The Nobel Prize Winner who Unraveled the Human Brain

Photography, medicine, and art: Explore the history of the pioneer of modern neuroscience, Santiago Ramón y Cajal.

By Royal Academy of Medicine of Spain

Real Academia Nacional de Medicina de España

Sculpture of Santiago Ramón y Cajal (2007) by Victor OchoaOriginal Source: Real Academia Nacional de Medicina de España

Cajal: Man and Science

To this day, Santiago Ramón y Cajal is still the most cited Spanish scientist in history.

The fact that he is often described as such is a testament to the importance of the Spanish Nobel Prize winner's work. The endurance of his legacy and the contribution he made to world science as a Spaniard are unrivaled.

His "neuron doctrine" became a central tenet in our understanding of the structure of the nervous system. His research showed that the nervous system is made up of independent cells called neurons, which are interlinked through specialized connections known as synapses.

Santiago Ramón y Cajal's first laboratory journalOriginal Source: Instituto Cajal (CSIC)

The 80th anniversary of his death was commemorated on October 17, 2014. To mark the occasion, a large part of the archive of his life and work was exhibited for the first time, allowing his career and the impact of his work as a full member of Spain's Royal Academy of Medicine (RANM) to be revisited.

At the same time the RANM, in partnership with the Cajal Institute (part of the Spanish National Research Council), with funding from the Tatiana Pérez de Guzmán el Bueno Foundation, put on a small exhibition. We have recreated this exhibition in a virtual format to reveal the 2 sides of Cajal: the man and the scientist. Neither one can be understood without the other.

The picture shows Santiago Ramón y Cajal's illustrated and handwritten scientific notebook on stains and laboratory tests.

1852–1875: The Early Years

Santiago Ramón y Cajal was born on May 1, 1852 in Petilla de Aragón. He was the son of a "second-class surgeon" by the name of Justo Ramón y Casasús, and Antonia Cajal Puente. Justo was a severe, tenacious man who would go on to achieve a degree in medicine and be an influence in the medical career of his first-born son.

Portrait of Justo Ramón Casasús, father of Santiago Ramón y CajalOriginal Source: Real Academia Nacional de Medicina de España

Justo spent the early days of his career in smaller places such as Larrés, Luna, and Valpalmas. He eventually settled in Ayerbe (near Huesca), by which time he was already a doctor. His family always accompanied him.

Santiago was not a particularly good student. He attended the Escolapios School in Jaca, where despite the incredibly strict environment, he leaned towards developing his natural talent for drawing and painting. These skills would go on to be an essential part of his work. He was later a student at the Huesca Institute but, when he misbehaved there too, his father put him to work as a barber's assistant and shoemaker.

In 1869 he finally completed his high school studies and began to study medicine in Zaragoza, where he was already living because his father had found work at the provincial charitable organization. He also worked as an interim lecturer in dissection at the Faculty of Medicine.

Santiago and Justo spent 3 years working together in the dissection laboratory at the Nuestra Señora de Gracia hospital, and it was here that their father-son relationship developed into one of respect and close collaboration.

Ramón y Cajal during his military service in Cuba (ca. 1874)Royal Academy of Medicine of Spain

Santiago was appointed Dissecting Assistant by Zaragoza's Faculty of Medicine in 1871. He graduated in 1873 and decided to join the Spanish Army as a medical officer.

A year later he was promoted to captain and posted to the island of Cuba. While there, he clashed with some of his military superiors over the poor sanitary conditions and use of the medical facilities. He ended up contracting dysentery and malaria: illnesses he would later say permanently blighted his health.

In 1875 and in very poor health, he returned to Spain, where he was appointed as an interim anatomy assistant at the University of Zaragoza.

Anatomical oil paintings (1872) by Santiago Ramón y CajalOriginal Source: Instituto Cajal (CSIC)

His meticulous observations of nature, his passion for drawing and painting (and later for photography), his enjoyment of literature, and his study of philosophy were constant and purposeful.

While studying in Zaragoza, he realized that he could combine his 2 great passions: art and medicine. It was there that he developed his drawing and painting skills, taking advantage of anatomy classes and dissection laboratories.

