Full Reviews:

LOS ANGELES TIMES, MARCH 21 2004

When the brain was named king
By Ross King

We live in what Carl Zimmer, one of our most gifted science writers, calls a Neurocentric Age, in which the physical workings of the brain are seen as inextricably linked to reason, emotion, language, morality and mental illness. How we came to that realization, which Zimmer describes in his fascinating book, Soul Made Flesh, amounted to a kind of second Copernican revolution -- one inside the body.

The thrilling story Zimmer tells begins 350 years ago in Oxford, a town that in the 17th century was to science what 15th century Florence had been to art: a smallish provincial city from which a clutch of trailblazing geniuses suddenly burst out of the blue. If Florence produced Brunelleschi, Ghiberti and Donatello in the span of a single generation, Oxford created its own renaissance in the 1650s through the efforts of the Oxford Experimental Philosophy Club, a group that came together on Thursday afternoons to debunk age-old textbooks by performing wide-ranging -- and often grisly -- experiments. Members included Robert Boyle, Robert Hooke and a young prodigy named Christopher Wren, who was at the time more celebrated for operating on dogs than for building churches. Also present at these sessions was a short, stammering and rather charmless red-haired country doctor named Thomas Willis. His contributions to the Oxford Experimental Philosophy Club were as pioneering as they were gruesome: "I addicted myself to the opening of heads," he later recalled, with typical sangfroid, of his groundbreaking studies of the human brain.

Willis is the subject of Zimmer's book, which seeks to rescue him from the relative obscurity into which he has faded despite far-reaching influences as the father of neuroscience and the author of the founding text on the anatomy of the central nervous system. Willis is too easily lost in the glare of other heroes of the 17th century's scientific revolution, such as Galileo, Harvey and Newton. But Zimmer makes a convincing case that Willis is just as pivotal a figure in the history of Western thought, having recognized that emotions and many illnesses were products of the brain, at a time when more often than not they were considered the work of comets or demons.

Despite his achievements, Willis is in many ways, as Zimmer shows, an improbable scientific hero. Unlike so many of his brilliant colleagues, he matured slowly, serving a long and obscure medical apprenticeship before launching himself on the world. After acquiring a medical degree from Oxford University in 1646, he spent more than a decade as a "pisse-prophet," inspecting the color of his patients' urine and prescribing time-honored but highly dubious remedies, such as ground-up millipedes, amulets of mistletoe and roasted apples stuffed with frankincense. Zimmer suggests that Willis would have turned into just another quack doctor had he not fallen under the spell of an enterprising young physician named William Petty, who arrived in Oxford in 1649 after studies in Leiden and Paris. Holding to the latest Parisian theory that the body was a mechanical contraption, Petty ignored the official medical textbooks and, with Willis at his side, began cutting open the cadavers of executed criminals to peer at their inner workings.

Armed with a new knowledge of anatomy, Willis ambitiously turned his attentions to the brain, hoping to, as he put it, "unlock the secret places of man's mind." The brain, as Zimmer shows, was still quite low in the hierarchy of body parts when Willis began opening heads. Taking their cue from Aristotle, who had situated the soul in the heart rather than the head, most writers believed the brain to be little more than, as the philosopher Henry More wrote in 1653, a "bowl of curds." Reason, will and passion were all assigned to more philosophically esteemed organs, such as the heart or the liver.

Occasional attempts had been made to give the brain its due: Galen had located the rational soul in the ventricles of the brain, Descartes in the pineal gland. But such hypotheses were undermined by the fact that neither Galen nor Descartes had ever actually dissected a human brain. Those who had done so -- such as Andreas Vesalius in the middle of the 16th century -- were plagued by both primitive techniques (Vesalius clumsily sawed slices off the top of the head as the brain steadily rotted) and very real anxieties that attempts to plant the soul in the inert-looking gray matter of the brain might be denounced as heretical.

Willis managed to clear these hurdles. Zimmer's nimble survey of the intellectual landscape of the 17th century reveals just how deeply his studies were influenced by both the scientific and political communities of which he was a part. Boyle's discovery that putrefaction could be halted by immersing organs in pure alcohol meant that Willis was able to preserve brains for as long as he wished, carving them up and studying them at his leisure, even making use of microscopes designed by Wren and Hooke. He was the beneficiary of numerous other recent scientific advances, including William Harvey's treatise on the circulation of the blood and Wren's innovative technique of intravenous injection. The fruit of Willis' labors was his 1664 work "Cerebri anatome," a landmark in the history of science that Zimmer claims has become part of the "bedrock of modern Western thought."

