Journal of the History of the Neurosciences

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Golgi, Cajal and the Neuron Doctrine

Edward G. Jones

To cite this article: Edward G. Jones (1999) Golgi, Cajal and the Neuron Doctrine, Journal of the
History of the Neurosciences, 8:2, 170-178, DOI: 10.1076/jhin.8.2.170.1838

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Journal of the History of the Neurosciences 0964-704X/99/0802-170$15.00
1999, Vol. 8, No. 2, pp. 170–178 © Swets & Zeitlinger

Golgi, Cajal and the Neuron Doctrine*

Edward G. Jones
Center for Neuroscience, University of California, Davis, Davis, USA

ABSTRACT

Camillo Golgi and Santiago Ramón y Cajal shared the Nobel Prize in 1906 for their work on the histology
of the nerve cell, but both held diametrically opposed views about the Neuron Doctrine which emphasizes
the structural, functional and developmental singularity of the nerve cell. Golgi’s reticularist views re-
mained entrenched and his work on the nervous system did not venture greatly into new territories after its
original flowering, which had greater impact than is now commonly credited. Cajal, by contrast, by the
time he was awarded the Nobel Prize, was already breaking new ground with a new staining technique in
the field of peripheral nerve regeneration, seeing the reconstruction of a severed nerve by sprouting from
the proximal stump as another manifestation of the Neuron Doctrine. Paradoxically, identical studies were
going on simultaneously in Golgi’s laboratory in the hands of Aldo Perroncito, but the findings did not
seem to influence Golgi’s thinking on the Neuron Doctrine.

Keywords: Cajal, Golgi, Perroncito, neurocytology, regeneration, neurotropism, catenary theory.

INTRODUCTION fact that significant developments that could

have substantially contributed to it and to its
The history of the Neuron Doctrine is one of acceptance as the fundamental basis of nervous
paradoxes. The theory was born in an intellec- function were already occurring in physiology.
tual milieu that was dominated by the German By 1891 the finite delay in the spinal transmis-
intellectual tradition in biology, a tradition that sion of the monosynaptic knee jerk reflex had
had seen the development of the Cell Theory been measured, insights had been obtained into
and which had produced some of the greatest the nature of the nervous impulse and, in 1890,
names in the history of biological science – all Langley and Dickinson had blocked transmis-
of whom contributed to the foundations of the sion through the sympathetic ganglion by paint-
Neuron Doctrine. Yet, paradoxically, it was the ing it with nicotine. Yet none of these observa-
contributions of two individuals, Golgi and tions that could have contributed to the Neuron
Cajal, working outside that tradition and in Doctrine as an hypothesis of communication
countries out of the mainstream of European between nerve cells by contact rather than conti-
science, that provided the breakthroughs, the nuity seems to have entered into the conscious-
one in technique, the other in wealth of data and ness of the chief actors in this drama. At least
fundamental insight, that permitted the defini- they did not enter into their writings; the first
tive formulation of the Neuron Doctrine by Wal- mention of Langley’s name, for example, in the
deyer in 1891. Of other paradoxes, one that no writings of Cajal comes in the work,
student of the history of Neuroscience can fail to ‘‘¿ Neuronismo o Reticularismo?’’ published in
remark upon, although it has escaped the notice 1933, just before his death.
of others, is that the Neuron Doctrine was com- Perhaps the greatest paradox of all, and one
pletely anatomical in its conception despite the that has been frequently commented upon is the

*
Address correspondence to: Dr. Edward G. Jones, Center for Neuroscience, 1544 Newton Court, Davis, CA
95616, USA. Tel: +1 530-757-8747. Fax: +1 530-754-9136. E-mail: ejones@ucdavis.edu.
 GOLGI, CAJAL AND THE NEURON DOCTRINE 171