"Continental" microscopeRoyal Academy of Medicine of Spain

1875–1900: The Beginning of his Investigative Work

Cajal was dedicated to his studies, and in 1877 he was awarded a doctorate by the Faculty of Medicine in Madrid. Influenced by the works of Professor Maestre de San Juan and some of his disciples (especially López Garcia), he decided to return to Zaragoza and set up a micrographic laboratory. In doing so, he spent all his savings on acquiring his first microscope (a Verick), a microtome, and other equipment.

Color portrait study of Ramón y Cajal and his wife, Silveria (ca. 1892)Original Source: Instituto Cajal (CSIC)

In 1879, he married Silveria Fañanás, with whom he would go on to have 7 children. In the same year, he was appointed director of the University of Zaragoza's Anatomy Museums.

Cajal in Barcelona (1888)Original Source: Instituto Cajal (CSIC)

Cajal's academic work didn't end there: in 1883 he was awarded a professorship in anatomy in Valencia, and 4 years later he moved to Barcelona, where he became Professor of Normal and Pathological Histology.

It was at this point that he learned Golgi's staining method, which was to be essential throughout his career.

Self-portrait of Ramón y Cajal with his children Santiago, Paula, Jorge, and Fe, in Barcelona (1888-1891) by Santiago Ramón y CajalOriginal Source: Instituto Cajal (CSIC)

When he was not yet 15, his fascination with photography was piqued by a band of traveling photographers. From then on, it became one of his main hobbies: he went on to publish some of his work and became an expert in the field.

Santiago Ramón y Cajal left behind a vast quantity of photographs that he had taken throughout his life. The photographs document his travels around the world, as well as his personal and professional life.

His knowledge of photography was also useful in his professional research.

Santiago Ramón y Cajal's first laboratory journal Santiago Ramón y Cajal's first laboratory journal (1877-1887) by Santiago Ramón y CajalOriginal Source: Instituto Cajal (CSIC)

In 1888 he discovered the structure of the nervous system, presented his neuron doctrine, and began to publish the Quarterly Journal of Normal and Pathological Histology.

This picture shows one of his annotated notebooks, in which he recorded his research, ideas, sketches, and more.

Santiago Ramón y Cajal's first laboratory journalOriginal Source: Instituto Cajal (CSIC)

A year later he published his Manual of Normal Histology and Micrographic Technique and went to Berlin, where a congress of the German Anatomical Society was being held. There, he shared his work with the highly respected Albert von Kölliker, who went on to introduce and defend his work among scholars.

Photograph of the Faculty of Medicine 1905–12 (1905 - 1912)Original Source: Real Academia Nacional de Medicina de España

In 1892 he was appointed to his final teaching position: Professor of Histology and Pathology in the Faculty of Medicine at Madrid's Central University, where he remained until his retirement in 1922. As a result of this post, he was awarded important national recognition by the Government.

Santiago Ramón y Cajal's first laboratory journalOriginal Source: Instituto Cajal (CSIC)

Cajal's Neuron Doctrine

This was Cajal's most productive period. He exclusively used Golgi's method to produce detailed descriptions of almost all the structures of the central nervous system.

Cajal's observations were so accurate and precise that his most well-known book, Histology of the Nervous System of Man and Vertebrates (1909–11), which summarizes his research, is still used as a reference in neuroscience laboratories today.

During the early years of his career, Cajal worked on gathering extensive evidence in support of his neuron doctrine: evidence that would also disprove the prevailing reticular theory.

Before the neuron doctrine was accepted as correct, it was assumed that the nervous system was a "reticulum" or single continuous network, rather than a system composed of individual cells. This was known as the reticular theory.

The first hindrance to acceptance of the neuron doctrine was partly due to the difficulty of viewing cells through microscopes, which were not technically advanced enough to provide a clear image of the nerves. Using the cell staining techniques of the time, a section of neuronal tissue would appear as a complex network under the microscope, and individual cells could not be made out.

Camillo GolgiOriginal Source: Instituto Cajal (CSIC)

Camillo Golgi was an Italian neuroscientist who received the Nobel Prize in 1906, together with Santiago Ramón y Cajal.

Golgi's method is a simple histological procedure by which the entire structure of a neuron can be observed in 3 dimensions. The method produces a formation of opaque silver chromate deposits in the cells—a product of the reaction between potassium dichromate and silver nitrate (known as the "black reaction").

