The Beautiful Brain and It’s Beholder, RAMON Y CAJAL: Love at First Sight :

Ramón y Cajal started out with an interest in the visual arts and photography — he even invented a method for making color photos.

Cajal was drawn to art from an early age, to a point of compulsion — as a boy, he was frequently possessed by what he called “manias” to draw everything in sight, and even drew his dreams.  He did not have the happiest of childhoods and it seems as if today he might even be called “abused”.   He found solace in a private room where he could engage in his dreamwork and work on his dreams

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His father, a fine Paris Review article, tells us. it seems was dogmatic and tyrannical,  pushed him into medical school. Without his artistic background, his work might not have had as much impact, Dr. Swanson said.  “He repudiated or despised all culture of a literary or of a purely ornamental or recreative nature,”

Cajal recalls. Only medical books were  .
Screenshot 2017-03-31 14.31.54allowed in the house—absolutely no fictionHis father, a fine Paris Review article, tells us. it seems was dogmatic and tyrannical,  pushed him into medical school. Without his artistic background, his work might not have had as much impact, Dr. Swanson said.  “He repudiated or despised all culture of a literary or of a purely ornamental or recreative nature,” Cajal recalls. Only medical books were allowed in the house—absolutely no fiction.
Art, Cajal’s father believed, was the symptom of a devastating illness. The human mind, Cajal’s father believed, was made for obtaining knowledge. Cajal used to retreat to his room which was his only sanctuary to dream and draw and imagine.
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After high school, Cajal’s father enrolled him in medical school, where the only subject that held his interest was anatomy. Though it had emerged decades earlier, cell theory was revolutionizing—or scandalizing—the field then.

Reading about it, Cajal encountered literary metaphors that drew him in, such as the famous line from the German pathologist Rudolf Virchow: “The body is a state in which every cell is a citizen.”  Surely that resonated with him.

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Cajal’s first look through a microscope confirmed this idea, showing him, in his own words, “captivating scenes from life of the infinitely small.  For twenty continuous hours—or so he claimed—he watched the movement of a leucocyte away from a capillary, akin, in his vivid imagination, to high-stakes escape.  leucocyte away from a capillary, akin, in his vivid imagination, to high-stakes escape.

Escape that surely had been long on his mind. He even wrote and illustrated a novel about a miniature man—about the size of a cell—traveling through bodies of gargantuan beings on Jupiter.

Ramon Y Cajal did not produce lengthy treatises or inscrutable charts and tables, fiddled with statistics, all he needed was his own eye and his own hand.   The rest was done without words.

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“A graphic representation of the object observed guarantees the exactness of the observation itself”…he said. But we believe that he was telling us a bit of  “white lie” here.  When he looked through is lens at the “world of the very small’  he somehow managed to see more than others who had looked through that same lens.

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He graduated in medicine at the University of Zaragoza in 1873. Shortly after his degree he was drafted into the army and dispatched to Cuba, at that time under Spanish rule, as a medical officer.

Cajal returned to Spain very sick (he had contracted malaria in Cuba, and then tuberculosis), and at the end of 1875 he started his academic career as “Auxiliary Professor” of Anatomy at the University of Zaragoza.

Screenshot 2017-03-31 14.32.04It was in Zaragoza, that Cajal purchased in 1877. two years before he married,  with his own funds (“using every peseta saved from the service in Cuba”), an old-fashioned microscope and started his scientific activity.  His first studies were devoted to inflammation and to the structure of muscle fibers. It would be another eight years before he was able to work on an up-to-date Zeiss microscope–a gift of the Zaragoza provincial government in return for Cajal’s volunteer work during a cholera epidemic.

He  realized that while he was not destined to become a successful artist, he could succeed with his meticulous drawings by making precise records of the cells and other tissue structures that he saw. This was long before cameras could be attached to a microscope, and his art became invaluable to science.