fact that the two most prominent figures in the tetroxide and carmine or gold chloride staining
establishment of the Neuron Doctrine, Golgi and the most that could be revealed of a nerve cell
Cajal, who shared the Nobel Prize for Physiol- was the soma, the proximal and with luck the
ogy or Medicine in 1906, were at opposite ends secondary dendrites, and the initial segment of
of the spectrum of ideas associated with it, the the axon. Some of Golgi’s early pictures of
one an ardent reticularist, the other an equally nerve cells can be seen, for example, in his
ardent connectionist from whose hands flowed 1871–1872 publications on the finer anatomy of
most of the knowledge about the intrinsic cir- the central nervous system in Rivista Clinica
cuitry of the brain centers that we continue to (Opera Omnia, pp. 5–70). After 1873, following
use to this day. the discovery of the black reaction, his drawings
Neither of these two great scientists ever con- underwent a radical transformation, not only in
ceded much to the other in their writings, al- their beauty but in the wealth of detail about in-
though they did accord one another the common dividual nerve cells, hitherto undreamed of.
courtesies natural to their times but so sadly Among Golgi’s original observations that are
missing from our own. The verdict of history often forgotten in the haste to debunk him for
must be, of course, that Golgi was in error but his failure to accept the Neuron Doctrine are:
his reasons for disavowing the Neuron Doctrine tracing of axons over longer distances than ever
throughout his career are by no means unin- before; the first visualization of axon collaterals;
formed. I shall allude to some of them below. the recognition of the dense axon plexuses of the
But this brings us to one of the most remarkable central nervous system; the first demonstration
paradoxes of all, that I shall try to deal with in of the full extent of the dendritic trees of neu-
some detail. Exactly at the time of the Nobel rons; the recognition of intrinsic (‘sensory’ or
Prize, and during the subsequent five or six type II) and projection (‘motor’ or type I) neu-
years, when the Neuron Doctrine was entering rons as separate classes. I believe that one can
its second phase and Cajal was working inten- also identify dendritic spines even in his early
sively to establish that severed peripheral nerves drawings of Purkinje cells in the cerebellum,
regenerated by sprouting of axons from the although he did not mention them.
proximal stump and not by coalescence out of Cajal was accustomed to accuse Golgi of add-
chains of Schwann cells, a scientist working in ing the spines to his later drawings, e.g. in those
Golgi’s laboratory, Aldo Perroncito, was coming which accompanied his Nobel lecture. I think
to exactly the same conclusions and his findings that this was unfair. It is true that Golgi gave
were sometimes in advance of those of Cajal – them little functional importance, mainly be-
much to the concern of the latter. cause he could see similar protrusions on neuro-
glial cells.
Out of Golgi’s studies prior to 1886 came a
GOLGI AND THE STRUCTURE OF wealth of information not only about the struc-
NEURONS ture of the nerve cell but also about the relation-
ships among nerve cells that hold some of the
Before turning to examine this second phase in keys to understanding their organization in an
the exposition of the Neuron Doctrine, let us inter-communicating network. By demonstrating
examine some of the background prior to 1891, the free endings of the dendrites, he overthrew
when Golgi made the majority of his contribu- Gerlach’s belief in anastomotic union of these
tions and Cajal first burst upon the scene. Prior structures, but it also led him to a belief in their
to his discovery of the reazione nera in 1873, primary association with the brain surface or
Golgi’s published representations of nerve cells with blood vessels and to his considering them
were typical of those of the time when brain tis- solely as nourishing channels for the cell soma.
sue was customarily teased apart after compres- By demonstrating that some nerve cells were
sion between cover glasses in water or alkali and restricted to their brain region while others sent
when even with the added benefits of osmium long axons into the white matter, he laid one
172 EDWARD G. JONES

