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40. RAMON Y CAJAL: CHARTING THE NERVOUS SYSTEM

THE STERN fathers at the Latin school in Jaca were agreed: Santiago Ramon y Cajal probably wouldn’t amount to much. According to their report, he was a poor student; he didn’t use his memory; his flair for art was used more often as on outlet for his resentments than for studious purposes; he seemed stubborn and inflexible: no amount of flogging or denial of suppers would change his ways. So, bruised and half-starved, the boy was returned to his father, a country surgeon who eked out a precarious living in the Spanish Pyrenees village of Ayerbe. The busy doctor was both furious and frustrated. He had hoped his body would become a physician, too; but perhaps, as teachers predicted, he was destined only to be a tradesman.

From such boyhood experiences came the young man who was destined to become Spain’s leading scientist, histologist, neuroanatomist, and a personage revered equally by contemporary scientists, by politicians, by educators, and by peasants.

Santiago had been born eleven years earlier, on May 1, 1852, in Petilla, a tiny village high in the Pyrenees. He was the eldest of the rapidly growing family of Don Justo Ramon Casasus and Dona Antonia Cajal. In the Spanish custom, the boy’s surname was compounded of both father’s and mother’s family names – Ramon y Cajal. Young Santiago early learned the advantages of solitude to one whose mind runs in channels other than those locally considered conventional. He was interested in the outdoors; in natural history; and, most of all, in art. He devised many unusual pranks to further his interests, much to the consternation of his father and his neighbors. Repeatedly, the boy was placed in formal schools; repeatedly he was turned out of them as a failure. He preferred painting and hiking in the hills. In between courses, as disciplinary measures, his father had him apprenticed once to a barber, and once to a shoemaker. Finally, Don Justo sent his son to Zaaragoza University and enrolled him in the premedical course.

Fortunately, in the following year, 1869, the elder Ramon received appointment as professor of anatomy on the Faculty of Medicine at Zaragoza. He was at once filled with zeal to train his son as a skilled dissector. Thus, father and son finally found a common interest, and Santiago’s artistic abilities at last were compatible with his father’s ambitions. Together, they studies the anatomy of bones and bodies structures their studies revealed. Proudly, Don Justo thought of publishing his son’s sketches and water colors as an atlas of anatomy; but local facilities in graphic arts were not developed sufficiently to assure satisfactory reproductions.

In 1873, Santiago reached his majority, received his degree as licentiate in medicine, and was drafted into the Spanish army. After service in the medical corps during several strategic but nonsanguine Spanish counterrevolutionary campaigns, he was promoted to a rank equivalent to captain, and was assigned to service overseas in rebellious Cuba. He was placed in charge of an inadequately supplied infirmary at Vista Hermosa, on the edge of swamplands. Santiago soon was suffering along with his patients, from a combination of malaria, dysentery, and poor nutrition. By the spring of 1875, when his request for resignation finally was granted, he was a very sick man. In addition to his infirmities, he had been paid but once during his Cuban service.

After a period of recovery at home, Sangiago Ramon y Cajal was appointed assistant instructor in anatomy at the Faculty of Medicing, University of Zaragoza. In Juna, 1877, he went to Madrid to take examinations for his doctorate in medicine. While in Madrid, he had an experience that was to change his life: one of the professors at the University showed him a microscope and some microscopic preparations. Intensely intrigued, Ramon y Cajal spent his savings for a microscope, a microtome, and a few supplies. Thus, in Zaragoza, he possessed the only good microscopic equipment of which the University could boast.

Life was not to be smooth for the young teacher, however. Weakened by malarial attacks, in 1878 Ramon y Cajal experienced symptoms of active tuberculosis. Another long period of convalescence was necessary. In the course of treatment in Panticosa, nursed by his sister Paula, Santiago took to hiking in the mountains, pursuing his hobby of photography. The combination of fresh air, adequate food, and renewed zest for life helped bring about recovery.

Returning to Zaragoza, Ramon y Cajal received an advancement in faculty position, becoming director of the Anatomical Museum. With this assurance of modest security, the young professor married Dona Silveria Fananas Garcia – much to his family’s consternation. Despite their misgivings, the marriage proved beneficial both to his health and the stability of the young professor’s career. Senora de Ramon y Cajal encouraged her husband’s scientific work while exercising great care over their growing family.