Through dissection and careful observation, he recognized that the brain communicated back and forth with the muscles and organs, receiving signals and giving commands via a complex network of nerves. This realization had far-reaching consequences, and not just for anatomy. By demonstrating how the cerebellum controlled the beating of the heart through a network of nerves running down the spinal column, Willis proved for the first time that the brain, not the heart, was the primum mobile. Or, as Zimmer puts it, "the heart was no longer the king of the body. Willis handed that title to the brain." The clues to human intellect, passion and memory could be found, therefore, by anatomizing the brain.

Such a perception, a few years earlier, would have landed Willis in trouble. As Zimmer notes, Vesalius had stopped short in his speculations about the powers of the brain "lest I come into collision with some scandalmonger or censor of heresy." Willis, however, prudently declined to banish the soul from his map of the brain. He was careful to wed his new science to an old theology, eluding charges of materialism by stressing that although the rational soul was located in the gray matter of the brain -- specifically, in the corpus callosum -- it survived the death and decomposition of its host.

This foray into theological matters notwithstanding, Willis' interest in the brain was above all practical, as befitted a doctor. He spent the remainder of his life building up a lucrative medical practice in Oxford and studying the brain's many diseases. He coined the word "neurology" to describe his new type of medicine and gave precise clinical descriptions of epilepsy, narcolepsy and migraines. If his cures still bordered on quackery (his lack of success in treating his patients seems to have ensured a steady stream of corpses for dissection), his overall diagnosis of the brain's diseases was revealing. Most physical and mental ailments were, he maintained, the result of a "civil war" in the body -- a battle waged by the "lower" soul, or the bearer of sense impressions, against the rational soul housed in the corpus callosum. Zimmer shows how the studies of Willis, an ardent Royalist, constituted a search for scientific assurances in an age when England had been ravaged by war, regicide and sectarianism -- when the brutish subordinates had risen up to dethrone the ruling monarch and plunge the nation into chaos. Willis' final conception of a healthy relationship between brain and body was thus, Zimmer notes, a nostalgic evocation of harmonious social relations in pre-Cromwell England: the rational soul seated on its throne in the corpus callosum, with the lower soul keeping to its place like an obedient servant.

Soul Made Flesh may not be for the fainthearted, with its accounts of repulsive diseases and their even more repulsive cures. We learn, for example, how holes were drilled into the heads of migraine sufferers, and how other patients were subjected to transfusions of lamb's blood and remedies concocted from carved-up puppies. (One of the more uncongenial aspects of the Oxford Experimental Philosophy Club was its incredibly callous attitude toward animals.) But Zimmer has produced a top-notch work of popular science, chock-full of fascinating lore and inspired quotations.

Hosts of knotty concepts are treated to lucid descriptions, and his fluent prose and vivid narration prove themselves as much at home among the complex historical and political crosscurrents of the 17th century as they are with finely tuned accounts of biochemistry or MRI scanners.

In the end, Zimmer casts doubt on the obsessions of our Neurocentric Age, with its faith in the scientific ability to trace every decision or emotion to a chemical reaction in the brain and, by so doing, to banish from the mind-body equation the incorporeal soul that Willis had so scrupulously preserved. This materialism may have hit the buffers in any case. Zimmer claims that the images of the brain produced by today's neuroscientists are, for all their sophistication, the equivalent of early mariners' maps of unexplored continents. It's comforting to know that there are still more things in heaven and earth than are dreamt of in scientific laboratories.

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THE SUNDAY TELEGRAPH (LONDON), APRIL 4, 2004

The Brains Behind The Brain
By Blair Worden

In what conditions does science advance? Scientists will tell you that its progress depends on the institutional security, and on the ample funding, of specialised research. Yet 17th-century England tells a different story. The scientific revolution throve on institutional anarchy, financial hardship, and the versatility of thinkers to whom boundaries of specialisation were unimaginable.

Its crucible was the Oxford of the civil wars. Before the quarrel of king and parliament, Oxford and Cambridge waxed stable and prosperous, thanks to the enlargement of their role during the Renaissance and Reformation. In the Middle Ages they had trained the clergy. Now they also educated the lay ruling class, which had taken over the clergy's political and administrative duties. Endowment expanded, student numbers rose, new chairs were founded.

