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https://www.quantamagazine.org/why-the-first-drawings-of-neurons-were-defaced-20170928/ September 28, 2017

Why the First Drawings of Neurons Were DefacedEvery exquisite drawing by Santiago Ramón y Cajal, the founder of modern neuroscience, is marredby a curious mark. Here is the little-known story behind it.

By R. Douglas Fields

Courtesy of the Cajal Institute and the Spanish National Research Council

Generations of neuroscientists have wondered why the elegant and historically important drawings of SantiagoRamón y Cajal, the field’s founder, are marred by a prominent blue stamp. The answer has finally come to light.

Working alone at the turn of the 20th century in Spain, Santiago Ramón y Cajal (1852-1934)ventured into science as both an artist and a pathologist, and became the first person to see aneuron. Working by gaslight, he made thin slices of brain tissue and subjected them to the samesilver-nitrate chemistry he used to capture images on photographic plates.

Peering through a microscope at the silver-stained tissue, Cajal saw a thicket of bizarre black shapesresembling swarms of spiny insects embedded in translucent amber. Other scientists examiningsimilar preparations perceived only a bewildering tangle of continuous fibers, which they presumedtransmitted nervous energy throughout the brain, like vibrations through a spiderweb. But Cajalobserved his slides with an artist’s keen eye for discerning form and function amid chaos, and hesaw neurons — individual cells, each one a separate, unique jewel of intricate beauty.

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Moreover, Cajal saw that the neuron is not a knot in a network that broadcasts signals in everydirection: The neuron, he concluded, must pass electrical information in only one direction. Simplyfrom their form, Cajal deduced that nervous signals enter the neuron through its elaborate rootlikedendrites and exit through its single slender axon, and that one neuron relays messages to the nextby passing information across a gap of separation, the synapse.

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Courtesy of the Cajal Institute and the Spanish National Research Council

Cajal’s graceful drawings of neurons show them as separate, individual cells. He was the first to realize that thenervous system is not a network of continuous fibers, as was widely believed at the time.

Cajal’s two brilliant insights — that every neuron in the brain is separate and that neuronscommunicate across synapses — came to be known as the neuron doctrine. Because that gapbetween neurons is too small to see through a light microscope, Camillo Golgi and other rigorousscientists of Cajal’s day at first dismissed the neuron doctrine as a fantasy. It would take anotherhalf-century until a new instrument, the electron microscope, could finally confirm what Cajal hadseen in his mind’s eye — and carefully sketched out in thousands of stunning pen-and-ink diagrams.

But long before the synapse was visible, Cajal’s neuron doctrine had transformed scientists’understanding of the nervous system and formed the bedrock upon which neuroscience is built. Forthat reason, Cajal was awarded the 1906 Nobel Prize in physiology or medicine (an honor that, in anironic twist, he shared with Golgi, who had invented the silver-staining technique that made Cajal’sobservations possible). And Cajal’s exquisite, meticulous drawings of neurons in the brain and spinalcord proved to be powerful tools for persuasively communicating his vision to the scientific world.Even today, they continue to inspire neuroscientists.

The strange thing is that every one of Cajal’s immortal drawings is marred by an odd bit ofdeliberate vandalism: a blue cataloging stamp, often placed directly in the middle of the artwork.The first time I saw one of his drawings of neurons, when I was a neuroscience graduate student atthe University of California, San Diego, I was struck by its beauty and intricacy, but I thought it wasa postcard because it was defaced by what looked like an ugly postmark. My mentor, theneuroethologist Theodore H. Bullock, assured me that all of Cajal’s drawings had that stamp onthem. Why? He didn’t know. In the decades since, when I’ve talked about this with others inneuroscience, no one could solve the mystery.

Last year, I finally learned the truth during a visit to the Cajal Institute in Madrid. Those blue inkstamps were the work of a single man over decades. But in a surprising twist, I also discovered thatwhile they may in a sense disfigure the drawings, they also helped to save them.

Inside the Cajal Institute, a spiral staircase ascends from the small lobby through three floors oflaboratories, each concealed behind a green door with a round porthole, giving visitors the feeling ofbeing on a ship. The ground-floor library contains an exhibit dedicated to Cajal’s drawings andscientific instruments. But during my visit, Ignacio Torres Alemán, a neuroscientist who was thedirector of the institute at the time, and Ricardo Martinez Murillo, an expert in the blood-brainbarrier who was then the vice director, were gracious enough to take me to a room that is not opento the public and is filled with all manner of artifacts from Cajal’s laboratory. The collection includeseverything: his microscopes, the microtomes he used to cut brains into thin slices, the boxes ofmicroscope slides he stained by hand to reveal neurons, and his artwork, including drawings andpaintings from when he was a child, the oil paintings of cadavers dissected by his physician fatherthat he made as a teenager, and his black-and-white photographs, negatives, stereographs and colorphotography.

