The Dreams of Santiago Ramón y Cajal
by Benjamin Ehrlich.

Oxford University Press 2017 | 160pp | Paperback £25.99 $39.95

The Beautiful Brain: The Drawings of Santiago Ramón y Cajal
by Larry W. Swanson, Eric Newman, Alfonso Araque, Janet M. Dubinsky

Abrams, New York 2016 | 208pp | Hardcover £25.00 $28.53

Cajal beyond the brain
by Lazaros C. Triarhou

Corpus Callosum, Indianapolis, IN, 2015 | 280pp | Paperback £15.50 $22.50

By CHARLES J. VECHT, MD PhD FAAN

BORN IN 1852 in Navarre, Santiago Ramón y Cajal is the father of modern neuroscience and a 1906 Nobel prize-winner. In The Dreams of Santiago Ramón y Cajal by Benjamin Ehrlich, the hard core of scientific progress is opposed to the softer phenomena of the mind. At the second half of the nineteenth century, there was a strong popular interest in psychology including the mystery of the unconscious. Cajal was not left untouched by this, and became interested in hypnosis and dreams, although he also had second thoughts about Freud’s theories.

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A rebel in his youth, he also showed an early passion for drawing and painting, often in a romantic style and for a couple of years he went to art-school with instructors enthusiastic about his progress. His father, quite ambivalent about his son’s aspirations, took him away from it. He wanted him to follow into his footsteps as a physician, and started teaching him anatomy by dissecting human bodies as a preparation for medical school. One night he even took Santiago to a graveyard to dig up skulls and bones. After his studies Cajal went as medical officer with the Spanish army to Cuba where he contracted dysentery and malaria. After his return to Spain, he started coughing blood and was diagnosed with tuberculosis, an almost a deadly verdict at the time. He miraculously recovered, though was mentally shaken. Considering the practice of medicine physically too heavy, he obtained a modest position at the Medical School of Zaragoza. Scientific insights in medicine on how the human body functioned had just started. One new field was microbiology, with major contributions by Edward Jenner on smallpox in the late eighteenth century in England and by Louis Pasteur on rabies 100 years later in Paris. The other field centred on the microscope which had allowed Rudolf Virchow in Berlin and his followers to identify the cell body, its nucleus and other organelles as the essential element of tissues. By applying different colouring techniques, one could differentiate between cellular structures.

In 1878, when Cajal was 26, a professor in anatomy introduced him to what a microscope could reveal, and convinced him to choose the field of histology (the science of tissues). With not a single microscope to be found in Zaragoza, Cajal set up his own laboratory and, with his own funds, bought one. In his earliest studies, he concentrated on more general subjects like the origin of inflammation, but having achieved the best score on a competitive examination, in 1884 he was nominated professor of anatomy in Valencia. Soon thereafter, a cholera epidemic broke out in Spain and the province of Zaragoza asked him back to help eradicating it. He started culturing infected tissues and confirmed the presence of the cholera bacillus identified two years earlier by Robert Koch as cause of the disease, besides carrying out vaccination studies. Out of gratitude for his efforts, the people of Zaragoza offered him the newest Zeiss microscope. Despite this success in microbiology, it convinced Cajal of his preference for histology as a quieter discipline than inoculating and observing guinea pigs.

His big turnaround came in 1887 when he was shown pictures of nerve cells made visible by a staining technique of silver-nitrate developed by Camillo Golgi in Italy. “La reazione nera” only colors nerve cells, becoming clearly perceptible in thin black lines like Chinese ink. By this method, Golgi had made important contributions on visualizing the nervous system. Cajal was impressed how this technique allowed studying the structure of nerve cells in isolation without the need of interpreting a complex picture with numerous glial cells and blood vessels in between. Nevertheless, Golgi’s method had hardly been in use since its introduction 15 years before because of the difficulties applying it. The experience of Cajal being familiar with coloring techniques enabled him to improve on the method. Immediately excited about the opportunities and despite a family of seven, he started out to work from nine until midnight. Now he could exploit his talents as artist and scientist by drawing all types of neurons (synonym for nerve cells), located in either the cerebral or cerebellar hemispheres, spinal cord or sensory organs. Watching with one eye through his microscope and with the other one drawing what he observed, he produced accurate and striking illustrations of nerve cells in all their details. As photography yet hardly existed, the only way to reveal his findings was by making illustrations of neurons which were almost invariably part of his publications.