foundation essential for the construction of cir- bly the result of learning from Retzius of the
cuits for the flow of information through a re- merits of the new technique. Although not
gion, something at which Cajal was later to ex- agreeing with many of Golgi’s interpretations,
cel. He has again been criticized, from Cajal on, Kölliker in 1887 clearly stated the potential ad-
for his use of the designators ‘sensory’ and ‘mo- vantages of the technique and in that year, at the
tor’ for the two classes of cell. This criticism is age of 70, visited Golgi in Pavia to learn the
probably unjustified for, as he pointed out in his technique. It is reported that on returning to
Nobel lecture, outside the spinal cord, he was Würzburg and trying out the method for himself,
largely using these terms by analogy with the he was to obtain only indifferent results. This
cells of the cord. did not prevent an enduring friendship from de-
Gogli’s attitude to the nervous network was veloping between Kölliker and Golgi, one ce-
especially conditioned by his observations of the mented by frequent visits to Italy lasting into
remarkable density of the fiber meshworks of Kölliker’s 80s.
the granular layer of the cerebellum and plexi-
form layer of the dentate gyrus. In them, he saw
the afferent axons and the axons of the intrinsic CAJAL AND CONNECTIONS BY CON-
neurons lose themselves in progressively TACT
branching arborizations, while the collaterals of
the efferent neurons furnished re-entrant inputs. In 1887, Santiago Ramón y Cajal first learned of
In the meshwork he considered that the integra- the Golgi technique from a Spanish amateur his-
tive properties of the nervous system had their tologist, Luis Simarro, who had picked up the
seats. It is a concept but little removed from the method in Paris (Cajal, 1917). From whom is
ideas of Leydig and others on the nature and not recorded but it is indicative of the wide-
functions of the neuropil in the ganglia of inver- spread knowledge, if not universally successful
tebrates – ideas that played a substantial role in implementation, of the new technique. Simarro,
promoting the view of the nervous system as an according to Cajal, after some early success,
anastomosing network. later gave it up. Not so Cajal himself, who in a
In recognizing Golgi’s errors of interpreta- flash of enlightenment (he says) recognized the
tion, recent generations of neuroscientists have importance of the method as a means of tracing
tended to neglect the importance of his observa- connectivity in the nervous system. That he
tions on the basic structure of the nerve cell. should have focused on connectivity from the
That his technique met with a mixed response outset is remarkable only if one thinks that his-
that sometimes tended to the disdainful is un- tologists of that era had little concept of path-
doubtedly true. Cajal points out, for example, ways underlying reflex action and supporting
that Ranvier’s handbook of histological tech- the flow of sensory information and motor com-
nique that he, Cajal, initially regarded as his mands. That this is patently untrue can be deter-
technical bible, was dismissive of the merits of mined by reference to any textbook of the era
the Golgi technique. But it is incorrect to regard from Claude Bernard on. Even the reticularists,
Golgi’s technique as having been ignored by of whom Golgi was one, were striving for a
other European scientists. As Ennio Pannese mechanism that would explain the fundamental
(1996) has pointed out, Boll had summarized in capacity of one part of the nervous system to
German Golgi’s original note soon after its pub- communicate with other parts.
lication in 1873; there were other brief reports of Within the four years from his first applica-
its use through the 1880s and during this period tion of the Golgi technique in 1887 to the formal
Golgi distributed some of his slides to other sci- enunciation of the Neuron Doctrine in 1891,
entists such as Kölliker and Retzius (see G. Cajal had published some 45 papers (Pérez-de-
Grant in this volume). The expedition of Tudela, 1983) in which the foundations of the
Fridtjoff Nansen to the Naples marine station in Neuron Doctrine were well and truly laid and on
1887, with its side trip to visit Golgi, was proba- which Waldeyer was to draw heavily in making
 GOLGI, CAJAL AND THE NEURON DOCTRINE 173

the case for it. The reasons for Cajal’s success huchten 1892; Cajal 1892), Cajal could com-
are several (De Felipe and Jones, 1992). Un- mence putting his typical arrows on his draw-
doubtedly at the forefront was his improvement ings, indicating the direction of afferent and ef-
of the technique by introducing the procedure of ferent conduction through a center such as the
multiple re-impregnations in the dichromate and cerebellum, retina or olfactory bulb. Our knowl-
silver solutions, controlling the level of impreg- edge of the elementary circuitry of the nervous
nation by cutting sample sections at intervals system at the cellular level stems from this era.
throughout its course. Aiding and abetting this Cajal’s genius lay as much in his insights into
was his preference for the brains of immature the fundamental biology of the nervous system
animals and for those of birds and small mam- as in his technical innovations and the remark-
mals, in all of which the relative lack of myelin able volume of work he produced in the early,
does not impede impregnation and the simplicity formative years of the Neuron Doctrine. To
of the axonal plexuses permits individual axonal claim that his success rested solely in his mas-
ramifications to be resolved. Once other scien- tery of the Golgi stain would be inappropriate
tists recognized the merits of these two ap- since, despite the failures alluded to above, there
proaches, the way was clear for widespread ap- were contemporaries who were producing mate-
plication and for rapid confirmation of Cajal’s rial as good as Cajal’s and often published in
observations. It is likely that their earlier diffi- plates of greater elegance. Golgi himself was
culties in applying the stain had stemmed from one and Cajal’s preparations of the retina pub-
concentrating most of their efforts, as Golgi had lished in 1888 and 1889 are surpassed in beauty
done, on the human brain. by those of Tartuferi (1888). Tartuferi, like
Apart from his improvements in technique, it Golgi, however, was a reticularist.
is likely that Cajal’s early success lay in his
choice of highly laminated structures, such as
the cerebellar cortex and retina, as the objects of GOLGI’S VIEWPOINT
his investigations. In these, the regularity of or-
ganization and the clear stratification of cell The reasons why Golgi and other individuals
types and axonal plexuses facilitates the extrac- who made seminal contributions to the under-
tion of individual cells and their processes from standing of the structure of the nervous system,
the total pattern and permits their position in the notably Nissl (1903), remained committed to a
circuitry running through the structure to be de- reticularist viewpoint in the face of overwhelm-
termined. In his first paper with the Golgi tech- ing evidence against it, have never been fully
nique, on the cerebellum of birds, published in explored. In Golgi’s case a focus on the densely
1888, Cajal recognized that the axons of basket intertwined mass of axons in the plexuses of the
cells, seemingly conforming to Golgi’s type I cerebellum and hippocampus may have influ-
cells, because they did not immediately breakup enced him. Possibly a conscious or unconscious
into plexuses typical of type II cells, actually commitment to the neuropil as the center for all
ended by embracing the cell somata of Purkinje integrative actions of the nervous system deriv-
cells and thus could only exert their influence ing from the earlier studies of Leydig and others
upon the white matter via the Purkinje cells. on the ganglia of invertebrates in which the neu-
This was the key to his recognition of connec- ronal somata were seen as merely nourishing
tions by contact rather than by protoplasmic elements for the more important neuropil (see
continuity between neurons, and to his develop- Shepherd, 1991), may have helped. We do not
ing his analysis of the intrinsic structure of the know what microscopes Golgi used in his early
nervous system in terms of circuits for the flow years, but it is unlikely that they were capable of
of information from neuron to neuron. Once the resolving, separately, the arborizations of indi-
law of dynamic polarization, which stipulates vidual axons in the dense plexuses upon which
that dendrites conduct towards the soma and the Golgi placed so much importance. One point
axon away from it, was formulated (Van Ge- repeatedly made by Golgi and re-echoed in his
174 EDWARD G. JONES

