Santiago Ramón y Cajal (1852–1934)

Perhaps thrity years ago, someone or something I read recommended this book which was described, I now know justly, as one of the greatest scientific autobiographies by one of history’s truly great scientists, Santiago Ramon y Cajal (1852-1934). First published in Madrid eary in the 20th Century, Cajal divides the work into two: his early life from boyhood through service as a physician in Cuba during a nineteenth century insurrection (My Childhood and Youth) and his professional life as a peerless scientific investigator (The Story of My Scientific Work).

Cajal grew up in a small, northern Spanish town, his father the local physician and surgeon. His interestests were not academic, he loved rambling through nature and drew obsessively. He later would combine these loves in his career. He wanted to be an artist but was thwarted in this ambition by his father who wanted him to become a doctor. After long, unhappy and rebellious experiences in school, Cajal settled down to medical studies after his father forced him to work for a year as a shoemakers assistant. His father was an expert dissector and togehter they stole bodies from cemeteries as father passed this art to son in preparation for his medical school exams. Cajal, an intensely visual lerner, was fascinated by these dissections and the expertise he developed in preparation for medical school along with his artistic skill were to become the foundation stones of his scientific career.

His first and last medical assignment was as an officer in the Spanish Medical Corps. He served in Cuba and between malaria and diptheria barely survived the experience. Sent home to recuperate, he resigned from the Army and determined that he would pursue a University Professorial career rather than medicine. His dissection skills and the diagrams he produced were the winning edges in the very difficult and highly competitive examinations through which he earned his first university appointment.

As is the case for most autobiographies, the early years described in My Childhood and Youth are most interesting for the clues they offer for the half-century of supreme achievement that followed. The Story of My Scientific Work begins with Cajal’s first professorship at Zaragosa. From the outset of his university career, Cajal established a small laboratory and worked obsessively dissessecting the nervous systems of creatures all across the animal spectrum. His workdays started early and typically extended until midnight: dissection, staining and slide prep, observing and drawing. One can picture him with his eye moving from the ocular of a small microscope to pen and paper as he observed and sketched, always looking for clues as to the relationship between structure and function.

He became a master at staining, using the stain created by his great rival Professor Golgi, and was able to see and beautifully record microstructures that eluded others. This was the foundation of his research. He started with various sensory organs (primarily the retina and olfactory system) and motor neurons, worked his way to the spinal cord and then ultimately the brain; he compared these structures at various points in embryonic, juvenile and adult development and he studied them in insects, fish, birds and mammals. He studied patologies and injuries to the nervous system and nerve regeneration. By the end of his career, his bibliography of articles listed at the end of the book ran almost twenty pages of very small print and his publications ranged from simple studies to thousand page reference texts with hundreds of different illustrations by his own hand, and all of this at a time when authorship meant that you actually did your own research and wrote your own paper! It’s awesome.

Cajal is rightfully considered the father of modern neuroscience because it was he who proposed and proved the theory of the neuron and how signal transduction worked as the cellular level. The brilliance of his drawings was matched by the brilliance of his analysis and writing. I was particularly blown away by a chapter in which he undertook to support his observations of a particular retinal structure (homolateral fibers) which others were unable to see due to inferior microscopic technique. With the use of spectacular diagrams that conveyed his point with stunning persuasiveness, he compared panaromic (e.g., fish) and binocular (e.g., mammal) vision through lenticular eyes, demonstrated how the optic chiasma was necessary to imprint the image correctly on the brain in both instances and how the homolateral fibers were necessary to produce stereoscopic vision. I found it stunning that Cajal had the ability to marshall this explanation in support of his observations when the pedestrian scientific response would have been along the lines of “you need to produce a better section, practice your staining technique and look more carefully.” The reader senses the pleasure Cajal must have derived from this achievement.

And the drawings! A few years ago, I visited an exhibition of Cajal’s drawings in New York. They are so intricately beautiful, so full of the sense of beauty and awe that must have filled Cajal as he drew them. I think that Cajal’s love of art drove him in his work, gave him the pleasure to push so hard for so many years. He alludes at one point to the peace he derived from observing and drawing in his lab late at night following the death of one of his children. And although he writes very little about his personal life in the second part of the autobiography, there is a touching aside when he describes a book on color photography that he edited to help establish a sickly son in the book business but which he had to complete as author following his son’s death. “But why dwell on sadness?”

