Of Art & Science: Santiago Ramón y Cajal.

It was during a visit with my family at the Museo De Las Sciencias Príncipe Felipe (Science Museum Prince Felipe) at the Ciudad De Las Artes Y Las Ciencias in Valencia this month that I was pleasantly surprised that there was an exhibition of the famous Dr. Santiago Ramón y Cajal. His work is truly inspiring and it shows how he not only did a brilliant job in advancing neuroscience but also how artistic this man was. This remarkable combination of art and science made him one of the fathers of modern neuroscience. His glimpses under the microscope, using his Golgi improved staining techniques, and artistic skills gave birth to two ideas that would revolutionize neuroscience as it was. The first one was the theory that the unit of organization in the brain is the individual cell or neuron which would give rise to what has come to be known the Neuron Doctrine. The doctrine was formally stated by German anatomist Wilhelm von Waldeyer-Hartz in 1891. The second theory of cells communicating or signalling each other along dendrites and axons would only be proven after the invention of the electron microscope. His breathtaking drawings are not only beautiful, but almost mystical and are a remarkable synergy of art and science.

"Todo hombre puede ser, si se lo propone, escultor de su proprio cerebro" (Every man can be, if he so desires, the sculptor of his own brain). - Santiago Ramón y Cajal -

Born on the first of May 1852, at Petilla de Aragón in Spain, Santiago Ramón y Cajal was first apprenticed to be a barber and later to be a cobbler. But his wish was to be an artist. It was his father, a Professor of Applied Anatomy at the university of Saragossa, who persuaded him to study medicine by taking him to graveyards to find human bones for anatomical study, which Santiago would sketch.1 He did so chiefly under the direction of his father, and in 1873 he took his Licentiate in Medicine at Zaragoza, Spain. In Cuba, serving as an army doctor he contracted malaria and tuberculosis. On his return in 1875 he became an assistant in the school of anatomy in the faculty of medicine at Zaragoza. In 1877 he obtained the degree of Doctor of Medicine at Madrid. In 1879 Cajal married Do?a Silvería Fa?anás García. They had four daughters and three sons.

Figure 1: A picture of Santiago Ramón y Cajal using his microtome. Picture taken at the Museo De Las Sciencias Príncipe Felipe, Ciudad De Las Artes Y Las Ciencias, Valencia, January 2017.

In 1880 he began to publish scientific works. His early works at the universities of Zaragoza and Valencia concentrated on the pathology of inflammations, the microbiology of cholera and the structure of epithelial cells. In 1884 the first edition of the “Manual de Histología normal y de Técnica Micrográfica” (manual of normal histology and micrographic technique) is published (2nd ed., 1893).

Figure 2: Cover of the Manual “Histología Normal y de Técnica Micrográfica” from 1884. Courtesy: The original is conserved at the Instituto Cajal, CSIC, Madrid. Picture taken at the Museo De Las Sciencias Príncipe Felipe, Ciudad De Las Artes Y Las Ciencias, Valencia, January 2017.

A summary of this manual appeared under the title “Elementos de Histología, etc.” (Elements of histology, etc.). In 1890 (3rd ed., 1900), “Anatomía Pathológica General” (Manual of general pathological anatomy) is published and in 1894 “Les nouvelles idées sur la fine anatomie des centres nerveux” (New ideas on the fine anatomy of the nerve centres. Noteworthy are also: “Textura del Sistema Nervioso del Hombre y de los Vertebrados” (Textbook on the nervous system of man and the vertebrates) 1897-1899, and “Die Retina der Wirbelthiere” (The retina of vertebrates) in 1894.

Apart from these works he also published more than 100 articles in Spanish and French scientific periodicals, especially on the fine structure of the nervous system of the brain and spinal cord, but also including that of muscles and other tissues, as well as various topics in the field of general pathology.

Figure 3: “Célula nerviosa motriz (1913)” (Motor nerve cell) by Santiago Ramón y Cajal. The original is conserved at the Instituto Cajal, CSIC, Madrid. Courtesy: The original is conserved at the Instituto Cajal, CSIC, Madrid. Picture taken at the Museo De Las Sciencias Príncipe Felipe, Ciudad De Las Artes Y Las Ciencias, Valencia, January 2017.

