SOURCE: "Santiago Ramón y Cajal (1852-1934)," in Annals of Medical History, Vol. VIII, No. 5, September, 1936, pp. 385-94.

[In the following essay, Gibson details Ramón y Cajal's life, work, and influence on the field of medical science.]

The ideal of science is to elucidate the dark mysteries and unknown forces which invest us, for the benefit of our descendants, and to make the world more agreeable and intelligible, while we ourselves are forgotten like the seed in the furrow.—CAJAL.

The beginning of the second half of the nineteenth century saw Helmholz, Ludwig, Virchow and Claude Bernard laying the foundations of scientific medicine. The new discoveries in physiology had been the signal for a concerted study of the minute structures of the body. Little was it realized that a new figure, Ramón y Cajal, had appeared on the horizon, in the far-off village of Petilla in the Pyrenees.

Cajal was born of the hardy peasant stock of Upper Aragón and Navarre. His father, a "surgeon of the second class," was famed throughout the mountains for his surgery, and not less for his hunting. Despite the greatest hardships, he entertained the burning hope that he might some day achieve the doctorate in medicine and surgery, and that his son Santiago should become a good doctor. In a tribute to his father written years afterwards, Cajal has said:

He bequeathed to me his moral qualities to which I owe what I am; the religion of the sovereignty of the will, faith in hard work, the conviction that a spirit of steadfast and unrelenting determination is capable of moulding and integrating everything from the muscle to the brain, making good the deficiencies of Nature and even overcoming the misfortunes of character, the most niggardly and refractory phenomena of life. It was from him also that I acquired the commendable ambition to be something, and the resolution neither to consider any sacrifice too great for the realization of my aspirations nor ever to change my course for any secondary considerations.

The earliest recollections of Ramón the younger were of the Spanish victories in Africa in the eighteen hundred and fifties, of a lightning storm which destroyed the school, killing some of the pupils, and of an eclipse of the sun. By the age of four he was learning French under his father's tutelage in a smoky shepherd's cave near his home in Valpamas. When only six years old he had, in addition to ideas of arithmetic and geography, a capacity for writing correctly, and on one occasion acted as scribe for his family during his father's absence in Madrid. An insatiable desire to observe and to sketch birds often led to the most dangerous excursions along the cliffsides, which, together with long absences from the village, caused his mother much anxiety. His ingenuity in fashioning cages of willows was rewarded in a collection of twenty kinds of birds and of innumerable eggs. In many ways Cajal's early years are reminiscent of the boyhood of another young naturalist, surveying ponds and woods for animal life in Ontario, William Osler.

When eight years of age the boy moved with his family to the town of Ayerbe; in order that his father might have a better practice and that the "children might have a better education." Santiago's artistic instinct came to the fore as he sketched the castles and the ravines of this quiet countryside, now a national park. Because his family abominated this "useless distraction" he was forced to buy his crayons and paper secretly, and to go out into the surrounding country to sit by the road; drawing the peasants passing by with their tiny mule carts. But when he could not buy colours he had the most ingenious methods of scraping paint off stone walls, or of soaking the bright dye stuffs out of the covers of books of cigarette paper. His artistic exploits were effectively stopped when an "authority" commissioned to decorate the church walls declared that Santiago's attempt at painting St. James the Apostle was a "crude daubing" and concluded "the boy will never be an artist."

He begged his father to send him to Huesca or to Zaragossa where he might attend a drawing school; but his father wanted him to study the classics in preparation for a medical training. The boy was sent off to the school of the Aesculapian Fathers at Jaca, a mountain town. The description of this school experience which Cajal has left us is too ghastly to bear repetition in the twentieth century. Memorizing Latin verbs was nauseating to him; and was like "hammering nails into a wall." He was shamefully flogged and beaten, and starved in a dungeon as an impetus to the loathsome work of memorizing. After five months of disgraceful torture he was withdrawn from school in a sorry condition.

