THE WAR OF THE SOUPS AND THE SPARKS THE STORY OF NEURONAL COMMUNICATION THE DISCOVERY OF NEUROTRANSMITTERS John Newport Langley (1852-1925) • Established the foundation of what is known about the autonomic nervous system THE DISCOVERY OF NEUROTRANSMITTERS The discovery of neurotransmitters in the PNS arose out of studies of the effects of drugs on visceral organs and skeletal muscles. John Newport Langley (1852-1925) • Adrenaline had the same effect on organs even after their nerves had been cut and had degenerated JOHN NEWPORT LANGLEY (A SPARK)

“The known physical character of drugs are insufficient to account for the effects they produce; in consequence I consider that there is a chemical combination between the drug and a constituent of the cell – the receptive substance . . . There are two broad classes of receptive substances: those which give rise to contraction and those which give rise to inhibition.” THOMAS RENTON ELLIOTT (A SOUP)

Thomas Renton Elliott (1877-1961) • Student of Langley • First to suggest that sympathetic nerves secrete adrenaline • Largely ignored HENRY HALLETT DALE (A SOUP WANNABE)

Henry Hallett Dale (1875-1968) • Student of Langley • Observed that acetylcholine, more than any other drug, duplicated the effects of parasympathetic nerve stimulation • Did not speculate that parasympathetic nerves might secrete acetylcholine • Anticipated the discovery of cholinesterase due to the short duration of acetylcholine’s action OTTO LOEWI (A SOUP) Otto Loewi (1873-1961) “The night before Easter Sunday of that year I awoke, turned on the light, and jotted down a few notes on a tiny slip of thin paper. The I fell asleep again. It occurred to me at six o’clock in the morning that during the night I had written down something most important, but I was unable to decipher the scrawl. The next night, at three o’clock, the idea returned, It was the design of an experiment to determine whether or not the hypothesis of chemical transmission that I had uttered seventeen years ago was correct. I go up immediately, went to the laboratory, and performed a simple experiment on a frog heart according to the nocturnal design.” OTTO LOEWI (A SOUP) The Experiment – “Vagusstoff” and “Acceleransstoff” THE 1936 NOBEL PRIZE Physiology or Medicine

Henry Dale & Otto Loewi JOHN ECCLES (A SPARK) John Eccles (1903-1997) • Friendly disagreements with Dale • Suggested to bioassay their tennis socks after Dale remarked that their sweat was undoubtedly the result of acetylcholine secretion • Problem with chemical transmission – difficulty in repeating the results of the experiment • Problem with electrical transmission – explaining inhibition • “Acetylcholine is all wet.” Response - “Prefer wet acetylcholine to dry eddy currents.”