Loewi and chemical nerve transmission

The usual view in 1921 was that nerve impulses acted directly on muscles and glands. There were hints of another mechanism. In 1904 T. R. Elliott, working in Cambridge, suggested that sympathetic nerves act by releasing adrenaline at their endings, and ten years later Henry Dale showed that acetylcholine mimicked the effects of parasympathetic nerves. But acetylcholine had not been found in the body, and neither idea had been proved.

Otto Loewi, professor of pharmacology at Graz, had voiced a chemical hypothesis 17 years earlier. By his own later account, the test came to him in a dream the night before Easter Sunday. He woke, scribbled notes, and in the morning could not read them. When the idea returned at 3 a.m. the next night he went straight to the laboratory. He set up two beating frog hearts, each in its own small chamber of fluid, one with its vagus nerve attached. Stimulating the vagus slowed the first heart, as expected. Fluid taken from that heart and given to the second slowed it too. Fluid from a heart whose accelerator nerve had been stimulated made the second heart beat faster.

Loewi named the slowing agent Vagusstoff and reported the result in Pflügers Archiv in 1921. Blood and tissue broke it down quickly, which made it hard to identify, until he and Navratil found that physostigmine prevented the breakdown. He went on to show that Vagusstoff was acetylcholine, and that a substance closely related to adrenaline did the corresponding work at sympathetic nerve endings. Dale and Dudley also prepared small amounts of acetylcholine from the body, and Dale's group showed it released in autonomic ganglia (with Feldberg and Gaddum) and at the junction of motor nerves and muscle.

Loewi and Dale shared the 1936 Nobel Prize in Physiology or Medicine. After German troops entered Austria in 1938, the Gestapo arrested Loewi and two of his sons. He was allowed to leave only after being made to instruct his Stockholm bank to transfer the prize money to a Nazi-controlled bank. He reached England that September, stayed with Dale, worked in Oxford and then at New York University, and became an American citizen in 1946. He died on 25 December 1961.