In ‘Beautiful Brain,’ the secrets of neurons emerge in Nobel-winning scientist’s ink and pencil drawings

Asking scientists what career they would have pursued if they hadn’t gone into science is a crapshoot: It can either stop the conversation cold or uncork misty-eyed reminiscences about the road not taken. If you’d tried it with Nobel-winning neuroanatomist Santiago Ramón y Cajal (who lived from 1852-1934), you would likely have been treated to the latter.

As an exhibit opening at the MIT Museum on Thursday shows, if his father had not insisted he go to medical school, setting Cajal on a path toward world-changing discoveries about the brain, he might well have achieved his dream of becoming an artist.

As it was, Cajal’s depictions of the nerve cells he scrutinized under his microscope were key components of his science. Look what I saw, his intricate pencil and ink drawings told the world; this is how your brain is put together. The neurons that allow you to think and feel and move are discrete, individual cells, not the continuous skein that anatomy textbooks taught in the 19th century.

This was Cajal’s “neuron doctrine,” explained neurobiologist Eric Newman of the University of Minnesota, whose Weisman Art Museum created the traveling exhibit “The Beautiful Brain: Drawings of Santiago Ramón y Cajal,” which Newman and two colleagues curated. Look, Cajal’s Miró-esque drawings call out: Nerve cells conduct signals down their axon, into dendrites on the receiving cell, through the body of the receiving cell, and out its axons to the next cell in the circuit.

The neuron-to-neuron handoff occurs at gaps between cells. That is, the events that animate the most sophisticated structure in the known universe — the transmission of signals from one neuron to the next — occur in … empty space.

“What looked like continuous connections were actually spaces” between neurons, Newman said, “and by the 1890s he had convinced most scientists that his neuron doctrine was right” — in part through his drawings.

Like artists of cliché, Cajal worked in scientific isolation (Germany, not Spain, was the center of biology in the late 19th century), even publishing his papers in a journal he founded and supported. That might have “insulated him from the prevailing views in the rest of Europe and enabled him to look at the same appearances as everybody else — but with an unbiased eye,” wrote one neurologist.

Cajal made some 2,900 scientific drawings. From the evidence of the 80 in “Beautiful Brain,” his eye was more than unbiased. It saw the brain’s deepest secrets with a clarity it would take technology years to catch up to.

What is probably Cajal’s most famous drawing stands out not only for its stark arboreal beauty but also for encapsulating his neuron doctrine. It shows a single pyramidal cell, the largest kind in the brain. Its lone axon, pointing straight down, and whiskery dendritic spines, which receive signals from neighboring neurons, alone in an empty landscape: the canonical depiction of Cajal’s discovery that neurons are distinct entities.

Virtually everyone who sees this 1890 drawing of tumor cells in the brain’s covering (meninges) thinks, Van Gogh’s “Starry Night.” The whorl-like structure is typical of such cells.

No single brain sample would display this great a variety of injured Purkinje neurons in the cerebellum (a cat’s), but Cajal showed it this way in his 1914 drawing to convey the sequence of cellular degeneration. The central empty spaces are vacuoles, which get larger and larger as injured cells approach death. No brain cells are penguin-shaped, but Cajal’s imaginative eye saw a hint of the bird in the dying cells, and impishly let his inner artist trump the serious scientist he had become.

Cajal drew the inner world of the brain because he felt it captured more accurate and complete information than the photographic techniques of the day were able to. But he was a master photographer, as shown by this 1876 self portrait.

This cross section of a mouse spinal cord, from 1899, shows radial glia cells, the Rodney Dangerfields of brain cells. Cajal guessed, rightly, that glial cells are not mere support cells, as was widely assumed, but give rise to neurons, regulate blood flow in the brain, and influence the electrical properties of neurons. Later neuroscientists completely dismissed glial cells, whose importance was rediscovered in the 1960s, when researchers discovered that Cajal was correct in virtually all his speculations about their role.

Cajal would never have seen such wildly different forms of astrocytes, a type of glial cell, in his microscope. But he intended his 1904 drawing of cells in the cerebral cortex of a child to catalogue the pyrotechnic menagerie that brains contain.

Compare these pyramidal cells, photographed through a confocal microscope, to Cajal’s drawing of a single one. This “Brainbow,” from 2007, shows cells that were genetically engineered by Harvard’s Jeff Lichtman, Joshua Sanes, and Jean Livet to express genes encoding green, yellow, orange, and red fluorescent proteins.