The Story of Camillo Golgi and the Visualization of the Neuron

It is commonplace in public discourse to complain that one’s opponent continues to hold a fixed belief long after evidence to the contrary. The opponent either benefits from professing the belief, or that they somehow lack wisdom or perceptiveness. I cannot comment on the former, as it would have to be addressed case by case. But I will address the latter by telling the story of a remarkably brilliant person, 1906 Nobel Prize-winner Camillo Golgi—who retained an incorrect notion for the rest of his life, despite the accumulated evidence and acceptance of the scientific community that it was wrong.

Olfactory bulb neurons visualized by Golgi, 1875.

Source: Golgi, C. in Wikimedia Commons/Public domain

The Story of Golgi

Golgi was born in 1843 in the small village of Corteno in the Kingdom of Lombardy, now Italy. Like his father, he became a physician, graduating from the University of Pavia with average grades in 1868. During those years he had come to admire the work of Giulio Bizzozero, a young histologist who was developing a reputation for his studies of the nervous system. Golgi took a position as a secondary physician, spending as much time as possible in Bizzozero’s Institute of General Pathology. Although the papers on glial cells that he began to publish in 1870 seemed to be well received, his meager salary was stressed by the costs of publication. When his mentor announced plans to move to Switzerland, Golgi had little prospect of a faculty position, and on the advice of his father, he took a better-paying assignment as the chief medical officer at a hospital for chronic patients. It had no laboratory facilities; he continued his work by setting up equipment in his apartment kitchen. It was there that he made his breakthrough discovery of looking at neurons microscopically.

In trying to better visualize neurons, Golgi used silver solutions that were becoming available through advances in photography. In 1873, he reported a new method that involved hardening tissue with potassium dichromate, then impregnating it with silver nitrate. As the neurons then appeared as black structures that clearly stood out from the yellow background, the process became known as the black reaction.

One advantage of Golgi’s technique is that it stained only 1 to 5 percent of the tissue. Previous methods, which stained all the cells, presented the microscopist with a mélange of densely packed cells that were difficult to interpret. Now individual cells could be clearly seen. Unlike earlier methods, it also made it possible to visualize not only the cell bodies but also their processes (dendrites and axons). Over the years, Golgi went on to make many other contributions that are beyond the scope of this post, such as the discovery of the intracellular Golgi Complex, the Golgi Cells of the cerebellum, and the Golgi Tendon Organ, but this focus will be on his view of the interconnections inside nerve tissue.

The Birth of Reticular Theory

Golgi had clearly visualized axons leading from nerve cells (as they were then known), and came to believe that they were anatomically joined together, with continuity of cytoplasm, in a diffuse nervous net. In retrospect, it is suspected that this resulted from what has been described as "a mistaken microscopic image created by superimposition and interlocking of the axons of the diverse cells".¹ The notion that the brain was made up of a single complex network had been suggested by Joseph von Gerlach in 1871, and Golgi’s work gave it anatomical form. In effect, they were arguing that brain tissue is an exception to the principle that the cell is the basic building block in animal bodies. As Golgi believed that neurons of the gray matter were all anatomically connected in a multi-nucleated syncytium, or reticulum, the notion came to be known as reticular theory.

The Neuron Doctrine

In the meantime, there was growing interest in the opposing notion that neurons were the basic anatomic and physiologic building blocks of the nervous system. In 1887, the Spanish histologist Santiago Ramón y Cajal, a decade younger than Golgi, learned of his technique and began work on improving it. By 1888, he published remarkably precise drawings of star-shaped cells in the bird cerebellum, whose axons created a basket-like formation around Purkinje cells. There was an element of luck involved, likened by some to winning the lottery the first time for having chosen the cerebellum as the first tissue he examined, as these cells were arranged in a way more easily visualized using his improved Golgi method.²

He also described gaps between the projection of one cell and another, across which he believed communication took place. It thus became clear that, in an often-used phrase, cells were associated by contiguity, not continuity. By 1891, the German anatomist Wilhelm von Waldeyer-Hartz named these cells neurons (he also coined the term chromosomes), and expressed the neuron doctrine, which indicated that the neuron is the basic unit in the nervous system in terms of both structure and function. There was growing recognition that neurons communicated across the gaps Cajal had described, which the English physiologist Charles Scott Sherrington named synapses in 1897.

A Persistent Belief

Golgi was never able to accept the notion of neurons as individual units, continuing to believe that the reticulum he described formed a nerve organ, which accounted for the brain’s unity of action. When both men were jointly awarded the Nobel Prize in 1906—the only time they ever met in person—Golgi used his Nobel lecture to rail against the neuron doctrine, as if the research of the last two decades had had no impact. His viewpoint was static, while the rest of the community had moved on. Ultimately in the 1950s, electron microscopic images of synapses began to appear, leaving no doubt whatsoever about the relationship between the vast majority of neurons.

Why Couldn’t He Change His Mind?

Why did Golgi persist in his mistaken notion? This may be a potent example of the phenomenon of belief perseverance, the tendency to retain one’s viewpoint in the face of conflicting data.³ Another aspect may have involved confirmation bias, which suggests that a person undervalues new information that goes against one’s beliefs, and overvalues information that would seem to confirm them. In Golgi’s case, we will probably never fully know, but I guess partly it was because this man of ideas was in love with the beauty of the concept of the brain as one completely integrated whole, functioning as one unit. Ideas can be compelling, either through their attractiveness or because they resonate with some deep-seated way of looking at the world.

Neuroscience Essential Reads

How the Brain Learns to Perform Quickly Without Overthinking

The Upcoming Solar Eclipse Is a Natural Wonder

Other examples of brilliant men being resistant to new models include Einstein’s view that quantum mechanics was wrong, or at least incomplete, because he believed that God “does not play dice.”^4,5 This of course was a casual and colorful phrasing of a view based on complex mathematics, but one cannot help but believe that at least some of his resistance was because quantum theory, with its emphasis on uncertainty and randomness, ran against his deep-seated belief of how the world works.

In Golgi’s case, it was certainly not that this brilliant man did not understand the concepts of the neuron doctrine or the studies that supported it. His story goes against the view that persons who hold fixed false beliefs may have trouble grasping opposing views, and that surely if they understood the data they would change their minds. Coming back to the topic of public discourse, one implication is that when dealing with people with fixed opposing ideas, it may be wiser to not focus on the immediate difference, but rather to step back and consider the disparity in broader beliefs and world views that underlie them.

Portions of this article are adapted from The Battle Over the Butterflies of the Soul: Camillo Golgi, Santiago Ramon y Cajal, and the Birth of Neuroscience.