Copyright © 1999 Massachusetts Institute of Technology
Santiago Ramón y Cajal (1852-1934) was one of the most outstanding neuroscientists of all time. He was born in Petil-la de Aragón, a small village in the north of Spain. He studied medicine in the Faculty of Medicine in Zaragoza. In 1883, Cajal was appointed in 1892 as chair of Descriptive and General Anatomy at the University of Valencia. In 1887, he moved to the University of Barcelona, where he was appointed to the chair of Histology and Pathological Anatomy. At the University of Madrid, where he remained until retirement, he was appointed to the chair of Histology and Pathological Anatomy. Dr. Cajal received numerous prizes, honorary degrees, and distinctions, among the most important being the 1906 Nobel Prize for physiology or medicine. To describe the work of Cajal is rather a difficult task, because, unlike other great scientists, he is not known for one discovery only, but for his many and important contributions to our knowledge of the organization of the nervous system. Those readers interested in his life should consult his autobiography (Cajal 1917), where there is also a brief description of his main discoveries and theoretical ideas.
The detailed study of the nervous system began in the middle of the last century. Before Cajal's discoveries, very little was known about the neuronal elements of the nervous system, and knowledge about the connections between its different parts was purely speculative. The origin of nerve fibers was a mystery, and it was speculated that they arose from the gray matter independently of the nerve cells (neurons). This lack of knowledge was due mainly to the fact that appropriate methods for visualizing neurons were not available; the early methods of staining only permitted the visualization of neuronal cell bodies, a small portion of their proximal processes, and some isolated and rather poorly stained fibers. It was in 1873 that the method of Camillo GOLGI (1843-1926) appeared; for the first time, neurons were readily observed in histological preparations with all their parts: soma, dendrites, and axon. Furthermore, Golgi-stained cells displayed the finest morphological details with an extraordinary elegance, which led to the characterization and classification of neurons, as well as to the study of their possible connections. In 1906 Golgi was awarded the Nobel Prize for physiology or medicine for discovering this technique. Cajal shared the Nobel Prize with Golgi in the same year, for his masterful interpretations of his preparations in which he applied the method of Golgi.
Cajal was not introduced to a scientific career under the direction of any scientist, as then usually occurred with most scientists, but rather he became a prominent neurohistologist on his own. The career of Cajal can be divided into three major phases (DeFelipe and Jones 1991).
The first phase extended from the beginning in 1877 until 1887, when he was introduced to Golgi's method. During this period he published a variety of histological and microbiological studies, but they were of little significance.
The second phase (1887-1903) was characterized by very productive research, in which he exploited the Golgi method in order to describe in detail almost every part of the central nervous system. These descriptions were so accurate that his classic book Histologie (Cajal 1909, 1911), in which these studies are summarized, is still a reference book in all neuroscience laboratories. Also, during the first few years of this second phase, Cajal found much evidence in favor of the neuron doctrine, which contrasted with the other more commonly accepted reticular theory. The neuron doctrine, the fundamental organizational and functional principle of the nervous system, states that the neuron is the anatomical, physiological, genetic, and metabolic unit of the nervous system, whereas for the reticular theory the nervous system consists of a diffuse nerve network formed by the anastomosing branches of nerve cell processes (either both dendritic and axonal, or only axonal), with the cell somata having mostly a nourishing role (for review, see Shepherd 1991; Jones 1994).
The third phase of Cajal's career began in 1903, with his discovery of the reduced silver nitrate method, and ended with his death in 1934; this period was devoted mainly to the investigation of traumatic degeneration and regeneration of the nervous system. He published numerous scientific papers about this subject that were of great relevance, and which were summarized in another classic book, Degeneration and Regeneration (Cajal 1913-1914). During this phase, Cajal also published some important papers on the structure of the RETINA and optic centers of invertebrates.
Interestingly, Golgi, as well as most neurologists, neuroanatomists, and neurohistologists of his time, was a fervent believer in the reticular theory of nerve continuity. However, for Cajal the neuron doctrine was crystal clear. Microphotography was not well developed at that time, and virtually the only way to illustrate observations was by means of drawings, which were open to skepticism (DeFelipe and Jones 1992). Some of Cajal's drawings were considered artistic interpretations rather than accurate copies of his preparations. Nevertheless, examination of Cajal's preparations, housed in the Cajal Museum at the Cajal Institute, proves the exactness of his drawings (DeFelipe and Jones 1988, 1992). Although Cajal had the same microscopes and produced similar histological preparations with comparable quality of staining as the majority of the neurohistologists of his time, he saw differently than they did. This was the genius of Cajal.
Cajal, S. R. (1909, 1911). Histologie du Système Nerveux de l'Homme et des Vertébrés, L. Azoulay, trans. Paris: Maloine. Translated into English as Histology of the Nervous System of Man and Vertebrates (N. Swanson and L.W. Swanson, trans.). New York: Oxford University Press, 1995.
Cajal, S. R. (1913-1914). Estudios sobre la Degeneración y Regeneración del Sistema Nervioso. Madrid: Moya. Translated into English as Degeneration and Regeneration of the Nervous System (R. M. May, tran. and Ed.). London: Oxford University Press, 1928. Reprinted and edited with additional translations by J. DeFelipe and E. G. Jones (1991), Cajal's Degeneration and Regeneration of the Nervous System. New York: Oxford University Press.
Cajal, S. R. (1917). Recuerdos de mi Vida, Vol. 2: Historia de mi Labor Científica. Madrid: Moya. Translated into English as Recollections of My Life (E. H. Craigie and J. Cano, trans.). Philadelphia: American Philosophical Society, 1937. Reprinted, Cambridge, MA: MIT Press, 1989.
DeFelipe, J., and E. G. Jones. (1988) Cajal on the Cerebral Cortex. New York: Oxford University Press.
DeFelipe, J., and E. G. Jones. (1991). Cajal's Degeneration and Regeneration of the Nervous System. New York: Oxford University Press.
DeFelipe, J., and E. G. Jones. (1992). Santiago Ramón y Cajal and methods in neurohistology. Trends in Neuroscience 15:237-246.
Jones, E. G. (1994). The neuron doctrine. Journal of History of Neuroscience 3:3-20.
Shepherd, G. M. (1991). Foundations of the Neuron Doctrine. New York: Oxford University Press
Copyright © 1999 Massachusetts Institute of Technology