During months of recuperation he planned a great wooden cannon with which to seek revenge. All the neighbourhood came to see a trial shot and the explosion was of such proportions that the boy was sentenced to jail for three days, and on the recommendation of his father was deprived of food. Unable to tolerate the jeering crowds outside his cell, he hurled stones at them through the bars.

Next he was given a trial at the Lyceum, Huesca, where mathematics and science were well taught. Safely placed in a family of the village by his father, he lost no time in finding subjects to paint, to the utter neglect of his studies. On passing his terminal examinations he returned home to Ayerbe where he retailed to his former comrades stories of his adventurous and unencumbered year "abroad." His father, however, decided that Santiago would do well to spend his vacation rereading all his school textbooks to make up the evident deficiencies, and to this end he allowed him to work in the solitude of an unused pigeon house. Needless to say a means of escape was found, leading through the granary outside, to freedom.

A friendly confectioner in the town had, in his attic, a large number of books which he allowed Ramón to peruse. How great was the boy's surprise and delight on finding "Don Quixote," "Robinson Crusoe," and the "Voyages of Captain Cook" along with several volumes of Hugo, Dumas, the comedies of Calderon, and the poems of Quevedo! In a short time he produced a miniature Robinson Crusoe, under the influence of these romantics.

Returning for his third year at Huesca, in company with his brother Pedro, Santiago was apprenticed by his father to a barber, while his brother was located in the usual manner with a town family. Ramón the elder was determined that should everything else fail, his son should at least have the status of a hairdresser, as well as an acquaintance with the phylogeny of the art of surgery. In later years Cajal often remarked how much he owed to this experience, but at the time it was irksome and hateful to be "a romantic apprenticed to a barber." Rebelliously he joined the town vandals and became a notorious ruffian with great agility at stripping orchards and scaling walls. After bating the professor of Greek for a term, and making little progress with his work, he returned to Ayerbe to enter an apprenticeship under a rather dour cobbler. A more progressive shoe-maker induced the family to allow the boy to work with him for a year, and the former village ruffian became a most adept craftsman.

This year of interesting work was followed by another fling at school, this time at a drawing school. It was not long before all the stock models for drawing had been exhausted, and the art teacher, greatly taken with the boy, journeyed the considerable distance from Huesca to Jaca to try to convince the father that the boy's future lay in art. But it was not to be, and Santiago was again refused, with the result that he again became unruly at school. One night while passing along the Santa Domingo he saw by the light of the moon a freshly whitened wall, whose attraction he could not resist. With a piece of charcoal he drew a most malicious caricature of the much-disliked professor of psychology, with sad results in his viva voce examination. He became so defiant in the end that he joined a group of young adventurers and packed off in the bravado fashion into the hills to "begin anew," only to return in a short time a vanquished Don Quixote.

The father then capitalized on the boy's interest in drawing, and induced him to study osteology. After the manner of the time, this sixteen-year-old student made his first acquaintance with the bones of the human frame in a cemetery by moonlight. As he packed the white objects into a sack and climbed the wall he could hear the rattling voices of departed spirits screaming curses on these "profanateurs de la mort." In the granary the father gave all his leisure time to teaching Santiago, whose single purpose was to sketch bones, from every angle, and to try to explain their function. In two months he was able to name all the minute foraminae in the skull, together with the structures passing through them. With a truly amazing grasp of anatomy, he was matriculated at the medical school in Zaragossa, to study for the licentiate.

In a short time Ramón the elder moved to Zaragossa to join the staff of the medical school, where he became an ardent and renowned teacher of anatomy. His son, through diligent study and dissection, became an assistant in the anatomy laboratory in his third year, and prepared a large atlas of human anatomy. Because of the technical difficulties in printing such a large volume of colour plates, the book was never published. (Some of the plates are preserved at the Instituto Cajal, in Madrid, while the remainder are in the library of Cajal' s brother, Pedro Ramón, professor emeritus of gynecology at Zaragossa.)

