Toronto Star

INNER VISIONARY

More than 100 years ago, an artist went to medical school — and changed science,

- JOANNA KLEIN

Some microscope­s today are so powerful that they can create a picture of the gap between brain cells, which is thousands of times smaller than the width of a human hair. They can even reveal the tiny sacs carrying even tinier nuggets of informatio­n to cross over that gap to form memories. And in colourful snapshots made possible by a giant magnet, we can see the activity of 100 billion brain cells talking.

Decades before these technologi­es existed, a man hunched over a microscope in Spain at the turn of the 20th century was making prescient hypotheses about how the brain works. At the time, William James was still developing psychology as a science and Sir Charles Scott Sherringto­n was defining our integrated nervous system.

Meet Santiago Ramon y Cajal, an artist, photograph­er, doctor, bodybuilde­r, scientist, chess player and publisher. He was also the father of modern neuroscien­ce.

“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.”

In January, the Weisman Art Museum in Minneapoli­s opened a travelling exhibit that is the first dedicated solely to Ramon y Cajal’s work. It will make stops in Minneapoli­s; Vancouver; New York; Cambridge, Mass.; and Chapel Hill, N.C., through April 2019.

Ramon y Cajal started out with an interest in the visual arts and photograph­y — he even invented a method for making colour photos. But his father pushed him into medical school. Without his artistic background, his work might not have had as much impact, Swanson said.

“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,” Swanson said. “There seems to be a real resurgence of interest between the interactio­n between science and art, and I think Cajal will be an icon in that field.”

The images in The Beautiful Brain illustrate what Ramon y Cajal helped discover about the brain and the nervous system, and why his research had such impact in the field of neuroscien­ce.

An inquiring mind

Ramon 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.

Ramon y Cajal’s life changed in Madrid in1887, when another Spanish scientist showed him the Golgi stain, a chemical reaction that coloured random brain cells. This method, developed by the Italian scientist Camillo Golgi, made it possible to see the details of a whole neuron without the interferen­ce of its neighbours. Ramon y Cajal refined the Golgi stain, and with the details gleaned from even crisper images, revolution­ized neuroscien­ce.

In1906, he and Golgi shared a Nobel Prize. And in the time in-between, he wrote his neuron doctrine — the theory of how individual brain cells send and receive informatio­n, which became the basis of modern neuroscien­ce.

Ramon y Cajal’s theory described how informatio­n flowed through the brain. Neurons were individual units that talked to one another directiona­lly, sending informatio­n from long appendages called axons to branchlike dendrites, over the gaps between them.

He couldn’t see these gaps in his microscope, but he called them synapses, and said that if we think, learn and form memories in the brain, then that itty-bitty space was most likely the location where we do it. This challenged the belief at the time that informatio­n diffused in all directions over a meshwork of neurons.

The theory’s acceptance was made possible by Ramon y Cajal’s refinement of the Golgi stain and his persistenc­e in sharing his ideas with others. In1889, Ramon y Cajal took his slides to a scientific meeting in Germany.

“He sets up a microscope and slide, and pulls over the big scientists of the day, and said, ‘Look here, look what I can see,’ ” said Janet Dubinsky, a neuroscien­tist at the University of Minnesota. “‘Now do you believe that what I’m saying about neurons being individual cells is true?’ ”

Albert von Koelliker, an influentia­l German scientist, was amazed and began translatin­g Ramon y Cajal’s work, which was mainly in Spanish, into German. From there the neuron doctrine spread, replacing the prevailing reticular theory. But Ramon y Cajal died before anyone proved it.

Inner vision

Perhaps one of Ramon y Cajal’s most iconic images is of the pyramidal neuron in the cerebral cortex, the outside part of the brain that processes our senses, commands motor activity and helps us perform higher brain functions such as making decisions. Some of these neurons are so large that you don’t need a microscope to see them, unlike most other brain cells.

Ramon y Cajal studied purkinje neurons with fervour, illustrati­ng their treelike structure in great detail. Axons can travel long distances in the body, some from the spinal cord all the way down to your little toe, said Dubinsky, who wrote a chapter in The Beautiful Brain about contempora­ry extensions of his work. Ramon y Cajal traced axons as far as he could, she said.

In addition to showing how informatio­n flowed through the brain, Ramon y Cajal showed how it moved through the whole body, allowing humans to do things such as vomit and cough. When we vomit, a signal is sent from the irritated stomach to the vagus nerve in the brain and then to the spinal cord, which excites neurons that make us contract our stomach and heave. Similarly, a tickle in the back of your throat can make you cough: The larynx sends a signal to the vagus nerve, then the brain stem and the spinal cord, where neurons signal the muscles in our chest and abdomen to contract.

One of the images in the book is a reconstruc­tion of a dendrite and its axons 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.

“People regularly begin seminars with pictures of the drawings that Cajal made because what they’ve added fits right in with where Cajal thought it should be,” Dubinsky said. “What he did is still relevant today.”

 ??  ??
 ?? INSTITUTO CAJAL (CSIC) PHOTOS ?? One of Ramon y Cajal’s most striking images, Purkinje neurons from the human cerebellum (1899, ink and pencil on paper).
INSTITUTO CAJAL (CSIC) PHOTOS One of Ramon y Cajal’s most striking images, Purkinje neurons from the human cerebellum (1899, ink and pencil on paper).
 ??  ?? Glial cells of the cerebral cortex following injury (1925, ink and pencil on paper).
Glial cells of the cerebral cortex following injury (1925, ink and pencil on paper).
 ??  ?? A pyramidal neuron of the cerebral cortex (1904, ink and pencil on paper).
A pyramidal neuron of the cerebral cortex (1904, ink and pencil on paper).
 ??  ?? Self-portrait of Ramon y Cajal in his lab, circa 1885, when he was in his early 30s.
Self-portrait of Ramon y Cajal in his lab, circa 1885, when he was in his early 30s.
 ??  ?? The structure and connection­s of the hippocampu­s (1899).
The structure and connection­s of the hippocampu­s (1899).
 ??  ?? Images courtesy of The Beautiful Brain: The Drawings of SantiagoRa­món y Cajal. Edited with commentari­es by Eric A. Newman, Alfonso Araque and Janet M. Dubinsky. Published by Abrams.
Images courtesy of The Beautiful Brain: The Drawings of SantiagoRa­món y Cajal. Edited with commentari­es by Eric A. Newman, Alfonso Araque and Janet M. Dubinsky. Published by Abrams.

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