Valenstein - The war of the soups and the sparks : the discovery of neurotransmitters and the dispute over how nerves communicate

THE

WAR

OF THE

SOUPS

AND THE

SPARKS

THE

WAR

OF THE

SOUPS

AND THE

SPARKS

The Discovery of Neurotransmitters and the Dispute Over How Nerves Communicate

ELLIOT S. VALENSTEIN

Columbia University Press

NEW YORK

Columbia University Press

Publishers Since 1893

New York Chichester, West Sussex

cup.columbia.edu

Copyright 2005 Columbia University Press

All rights reserved

E-ISBN 978-0-231-50973-2

Library of Congress Cataloging-in-Publication Data

Valenstein, Elliot S.
The war of the soups and the sparks : the discovery of neurotransmitters and the dispute over how nerves communicate / Elliot S. Valenstein.
p. cm.
Includes bibliographical references and index.

ISBN 978-0-231-13588-7(cl. : alk. paper)
ISBN 978-0-231-13589-4 (pbk. : alk. paper)
ISBN 978-0-231-50973-2 (elec.)

1. NeurotransmittersHistory. 2. Neural transmissionHistory. I. Title.

QP364.7.V34 2005

612.8dc22

2005042103

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This book is dedicated to two institutions and two people. To the City College of New York, for providing a returning World War II veteran with the opportunity to make a fresh start. At CCNY, I first learned what scholarship really meant. There professors encouraged even undergraduates to question everything and everyone, including themselves. My professional career ended up at The University of Michigan, where for more than 35 happy years I have been continually stimulated, challenged, and helped by my colleagues.

This book is also dedicated to the memory of Professors William C. Young and Walle J. H. Nauta. In graduate school, Bill Young taught me by his example how to select research problems worth pursuing and to appreciate that every manuscript can be improved with more thought and still another draft.

After completing my Ph.D., I went to work at The Walter Reed Institute of Research. Because of the crowded conditions at the Institute, I shared an office with Walle Nauta, at the time probably the leading neuroanatomist in the world. A constant stream of eminent neuroscientists came to consult with Walle, and he always insisted that I sit in on their discussions about brain and behavior. Even though it was often not true, he always made me feel like I had something to contribute. No one could have had a more stimulating environment to grow intellectually.

CONTENTS

Basic organization of the sympathetic and parasympathetic divisions of the autonomic nervous system.

Henry Hallett Dale in his thirties, and in his sixties.

Professor Otto Loewi.

Otto Loewi demonstrating neurohumoral transmission in 1926 at the International Physiology Congress in Stockholm.

Apparatus used by R. H. Kahn.

The leech muscle technique introduced by Bruno Minz and Wilhelm Feldberg.

Sir Henry Dale and Professor Otto Loewi in Stockholm in 1936 on the occasion of the awarding of their Nobel Prize.

Walter Bradford Cannon in his laboratory.

John Eccles in his laboratory.

Otto Loewi talking to students at Woods Hole.

Henry Hallett Dale on his eighty-fifth birthday.

Ivan Pavlov and Walter Cannon in Boston.

Part of a group picture taken in Professor Bykovs laboratory on the occasion of the XIVth International Congress of Physiology held in Leningrad in August 1935.

Arturo Rosenblueth and Walter Cannon in Mexico City.

During the past fifty years I have seen many advances in our understanding of how the brain works. None of these advances, however, has had a more revolutionary impact on our ideas about the brain than the discovery that nerves secrete chemical neurotransmitters when communicating with other nerves and the muscles they innervate. Yet few people, including most neuroscientists, know much about how neurotransmitters were discovered, the fierce and lengthy dispute about their very existence, or the scientists involved and the social and political events that affected their lives and work.

I first became interested in how neurotransmitters were discovered when I was writing the book Blaming the Brain. After I became aware that all the early drugs used to treat mental illness had been discovered accidentally, it occurred to me that such discoveries could not have happened any other way. So little was known about brain chemistry in the 1950s that it would not have been possible to predict the physiological or psychological effects of any of these drugs. Moreover, because neurotransmitters were not thought to exist in the brain, for a number of years it was not even possible to offer a reasonable explanation of what the drugs might be doing there even after their effects were discovered.

When I finished Blaming the Brain, I started to look into the history of the discovery of neurotransmitters, to satisfy my own curiosity. I was soon captivated by what I found to be a fascinating story. When I talked to my friends about what I was uncovering, it became clear that very few knew much, if anything, about this history. Here was a little-known and fascinating account of an important subject. I decided to make this history the focus of my next book.

Initially I concentrated on learning how the evidence for neurotransmitters had been acquired. As I learned more about the scientists involved, however, I felt that it was essential to include in my book something about their lives, how their scientific interests developed, and the different ways they responded to evidence suggesting that chemical substances were involved in transmission of the neural impulse. I have therefore included considerable information about the lives of many of the scientists and more extensive biographical details about Henry Hallett Dale, Otto Loewi, and Walter Bradford Cannon, the three most central to this history. The first two shared the Nobel Prize for the discovery of neurotransmitters, and Walter Cannon might have shared the prize with them had he not been persuaded to adopt and defend a controversial theory.

Political events greatly affected the lives and work of a number of the scientists important to this history. During World War I, many changed the direction of their research in order to contribute to the war effort. For some, the disruption was much greater during the period leading up to World War II. Otto Loewi, for example, already a Nobel laureate, was arrested by Nazi storm troopers and thrown in jail. Many German scientists were dismissed from their positions because of the Nazi racial policies, and the more fortunate were able, often with the help of colleagues and money from the Rockefeller Foundation, to join laboratories abroad. There an impressive number made major contributions to science, some of which are relevant to this history. I have included several accounts of these events because the historical context is necessary for understanding what transpired.

An important part of this history involves the episode called the War of the Soups and the Sparks, a dispute over whether nerve impulses are transmitted chemically or electrically. The dispute was mainly between pharmacologists, who had uncovered the first evidence of chemical transmission, and neurophysiologists, experts on the nervous system, who dismissed these new findings and remained committed to electrical explanations of neural transmission. Although initially there were good scientific reasons to question the possibility of chemical transmission, the controversy was sustained and fueled by the competing interests of the two disciplines.

There is always the question of where to begin the history of any topic. It seemed to me that the logical place to begin this story is the period around 1900. It was then that, after several decades of controversy, the neuron doctrine was finally accepted. This doctrine asserted that the nervous system is comprised of nerve cells separated from each other. Although the instruments that eventually made it possible to see the gap between nerve cells would not be available for another fifty years, there were good arguments, although these were disputed, that at least a functional gap existed between the terminals of neurons. This controversy, and how it set the stage for investigating whether the gap was bridged electrically or chemically, is the subject of the first chapter.