Yet in that flourishing pre-war era, scientific inquiry made little headway in Oxford (and still less in Cambridge). The ancient orthodoxies of Aristotle and Galen saw off the new spirit of experiment and observation. The change came after Oxford had become Charles I's military headquarters, when student enrolment and the teaching system collapsed. The king's defeat, and the subsequent Puritan purge of the university, further depleted morale and resources.

Out of that chaos there grew the Oxford Experimental Philosophy Club, from which, at the Restoration in 1660, the Royal Society would emerge. The learned diarist John Evelyn, visiting Oxford in 1654, met the leading scientists, heard their disputations, visited the Anatomy School and the Physic Garden, and concluded that this "is doubtless the leading university now in the whole world".

Historians sometimes attribute the scientific revolution to the ideological energy of Puritanism, but there were more royalists than Puritans among the Oxford scientists. Christopher Wren (whom posterity knows as an architect but who, in that pre-specialist age, was first famed as an astronomer and as the man who could remove the spleen from a dog) came of a royalist family despoiled by the civil war. So did the pioneering chemist Robert Hooke. And so did the central figure of Carl Zimmer's remarkable book, Thomas Willis, who enlisted in Charles's army. It was in Willis's house in Merton Street that the conquered royalists gathered for forbidden Anglican services under the noses of the Puritan authorities.

Today a scientist as gifted as Willis would tread a well-worn path of promotion and preferment. Seventeenth-century routes to recognition were less conventional. He learned medicine, and financed his studies, by working for a don's wife who dispensed homely remedies to patients unable to afford a physician. He joined the ranks of the "piss-prophets" who competed for medical business on market days in the towns around Oxford, choosing cures on the evidence of urine brought by friends of the bedridden.

In time Willis would become a rich and respectable doctor, but it was his performances in the laboratory and lecture-hall that earned his lasting fame. With them the modern understanding of the brain, and of its command of the nervous system, began.

Previous medicine, ancient and modern, had generally disparaged the brain, instead locating the seat of thought and emotion in the heart or the soul. How, after all, could God have placed man's controlling faculties in the brain, which, to an anatomist lacking modern methods of preservation, quickly looks and feels like custard? The rise in the brain's status which Willis effected is revealed by the drawings, attractively reproduced in Zimmer's pages, with which Wren illustrated his findings. They portray the brain as a delicate, complex organ with the beauty of an orchid.

Scientific discovery is rarely the sudden victory of truth over error or the abrupt abandonment of old assumptions for new. The novel findings of Willis and his friends jostled in their minds with ancient ideas of alchemy and of the operation of divine providence. Only in the next century, when what Willis had traditionally thought of as animal spirits were gradually recognised as impulses of electricity, could the study of the brain be separated from the presuppositions about man's relationship to God and the universe that had obscured it.

Soul Made Flesh is a tour de force, eloquently and excitingly written, powerfully re-creating the atmosphere and personalities of the time, and making the science agreeably intelligible to the non-scientist. Exacting readers will sometimes wish that Zimmer had identified his sources more fully and drawn a firmer line between fact and speculation. Squeamish ones may blanch at his unsparing accounts of the sawing and slicing of the skulls and brains of executed criminals, who provided the anatomists with their standard source of human cadavers.

Be brave, for few books of recent times have brought the skills of science and history so instructively and enjoyably together.

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NEW YORK TIMES, APRIL 4, 2004

Mind Made Matter
Reviewed by Adam Zeman

In the beginning soul was everywhere -- in fire, air, earth and water. There were ''tongues in trees, books in the running brooks, / Sermons in stones, and good in everything.'' The human impulse to anthropomorphize, to explain the workings of nature in human terms, was irresistible. As scientific culture took shape, the spiritual, anthropomorphic element of nature was beaten back. Anima -- the breath of life, the soul -- was chased from trees and running brooks into the human heart, its home in many classical and medieval writings. Since then, the progress of science has driven it into the brain, where most of us locate it now, though even here it is an endangered species.

Unlike their scientific colleagues, artists never repudiated our perennial tendency to experience ourselves at the center of a spiritual universe. Looking out at an Irish mountain stream, W. B. Yeats could ask: ''What's water but the generated soul?'' The ''melancholy, long, withdrawing roar'' of faith in a spiritual reality had troubled the poet and critic Matthew Arnold 50 years earlier, but his pessimism may have been premature: a recent survey of students in my home city of Edinburgh reveals that a majority believe that some spiritual part of us lives on after our death; the popularity of magical fiction testifies to our continuing fascination with the elastic boundaries of mind evidenced by telepathy, telekinesis and prophetic dreams. Reports of the death of the soul are exaggerated.

