Santiago Ramon y Cajal
Ramón Y Cajal, Santiago
RAMóN Y CAJAL, SANTIAGO
(b. Petilla de Aragón, Spain, 1 May 1852; d. Madrid, Spain, 18 October 1934)
Santiago Ramón y Cajal was born in a poverty stricken and isolated village in Navarre, the son of Justo Ramón y Casasús, a barber-surgeon who some years later—by hard work and considerable sacrifice—acquired a medical degree, and of his wife Antonia. Ramón y Cajal has left us a very full autobiographical record. His early educational experiences were troubled. An interest in art displeased his authoritarian father, who decreed that his son study medicine. The son, predictably, became totally unamenable to any sort of discipline and showed contempt for his teachers and for the whole educational process. Eventually, and possibly aided by enforced apprenticeship to a barber and then to a shoemaker, he acquired sufficient formal learning to enable him to begin the study of medicine at the University of Zaragoza, from which he graduated in 1873. He then joined the army medical service and in the following year was sent to Cuba. There he contracted malaria and within twelve months had to be discharged from the service and sent back to Spain.
Ramón y Cajal determined on an academic career—anatomy was the only subject of his medical course in which he showed any real interest or ability—and spent a further two years at Zaragoza studying for his doctorate. In 1883 he was appointed to the chair of anatomy at Valencia, having in the meanwhile made himself, virtually without aid, a highly competent microscopist and histologist. He had also, while convalescing from tuberculosis, become a skilled photographer. In 1887 Ramón y Cajal was appointed to the chair of histology at Barcelona and, in 1892, to the chair of histology and pathological anatomy at Madrid, which he held until his retirement in 1922.
Cajal was the recipient of numerous prizes, honorary degrees, and distinctions, both Spanish and foreign. In 1894 he was invited to give the Croonian lecture to the Royal Society, and in 1899 he was special lecturer at Clark University, Worcester, Massachusetts. He was elected a foreign member of the Royal Society in 1909. In 1906 he shared the Nobel prize for physiology or medicine with Golgi. He married Silveria Fanañás Garcia in 1880; they had four sons and four daughters.
The picture of Ramón y Cajal that emerges from his own writings is full and candid. Interested in things rather than people, dedicated to neurohistology to the point of obsession, and prepared to submit his wife and family, at least in the earlier years, to considerable hardship while he financed his own laboratory and publications, Ramón y Cajal appears as proud, ashamed of his country’s administrative inefficiency, corruption, and scientific backwardness, ambivalent in that he recognized the need to publish in one of the major scientific languages of Europe, but resented foreign ignorance of the language of Cervantes, and intensely patriotic and determined that Spain should have a place on the scientific and intellectual stage. He succeeded in founding a Spanish school of histology, and his many distinguished pupils included P. del Rio-Hortega, F. de Castro, and R. Lorente de Nó.
In the course of more than half a century from 1880, Ramón y Cajal published numerous scientific papers and an imposing number of books. In the twenty years of his most intense activity, 1886–1906, he may be said to have laid the histological foundations of our present knowledge of the nervous system. He came to study the subject partly because he was systematically teaching himself the whole of histology, but partly also because he saw in the fine structure of the nervous system the material basis of thought and in the elucidation of that structure the answer to many of the problems of physiology and psychology.
Ramón y Cajal found that there was no clear notion of something so fundamental as how a sensory impulse was conducted to a motor fiber, since contemporary histological technique apparently was incapable of defining the course of nerve-cell processes in the gray matter of the central nervous system and, hence, the relationship of one nerve cell to another. He solved this problem by adopting Golgi’s then largely unknown potassium dichromate-silver nitrate technique and applying it to thick sections of embryonic, as opposed to adult, material. The majority of neurologists at this time believed in the reticular theory of nervous interconnection, the only prominent dissentients being His and Forel. Schäfer’s work on Medusa, published in 1878, seems to have been completely ignored.
