Santiago Ramón y Cajal and the Microscopic Structure of the Brain

Santiago Ramón y Cajal in his laboratory.

Santiago Ramón y Cajal in his laboratory.

On May 1, 1852Spanish pathologist, histologist, neuroscientist, and Nobel laureate Santiago Ramón y Cajal was born. Cajal’s original pioneering investigations of the microscopic structure of the brain have led to his being designated by many as the father of modern neuroscience. His medical artistry was legendary, and hundreds of his drawings illustrating the delicate arborizations of brain cells are still in use for educational and training purposes.

“Any man could, if he were so inclined, be the sculptor of his own brain.”
Santiago Ramón y Cajal, Advice for a Young Investigator (1897), p. xv

How to Motivate to Study Medicine

During his early years, Santiago Ramón y Cajal apparently showed talents as a painter, artist, and gymnast. However, it is believed that these were not supported by his family and he was apprenticed to a shoemaker and barber. However, in 1868, his father took him to the graveyards. It is believed that his father wanted to find human remains and hoped to spark his son’s interest for anatomy and medicine. Indeed, he was inspired to study medicine and enrolled at the University of Zaragoza, graduating in 1873.

Cajal as Medical Officer and Professor

Ramón y Cajal became a medical officer in the Spanish Army, serving in an expedition in Cuba during the 1870s. Later that decade, he received his doctorate in medicine and was appointed professor at the University of Valencia in 1883. Later on, he was also professor in Barcelona and Madrid.

Drawing of the neural circuitry of the rodent hippocampus. By Santiago Ramón y Cajal.

Drawing of the neural circuitry of the rodent hippocampus. By Santiago Ramón y Cajal.

Improving Golgi’s Method

During his early years in medicine, Santiago Ramón y Cajal worked on the pathology of inflammation, the microbiology of cholera as well as the structure of epithelial cells and tissues. In Barcelona, during the 1880s, he learned about Camillo Golgi,[5] who in 1906 shared the Nobel Prize with him. Golgi used potassium dichromate and silver nitrate in order to stain a few neurons a dark black color, while leaving the surrounding cells transparent. When Ramón y Cajal was able to improve this method further, he was able to bring focus on the central nervous system. It became then possible to research the brain and spinal cord, when previously, standard microscopic inspection would be nearly impossible. However, the different results that Golgi’s staining method produced at Golgi and Cajal led to an enmity between the two. But where Golgi felt that the neurons were connected, Cajal argued that the brain consisted of autonomous cells.

Evidence of the Neuron

Santiago Ramón y Cajal created his first detailed drawings of neural material, covering major regions of the brain. He postulated that the growth direction and the speed of growth of the nerve processes (axons) are controlled by a growth cone at their ends. He had discovered that neuronal cells could receive chemical signals that indicated a direction for growth (chemotaxis). He further demonstrated experimentally that the relationship between nerve cells was not continuous, but contiguous. This discovery later provided evidence for the “neuron doctrine”, today considered the foundation of modern neuroscience. Further, he supported the existence of dendritic spines and discovered a new type of cell, which was subsequently named after him: the interstitial cell of Cajal. In 1894, he suggested that cortical pyramidal cells may become more elaborate with time, as a tree grows and extends its branches.

Further Study of the Brain

Ramón y Cajal conducted intensive studies to demonstrate qualitative differences between the brains of humans and animals. He hypothesized: “The functional superiority of the human brain is very closely related to the amazing abundance and unusual variety of forms of the so-called neurons with short axons“. This was the core of the problem of the cerebral cortex, and finally he had to admit: “… the indescribable complexity of the structure of the grey matter is so complicated that it defies the stubborn curiosity of researchers and will defy many centuries to come“.

The Nobel Prize in Medicine

During his career, Santiago Ramón y Cajal became the director of the Zaragoza Museum and the director of the Instituto Nacional de Higiene. He was further the founder of the Laboratorio de Investigaciones Biológicas. He received the Nobel Prize in Physiology or Medicine in 1906, together with the Italian scientist Camillo Golgi “in recognition of their work on the structure of the nervous system”.[5]

“The history of civilization proves beyond doubt just how sterile the repeated attempts of metaphysics to guess at nature’ s laws have been. Instead, there is every reason to believe that when the human intellect ignores reality and concentrates within, it can no longer explain the simplest inner workings of life’ s machinery or of the world around us.”
– Santiago Ramón y Cajal, Advice for a Young Investigator (1897), p. 2

Later Years

In his last years he continued to work, preparing publications and reissues, and he devoted himself to his students. Several of them (especially his favorite disciple since 1905, Jorge Francisco Tello, who had succeeded him in his professorship and in the direction of the Institute), at the express wish of Ramón y Cajal himself, accompanied him in his death on October 17, 1934, after the worsening of an intestinal illness that weakened his heart.

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