Nobel lecture of 1906 is his belief that recovery work done in the interim following publication
of function in the nervous system, such as oc- of the original Spanish version (1899, 1904). In
curs after a stroke, could only be possible if these studies, the neurofibrillar character of the
nerve cells were in continuity with one another. nerve cell is clearly revealed. Cajal quickly real-
Another, is that structures such as the hippocam- ized, however, that the capacity to stain neuro-
pus and cerebellum function as single entities, fibrils (now known to be bundles of intermediate
their nerve cells operating in collective mass filaments) offered the opportunity to study the
action and not as individual elements. It is this growth of axons in the regeneration of severed
holistic view that led him to reject the concept of peripheral nerves. He was conscious that recent
cortical localization of function. developments in this field posed a threat to the
In reading the 1906 Nobel lectures of Golgi universality of the Neuron Doctrine. With his
and Cajal, one cannot help but remark on the usual insight, he also recognized that issues
contrast in styles, and it is difficult not to be sad- raised in the increasingly vehement debate about
dened by that of Golgi. Golgi is clearly looking the nature of peripheral nerve regeneration had
to the past, referring mainly to older work, de- important implications for the normal develop-
fending an untenable position and presenting his ment of the nervous system and for any hopes of
case with an air of negativism. Cajal’s presenta- promoting regeneration in the injured central
tion is much more in line with that of a modern nervous system.
seminar in which the speaker rapidly summa- Many years previously, the anatomist, Viktor
rizes his past work and quickly proceeds enthu- Hensen (1864) had proposed that newly growing
siastically to describe his latest observations peripheral nerve fibers in the developing frog
made with new techniques on fresh experimental were formed by coalescence out of linear chains
paradigms. In Cajal’s case, it is the application of Schwann cells. This ‘catenary’ theory was
of the reduced silver nitrate method, discovered ruled out as a developmental process by the in-
independently by Cajal and Bielschowsky in vestigations of His (1887) and the later Golgi-
1902/1903, to the structure of the nerve cell and based studies of Lenhossék (1890) and Cajal
to the regeneration of peripheral nerves on (1890) in which the growth cone was identified
which he had been working for two years. for the first time. However, it had also been pro-
Throughout Cajal’s whole talk, however, runs posed by Vulpian (1866) as the mechanism by
the theme of the Neuron Doctrine and the indi- which a new distal axon segment could be
viduality of the nerve cell. Cajal’s new studies formed and reunited with its proximal stump in
on the peripheral nervous system were initiated the process of peripheral nerve repair, the distal
to counter a growing threat to this fundamental axon segment being formed within the chains of
tenet. It is a matter of great surprise that identi- Schwann cells in the distal stump and later
cal work was simultaneously going on in Gol- joined with the proximal segment. The idea was
gi’s own laboratory at the hands of his nephew, to be resurrected in the early 1900s by Albrecht
adopted son, and successor in the Chair of His- Bethe (1901, 1903, 1907) and Hans Held (1907,
tology at Pavia, Aldo Perroncito. 1909). The prevailing view dating to Waller
(1850) and reinforced by Ranvier (1878) was
that the proximal stump sprouted new axons that
CAJAL, PERRONCITO, AND REGENERA- invaded the distal stump and restored continuity.
TION OF PERIPHERAL NERVES To Cajal, the resurrection of the catenary theory
was a serious threat to his theory of neurotro-
Cajal applied the reduced silver stain initially to pism, first formulated in his 1892 study of the
examine the internal structure of the nerve cell retina, which depended on outgrowth of axons
and most of the material added to the French from single nerve cell somata under the influ-
version of his textbook of the histology of the ences of trophic signals and, by extension, de-
nervous system (1909, 1911) comes from appli- manded that repair of a cut peripheral nerve de-
cation of the reduced silver technique, reflecting pended upon sprouting from the proximal stump
 GOLGI, CAJAL AND THE NEURON DOCTRINE 175