Histological preparations by Santiago Ramón y CajalOriginal Source: Instituto Cajal (CSIC)

Cajal studied and became familiar with Golgi's method for staining samples of the brain. He used his extensive knowledge of taking and developing photographs to improve how these samples appeared under the microscope.

Ramón y Cajal's Reduced Silver Nitrate Technique, 2009, From the collection of: Royal Academy of Medicine of Spain
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The drawings of Ramón y Cajal by Santiago Ramón y CajalOriginal Source: Instituto Cajal (CSIC)

This staining technique was based on a silver solution and only stained 1 cell out of every 100, making it possible to isolate and view the cell. This allowed Cajal to observe that they were individual cells and not part of a continuous network. As a result, he was able to clearly make out the neurons and draw pictures of them, like the image on the left.

Current home of the Cajal Institute on Avenida Doctor Arce in MadridOriginal Source: Real Academia Nacional de Medicina de España

1901–1934: Recognition

His work was recognized nationally and internationally, and widely acclaimed and commended by scientists and institutions who were astonished by his findings.

In 1901 the Laboratory for Biological Research was set up in a small hotel. The following year, it moved to Dr. Velasco's Anthropological Museum.

This laboratory would go on to produce many great researchers and disciples of Cajal's teaching, such as Jorge Francisco Tello and Fernando de Castro, as well as his own son, Jorge Ramón Fañanás.

In 1920 the Government decreed that the laboratory should become part of a new Institute for Biological Research that would be named after Ramón y Cajal. However, the institute was not completed until 1932, by which time Cajal was too elderly to take on the role of director. This position was given to Francisco Tello.

Nobel Prize Diploma (1906)Original Source: Instituto Cajal (CSIC)

In 1905 he was awarded the Hermann von Helmholtz Gold Medal by the Academy of Sciences in Berlin: a biannual prize awarded to scientists whose work has made a significant contribution to any branch of science.

This medal was the prelude to an outstanding award. On December 10, 1906 he went on to receive the Nobel Prize in Physiology or Medicine: undoubtedly a great, if not the greatest, international achievement in Spanish science.

Santiago Ramón y Cajal's first laboratory journalOriginal Source: Instituto Cajal (CSIC)

However, the recurring theme of Cajal's work was research, and his work was documented in prestigious publications. These included Texture of the Nervous System of Man and the Vertebrates (1904), which was also published in France 7 years later, and Degeneration and Regeneration of the Nervous System (1914).It was not until almost 2 decades later, in 1933, that the book Neuronism or Reticularism? would be published, setting out his neuron doctrine. This is the book that came to be regarded as his scientific legacy.

The writings and published works that this scholar left behind will always be a first-class reference in the world of neuroscience.

Portrait of Ramón y Cajal with a handwritten inscription (1922) by PadróOriginal Source: Real Academia Nacional de Medicina de España

Santiago Ramón y Cajal went on to become a national hero and was the subject of a book by the renowned researcher Pedro Laín Entralgo.

In the year that he was awarded the Nobel Prize, Cajal turned down a post offered to him by the Spanish Prime Minister, Segismundo Moret, in the Ministry of Public Education. He did so because he wanted to devote his time entirely to research and teaching. However, he felt morally obliged to accept relevant appointments such as the directorship of the Alfonso XIII National Institute of Hygiene and the presidency of the Board for the Expansion of Scientific Research and Studies (established in 1907). He had been a driving force in setting up this board, the purpose of which was to enable young Spanish researchers to complete an appropriate formative stage of their careers abroad. He held this post until his death.

Cajal was dedicated to education. Evidence of this can be seen in the inscription in Cajal's own handwriting below this photographic portrait which says:

So often has it been said that the problem with Spain is a cultural one. Indeed, if we wish to be part of the civilized world, it is mandatory that we cultivate the barrenness of our land and of our minds, rescuing for posterity and for the motherland all the rivers that are lost in the sea and all the talent that is wasted in ignorance.

Seat number 38 of the Royal Academy of MedicineOriginal Source: Real Academia Nacional de Medicina de España

Cajal the Academic

In 1896 the Spanish Royal Academy of Medicine awarded Santiago Ramón y Cajal the Dr. Pedro María Rubio prize, and in 1901 the Martínez Molina prize—the latter together with his brother, Pedro Ramón y Cajal.