Neuron Doctrine

In 1883 he was appointed Professor of Histology and Pathological Anatomy at Barcelona. It is here that he got in contact with the neurological colouring- and impregnation techniques of Franz Nissl and Camillo Golgi and started his attention to the central nervous system. Subsequently he improved Golgi’s techniques and developed his own silver impregnation for nervous elements. It is during this period Cajal starts extensive studies of nervous tissues in animals and important parts of the brain.  Leaving behind a legacy of detailed drawings Ramón y Cajal made major contributions to neuroanatomy and discovered the axonal growth cone. He also demonstrated experimentally that the relationship between nerves cells was not continuous but rather contiguous, which provided the evidence for what would be later known as the “neuron doctrine” (1). Nowadays this is considered the foundation of modern neuroscience. Ramón y Cajal was a fierce defender of the neuron theory in debating neuronal network theories, whereas Golgi was of the conviction that the nervous system was a singular network, not made of separate cells, which is called the “reticular theory” (2). Ramón y Cajal used his artistic skills to produce depictions of structures and connectivity as well as detailed descriptions of cell types associated with neural structures. He even discovered a new type of cell, which was named after him: the interstitial cell of Cajal (ICC). He was an advocate of the existence of dendritic spines, although he did not recognize them as the site of contact from presynaptic cells. His student Rafael Lorente de Nó, would continue Cajal’s study of nerve cell function as input-output systems into cable theory and some of the earliest circuit analysis of neural structures.

Figure 4: Primary, secondary and tertiary layers of the frontal ascending convolution from a one month old boy (1904). A,B,C: Little pyramidal cells; D,E: Medium pyramidal cell; F: double-celled cell whose axon formed terminal nests; G: Protoplasmic stems emanating from a thick pyramidal cell of the fourth zone; H,I: Dendritic thin stems of the corpuscles of the fifth and sixth layer; J: Small double-celled elements; K: Fusiform cell of a large axon. The original is conserved at the Instituto Cajal, CSIC, Madrid. Picture taken at the Museo De Las Sciencias Príncipe Felipe, Ciudad De Las Artes Y Las Ciencias, Valencia, January 2017.

In 1892 he was appointed Professor of Histology and Pathological Anatomy at Madrid. In 1900-1901 he was appointed Director of the “Instituto Nacional de Higiene” and of the “Investigaciones Biológicas”.

"To know the brain...is equivalent to ascertaining the material course of thought and will, to discovering the intimate history of life in its perpetual duel with external forces" - Santiago Ramón y Cajal

His studies on the structure of the cortex of the brain have been partly grouped together and translated into German by J. Bresler (1900-1901). He is also the author of “Reglas y Consejos sobre Investigacion Cientifica” (Rules and advices on scientific investigation) which was also translated into German (1933).

Ramón y Cajal received many prizes, distinctions and societal memberships during his career, including honorary doctorates in medicine of the University of Cambridge (1894), Würzburg (1896) and in philosophy from Clark University. Among the distinctions won by Cajal are the following: Member of the Royal Academy of Sciences of Madrid (1895); of the Royal Academy of Medicine of Madrid (1897); of the Spanish Society of Natural History and of the Academy of Sciences of Lisbon (1897); Honorary Member of the Spanish Medical and Surgical Academy and also of several other Spanish societies (3,4).

Cajal was also a corresponding member of several societies: the Physical-Medical Society of Würzburg (1895); the Medical Society of Berlin (1895); the Society of Medical Sciences of Lisbon (1896); the Vienna Society for Psychiatry and Neurology (1896); the Society of Biology of Paris (1887); the National Medical Academy of Lima (1897); Conimbricensis Instituti Societas (Coimbra, 1898); and Member of Honour of the Italian Psychiatric Society (1896) as well as of the Medical Society of Ghent (Belgium, 1900). In 1906 he was elected an Associate Member of the Academy of Medicine, Paris; in 1916 he became a member of the Swedish Academy of Sciences (3).

