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 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.
"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; 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 impact in 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.
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 of how individual brain cells send and receive information, which became the basis of modern neuroscience.
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.
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."