ARVID CARLSSON'S COLUMN





BOOK REVIEW

In his first column, Arvid reviews "The War of the Soups and the Sparks" by Elliot Valenstein. This book is about an exciting period of the medical history - when the knowledge emerged of how the neurons communicate.



Introduction

For the nervous system to function, the nerve cells must be able to talk to each other, that is, signals have to be transmitted from one neuron to another. But how does this occur? For a long time it was assumed that the signals were electrical. But today we know that the nerve cells communicate with each other via chemical substances, so-called neurotransmitters.

The exciting story of how this new knowledge emerged has been written by Elliot Valenstein in his recently published book "The War of the Soups and the Sparks: The Discovery of Neurotransmitters and the Dispute over How Nerves Communicate." The book is reviewed here by Arvid Carlsson.

This review was first published in
Science, Vol 310, 18th Nov, 2005, pages 1120-1121
www.sciencemag.org


Review

The War of the Soups and the Sparks.
The Discovery of Neurotransmitters and the Dispute over how Nerve Cells Communicate

Columbia University Press, New York 2005.
225 pp. $31, £19.50. ISBN 0-231-13588-2.



The War of the Soups and the Sparks:
Nerves as Chemical Messengers

During the greater part of the previous century, neuroscience was dominated by neurophysiology. Electrical stimulation and recording of the activity of nerve cells contributed much to our understanding of nerve function, and this further strengthened the prestige of neurophysiology.

But there were some early indications that not everything could be explained by electrical signaling. More than a century ago, some pharmacologists reported that certain drugs caused effects on blood pressure, heart rate, and so on that were very similar to the changes induced by electrical stimulation of the autonomic nervous system. The hypothesis was put forward that endogenous chemical compounds similar to these drugs existed and were released from nerve endings to trigger the response.

In the early 1920s, an ingenious experiment on the frog heart by the German pharmacologist Otto Loewi (which showed that the vagus nerve secretes acetylcholine) provided the first proof of this hypothesis. Subsequently, a number of skillful pharmacologists, including Henry Dale in London, demonstrated chemical transmission in various parts of the mammalian peripheral nervous system. Loewi and Dale shared the Nobel Prize in 1936.

Through the 1930s and into the 1950s, the pharmacologists' interpretation that these effects were due to a chemical signal was vigorously attacked by the neurorophysiologists, headed by the Australian John Eccles. This clash of opposing explanations, the "war between the soups and the sparks," f inally ended with a victory for the soups.

In The War of the Soups and the Sparks, Elliot Valenstein rightly remarks that no advances in brain research during the past 50 years have had a greater impact on our ideas about the brain than the discovery that the nerves secrete neurotransmitters when communicating with other nerves and cells they innervate. Valenstein's masterful account of this development fills a serious gap in the literature. The book will certainly be enjoyed not only by the educated public but also by scientists—and not least by those actually working in the field. It shows that the author (an emeritus professor of neuroscience at the University of Michigan) has perused an enormous scientific literature.

In addition, Valenstein offers fascinating accounts of the lives of several of the key people involved in the discovery. He rightly emphasizes the researchers'markedly different personalities, which probably helped to speed the discoveries. Many of them communicated with each other in a mostly friendly and fruitful way. Even Dale and Eccles, the two fiercest combatants, developed great respect for each other. That is evident, albeit mingled with subtle irony, in the published correspondence between them, which extends over a quarter century.

In Valenstein's story, like so many others, it is remarkable how much resistance truly revolutionary discoveries often meet. That resistance, reflected in the book's title, shows up (in a sometimes dramatic manner) at every step of this complex discovery process. Loewi struggled for several years to gain acceptance of his findings. To convince the scientif ic community, he personally demonstrated his crucial experiment at an international physiology congress in 1926, and even after this success several researchers expressed serious doubts. After the novel discoveries were finally accepted within the scientific community, it took another several years (sometimes more than a decade) until they entered the standard physiology textbooks.

As Valenstein mentions, I witnessed considerable resistance myself, when at a 1960 meeting in London I advocated a role for dopamine and norepinephrine as brain neurotransmitters. Surprisingly, this opposition was expressed by some of the major proponents of chemical transmission in the peripheral nervous system, headed by Dale himself. These pioneers apparently felt considerable hesitation when it came to the question of chemical transmission in the central nervous system. Perhaps the vigorous debate between the soups and the sparks not so many years earlier had made them especially cautious regarding the central nervous system. Their reaction may also have reflected the fact that so many seemingly revolutionary scientif ic discoveries turn out to have a short life span, thus providing good reason for skepticism.

A dramatic interval in the scientific developments described in the book coincided with an equally dramatic moment in 20th-century political history. Several German scientists played a decisive role, but they did so mainly as refugees in the United Kingdom after being expelled from their country by the Nazi regime. (Loewi, who fled from Austria in 1938, ended up in New York.) Their presence in Britain facilitated a fruitful collaboration with the British scientists, certainly sped up the discovery process, and raised British neuropharmacology into glory. Progress in Germany came to a halt, and the British dominance of the field would last for two decades. Then, after the great pioneers had clearly won the war against the sparks, they missed the final triumph by leaving to others the problem of proving the presence of neurotransmitters in the brain.

The author was drawn to the history of the discovery of neurotransmitters while writing an earlier book on drugs and mental health (1). In that book he writes: In pursuing the biochemical approach to mental disorders an enormous amount has been learned, but it is questionable how much has been learned about mental illness. We do not really know if a biochemical imbalance is the cause of any mental disorder, and we do not know how even the hypothesized biochemical imbalances could produce the emotional, cognitive, and behavioral symptoms that characterize any mental disorder.

I suppose that many readers would like to know how Valenstein reconciles his strong belief in the role of neurotransmitters for normal brain function with his doubts about a role for biochemical imbalances in mental disorders. For example, certain drugs are known to mimic mental disorders rather faithfully and at the same time to induce striking neurotransmitter imbalances. Is it far-fetched in such cases to propose some relation between biochemical and functional aberrations?

But my concern is somewhat tangential. The War of the Soups and the Sparks offers an excellent introduction to discoveries that provided the foundations for modern neuroscience. Valenstein's well-narrated account of one of the most fascinating chapters in the history of medical research can be strongly recommended.

Reference
1. E. Valenstein, Blaming the Brain: The Truth About Drugs and Mental Health ( Free Press,
New York, 1998).

november 2005
Arvid Carlsson


Explanation of words

Acetylcholine: Neurotransmitter in the brain and in the body. Among other things, acetylcholine transfers messages from nerves to muscle cells in the body.

Autonomic nervous system: That part of the nervous system which cannot be controlled at will.

Central nervous system: The brain and the spinal cord.

Neuropharmacology: The science of drugs that influence the nervous system.

Neurophysiology: The science of the functions of the nervous system.

Neuroscience: The science of the nervous system.

Peripheral nervous system: The part of the nervous system that is situated outside the brain and the spinal cord.

Vagus nerve: A nerve originating in the lower brainstem and innervating, for example, the heart, lungs and digestive tract.










   Otto Loewi Nobel Prize Winner 1936   
© Nobelstiftelsen           
  





   Henry Dale Nobel Prize Winner 1936   
© Nobelstiftelsen           
  




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