Santiago Ramón y Cajal

His original investigations of the microscopic structure of the brain made him a pioneer of modern neuroscience. Hundreds of his drawings illustrating the arborization (tree-like growth) of brain cells are still in use, since the mid-20th century, for educational and training purposes.

• Name — Santiago Ramón y Cajal • Born — 1 May 1852 • Birthplace — Petilla de Aragón, Spain • Died — 17 October 1934 • Place of death — Madrid, Spain • Education — University of Zaragoza • Known for — Fathering modern neuroscience Discovery of the neuron Cajal body, Cajal–Retzius cell, Interstitial cell of Cajal, Neuron doctrine, Growth cone, Dendritic spine, Long-term potentiation, Mossy fiber, Neurotrophic theory, Axo-axonic synapse, Pioneer axon, Pyramidal cell, Radial glial cell, Retinal ganglion cell, Trisynaptic circuit, Visual map theory • Awards — Nobel Prize in Physiology or Medicine (1906) • Field — Neuroscience Pathology Histology • Workplaces — University of Valencia Complutense University of Madrid University of Barcelona Santiago Ramón y Cajal (lang; 1 May 1852 – 17 October 1934) was a Spanish neuroscientist, pathologist, and histologist specialising in neuroanatomy, and the central nervous system. He and Camillo Golgi received the Nobel Prize in Physiology or Medicine in 1906. Ramón y Cajal was the first Spaniard to win a scientific Nobel Prize. His original investigations of the microscopic structure of the brain made him a pioneer of modern neuroscience. Hundreds of his drawings illustrating the arborization (tree-like growth) of brain cells are still in use, since the mid-20th century, for educational and training purposes.

Santiago Ramón y Cajal was born on 1 May 1852, in the town of Petilla de Aragón, Navarre, Spain. As a child, he was transferred many times from one school to another because of behavior that was declared poor, rebellious, and anti-authoritarian. An extreme example of his precociousness and rebelliousness at the age of eleven is his 1863 imprisonment for destroying his neighbor's yard gate with a homemade cannon. He was a keen painter, artist, and gymnast, but his father neither appreciated nor encouraged these abilities, even though these artistic talents would contribute to his success later in life. His father apprenticed him to a shoemaker and barber, to "try and give his son much-needed discipline and stability." • Illustration — Ramón y Cajal, captain in the Ten Years' War, Cuba, 1874 Over the summer of 1868, his father took him to graveyards to find human remains for anatomical study. Early sketches of bones moved him to pursue medical studies. Ramón y Cajal attended the medical school of the University of Zaragoza, where his father worked as an anatomy teacher. He graduated in 1873, aged 21, and then served as a medical officer in the Spanish Army. He took part in an expedition to Cuba in 1874–1875, where he contracted malaria and tuberculosis. To aid his recovery, Ramón y Cajal spent time in the spa-town Panticosa in the Pyrenees mountain range. After returning to Spain, he received his doctorate in medicine in Madrid in 1877. Two years later, he became director of the Anatomical Museum at the University of Zaragoza and married Silveria Fañanás García, with whom he would have seven daughters and five sons. Ramón y Cajal worked at the University of Zaragoza until 1883, when he was awarded the position of anatomy professor of the University of Valencia. His early work at these two universities focused on the pathology of inflammation, the microbiology of cholera, and the structure of epithelial cells and tissues. • Illustration — Self-portrait as a student, 1870s In 1887 Ramón y Cajal moved to Barcelona for a professorship. There he first learned about Golgi's method, a cell staining method which uses potassium dichromate and silver nitrate to stain a subset of neurons a dark black color, while leaving the surrounding cells transparent. This method, which he improved, was central to his work, allowing him to turn his attention to the central nervous system (brain and spinal cord), in which neurons are so densely intertwined that standard microscopic inspection would be nearly impossible. During this period he made extensive detailed drawings of neural material, covering many species and most major regions of the brain. • Illustration — J. Harley Williams called Cajal the “Don Quixote of the microscope”. In 1892, he became professor at Madrid. In 1899 he became director of the Instituto Nacional de Higiene – translated as National Institute of Hygiene, and in 1922 founder of the Laboratorio de Investigaciones Biológicas – translated as Laboratory of Biological Investigations, later renamed to Instituto Cajal, or Cajal Institute. He died in Madrid on October 17, 1934, at the age of 82, continuing to work even on his deathbed.

