Colgi, Cajal and the Neuron Doctrine

Camillo Golgi and Santiago Ramon 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 remained 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.     

Cajal's Views on the Nobel Prize for Physiology and Medicine (October 1904)

In this report we present and discuss an unpublished letter written by Santiago Ramón y Cajal in October 1904 in relation to his possible nomination for the Nobel Prize for Physiology and Medicine. This letter shows that Cajal was aware of his previous nominations for the Prize. He was convinced that these nominations had not been successful because neither anatomy nor histology were among the sciences included in the Nobel Statutes' definition of Physiology or Medicine. He gives a list of the merits he thought might be used for a new nomination, which included only works concluded during the previous five years.     

Cajal's Brief Experimentation with Hypnotic Suggestion

Spanish histologist Santiago Ramón y Cajal, one of the most notable figures in Neuroscience, and winner, along with Camillo Golgi, of the 1906 Nobel Prize in Physiology or Medicine for his discoveries on the structure of the nervous system, did not escape experimenting with some of the psychiatric techniques available at the time, mainly hypnotic suggestion, albeit briefly. While a physician in his thirties, Cajal published a short article under the title, “Pains of labour considerably attenuated by hypnotic suggestion” in Gaceta Médica Catalana. That study may be Cajal's only documented case in the field of experimental psychology. We here provide an English translation of the original Spanish text, placing it historically within Cajal's involvement with some of the key scientific and philosophical issues at the time.     

Cajal's views on the Nobel Prize for physiology and medicine (October 1904)

In this report we present and discuss an unpublished letter written by Santiago Ramon y Cajal in October 1904 in relation to his possible nomination for the Nobel Prize for Physiology and Medicine. This letter shows that Cajal was aware of his previous nominations for the Prize. He was convinced that these nominations had not been successful because neither anatomy nor histology were among the sciences included in the Nobel Statutes' definition of Physiology or Medicine. He gives a list of the merits he thought might be used for a new nomination, which included only works concluded during the previous five years.     

Pavlov and Cajal: Two different pathways to a Nobel Prize

Ivan Pavlov (1849–1936) and Santiago Ramón y Cajal (1852–1934) were two contemporary scientists who not only had a great impact on Russian and Spanish science but also on the international stage. Both shared several common features in their life and work, yet they followed fundamentally different paths during their training as scientists. While Pavlov received his laboratory training under the guidance of Ilya Tsion (1843–1912), Cajal did not receive any formal training within a particular laboratory nor did he have a mentor in the traditional sense, rather he was mainly self-taught, although he was supported by key figures like Maestre de San Juan (1828–1890) and Luis Simarro (1851–1921). In this article, we compare the scientific training of these two Nobel Prize laureates and the influences they received during their scientific lives.     

The impossible interview with the man of the hidden biological structures. Interview by Paolo Mazzarello

This paper presents an "impossible interview" to Professor Camillo Golgi, placed in time in December 1906. The Italian Professor Golgi from Pavia has been awarded the Nobel Prize for Physiology or Medicine ex aequo with the Spanish anatomist Santiago Ramón y Cajal. Both scientists have obtained the award for their work on the anatomy of the nervous system. However, they have opposite views on the mechanisms underlying nervous functions. Golgi believes that the axons stained by his "black reaction" form a continuous anatomical or functional network along which nervous impulses propagate. Ramón y Cajal is the paladin of the neuron theory, a hypothesis questioned by Golgi in his Nobel lecture of Tuesday, December 11. After the ceremony, an independent journalist has interviewed Professor Golgi in the Grand Hotel in Stockholm. Excerpts about his education, his main scientific discoveries, and his personal life are here given (reconstructing the "impossible interview" on the basis of Golgi's original writings).     

