S. Ramón y Cajal, R. G. Harrison, and the Beginnings of Neuroembryology

5. RAMÓN Y CAJAL, R. G HARRISON, AND THE BEGINNINGS OF NEUROEMBRYOLOGY VIKTOR HAMBURGER* Santiago Ramón y Cajal (1852-1934) It is rare that the birth date of a branch of science can be determined rather precisely. The beginnings of modern developmental neurobiology can be traced to the eighties of the last century and to two eminent men: the German embryologist and anatomist Wilhelm His (1831-1904) and the Spanish neurologist Santiago Ramón y Cajal (1852-1934). Of course, the development of the nervous system had been studied before, but the foundations of our present view were laid by these men during the years 1886-1890. Since our focus will be on Ramón y Cajal, he should be introduced briefly to nonneurologists. I rank him among the leading biologists of the last century, a peer to Darwin, Carl Ernst von Baer, Pasteur, Johannes Müller, von Helmholtz. He is the founder of modern neurology, which is also the basis of neurophysiology, neuropathology, and physiological psychology. Almost singlehandedly, he unraveled the design of the central nervous system of the vertebrates and man and traced its structure to the most intricate details. Some of his drawings, all of which bear the stamp ofhis originality, may still be found in modern textbooks, testifying to the amazing accuracy of his observations. His monumental Histologie du système nerveux de l'homme et des vertébrés (1904) is still a standard work. The combination of extraordinary conceptual insight and observational power which characterizes his genius were displayed right at the beginning of his work, around 1887 and 1888, in a breakthrough which liberated neurology from a fallacy that had hindered all progress and at the same time set it on the right track. The then-prevailing conception of the structure of the nervous system was embodied in the reticular theory. It envisaged the nervous system as a syncytial network of nerve ?Professor emeritus, Department of Biology, Washington University, St. Louis, Missouri 63130.© 1980 by The University of Chicago. 0031-5982/80/2304-0134$01.00 600 I Viktor Hamburger ¦ S. Ramón y Cajal and R. G. Harrison fibers which were continuous with each other; the cell bodies were considered as trophic elements, at the intersection ofthe web. The fatal flaw of this theory is obvious: it obviates the establishment of specific pathways and connections, which are the necessary prerequisites of integrated function. Cajal revolutionized the concept of the nervous system by asserting—and demonstrating—that nerve fibers are not continuous but contiguous, that they possess terminal structures which contact other nerve cells but do not fuse with them. The contacts are now called "synapses." The hypothesis of contiguity had been proposed independently , then unknown to Cajal, by two German investigators, A. Forel and W. His. But, as Cajal points out, their hypothesis, based largely on inferences, does not take us much farther than the reticular theory as long as the possibility of diffuseness of contacts is not ruled out. He states: "To settle the question [of contiguity vs. continuity] definitely, it was necessary to demonstrate clearly, precisely, and indisputably the final ramifications of the central nerve fibers, which no one had seen, and to determine which parts of the cells made the imagined contacts" [1, pp. 337-338]. The momentous discovery ofthe synapse was made in 1888. During an investigation ofthe structure ofthe cerebellum ofbirds, he observed that terminal branches of the axons of the so-called stellate cells "applied closely to the bodies of the cells of Purkinje about which they form a kind of complicated nests or baskets" [1, p. 330]. Other synapses of different types were observed in rapid succession, and synaptic contact was recognized as a basic phenomenon. Ironically, Cajal 's success in demonstrating synapses was based on the method of chrome-silver impregnation of nerve fibers which had been introduced by the Italian neurologist C. Golgi, the major proponent of the reticular theory. The same method, later improved by Cajal himself, enabled him to identify specific nerve centers and specific connections of nerve centers on a large scale. The idea that individual nerve cells, or neurons, are the basic units of the structure of...