This is chapter 2 of a book on the brain I was writing in the 2010’s. The first 4 chapters are here, but I’m posting it as a single post. It tells the story of the origins of neuroscience in modern form, with Thomas Wilis and the Oxford circle making the first complete dissections of the brain, and publishing ‘cerebri anatome’.
Chapter 2 – The Anatomy of the Soul
‘Now then, listen. In order for you to fully comprehend
That minds and flimsy spirits have a birthday and an end,
I’ve spent long hours hunting the right words, and labour of love,
To set forth for you in poetry that’s worthy of
Your life’s calling. But do this favour for me just the same,
And yoke both of these concepts underneath a single name,
So that, say, when I speak of spirit, teaching that it dies,
Understand I am referring to the mind likewise,
Seeing that a single soul is formed out of their union’
Lucretius, De Rerum Natura, 1st century BC.
Book 3, lines 417-25
Thought found its location only gradually. It began by entertaining a hypothesis that remains astonishing to this day: that our thoughts come from an organ of the body, of physical matter. In short, that thoughts are flesh.
We begin this story over 2,000 years ago, in ancient Rome. That thought was the product of a physical structure had been inferred by the great Roman atomist philosophers, who believed that everything, however complex, was a product of the combination of the simplest of elements. One of these philosophers was Lucretius, who was quoted by Montaigne in The Essays:
‘We feel the soul is with the body born,
Grows up with it, and with it waxes old.’
Lucretius goes on, more directly:
‘That mind must be corporeal is quite plain,
Since darts and thrusts corporeal give it pain.’
So Lucretius viewed the mind as being physical 2,000 years ago, based upon simple observation, thus beginning the search for the anatomy of the soul. However, Lucretius’ linkage still leaves the nature of thought poorly defined, without mechanism or specific structure. There were two central hurdles to achieving an explanation of the mind that moved beyond this early insight.
The first hurdle was philosophical. To render the spirit physical was to render God physical, an act akin to atheism. The spirit was something deeply spiritual, religious, divine: the greatest of God’s gifts, and that gift which made us a special species. Even when people could overcome the intuitive hurdles of thinking that conscious experience arises from the brain, these religious attitudes made the quest daunting. The hostility led Vesalius, perhaps the greatest anatomist of all time, to ‘wholly abstain from consideration of the divisions of the soul and their locations’. Even today, the view that there is some separation between brain and mind is common.
Yet for those willing to try to lay the detail onto Lucretius’ conjecture, a second major hurdle still existed, this time technical – how do you actually study the brain?
The elusive organ
‘This lax pith or marrow in man’s head shows no more capacity for thought than a cake of suet or a bowl of curds.’
Henry More, 1652, An antidote against Atheism.
The early advances in understanding the physiology of the body came from making links between structure and function. What is needed is some feature of anatomy, some pattern in the organization of the physical matter, that gives clues as to how function arises. Hearts connect to the blood vessels, lungs to the airways, stomachs to the mouth and intestine. This principle of linking anatomy to function is now at the foundation of biology, and act as a guiding light for experimental scientists. In the words of Sydney Brenner, ‘When it’s too difficult to study function, you study structure…. Once you know anatomy you get bits of physiology for free.’ So understanding the organizational logic of physical structure helps you to see how it gives rise to function.
However, even for the heart, an organ whose form is extremely closely linked to its function, this inference was historically challenging one to make. Things that are obvious retrospectively are not so obvious at the time. Even Leonardo da Vinci himself, despite fully understanding the basic anatomy of the heart, did not realize that it implied a circulatory mechanism. Only centuries later did scientists make this link.
For the brain, the task is far harder than for other organs. The brain’s form rapidly deteriorates after death, making it hard to dissect and examine. Even removing the brain intact from the skull was not possible until the seventeenth century; investigators were left with lumps of goo rather than neat anatomical specimens. Further, even if one could extract the brain intact from the skull, the brain’s appearance does not immediately suggest that it is the organ of thought. It looks like a collection of mushy walnuts, with varying folds and bumps, and different greyish hues dispersed seemingly at random. It appears to offer few clues to the investigator. Even the clear distinctions between different brain areas shown in anatomy books are not at all obvious to the naked, unprepared eye. This mess may have been what led many medical researchers, including Galen and Da Vinci, to focus instead on the fluid-filled ventricles weaving through the brain, an area that we now know is the only brain area not directly involved in thought.
