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.

bibliography

Primary Sources

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.

Secondary Sources

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