Sketching the secrets of how the brain works

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.

Artistic impacts

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, USA, who contributed a biographical section to the new book, The Beautiful Brain: The Drawings of Santiago Ramon 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, USA opened a travelling exhibit that is the first dedicated solely to Ramon y Cajal’s work.

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, Larry 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,” Larry said. “There seems to be a real resurgence of interest between the interaction between science and art, and I think Ramon 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.

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 in 1887, 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.

Refining the Golgi stain

Ramon y Cajal refined the Golgi stain, and with the details gleaned from even crisper images, revolutionised neuroscience. In 1906, 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. In 1889, 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. “People regularly begin seminars with pictures of the drawings that Ramon made because what they’ve added fits right in with where Ramon thought it should be,” Janet said. “What he did is still relevant today.”