| 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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