The impossible interview with the man of the neuron doctrine. Interview by Edward G Jones

This paper follows the form of that by Mazzarello that precedes it (Mazzarello, 2006) and presents an imaginary interview with Santiago Ramón y Cajal in December 1906. A few days earlier Cajal had been awarded the Nobel Prize for Physiology or Medicine, an award that he shared equally with Professor Camillo Golgi. Golgi had been recognized for his work as a pioneer into investigations of the nervous system, primarily on account of his discovery of the "black reaction" of silver chromate impregnation of whole nerve cells and their processes. Cajal had been recognized for his implementation of that method and for laying with it the foundations of what was to become modern neuroanatomical science. Paradoxically, the two awardees had been led by their researches to diametrically opposed views of the organization of the nervous system. Golgi believed in a continuous network of axons that formed the basis of all the integrative properties of the nervous system, while Cajal had provided the information that led to the formulation of the neuron doctrine that saw the nervous system as being made up of chains of discontinuous cells joined by polarized functional contacts that we now call synapses. The paper takes the form of an interview with Professor Cajal in the Grand Hotel Stockholm. His responses to questions posed by the imaginary interviewer are all taken from Cajal's own writings.     

Revisiting the 1981 Nobel Prize to Roger Sperry, David Hubel, and Torsten Wiesel on the occasion of the centennial of the Prize to Golgi and Cajal

In 1981 the Nobel Prize for Medicine or Physiology was awarded to Roger Sperry for his work on the functional specialization of the cerebral hemispheres, and to David Hubel and Torsten Wiesel for their work on information processing in the visual system. The present paper points to some important links between the work of Sperry and that of Hubel and Wiesel and to their influences on neuroscience in the best tradition going back to Cajal.     

Egas Moniz and the Origins of Psychosurgery: A Review Commemorating the 50th Anniversary of Moniz's Nobel Prize

Modern psychosurgery began in 1936 with the work of the Portuguese neurologist, Egas Moniz, who attempted to treat the symptoms of mental illness by severing neural tracts in the frontal lobes. This procedure eventually became widespread and applied to thousands of institutionalized, psychotic patients in the United States and other countries. Despite serious side effects associated with psychosurgery, the apparent importance and validity of the treatment was recognized in 1949 when Moniz received the Nobel Prize for his innovation. Psychosurgery was largely replaced by anti-psychotic drugs in the mid-1950s, and the procedure and its practitioners rapidly fell into disrepute. This article reviews Moniz's career, the factors that led up to his first clinical trials of frontal lobe surgery, and the circumstances that allowed psychosurgery to flourish in the 1940s, eventually leading to Moniz's Nobel Prize.     

The Legacy of Camillo Golgi for Modern Concepts of Brain Organization

The experimental advance made by Camillo Golgi's ‘black reaction’ has been universally recognized as the start of the modern revolution in the study of the nervous system. By contrast, his concepts of nervous organization, particularly his support for the idea of a ‘nervous reticulum’, have been universally rejected. The premise of the present paper is that the ideas of a biologist of this stature deserve re-examination. Golgi's arguments for considering the holistic function of the brain seem to come from his experience as a physician, and presage the views of the gestaltists and, more recently, the conceptual underpinnings of artificial neural networks. His interest in the possible nutritional roles of neuronal dendrites can be seen to anticipate current investigations, at the cellular level, of the metabolic basis of brain imaging. These and other currents in Golgi's thought deserve further study.     

Cajal's brief experimentation with hypnotic suggestion

Spanish histologist Santiago Ramón y Cajal, one of the most notable figures in Neuroscience, and winner, along with Camillo Golgi, of the 1906 Nobel Prize in Physiology or Medicine for his discoveries on the structure of the nervous system, did not escape experimenting with some of the psychiatric techniques available at the time, mainly hypnotic suggestion, albeit briefly. While a physician in his thirties, Cajal published a short article under the title, "Pains of labour considerably attenuated by hypnotic suggestion" in Gaceta Médica Catalana. That study may be Cajal's only documented case in the field of experimental psychology. We here provide an English translation of the original Spanish text, placing it historically within Cajal's involvement with some of the key scientific and philosophical issues at the time.     

Camillo Golgi on the Structure of the Hippocampus

Golgi's only paper on the pes Hippocampi major was published in 1883 and then reprinted and translated a number of times. In it he stated that the fascia dentata provided the best information available to date on how nerve fibers and nerve cells are related. Based on the revolutionary silver chromate method he had introduced a decade earlier, Golgi described two sources of axons from the fascia dentata: one consisted of direct axons from the granule cells, and the other consisted of indirect axons from a diffuse neural net or reticulum that was generated from collaterals of the direct axons. The same basic arrangement was described for Ammon's horn, but neither was illustrated, and it is important to bear in mind that this work was published before the ‘neuron doctrine’ and ‘law of functional polarity’ were elaborated in the 1890s.     