Despite using the same technique, Golgi and Cajal came to different conclusions on how the nervous system functions. Golgi was a supporter of the existing theory of the nervous system as a continuous network of nerve cells without boundaries in between, somewhat similar to ivy. Cajal concluded that nerve cells communicate with each other, though remain individual units, more like trees in wintertime touching each other by their branches. One argument for his conviction were observations that if one cuts a nerve fibre, only its outer part degenerates without damage, however, to the cell body of a neighbouring nerve cell. His interpretation became known as the “neuron doctrine”, still valid.

One knew at the time that nerve cells contain numerous branches at one side of their cell body, the “dendrites” (trees) characterized by little horns (“spinae”) alongside their fibres, later identified as the synaps or the site where one neuron connects with another one. At the other side of the cell body a single branch sprouts, the axis-cylinder or “axon” often with many branches at its terminal end. The nerve cells contact each other by the endings of axons upon dendrites, and in this way a nerve cell influences the activity of a neighbouring cell. From this Cajal concluded that nerve cells enter into a chain of transmission, either by electric conduction or by inductive chemical effects.

ONE TYPE OF nerve cell he identified was the pyramidal cell. This neuron is mainly located in the neocortex of the brain often having extraordinarily long axons which can span large distances within the brain and down to the spinal cord. Familiar with the findings of Luigi Galvani a century earlier, Cajal proposed that nerve cells propagate electric currents and do so by own-way traffic from the dendrites via the cell body towards the axon. This insight became known as the concept of “dynamic polarization”. He also did studies on neuroplasticity by observing that small nerve fibers can sprout from the outer end of a damaged axon, stimulated by a “neurotropic factor” in its direct environment. On the subject of conscious awareness, he proposed that upon stimulation of a single sensory cell in the retina of the eye or in the auditory apparatus, the terminal sprouting of its axon results in concurrent stimulation of many pyramidal cells – baptizing these ”psychic cells” – leading to an avalanche of consciousness. He even noted the importance of attention is as a decisive element on how images or events are perceived or remembered. Nevertheless, he realized that his thoughts were rather conjectures, not based on true observations. Only two years after his applying Golgi’s method that recognition of his findings followed at a congress in Berlin where the significance of his observations was immediately accepted by histologists of fame. Not long thereafter he was invited to London for the Croonian lecture talking on “’La fine structure des centres nerveux” on the initiative of Charles Sherrington being inspired by Cajal to choose the field of neurophysiology.

It took another fifty years for the electronic microscope to confirm Cajal’s interpretation that nerve cells are not in direct connection with each other…

His ultimate recognition followed in 1906 receiving the Nobel Prize. The co-winner was Camillo Golgi still holding to the view that nerve cells form a continuum, which judgement had meanwhile become obsolete and was no longer supported by neurohistologists. In Stockholm, Golgi declared that the nervous network exists of an “anatomical and functional continuity between nerve cells “. The next day, Cajal stated that “If the said intercellular unions are not the result of an illusion…. whose value would almost be nil in the face of the nearly infinite quantity of the perfectly observed facts of free nerve endings “. Since, such controversy between Nobel Prize sharers has not happened again. It took another fifty years for the electronic microscope to confirm Cajal’s interpretation that nerve cells are not in direct connection with each other, but communicate via a synaptic cleft in between the nerve cells. In this small structure, the axonal ending releases specific molecules called neurotransmitters which either increase or diminish the electrical polarity of the dendrites of neighbouring nerve cells. In that way, the next neuron becomes either more polarized and thus inhibited to discharge its electrical activity, or in case of depolarization ready to fire and deliver its neurotransmitter to the next neuron.

