Science & People

Santiago Ramon y Cajal | Biography, discoveries, neuron theory

When old Santiago Ramon y Cajal was a young anatomist in 1887, he saw the nerve fibers stained by the new method described by Italian scientist and medical doctor Camillo Golgi for the first time. He described this moment of enlightenment as follows:

What an unexpected sight! Sparse, smooth and thin black filaments or thorny, thick, triangular, stellate, or fusiform black cells could be seen against a perfectly translucent yellow background! One might almost liken the images to Chinese ink drawings on transparent Japanese paper […] this is the Golgi method

Santiago Ramon y Cajal, Histologie du Systeme Nerveux de L’Homme et des Vertebres (Histology of the nervous system of man and vertebrates), 1909

Who is Santiago Ramon y Cajal?

Cajal was born on May 1, 1852, in a small village in the Spanish countryside, his father was a barber-surgeon. Later, with great efforts, he managed to get a medical diploma and asked his son to go to medical school. But like many talented young men, Cajal was a rebellious adolescent and he didn’t like the strict discipline of the school. He intended to become an artist as he was talented at it from an early age. This idea terrified his father and his father eventually won; Cajal graduated from the medical school in Zaragoza in 1873. He immediately joined the medical service in the army. But, in less than a year he contracted malaria, and tuberculosis in Cuba, was sent home. Santiago Ramon decided to start a career that relied heavily on his artistic skills as anatomy was the only subject in which he was interested or inclined. He reached increasingly prestigious academic positions in Valencia, Barcelona and Madrid, was internationally recognized for his discoveries in the cellular architecture of the nervous system, and in 1906 he won the Nobel in Physiology and Medicine with Golgi.

Seeing inside the brain

Pyramidal Cell stained via Golgi technique
The appearance of the neuron via the Golgi staining technique shows the fine structure of dendrites and axons.

Until the middle of the 19th century, the use of a microscope to examine cells and tissues was limited to primitive techniques. This was a particular problem, especially when examining the nervous system. The “cell theory“–the argument that all living things are made up of cells–was explicitly stated in 1839 and considered valid for almost all organs, only the nervous system was an exception. Yes, the nervous system was functioning with electricity, but how electricity was produced and transferred, and what was its relationship with this fine structure?

Even the brain and spinal cord seemed to consist mostly of fibers. Although the cells were seen, they were hardly distinguishable in the middle of the fiber masses, and it was not known whether they served a secondary purpose, such as feeding the fibers, or whether they had a greater significance. Golgi provided a solution by discovering the method of staining nerve tissues with silver chromate, which allowed the nerve cell pathways in the brain to be seen for the first time since it provided a limited number of cells to be stained in integrity.

But Golgi staining was not very reliable, it was difficult to reproduce, and was not used much in the 1880-1885 period, as Golgi reported. Golgi’s courage was broken that he moved away from neurohistology and started working on malaria, which had brought him new fame. Santiago Ramon took over his method, made innovations in the staining technique, and had progressed to make many original discoveries over the years. He had observed numerous different types of nerve cells–now called neurons–and their relationships with each other in different parts of the central nervous system. The depth and breadth of his observations are such impressive that today’s neuroanatomists still refer to him when they write their own findings today.

Santiago Ramon y Cajal’s talent

Drawing of a Purkinje neuron from the human cerebellum by Santiago Ramon y Cajal, 1899
Drawing of a Purkinje neuron from the human cerebellum by Santiago Ramon y Cajal, 1899

Certain features of Cajal’s personality had important effects on his success. He had the imagination to choose the most important problems to work on and to identify exactly where they are in the central nervous system. Since it was rare to see the entire neuron at a glance, and it was never seen for most people, he traced patiently and meticulously, by taking different looks at the neuron. Later on, he synthesized the details of these glances, describing what he saw clearly.

He had no equal in capturing the relationship between the neurons rarely seen together at a glance from a microscope. His strongest part was not to trace long paths along with the nervous system, but rather to evaluate the connection between cells in certain areas, such as the cerebellum, brain shell, and web layer. He would not avoid drawing a gap between a neuron and the fibers of the adjacent neuron to highlight the discontinuity he felt was there, when it was not possible to see it.

The founder of modern neuroscience

Drawing of Cajal showing complex connections between layers in the hippocampal region in the rat brain.
Drawing of Cajal showing complex connections between layers in the hippocampal region in the rat brain, emphasizing the one-way pathway of nerve impulses along dendrites, cell body, and axons.

His work was important in establishing the main principles that we consider essential in understanding the nervous system today. The first principle is about the basic units of the neuron system. Shorter dendrites and longer axons branch out of the cell body that provides nutrition to these elongated ridges. The second principle is the nerve impulses that move only in one direction in one neuron, from dendrites to the cell body, then from the cell body to dendrites or axons and branches that connect to the cell body of another neuron. The third principle is that each neuron maintains its individual integrity. There is a physical discontinuity between neurons: connections do not involve physical association with the extensions of another neuron. Nerve stimulation only moves in one direction during this discontinuity (later called the synapse); that is, nerve pathways are neuron and synapse chains.

He was an uncompromising advocate of the concept of autonomous neurons that follow restricted conduction pathways throughout the nervous system, known as the Cajal neuron doctrine. He thought that he could explain the rapidly evolving evidence with the localization of certain functions in certain places in the brain and spinal cord. It was especially beneficial to study the cells in the brain shell. These were the basis for mapping the visual, tactile, and motor representation at different locations in the shell.

The neuron theory continued to evolve, and had such a great power of explanation and foresight in the physiology and pathology of the 20th century that the theory was considered as the foundation of modern neurobiology, where Cajal was the founder of modern neuroscience. However, there were criticisms of the neuron theory when Cajal was still alive. When Cajal died in 1934, he was still defending the theory. The theory was proven only in the 1950s by the visualization of synapses with an electronic microscope.

Santiago Ramon y Cajal quotes

  • “Any man could, if he were so inclined, be the sculptor of his own brain.”
  • “As long as our brain is a mystery, the universe, the reflection of the structure of the brain will also be a mystery.”
  • “Perseverance is a virtue of the less brilliant.”
  • “Nothing inspires more reverence and awe in me than an old man who knows how to change his mind.”
  • “Heroes and scholars represent the opposite extremes… The scholar struggles for the benefit of all humanity, sometimes to reduce physical effort, sometimes to reduce pain, and sometimes to postpone death, or at least render it more bearable. In contrast, the patriot sacrifices a rather substantial part of humanity for the sake of his own prestige. His statue is always erected on a pedestal of ruins and corpses… In contrast, all humanity crowns a scholar, love forms the pedestal of his statues, and his triumphs defy the desecration of time and the judgment of history.”
  • “The mediocre can be educated; geniuses educate themselves.”