Evolution of the Concept of ‘Extracellular Matrix’ in the Brain

The question as to whether an extracellular matrix exists between cells in the adult brain has been debated since the end of the last century. In the early years, zones containing neuropil and glial processes were mistakenly believed to represent this substance. But Golgi's discovery of the “perineuronal net” paved the way for future study of the true extracellular matrix. In the 1950s, application of histochemical techniques established the existence of interstitial material between nerve cells. Unfortunately the similarity between the pericellular distribution of this material and Golgi's “pericellular nets” was overlooked. The detection of an extracellular volume fraction in the central nervous system furnished further indirect proof for the existence of an extracellular matrix in the brain. However, the repeated failure of electron microscopy to reveal a substantial space between cell processes undermined the acceptance of the concept of “extracellular matrix” in the central nervous system. Nowadays this concept has, however, been firmly established.     

Ramón y Cajal erroneously identified as Camillo Golgi on a souvenir postage stamp

Focusing on a philatelic oddity that erringly identifies a picture of Santiago Ramón y Cajal as that of Camillo Golgi, this brief article examines official and unofficial stamp issues honoring the two great neuroanatomists, one from Spain and the other from Italy, who were early Nobel Prize winners in Physiology or Medicine.     

Book Review

Gustaf Retzius (1842–1919), the Swedish anatomist and anthropologist, and Camillo Golgi were contemporaries. They met on several occasions and came in closer contact when Golgi, together with Ramón y Cajal, was awarded the Nobel Prize in Physiology or Medicine in Stockholm in 1906. Retzius came from an illustrious family. His father was professor of anatomy at Karolinska Institutet and Gustaf himself made a fast career. At 35, he was appointed to a professorship in histology, especially created for him at Karolinska Institutet, and later he became professor of anatomy in the same institution. Retzius was exceedingly productive, and published more than 300 scientific papers, most of which dealt with the nervous system and sensory organs. The majority of these were included in his magnificent volumes Biologische Untersuchungen, Neue Folge (Biological Investigations, New Series), which appeared from 1890 to 1921, and in Das Gehörorgan der Wirbelthiere (“The Acoustic Organ of Vertebrates”, 1881 and 1884), which may be his internationally better known contribution. Much of his work, especially on invertebrates, was based on Ehrlich's methylene blue method, but he also used the Golgi method early on. Particularly his studies of the innervation of the sensory organs became of great importance for the support of the neuron doctrine. His standing internationally was reflected in his membership in many of the most prominent academies abroad, as well as in invitations to him to give a “Croonian Lecture” in 1908 and “The Huxley Lecture” in 1909.     

Some Aspects of the History of the Law of Dynamic Polarization of the Neuron. From William James to Sherrington,from Cajal and Van Gehuchten to Golgi

William James was the first to suggest that propagation of impulses in the nervous system proceeds in one direction, from sensory to motor neurons, but not viceversa. His law of forward direction preceded the formulation of the law of dynamic polarization of van Gehuchten and Cajal, which assumed that nerve impulses are conducted cellulipetally along dendrites and cellulifugally along axons, based on different anatomo-functional properties of these neuronal components. Golgi did not accept the law of dynamic polarization because he believed that dendrites are involved in the nutrition of the neuron rather than in impulse propagation, and that impulses can travel in any direction in the axonal components of the diffuse nerve network. Sherrington in turn experimentally demonstrated that intraneuronic conduction is reversible, whereas, in accord with James's law, propagation of impulses along neuronal chains is irreversible, due to the valve-like action of synapses. The story of the law of dynamic polarization shows that neither Golgi nor Cajal paid much heed to Sherrington's findings and to neurophysiological studies in general, probably because they felt that histology alone could provide the key for understanding the general functioning of the nervous system. It is argued here that this attitude was detrimental to the progress of the neurosciences, because a multidisciplinary approach based on different techniques is inevitably called for in order to develop a plausible theory of the nervous system.     