Eighteenth century vitalism still reigned in this medical school, the teaching in obstetrics was entirely oral, and to Cajal's dismay the greatest emphasis was still placed on book learning. His studies therefore contributed little to his development, and he had "three manias" outside the university: literature, gymnastics and philosophy. Of the first we know little except that he wrote, in company with many youthful spirits of this first liberal period in Spain, many poems, and even a novel under the spell of Victor Hugo.

Because he was defeated in a test of strength with a fellow student, Cajal took up gymnastics of the most vigorous sort, exchanging lessons in muscle physiology with the trainer of a local athletic club. Having developed his biceps to an unbelievable size, and his chest measurement to 45 inches, he found that on attempting to study at night his head "dropped on the books with the weight of a paper press." It seemed to him that individuals as well as nations tended to become bellicose as their physical forces increased.

His mania for philosophy was in part a reaction to his regime of gymnastics and their enforced solitude, and in part to the early revolution in the 1870's. After exhausting the university library in metaphysics he finally adopted what he describes as "absolute idealism."

After gaining the licentiate in medicine, without distinction, the young doctor joined the medical corps to serve his military year. After eight months of pursuing insurrectionists in Spain he was made a captain and sent to Cuba. But the New World presented no primeval forest and no freshness; in fact it was a sad scene of inefficiency and lack of organization, a waste of men and supplies. At the hospital at Puerto Principe Cajal contracted malaria and tuberculosis, and was forced to return to Spain in 1875.

For the next two years he carried on dissection and clinical work with his father, and was given a temporary appointment in the faculty at Zaragossa. For the doctorate of the University of Madrid he had to attend examinations in the history of medicine, analytical chemistry, and in normal and pathological histology. Having studied the last subject with the aid of textbooks only, he was somewhat overcome on being shown his first microscopic preparations in Madrid by Maestre de San Juan. Passing the doctorate with ease, he hastened back to Zaragossa to set up a histological laboratory, and for the purpose secured an old microscope, long forgotten in the Department of Physiology. A friendly professor showed him for the first time in his life the circulation of the blood, in a frog. Immediately his imagination was fired with the possibilities of microscopic study. He spent all his army pay from Cuba on a Verick microscope and a few reagents, to be followed later by a Ranvier microtome which he had seen in Madrid. His first books were Beale's "Microscope in Medicine" and "Protoplasm and Life," which, with Henley's "L'Anatomie Générale" and Ranvier's "Manuel de Technique d'Histologie," may still be seen in the Instituto Cajal. Despite the reproach of the professors at Zaragossa that microscopic anatomy was "celestial and fantastic," Cajal began his examination of the body tissues, beginning with muscle and skin, and leaving the nervous system to the last.

Hardly had he received the appointment as Director of the Anatomical Museum at Zaragossa than he was seized with three severe haemoptyses, and was forced to recuperate for an unbearably long time at San Juan de la Peña. Here he became completely absorbed in photography and discovered a method of making bromide plates, far superior to anything then existing in Spain. This method led to a photolithographic application used to illustrate his earliest publications in Zaragossa. These consisted of a study of tissues in inflammation (1880) and one on the nerve endings in voluntary muscle (1881).

The professors at Zaragossa considered the microscope an impediment to the future progress of biology and cared little for Cajal's research in the meagre laboratory in his home. Some even remarked, "Who is this Cajal to pass judgment on foreign savants?" Little wonder indeed that Cajal competed for the vacant chair of anatomy at Valencia. This he successfully won, and commenced his work at the small salary of five hundred dollars. Having already married on the merest pittance he now felt himself a man worthy of a larger microtome, and at least one new foreign microscopical journal.