This academic institution had a deservedly prestigious reputation and, although Cajal was already a professor in the Faculty of Medicine at Madrid's Central University by that time, an award from the academy was still a significant addition to his already considerable list of accolades. On November 13, 1897 Cajal was elected a full member of the Anatomy and Physiology branch of the academy by a large majority of votes.

It would, however, be another 10 years before he took up his post, on Sunday June 30, 1907 "at 3 o'clock in the afternoon," in the academy's headquarters at the time, at No. 6 Calle Mayor.

Invitation to become an academic of the Royal Academy of Medicine (1907)Original Source: Real Academia Nacional de Medicina de España

His inaugural lecture was entitled The Regeneration of the Nervous System, and the response was given by his good friend and colleague Federico Olóriz Aguilera. The pair shared a deep friendship and mutual admiration, as well as some long games of chess played during summer holidays spent together.

Cajal already had the public's admiration when he became a member of the academy, having been awarded the Nobel Prize just a few months previously. He was now a renowned national scientific expert and was established as a leading international figure in the field of research. Cajal remained an active member of the academy until his death in the same year as the academy's bicentenary.

However, this was not the only academy to offer him membership. He was also invited to become a full member of the Spanish Royal Academy of Sciences (in 1895) and the Royal Academy of the Spanish Language (in 1905), although he did not take up his membership of the latter.

Armchair 38 of the Royal National Academy of Medicine: Ramón y CajalRoyal Academy of Medicine of Spain

Santiago Ramón y Cajal at his home in Madrid with a microscope by Santiago Ramón y CajalOriginal Source: Instituto Cajal (CSIC)

The Final Years

During the last years of his research, he concentrated mainly on the study of the traumatic degeneration and regeneration of the nervous system. He published a great many scientific articles on this subject, which were hugely important and which were compiled in another of his most influential books, Degeneration and Regeneration of the Nervous System (Cajal, 1913–14). At that time, Cajal also published some important articles on the structure of the optic centers of invertebrates.

Press cutting from "Estampa" magazine (ca. 1930)Original Source: Real Academia Nacional de Medicina de España

Just as he had done when living in Valencia and Barcelona, Cajal used to meet up with people over coffee on a daily basis. In Madrid, he frequented Cafe Prado and Cafe Suizo, where he spent time in the company of great intellectuals: politicians, philosophers, professors, and military officers, as well as some of his colleagues from the Faculty of Medicine.

Cajal was a visible and respected presence in the city, and unwittingly became one of Madrid's most famous residents. As well as his social gatherings and lectures, he was also an active member of the Ateneo de Madrid institute, where he gave lectures and conferences that were open to anyone interested in attending.

The significance of his work was such that his life became a subject of enormous public interest. This page from "Estampa" magazine shows an article describing a stroll that he took around Madrid, and his day-to-day life.

Cajal walking around MadridRoyal Academy of Medicine of Spain

He was a regular walker, an expert in his field, a daily participant in social gatherings, and he frequently attended the Ateneo. Prestigious research centers were built in his honor, and a walk around these institutions is an interesting way of exploring his life.

He died in Madrid at 10.45 p.m. on the night of October 17, 1934, surrounded by his children, his housekeeper, his secretary, his pupils Tello and De Castro, and the doctors Carro, Calderón, Jiménez Díaz, and Teófilo Hernando.

The latter wrote: Finally, placidly, that magnificent brain ceased to move and became inert matter. He was 82 years old. Madrid's bookshops had just received a new title: his book, The World Seen at 80: Impressions of an Arteriosclerotic.

The drawings of Ramón y Cajal by Santiago Ramón y CajalOriginal Source: Instituto Cajal (CSIC)

Cajal's Legacy

The Cajal Institute of the Spanish National Research Council (CSIC), which houses the "Cajal Legacy," has responsibility for the care of the mainly scientific belongings that Cajal wanted to be preserved in his institute after his death.

The drawings of Ramón y Cajal by Santiago Ramón y CajalOriginal Source: Instituto Cajal (CSIC)

The collection includes furniture, laboratory equipment such as microscopes, microtomes, and histological preparations, and a large collection of Cajal's drawings. This collection of drawings recreates in almost photographic detail what Cajal saw through the microscope. They are drawn in ink and are exceptionally precise, showing the skill and aptitude that Cajal had for drawing.

