Artistic Elements: Staining the Brain

[The last in a series of posts on the elements in art, by D.C. writer and Sci-Arts guest blogger Sam Kean.]

Science often inspires great art; but sometimes art can inspire great science. That was certainly the case with early studies of the neuron, which owes its discovery to two artistically minded anatomists and one obscure element on the periodic table.

Scientists in the mid-1800s faced a small problem when studying the brain’s micro-architecture: they had no idea what they were looking at. Brain cells were tiny; they came in a confusing variety of shapes; and unlike the brick-like cells in other organs, they were densely entangled, like snarls of ivy.

Worse, the traditional way to create images of cells to study—inject a dye and stain them—didn’t work with highly tangled cells: They all ended up stained the same color and scientists still couldn’t tell them apart. In fact, these problems with visualizing cells led most neuroscientists to conclude the brain didn’t contain discrete cells at all. They promoted a “reticular theory” of the brain instead, where cells were fused into a continuous “net” with no breaks or gaps.

One “reticulist,” Camillo Golgi, finally solved the staining problem in the 1870s, after a serendipitous accident. Golgi worked in an unusual lab—a candlelit kitchen beneath a psychiatric hospital in Pavia, Italy. As the legend goes, one night Golgi was preparing to stain an owl brain that had been soaking for months in potassium and chromium (among other chemicals). But he clumsily knocked a container of silver nitrate onto the tissue, ruining months of work. Except that, after cleaning up the spill, he noticed the slice of brain tissue had been stained with perfect clarity. (Another version of the legend says Golgi’s cleaning woman deserves credit: she supposedly threw the owl brains away one night into a refuse can with silver nitrate in it, and only when Golgi fished the samples out did he see what had happened.)

Stained cerebellum cells from an original preparation from Golgi's laboratory

That silver could stain tissue wasn’t a total surprise—silver had become quite important in photography by then (see this previous post on elements in photography). But to Golgi’s shock, the silver colored only random fibers of the tangled net, allowing him to differentiate individual strands. What’s more, the dye impregnated the entire strand, down to its smallest, finest fiber. Basically, he’d discovered a method for creating intricate silhouettes of some cells—and, crucially, leaving their neighbors blank. He called his method la reazione nera, the black reaction, and it gave scientists their first chance to study the brain’s microscopic structure.

Golgi's drawing of a stained hippocampus

The drawback to Golgi’s method was its excruciating slowness—each stain required months of prep time. So few scientists adopted it. But like any good artist, Golgi revised his work, and under the candlelight a few years later, he hit upon something new. He found that if he pre-treated brain tissue with the element osmium, it slurped up the silver dye, and without sacrificing the quality of the visuals. The osmium method became known as the rapid Golgi technique, and cut the staining time down from months to days. This time, Golgi’s peers were ecstatic. Many felt the same gratification as the great Spanish neuroscientist Santiago Ramón y Cajal, who gushed, “Golgi is responsible for a method that renders anatomical analysis both a joy and a pleasure.”

Ironically, the success of the rapid osmium stain led to the undoing of Golgi and all the other reticulists. Though somewhat ambiguous, his osmium stains hinted that the brain was not made of a continuous net—it contained individual cells. Golgi continued to champion the venerated old theory, but younger scientists with less investment in it weren’t so reverent. Chief among them was Cajal.

In fact, if anyone was primed to use art to make a breakthrough in science, it was Cajal. He had been an avid artist as a child, until his autocratic father took away his pencils and brushes and pushed him toward science. Golgi’s osmium staining provided an artistic outlet, and though Cajal worked in obscurity for years, he spent many happy hours producing silhouettes of cells and using his trained eye to sketch neurons for publication in scientific journals. Almost single-handedly, Cajal revived the long-dead debate about whether the brain had individual cells (called neurons). Cajal even used his drawings to deduce (correctly) that impulses flow through neurons in one direction only, a major breakthrough.

Cajal's drawing of a stained cerebellar cortex

The final irony of this story happened in 1906. The Nobel Prize committee had been debating since 1901 (the first year of the prizes) about giving a Nobel to Golgi for his osmium staining, among other work. But it quickly became clear that Cajal’s gorgeous work with neurons was already dismantling the reticulist doctrine. Various factions voted down the nominations of both men, but in 1906, in a surprise move, the Nobel committee divided the award between them—the first split prize first split prize in Nobel history.

Both men continued to debate their pet theories in their Nobel acceptance speeches, each arguing that the osmium and other staining techniques supported their cause. It wouldn’t be the last time, in science or elsewhere, where two people would see the same piece of art and come up entirely different interpretations.