Ramón y Cajal established first that axons end in the gray matter of the central nervous system in a number of different ways, but always independently and never so as to form a network with other axon terminals. He showed next that although these terminals were in close contact with the dendrites and cell bodies of other nerve cells, there was no physical continuity between one such cell and another. He thus confirmed what had been tentatively suggested by His and by Forel: that the nervous system was an agglomeration of discrete and definable units. The implications for theories of nervous function of such a structural scheme—the neuron doctrine, as it came to be known —are of course profound. It becomes possible to imagine much more clearly the existence of distinct functional pathways, in that a group of axons may be shown to terminate around one group of nerve cells and not another, instead of losing their identity in a reticulum. On the other hand, it poses acutely the problem of how “information” is passed across anatomical “gaps”—synaptic transmission in other words. Ramón y Cajal’s studies at this time, mainly on the cerebellum, spinal cord, retina, and olfactory mucosa, also convinced him of the truth of what he called the “theory of dynamic polarization”: that the transmission of the nerve impulse is always from dendrites and cell body to axon.
Ramón y Cajal’s success in delineating nerve cells all the way to the termination of their finest processes had already enabled him—for example, in the cerebellum and spinal cord—to classify neurons according to the form and direction taken by those terminal fibers. In 1897–1900, having adopted Ehrlich’s methylene blue stain in addition to Golgi’s, he extended his studies to the human cerebral cortex, where he was able to demonstrate the terminal arborizations of the afferent sensory fibers. He again described and classified the various types of neurons in such a way, he believed, as to permit the ascribing of specific structural patterns to different areas of the cortex; hence he was able to place the concept of cerebral localization on firm histological foundations. His descriptions of the cerebral cortex are still the most authoritative.1 They led to the cytoarchitectonics of W. Campbell, K. Brodman, the Vogts, and later workers. Ample tribute has also been paid to the continuing value of his work on the cerebellum.2
If the cell body itself was concerned with conduction rather than, or as well as, mere nutrition, then a knowledge of its fine structure was obviously of importance. Neurofibrils had been described, but their staining was a highly uncertain business. In his autobiography Ramón y Cajal describes how in 1903 he discovered the reduced silver nitrate method for displaying these structures. Although he does not say so, his photographic expertise may well have been a subconscious factor.
In 1904 Ramón y Cajal published Textura del sistema nervioso del hombre y de los vertebrados, in which he brought together the results of the previous fifteen years and which must rank as a classic of medical science. This massive work, more than any other, contains the cytological and histological foundations of modern neurology, yet structural detail is seen never as an end in itself but only as a preliminary to the answering of three questions: What is the functional meaning of this pattern? How does it work? By what physicochemical processes has it reached its present state across the paths of phylogenetic and ontogenetic history?
Ramón y Cajal next turned his attention to the problem of traumatic degeneration and regeneration of nervous structures. He did this in response to what he considered a dangerous revival of the reticularist theory. The main facts had not been in dispute since the work of Waller, Rainier, and others nearly half a century earlier; but there were two schools of thought about precisely how the degenerated peripheral end of the cut axon was restored to structural and functional continuity with its nerve cell. The polygenesists, who earlier had included E. F. A. Vulpian and C. E. Brown-Séquard and whose leader at the time was A. T. J. Bethe, maintained that the regenerated peripheral fibers were the result of progressive transformation and eventual fusion of the Schwann cells which had sheathed the degenerated fibers. The monogenesists, to whom Ramón y Cajal belonged, said that the regenerated fibers were the result of sprouting from the cylinders of the central stump, still in continuity with their nerve cells, and saw their opponents as reviving the reticular theory of nerve continuity in thinly disguised form. Ramón y Cajal, using his reduced silver nitrate method of staining, fully confirmed the monogenesist theory. The results of these researches were collected and published in 1913–1914 as Estudios sobre la degeneración y regeneración del sistema nervioso, still the fullest account of the subject.
Ramón y Cajal had always felt isolated from the mainstream of science, living in Spain and publishing almost exclusively in Spanish; and his isolation was increased by World War I. Nevertheless he continued to publish papers. The most important work of his later years centered on his discovery in 1913 of the gold sublimate method which he applied to the staining of neuroglia, first described by Virchow3 and until recently believed to be merely a supporting skeleton for the nervous elements. This work did much to lay the foundation of current knowledge of the pathology of tumors of the central nervous system.
After formal retirement Ramón y Cajal remained director of the institute which the government had erected and named for him; he also continued to work with the tirelessness and patience which had characterized his adult life.