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And his eye became invaluable to science as well. Microscopes could not differentiate the tangles of fibers that became so fine, with the fine filaments called the dendrite at one end and the branches of nerve endings at the other, that nobody could see whether these were individual cells, or an interconnected structure. This was about the time that scientists started calling the mysterious stuff “gray matter.”

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The equally legendary Charles Sherrington, his lifelong friend and fellow Nobel Laureate, recalled, “Cajal treated the microscopic scene as though it were alive,” “and were inhabited by beings which felt and did and hoped and tried even as we do.” To anthropomorphize as he watched and observed through the microscope, was both Cajal’s need and his genius.  Such an approach seemed unscientific, to say the least, and exactitude did not totally dominant his vision.

A FLASH OF LIGHTNING

The key event for Cajal’s scientific career and for the development of modern neuroscience took place in Madrid in 1887, when Cajal was 35 years old. In this year, Luis Simarro Lacabra, a brilliant psychiatrist interested in histological research, showed to Cajal, who had traveled from Valencia to get an update on technological advances, material impregnated with the Golgi staining.

Dr. Simarro had just returned from Paris, and had brought specimens stained by the new technique of silver impregnation (the reazione nera), that had been discovered 14 years earlier by Camillo Golgi but still had a very limited diffusion.

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Cajal wrote in his autobiography “it was there, in the house of Dr. Simarro…that for the first time I had an opportunity to admire…those famous sections of the brain impregnated by the silver method of the Savant of Pavia.”

The observation of preparations impregnated by the Golgi stain was a flash of lightning: “a look was enough” and Cajal was enraptured. Nerve cells appeared “coloured brownish black even to their finest branchlets, standing out with unsurpassable clarity upon a transparent yellow background. All was sharp as a sketch with Chinese ink,” Cajal wrote in his autobiography.

 

 

As Sherrington noted aptly,  the drama he witnessed,  aided the unorthodox Spaniard’s ability to visualize the brain.  “If we would enter adequately into Cajal’s thought in this field,” Sherrington continues, “we must suppose his entrance, through the microscope, into a world populated by tiny beings actuated by motives and striving and satisfactions not very remotely different from our own.  Screenshot 2017-03-28 17.54.56

In a feverish burst of activity (“…as new facts appeared in my preparations, ideas boiled up and jostled each other in my mind. A fever for publication devoured me”), Cajal worked on the retina, the cerebellum and the spinal cord, applying to the tissue the Golgi stain, of which he worked out some modifications.

cajal-3_custom-a0256c8e90daa80205e1604511b7157cb7fb4289-s700-c85There was an almost daredevil aspect to Cajal’s choice to study the brain — the often controversial and infinitely challenging Everest of science at the end of the nineteenth century.

At best, a brain slice seen through a microscope is notoriously difficult to interpret. Perhaps if he had sought to  “glimpse and tell his story” about the cells in the brain and the vicissitudes of their lives and he did so in images that echoed an  anthrophormorhic identification he clearly felt with citizens of the brain community that would have seemed out of joint if had been put into the pedestrian march of words.

But there is a benefit of working without words and through more immediate means, as Einstein also pointed out.  The words do not ever capture or predict or depict what is either “seen” by the real eye or observed in the ‘mind’s eye’, and they do an even worse job at communicating the exquisite detail of what they purportedly are meant to “describe”. That is not what words do. But that is what art does.  The immediacy of translation from the eye to Cajal’s hand and thence to the eye of the scientists he influenced so strongly was beyond the inadequacy and corruption of verbalizations.

 

The great Victorian art critic John Ruskin had argued that drawing cultivates the art of observation and helps one see the world more clearly. Cajal brought this ethos to his scientific work, using his illustrations — which he preferred to do freehand, rather than tracing images projected from a microscope — to deduce the framework of how the brain works.

Screenshot 2017-03-31 14.31.31To borrow one of Cajal’s favorite metaphors, imagine entering a forest with a hundred billion trees armed only with a sketchbook, looking each day at blurry pieces of a few of those trees entangled with one another, and, after a few years of this, trying to write an illustrated field guide to the forest.