Of these trying but hopeful days he has written in his Recuerdos de mi vida and has given us the following paragraph about his wife:

Eulogies do not flow readily from my pen, but I delight to say that, with beauty which seemed formed to shine in promenades, visits and receptions, my wife cheerfully condemned herself to the obscurity of my lot, remaining simple in her tastes, and with few aspirations other than tranquil contentment, order and system in the management of the home, and the happiness of her husband and her children.

On taking up his post at Valencia he avowed his intention of gaining international recognition within ten years, saying: "It is a disgrace that among so many thousands of discoveries in anatomy, there is not one to which the name of a Spaniard is attached." With an inner urge and fury he threw himself into his investigations and his "inspired curiosity" unravelled many of the mysteries of the nervous system. Because he was miserably poor he used small animals, chiefly mice, and put a dozen different specimens on a slide.

The cholera epidemic of 1894 brought Cajal into prominence as a microscopist, and the Central Committee presented him with a fine Zeiss instrument for his work in his former home at Zaragossa. With a staining method of his own he was the first in Spain to show the causal relation of the Koch (comma) bacillus.

At the age of thirty-five he exchanged his professorship for the chair of histology at Barcelona. "Isolated by language and tradition from the main current of science he had grown and ripened in Spain in the leisurely tempo of life in Latin countries." From Dr. Luis Simarra, a psychiatrist in Madrid, Cajal learned of the Golgi chrome-silver method for staining nervous tissue, which Simarra had discarded as capricious. A modification of this technique, and its application to innumerable specimens, showed a new world for research. Cajal's systematic study and masterly drawings meant little to a doubting Europe. Recognition came only after a demonstration of his preparations, chiefly of retina and cerebellum, before the German Society of Anatomists in Berlin. Kölliker was so impressed with what he saw, that he immediately took up the silver methods and confirmed Cajal's earlier work. Returning triumphantly from Germany, Cajal won the professorship of histological and pathological anatomy in the University of Madrid. At the age of forty he was just beginning. The next forty years were to be his best.

The Royal Society of London invited the newly appointed professor to give the Croonian Lecture for 1894, a very high honour following such men as Virchow and Kölliker. The lecture, which he gave in French, on "La structure fine des centres nerveux" was enthusiastically received by English physiologists. Visits were paid to the laboratories of Ferrier, Mott, and Horsley along with his host, Prof. Charles Sherrington. His visit occasioned much celebration, and he received an honorary doctorate at Cambridge, and was later made a Foreign Member of the Royal Society, the first Spaniard to achieve the honour in a century and a half. It has been recounted that while in London, Cajal converted his bedroom, in the home of Professor Sherrington, into a miniature laboratory with the cupboards full of specimen bottles and slides. On the day set for conferring his degree at Cambridge, Cajal arrived much earlier than was expected, and wandered into one of the beautiful college gardens, where he was lost until perilously near the degree ceremony.

In 1899, along with four other European savants, Mosso, Forel, Picard and Boltzmann, Cajal took part in the Decennial Celebration at Clark University, at Worcester, Massachusetts. He gave three discourses on "The Comparative Study of the Sensory Areas of the Human Cortex" and demonstrated his microscopic preparations to his interested admirers. Despite the fact that the Spanish-American war was but a year past, he characterized America as the "home of tolerance and freedom," and remarked upon the lack of prejudice in the new schools of scientific work. An honorary degree was conferred on him, not so much because of his position as rector of the University of Madrid and life senator of Spain, but rather as a distinguished investigator in the field of neurology.

Returning to Spain he was made the first director of the Instituto Nacional de Higiene de Alfonso XIII. Then there followed the "Moscow Prize" for medical research, presented at the International Medical Congress which met in Paris in 1900. In 1906 Cajal shared the Nobel Prize in Medicine with the brilliant Italian neurohistologist Camillo Golgi. The presentation in Stockholm was notable for the lecture which Cajal gave, in which he was profuse in his tributes to his elders, among them Golgi, Kölliker, Van Gehüchten, and especially the native Retzius.

