Andrew P. Wickens (a winner of the British Psychological Society’s Book Award) considers their historical significance.
Five depictions of the brain
The history of neuroscience is rarely taught in universities, and few books trace developments from the ancient past to the present. Here, I present five of my favourite illustrations from my book, A History of the Brain, and consider their importance for contemporary understanding.
The first illustrations of the human brain are believed to have been drawn in Alexandria around 300bc, the only place in which anatomical dissection of corpses was allowed between Antiquity and the early European Renaissance. This practice appears to have been sanctioned by Ptolemy, a possible half-brother to Alexander the Great, who declared himself king of Egypt in 323bc. Although it helped advance medical knowledge, the practice of human dissection only lasted for a short period of time, perhaps no more than 20 or 30 years. One researcher taking advantage of this situation was Herophilus. He noticed the body contained thread-like pathways, which he recognised as the nervous system, possibly the single most profound insight into the workings of the body made by any individual. He also elucidated the internal anatomy of the human brain, including its ventricular system. Another renowned anatomist in Alexandria was Erasistratus, who compared the surface of the cerebral hemispheres with the coils of the small intestine. Believing these to be more extensive in humans than in animals, Erasistratus reasoned (according to the later writings of Galen) that they correlated with intelligence. Both men are known to have written several books, presumably on papyrus using reed pens, although only small extracts have survived.
It would be surprising if neither Herophilus nor Eraistratus drew what they had observed, although no such drawings exist or are referenced in ancient texts. Nonetheless, a group of drawings known as the ‘five figure series’, believed to be copied from a much earlier source, are found in a number of Eastern and Western medical manuscripts. According to the medical historian Karl Sudhoff, the originals were composed in Alexandria. If he is correct, it is possible one of the five figures showing the body’s venous system presents us with the earliest depiction of the brain. This can be seen in Figure 1, which was copied onto parchment in Salerno around 1250.
One of five drawings found in a number of Eastern and Western medical manuscripts which are believed to be derived from a much earlier source – possibly Alexandrian circa 300bc. This example is believed to have been copied from another illustration in Salerno around 1250. The insert (above) shows a depiction of the brain.
The sketch shows two vessels entering the brain, identifiable by the wrinkled outer surface of its cortex. The text accompanying the drawing also attributes the brain with imaginativa, logistica and memoria, thereby showing knowledge of a medieval doctrine known as the cell doctrine. In this, each ventricle of the brain was attributed with a mental function. It is assumed the text was added at a later date than the original drawing.
The depictions portrayed in the five figure series can hardly be said to be realistic or aesthetically pleasing since all have an odd, splayed posture with no sense of depth. Much later in the 15th century, however, a new understanding of perspective allowed greater realism, initiating a revolution in art. This was one of the key developments of the Renaissance, and it led some artists to take a new interest in the human form. Arguably, the greatest was Leonardo da Vinci (1452–1519), who was even famous in his own lifetime for paintings such as the Mona Lisa. Leonardo’s talents took in many other disciplines, including engineering, mathematics and mechanics, and his fertile imagination contemplated subjects far ahead of their time, including armoured vehicles, parachutes and flying machines. But the artistic pursuit that interested him the most was drawing the human body, and he took this interest to extraordinary lengths, obtaining permission as a young artist to undertake dissection of human corpses at the medical school in Milan. This began a quest lasting many years, resulting in over 700 anatomical drawings that were to remain largely secret for over 200 years. Leonardo’s obsession was not just for art’s sake: it was to reveal the design and purpose of the human body, especially its physical mechanics. This is highlighted by his extensive anatomical folios that contain detailed commentaries about his sketches. For Leonardo, drawing was to understand and, when asked about his genius, he was known to reply ‘saper vedere’, meaning to see what others don’t. This new vision also extended to the brain.
