Ramón y Cajal and Methods of Neuroanatomical Research

RAMÓN Y CAJAL AND METHODS OF NEUROANATOMICAL RESEARCH Edited and translated by ARTHUR D. LOEWY* Introduction Santiago Ramón y Cajal (1852-1934), more than any other single investigator, has added new dimensions to our knowledge of the organization of the nervous system. His studies laid the foundation for much of our current understanding of neuroanatomy, neuroembryology , and neuropathology. Cajal was born in the mountain village of Pétilla in Spain, and as he recounts in his autobiography [1] his early interests were in art, but his father, a doctor, wanted him to study medicine. However, Cajal's early academic performances were so mediocre that his father removed him from school and apprenticed him first to a barber and then later to a shoemaker. He demonstrated no ability in either field, and in the summer of 1868 he had his first introduction to anatomy when he began the study of osteology under his father's tutelage. He did not study books on bones, but the bones themselves, which were taken from a local cemetery. Cajal's basic tenet concerning knowledge was that one must learn by direct observation and that books are mainly catalogues of names and classifications. Direct observation was also to be Cajal's approach to the nervous system. He eventually completed his university work and went on to obtain his medical degree from the University of Zaragoza in 1873. Cajal's academic work was average, but he developed an interest in dissection of the human body, which he learned from his father. He was appointed an assistant in dissection at the end of his second year in medical school. After graduation, he enlisted in the Spanish army, and upon * Department of Neurosurgery, Mayo Clinic, Rochester, Minnesota 55901. This paper was prepared while the author was at the University of Chicago. Work was supported in part by USPHS grant NS-07376-03. Earlier versions of the manuscript were begun under the direction of Dr. A. L. Berman at the University of Wisconsin, Madison, Wisconsin . The valuable assistance with the references obtained from Miss Virginia R. Reed, formerly reference librarian at the University of Chicago, is kindly acknowledged. Perspectives in Biology and Medicine · Autumn 1971 | 7 completing his military service he returned to Spain to begin his career in anatomy. He succeeded in obtaining a position at the University of Valencia. Cajal's research career began in an attic with just a few reagents, little equipment, and an intense desire to observe and to do original investigative work. His style was unorthodox, and he was unhampered by academic rules or scientific styles. His laboratory was financed from his military savings and by fees collected from private tutoring in anatomy. All he could afford were a few books on histology and subscriptions to a few journals dealing with microscopic anatomy. His laboratory techniques were entirely self-taught. Cajal had no teachers and he wanted none. In 1880, he produced his first publication on microscope observations of inflammation in the mesentery , cornea, and cartilage, and this was followed by a study of the nerve endings in skeletal muscle. Both were illustrated by lithographic plates he had made. A critical event occurred in 1887 when Cajal was asked to participate as a judge for the examinations for professorships in descriptive anatomy in Madrid. By coincidence, one evening while in Madrid he was invited to the home of Dr. Luis Simarro, who had recently returned from Paris. Simarro had obtained some microscopic slides of nervous tissue that were stained with some of the most recent microscopic techniques. It was during this meeting that Cajal was shown examples of nerve cells stained by Golgi's potassium dichromate -silver nitrate method and other neurohistological preparations stained by the Weigert-Pal method for myelin. This demonstration served as the catalyst for Cajal to redirect his research interests. On his return to Valencia, he decided to try the Golgi method because it allowed him to see individual nerve cells impregnated in black against a transparent background of the surrounding tissue. He used this method systematically to study the nervous system, but in his early studies he found that this method was unpredictable. In time, he mastered...