1. See Edwin Clarke and C. D. O’Malley, The Human Brain and Spinal Cord, 446.
3. See Clarke and O’Malley, op. cit., 84.
I. Original Works. The foreign student of Ramón y Cajal’s original work faces certain difficulties. He wrote some 20 books and 250 scientific papers. Many of his earlier papers were published in Boletin médico valenciano, Gaceta médica catalana and Gaceta sanitaria Barcelona which outside Spain are likely to be found only in the largest and best-equipped medical libraries. Of the early numbers of Revista trimestral de histologca normal y patoldgica financed and largely written by Ramón y Cajal himself, only 60 copies were published and have long ranked as rarities. He himself reckoned that less than one third of his output had been read by foreign scientists. Only 800 copies of his magnum opus, Textura del sistema nervioso del hombre y de los vertebrados, , 3 vols. (Madrid, 1894–1904), were printed. Most workers must use the French trans., altered and brought up to date by L. Azoulay, Histologie du système nerveux de l’homme et des vertébrés, 2 vols. (Paris, 1909). His Estudios sobre la degeneratión y regeneración del sistema nervioso, 2 vols. (Madrid, 1913–1914), was translated into English and edited by Raoul M. May as Degeneration and Regeneration of the Nervous System, 2 vols. (London, 1928).
Of great value and interest for the light they shed on Ramón y Cajal’s personality are Reglas y consejos sobre investigación scientifica, 7th ed. (Madrid, 1935), based on Ramón y Caja’s inaugural address following his election to the Royal Academy of Sciences in Madrid, translated by J. M. Sánchez-Pérez and edited and annotated by Cyril B. Courville, as Precepts and Counsels on Scientific Investigation (Mountain View, Calif., 1951); and Recuerdos de mi vida, 2 vols. (Madrid, 1901–1907), translated (with some abridgment) by E. Horne Craigie with the assistance of Juan Cano, as Recollections of My Life in Memoirs of the American Philosophical Society, 8 (1937), repr. as a book (Cambridge, Mass.-London, 1966). These books contain much good advice; they also exhibit a characteristically late nineteenth-century attitude to science, and a worship of “hard facts” which many no longer find congenial, together with a moralizing on science and scientists which reads less well when one bears in mind the polemical tone of some of Ramón y Cajal’s scientific polemical tone of some of Ramdn y Caja’s scientific papers. For his general outlook on life see Charlas de café; pensiamentos anécdotas y confidencias, por S. R. Cajal (Madrid, 1920), parts of which are trans, in The World of Ramón y Cajal with selections from his non-scientific writings, E. Horne Craigie and William C. Gibson, eds. (Springfield, III., 1968), and El mundo visto a las ochenta años. Impresiones de un arteriosclerótico, 2nd ed. (Madrid, 1934).
Ramón y Cajai’s Croonian Lecture, “La fine structure des centres nerveux” is in Proceedings of the Royal Society of London, 53 (1894), 444–468. A number of his most important papers have been translated into English: “Estructura del asta de Ammion y fascia dentada” in Anales de la Sociedad española de historia natural, 22 (1893), 53–114, translated by Lisbeth M. Kraft as The Structure of Ammon’s Horn (Springfield, III.. 1968); and four papers on the limbic cortex in Trabajos del Laboratorio de investigaciones biológicas de la Universidad de Madrid, 1 (1901–1902), 1, 141, 159, 189, translated by Lisbeth M. Kraft as Studies on the Cerebral Cortex [with Limbic Structures] (London, 1955). His work on the development of various nervous structures, published intermittently over a long period, was collected and translated into French as Études sur la neurogenèse de quelques vertébrés (Madrid, 1929); this French text was translated into English by Lloyd Guth as Studies on Vertebrate Neurogenesis (Springfield, Ill. 1960). Studies on the Diencephalon, compiled and translated by Enrique Ramon-Moliner (Springfield, III., 1966), is an anthology of papers and chapters, including some from the Histologie du système nerveux. Similarly, The Structure of the Retina, Sylvia H. Thorpe and Mitchell Gluckstein, trans. and eds. (Springfield, III., 1972), is based on three texts: “La rétine des vertebres,” in Cellule, 9 (1892) 121–246; the German trans. by R. Greeff, Die Retina der Wirbeltiere (Wiesbaden, 1894); and Ramón y Cajal’s revision of his original article in Travaux du laboratoire des recherches biologiques de l’université de Madrid, 28 (1933).
