Nobel Stories

Santiago Ramón y Cajal – Father of neuroscience

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Modern microscopy techniques allow us to look inside tissues, going deep down to a cellular and subcellular level to identify proteins revealed by immunofluorescent tags. Thus, confocal microscopes grant us a view of the diverse cell types and their organisation within tissues, while the newest super-resolution microscopy methods permit visualisation of nuclear structures or single cytoskeletal fibres at a super-resolution level. Isn’t that amazing?

Now, between the 19th and 20th century, long before the invention of such modern imaging techniques, Santiago Ramón y Cajal used Golgi stainings to detect nerve cells of various animals at different developmental stages. His observations, made with a simple light microscope, brought him to describe, for the first time with extreme accuracy, the structure and architectural organisation of nerve cells and nerve fibres. Until that time, it was believed that nerve cells built a continuous, interconnected network, as inferred by Italian biologist and pathologist Camillo Golgi upon analysis of nerve tissue samples stained with silver nitrate (a technique that he developed and is known to us as his namesake). Conversely, Ramón y Cajal showed that “the nerve elements possess reciprocal relationships in contiguity but not in continuity. He also performed nerve injury experiments and analysed nerve fibres at the injury site. For the first time, he described the regeneration of axons in mammals, through the presence of budding neurofibrillae in close vicinity to necrotic segments. For these observations, he was awarded the Nobel Prize in Physiology or Medicine in 1906, which he shared with Golgi, “in recognition of their work on the structure of the nervous system”. The level of microscopic structures revealed, observed, and described by Cajal is unbelievably detailed, given the methods available at the time. Now, isn’t THAT astounding? As he reports in his Nobel Lecture:

In spite of its great complication, the retina can be considered as a nerve ganglion formed by three rows of neurons or nerve corpuscles: the first row encloses the rods and cones with their descending prolongations forming the external granular layer; the second is made up of the bipolar cells and the third contains the ganglionic neurons; the three series of nerve corpuscles interconnect at the level of the said molecular or plexiform layers, internal and external.

Santiago Ramón y Cajal

Santiago Ramón y Cajal’s story actually begins in Petilla de Aragón, Spain, where he was born in 1852. His youth dream was to become an artist, but he was prevailed over by his father, an Anatomy Professor at the University of Saragossa, and went on to study medicine. His artistic inclination was not completely suppressed, though. In fact, Cajal’s heritage is best exemplified by his renowned hand-made drawings of neural cells and microscopic brain structures: a fortunate sway of his. While today we collect pictures through cameras connected to a microscope, Cajal would use his skills to transform ink on paper into accurate representations of what he observed under the objective. If I think about it, I almost feel like I am cheating each time I go to the confocal...

The gold medal and the diploma of the Nobel Prize awarded to Cajal are in a showcase in the seminar room of the Cajal Institute in Madrid, Spain. Following the Nobel Prize award in Physiology or Medicine, a royal decree by king Alfonso XIII established in fact the construction of a new research building in Madrid focussed on the investigation of the nervous system, in 1920. Cajal was appointed the first director and in 1932 the building’s name was changed to honour the memory of the deceased Nobel laureate. The Cajal Institute is the oldest neurobiology institute in Spain and hosts several labs working on development, connectivity, structure of the nervous system, as well as a state-of-the art microscopy unit.

During my PhD, I collaborated with a group at the Cajal Institute. This allowed me to visit the institute and its library, where some of Cajal’s original possessions are kept after he bequeathed them to the institute - the so called “Cajal’s Legacy”. Behind a glass-screen there is his laboratory, including his desk, his Professor’s robe, several of his instruments, books, and personal items. He also left his microscopes, a Zeiss model and a Leitz one. Around the library, a little treasure of drawings and books by Cajal are on display, as well as his photographic camera, and some family pictures. An all-fields pioneer/vanguard, Cajal’s most notable pictures are his self-portraits. Protected in a room accessible only by the curator of the “Cajal’s Legacy” are the original drawings, books, and correspondence. Recently, the material has been digitised. In 2015, a campaign to collect signatures in order to integrate the “Cajal’s Legacy” into the UNESCO World Heritage has been launched by the president of the International Cajal Legacy Group. In 2017, UNESCO inscribed the “Archives of Santiago Ramón y Cajal and the Spanish Neurohistological School” into the Memory of the World Archives, in recognition of their historical and cultural value.

If you travel to Madrid, I recommend you to get an appointment to visit the Cajal’s Legacy: r.martinez[at]cajal.csic.es. You won’t easily have another opportunity to be in front of such an important and astounding heritage of the history of neuroscience.

Written by Chiara Galante; Edited by Fazi Bekbulat. Featured Image: NGC/Margaryta Tevosian.

Sources:

Webpage of the Instituto Cajal: http://www.cajal.csic.es/ingles/index.html

Webpage of the Nobel Prize: https://www.nobelprize.org/prizes/medicine/1906/cajal/facts/

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