and growth of the sprouts across the gap and investigators. Among these were Aldo Perron-
down the distal segment of the nerve, under the cito in Golgi’s laboratory and an active Roma-
same kinds of trophic influences. nian group led by the neurologist, Georges Ma-
As pointed out in our introduction to a new rinesco. Apart from the competition between the
edition of Cajal’s Degeneration and Regenera- proponents of the catenary and sprouting
tion of the Nervous System (De Felipe & Jones schools, which was at times highly polemical,
1991), there were two principal arguments there was considerable competition between
raised by Bethe and others in support of the cat- those who were most active in the application of
enary (or ‘polygenic’) theory: (1) growing axons the reduced silver technique to the issue of pe-
could never be histologically demonstrated ripheral nerve regeneration. Perroncito was defi-
crossing the gap or scar between the proximal nitely ahead of Cajal in describing the earliest
and distal stumps of a cut peripheral nerve; (2) phenomena occurring in the central stump of a
reinnervation of a distal stump and restoration of divided nerve. Between 1905 and 1909,
motor function could occur even when obstacles Perroncito published a series of relatively short
were introduced that prevented re-union of the papers on his observations in the Bulletin of the
proximal and distal stumps. The first of these Medico-Surgical Society of Pavia (Perroncito,
arguments was clearly based upon the inability 1905a,b, 1906, 1908, 1909), a more extensive
of available methods to stain individual axons, summary and review of the whole field appear-
contemporary workers having to rely upon the ing in German in 1907 (Perroncito, 1907). He
staining of the Schwann sheath or the myelin points out in a footnote to his December 1905
sheath, both of which appear only after axons paper that the work formed part of his thesis and
have crossed the gap. The first applications of that, just as he was about to publish it, Cajal
the reduced silver stain at the hands of Cajal (1905) and Marinesco and Minea (1905) had
(1905) and Perroncito (1905a) were to resolve independently published short preliminary com-
this issue by clearly demonstrating the sprouting munications on the same subject. Cajal, ever
of proximal cut axons and the early presence of sensitive to issues of priority, wrote on the first
naked, regenerating axons with growth cones, reprints sent to him by Perroncito that they were
crossing the gap and invading the distal stump. received on 28th September and 4th of Decem-
The second argument was for a time perhaps ber 1905 and on the latter that it followed his
more cogent, although from a modern perspec- own presentation to the Society of Biology and
tive it can be seen as indicative of the enormous his two published notes of 1905 (Cajal, 1905).
capacity of growing or regenerating peripheral In writing about this in his 1913 book he was
axons to circumvent obstacles in reaching their forced to concede, however, that although pub-
appropriate targets. A number of ingenious ex- lished in September, it was the May number of
periments by Cajal resolved the issue by demon- the Journal that carried the first paper.
strating the capacity of regenerating axons to Perroncito, working on dogs in which he had
correct inappropriate orientations, negotiate ob- cut the sciatic nerve, independently made the
stacles, and reach their targets by highly devious same observations as Cajal on the retraction of
routes. This turned out to be the supreme vindi- the proximal ends of cut axons, the sprouting of
cation of the neurotropic theory. new branches, the naked axons making their
Volume I of Cajal’s two volume work, way across the gap, their entry into the distal
Estudios Sobre la Regeneración del Sistema stump, and the degenerative changes occurring
Nervioso, first published in 1913, contains one in the distal stump. He was ahead of Cajal in
of the most extensive studies of the histological observing sprouting occurring as early as twenty
phenomena associated with degeneration and four hours after nerve section and sprouts invad-
regeneration of peripheral nerves ever pub- ing the gap between the stumps on the second
lished. It can easily be viewed as the definitive day. He is also responsible for first describing
word on the subject but this is to ignore the con- the unusual ‘apparatuses of Perroncito’ (Cajal’s
tributions of a number of other contemporary name), a peculiar mixture of bundles, rings, spi-
176 EDWARD G. JONES