Some of Leonardo’s earliest anatomical drawings date from 1487 to 1493 and they include depictions of the head, skull and brain’s surface. They are sketched in chalk, ink and crayon. In one famous drawing, where he compares the scalp’s layers to those of an onion, Leonardo provides us with a diagrammatical representation of the ventricles, drawn as three connected round cavities inside the head. The anterior cell is illustrated receiving channels from the eyes and ears, presumably representing the visual and auditory nerves. From this, it is apparent that Leonardo was acquainted with the cell doctrine, which remained the standard explanation of brain function at the time. Another important concern of medieval psychologists was the location of the sensus communis – a term derived from Aristotle denoting the site where all the senses were believed to merge. In line with other medieval writers, such as Avicenna and Albertus Magnus, Leonardo placed this in the first cell. But Leonardo was interested in the sensus communis for another significant reason: he believed it was the place where the soul resided. Or as he put it: ‘The soul seems to reside in judgement, and the judgement would seem to be seated in the part where all the senses meet; and this is called the sensus communis’. Another drawing of the period leaves no doubt where Leonardo thought this confluence of senses lay, for he would draw the interior of the skull and place a large cross to pinpoint its location.
Breaking the stranglehold of tradition
Although the brain’s ventricles had been described in ancient times, their true intricate shape and connectivity was not fully appreciated since they were difficult to visualise once the brain was sliced open. This was largely because there were no effective fixative methods available to enable the brain to be sufficiently hardened for serial cutting and slicing. This problem was overcome by Leonardo in his second Milanese period (1508–1513) when he made a cast model of the ventricles. He did this by injecting molten wax into the middle ventricle of an ox, after it had been prepared with two vent holes allowing the internal fluid and air to escape. Once the wax had hardened, Leonardo cut away the soft tissue to expose the cast, which modelled the shape of the ventricular system. By this method, Leonardo was able to draw, or perhaps more accurately imagine, the interior of the brain in a highly naturalistic way. An example of this is shown in Figure 2. Here, the two lateral ventricles nestling in each cerebral hemisphere are linked to a middle ventricle that feeds into the posterior ventricle. Interestingly, it is the middle ventricle that is now labelled as the sensus communis, showing Leonardo had changed his mind regarding its placement in the brain.
Figure 2. Drawings of the ventricles by Leonardo da Vinci after he had assessed their shape from making a wax cast (circa 1508). The two lateral ventricles are labelled with the word imprensiva, the middle ventricle is designated as the sensus communis and the posterior ventricle is given the function of memoria. The bottommost drawing shows the base of the brain and the rete mirabile.
If any one year can be said to mark the point at which the medieval world ended and the modern one began, a strong case can be made for 1543. In this year, two books were published, within one week of each other, which helped break the stranglehold of traditional thought that had held sway in the West for several hundred years. The first was De Revolutionibus Orbium Coelestium (On the Revolutions of the Heavenly Spheres) by Copernicus, a work denying the Earth lay at the centre of the universe – a truth that greatly undermined the prevailing Aristotelianism and Christian teaching. The second was De Humani Corporis Fabrica (On the Structure of the Human Body) by Andreas Vesalius (1514–1564). This ridiculed the teachings of Galen, sacrosanct at the time, and led to a thorough revision of concepts concerning the structure and function of the human body.
The son of a doctor with royal patronage, Vesalius was so intent on learning anatomy as a young boy that he dissected small animals caught in the fields near his home. Later, as a student, he collected human bones, some of them taken from public cemeteries, an activity enabling him to recognise any bone in the body by touch alone. His obsession with anatomy also led to a lecturer’s position at the University of Padua when only 23 – a remarkable achievement, for Padua was the greatest medical university of its day, and famed for its demonstrations of human dissection that took place in a purpose-built theatre. Vesalius soon built himself a reputation as a teacher, taking scalpel in hand rather than reading from notes, and typically using several cadavers at the same time in various states of dissection for his demonstrations. This was a time when Galen’s works formed the main basis of all anatomical education and many believed further progress was impossible. But Vesalius began to have doubts, and in 1540, when asked to translate Galen’s great work On Anatomical Procedures, which had remained beyond reproach for over 1300 years, he realised with astonishment that Galen had never dissected a human body. Instead, he had extrapolated all his anatomy from cattle, pigs and monkeys. Vesalius’ response was to write De Humani Corporis Fabrica (On the Structure of the Human Body) – in which over 200 instances of Galen’s work was shown to be in error.
The Fabrica is one of the most magnificent collections of anatomical drawings ever produced. Comprising over 700 folio pages with 83 anatomical plates made up of 420 illustrations, it attempts a complete study of the human body. Vesalius also went to great lengths to employ the best artists and wood-block cutters of his day, and this resulted in highly realistic illustrations, many of which filled a complete page. For example, the first illustration of the seventh chapter shows a head with the skull’s roof removed to leave the brain exposed to observation. The brain’s gyri and sulci are realistically portrayed as are the blood vessels and sinuses, along with the tough fibrous outer layer known as the dura. This type of detail had not been seen before. Another innovation of Vesalius was to make a series of horizontal slices through the skull with the brain left in situ (see Figure 3). This way of cutting the brain was effective in exposing the ventricles at different levels while also helping to reveal the surrounding areas of grey and white matter. Using this method, Vesalius illustrated several brain regions for the first time including the thalamus, striatum, colliculi and stria terminalis.