Ramón y Cajal’s address on receipt of the Nobel prize and useful biographical information are in Nobel Lectures Including Presentation Speeches and Laureates’ Biographies. Physiology or Medicine, 1901–1921 (Amsterdam-London-New York, 1967), 220–267. Not long before he died, Ramón y Cajal published “Neuronismo o reticularismo?” in Archivos de neurobiologia, 13 (1933), 217–291, 579–646, translated by M. Ubeda Purkiss and Clement A. Fox as Neuron Theory or Reticular Theory? Objective Evidence of the Anatomical Unity of Nerve Cells (Madrid, 1954). Translated excerpts from his writings in historical context are Edwin Clarke and C. D. O’Malley, The Human Brain and Spinal Cord (Berkeley-Los Angeles, 1968).
II. Secondary Literature. A. D. Loewy, “Ramón y Cajal and Methods of Neuroanatomical Research,” in Perspectives in Biology and Medicine, 15 (1971), 7–36; F. H. Garrison, “Ramón y Cajal,” in Bulletin of the New York Academy of Medicine, 5 (1929), 483–508; W. C. Gibson, “Santiago Ramón y Cajal (1852–1934),” in Annals of Medical History, n.s. 8 (1936), 385–394; and C. S. Sherrington, in Obituary Notices of Fellows of the Royal Society of London, 1, no. 4 (1935), 425–441.
Douglass W. Taylor
Cajal, Santiago Ramón y
CAJAL, SANTIAGO RAMÓN Y
CAJAL, SANTIAGO RAMÓNY (1852–1934), Spanish biologist.
The reputation of Santiago Ramón y Cajal (1852–1934) as the greatest of the nineteenth-century pioneers of twentieth-century neuroscience seems secure. In 1889, when he showed his most important discovery, the neuron, to the Congress of Anatomists in Berlin, the field of neuroscience had yet to be named. Not long after he died, the neuron doctrine and his other four hypotheses about brain-cell structure and development were the central doctrines of the new field.
Cajal made his mark in the area he called "histology," or the study of tissue structure, a field first laid out by Marie-François-Xavier Bichat (1771–1802) in the early years of the nineteenth century. Histology used the nineteenth century's preeminent tool, the optical microscope, to find and describe the cell structure of tissue like heart muscle, not only to discover how it worked and how it might go wrong but also to essentially classify it, that is, to offer a taxonomy of the different tissues and the cells within those tissues. It was a strongly materialist pursuit, and Cajal was a strong materialist. This was unusual at the time in Spain, a country that was both popularly idealist and officially Catholic.
Cajal had a very tenacious character. His autobiography, Recuerdos de mi Vida (Recollections of my life), recounts a patient pursuit of mastery, starting in childhood, of everything from bodybuilding to championship chess. His earliest ambition was to become a painter. Discouraged by his parents, who he says thought painting "a sinful amusement," and the monastics who were his teachers, Cajal nevertheless mastered drawing skills that were indispensable to histological illustration before microphotography.
The ruling hypothesis of nineteenth-century biology, the 1839 "cell theory" of Matthia Jakob Schleiden (1804–1881) and Theodor Ambrose Hubert Schwann (1810–1882), reduced all living things to separate parts, but most of the central nervous system looked like a partless mass to nineteenth-century scientists. The central nervous system in Homo sapiens, which is now known to contain something on the order of ten billion separate cells with perhaps a trillion connections, appeared to leading investigators like Rudolf Albert von Kölliker (1817–1905) to be a tangle of fibers, interrupted only occasionally by recognizable cells. Massed fibers were dubbed "gray matter" and "white matter," the fibers usually thinning down beyond the resolving power of optical microscopes, even those with oil-immersion lenses. Microdissecting the fibers seemed beyond human skill. Otto Deiters (1834–1863) died young after years of teasing apart the neural net under a microscope using threadlike needles, but he did leave notes about axons (extended, single fibers) that did not branch and tiny "protoplasmic processes" (now called "dendrites") that branched out from them. Some histologists fixed on the chemical dyes and stains that might make nerves stand out against their cloudy background by coloring only one or two at a time, but the dyes proved unpredictable and unreliable. If they worked once they might not work again. In the spirit of trying everything, in 1872 Joseph von Gerlach (1820–1896), the inventor of the carmine dye, tried gold.