rals and bulbs formed on the ends of early re- alluding to attractant properties of Schwann
generating nerve fibers. Although he perhaps cells for growing axons, Cajal’s was by far the
saw the earliest outgrowth of new sprouts, he major contribution.
did not agree with Cajal about the growth cones, By 1908, Perroncito was as embroiled as
seeing them as responses to obstructions or in- Cajal in the debate with Albrecht Bethe, Profes-
dicative of aborted regeneration. sor of Anatomy at Strassburg, who was the chief
Cajal, although highly complimentary in re- polemicist on the side of the catenary or poly-
ferring to Perroncito in his later (1913) book on genic theory of nerve regeneration. Papers by
degeneration of peripheral nerves, in 1905 and Bethe published in 1907 personally attacked the
1906 was watchful of this work emerging from work of both investigators, at one point accusing
Golgi’s laboratory. The pages of many of the Perroncito of ‘‘supine ignorance’’ of the facts of
reprints sent to Cajal by Perroncito and currently physiology. Despite the new evidence emerging
in the library of the Instituto Cajal, are covered from the Italian, Spanish and Romanian labora-
with comments in Cajal’s handwriting, a number tories, Bethe continued to belabor the idea of
of which reflect a desire to assert his own claims nerve regeneration as the reunion of chains of
to priority. The truth is that many of Cajal’s ob- supporting cells. These papers met with as vig-
servations emerged in very short formats and his orous a response from Perroncito (1908) as they
definitive work appeared well after the publica- did from Cajal (1907), Perroncito terming the
tions of Perroncito and even after those of attacks ‘indecent’. Gradually, Bethe was to give
Marinesco, whose work with Minea in 1905 ground, admitting first the phenomenon of
contained many of the same observations as that sprouting and some invasion of the distal stump
of Perroncito. (It is to Minea (1909) that we owe and finally, in 1922, that all new fibers came
the introduction of that now popular term from the proximal stump. In return, Cajal re-
‘neuroplasticity’). Although we may express moved certain personal comments about Bethe
distaste for Cajal’s at times unseemly competi- from the second edition of his autobiography
tiveness, and possibly deny him full priority for (De Felipe and Jones, 1991). It was only Cajal,
these findings, there can be little doubt about the however, who continually linked the contro-
monumental character of his overall, definitive versy to the Neuron Doctrine and the singularity
work. Nor can one deny him credit for those of the nerve cell as the unit of organization of
fundamental biological insights that were part of the nervous system. One can detect nothing in
his genius. Apart from recognizing that nerve the writings of Perroncito or Golgi from that
regeneration had to be a recapitulation of nerve time to suggest that the drama of peripheral
growth in development, he was able to see, far nerve regeneration being played out to a large
more clear sightedly than others at the time, that extent in his own laboratory over influenced
regeneration, the reconstitution of a nerve and Golgi’s thinking on the Neuron Doctrine. The
the reestablishment of connections with appro- Neuron Doctrine does not warrant mention in
priate nerve endings, such as motor end plates Perroncito’s lengthy German review in 1907,
and muscle spindles, must involve a variety of whereas it forms the entrée for Cajal’s whole
chemical signals, some trophic, some tropic, work on regeneration.
some local, some long distance, some non-spe-
cific, others specific, some chemical, others me-
chanical. This was all part of his theory of neu- CONCLUSION
rotropism, a term he obtained from Forssman
(1900). At one point in his 1913-1914 book, he As recognized by the Nobel Committee, Camillo
even hints that he had some comprehension of Golgi and Santiago Ramón y Cajal extended the
the necessity for interactions between tropic investigation of the nerve cell to a level of reso-
molecules and receptors on the growth cones. lution far beyond that achieved by any of their
Although not completely alone in conceiving the predecessors, the one by his introduction of a
neurotropic theory, Marinesco, for example, also vastly improved analytic technique, the other by
 GOLGI, CAJAL AND THE NEURON DOCTRINE 177