Figure 3. Plate 68 from De Humani Corporis Fabrica (On the Structure of the Human Body) by Andreas Vesalius (1543). The two lateral ventricles are now coming into view with the corpus callosum (L and M) more anteriorly. Most
of the other letters refer to areas of grey and white matter.
The 17th century is generally recognised as an age of transformation in which the intellectual landscape of Britain was radically redrawn by the rise of modern science. It also saw the founding of the Royal Society, with one of its most distinguished members being the English physician Thomas Willis (1621–1675). A staunch churchman and Royalist during the English Civil War, Willis was appointed Sedleian Professor of Natural Philosophy at Oxford when approaching his 40th birthday. He would use this opportunity to study the brain and nervous system. Indeed, Willis set about this task with remarkable fervour, forming what can be regarded as the first neuroscientific interdisciplinary research team, including Christopher Wren, who drew many of the illustrations (actually engraved on copper plate, which provided far superior detail than woodcuts); Robert Boyle who discovered new ways of preserving and hardening the brain with alcohol; and Richard Lower, responsible for much of the dissection. Keen to use every corpse at his disposal, Willis confessed he became ‘addicted…to the opening of heads’. Fortunately, Oxford had been given Royal dispensation to claim the body of anyone executed within its boundaries, and Willis took full advantage – often dissecting in the inns and houses where the dead bodies lay.
The result of his endeavour was a book of 150 folio pages, along with 15 plates of illustrations, devoted exclusively to the brain and nervous system, entitled Cerebri Anatome. Written in Latin and published in 1664, the book abounded with so much new information it was to be authoritative for the next two centuries and would pass through 23 editions. Unlike Vesalius, Willis removed the brain from its cranium and used knives to cut it open – a procedure enabling him to use magnifying glasses to examine it in great detail. This technique led to the discovery of a number of new brain areas, with many anglicised terms from the Anatome entering the English vocabulary and remaining in use today. These include, for example, the anterior commissure, corpus striatum, and inferior olives. Willis also used the Greek word neurolgia, which was later translated into English as ‘neurology’ by Samuel Pordage in 1681, who defined it as the doctrine of the nerves.
For many, the highlight of Cerebri Anatome is its depiction of the blood vessels at the base of the brain. These had proven controversial in the past, with Galen confusing them with a vascular network in oxen called the rete mirable – a mistake rectified by Vesalius. Although the human brain had no rete mirable, Willis showed it did have a large ring of arteries (see Figure 4) which received blood from the two ascending carotid arteries. Importantly, Willis also recognised the ring’s functional significance – realising the arteries were arranged in this way to ensure a constant supply of blood to the brain, even when part of it was occluded. Today it is known as the Circle of Willis. Another significant feature of Cerebri Anatome was its innovative use of research techniques – including one used to trace the course of blood vessels through the brain. This was achieved by injecting ink, using a syringe made from a quill and a dog’s bladder, into the carotid arteries of a cadaver, leading to small dark spots appearing on the outer surface of the cerebral cortex. After this, there was little doubt that blood flowed into the brain from the arteries: it was then distributed throughout its tissues in a vast network of very fine vessels. This was a very important finding in providing a new understanding of stroke, and helped dispel the idea, still held by some, that the condition resulted from a blockage of animal spirits rather than blood.
Figure 4. Figure from Cerebri Anatome showing the base of the brain drawn by Christopher Wren. It illustrates the circle of Willis (E), the olfactory bulbs (D), the corpora quadrigemina (Y), and the cerebellum (B). The origin of 10 pairs of cranial nerves can also be seen.