How, then, was this impasse overcome?
Putting nature to the torture
‘For either by this way, by Wounds and Death, by Anatomy, and a Caesarean Birth, Truth will be brought to Light, or forever lye hid.’
Thomas Willis, Preface to Cerebri Anatome, 1664
The link between the physical and mental, the ‘union’ referred to by Lucretius, was definitively demonstrated in Oxford in the seventeenth century. This was, for all intents and purposes, the beginning of neuroscience. Indeed, this was a time when science itself was new. Nature was, in the words of Francis Bacon, being ‘put to the torture’ by the new tool of inquiry – the experiment – relentlessly probing and testing nature to reveal her secrets.
In Oxford, a group of self-styled ‘natural philosophers’ formed a club dedicated to these experiments. This was the ‘Experimental Philosophical Club’, which later became the famous Royal Society. It grew out of the new coffee club culture, and was a social circle of investigators using natural philosophy almost as a kind of entertainment. The group would meet weekly to discuss and share demonstrations, refine and share methods, and drink that newly-found elixir, coffee. Such luminaries as Robert Boyle, John Locke and Robert Hooke were present in these circles, working on the so-called clockwork universe, discovering laws and explanations to simplify the everyday world into mechanisms free of mystery.
No subject was fully off limits to these men. Hooke’s law was devised, the Micrografia written, Boyle’s chemical experiments completed, all within a few short years. In secret, a futile search for the alchemical philosopher’s stone was underway, a feat that later captivated Newton. Even the properties of marijuana were investigated. Nature was indeed put to the torture. But whilst these scientists sought to uncover the clockwork universe, only one sought to uncover the clockwork mind.
The man who was addicted to the opening of heads
‘Willis put the brain and nervous system on their modern footing, so far as that could be then done.’
Charles Sherrington, Nobel Laureate, 20th century.
This scientist was Thomas Willis, the world’s ‘first clinical neurologist’. It is Willis who is quoted at the beginning of this book, and in the preceding section. In a series of books, first and most famously Cerebri Anatome (The Anatomy of the Brain) in 1664, he laid out a set of landmark observations about the basic organization of brains. Cerebri Anatome was the first ever neuroscience book, a catalog of the brain for the first time in history, filled with speculations and details about its working. The outcome, in Carl Zimmer’s words, was the idea of a ‘Soul Made Flesh’, a physical brain, with its structure linked to function, and its function linked to thought.
Willis’ path to this idea was the result of the convergence of two character traits common to many great scientists. First, he had a rebellious streak, embodying the subsequent motto of the Royal Society – Nullius in verba, or Take nobody’s word for it. He described his own profession of medicine as a ‘sword in a blind man’s hand’, and openly questioned the wisdom of the ancient doctor Galen, who was still greatly revered, even idolized, in seventeenth-century England. He saw the clear conflict between Galen’s theories and his own clinical experience as a doctor, and chose to believe his own eyes.
Willis’s second crucial trait was that he not only disbelieved existing wisdom; he actively sought to overturn it with his own observations. He was a Sherlock Holmes-like figure, with a masterful eye for detail and how those details connect. Prior to working on the brain, he had already written the first case reports of influenza, and made the first link between diabetes and glucose by noticing that flies were especially attracted to the urine samples of his diabetic patients. Observation was thus a central tool for Willis, and his skill at connecting his observations was ideally suited to the problems that he was to tackle.
It was in the early 1660’s that Willis used these two traits to forge a path for the study of thought, resolving to see the brain for himself rather than trust the claims of the ancients:
‘….I determined with myself seriously to enter presently upon a new course, and to rely on this one thing, not to pin my faith on the received opinions of others, nor on the suspicions and guesses of my own mind, but for the future to believe Nature and ocular demonstrations.’
He launched vigorously into this effort, often gathering corpses from executions to fuel his investigation:
‘I betook my self wholly to the study of Anatomy: and as I did chiefly inquire into the offices and uses of the Brain and its nervous Appendix, I addicted myself to the opening of Heads.’
Through this approach, he promised that ‘the impressions, influences, and secret ways of working of the sensitive Soul itself will be discovered.’
These quotes are all from the beginning of Cerebri Anatome. Willis lived before the tyranny of journal editors and academicese had infected science, and so his writings blended his own story, his observations and his speculations. This allows us to retrace his steps as he ‘established links that are still astonishing to us 300 years on’.
