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Authors: Andrew Koob

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But Hippocrates, who lived from 460–379 BC, challenged this view. To Hippocrates, the evidence of traumatic injury to the head and the resulting deficits in language and emotion were because the brain was the seat of intelligence. Trepanation—the drilling of a hole in the head to release pressure and a technique still employed by brain surgeons today to alleviate some symptoms of injury—was also evidence for his theory.

Hippocrates wrote, “Men ought to know that from nothing else but the brain come joys, delights, laughter and sports, and sorrows, grief,
despondency, and lamentations. And by this, in an especial manner, we acquire wisdom and knowledge, and see and hear and know what are foul and what are fair, what are bad and what are good, what are sweet and what are unsavory…in these ways, I am of the opinion that the brain exercises the greatest power in man.”

He would also conclude that we suffer when the brain is hot, cold, moist, or dry. He thought madness occurred when the brain was moist and that only when the brain is “still” could a man think properly. These last sentiments might not be entirely true, but they were to inspire Aristotle (384–322 BC). Aristotle tried to include Hippocrates’ studies with those in the heart camp. He still believed the heart was the seat of higher thinking, but that the brain cooled the heart when it overheated with emotion. Rational humans were those with better brain-cooling capacity.

In Roman times, the physician to the gladiators, Galen (AD 130–200), was and still is most prominent. He sided with Hippocrates’ view. He spent careful time dissecting animals, such as sheep, and looking at gladiators who suffered traumatic injury. His conclusions definitively set the seat of intelligence in the brain.

Cavities called ventricles in the center of our brains and the spinal cord contain cerebrospinal fluid. At this time, there was a perception of the existence of four vital fluids to the body: blood, phlegm, black bile, and yellow bile. To Galen, the ventricles contained yellow bile. To control thought and movement, the brain somehow sloshed the yellow bile throughout the nerves that extended into the body. His view lasted for 1500 years until Descartes (1596–1650).

Descartes didn’t necessarily create a different view, but sought an anatomical idea of the human based on the perceived undeniable truths of religion. He thought the brain worked as a center for the spirits of the soul. The spirits were the fluids, and like Galen, Descartes believed they controlled our thoughts and then flowed through the body to cause movement.

But Descartes believed Galen’s explanation for humans as similar to sheep could not be reconciled with the notion that humans were created in God’s image. He thought the mind stood separate from the physical body as a wisp in the ether that could act on the body. The pituitary gland was a pump through which the mind controlled the spirits. As modern technical inventions have influenced how we understand the workings of
the brain, the invention of hydraulics at this time in France solidified Descartes’ idea. The pumping of the pituitary by the mind created fluid to reach the muscles and cause them to contract, much like a hydraulic instrument when pumped.

With the advent of the microscope in the seventeenth century, scientists were enthralled by the prospect of seeing for the first time a view of the nerves through which spirits flowed. If they could see what was responsible for the soul, they could become closer to God. When the nervous system was first analyzed with the microscope in the late seventeenth and early eighteenth century by Dutch scientist Anton von Leeuwenhoek (1632–1723), parts of the tissue were mashed between two glass slides like squashed mud. In the peripheral nerves, he saw what looked like cylindrical tunnels. Descartes’ tubes for the transfer of spirits were confirmed.

This belief stood for a century and a half until the microscope became more reliable at the beginning of the nineteenth century and the term “cell” was in use to describe the functional unit of other organs and lower life forms such as the single-cell amoeba. It became obvious the brain was comprised of cells as well. Then Hermann von Helmholtz (1821–1894) discovered that when the brain was placed in wine alcohol, it wouldn’t decompose and would extract water from the tissue, leaving behind the cells for analysis. Whatever thought led Helmholtz to toss someone else’s decaying brain into his wine is certainly evidence for the limitlessness of human original thought and creativity,

Descartes’ notion of spirits was challenged when religion took a back burner to science. Before alcohol fixation (and formaldehyde at the turn of the twentieth century) when the brain was removed initially after death, it looked like a gob of sticky grey goo, which was connected by long white fibers. The fibers were attributed the most importance—the avenues for Descartes’ spirits and the housing for the method of thought.

Glia are everything else outside the fibers. The term glia comes from ancient Greek meaning something slimy or sticky in appearance. In modern Greek, and perhaps fittingly for those that believe in the predominance of neurons, the root glia remains in a word that means a filthy and morally debased person. Of course, this can be a badge of pride for glia proponents. In Herodotus, the word means “gum” and in the plays of Aristophanes, it means “sticky” or “knavish.” The man who took this word from Greek and applied it to the brain was Rudolf Virchow
(1821–1902). In 1858, while looking at glia cells, he thought they were “nerve putty.” These ubiquitous cells throughout the brain didn’t seem to be the root of the fibers going out to the body, the important containers of the yellow bile, the spirits. And now it was believed the white fibers were obviously conducting electricity, but where did they come from?