His teaching of anatomy at Zaragoza readily led Ramon y Cajal to develop interesst in histology – the study of tissues. His microscope revealed to him secrets of minute structures hidden from the unaided eye. His equipment consisted of his beloved microscope, a few text-books of doubtful authority, and one or two foreign journals. But to these were added an insatiable curiosity and an ability to concentrate and to work with almost frenzied dedication. His progress in this field is the more amazing in view of the facts: his university appointments up to this time had been undistinguished; he had not met any of the great medical investigators of the day. In his own words, by language and by tradition he was isolated from the main stream of science.

In 1884, Ramon y Cajal was appointed professor of anatomy at the university in Valencia. A cholera epidemic in 1885 diverted his attention temporarily to the study of bacteriology, and his work in this new field attracted some favorable governmental attention. However, he chose to return to the study of histology: and in 1887, he was called to accept the professorship of histology at the University of Barcelona.

In Barcelona, Ramon y Cajal, then 35 years of age, seriously began the work that was to give him distinction and to strengthen his position as a medical researcher. At the beginning, he noted that nearly every published finding on histology was incomplete, and needed further study. This intrigued his curiosity. Also, he had learned from a Valencian neuropsychiatrist, Dr. Luis Simarro, of the chrome silver stain for nerve tissues developed by Camillo Golgi, of Pavia, Italy. Dr. Dimarro, like many other workers, including, eventually, Golgi himself, had ceased using the method, having found it unreliable. Ramon y Cajal’s first important step was to draw upon his experience with photography to make improvements in methods of using Golgi’s stain. Then he began a systematic study of the entire nervous system, staining cells and tissues with a clarity which never had been achieved before. Further, he discovered that far better results were obtained by staining nerve cells of specimens form chick embryos, birds, and young animals, before myelin sheaths formed about axis cylinders of nerve cells, hiding them from the revealing stains. To these techniques he added his other great talent: drawing. His skillful illustrations made it possible for him to demonstrate what he saw. He began, rather timidly, to publish his findings and to disagree with the opinions of histologists in off histologists in other countries. The reaction was skepticism of the validity of his work; and questioning, by some of his own countrymen, as to his audacity in challenging the pronouncements of foreign professors of histology.

To equalize this development, Ramon y Cajal launched upon another phase of his life with intensity equal to his scientific investigation: he joined the German Society of Anatomists; he undertook to learn the German language, so that he could read German medical literature, and communicate in German.

Ramon y Cajal determined to demonstrate his work to his German colleagues. From his meager savings, he took enough to finance attendance, in October, 1889, at a meeting of the German Society of Anatomists at the University of Berlin. Into his bag went the best of his prized microscopic slide specimens and his sketches.

Met only with curiosity and more skepticism, Ramon y Cajal patiently awaited opportunity to demonstrate his findings. First of all, to have a Spaniard among them was regarded by members of the society as without precedent. Spain had no recognized histologists. Further, most of those present were smugly sure of their own concepts. However, the opportunity finally came. With assistance of two or three microscopes, Ramon y Cajal, in broken French, sought to explain his preparations. It was not long before the few men who had been courteous enough to attend the demonstration had shaken off skepticism and were congratulating their courageous Spanish colleague. How, they asked, had be been able to get such results, when they had experienced only failures? He explained his methods. His demonstrations won Ramon y Cajal the support and lifelong friendship of Alber von Kolliker, dean of German histologists; and through him, of Waldeyer, His, van Gehuchten, Bardeleben, Schwalbe, and the Swedish histologist Retzius. Said Killiker: “I am glad that the first histologist Spain had produced is a man as distinguished as you, a man worthy of the nobility of science”.

Ramon y Cajal’s work, now recognized internationally, gained acceptance and appreciation at home. In 1892, he was called to assume the chair of Normal Histology and Pathological Anatomy at the University of Madrid. His new findings received wide publications, and from one country after another came honors. In 1894, he received the highest recognition English scientists could bestow: Sir Michael Foster, secretary of the Royal Society of London, invited him to deliver the Croonian Lecture before that body; and Cambridge University conferred a doctorate upon him.
There was no lack of appreciation of these honors on Ramon y Cajal’s part; he chose, however, to regard them as honors accruing to his homeland rather than to him personally. For himself, he asked only to be allowed to continue his work – and life was to grant him another 40 years of productive activity. He was concerned that his work should continue after him; and indeed it did, in the researches of his more renowned students, among whom were del Rio Hortega, Nicholas Achucarro, Tello, de Castro, Villaverde, Sanchez, his own son Jorge Ramon y Cajal Fananas, and his brother Pedro.