If one person above all others can be regarded as the father of modern neuroscience, then it is surely Santiago Ramón y Cajal (1852–1934). The son of a struggling country doctor from northern Spain, Cajal experienced a life-changing event in 1887 when shown glass slides of nervous material stained by Golgi’s silver impregnation method. This histological technique, discovered by the Italian Camillo Golgi in 1873, was unique for it only highlighted a small percentage of nerve cells in any given sample. This was far from being disadvantageous, as it allowed the few neurons that had taken up the stain to be seen in their entirety. This was one of the biggest breakthroughs in the history of neuroscience, since the full structure of the nerve cell with is tree-like dendrites, cell body and axons could now be visualised – something that had not happened before. The Golgi stain, however, often produced inconsistent results and Cajal’s first attempts were disappointing. Undaunted, he set about improving the technique by developing a more intense colouring reaction, and used it primarily on fetal and immature nervous tissue, taken before the myelination of the axons had taken place. This procedure was successful in allowing the nerve fibres and connections to be visualised much more clearly.
At this point, Cajal engaged in a feverish burst of research activity. He also began publishing a journal so his findings could be disseminated to scientists abroad. The inaugural copy appeared in 1888 and its first paper concerned the anatomy of the bird’s cerebellum (see Figure 5). Although much of this was already known, Cajal’s genius lay in the way he illustrated the cerebellum’s fine structure, showing the different types of cell and the way they were joined together. The cellular structure of a brain region had never been illustrated in such precise detail before, and Cajal was to show each region had its own distinct neural organisation. In fact, his illustrations were a composite of many different drawings, based on long hours of meticulous microscopic examination, and then expressed with some degree of artistic imagination. Moreover, one would never see such an image peering down a microscope. Nonetheless, they captured perfectly the complexity of the brain’s structure. Even today, over 130 years later, Cajal’s drawings of the nervous system have not been significantly improved upon.
Figure 5. An illustration of the pigeon’s cerebellum using the Golgi stain drawn by Santiago y Ramon Cajal, which appeared in the first edition of his journal Revista Trimestral de Histologia Normal y Patologica, published in 1888. It shows a number of cell types including the heavily branched stellate cells (D) and mossy fibres (E).
When Cajal first started his research, most anatomists including Golgi were reticularists, believing the nervous system contained a continuous network of interconnected fibres with fused axons. However, right from the very beginning, Cajal could not find any evidence to support this idea. Instead, each neuron appeared to be an independent unit much like any other cell in the body. Indeed, Cajal’s observations would be shown to be correct and led to the general acceptance of the neuron doctrine (a term invented in 1891 by Wilhelm Waldeyer), whose basic tenet was that nerve cells form the fundamental structural and functional unit of the nervous system. In addition, Cajal observed that the axon endings nearly always terminated in the grey matter, where dendrites were known to be located. This would lead to another profound insight, as Cajal realised information must flow in one direction through a neuron, from the dendrites, through the cell body, to the axon. This was a revolutionary idea since it implied the dendrites served as the receptive part of the nerve cell, whilst the axon transmitted the nerve impulse – a position totally at odds with Golgi, who believed dendrites only had a nutritive role. But this also led to a baffling question: How could information flow within an ‘infinitely fragmented’ nervous system? One person to offer an answer was Cajal’s great friend Charles Sherrington, who believed there was a point of contact between the axon ending and dendrite, which he called a synapse. It would take many years before this idea was fully proven, and recognition of the existence of chemical neurotransmission in the CNS took longer still, but Cajal and Sherrington’s conception of nervous function would be vindicated.
If these were Cajal’s only achievements then they alone would have placed him in the pantheon of the greatest anatomists of all time, but there was much more. He undertook pioneering work on axonal growth and nerve regeneration, and discovered neurofibrils, dendritic spines, growth cones and many types of different cell. Cajal also wrote several books, including his magnificent Histologie du Système Nerveux in 1911. Containing nearly 2000 pages and 887 intricate illustrations of nearly every region in the brain, it cannot fail to impress even the most informed contemporary reader today. He also won the Nobel Prize along with Golgi in 1906. After Cajal’s death in 1934, the Italian neurologist Ernesto Lugaro in an obituary wrote that Cajal had contributed more to neuroscience than all the efforts of his colleagues put together. It is hard not to agree.
About the author
‘I’ve always tried to incorporate historical themes into my teaching: it helps add a narrative, and allows students to understand where ideas have originated and what further developments might occur. Some ten years ago it dawned on me that there were no neuroscience textbooks that traced the flow of historical development from the ancient past to the present. The seeds were sown for my book, A History of the Brain.’
Andrew Wickens is Senior Lecturer at the University of Central Lancashire
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