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BRAIN
A JOURNAL OF NEUROLOGY
BOOK REVIEW
Golgi: a life in science
In 1906, the professors of the Karolinska Institute had a problem;
who should get the Nobel Prize in Physiology or Medicine? In the
previous 25 years, understanding of the structure of the brain and
spinal cord had greatly increased. The nerve cell, or neuron, had
been identified as the fundamental unit of the nervous system.
The new discoveries had helped to understand the normal functions of the brain and spinal cord and to interpret the causes of
neurological disease. The work of two men had led to these advances. One, the Spaniard Santiago Ramon y Cajal (1852–1934)
and the other, the Italian Camillo Golgi (1843–1926). Cajal’s great
contribution was recognized in his own day, and he continues to
be revered. Golgi is acknowledged, but far less well known. Golgi:
a biography of the founder of modern neuroscience by Paolo
Mazzarello (2009) is explicit in its claims and goes some way to
redressing the imbalance.
Before Golgi’s work, the structure of individual nerve cells was
poorly understood. The available methods for preserving and
staining nervous tissue yielded an incomplete picture. The painstaking work of Otto Friedrich Karl Deiters [(1834–63); 1865] had
demonstrated the continuity between the nerve cell and its dendrites and axon, but his work involved tedious dissection of hardened tissue, and was most feasible for spinal motor neurons. The
many shapes of nerve cells in the brain and spinal cord could not
easily be established using his methods. Golgi’s discovery changed
all that. Golgi was studying blocks of brain that had been fixed in
potassium dichromate and then stained with silver nitrate. In
1873, for the first time, he tentatively announced his discovery
of ‘La reazione nera’, the black reaction. It was several years
before the profound importance of the Golgi method was recognized. Appreciation was eventually given less to the rather diffident Golgi, than to the more outgoing Ramon y Cajal.
In 1887, Cajal visited the Spanish psychiatrist Luis Simarro
Lacabra (1851–1921) in Madrid. Simarro had returned to Spain
after studying with Jean-Martin Charcot (1825–93) and
Louis-Antoine Ranvier (1835–1922) in Paris, and was working
with the Golgi method. When Cajal looked at a Golgi preparation
in Simarro’s house, he was overwhelmed with the beauty and
clarity with which individual nerve cells could be seen. He resolved
to study every part of the nervous system with this miraculous
new method. In the following years, Cajal described the structure
of many of the elements of the retina, brain and spinal cord,
culminating in his massive and authoritative Textura del sistema
GOLGI: A BIOGRAPHY OF
THE FOUNDER OF MODERN
NEUROSCIENCE
By Paolo Mazzarello 2009.
New York: Oxford University
Press
Price: £45.00/$US69.95
ISBN: 978-0-19-533784-6
nervioso (1899), later translated into French and finally into
English.
Cajal’s magnificent work and his enthusiastic use of the Golgi
stain increased the international recognition of Golgi’s great contribution. However, there was a fundamental problem of interpretation. This book traces the early disagreement that led finally to
hostility between Golgi and Cajal. Golgi believed in a reticular view
of the structure of the nervous system, whereas Cajal supported
the neuron doctrine. According to the reticular theory, there is
fusion among neural elements; axons cross and re-cross one another fusing and forming a large neural network. Golgi saw in the
widespread bifurcation of axons the basis for a broad reticulum
within the brain and spinal cord. In sharp contrast, according to
the neuron doctrine, the brain and spinal cord are made of individual elements, called neurons. Neurons may touch, but they do
not fuse. The book contrasts the personalities of the two men,
perhaps a bit unfairly. Golgi emerges as reserved, and somewhat
reticent; Cajal as a shameless promoter of his own work. But it
was Cajal’s evidence, not his personality that made the difference.
Even hardened reticularists changed sides. Within a few years of
Cajal’s use of the Golgi method, nearly all neuroscientists accepted
the neuron doctrine.
The book makes it easy to understand the situation from Golgi’s
point of view. He had invented a totally new method for the study
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| Brain 2012: 135; 301–303
Book Review
Figure 1 (A) Golgi cells of the cerebellum from Golgi’s Opera Omnia. (B) Golgi cell Purkinje cell.
of nervous system structure and saw in his slides evidence for
structural continuity of axons; a reticulum as the main functional
unit of the brain and cord. Then, a younger man used his method
to champion a radically different view. Although Cajal’s interpretations were to prove correct, it was not until the application of the
electron microscope many years later that his views could finally
be proven. Nerves touch one another, they do not fuse. Golgi was
angered and hurt at the widespread abandonment of the reticular
theory and acceptance of the neuron doctrine by most of his
fellow scientists. He made defence of the reticular theory the
key element in his Nobel Prize speech. Cajal seemed more embarrassed than outraged at the speech.