Today, these drawings are still used as a reference, influence, and object of study by modern neuroscientists.

The image shows a freehand scientific drawing by Santiago Ramón y Cajal: various types of large monopolar cells in a bee's retina.

The drawings of Ramón y Cajal by Santiago Ramón y CajalOriginal Source: Instituto Cajal (CSIC)

We need to shake vigorously the forest of our dormant neurons; we need to shake them with the emotion of the new, and infuse in them noble and elevated quests.

The image shows a scientific drawing by Santiago Ramón y Cajal: diagram showing the mechanisms that control breathing.

The drawings of Ramón y Cajal by Santiago Ramón y CajalOriginal Source: Instituto Cajal (CSIC)

[Neurons are] cells with delicate and elegant forms, the mysterious butterflies of the soul, the beating of whose wings may some day (who knows?) clarify the secret of mental life.

The image shows a freehand drawing by Ramón y Cajal: microglia in the cerebral cortex of a normal man. Cut of the brain stained using the Bielschowsky technique.

The drawings of Ramón y Cajal by Santiago Ramón y CajalOriginal Source: Instituto Cajal (CSIC)

Any man could, if he were so inclined, be the sculptor of his own brain.

The image shows a scientific drawing by Santiago Ramón y Cajal: pyramidal cells of layer V of the cerebral cortex.

Street sign for "Calle Ramón y Cajal"Original Source: Real Academia Nacional de Medicina de España

Paying Tribute to Cajal

There are countless tributes to the memory of Cajal. For example, it would be difficult to find a Spanish town that has not named an important street after the Spanish Nobel Prize winner, despite the fact that he felt uncomfortable with tributes of this kind.

Ramón y Cajal and BenlliureOriginal Source: Fundación Mariano Benlliure

The sculptor Mariano Benlliure (Valencia, 1862 – Madrid, 1947) created several works based on Cajal, and a great friendship developed between the 2 men.

In the summer of 1922 Benlliure traveled by car to Cercedilla, where the Nobel Prize winner was on holiday, in order to take him to his studio in Villalba. Benlliure was working on the seated statue of the scholar, which is currently housed in the auditorium of the University of Zaragoza.

One day, they were involved in an accident. Cajal and Benlliure's secretary and driver experienced only minor injuries, but Benlliure suffered a head injury and was bleeding profusely. They drove to a roadside inn and one of them tried to dissuade Cajal from helping the artist. "Get away, sir, and let me do it, because you surely do not know anything about these things," he said to Cajal.

This montage of 3 photographs shows Cajal and Benlliure. The artist can be seen working on one of his sculptures of the Nobel Prize winner.

Neurolab Project. Ramón y Cajal's telescopeOriginal Source: Instituto Cajal (CSIC)

As long as our brain is a mystery, the universe [...] will also be a mystery.

STS-90 was a mission flown by the Space Shuttle Columbia. As part of it, the Spacelab module mission, Neurolab, studied the effects of microgravity on the nervous system.
Its aims were to study basic research questions and to increase the understanding of the mechanisms responsible for neurological and behavioral changes in space.

In memory of Cajal, the father of neuroscience, Mission STS-90 carried on board 10 of Cajal's original histological preparations, on loan to the mission from the Cajal Institute (CSIC). In addition, a collection of 6 of Cajal's original histological drawings was sent to NASA to be exhibited on American soil while the space mission was taking place.

Google tribute to Ramón y Cajal from 2014Royal Academy of Medicine of Spain

Cajal will live on in scientific and cultural history. Generation after generation will feed on his knowledge in order to progress because, as he himself said, We are men and, as such, we are eager to know and to express ourselves.

Google Doodle tribute to Ramón y Cajal from 2014, commemorating the 80th anniversary of his death.

Credits: Story

Spanish Royal Academy of Medicine
Cajal Institute. CSIC
Infanta Margarita Museum of Medicine
Mariano Benlliure Foundation

Tatiana Pérez de Guzmán el Bueno Foundation
Spanish Royal Academy of Medicine Foundation

SENC, FENS, Library of the Spanish Royal
Academy of Medicine and the Royal Academy of Medicine of Eastern Andalusia

Credits: All media
The story featured may in some cases have been created by an independent third party and may not always represent the views of the institutions, listed below, who have supplied the content.
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