In the end, however, it was not gold that did the trick, but silver: silver nitrate, in fact, the chemical that made photography possible at the beginning of the century. The Italian histologist Camillo Golgi (1843 or 1844–1926) was the first scientist to use it productively, publishing his first papers "on the structure of the gray matter" in summer 1873. He used a soak of potassium bichromate, to which he added a dilute solution of silver nitrate. The bichromate already in the cells reduced the silver nitrate to metallic silver, which precipitated and stained the inside of the entire cell black, magnificently distinct against the yellow left by the chromates. Somehow it could stain cells in the middle of a three-dimensional cube of tissue, one cell at a time, all the way out to their ends, so that they stood out clearly. The stain was very temperamental. Golgi never stopped working on it. His most comprehensive work, published in 1886, would lead to a Nobel prize in medicine in 1906.
Working as an assistant in the Zaragoza Medical Faculty in 1880, Cajal used gold-chloride staining in his first published paper and suggested ammoniacal silver nitrate in his second. As a professor of histology at the University of Valencia in 1883, he had no colleague who knew Golgi and his stain. Cajal saw the Golgi technique only in 1887 when he paid a visit to Madrid before joining the faculty at Barcelona and saw examples of silver-bichromate staining in the house and lab of Luís Simarro Lacabra (1851–1921), who had just returned from France. He immediately gave up all other methods and improved on this one in 1888 by making two separate soaks out of what had been a continuous procedure. Cajal found his method just in time. The extraordinary hypothesis that the entire mass of the central nervous system was composed of the extensions of separate and distinct cells had already been advanced in October 1886 by Wilhelm His (1831–1904) of Leipzig, in January 1887; by Auguste Henri Forel (1848–1931), the Director of the Burghölzli Asylum in Zurich; and four months later in Oslo, Norway, by Fridtjof Nansen (1861–1930) in his Ph.D. thesis, just before he set off for Greenland. Their proof was unsatisfactory, however, and in 1887 the old hypothesis that all the nerve fibers of the gray matter were mutually connected in a single network, the so-called reticular hypothesis (from Latin reticulum, network), was still being vigorously promoted by von Gerlach, the pioneer of carmine and later of gold chloride, and subscribed to by most histologists, including the budding neuroanatomist Sigmund Freud (1856–1939) and his mentor Theodor Meynert (1833–1898) in Vienna. Its great champion was in fact none other than the discoverer of silver-chromate dye, Camillo Golgi himself. "Ruled by the theory," Cajal remembered, "we who were active in histology then saw networks everywhere." It was a beautiful theory and, he wrote, "as always, reason is silent before beauty" (Recollections, p. 303).
In 1888 Cajal set up a laboratory in the back room of his house in Barcelona and made one more change in the method, using unhatched chick brains to study the central nervous system, which in vertebrate embryos is incomplete at birth. Some nerves have grown dendrites and axons, but not all are fully extended; and the "glial" cells have hardly begun covering the nerve extensions with myelin. Even the Golgi stain works better in embryos. Cajal was able to see very long unmyelinated axons whose tips came up close enough to another cell to touch it but never actually penetrated, or even touched, its cell wall. His conclusion: the famous central network, "that sort of unfathomable physiological sea, into which, on the one hand, were supposed to pour the streams arising from the sense organs, and from which, on the other hand, the motor or centrifugal conductors were supposed to spring like rivers originating in mountain lakes" (Recollections, p. 336) did not exist at all. The right metaphor was not hydraulic but electronic, something like a contemporary telephone exchange.
In 1889 Cajal brought his new idea, together with the indispensable hard-won proof, to the anatomists' conference in Berlin. The patriarch of the society, Rudolf Albert von Kölliker (1817–1905), swept Cajal into his carriage, took him to his hotel, and gave him a dinner, promising to have everything Cajal wrote published in Germany. In 1891 the formidable Berlin expert Heinrich Wilhelm G. von Waldeyer-Hartz (1836–1921) published a series of six long articles in the German Medical Weekly in which he attributed the new gray-matter-discontinuity hypothesis to Cajal and gave it the name neurone doctrine. The publication secured Cajal's scientific reputation for the rest of his life. News of his discovery passed beyond the small world of histology and became an example of "science," ever progressing in the nineteenth-century manner. In 1894 the British Royal Society offered him its most prestigious award in biology, the Croonian Lectureship, at the behest of England's leading neuroanatomist, Charles Scott Sherrington (1857–1952). In 1899 Cajal was among the presenters at Clark University's anniversary international conference in Worcester, Massachusetts, ten years before Freud received the same honor.
