Santiago Ramon y Cajal: father of modern neuroscience
by Rebecca Oramas
The discovery that the nervous system is comprised by a myriad of individual specialized cells – caled neurons - is more recent than you think. This 100-year-old finding is so relevant that it was attributed the Nobel Prize for Physiology or Medicine in 1906, and interestingly, it required the convergence between science and art.
In the 1870s, a scientist called Camillo Golgi developed a method called the “black reaction” (later referred to as Golgi’s method), which allowed cells to be colored and visualized using silver nitrate. Golgi believed that the nervous system was comprised of a continuous interconnected network. However, the Spanish neuroanatomist Santiago Ramón y Cajal, disagreed.
Santiago Ramón y Cajal was born in the 1850s in Spain. Early in his life, he wanted to be an artist. His father - a Professor of Applied Anatomy- had different plans for him and convinced him to pursue his studies in medicine, which he completed in the 1870s. In the 1880s he became a professor, first of Descriptive Anatomy at the University of Valencia, and then of Histology and Pathological Anatomy at the at the universities of Barcelona and Madrid. It was during these years that he started publishing his scientific work in the topics of histology and anatomy, and when his interest in the nervous system sparked.
Cartoon of Santiago Ramón y Cajal observing through his microscope. By Rebecca Oramas
Ramón y Cajal, contrary to Golgi, believed that the nervous system was made up of individual cells. To demonstrate this, he began using the Golgi Stain (1887) - along with other innovative staining methods - to uncover the structures of cells and understand their organization within the body.
Driven by his curiosity, Ramón y Cajal developed many staining methods that would improve the visualization of cells in specific cell types. In the late 1890s and early 1900s, he invented the trichomic method (to stain neoplasias - abnormal masses of tissue), reduced silver nitrate method (to visualize neurofibrils - filaments found in neurons), formalin uranium nitrate method (to label the Golgi Apparatus organelle), and the gold stain method (to observe glial neurons – explained below). Additionally, he created improved variations of the pre-existing Golgi Stain and methylene blue staining methods, all of which were later on used by scientists across disciplines for major scientific discoveries. He found that developing unique staining procedures for distinct cell types, improved the quality of the images he could observe under his microscope and ultimately his ability to draw them.
Ramón y Cajal used a wide variety of drawing materials and techniques throughout his career. Most of his work was done using indian ink, graphite pencil, watercolors, and white wax. The media and techniques he used for his drawings was determined by the staining method used in the cells he was visualizing. Usually he would begin by sketching the outline of cells using a graphite pencil. He would then proceed to fill the interior of these cells with Indian ink (for the silver nitrate stain method), a graphite pencil and gray/sepia watercolors (for the formalin-uranium nitrate and gold stain method) or colored watercolors (for the gold stain method), attempting to mimic the colors of the staining method he was observing under the microscope. He would also use watercolors to draw cells located at a deeper plane (generating a 3D effect) or when he wanted to highlight specific structures within a cell.
The staining methods that Ramón y Cajal developed allowed him to label neurons (usually brown/black) in their entirety, allowing him to study their individual structures and the way in which they interacted with other cells to form the nervous system network. By studying neurons under a microscope and drawing them, Cajal established that each of the neurons that make up the nervous system are independent entities that form contact areas – called synapses - to transfer information (in the form of electrical impulses) with one another. He also characterized the anatomical structures of a neuron: the dendritic arbor, the cell body (or soma) and the axon (drawn below!).
Anatomical structures of a neuron. By Rebecca Oramas.
All of these discoveries, which where then collectively referred to as the “neuron doctrine” would not have been possible without the combination of Ramón y Cajal’s medicinal/anatomical knowledge and his visual/artistic approach to study what he was observing under the microscope. Ramón y Cajal’s success highlights the importance of addressing situations with a multi-disciplinary and open-minded view, which often result in more creative and unique outcomes.
Want to learn more about the cells within the nervous system that Ramón y Cajal studied using the Golgi stain and his beautiful drawings?
Purkinje cells of the cerebellum: Large neurons located in the cerebellum that can be easily identified by 1) their flask-like shape cell bodies (soma), 2) the presence of a single long axon and 3) their high numbers of branching dendritic arbors. These neurons play a role in muscle movement coordination and usually release an inhibitory neurotransmitter called GABA (gamma-aminobutyric acid) that inhibits the transmission of electrical impulses.
Purkinje cells of the human cerebellum
(Credit: Cajal Institute, Madrid)
Pyramidal Neuron of the cerebral cortex: Pyramidal cells comprise 70-90% of the neurons in the cerebral cortex, and usually release the excitatory neurotransmitter Glutamate, which increases the transmission of electrical impulses. These cells have 1) a large pyramidal-shaped cell body (20–120 µm in diameter), 2) numerous apical and basal dendrites and 3) a single axon. These neurons play a role in motor functions and cognitive abilities.
Pyramidal Neuron of the cerebral cortex: (Credit: Cajal Institute, Madrid)
Glial cells of the cerebral cortex: Glial cells (also referred to as neuroglia or “nerve glue”) are a type of non-neuronal cells that function to provide neurons with: 1) oxygen and nutrients 2) support, 3) insulation, 4) protection against pathogens, and 5) removal mechanisms after death (clean-up). These cells do not produce electrical impulses and can be easily distinguished from neurons because they do not have axons and they do not form synapses.
Glial Neurons of the cerebral cortex: (Credit: Cajal Institute, Madrid)
Sources/References: 1. https://www.nobelprize.org/prizes/medicine/1906/golgi/biographical/ 2. https://www.nobelprize.org/prizes/medicine/1906/golgi/facts/ 3. https://history.nih.gov/pages/viewpage.action?pageId=1016727 4. https://www.britannica.com/biography/Santiago-Ramon-y-Cajal 5. https://www.britannica.com/science/neuroglia 6. https://www.britannica.com/science/Purkinje-cell 7. Jäkel, S. and Dimou, L., 2017. Glial cells and their function in the adult brain: a journey through the history of their ablation. Frontiers in cellular neuroscience, 11, p.24. 8. Arbas, E.A., Meinertzhagen, I.A. and Shaw, S.R., 1991. Evolution in nervous systems. Annual review of neuroscience, 14(1), pp.9-38. 9. Johns, P., 2014. Neurons and glial cells. Clinical Neuroscience, pp.61-69. 10.Garcia-Lopez, P., Garcia-Marin, V. and Freire, M., 2010. The histological slides and drawings of Cajal. Frontiers in neuroanatomy, 4, p.9.