Following these international honours came latent recognition at home. Although offered the Ministry of Public Instruction in the Spanish cabinet, Cajal wisely refused. Medals were struck in his honour by the Spanish medical students. In the Bueno Retiro Park, near his favorite walk, the citizens of Madrid erected a statue, depicting the great biologist gazing into the pool of everchanging life.

A stamp issue was proposed in his honour, but he opposed it as long as he lived. After his death in 1934, a very artistic stamp was produced, portraying the man and his microscope. Many pictures of Cajal have appeared at various times, but none so interesting as those which he always retouched with his pen before presenting them to visitors at his laboratory.

But these years marked by honours were also years of unceasing work. A Spanish school of histology was being built up, which has come to include such men as Rio-Hortega, the late Nicholas Achucarro, Villaverde, Sanchez, De Castro, Wilder Penfield, Director of the Montreal Neurological Institute, and Tello, Director of the Instituto Cajal, Madrid. By developing the silver nitrate and gold stains for the cells of the nervous system, Cajal brought our knowledge of the most delicate mechanism in the human body to a new level. "Years from now, investigators unfamiliar with them will no doubt continue to rediscover what Cajal found at the turn of the century." How often we have failed to give this man his due. With arduous and endless microscopic preparations he reduced the "forest" of the nervous system to an intelligible order, from which has emerged Cajal's greatest contribution, his "law of the polarization of the nerve cell." This is the fundamental conception underlying all our clinical and physiological work today.

The later years brought less laboratory work for Cajal but his restless pen elaborated former discoveries in support of his original hypothesis of the discontinuity between the units of the nervous system. Though the government built him the massive new Instituto Cajal, he would not leave the meagre laboratory in his home, where he had spent half his lifetime.

The publications of the man are perhaps his greatest and most lasting contribution to science and literature. Beginning in Barcelona he published the Revista Trimestral de Histología Normal y Patológica in which his own researches as well as those of his pupils were communicated. With the move to Madrid the journal became the Revista Trimestral Micrográfica, and has since become the familiar Trabajos, or Travaux, of the Laboratory of Biological Investigation of the University of Madrid. The change from Spanish to French in the publications was made in the hope that the work of his pupils would be more widely recognized than his own had been.

Among his 286 contributions the best known is the three-volume work, Textura del sistema nervioso del hombre y de los vertebrados, published first in 1904 and translated into French in 1909. His work, Degeneration and Regeneration of the Nervous System, is the most complete treatise on the subject ever written. Its publication was made possible by a large subscription collected by the Spanish physicians and surgeons in the Argentine. His monumental Histology of the Nervous System in two volumes contains 925 original illustrations. Besides a handbook of histology which he, like Osler, wrote for his first students, he has contributed many original observations in his book on colour photography. It is to be hoped that with American and European support it will be possible to republish the early works of this benefactor, and to make his contributions to knowledge and literature more widely known.

Cajal's autobiography, Recuerdos de mi vida, has become a classic in Spain, and its early chapters are used as a Spanish text in many American colleges today. For his literary works, he was presented, along with Menéndez Pidal, for an honorary doctorate at the Sorbonne in 1924.

As a "diastole of rest" after a "systole of work," Don Santiago, as he was known, loved to sit with his friends in the sidewalk cafés, discussing the news of the capital. His pen often became restless and covered the table-cloth with sketches, just as it spattered his library wall with ink, when, in his last year, he was propped up in bed, writing polemics reminiscent of his younger days.

From his charming Charlas de cafe (Coffee-house Chatter) the following extracts have been made:

Reality overruns every concise phrase, like liquid poured into a tiny cup.

Grey matter abounds in countries with grey skies.

Genius, like the inhabitants of the depths of the sea, moves by its own light.

Only the doctor and the dramatist enjoy the rare privilege of charging us for the annoyance they give us.