Carl Zimmer's illuminating book charts a fascinating chapter in the soul's journey; it is distilled from the writings of Oxford's 17th-century ''virtuosi,'' depicted against the turbulent, sometimes tormented, background of the English Civil War, the plague and the Great Fire of London. The principal characters are a formidable group who transformed the understanding of our bodies and minds: William Harvey, who established the circulation of the blood; Robert Hooke, who coined the term ''cell'' for the smallest functional unit of biology; Robert Boyle, who dared ''speak positively of very few things'' yet fathered a great brood of profound experiments; Christopher Wren, astronomer, illustrator, architect; and, at the center, the physician Thomas Willis, whose studies of the brain and its functions created a ''neurologie,'' a ''doctrine of the nerves,'' which, Zimmer argues, has come to its fruition in our present ''neurocentric age.''

Willis grew up outside Oxford in a Royalist family, became a student at the university in 1638 at 17, and volunteered as a soldier in King Charles I's army in 1644. Despite his affiliation with the defeated Royalist cause, Willis managed to establish a successful medical practice. He, Wren and others formed the ''Oxford Experimental Philosophy Club,'' whose activities included the creation of a universal language, the microscopic description of insects and the telescopic interrogation of the moon. In 1660, with the Royalists back in the kingdom's saddle after the restoration of King Charles II, Willis was appointed professor of natural philosophy at Oxford. He turned from the contemporary preoccupation with the work of the heart and lungs to a more obscure project: ''to unlock the secret places of man's mind.'' To do so, he wrote, ''I addicted myself to the opening of heads.''

Willis dissected human brains in his Oxford house, Beam Hall, exploiting techniques of preservation, injection and microscopy developed by his colleagues. His theories were guided by his experience with patients and tested in animal experiments. He was intrigued by the network of blood vessels covering the brain, giving it the appearance of a ''curious quilted ball''; he described the arterial circle at its base that still bears his name; concluded that the fluid-filled ventricles at its center, considered crucial by previous theories, were a mere ''complication of the brain infoldings''; and traced the intricate network of nerves that emanates from the brain to coordinate the workings of our organs. In a series of books -- ''Anatomy of the Brain,'' ''Cerebral Pathology'' and ''Two Discourses Concerning the Soul of Brutes'' -- he developed ideas that Zimmer reasonably describes as the foundation stones of contemporary neuroscience: that the nervous system is a network designed to transmit signals (regarded by Willis, well prior to the science of electricity, as ''animal spirits''); its parts are specialized for particular functions; it shares much of its anatomy and function with the brains of animals, and its afflictions, both neurological and psychological, can be cured by ''manipulating the atoms which compose it.'

But although Willis believed that most brain functions could be explicated ''according to the Rules, Canons and Laws of a Mechanick,'' he could not bring himself to identify the soul with its bodily home. The brain might be the ''mind's presence room,'' in the words of his student John Locke, but Willis proposed that man, alone, was ''a double-soul'd animal.'' An immaterial, rational soul cohabited with its material counterpart in the brain. Robert Boyle described this ethereal being as ''a kind of imprisoned angel.''

There are unexpected echoes of contemporary debates. In England then, just as now, there was a tension between physicians who favored the pursuit of basic science and those who preferred to see what worked and put it to use, like this English surgeon: ''If I find anything that may be to the good of my patients, be it either in Galen or Paracelsus, yea Turk, Jew or any other infidel, I will not refuse it but be thankful to God for the same.'' Then as now, our premier universities were under threat by those who wished that students would abandon scholarship for ''useful trades.'' And then as now, many conservatives were eager to condemn the ''lechery of the wanton mind and the mad itch for innovation.''

Carl Zimmer successfully communicates his enthusiasm for the energetic minds and busy pens of his heroes. The background to their thoughts and lives is sometimes indistinct, but this is scarcely culpable given that the relevant contexts are so various. His book is timely. As he demonstrates in his concluding chapter, the explosion of contemporary neuroscience is forcing philosophers into the laboratory once again to reconceive the soul. Techniques that allow us to image the working brain, and the looming possibility that we might build a conscious machine, are carrying us headlong down the intellectual avenue opened up by Willis and his colleagues. Like their troubled century, this is a disturbing, exciting time for the science of mind. The imprisoned angel may soon be soaring free.