Figure 5: Drawings by Santiago Ramón y Cajal. Upper left: General diagram of the relations of the optical centers and the flow of the currents (1901); 2nd picture from the top left: Pigeon cerebellum (Purkinje cells and granule cells, 1899); 3rd picture from the top left: Schema of the pathways of the mammillary apparatus, ganglion of the habenula and dorsal thalamic nucleus (1904); Lower left: Cross-section of the midbrain portion below the Sylvian aqueduct (1901). Courtesy: The originals are conserved at the Instituto Cajal, CSIC, Madrid. Picture taken at the Museo De Las Sciencias Príncipe Felipe, Ciudad De Las Artes Y Las Ciencias, Valencia, January 2017.

Cajàl has been awarded several prizes, for example the Rubio Prize for his “Elementos de Histología, etc.”, the Fauvelle Prize of the Society of Biology of Paris (1896); the Moscow Prize, established by the Congress of Moscow (1897) to reward medical works which, published during the latter three years, have rendered the greatest services to science and humanity was awarded to Ramon y Cajàl by the International Congress of Medicine in Paris (1900). In 1905, the Royal Academy of Sciences of Berlin awarded him the Helmholtz Medal (3).

In 1894 Santiago Ramón y Cajal was summoned to London to give the Croonian Lecture “La fine structure des centres nerveux” (The fine structure of the nervous system) in which he suggested (in an extended metaphor) that cortical pyramidal cells may become more elaborate with time, as a tree grows and extends its branches.

Nobel Prize, 1906

In 1906 he was awarded his most famous distinction, the Nobel Prize in Physiology or Medicine. He shared the Nobel Prize with Camillo Golgi in recognition of their work on the structure of the nervous system. This caused some controversy because Golgi supported his discredited reticular theory even in his Nobel lecture, whereas Ramón y Cajal disagreed supporting the neuron doctrine.

Figure 6: Picture of his Nobel Prize in 1906 recognizing his work on the structure of the nervous system. Courtesy: The original is conserved at the Instituto Cajal, CSIC, Madrid. Picture taken at the Museo De Las Sciencias Príncipe Felipe, Ciudad De Las Artes Y Las Ciencias, Valencia, January 2017.

Fundamental Neuroscience - Art - History taken into space...

Less known maybe is the fact that in honor of Santiago Ramón y Cajal, the STS-90 mission brought microscope slides and drawings from the Cajal Institute aboard the Space Shuttle Columbia. The 16-day flight (April 17 to May 3, 1998), called Neurolab, was dedicated to the advancement of neuroscience research, investigating effects of microgravity on the brain and nervous system. Also, the asteroid 117413 was named in his honor as Ramonycajal.

Figure 7: Picture of the Neurolab space mission in 1998, when Ramón y Cajal was honoured for his work and to bring it to the attention of the general public. Courtesy: The original is conserved at the Instituto Cajal, CSIC, Madrid. The drawing shows a section of the spinal cord. Picture taken at the Museo De Las Sciencias Príncipe Felipe, Ciudad De Las Artes Y Las Ciencias, Valencia, January 2017.

Santiago Ramón y Cajal died in Madrid on October 18, 1934 at the age of 82.

"In summary, all great work is the fruit of patience and perseverance, combined with tenacious concentration on a subject over a period of months or years" - Santiago Ramón y Cajal -

Recommended further reading:

"The Art Of The Brain, On Exhibit" by Alva No?.

References:

1.    Finger, Stanley (2000). "Chapter 13: Santiago Ramon y Cajal. From nerve nets to neuron doctrine". Minds behind the brain: A history of the pioneers and their discoveries. New York: Oxford University Press. pp. 197–216.

2.    Marina Bentivoglio (20 April 1998). “Life and Discoveries of Camillo Golgi”. Nobelprize.org. Nobel Media.

3.    "Santiago Ramón y Cajal - Biographical". Nobelprize.org. Nobel Media AB 2014. Web. 25 Jan 2017. https://www.nobelprize.org/nobel_prizes/medicine/laureates/1906/cajal-bio.html.

4.    “Santiago Ramón y Cajal” https://en.wikipedia.org/wiki/Santiago_Ramón_y_Cajal.