Neuroscience’s Dark Side of the Moon
‘The parts of the Brain it self are so complicated and involved, and their respects and habitudes to one another so hard to be extricated, that it may seem a more hard task to institute its perfect Anatomy, than to delineate on a plain, the flexions and Meanders of some Labyrinth’
Thomas Willis, Cerebri Anatome
Yet Willis did not work alone. His ambitions combined with the spirit of collaboration in Oxford at the time, with him forging a team of young investigators to work on his task. They worked tirelessly, ‘almost no day past over without some Anatomical administration’, using Willis’ house on Merton Street in the center of Oxford as a dissection chamber.
We can envisage this crowded hall, still in place today, filled with the meetings of Willis’ investigators. We might see Richard Lower, who later performed history’s first blood transfusion, providing help through ‘his most skillful dissecting hand’, whilst Christopher Wren, of later architectural fame, was also frequently present, ‘delineat[ing] with his own most skilful hands many Figures of the Brain and Skull, whereby the work might be more exact.’ Wren’s beautiful illustrations are reprinted to this day. Willis’ group had thus unwittingly followed Da Vinci’s unpublished advice to not only dissect well, but to also draw well, in order to reveal anatomy in ways that words could not capture (Arraez-Aybar et al 2015).
The approach that the team took differed radically from earlier scientists, enabling them to see the brain in a very different way. Willis noticed that the critical error of previous anatomists was to remove the brain from the top of the skull in pieces. The brain then lost its shape and form, such that ‘the Phaenomena arising by chance from such a dissection, they easily esteemed for true parts of the Brain’. Willis instead removed the brain intact, by breaking open the skull from the bottom. He described this innovation in some detail in his writings, testifying to its importance.
These novel dissections revealed the brain as it had never been seen before. There, lying before this group of Oxford mavericks, was the soul in physical form. Beneath the cerebrum atop the brain lay a vast complex of structures, most of which had only been glimpsed at in previous dissections, having been disfigured by the earlier dissection method. Many of these structures were named by Willis, or after him in his honour, including the arterial Circle of Willis. To hold an intact human brain in one’s hands was Willis’ first major advance.
From this new visual perspective came one of the most famous images in the history of neuroscience: Christopher Wren’s drawing of the underside of the brain, neuroscience’s equivalent of seeing the dark side of the moon for the first time.
Wren’s illustration of the underside of the brain, Cerebri Anatome, 1664 < I own an original first edition print of this image and can take a better version when the time comes
Willis had come a long way from his early days struggling to remove the brain from the skull, a time when he found it difficult to even discriminate between what was brain and what was not. The image had shown that the brain was not merely a ‘lax pith or marrow’, as Henry More had so derisively called it, but a layered, detailed, labyrinthine structure. It was an organ of the highest complexity.
Yet Willis still had a problem. This image alone did not appear to reveal many secrets about how the brain actually worked. The image asked much more than it answered, and thus represented a beginning, not an end, to Willis’s research. Obvious questions protruded from the lump of flesh that he had extracted. Why was the brain he saw not homogenous, a single entity matching the single entity of the soul? What was the reason for this variety of structures? If thought was not homogenous, what was the pattern of this heterogeneity? Most radically, could you link specific variation in the patterns of this flesh to specific variation in the soul? These questions were Willis’ new canvas, onto which were laid new dissections and speculations.
With twenty-first-century hindsight, at least some of the answers to these seventeenth-century questions may seem deceptively obvious, as we are taught from a young age that different brain areas do different things. But instead of jumping to this conclusion, let’s consider what Wren’s drawing shows, and how ambiguous its interpretation could be. At the bottom of the image is the white tube of brainstem, which links seamlessly with the spinal cord. This is what feeds into your neck, and down to the rest of the body. The largest, richly folded structure, farthest from the brain stem, is the cerebrum, the walnut-like structure. So, what do they do?
With modern knowledge, we may see an obvious solution. The proximity of these lower brain regions to the spinal cord must surely suggest a simpler, more primitive role, whilst the richly folded cerebrum, being further away, would be a more advanced, ‘higher’ structure, serving uniquely human cognition? This inference is partly a product of hindsight bias. An equally persuasive but thoroughly wrong argument and arrangement could be devised. Might one not put the more uniquely human brain areas, the ‘soul’, deeper within the brain, to be more protected? Might the more uniform and exposed cerebrum not be a simple structure, with the deeper and varied labyrinths being the seat of higher complexity and thus of complex thought? Willis used two approaches to circumvent these uncertainties, finding a way to ask Nature questions more directly.