In the 1890s Cajal advanced and provided evidence for four additional hypotheses about the nervous system. The first of these, which has acquired the name of the Law of Dynamic Polarization, asserts that the axons of nerve cells are always outputs for nerve impulses and that dendrites are always inputs. The second hypothesis is the idea that neurons grow from the ends of the axons at a point analogous to the root hair of a plant. Cajal found this in chick embryos in 1890 and called it the "cone of growth." The third of these ideas Cajal advanced in 1892 and eventually called the "Chemotactic Hypothesis," that the growth cones of axons find their way along one trajectory instead of another by following trails of chemicals already laid down among the other nerves. These three hypotheses are now conventional wisdom so taken for granted that Cajal's name has become completely detached from them and they are taught as if anatomists had always known them. Not that Cajal himself ever found a proof for them, or indeed had anything in his experimental repertoire that could have provided one. Cajal's fourth hypothesis, however, remained very much in the center of debate in the last decade of the twentieth century—the Decade of the Brain. This is the view that the phenomenon we call memory is a product of particular states of the entire central nervous system. Memory, thought Cajal, was not the effect of some chemical or of changes in one or a few nerve cells. It was, he thought, a global property of the brain as a whole. The mind may not govern, as the nineteenth-century thought. It may simply "emerge," an undetermined consequence of the simple interactions of more than ten billion cells making a trillion connections.
In 1906 Cajal's disciple Sherrington coined the word synapse to describe the gap at the junction between one nerve cell and another. In the same year Cajal was awarded half of the sixth Nobel prize in medicine. The other half went to Camillo Golgi, who met Cajal for the first time at the ceremony. The next day Golgi gave his Nobel acceptance lecture and the day after that, Cajal gave his (both in French). Golgi's lecture, "The Neuron Doctrine, Theory and Facts," was a sustained attack on the independence of the neuron. Cajal's address, "The Structure and Connexions of Neurons," was a sustained defense of the same idea.
The neuron doctrine is a twentieth-century idea that emerged in a nineteenth-century context. Separate and atomized units, interacting without an overall plan, give rise to minds as well as molecules, neither entirely predictable.
See alsoScience and Technology.
Cajal, Santiago Ramón y. Histologie du système nerveux de l'homme et les vertebras. 1909. Translated by L. Azoulay. 2 vols. Paris, 1911. Cajal's definitive textbook on neuroanatomy.
——. Recollections of My Life. Translated by E. Horne Craigie. 1937. Cambridge, Mass., 1989.
——. Cajal on the Cerebral Cortex: An Annotated Translation of the Complete Writings. Edited by Javier DeFelipe and Edward G. Jones. New York, 1988.
——. New Ideas on the Structure of the Nervous System in Man and Vertebrates. Cambridge, Mass., 1990.
Cannon, Dorothy F. Explorer of the Human Brain: The Life of Santiago Ramón y Cajal (1852–1934). New York, 1949.
Everdell, William R. "Santiago Ramón y Cajal: The Atoms of Brain, 1889." In The First Moderns: Profiles in the Origins of Twentieth-Century Thought, 1872–1913. Chicago, 1997. Reprinted in Jennifer Blaise, ed., Twentieth-Century Literary Criticism, new edition. Detroit, 2000.
Grisolía, Santiago, et al., eds. Ramón y Cajal's Contribution to the Neurosciences. New York, 1988.
Hydén, H., ed. The Neuron. Amsterdam, 1967.
Marijuán, Pedro C., ed. Cajal and Consciousness: Scientific Approaches to Consciousness on the Centennial of Ramón y Cajal's Textura. Proceedings of a November–December, 2000 Conference. New York, 2001.
Shepherd, Gordon M. Foundations of the Neuron Doctrine. New York, 1991.
William R. Everdell