverse the effects of epinephrine and could induce a state of apathy or indifference. Rhône-Poulenc marketed the drug in Europe for vomiting, pain, nausea, and convulsions as Largactil in 1952. Laborit is said to have named the drug, a blended word for "large activity".

He, Huguenard and an associate named R. Alluaume published "A new vegetative stabilizer: 4560 RP." in La Presse Medicale in February 1952. According to Max Bennett, "the effect of the drug to produce 'disinterest' is mentioned together with the possibility that this property might make it of psychiatric use."

Immediately following its synthesis at Rhône-Poulenc in December 1951, Laborit requested a sample of 4560 RP to test for the purpose of reducing shock in injured soldiers. His observation that people treated with this drug showed reduced interest in their surroundings led him to suggest the first test of antipsychotics by Hamon, Paraire and Velluz. A 24-year-old patient with mania was released from Val-de-Grâce and ready "to resume a normal life" after 20 days treatment with chlorpromazine and barbiturates.

Although it had severe side effects, chlorpromazine "helped change the face of serious mental illness" and allowed many patients to live outside mental asylums; in the United States, the inpatient population of mental institutions dropped from 559,000 in 1955 to 452,000 ten years later."

Lasker award

Laborit shared the prestigious Lasker-DeBakey Clinical Medical Research Award in 1957 with Pierre Deniker and Heinz Lehmann for contributions towards the general use of chlorpromazine. No one won a Nobel Prize for the discovery, and Jean Delay of the Centre hospitalier Sainte-Anne, who wanted to win himself, sat on the Nobel committee but was opposed to giving it to Laborit. Laborit found himself at odds with Sainte-Anne hospital's staff for the rest of his life.

In 1957, the Lasker Foundation also recognized Nathan S. Kline and Robert H. Noce, both of whom advanced reserpine as a treatment for mental illness, as well as Rustom Jal Vakil for treating hypertension with reserpine, and, unrelated, Richard E. Shope for pioneering our understanding of viruses.

Career

Laborit became director of the Laboratoire d'Eutonologie at Boucicault Hospital in Paris. His interests included psychotropic drugs and memory.

Alexander Zaytsev synthesized GHB in 1874, and Laborit synthesized the drug in 1960. He was researching GHB as a precursor to the neurotransmitter GABA. Laborit published "Sodium 4-hydroxybutyrate" in the International Journal of Neuropharmacology in September 1964.

Death and legacy

Healy writes that Laborit felt cheated of his recognition and that he died a bitter man. Healy notes a few attempts to set the record straight: a 1980 book by Jean Thuillier that credits Delay and Deniker and Laborit, a 1960s book by Ann Caldwell that sided with Laborit, and a 1974 book by Judith Swazey, Chlorpromazine in Psychiatry, which gave credit to both sides. A 1992 commemoration by Rhône-Poulenc gave Laborit credit for anesthesia but gave Deniker and Delay credit for application of chlorpromazine to psychiatry. In 1994, on the 200th anniversary of the founding of Val-de-Grâce, a plaque was placed there commemorating the discovery of chlorpromazine by Laborit, Harmon, Paraire, and Velluz in 1952.