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

JOANNA KLEIN

Illustrations by Santiago Ramón y
Cajal, the Spanish neuroscientist, from the book “The Beautiful Brain.”
From left: A diagram suggesting how the eyes might transmit a unified
picture of the world to the brain; a purkinje neuron from the human
cerebellum; and a diagram showing the flow of information through the
hippocampus in the brain.

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 colorful snapshots made possible by a giant magnet, we can see the activity of close to 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 Ramón y Cajal,
an artist, photographer, doctor, bodybuilder, scientist, chess player
and publisher. He was also the father of modern neuroscience.

A self-portrait of Ramón y Cajal in his laboratory in Valencia, Spain, about 1885.

“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.”

Last month, the Weisman Art Museum in Minneapolis opened a traveling exhibit that
is the first dedicated solely to Ramón y Cajal’s work. It will make
stops in Minneapolis; Vancouver, British Columbia; New York City;
Cambridge, Mass.; and Chapel Hill, N.C., through April 2019.

Ramón
y Cajal started out with an interest in the visual arts and photography
— he even invented a method for making color photos. But his father
pushed him into medical school. Without his artistic background, his
work might not have had as much impact, Dr. 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,” Dr. 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 Ramón y Cajal helped
discover about the brain and the nervous system, and why his research
had such an effect on the field of neuroscience.

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.

Pyramidal cells stained with the Golgi method by Ramón y Cajal.

Ramón
y Cajal’s life changed in Madrid in 1887, when another Spanish
scientist showed him the Golgi stain, a chemical reaction that colored
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 neighbors. Ramón y Cajal refined the Golgi stain,
and with the details gleaned from even crisper images, revolutionized
neuroscience.

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.

Ramón y Cajal's illustrations
of two contrasting theories of the brain’s composition: the reticular
theory, left, and the neuron doctrine that he proposed.

Ramón 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 Ramón y Cajal’s refinement of
the Golgi stain and his persistence in sharing his ideas with others. In
1889, Ramón 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 Kölliker, an influential German scientist, was amazed and began
translating Ramón y Cajal’s work, which was mainly in Spanish, into
German. From there the neuron doctrine spread, replacing the prevailing
reticular theory. But Ramón y Cajal died before anyone proved it.

Perhaps
one of Ramón y Cajal’s most iconic images is this 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 like making decisions. Some of these neurons are so large that
you don’t need a microscope to see them, unlike most other brain cells.

Ramón
y Cajal studied Purkinje neurons with fervor, illustrating their
treelike structure in great detail, like this one from the cerebellum.
Axons, such as the one indicated by an “a” in the picture, can travel
long distances in the body, some from the spinal cord all the way down
to your little toe, said Dr. Dubinsky, who wrote a chapter in “The
Beautiful Brain” about contemporary extensions of his work. Ramón y
Cajal traced axons as far as he could, she said.

A
few of his drawings had features that resembled the work of other
artists. In some, Vincent van Gogh appeared influential. In this drawing
of the glial cells in the cerebral cortex of a man who suffered from
paralysis, the three nuclei (or nucleoli) in the upper left corner
resemble Edvard Munch’s “The Scream.”

In
addition to showing how information flowed through the brain, Ramón y
Cajal showed how it moved through the whole body, allowing humans to do
things like 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 brainstem
and the spinal cord, where neurons signal the muscles in our chest and
abdomen to contract. Ahem.

CreditD. Berger, N. Kasthuri and J.W. Lichtman

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.

“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,” Dr. Dubinsky said. “What he did is still relevant today.”

________

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Correction: February 17, 2017

Because of an editing error, a
capsule summary with an earlier version of this article misstated the
title of a book. It is “The Beautiful Brain: The Drawings of Santiago
Ramón y Cajal," not "The Beautiful Mind."