The father of modern neuroscience and the discovery of the basic unit of the nervous system

پدر علوم اعصاب مدرن و کشف واحد اساسی سیستم عصبی
Purkinje cells behind the human hand that are responsible for maintaining balance. Painting by Santiago Ramونn Cajal

For years, Santiago Ramón y Cajal spent hours alone in his laboratory. With his head bowed and his back bent, he stared into his microscopic eye with his black eyes; The only means of connecting him to the outside world.

His wide forehead and beak nose gave him the appearance of a prominent and royal man, despite the fact that his head looked like a bald priest. All he had for his guests were glass bottles of different sizes and shapes containing powders and colored liquids sealed with cork.

Magazines and notebooks were piled on the chairs, and no one could sit down. Desktop designs and paintings were replaced by color, ink, and blood.

Colorful, transparent slides, strewn with neural tissue fragments of sacrificial animals preserved with their fresh chemicals, were scattered on the desk.

Kakhal used his left fingers to adjust the slides like a miniature painting under a microscope lens. With his right hand, he rotates the brass screw of the microscope and focuses the image with many grunts.

Brown-black bodies resembling ink spots with glowing, filamentous tails on a yellow, clear background. With this image, an amazing view of the brain was finally revealed to him; More real than he could have imagined.

In the late 19th century, most scientists believed that the brain was composed of a tortuous, labyrinth-like mass of fiber. Cachal is the first real evidence that the brain is made up of single cells (later called neurons) that are essentially no different from cells in the rest of the living world.

Santiago Ramونn Cachal is the father of neuroscience
A portrait of a cuckoo in his youth

He believed that neurons act as storage units for mental activities such as thoughts and emotions, resulting in the experience of being alive.

“Knowing the brain is tantamount to identifying the material path of thoughts and will,” he writes. Kakhal states that the highest ideal for a biologist is to solve his riddle. He thought he had found the house of consciousness in the structure of neurons.

Kakhal is known as the founder of modern neuroscience. Historians place him alongside Pasteur and Darwin as one of the greatest biologists of the 19th century, and alongside Copernicus, Galileo, and Newton as one of history’s greatest scientists.

His masterpiece, Tissue of human nervous system and vertebrates (Texture of the Nervous System of Man and the Vertebrates), Is one of the basic books of neuroscience; Similar The origin of the species Darwin’s effect on evolutionary biology.

Kakhal was awarded the Nobel Prize in 1906 for his dedicated and compassionate work on the structure of nerves, their birth, growth, decline and death, as if they were human beings.

He created thousands of beautiful and intricate paintings of neurons that are still published in neuroanatomy books and displayed in museums. In his own words, “only real artists are attracted to science.” More than a thousand years after Kakhel’s Nobel Prize, we owe our knowledge of the appearance of the nervous system to him.

A new truth

Painting by Santiago Ramon E. Cachal of Neurons
Cachal drawing of the end of a mouse’s thalamic neurons

In the time of Kakhal, the most advanced method for imaging cells was histology; A delicate and sensitive process of staining tissues described by chemicals whose molecules adhered to the microcellular architecture and revealed them under a light microscope.

Despite the primitive colors, scientists across Europe failed to figure out the nature of what was in the brain (the organ that was considered the organ of the mind).

Then in 1873, in the kitchen of an apartment in Abbategrasso outside Milan, the Italian scientist Camillo Golgi developed by chance and skill a technique that transformed neuroanatomy.

“I have achieved extraordinary results and I hope it gets better in the future,” Golji wrote in a letter to a friend. He considered his method so powerful that it could even reveal the structure of brain tissue to the blind. Golji called this achievement the Black Reaction.

Kakhal, who first saw the technique at the home of a colleague who had just returned from Paris, was surprised. He writes in his memoirs:

“On a completely pale yellow background, scattered black streaks appeared, which were soft and thin or thick and oblong, like triangular stars or bifurcated bodies!” They could be thought of as designs with Chinese ink on transparent Japanese paper … Everything here was simple, clear and tidy … one could not take one’s eyes off this ecstasy. “This dream technique is a reality!”

Although the black reaction reduced the number of neural elements visible under a microscope slide, these elements were still too compact to distinguish their fibers.

Typically, researchers found nerve tissue in the nervous system of adults who had died naturally after a long life. The problem was that in the adult nervous system, the fibers were fully developed and in their most complex structural state.

Astrocyte Neurosis Santiago E. Cachal
Astrocytes, the supporting cells of neurons

To solve this problem, Kakhal turned to embryology or ontogeny. “If we look at the natural process in reverse, it is not surprising that many of the structural complexities of the nervous system disappear over time,” he says.

In the nervous system, younger specimens of cells are theoretically simpler, the fibers are shorter and shorter, and the connection between them is easier to detect.

The nervous system is also well adapted to the embryonic method, because as axons grow, myelin sheaths – the covering layers of fat and protein – are formed that push back the silver microcrystals and prevent the fibers inside from staining. Young axons absorb color completely without thick pods.