One may wonder what made Cajal so successful among the scientists who like him studied the nervous system applying the same techniques. One advantage over his competitors was his experience in painting and drawing nature, which had given him a trained and sharp eye. Nevertheless, in the beginning Ramón y Cajal faced many obstacles. He came from a rather modest background and lacked a role-model. In his youth, he had showed himself to be quite independent, showing lots of energy and the character to carry on despite opposition of his father or disapproval of teachers. In many ways he was an autodidact, which in the end was rather an advantage than a handicap. Well aware of the importance of unbiased observations, he did not easily give in once convinced of his conclusions. His genius was that purely based on static images so accurately displayed, he could conclude on how nerve cells communicate and function. In order to follow the precise itinerary and endings of individual axons in between a dense network of fibres, he colored just a few nerve cells in a thick slice of tissue with Golgi’s black reaction, illustrates his inventiveness. The idea to apply neuro-embryology in chicken embryos to observe the sprouting of nerve fibres may have facilitated his dynamic way of thinking on how the nervous system works.

At the time, research existed of doing experiments or making meticulous observations by single scientists and from there to make careful and unbiased interpretations. In that way he resembles men like Linnaeus, Von Humboldt or Darwin who all had proposed theories now generally accepted, purely based on accurate observing of surrounding nature with the naked eye. Today, investigations are carried out in groups because of the opportunity or necessity of combining numerous techniques in research projects. At Cajal’s time with only a microscope and staining methods of tissues available, a single man could do the job.

HIS SPLENDID PICTURES of nerve cells are revealed in The Beautiful Brain: The Drawings of Santiago Ramón y Cajal by Larry Swanson and colleagues. It handsomely shows some eighty pictures of different neurons and their details with explanations on location and function. In fact, Cajal’s drawing gifts enabled him to produce practically comparable results to that of microphotography. His artistic talent also explains his early interest in photography. Daguerreo types inspired him, not only for his microscopic studies, though also for taking scenes from daily life, making portraits, and coloured still-lifes.

Another talent was his writing skill. He was a prolific author, publishing virtually all his findings. He felt the compulsion of being first on reporting new findings and showed a competitive streak. Frustrated by delays getting his work out and speaking only Spanish, he published his first papers in a journal he founded himself, paid of his own means. His style was direct, expressing himself in clear, simple sentences with little room for ambiguity, only stating what he regarded as true. Feelings of rivalry and a harshness in his character may explain that he dismissed his gifted collaborator and neuroscientist Rio del Hortega. Cajal also structured the field of anatomy and histology of the nervous system to physicians and scientists by writing a three-volume standard textbook, translated in French, later in English. In Cajal beyond the brain by Lazaros Triarhou who has annotated a good number of his essays in translation, one appreciates his language.

An important element in the character of Ramón y Cajal is his social side. He was a lifelong member of the Spanish “tertulias”, coffee-house circles where he met his friends at the end of the day. In a small book Charlas de café, Cajal brings to life the chats and aphorisms they exchanged. Like his contemporaries, Cajal was attracted by phenomena like hypnosis, hysteria, somnambulism, sleep and dreams which fascinated the people at the time. In The Dreams of Santiago Ramón y Cajal Ehrlich tells the story of public interest in parapsychology and psychology. At the end of the eighteenth century, the Viennese physician Anton Mesmer had become popular by “animal magnetism” to restore health by activating natural fluids by moving a magnet over the body. Even Marie-Antoinette of France and Wolfgang Mozart were “mesmerized”, inspiring the composer in Cosi fan tutte to let Despina disguised as physician apply a magnet stone.

Seemingly more sound methods were introduced by Charcot in Paris and Bernheim in Nancy, attracting lots of interest by lectures, often open to the public. Jean-Marie Charcot, considered the father of neurology, concentrated on hypnosis to cure hysteria. In his opinion a positive reaction to hypnosis confirmed the presence of an underlying neurological disease. The school of Hippolyte Bernheim rather felt that the effects of hypnosis are best explained by the effects of suggestion. Sigmund Freud from Vienna was strongly impressed by Charcot despite Charcot’s belief in neurological determinism.

