The Neuron: One Stain, Two Men, Opposite Conclusions

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Welcome to Origins. In this program we explore the technological and scientific roots of the modern world. Let's begin.

In December of 1906, two men stood on a stage in Stockholm to share a Nobel Prize for revealing the structure of the nervous system. They had never met before that week. The next day, the first of them gave his Nobel lecture, and used it to argue that the other man's central idea was wrong.

The idea was the neuron: the claim that the brain is built from separate cells. Today that sounds too obvious to need defending. In the nineteenth century it was the one place in the body where the cell seemed to fail.

By the 1840s, biologists were coming to agree that living tissue is made of cells. Skin, muscle, leaf, liver: put it under a microscope and there are the little compartments. Brain tissue refused to cooperate. Under the lens it looked like felt. Anatomists could see cell bodies, and they could see fibers running everywhere, but the fibers were so fine and so densely tangled that nobody could follow one to its end. Dyes made it worse, because they colored everything at once. The leading view held that the fibers fused into one continuous web, a net running through the whole brain. This was the reticular theory.

In 1872, a young Italian doctor named Camillo Golgi ran short of money and took a job as chief physician at a hospital for the chronically ill in Abbiategrasso, a small town near Milan. The job took him out of academic life. He turned a little kitchen into a laboratory and kept working, often by candlelight.

Early in 1873 he found what he was after. He hardened pieces of brain in potassium dichromate and then soaked them in silver nitrate, a slow process that could take weeks. Under the microscope, a few nerve cells had turned solid black against a clear yellow background, every branch filled in to the tip. He called it the black reaction. He wrote to a friend that the structure of the brain could now be shown "even to the blind."

The stain colors only a few cells, generally fewer than one in twenty, apparently at random. A century and a half later, nobody is sure why. But that failure is the whole trick. If every cell took the stain, the slide would be a black smear. Because nearly all of them refuse it, the few that accept stand alone, like single trees picked out in a fog.

Golgi looked at his black cells and still saw the net. And the method spread slowly. Fourteen years later, it was still little used.

One who eventually did was Santiago Ramón y Cajal. He was born in 1852 in a mountain village in northeastern Spain, the son of the village surgeon. He was a difficult boy. At eleven he was jailed for blowing apart a neighbor's gate with a homemade cannon. He wanted to be a painter. His father apprenticed him to a shoemaker and a barber instead, and finally steered him into medicine. After army service in Cuba, where he caught malaria, he spent his savings on an old-fashioned microscope.

In 1887, on a visit to Madrid, a colleague just back from Paris showed him slides made with Golgi's method. Cajal later wrote that one look was enough. The cells stood out, he said, "sharp as a sketch with Chinese ink."

He went home and got to work, and he made one shrewd change. Adult brain tissue was too dense, even with the stain. So he turned to very young animals, where the cells are fewer and the fibers shorter. As he put it: "Since the full-grown forest turns out to be impenetrable and indefinable, why not revert to the study of the young wood in the nursery stage?" He sliced the tissue by hand with a razor, a skill left over from the barbershop.

In the spring of 1888, looking at the cerebellum of a very young pigeon, he followed fibers all the way out to their tips. They wrapped around neighboring cells like baskets. They came very close. They did not fuse. Each cell ended freely. The brain, Cajal concluded, is made of individuals that touch without joining.

Then came the problem of being a Spanish anatomist in 1888. He started his own journal to publish the work and mailed some sixty copies to scientists around Europe. Almost nobody answered.

So in October of 1889 he packed his slides and his microscope and travelled to Berlin, to the congress of the German Anatomical Society. He had come to show his slides to the leading anatomists of the day. One of them was Albert von Kölliker, in his seventies and the grand old man of the field. Kölliker looked, then swept Cajal into his carriage, took him to dinner, and promised to see his work published in Germany. Two years later another German anatomist, Wilhelm Waldeyer, summed up the evidence and gave the unit its name: the neuron.

Golgi was not persuaded, and he had a point. Nobody could actually see a gap between two neurons. Cajal saw fibers stop. A defender of the net could always say the join was simply too fine to make out. Both men were arguing past the limit of the light microscope. In 1897 the English physiologist Charles Sherrington gave the unseen junction a name: the synapse, from Greek words for fastening together.

That brings the story back to Stockholm. Golgi's lecture was titled "The Neuron Doctrine: Theory and Facts." He called the doctrine an idea "going out of favor" and declared, "I cannot abandon the idea of a unitary action of the nervous system." Cajal spoke the following day. A continuous net would be convenient, he allowed. "Unfortunately, nature seems unaware of our intellectual need for convenience and unity, and very often takes delight in complication and diversity."

Both men died with the gap still unseen. It took the electron microscope. In 1956 the American scientist Sanford Palay published pictures of synapses in rat brain. The two membranes face each other across a cleft about twenty billionths of a meter wide, roughly ten times too fine for any light microscope to resolve. Cajal had been right about something he could not see.

Golgi was not entirely wrong, either. Some neurons, it turns out, are linked by direct channels that pass current straight from cell to cell. And his worry about the whole has not gone away. How billions of separate cells add up to one mind is still an open question.

The brain learned what it is made of in a kitchen, from a stain that fails at least nineteen times in twenty, read by a man who had wanted to paint. Even the networks behind today's AI models carry the idea forward: separate units, and everything that matters happening at the connections between them.

Thanks for listening to Origins.