Portier, Richet and the discovery of anaphylaxis

Sailors on Prince Albert I of Monaco's research yachts who brushed against the Portuguese man-of-war, Physalia physalis, felt a pain sharp enough to make some of them faint. The prince suspected a venom. For his Atlantic cruise of summer 1901 aboard the Princesse Alice II he invited two Paris physiologists to find it: Charles Richet, professor at the Faculty of Medicine, and Paul Portier, an assistant in physiology at the Sorbonne. Off the Cape Verde Islands in July they ground Physalia specimens with sand and seawater, filtered the mixture and injected it into pigeons and guinea pigs, which sank into deep anesthesia.

Whether repeated small doses at long intervals would make an animal immune could not be tested at sea, so in Paris they switched to an extract of sea anemones (Actinia) and injected dogs. A dog named Neptune survived an injection of 0.10 cc per kilogram, below the 0.15 cc that killed normal dogs; 22 days later the same dose killed him in 25 minutes. A dose that was only a fraction of the lethal amount for an untreated dog could kill a sensitized one within minutes, yet two doses given together or a few days apart did nothing.

Richet called the state anaphylaxis, the opposite of phylaxis, or protection. The two men reported it in two short papers in the Comptes rendus of the Société de biologie, the first from its meeting of 15 February 1902. Portier soon went back to the Faculty of Sciences. Richet carried on alone.

Over the next decade Richet showed that the reaction was specific to the substance that caused it, needed an incubation period, and could be passed to an untreated animal with serum from a sensitized one. The symptoms were much the same whatever the protein: falling blood pressure, labored breathing, low body temperature and loss of higher brain function. Milk, egg white, fish, oysters and pollen could all sensitize. His 1912 monograph L'Anaphylaxie collected the work.

Richet alone received the 1913 Nobel Prize in Physiology or Medicine for his work on anaphylaxis. By then, his Nobel biography says, more than 4,000 papers on it had been published. Portier's share in the discovery was recognized only gradually. Richet died in Paris on 4 December 1935, Portier in Bourg-la-Reine on 26 January 1962.