His drawings not only captured the details but were strikingly interpretative and deeply personal, blurring the line between abstraction and representation. After viewing many cells, Cajal distilled their features to a type.  His images are composites, highlights, even exaggerations of actual neurons; It is said that he often drew from memory after taking long walks through the park

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The “reality” he captured was of what he had seen  after long hours of intense fascination with the lives of these cells, but it was also etched with the drama that Cajal felt in common with the cells whose lives he eavesdropped upon. Cajal called them “pieces of reality,” these tactfully fictionalized depictions

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In 1888, working alone at the microscope in his home laboratory, Cajal observed the endpoint of a nerve fiber, a nearly imperceptible phenomenon that led him to declare that nerve cells were independent.

 

Of course, Cajal was destined to have a “love affair’ with those incredible and extraordinarily complex individual cells in the brain, and the complexity of the drama of their lives in the brain.  Thus that enchantment, love at first sight. was the  beginning of he saga of modern neuroscience.

 

The history of neuroscience truly starts here.dpp_0093

Cajal — as a fine Essay in Brain Pickings tells us,–  given the magnitude of his contributions, ought to be as much of a household name as Darwin and Pasteur — created hundreds of exquisite, exceptionally skilled drawings to illustrate his scientific papers.

“He’s one of these guys who was really every bit as influential as Pasteur and Darwin in the 19th century,” said Larry Swanson, a neurobiologist at the University of Southern California who contributed a biographical section to the new book “The Beautiful Brain: The Drawings of Santiago Ramón y Cajal.” “He’s harder to explain to the general public, which is probably why he’s not as famous.”

Screenshot 2017-03-31 14.30.07Both in scope and in promise, histology fell part way between anatomy, which had been a staple of medicine for centuries, and microbiology, which Pasteur had rendered a research field du jour. The obscure discipline was in its infancy, its growth only recently accelerated by innovations in optical technology in the 1830s, but Cajal saw it as full of possibility. He would later write his poetic autobiography, Recollections of My Life:

Ramón y Cajal wanted to know something no one really understood: How did a neural impulse travel through the brain? But he had to lean on his own observations and reasoning to answer this question.

 

3134In them, he laid out the basic architecture of the nervous system and tackled the grand unanswered question of his era: How do nerve impulses travel between separate cells, or, what is the neurological basis of reflexes?

It was from this transfixed vantage point at the eyepiece of the microscope that Cajal, who always considered himself “a visual type,” first saw the potential of fusing science with art in advancing discovery.

As Ramon Y Cajal  said later in life, ‘”There are no small problems. Problems that appear small are large problems that are not understood”

And  Cajal was able to convey the wisdom derived from his knowledge as few scientists could.  Without words.  When he first presented his results of his observations at a conference of German scientists, he prepared some explanatory papers.  They were delivered to the German scientists in advance, but few who tried to read them knew any Spanish. Cajal then delivered a speech in fractured French, but still made his point and won his case on the strength of his drawings and slides.

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The Nobel Prize in 1906:  An Odd Couple

In 1906 he and Golgi shared a Nobel Prize. And in the time in between, he wrote his neuron doctrine — the theory that neurons were individual brain cells, leading to his realization of how individual brain cells send and receive information, which became the basis of modern neuroscience.

Golgi and Cajal, who shared the Nobel Prize  met only in Stockholm, to receive the award. Golgi gave his Nobel lecture first, in which he tied to his belief in “reticular” neural networks, which was entirely contradicted by Cajal’s Nobel lecture.

 

Cajal was quite opposed to Golgi and decades ahead of his time, since the first observations and in his subsequent studies,  Cajal’s imagination was fired by the idea that the nervous system is made up of billions of separate nerve cells, that “community of citizens”.

Screenshot 2017-03-31 14.32.52While no one had yet seen an entire nerve cell, or could tell whether it was independent or just part of a larger structure, some scientists already questioned the old “single network

In 1887, few histologists knew that in 1873 an Italian colleague, Camillo Golgi, had already developed a stain of silver nitrate that produced successful results.