Murillo unlocked the double doors of a fireproof safe containing approximately 3,000 of Cajal’sdrawings of neurons from the brain and spinal cord of almost every animal imaginable, includinghumans. He also brought me a book cataloging the collection, with every item identified by a neatlypenned number. We were soon joined by Adolfo Toledano Gasca, the former secretary of the

Quanta Magazine

https://www.quantamagazine.org/why-the-first-drawings-of-neurons-were-defaced-20170928/ September 28, 2017

institute who, as an emeritus professor since 2015, continues to study neurodegenerative disease.From them, I learned that almost all the cataloging and stamping of Cajal’s drawings was the workof one man, Pedro Manzano, who started shortly after the end of the second World War.

Manzano was a low-level caretaker of the institute building who had been given the job for savingthe life of the president of Spain’s research council during the war. He had applied for a permanentjob there but was rejected in part because he was unqualified for it. Nevertheless, in 1945 thedirector of the institute instructed him to collect and catalog Cajal’s artifacts. Manzano had noexperience or training in exhibit curation, but no one else was available for the task at the time. AsTorres Alemán emphasized to me, “What needs to be appreciated is the urgency of the situation.”

“[Cajal’s] drawings were all over the institute,” Murillo explained. “They were disappearing. Peoplewould take them.”

Manzano brought together about 1,200 of Cajal’s drawings during this postwar period, and hestamped each one with a unique number, which he entered in the ledger I had seen. When Toledanoarrived at the institute in 1967 as its secretary, he took it upon himself to collect Cajal’s works forposterity more aggressively, even though funds and professional curatorial help were still notavailable to preserve the priceless works. “All the things of Cajal were dispersed all over thecountry, in Zaragoza, Barcelona, Valencia and a lot of other places,” Toledano said. He worked withthe artist’s youngest son to locate the drawings and instruments scattered about the country. Thiseffort paid off, bringing together the largest share of the artworks and other items in the collection.But they too were stamped by Manzano in his customary way: squarely in the center, with theapparent indifference of a border agent stamping a passport.

“The stamps were placed directly on Cajal’s drawings, in many cases right over the work, not off tothe side,” I said. “Don’t you feel this defaced the work?”

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https://www.quantamagazine.org/why-the-first-drawings-of-neurons-were-defaced-20170928/ September 28, 2017

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Courtesy of the Cajal Institute and the Spanish National Research Council

Cajal’s drawing of neurons in the hippocampus, a region of the brain important to memory and other functions, isannotated with arrows showing the flow of information through the nervous system. From the shape of individualneurons, Cajal intuited that signals must move through the cells in only one direction.

“Now it is horrible, but at this time in history it was not,” Toledano said. “In the National Library andin the universities at the time, this was normal. The most important thing was that the stamp wasplaced in the center of the page of the books and the drawings and so on.” He explained that if thestamp had been placed to the side of the artwork or page in Cajal’s laboratory notebook, it couldsimply be trimmed away by a thief. Similarly, if it had been placed on the back of the work, it wouldhave been hidden from view, offering no disincentive to thieves. “During this period, many peopletook Cajal’s drawings home,” Toledano said.

Manzano died only two years ago. Today, when people see those blue ink stamps he left on everywork of Ramón y Cajal, their responses vary. To some, the stamps are an annoying blemish. Toothers, they are marks of devotion, because without the efforts of Toledano and Manzano, it is likelythat most of Cajal’s work would have been lost in Spain’s turbulent history.

“I’m not bothered by the stamp,” said Dawn Hunter, an associate professor in the School of VisualArt and Design at the University of South Carolina who creates new works inspired by Cajal’sdrawings. “It’s part of it now.”

The blue stamp also hasn’t prevented Cajal’s work from remaining popular in scientific circles. Evenin this age of electron microscopy and nuclear magnetic resonance imaging, his drawings retaintheir power to inspire and inform. While I was at the institute, Toledano opened one of the blackboxes of glass microscope slides and held up a histological section of human brain cut and stained byCajal at the turn of the 20th century. “This one I used in my new paper on senile dementia,” he saidwith a smile.