his mastery of that technique, the breadth and Cajal, S. Ramón y (1888b): Sobre las fibras nerviosas
depth of his work and his fundamental biologi- de la capa molecular del cerebelo. Rev. Trim.
Histol. Norm. patol. 1: 33-49.
cal insights. Golgi was not alone among contem-
Cajal, S. Ramón y (1891): Sur l’origine et les ramifi-
porary scientists in remaining wedded to the re- cations des fibres nerveuses de la moelle
ticular theory but this may have been as much embryonnaire. Anat. Anz. 5:85-95, 111-119.
due to his laying aside study of the nervous sys- Cajal, S. Ramón y (1892): El nuevo concepto de la
tem in favor of investigations in other fields, as histología de los centros nerviosos. Rev Ciencias
Méd. 18:457-476.
to his stated reasons. Cajal continued to adopt Cajal, S. Ramón y (1899, 1904): Textura del Sistema
new techniques as they became available and Nervioso del Hombre y de los Vertebrados. Ma-
new experimental preparations that would en- drid, Moya, 2 Vols in 3.
able him to continue to push forward the fron- Cajal, S. Ramón y (1903): Un sencillo método de
tiers of neurohistological analysis. He was not coloración del retículo protplásmico y sus efectos
en los diversos centros nerviosos de vertebrados e
alone in revealing the histological basis of pe- invertebrados. Trab. Lab. Invest. Biol. Univ. Ma-
ripheral nerve repair. But it was he who clearly drid. 2:129-221.
derived from it the underlying biological mecha- Cajal, S. Ramón y (1905): Sobre la degeneración y
nisms that governed this process, and who fore- regeneración de los nervios. Bol. Inst. Ser. Vac.
saw their relevance to the development of the Bact. Alfonso XIII. 1: 49-60, 113-119.
Cajal, S. Ramón y (1907): Regeneración de los
nervous system and to any hope of promoting Nervios. Madrid, Real Acad. Med.
regeneration of the injured central nervous sys- Cajal, S. Ramón y (1907): Les stuctures et les
tem. While Aldo Perroncito, working contempo- connexions des cellules nerveux. In: Les Prix No-
raneously in Golgi’s laboratory might have also bel, 1904-1906, Stockholm, Norstedt.
had some insight into these mechanisms and Cajal, S. Ramón y (1909, 1911): Histologie du
Système Nerveux de l’Homme et des Vertébrés.
their relevance, the most important aspect of the Trans by L. Azoulay, Paris, Malign, 2 Vols.
findings in these studies, clearly apparent to Cajal, S. Ramón y (1913): Estudios Sobre la De-
Cajal from the outset, namely their significance generación y Regeneración del Sistema Nervioso.
in relation to the Neuron Doctrine, seems to Vol. 1. Degeneración y Regeneración de los Ner-
have eluded both he and his master. viosos. Madrid, Moya.
Cajal, S. Ramón y (1917): Recuerdos di mi Vida, Vol.
2, Historia de mi Labor Scientifica. Madrid, Moya.
Cajal, S. Ramón y (1933): ¿Neuronismo o reticu-
REFERENCES larismo? Las preubas objetivas de la unidad ana-
tómico de las celulas nerviosas. Arch. Neurobiol.,
Bethe, A (1901): Ueber die Regeneration peri- Madrid 13: 1-144.
pherischen Nerven. Arch. Psychiat. NervenKr. 34: DeFelipe, J. and Jones, E. G. (1991): Cajal’s Degen-
1066-1073. eration and Regeneration of the Nervous System.
Bethe, A (1903): Allgemeine Anatomie und Physio- New York Oxford.
logie des Nervensystems. Leipzig, Thieme. DeFelipe, J. and Jones, E. G. (1992): Santiago Ramón
Bethe, A (1907): Neue Versuche über die Regenera- y Cajal and methods in neurohistology. Trends
tion der Nervenfasern. Arch. Physiol. Bonn 116: Neurosci.15:237-246.
385-478. Forssman, J. (1898): Ueber die Ursachen welche die
Bethe, A (1908): Die Nervenregeneration und die Wachsthumsrichtung der peripheren Nervenfasern
Verheilung durchschnittener Nerven. Folia Neuro- bei der Regeneration bestimmen. Beitr. Path. Anat.
biol. 1: 63-76. Allg. Path. 14:56-100.
Bethe, A (1922): Zur Theorie und Praxis der Ver- Golgi, C. (1873): Sulla sostanza grigia del cervello.
heilung durchtrennter Nerven. In: Libro in Honor Gaz. Med. Ital. Lombardia 6:244-246.
de D. S. Ramón y Cajal Vol. 2, pp.31-35 Madrid, Golgi, C. (1883): Recherches sur l’histologie des
Junta para el Homenaje a Cajal. centres nerveux. Arch. Ital. Biol. 3: 285-317.
Bielschowsky, M. (1902): Die Silberimprägnation der Golgi, C. (1884): Recherches sur l’histologie des
Axencylinder. Neurol. Centralbl. 21: 579-584. centres nerveux. Arch. Ital. Biol. 4:92-123.
Cajal, S. Ramón y (1888a): Estructura de los centros Golgi, C. (1903): Opera Omnia. Milan, Hoepli, 2
nerviosos de las aves. Rev. Trim. Histol. Norm. Vols.
patol. 1: 1-10. Golgi, C. (1907): La doctrine du neurone: théorie et
faits. In: Les Prix Nobel, 1904-1906. Stockholm,
Norstedt.
178 EDWARD G. JONES

