The War of the Soups and Sparks: The Discovery of Neurotransmitters and the Dispute over How Nerves Communicate (review)

Valenstein's The War of the Soups and Sparks portrays an exceptionally polarizing debate that separated the emerging field of neuroscience into two camps: neurophysiologists and pharmacologists. The matter of their dispute was one of neuroscience's most important questions: how do neurons communicate with one another?

As we understand it today, the nervous system forms neural circuits by connecting individual neurons through a vast array of highly specialized cell-cell contact sites—called synapses—that use two different modes of operation. Electrical synapses have the obvious advantage of transmitting signals without substantial delay, while the degree of modulating signal strength is rather limited. In contrast, chemical signal transmission is delayed by the secretion of neurotransmitters, but nevertheless provides a better means of computing the encoded information.

Valenstein's book describes the long and remarkably controversial development of this understanding. Around 1900, it became generally accepted that neurons are connected by synapses that leave a physical gap between cells. Initially, almost all neurophysiologists believed that the main mode of signal transmission in the brain had to be electrical (sparks). The concept of chemical transmission was developed in stages, and its general acceptance in the scientific community was marked by the old mistake of unreasonable opposition to new ideas. The first hint came from the observation that acetylcholine and adrenalin affect the function of organs in a way similar to the stimulation of the innervating nerves; the famous example is the slower heart rate produced by stimulating the vagus nerve. Although this was firmly established by Henry Dale's work, the idea that the innervating nerve might secrete chemicals was not seriously considered until Otto Loewi's discovery of the "Vagusstoff" in 1921, which led to the concept of neurotransmitters (soups). Since Loewi's work could not identify the origin of the secreted Vagusstoff, and because of the difficulties encountered in repeating his experiment, his work initially encountered vehement skepticism. Using a better system, Dale identified the Vagusstoff as acetylcholine and showed that it was indeed released from the nerve. However, despite the awarding of the Nobel Prize to Loewi and Dell in 1936, chemical transmission was still considered to be an isolated case. Neurophysiologists, like John Eccles, disputed the idea that transmitters might also mediate rapid signal transmission in the brain. For a number of years, the debate was fought vigorously but respectfully. A breakthrough occurred when Eccles, one of the staunchest opponents of chemical transmission, provided key evidence that synaptic transmission between motor nerves and skeletal muscles is indeed chemical, admitting that he and many others had been wrong all along. Ironically, just when the idea blossomed that all synapses might use neurotransmitters, a few electrical synapses were finally identified in the brain. In the end, less than one percent of all synapses turned out to rely on "sparks."

Valenstein's intent is not to give a comprehensive historical account of all the scientific developments that led to the discovery of neurotransmitters. Instead, he provides a vivid account of how scientific progress is interweaved with the personalities of the involved scientists, their working styles, their friendships and, most noteworthy, the influence of social and political events on their personal and scientific lives. To bring science to life, he tells the story of three principal scientists: namely, Otto Loewi and Henry Dale, who shared the Nobel Prize for the discovery of neurotransmitters, and Walter Cannon, the creative thinker who came close but not close enough.

Valenstein especially emphasizes the influence of the very different personalities and scientific styles of Otto Loewi, Henry Dale, and Walter Cannon. He describes Dale as a "conservative empiricist," who was hesitant to speculate beyond what he believed the evidence...