THE SUFFERING CAJAL endured in Cuba and following his return may have made him susceptible to these developments in a prospect of healing. This may explain why, during his tenure in Valencia, he started to study and apply hypnosis. Despising theatrics and glad to see that parapsychology was exchanged for psychology, he set up a committee for psychological investigation with some colleagues and friends who met in his house. In Recollections of My Life, he mentions a stream of “hysterics, neurasthenics, maniacs, and even accredited spiritualistic mediums” passing by. Cajal recalls observations on healthy individuals, often lawyers or physicians, in whom he could induce hallucinations, recovery of forgotten memories and abolition of the free will. Therapeutically, he observed instantaneous transitions from sadness to joy, restoration of appetite in individuals refusing to eat, forgetting painful or distressing episodes. Soon, Cajal was overwhelmed by people wanting to consult him. About the time  he was considering a new position in Barcelona, he felt his curiosity on hypnosis had been satisfied. He dismissed his patients and did not send any bills. In the end, he expressed surprise in observing cerebral automatisms that had deemed before as tricks of magicians, and disillusionment about how sensitive the human brain is to suggestion. He wrote a single paper on the subject, a case in which childbirth which went smoothly was hardly painful. In fact, it was the delivery by his own wife of their sixth child, carried out under hypnosis applied by himself.

‘The scientific rigor that Cajal attributed to reproducible observations made him critical of Freud’s theories…’

He also became interested in the theories of Sigmund Freud and his ideas on the unconscious. Freud and Cajal had much in common and were close contemporaries. Both came from simple backgrounds out of the mainland of their country, and shared an early interest in neuroanatomy. Also, they were productive and creative writers. Nevertheless, the scientific rigor that Cajal attributed to reproducible observations made him critical of Freud’s theories. He felt that Freud’s conclusions were based on interpreting stories and dreams of his patients in such a way that it confirmed a prior theory. Cajal might have felt strong rivalry with Freud because of all the admiration he had received in Spain, a country receptive to psycho-analysis. Although Cajal never expressed these opinions in public, he wrote in the margins of a copy of Freud’s The Psychopathology of Everyday Life, “I consider as collective lies both psychoanalysis and Freud’s theory of dreams “. Possibly motivated by his conviction of making even-handed observations and mistrust of Freud’s interpretations, he wrote down a good number of his own dreams during the last 15 years of his life. In Ehrlich’s The Dreams of Santiago Ramón y Cajal about 100 of his dreams are literally transcribed containing the first English translation of Cajal’s dream diary. About this he confessed that “In more than 500 dreams I have analysed, it is impossible to verify…the doctrines of the surly and somewhat egotistical Viennese author. Of this, I shall manage to write another book on dreams“.  Recurring themes were financial problems, fighting with soldiers, drowning of a girl, anxiety and distress by a dying friend, earthquakes, fears of teaching. With each of these subjects he had been confronted, including the loss of a daughter. Nevertheless, he concluded that his dreams did not contain any resemblance with the real world. Some indication of a decrease of his mental capabilities noted at the age of 70 may explain that he failed to see the obvious relationship between his nightmares and what he had endured during his lifetime.

Ehrlich’s book can be read not only as a biographical outline of Cajal’s achievements, but also as the history of an era of popular interest in bizarre psychological phenomena concurrent with the rapid changes in neuroscience.

The most remarkable side of Cajal’s multitalent as artist and scientist is his ability to draw original conclusions which have survived the test of time in a brand-new field of science.

The most remarkable side of Cajal’s multitalent as artist and scientist is his ability to draw original conclusions which have survived the test of time in a brand-new field of science. He was lyrical about the function of the pyramidal cell, about which he said, “… my attention hunted, in the flower garden of the grey matter, cells with delicate and elegant forms, the mysterious butterflies of the soul, the beating of whose wings may someday — who knows — clarify the secret of mental life “. Indeed, he came close by proposing that consciousness emerges as an avalanche produced by “psychic cells.“ Today, 100 years later, we know, based on the work of neuroscientists such as Stanislav Dehaene and Giulio Tononi, that the appearance of consciousness is indeed a more or less abrupt phenomenon: Converging stimuli from the unconscious leads to an outburst of fast oscillations between a great number of brain regions over long distances in the cerebral cortex, exercised by the long axons of pyramidal cells.

Maybe Ramón y Cajal is best characterized in his own words: “I have always aimed that my life should be lived as far as possible according to the counsel of the philosopher, that is, a living poem of intense action.” Remarkable for a scientist, less for an artist.

♦

Charles Vecht MD is a neurologist/neuro-oncologist who has worked and studied in the Netherlands, New York and Paris. He has  published many articles on clinical research in brain tumours. He now studies and writes on the effect of the human gaze on the social brain.