A notable analogy
‘Concerning the Heads of living Creatures, in the dissection of which it happened for us chiefly to be exercised, it was observed, as to the chief parts of the Head, that there was a notable Analogy between Man and four-footed Beasts’
Thomas Willis, Cerebri Anatome
The first approach Willis used relied upon comparison with animals. Animal dissections had already formed the basis of ancient knowledge of the body. The result was a surprisingly accurate portrait of human anatomy, with some notable errors.
Willis and his team also used animal brains extensively. The difference, however, was that Willis compared the brains of different animals with those of humans, which the ancients did not do. In doing so, Willis found a ‘notable analogy’ between them. It appeared that the brains of different ‘four-footed beasts’, by which Willis usually meant mammals, differed from one another, and from the human brain, more or less in magnitude alone:
Wherefore when the form and composition of the Brain in a Dog, Calf, Sheep, Hog, and many other four-footed beasts, were little different (the magnitude only excepted) from the figure of the same, and the disposition of the parts, in a man, I was the more satisfied to compose a certain Anatomy of the Brain by the frequent dissection of all sorts of living Creatures
Thomas Willis, Cerebri Anatome
In short, the brains of ‘beasts’ and humans were similar enough that the shape of the former could be used to inform the understanding of the latter. There was a remarkable conservation of the anatomy of the brain, such that in all of the mammals that Willis examined, he found the same set of brain areas. Even in light of our understanding of evolution, this is still somewhat counterintuitive even to this day. Generally speaking, Willis saw few fundamental differences between mammalian brains, including those of humans.
In all of them, he saw the brain connecting to the spinal cord at the base of the brain, through the brain stem. This brainstem structure then appeared to blossom into many other areas. There was the darker, richly folded little brain, or cerebellum. There was the striatum, named by willis, near the front of the brain, with streaks of white passing distinctly through it (hence, striations). There was the thalamus, the inner chamber resting at the brain’s core, and the cerebral cortex, the crowning outer structure, as well as a myriad of other areas of greatly varying size and form. For each area found in humans, an obvious parallel could be found in any mammal. The manner of brain folding was different, so that parts shifted slightly within the skull, but the deep similarity, even sameness, was striking.
Willis understood the implications of his observation. He could find nothing fundamentally different between the brains of humans and animals except size. Previously, the hearts, lungs, digestive and reproductive systems of animals and humans were known to be closely matched. Now brains were added to this list, a far more dramatic shot across the bow of human uniqueness.
So the brains of humans and animals were far more similar than a seventeenth century anatomist might have suspected. But how did they differ?
The seat of the soul
‘The cerebrum is the primary seat of the rational soul in man, and of the sensitive soul in animals. It is the source of movements and ideas.’
Thomas Willis, Cerebri Anatome
It was in finding differences between mammalian brains that Willis began to link structure and function more precisely. In Cerebri Anatome there is another version of the Wren drawing of the underside of the brain described above. It is the same view of the brain, but this time the brain is of a sheep, not of a human, is depicted. Willis’ pioneering neuroanatomy had peered deep within the brain, where others could not reach, away from the cerebrum sitting atop the brain. Ironically though, his eyes were now drawn back to the cerebrum, where he made one of his most impressive inferences.
The cerebrum, the term Willis used for what we now usually call the cerebral cortex, is a densely folded structure in humans. It is the large, walnut-like area that covers the rest of the brain. The human cerebrum is so large in surface area that it must literally be folded up to fit in the skull. However, Willis noticed that in non-human animals, such folds were much fewer, or even absent. This seemed to be related to the extent of cognition the animals had, that is, to their intelligence. This led him to his famous proposal that the ‘cerebrum is the primary seat of the rational soul in man’. Willis confirmed this link of cognitive ability and the cerebral cortex by dissecting the brain from somebody who had suffered from severe learning difficulties from birth, including an illustration of this with the description:
‘The Effigies of an humane Brain of a certain Touch that was foolish from his birth…..the bulk of whose Brain…..was thinner and lesser than is usual’
The image shows a particularly withered Cerebrum, helping to confirm Willis’ speculation that the cerebrum was indeed the site of the higher faculties. Through detective work, comparative anatomy and clinical case studies, thought had found its place. A specific variation in a piece of flesh had been linked to the very attributes that seemed to make humans unique: their thoughts.