Golgi had believed to have “seen” in his own preparations the demonstration that the nervous system was made of a widespread network of filaments in continuity one with the other (the rete nervosa diffusa, ‘diffuse neural network’). Cajal  was fiercely opposed to the idea that the nervous system was made up a network of continuous elements, as it had been stated by Joseph von Gerlach (1820-1896) and supported by Golgi himself.

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Cajal’s work however let to led to the opposite conclusion that the basic units of the nervous system were represented by individual cellular elements (which Waldeyer christened as “neurons” in 1891). This conclusion is the modern basic principle of the organization of the nervous system.

It was also Cajal who first applied the term plasticity to the brain to capture the arrangements and rearrangements and ensembles of neuron activity that could emerge from experience.  Cajal defined “the law of dynamic polarization,” stating that the nerve cells are polarized, receiving information on their cell bodies and dendrites, and conducting information to distant locations through axons, which turned out to be a basic principle of the functioning of neural connections.

BeautifulBrain_p064Golgi and Cajal certainly shared the same passion for science and dedication to science but their personalities were very different. “What a cruel irony of fate,” remarked Cajal, ” to pair together, like Siamese twins united by the shoulders, scientific adversaries of such contrasting character!

And indeed they were truly Siamese twins.  Without Golgi’s breakthrough in staining the cells that were to viewed in the microscope, Cajal’s eye would never have had the chance or the inspiration to look that deeply into what was going on..and what might be going on down there.

 

In one of the essays in the monograph, curator Lyndel King and editor Eric Himmel consider the visionary approach that elevated Cajal above the rest:

“As with Einstein’s theories, it has taken many decades for those of us who are not scientists to catch up with Cajal’s brain. It wasn’t until 1946, twelve years after Cajal’s death, that the first electronic computer flickered into life, hinting that a machine could be built that behaved like a brain.”

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“It’s fairly rare for a scientist to be a really good artist at the same time, and to illustrate all of their own work, brilliantly,” notes Swanson.  This description of the two aspects of Cajal’s work is not quite adequate to give us a glimpse into how that work arose, and it did not arise as the work of a theorist who then put on another hat and illustrated his theories. Not at all!

Art became the sandbox for testing his theories, which in turn became a centerpiece of modern science. While, reciprocally,  that science was part of his dreamwork of independence and escape from the mundane world around
In the small, small domain which he spied upon,  he managed to rebuild an entire world filled with individuals, learning, communication, community, an adventure that he no doubt dreamed about as youngster like others dream of traveling to far away lands. For Cajal he was indeed Gulliver traveling when he came to the denizens of the landscape of the brain he surveyed.

Who knows whether he managed to decipher both of the mysteries in both of the universes that bedeviled and bedazzled him at the same time, and we repeat, as our photo at the top of the blog quotes Cajal himself:

“As long as our Brain is a Mystery, the Universe, the reflection of the Structure of the Brain, will also be a Mystery”

 

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Hunched Over a Microscope, He Sketched the Secrets of How the Brain Works

This image is a reconstruction of a dendrite (red) and its axons (multicolored) in the outer part of a mouse’s brain. The dendrite has little knobby spines that stick out and receive chemical messages passed from another neuron’s axon across the synapse, or gap between them, via the tiny white sacs called vesicles.

Today we know that synapses are plastic, meaning they can get stronger or weaker with use or neglect. This enables us to think and learn. This is what Ramón y Cajal described in his neuron doctrine. 

Many of the drawings here were found in a video by the HUMAN BRAIN PROJECT

  PS:The best of his drawings, ranging from the iconic to the never-before-published, are now collected in Beautiful Brain: The Drawings of Santiago Ramón y Cajal (public library) — astonishingly detailed and deft illustrations,

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

“I would be the last to deny that the greatest scientific pioneers belonged to an aristocracy of the spirit and were exceptionally intelligent, something that we as modest investigators will never attain, no matter how much we exert ourselves, he said.

 

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