Hensen, V. (1864): Ueber die Entwickelung des Ge- biologia Santiago Ramón y Cajal’’. Trab. Inst.
webes und der Nerven im Schwanze der Frosch- Cajal. Madrid, 74:169-235.
larve. Virchow’s Arch. Path. Anat. 31: 51-73. Perroncito, A. (1905a): Sulla questione della
His, W. (1886): Zur Geschichte des menschlichen rigenerazione autogena delle fibre nervose. Boll.
Rückenmarks und der Nervenwurzeln. Abhandl. Soc. Med. Chir. Pavia 1905: 360-363.
Math. –Phys.Class Königl. Säch.Gesell. Wiss., Perroncito, A. (1905b): La rigenerazione delle fibre
Leipzig, 13: 147-209, 477-513. nervose. Boll. Soc. Med. Chir. Pavia 1905: 434-
Held, H. (1907): Kritische Bemerkungen zu der Ver- 444.
teidigung der Neuroblasten und der Neuronen- Perroncito, A. (1906): La rigenerazione delle fibre
theorie durch R. Cajal. Anat. Anz. 30: 369-391. nervose. Boll. Soc. Med. Chir. Pavia 1906: 94-105.
Held, H. (1909): Die Entwickelung der Nervengewebe Perroncito, A. (1907): Die Regeneration der Nerven.
bei den Wirbelthieren. Leipzig, Barth. Beitr. path. Anat. allg. Path. 42: 355-446.
Jones, E. G. (1994): The neuron doctrine, 1891. J. Perroncito, A. (1908): Sulla rigenerazione dei nervi.
Hist. Neurosci. 3: 3-20. Boll. Soc. Med. Chir. Pavia 1908: 97-107.
Kölliker, A. von (1887): Ueber Golgi’s Untersuchun- Perroncito, A. (1909): Gli elementi cellulari nel
gen, den feineren Bau des centralen Nervensystems processo di degenerazione dei nervi. Boll. Soc.
betreffend. Sitz. Phys. –Med. Ges. Würzburg. 1887: Med.-Chir. Pavia. 23: 108-117.
55-62, 68. Ranvier, L. A. (1878): Leçons sur l’Histologie du
Langley, J. N. and Dickinson, W. L. (1890): Pituitrin Système Nerveux. Compiled by E. Weber, Paris,
and nicotin. J. Physiol., Lond., 11: 265-306. Savy, 2 Vols.
Lenhossék, M. von (1891): Zur Kentniss der ersten Shepherd, G. M. (1991): Foundations of the Neuron
Entstehung der Nervenzellen und Nervenfasern Doctrine. New York, Oxford.
beim Vogelembryo. Verhandl. X Internat. Med. Tartuferi, F. (1887): Sull’anatomia della retina. Int.
Congr. Berlin, 1890, 2: 115-129. Monatsshr. Anat. Physiol., 4: 421-441.
Marinesco, G. and Minea J. (1906): Précocité des Van Gehuchten, A. (1891): La structure des centres
phénomènes de régénéresence des nerfs après leur nerveux: la moelle épinière et le cervelet. La Cel-
section. Compt. Rend. Soc. Biol. Paris. 61: 383- lule, 7: 79-122.
385. Vulpian, E. F. A. (1866): Leçons sur la Physiologie
Minea, J. (1909): Cercetari Experimentale asupra Générale et Comparée du Système Nerveux. Com-
Variatiunilor Morfologice ale Neuronului Sensitiu. piled by E. Bremónd, given at the Musée
Thesis, Bucharest, Brozer. d’Histoire Naturale, Paris, Germer-Bailliere.
Nansen, F. (1887): the Structure and Combination of Waldeyer, W, von (1891): Uber einige neuere
the Histological Elements of the Central Nervous Forshungen im Gebiete der Anatomie des centralen
System. Bergen, Bergens Mus. Aarsberetning, pp. Nervensystems. Deutsch. Med. Wochenschr.17:
29-214. 1213-1218; 1244-1246; 1267-1269; 1331-1332;
Nissl, F. (1903): Die Neuronenlehre und ihre An- 1352-1356.
hänger. Jena, Fischer. Waller, A. V. (1850): Experiments on the section of
Pannese, E. (1996): The black reaction. Brain Res. the glosso-pharyngeal and hypo-glossal nerves of
Bull. 41: 343-349. the frog, and observations of the alterations pro-
Pérez-de-Tudela, M. S. (1983): Publicaciones del duced thereby in the structure of their primitive
Prof. Dr. Santiago Ramón y Cajal existentes en los fibres. Phil. Trans. Roy. Soc. Lond. 140: 423-429.
fondos de la biblioteca del ‘‘Instituto de Neuro-