The rivers of animal spirits
“The animal Spirits flowing from the Brain….. irradiate the nervous System.”
Thomas Willis, Cerebri Anatome
But Willis was not quite done. He further speculated on the functions of multiple other brain regions, including the Cerebellum (meaning little brain), which he linked, correctly, to involuntary movement. He postulated that the parts of movement that were automated, without conscious thought were delegated by the cerebrum to the cerebellum in a division of labour. We shall explore this in later chapters. For now, what emerged from Willis’s work was a picture of a split soul, a brain with ‘provinces’, each dedicated to their own part of the mental firmament.
Willis, however, saw a problem in this view, and then provided the solution. How did the provinces of the brain influence one another, given their separation in space? To answer this, Willis spoke of ‘animal spirits’, which he imagined as travelling like the ‘explosion of gunpowder’ between brain regions. He was arguing that there was a nonphysical element of the mind that flowed between brain areas to carry thought.
It was not in the spirit of the Experimental Philosophy Club to settle for these mystical explanations, however. Instead, Willis theorised that these ‘spirits’ needed a method for travel. To work out how this could happen, he investigated a ‘simple’ type of thinking: vision. He started with the eyes. Here, he traced fiber-like pathways from the eyes to the middle of the brain, concluding that they were ideally suited for carrying the animal spirits from the eye to the brain. Willis could not prove this directly, but we now know that cutting these fiber projections leads to an incurable and total blindness. This means that those tiny fibers, scarcely a few millimetres in width, have provided the pathway for the entirety of the visual experience of your life. Everything you have ever seen has passed through two threads of biological string.
Willis wanted to prove that these rivers of animal spirits were not unique to vision, but were a general organizing principle underlying the exchange of thoughts within brains. To do this, he used another clinical case, this time involving a movement disorder. Willis obtained the body of a patient who, in life, had had severe problems with movement on only one side of their body, offering the ideal chance to track down the pathways of movement. If he could find a difference between the left and right side of the brain, he reasoned, he could isolate the change underlying the one-sided dysfunction. Willis and his team meticulously dissected the extracted brain, poring over each part for hints of asymmetry. They eventually found that a pathway from the top of the brain, the cerebral cortex, down to the bottom, the brainstem, was selectively and severely damaged, and on one side only. This part, the cerebral peduncle, we now definitively know to be the major conduit for signals from our motor cortex to our brainstem motor control areas. When you decide to move, signals flow down this pathway to your brainstem and onward, driving movement. The individual whose body Willis dissected was part-paralysed not because they could not think about making movement, but because those thoughts were forever trapped high in the brain, unable to pass down to the site of movement execution. The patient was unilaterally trapped.
These varied insights combined to form a simpler image as Willis saw and delineated these same tube-like pathways all over the brain. The different brain areas appeared to be linked in an elaborate web: the brain was a network for the flow of the animal spirits, which move along tiny fibrous pathways as they carry thoughts back and forth.
The doctrine of the nerves
Marcus Aurelius asks in Meditations, ‘If souls survive after death, how has the air above us found room for them all since time began?’ Willis’ answer, which Aurelius may have suspected, is that the soul is flesh, and thus rots away with our bodies. There is no paradox.
But Willis’ contribution was far more than this. He found poetic explanations of thought in the brain where others had found only an amorphous confusion. From Willis’ insights we can extract the fundamentals of neuroanatomy, what he called his ‘Doctrine of the nerves’. A simple distillation of his insights and his doctrine is as follows: thought comes from the physical brain, which is split into parts. Each part is specialized for a particular function, with a progressive elaboration of the higher brain areas: those closest to the tops of our heads are correlated with increased intelligence. The physical connections between these areas are what allows our thoughts to spread, and the pattern of these connections is crucial for determining what an area does. It is a theory of networks, of specializations, of flow.
The rest of this book is an examination of, and derivation from, Willis’ core insights. The fundamental approach of anatomizing, then understanding the connections and interactions between the resulting brain elements, is the basic logic of neuroscience. We must now turn our focus toward the question of the ‘animal spirits’: what they are, and what carries them.