In addition, mature axons, which sometimes grow to several tens of centimeters, can be cut in the cutting process. “Since an adult forest becomes impenetrable and indistinguishable, why not study young, growing forests?” Writes Kakhal.

At the age of 36, Kakhal returned to his favorite childhood hobby: hatchery. But this time, instead of waiting and seeing the newborn chicks transform, after a few days, they cut the eggshell and remove the embryos.

Cerebellum of Santiago Ramon E. Cachal
Purkinje axons of a drowned human cerebellum

The embryonic tissues were too thin to withstand the pressure of the microtome clamps. So holding the tissue between the thumbs and index finger of his left hand, Kakhal used to cut pieces with a razor blade – he had apprenticed with a hairdresser as a young man, but he never imagined that one day he would use this skill in this way.

A Cachel student in Barcelona who worked with him in the laboratory admits that his cut pieces – often between 15 and 20 microns thick – were perfectly cut with a machine.

In April 1888, Kakhal provided specimens of the cerebellum of a three-day-old pigeon embryo. From his microscope lens, he stared at a sharp, tiny axon that continued down the curve from the base of the cell – a soft, conical protrusion on the cell body.

The axon followed a curved path between its underlying cells and eventually branched out. In Kakhal’s eyes, Purkinje cells were seen under the black reaction as “the most delicate and leafy trees.”

He followed a branch from the “pearl-like” body of the cell to the end; Where it ended up in other cells (star cells), each of which formed a “basket” -like shape.

Despite the close connection, the “pearl” of one cell and the “basket” of the other cell had no contact with each other. A “new truth” formed in Kakhal’s mind: nerve cells were running out freely. They were single, isolated cells.

The forest is intertwined

Retina cells
Layers of retinal cells. Kakhal studied the retinal cells of different animals and found similarities.

Ever since scientists began studying the nervous system in ancient times, they have tended to compare its structure with that of contemporary technology.

The ancient Egyptians saw slag left over from the smelting of iron ore in the outer covering of the brain, with its cracks and twists. The ancient Greeks thought the brain worked like a catapult.

René Descartes believed that animal souls flowed from the brain to hollow nerves and contracted muscles; Just like moving hydraulic fluids through machines in the Royal Gardens of St. Germain.

In the 19th century, with the advent of the modern age of transportation, Otto Deiters, like many other anatomists of his day, considered the nervous system as a railroad through which traffic flows at intersections.

In the mid-19th century, the metaphor of the railroad was replaced by another technological advancement: the telegraph. The German School of Biophysics, led by Hermann von Helmholtz and Emil du Bois-Reymond, was responsible for this change.

Cortical glial cells
Glial cells of a child’s cerebral cortex

“The wonder of our time, the electronic telegraph, has been modeled on animals for a long time,” de Beauvais said in a lecture in 1851. He argued that the resemblance between the nervous system and the electric telegraph was profound: “It’s more than a resemblance. “The two are related, an agreement not only in works, but perhaps in causes.”

On the other hand, the engineers who designed the telegraph networks, including Samuel Morse and Werner von Siemens, considered the biological nervous system as a model for centralism and organization.

Despite people traveling between countries for the first time and establishing global communication, connecting countries became a social ideal.

Growing up in a pre-industrial village, Kakhal saw natural images of his childhood in the nervous system. “Is there a tree in our gardens that is thinner and more leafy than the cerebellum or cell cells, or in other words, the famous brain pyramid?” He asks.

He saw axon branches as “mosses and shrubs on a wall,” often accompanied by “a short, delicate root resembling a flower”; A year later, he coined the term “moss fibers.”

He found that these fibers terminate in “rose flowers” that approach the dendrites (branches) of other cells but still do not come into contact with them. These are “nests” or “ascending fibers” that “cling to the trunk of a tree like ivy or vines.”

After all, the cells looked like a “forest of tall trees.” Gray matter is an “orchard” and pyramidal cells form “impermeable groves”.

Comparing the complexity of an “adult forest” and a “young forest”, Kakhal found that the cerebral cortex was a “scary forest”; Just like the forests of Cuba when it fought the 10-year war.

He believed that human beings could, with the power of their will, turn this “intertwined forest of nerves” into a “regular and pleasant garden.” The underdeveloped landscapes of Kakhal’s childhood gave him a different perspective than his contemporaries.

Tumor cells of the brain of Santigo Ramon E. Cachal
Brain membrane tumor cells

Although Cajal sporadically referred to the metaphor of the telegraph, he rejected the metaphor altogether at the 1894 International Medical Conference in Rome. His opposition was rooted in his anatomical findings and mental insights.

He knew he could change his mind. For this reason, he opposed the metaphor of the network, which had a fixed structure. According to the nervous system, it must be able to change, and this change is vital for the life of the brain.

One of the terms Kakhal used a lot was “formability”. Although he was not the first to use the term, his speech in Rome probably made the term popular.

This idea is still one of Kahl’s most enduring contributions to science, influenced by his unique and unusual view of the world.

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