Copyright © 1999 Massachusetts Institute of Technology
Camillo Golgi (1843-1926) was one of a generation of great neurohistologists that included Kölliker, Gerlach, Nissl, and CAJAL. For these scientists, the cellular nature of nervous tissue was still enigmatic and controversial, decades after Schleiden and Schwann had promulgated the theory that cells are the basic architectonic units of living tissues. What we now somewhat nonchalantly identify as nerve cells had been visualized as early as 1836 (by Valentin); but, with the techniques then available, the relationship between cell bodies and their protoplasmic extensions could not be clear. A natural interpretation, bizarre as it may now seem, was that nerve cells were nodes, perhaps nutritive in function, embedded within a continuous reticulum of nerve fibers.
Golgi's unique and enduring contribution is generally cited as the discovery of the silver dichromate stain for nerve tissue, which for the first time allowed visualization of nerve cells in their entirety. The actual discovery is surrounded with a certain romanticism, an admixture of luck and perseverance. Golgi, the son of a medical practitioner, had taken his degree in medicine (1865), and spent six years (1865-71) tending patients at the Ospedale di San Matteo in Pavia while also doing research in brain histology in the laboratory of his younger friend and mentor, Giulio Cesare Bizzozero. The actual discovery, however, came while he was first resident physician in the home for incurables at Abbiategrasso. Working in the evenings by candlelight in the kitchen of his hospital apartment (da Fano 1926), he continued the research that led to the new technique. The resulting article, published in 1873 ("On the structure of the gray matter of the brain"), has a refreshing simplicity: "Using the method I have developed for staining brain elements . . . I was able to discover several facts about the structure of the grey brain matter which I believe worth making known" (in Corsi 1988).
The silver stain, although used to advantage by Golgi himself (who subsequently moved to the faculty at Pavia, as professor of general pathology and histology, where he remained until his retirement in 1918), was at first dismissed by the mainstream school of German histologists. In 1887 the Golgi stain was itself discovered by Ramon y Cajal, who used it to impressive advantage in the first great investigations of functional neuroanatomy. Throughout the twentieth century, the Golgi stain remained important in investigations of normative structure and of changes associated with development, pathology, or plasticity. It has to some extent been superseded by intracellular injection of tracers (such as biocytin or horseradish peroxidase), but remains a valuable method for visualizing larger populations of cells and when experimental injection is not feasible (i.e., in most human material). In tribute to the elegance of the original silver methods, high-quality cellular images, immunocytochemical or intracellular, are still evaluated as "pseudo-Golgi" or "Golgi-like."
Golgi further deserves acknowledgment for his role in the early polemics surrounding the NEURON doctrine. This debate was articulated dramatically, almost scandalously from the modern perspective, in the Nobel addresses for 1906, when Golgi and Cajal were jointly awarded the prize in physiology and medicine. Golgi defended the reticularist position, while Cajal championed the neuron doctrine (respectively representing the "continualists" and the "contiguists"; Van der Loos 1967). Golgi's position, in light of the facts, has come to be viewed as archaic, and an unfortunate example of dogma winning out over observation. In his defense, it is worth remembering that synaptic morphology -- and in particular the discontinuity of the pre- and post-synaptic elements -- was not definitively demonstrated until electron microscopic studies in the 1950s (see Peters, Palay, and de Webster 1991). Moreover, at least some of Golgi's reservations can be seen as an arguably legitimate concern about the neuron doctrine in its most stringent formulation. Thus, he makes the interesting distinction between a "nerve cell," which corresponds to a distinct histological entity, and a "neuron," the definition of which, he suggests, should include its functional operation. In the functional domain, the concept of the "neuron" is indeed elusive and continues to evolve even at the present moment.
Golgi's reticularist stance may have derived from a strong conviction in the unified or holistic nature of brain function, or at least a preoccupation with how unity (of perception, of consciousness) can result from individualized elements. So stated, this is not necessarily dissimilar from modern discussions of the BINDING PROBLEM. It is interesting to read Golgi's prose against the backdrop of current work on functional ensembles linked by temporal response properties ("l'action d'ensemble des cellules nerveuses, que j'ai ainsi définée par opposition à la prétendue action individuelle," Golgi 1908; "the group action of nerve cells which I have defined as being opposite to their alleged individual action," Golgi 1967: 202).
Golgi is also known for his discovery of the "internal reticular apparatus" (smooth endoplasmic reticulum or "Golgi apparatus;" see Peters, Palay, and de Webster 1991), and for his distinction between neurons with long or local axons (respectively, Golgi Type I and Type II, also observed early on by Cajal).
In summary, Golgi's silver stain has become, rightly or not, a favorite illustration of the role of serendipity in scientific discovery. It is an early example of the importance of new techniques for advancing the investigation of brain and cognitive processes. The story is also a lesson in the potential deceptiveness of "concrete" images -- whether we read it as a case of missed opportunity and intransigence, or of being right for the wrong reasons.
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Corsi, P. (1988). Camillo Golgi's morphological approach to neuroanatomy. In R. L. Masland, A. Portera Sanchez, and G. Toffano, Eds., Neuroplasticity: A New Therapeutic Tool in the CNS Pathology. Padova: Liviana Press -- Springer (Fidia Research Series 12), pp. 1-7.
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Mazzarello, P. (1996). La Struttura Segreta. Pavia: Edizioni Cisalpino.
Peters, A., S. L. Palay, and H. de Webster. (1991). The Fine Structure of the Neuron's System. 3rd ed. New York: Oxford University Press.
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Van der Loos, H. (1967). The history of the neuron. In H. Hyden, Ed., The Neuron. Amsterdam: Elsevier, pp. 1-47.
Selected Works by Golgi Golgi, C. (1903-1923). Opera Omnia. R. Fusati, G. Marenghi, and S. Sala, Eds., 4 vols. Milan: Hoepli.
Golgi, C. (1908). La doctrine du neurone. In Les Prix Nobel en 1906 Stockholm: P.A. Norstedt and Söner.
Golgi, C. (1967). The neuron doctrine -- theory and facts. In Nobel Lectures: Physiology or Medicine 1901-1921. Amsterdam: Elsevier, pp. 189 - 217.
Copyright © 1999 Massachusetts Institute of Technology