In 1877, the 25-year-old Ramón y Cajal joined a Masonic lodge. John Brande Trend wrote in 1965 that Ramón y Cajal "was a liberal in politics, an evolutionist in philosophy, an agnostic in religion". Nonetheless, Ramón y Cajal used the term soul "without any shame". In his final work, El mundo visto a los ochenta años (1934), Ramón y Cajal reflected on aging, mortality, and religion while continuing to be described by biographers as an agnostic. In a lecture given on December 5, 1897 at the Spanish Royal Academy of Sciences, he said the following: Esta nobleza, de la que se envanece con tanto mayor motivo cuanto que es su propia obra, consiste en ser ministro del progreso, sacerdote de la verdad y confidente del Creador. Él acierta exclusivamente a comprender algo de ese lenguaje misterioso que Dios ha escrito en los fenómenos de la Naturaleza; y a él solamente le ha sido dado desentrañar la maravillosa obra de la Creación para rendir a la Divinidad uno de los cultos más gratos y aceptos a un Supremo entendimiento, el de estudiar sus portentosas obras, para en ellas y por ellas conocerle, admirarle y reverenciarle.

In addition to being a regenerationist, Ramón y Cajal is considered a Spanish nationalist and centralist, and in this sense he interprets non-Spanish nationalisms, such as Catalan and Basque, describing them as separatist. Despite accepting the Statute of Núria, and, in the academic sphere, that classes could also be given in Catalan language at the university, he did not feel comfortable. Although he died in 1934, in 1937, in the midst of Spanish civil war, the Gaceta de Melilla uses an old speech of his about the need for an "iron surgeon" implicitly positioning him with the national-Catholic rebels against the Spanish Republic: “Whatever the defeatists and pusillanimous augurs may say, the impetus of our race is not easily extinguished... It is necessary to impose the moral unity of the Peninsula, to merge the dissonances and spiritual stridor into a grandiose symphony. But for this we need the iron surgeon that Costa spoke of”

• Illustration — Ramón y Cajal in his laboratory Ramón y Cajal made several major contributions to neuroanatomy. Excited by the discoveries of Frederick C. Kenyon, he explored the insect visual nervous system with his colleague Domingo Sánchez y Sánchez. He was stunned by the variety of neuron types. He discovered the axonal growth cone, and demonstrated experimentally that the relationship between nerve cells was not continuous, or a single system as per then extant reticular theory, but rather contiguous; there were gaps between neurons. This provided definitive evidence for what Heinrich Waldeyer would name "neuron theory", now widely considered the foundation of modern neuroscience. He is also considered by some to be the first "neuroscientist" since in 1894 he stated to the Royal Society of London: "The ability of neurons to grow in an adult and their power to create new connections can explain learning." This statement is considered to be the origin of the synaptic theory of memory. He was an advocate of the existence of dendritic spines, although he did not recognize them as the site of contact from presynaptic cells. He was a proponent of polarization of nerve cell function and his student, Rafael Lorente de Nó, would continue this study of input-output systems into cable theory and some of the earliest circuit analysis of neural structures. By producing depictions of neural structures and their connectivity and providing detailed descriptions of cell types he discovered a new type of cell, which was subsequently named after him, the interstitial cell of Cajal (ICC). This cell is found interleaved among neurons embedded within the smooth muscles lining the gut, serving as the generator and pacemaker of the slow waves of contraction which move material along the gastrointestinal tract, mediating neurotransmission from motor neurons to smooth muscle cells. In his 1894 Croonian Lecture, Ramón y Cajal suggested (in an extended metaphor) that cortical pyramidal cells may become more elaborate with time, as a tree grows and extends its branches. He studied some psychological phenomena, such as hypnotic suggestion to alleviate pain, which he used to help his wife during labor. A book he had written on these topics was lost during the Spanish Civil War. During his studies on the optic chiasma, Cajal developed a visual map-based theory offering an evolutionary explanation for the decussation of nerve fibres and the chiasm of the optic tract.

• Illustration — Ramón y Cajal's 1906 Nobel certificate; Museo Nacional de Ciencias Naturales, Madrid Ramón y Cajal received many prizes, distinctions, and societal memberships during his scientific career, including honorary doctorates in medicine from Cambridge University and Würzburg University and an honorary doctorate in philosophy from Clark University. In 1905, Cajal was named an honorary member of the American Association for Anatomy. Cajal crater on the Moon was named after him in 1973. The most famous distinction he was awarded was 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". This caused some controversy because Golgi, a staunch supporter of reticular theory, disagreed with Ramón y Cajal in his view of the neuron doctrine. Before Ramón y Cajal's work, Norwegian scientist Fridtjof Nansen had established the contiguous nature of nerve cells in his study of certain marine life, which Ramón y Cajal failed to cite. Ramón y Cajal was an International Member of both the United States National Academy of Sciences and the American Philosophical Society.