The writing is brilliant, ranging from the transcendant to the almost ludicrously esoteric. Here are examples of each:

“As the reader will remember, my devotion to the retina is ancient history. The subject always fascinated me because, to my idea, life never succeeded in constructing a machine so subtly devised and so perfectly adapted to an end as the visual apparatus. It is one of the rare cases, nevertheless, in which nature has deigned to employ physical means which are accessible to our present knowledge. I must not conceal that in my study of this membrane I for the first tinme felt my faith in Darwinism weakened, being amazed and confounded by the supreme constructive ingenuity revealed not only in the retina and in the dioptric apparatus of the vertebrates but even in the meanest insect eye. There, in fine, I felt more profoundly than in any other subject of study the shuddering sensation of the unfathomable mystery of life.” (Cajal goes on to lay out a number of instances in which he finds that it impossible to explain various anatomical arrangements “by the principles of gradual variation and selection of useful modifications.” Not surprisingly, many have used these observations to “disprove” natural selection, although it is clear from Cajal’s writings that he intended no such thing.)

On the esoteric and snarky side of the ledger: “As for S., the fiery naturalist of Klausenburg waited until 1907 [the year Cajal was awarded the Nobel prize] to feel himself aggrieved by the friendly objections which, in passing, his highly extravagant lucubration concerning the continuity of the neurofibrils in worms had suggested to me in 1903.”

Although he began in obscurity and at a disadvantage because of the low esteem for the Spanish scientific establishment, Cajal’s work was promoted by a renowned German colleague and by mid-career accolades and prizes (including the Nobel Prize for Medicine and Physiology) began to be heaped upon him. Cajal found himself at the apex of Spanish science at the University of Madrid. He was ambitious but driven mostly by idealism and the pursuit of knowledge for its own sake and for the betterment of humanity. He made decisive contributions to educational reform, establishment of a powerful “school” of Spanish neurobioloy and creation of a respected Spanish scientific establishment. He graciously acknowledged the honors and shouldered his many responsibilities, but really wanted to stay in the lab and continue his researches which he did up until his death at 82.

Cajal’s name belongs alongside Einstein, Darwin and Pasteur as one of the greatest scientists of this golden era of science.… (meer)

Before embarking on a painting, most artists first make an underdrawing - the style of which is unique to each painter. But the finished product masks it. Using Infrared Reflectography, scientists can now 'see' below the surface, by penetrating layers of varnish and pigments to produce an image of the underdrawing, useful for authenticating expensive paintings. The record sale price of over USD 40 million for Leonardo’s Salvator Mundi, at an auction in 2017 has brought the usefulness of scientific authentications in focus. Other sophisticated scientific techniques such as x-ray fluorescence using a synchrotron beam, Mass spectrometry and artificial intelligence are also being used to elucidate and analyze the hidden layers of a painting. Now over 500 years old, Leonardo da Vinci's famous notebooks have some drawings, which have become invisible to the naked eye because of the high copper content in the stylus he used. Using x-ray fluorescence and Ultra-Violet beams of light it has become possible to 'see' what was not visible to the naked eye, in them.

In 20 drawings and 1500 words, Leonardo da Vinci described the eddies of blood that help to close the aortic valve. It was only in 1980s that the pulsing image of a real-time MRI scan allowed anatomists to confirm the swirling eddies of blood after each beat of the heart, as postulated by Leonardo! Such eddies are crucial in closing the aortic valve when blood flow ceases after each beat of the heart.

Stunning drawings made by the Spanish anatomist Santiago Ramón y Cajal (1852 – 1934), while looking at thin silver-stained slices of brain/spine tissue, under a microscope, led him to propose his now-famous ‘neuron doctrine’ which became the bedrock of the field of neuroscience. Cajal’s ink and pencil drawings of the neurons (nerve cells) he saw under his microscope, showed them to be individual discreet cells. Using a simple microscope, and drawing tools of a typical art studio, Cajal made some 2,900 scientific drawings, showing brain’s secrets with clarity, using his artist eye, showing that neurons are distinct entities, and that neurons communicate with each other across a gap of separation, called the synapse. It took Electron Microscopy to arrive 50 years later, and confocal microscopy even after that, to confirm some of the ideas that Cajal had proposed through his drawings. Cajal is rightly credited with inventing the subject of 'neuroscience' and was awarded the Nobel Prize in 1906, which he shared with Golgi.… (meer)