Let the vicious and idle say what they choose, agreeable and useful work remains the best of distractions.

As long as our brain is a mystery, the universe, the reflection of the structure of the brain, will also be a mystery.

In his Rules and Counsels for the Scientific Investigator (translated into German by Professor Misckolczy) we find many interesting passages, a few of which follow:

The emotion lights the cerebral machine which acquires by it necessary heat, the forge where fortunate intuitions and hypotheses will be wrought.

No one ignores the fact that the one who knows and does is valuable compared to the one who knows and goes to sleep.

The sincerest and the most devoted scientist remains profoundly human; in his life for his fellow beings he exceeds the best, expanding his usefulness beyond present and local conditions. Thanks to these men of singular talent whose sight penetrates into the shadows of the future, and whose exquisite sensibility makes them regret the errors and the stagnation of routine, in scientific progress, only the genius can have the privilege of opposing the current and modifying the moral medium. His mission is not the adaptation of his ideas to those of society but the adaptation of society to his ideas, and if he is right (as he usually is) and proceeds with prudence and energy, without dismay, sooner or later humanity will follow him, applaud him and cover him with glory. Trusting in this pleasing tribute of veneration and justice, every investigator works with confidence because he knows that if individuals are capable of ungratefulness, communities very seldom are, if they reach full consciousness of the reality and utility of an idea.

Thus lived and wrote the colourful Don Santiago. Since his death in October, 1934, many tributes have been penned, none more aptly than that by Sir Charles Sherrington:

He had come to stand in some sort as a symbol of national cultural rebirth. Despite, perhaps partly because of, his retired and simple life and his advanced years, he and his scientific devotion and prestige were taken to typify to many of his fellow countrymen what a new Spain might cherish and accomplish; he was taken as a sort of forecast of what a new Spain should stand for. In this sense he caught the national imagination.

This man, whose name was magic for the Spanish peasant as for the struggling research worker, has been fittingly memorialized:

Where he found stagnation and a complete lack of interest in science he has left active universities, and a modern outlook. A true son of Spain, and the most modest of men, his chief, perhaps his only interest in the honours which he received was that through him, Spain was honoured.

Today there is rising a new University City on the edge of Madrid where 25,000 students will eventually come for an education, one-fifth of them in medicine. On a hill overlooking the capital, stands the new Laboratory of Normal and Pathological Histology, opened on the first anniversary of Cajal's death. Here are to be found men from the far corners of the earth, purusing post-graduate study under Pio del Rio-Hortega, one of the emerging national figures of the new Spain. A portrait of Cajal hangs in the large laboratory, with the following scrawled on it:

"It has been said many a time that the problem of Spain is a problem of culture. It is necessary in fact, if we would enroll ourselves with the civilized peoples, that we must cultivate intensely the desert of our land and brain, thus rescuing by prosperity and mental vigour all those national riches that have been lost in the sea, and all those talents which have been lost in ignorance."

Thus his patriotic soul, that could not forget his Aragonese ancestry whose glorious exploits had filled entire pages of history, spent a moment in exultation and reflection looking through the great windows of the world, his face a little lengthened by his beard, faintly reminiscent of Don Quixote, saying to future generations, that in Spain one might still make science, and great science, everlasting.

REFERENCES

Addison, W. H. F. Scient. Monthly, 31:1930.

Cortezo, D. El siglo med., 69:1922.

Garrison, F. H. Bull. Í. Y. Acad. Med., 5:483-508, 1929.

Hilton, W. A. Scient. Monthly, 36:225-235, 1933.

Obituary notice. Lancet, 2:959, 1934.

Penfield, W. Arch. Neurol. & Psychiat., 16:213-220, 1926. Ibid., 33:172-173, 1935.

Sherrington, C. S. Obituary Notices, Roy. Soc. London, 1:424-441, 1935.

Sprong, W. Arch. Neurol & Psychiat., 33:156-162, 1935.