Egas Moniz and the origins of psychosurgery: a review commemorating the 50th anniversary of Moniz's Nobel Prize

Modern psychosurgery began in 1936 with the work of the Portuguese neurologist, Egas Moniz, who attempted to treat the symptoms of mental illness by severing neural tracts in the frontal lobes. This procedure eventually became widespread and applied to thousands of institutionalized, psychotic patients in the United States and other countries. Despite serious side effects associated with psychosurgery, the apparent importance and validity of the treatment was recognized in 1949 when Moniz received the Nobel Prize for his innovation. Psychosurgery was largely replaced by anti-psychotic drugs in the mid-1950s, and the procedure and its practitioners rapidly fell into disrepute. This article reviews Moniz's career, the factors that led up to his first clinical trials of frontal lobe surgery, and the circumstances that allowed psychosurgery to flourish in the 1940s, eventually leading to Moniz's Nobel Prize.     

Camillo Golgi's Scientific Biography

Born in Corteno, a tiny village in the province of Brescia, Camillo Golgi studied at the University of Pavia where he graduated in medicine in 1865 under the guidance of the psychiatrist Cesare Lombroso who sparked his vocation to study the brain. Golgi then began to learn histological techniques under the direction of the pathologist Giulio Bizzozero. In 1872 he moved to Abbiategrasso as chief of a hospital for chronic diseases. In a rudimentary laboratory he developed the silver-bichromate staining technique, the ‘black reaction’, which was a breakthrough for nervous tissue structure research. While in Abbiategrasso Golgi demonstrated the branching of the axons, and observed striatal and cortical lesions in a case of chorea. He returned to Pavia as Professor of Histology and General Pathology, and made a series of important discoveries that still bear his name: the Golgi tendon organ, the Golgi-Mazzoni corpuscles, another Golgi method to stain nerve cells based on the use of potassium dichromate and mercuric chloride, the canaliculi of the parietal cells of the gastric glands (Müller-Golgi tubules), the Golgi-Rezzonico myelin's annular apparatus (or Golgi-Rezzonico horny funnels), the cycle of malarian parasites (Golgi cycle), the relationship between recurrent malarian fever bouts and the multiplication of the Plasmodium in the blood (Golgi law), the relationship between the vascular pole of the Malpighian glomerulus and the distal tubule, the Golgi's pericellular nets and finally, and most importantly, the cytoplasmic ‘internal reticular apparatus’ (Golgi apparatus). In 1906 Golgi was awarded the Nobel prize for Medicine or Physiology. He died in Pavia on 21 January 1921.     

The house gun: White writing,white fears and black justice (Respond to this article at http://www.therai.org.uk/at/debate)

One way of understanding the Pistorius case is through the powerful writings of white South African authors such as Nobel Prize laureate Nadine Gordimer's anticipatory post‐apartheid novel, The house gun, in which she imagined a scenario similar to the one played out in the Pistorius trial where white fears and black justice met in the courtroom. South Africa is not unique. The mobilization of white peoples' fear of black or brown ‘intruders’ has infected other divided nations, like the United States and Israel. Here the social and architectural construction of ‘white’ settler or settler‐like special enclosures fortified by the legal right to self‐defence with private weapons has reproduced a colonial ‘paranoid ethos’ and a dangerous denial of the violence that is nested like a coiled rattlesnake from within their own segregated and hypervigilant enclosures.     

Neurosciences and research on chemical weapons of mass destruction in Nazi Germany

As a side-product of industrial research, new chemical nerve agents (Tabun, Sarin, Soman) superior to those available to the Allied Forces were discovered in Nazi Germany. These agents were never used by Germany, even though they were produced at a large scale. This article explores the toxicological and physiological research into the mechanisms of action of these novel nerve agents, and the emergence of military research objectives in neurophysiological and neurotoxicological research. Recently declassified Allied military intelligence files document secret nerve agent research, leading to intensified research on anticholinesterase agents in the peripheral and the central nervous system. The article discusses the involvement of IG Farben scientists, educational, medical and military institutions, and of Nobel Prize laureate Richard Kuhn, director of the Kaiser Wilhelm Institute for Medical Research.