The record of scientific work achived by Ramon y Cajal during his long, active life is most impressive. In 1888, he increased the applicability of Golgi’s stain. In 1903, he worked out his own formula for a silver nitrate stain that demonstrated nerve cells and nerve fibers with clarity. In 1913, he employed a gold sublimate stain for astrocytes that brought another portion of nerve tissue under observation. Subsequently, his pupils carried these studies further with application of a silver carbonate stain. “For the world of the infinitely little,” wrote Garrison, “he was better visioned and consequently had better luck from the start than most investigators; and here, his artistic skill with pencil and brush was a powerful aid.”

Among Ramon y Cajal’s greater contributions to medical knowledge, and to the fields to neurology and psychiatry, according to Garrison, were elucidation “of the developmental and structural basis of the dynamics of the neuron; of transmission of impulse; of localization of function; and of degeneration and regeneration in the nervous system . . . His encyclopedic treatises on neurohistology and on degeneration and regeneration in the nervous system are his master-pieces . . .” He published over 250 scientific papers, edited a journal in his field, and wrote a number of books, including the three-volume Texture of The Nervous System of Man and of the Other Vertebrates(1897-1904), of which a French edition was issued in 1911; Degeneration and Regeneration In the Nervous System, in two volumes (1913-1914); and a two-volume autobiography. These publications have given to medical men and to neurosurgeons an understanding of the cell structure and mode of function of every part of the nervous system, and a better concept of brain structure and of characteristics of brain tumors by which they can be guided in meeting the needs of their patients.

The great scientist was not unaware of the need for balancing the rigors of the laboratory with other interests. His family, grown to include six children, received love and attention. His fascination with photography intrigued him to develop advanced methods, and in 1912 to write a book on color photography. He found much relief and recreation in long walks through Madrid’s parks and suburbs; and in the Spanish custom, nearly every afternoon he visited a favorite café, frequented by his friends, for relaxation and conversation. Out of the philosophic discussions over coffee came an interesting volume of anecdotes and aphorisms, entitled: Coffee-House Chatter.
Despite feelings aroused by the Spanish-American War in 1898, Ramon y Cajal was invited to the United States of America the following year to participate in a celebration at Clark University and to receive an honorary doctorate. In 1900, he received the Moscow prize at the International Medical Congress in Paris; and in 1904, the Helmholtz medal from the Royal Prussian Academy. In 1906, the Royal Caroline Institute of Sweden awarded the Nobel Prize for physiology and medicine jointly to Ramon y Cajal and to Golgi. It was the first time a histologist had been so honored. The medal was presented to him by the Swedish King, Oscar II, at a ceremony in Stockholm. With this recognition came a substantial financial award that was much needed.

In 1922, at age 70, Ramon y Cajal retired from the University of Madrid, closing a 30-year tenure there. But he continued to work, to write, and to guide students from his table in the café. In 1932, a new laboratory was built at government expense and named after him – EI Instituto Ramon y Cajal. He was invited to work in it; however, the rooms seemed too grand and the ceilings too lofty; he preferred the cramped little laboratory in his home at Avenida Alfonso XII. Though deafness and feebleness slowed his pace in his last years, according to Penfield, a former student who visited him, Santiago Ramon y Cajal continued to work with a fierce impatience, elaborating a final defense for the first child of his researches, the neuron doctrine. Also, during his last years, he wrote another significant work, entitle: The World as Seen at Eighty. Death overtook Ramon y Cajal in his eighty-third year, on October 17, 1934.

An insight into the philosophy that drove him on to greater and greater achievements throughout his life is revealed by Ramon y Cajal’s words, in Coffee-House Chatter: “When facts are faced squarely, we must admit that it is not so much the thought of our own death that grieves us as the realization that by it we are snatched from the bosom of humanity and thus robbed forever of hope of seeing the unfolding of the heroic struggle constantly being waged between the mind of an and the blind energy of natural forces.”

Ramon Y Cajal would have liked the Spanish government’s final tribute to his memory: it undertook a complete republication of his written works.