Finally, with Darwin’s theory of evolution in 1859, the cell as the functional unit and from which all life has evolved was common scientific belief.

Scientists were now on the brink of discovering the cellular unit in the brain that was responsible for thought—the same cells Darwin used to invent his theory. Because the fibers were perceived as the connections driving thought, researchers wanted to definitively know what they were. One of Virchow’s students, Otto Deiters (1834–1863), and Albreicht von Kolliker (1817–1905) began to make the first accurate drawings of nerve cells, which had tails on the ends of them. The sperm-like structures were intriguing, but it was not definitive that the tails were the fibers. The discovery of Robert Remak (1815–1865), who examined the nervous system of the ox, that the cell body in the spinal cord was attached to the fiber began to convince scientists that the fiber was part of a cell, and the tail-like structure reaching out was the fiber.

The idea that cells in the brain had tails on them (called processes) that emanated out into the body as fibers meant that these cells must hold all the information in the brain. They were subsequently called neurons. And everyone had jump to conclusions a tad early.

Two men stood at the forefront as advocates for the neuron. One was by all accounts a pompous self-promoter. His coiffure was well-groomed. His mustache rivaled Teddy Roosevelt’s. He was a dashing Italian who loved women, cigars, alcohol, and himself. He discovered one of the most important cell illuminating pigment stains in the history of science. His name was Camillo Golgi (1843–1926), and working in a small town in northern Italy, he discovered the silver nitrate staining method. Using silver nitrate on preserved tissue—an idea he got from early photography methods for staining film—Golgi could visualize the individual cells in the brain, and more importantly, he could visualize the tail-like processes extending from the cell bodies that make brain cells unique. He became a professor of histology and pathology at the University of Pavia, and the stain is now called the Golgi stain.

The other man was the grimacing, menacing Spanish histologist at the University of Madrid, Santiago Ramón y Cajal (1852–1934) (see
Figure 2.1
). Cajal was described as quiet and diligent. He was like a grumpy bear in the woods catching fish. He wrote volumes of clear and concise books on what he saw under the microscope using Golgi’s staining method and his own advancements using gold chromide. Determined, meticulous, and over-confident—three qualities valued in science—Cajal gained the utmost respect from his peers. One of the most important talents for a researcher during this time period was artistic ability. In order to represent what was seen in the microscope, a researcher had to draw it. Golgi’s artistic ability was unmatched, but Cajal detested the liberties Golgi took with his representations. Although Cajal couldn’t draw as well as Golgi, he believed he was more accurate. He peppered his books with his drawings of brain anatomy and writing about what he understood to be happening in the brain.

FIGURE 2.1 Santiago Ramón y Cajal, the dour curmudgeon

 

It wasn’t until Golgi (see
Figure 2.2
) developed his famous staining technique that researchers could definitively follow the tail-like process (now called an axon) throughout the brain, understand the fibers extending from a cell body, and confirm Remak’s findings. Based on the previous ideas from Galen, through Descartes to the present, this cell body was believed to be the important storage of the information and thoughts in the brain. Axons traversing from one side of the brain to the other and to the muscles were the long-distance communication of the information storage.

FIGURE 2.2 Golgi, the visionary

 

Golgi’s stain also visualized glial cells; they looked like little spiders throughout the brain surrounding the large cell bodies of neurons and axons.

Golgi believed the brain worked like a syncytium, or a net. He thought that all the cells were connected and not discernibly separated. They worked in the manner of a reticulum; in other words, he thought the cells in the brain responsible for thought functioned together fluidly and not incrementally. He believed the main function of glia was to feed neurons. This was because the glial processes seemed to connect with blood vessels and neurons.

Cajal and Golgi disliked each other immensely. Golgi rubbed Cajal’s meticulous manner the wrong way. Perhaps it was petty jealousy or simply blind rage, but Cajal completely discounted any idea Golgi formed. To Cajal, any blundering scientist could see from the staining method
that the brain was comprised of incremental cells like the rest of the body. These increments were divided into two main cell components: neurons and glia. Neurons were most important because the cells extended longer distances. The cell body was in the middle, and the processes reaching for information looked like the branches of the tree. Although it was clear information was transmitted down a long trunk called an axon, Cajal wasn’t sure what to think of glia.

A brilliant student of Virchow’s, Carl Ludwig Schleich (1859–1922) (see
Figure 2.3
), went against his mentor and was the first to propose that glia and neurons were able to signal to each other. This revolutionary idea completely abolished the “fiber-central” view passed down from the time of Galen and was a major leap of innovation in brain research. He thought the gaps between neurons signaling to each other made it possible for glial cells to modulate the connection. Glia must help inhibit neuronal signaling, he postulated.

FIGURE 2.3 Carl Ludwig Schleich lounging

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