The book highlights two types of scientist. A major contributor
to science may invent a new method and spend years observing
and describing their observations. However, great scientists go
beyond that. Based on their work, they come up with a profound
unifying principle to account for a great mass of data, and eventually prove the principle to be correct. In biology, the obvious
example of the latter type of scientist is Charles Darwin (1809–82)
who spent years systematically observing animals and plants,
breeding pigeons and studying molluscs; and followed this by
providing a profound insight that reset biology. Cajal had a similar
role in neuroanatomy. Heinrich Wilhelm Gottfried von
Waldeyer-Hartz (1836–1921) had coined the term ‘neuron’ for
the nerve cell and was an ardent supporter of the neuron doctrine.
It was Cajal who gave it the anatomical support. Cajal begrudgingly adopted the term neuron, but dismissed any claims that
Waldeyer-Hartz may have made to evidence supporting the
neuron doctrine. Although his reticular views are largely discredited, the book helps us to remember the great contributions
that Golgi did make. One of the most important is his early description of cerebellar cell types, an example being the prominent
element of the cerebellar cortex known as the Golgi cell (Fig. 1A).
Golgi described for the first time the characteristic Golgi cell of
the cerebellar cortex as well as the shape of cells first identified by
Jan Evangelista Purkinje (1787–1869) and the characteristic right
angle branching of their axons. Some of Golgi’s less successful
claims are not discussed in the book (Fig. 1B). For example, in
Golgi-stained sections of cerebral cortex and cerebellum, the dendrites of most neurons are covered with spines, which are the
major postsynaptic site.
Golgi thought that the spines were an artefact, and in his initial
publications he drew smooth dendrites (Fig. 2A). Cajal (1896)
eventually identified the spines using the entirely different
method of methylene blue staining (Fig. 2B).
As a scientific biography, the book is excellent. It documents all
of Golgi’s contributions to the study of the nervous system and
disease. For example, Golgi first described the characteristic receptor embedded in tendons that still bears his name; and he discovered the intracellular network of tubules, the Golgi apparatus.
Golgi also served as rector of his own University of Pavia for many
years, and defended it against the founding of a potentially competitive university in Milan. Golgi, the man, emerges only occasionally. He had a lifelong marriage to Lina Aletti, the niece of his
friend and colleague Giulio Bizzozero (1846–1901). The couple
had no children, but they took into their home and raised
Carolina, the daughter of Golgi’s brother Giuseppe. A most loyal
friend, Golgi remained close to Bizzozero for most of his life. A
supportive teacher, he encouraged his pupils and his younger colleagues, among them Adelchi Negri (1876–1912), who discovered
the characteristic inclusion bodies in rabies, and Edoardo
Perroncito (1847–1936), who saw the characteristic spiral form
of developing axon tips. Golgi the man is best seen in the cover
photo at the age of 77. Looking up from his desk amid a sea
of laboratory flasks and bottles, perhaps about to discover something new.
Book Review
Brain 2012: 135; 301–303
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Figure 2 (A) Golgi stained pyramidal cells from the cerebral cortex. From Golgi’s Opera Omnia. (B) Cajal (1896). Cerebral cortex.
Dendritic spines are clearly visible.
Mitchell Glickstein
University College London, Wolfson House, London NW1 2HE
References
Advance Access publication November 3, 2011
Cajal (Ramon y Cajal) S. Las espinas colateralesde las celulas del cerebrotenidas con el azul de metleno. Revistra trimestral micrografica;
1896.
Cajal (Ramon y Cajal) S. Textura del Sistema Nervioso. Madrid: Nicolas
Moya; 1899.
Deiters O. Untersuchungen über Gehirn und Rückenmark des Menschen
und der Säugetthiere. Braunschweig: Viewig u. Sohn; 1865.
Golgi C. Opera Omnia. Vol. 1–3. Milan: Hoepli; 1903.
Funding
This work has been supported by a grant from the Volkswagen
Foundation (to M. G., P. T. and S. B.).