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THE DAILY TELEGRAPH (LONDON), APRIL 24, 2004

Brain Power
By Benjamin Markovits

A scientist could go a long way in the 17th century simply by refusing to believe what he read. Aristotle had dominated "natural philosophy" for 2,000 years, but he had little interest in the kind of theories you could test. He explained the world by the ends not the means - a method that has its merits, though it does not teach one to look closely at the detail. The Greeks, for example, had a horror of dissecting men. This didn't prevent them from offering an account of human biology in which the heart served as the seat of reason, and the brain simply "temper[ed] the heat and seething of the heart". The second-century physician Galen mapped the body by dissecting animals and looking at the open wounds of gladiators. When, in 1537, Andreas Vesalius, a lecturer in anatomy at the university of Padua, began to sketch his dissections of human cadavers, he found that men weren't cows. Pirated copies of his drawings spread across Europe.

In 1600, the young English doctor William Harvey studied at Padua. He eventually discovered a fact as big and plain as a new world: that the "heart sends blood through the body in a loop". Harvey later served as a physician to Charles I, who introduced him to Viscount Montgomery. Montgomery had fallen from a horse when he was a boy, leaving a gap in his ribs, subsequently covered by a metal plate, which he was able to remove for Harvey. "I immediately saw a vast hole," Harvey wrote, somewhat overwhelmed. "I was almost tempted to think... that the motion of the heart was only to be comprehended by God." It is understandable, then, that Harvey still had trouble persuading his peers of his breakthrough. When Charles I ran into a spot of trouble with Parliament, the doctor followed him to Oxford and began teaching his theories to some of the students, including a young man named Thomas Willis, who - given the confusion of the times - had recently decided to pursue a career in medicine rather than the Church. Harvey now had his disciples, determined not only to trace the course of blood through the body but to follow his experimental methods. Willis eventually tracked the flow of blood to the brain. In attempting to understand its function there, he gave the first account of the network of nerves and blood vessels on which our own understanding of that organ is based.

Willis lies at the heart (or perhaps the head) of Carl Zimmer's account of the "mapping of the mind" that began during the English Civil War. He ushered in what Zimmer calls the "neurocentric age", in which, as he writes, "the brain is central not only to the body but to our conception of ourselves". And in which we think of the brain's operation as mechanical and chemical, rather than spiritual - its problems to be solved by pills.

The great strength of this book is its attention to the chain of acquaintance that led to this evolution: the cast list includes Descartes, Robert Boyle, Christopher Wren and Thomas Hobbes, each of whom, at various points, takes centre stage. Ideas follow lines of friendship as well as logic; and the story of the brain resembles the old comic song by Tom Lehrer, I Got It From Agnes. What they "got" in this case was a mechanistic or materialist view of the world: a world understood by the means rather than the ends. And politics played its part - not only the subtle positionings and jealousies among ambitious colleagues, but the crisis in monarchy, whose influence was both general and specific: both a climate of opinion and a set of practical circumstances, such as the enforced encampment at Oxford.

Naturally, Zimmer has to cover a lot of ground. The considerable charm of this book lies in the rate of travel, but the landscape occasionally blurs in the rush. Kant's contribution to our conception of the human mind fills half a paragraph. And sometimes the speed of play results in careless over- as well as under-statement: Hobbes's Leviathan, apparently, invented political science.

Zimmer writes better about biography, history and medicine than philosophy, and the worst of this book is its conclusion, which compares Willis's theories to a modern account of the neurons involved in particular thoughts. In this context, "electricity" has simply replaced Willis's more "spiritual" humours - a reading guilty of one of the subtler forms of anachronism.

The rational soul, Zimmer argues, has at last been subsumed by the mechanical operation of the body: "while other parts of the prefrontal cortex handle the 'how' and 'what' questions in life, the orbitofrontal cortex appears to handle the 'why'. Discoveries like these show how foolish it is to try to dig a deep trench between emotions and rational thought." Not quite. These are deep philosophical waters: you can't fish them with such a short line. Still, Zimmer 's prose is wonderfully lucid, his curiosity wide. Readers should perhaps suffer more for their knowledge, but it is very pleasant for once not to.

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THE SUNDAY TIMES (LONDON), APRIL 4, 2004

Mind: how you go
By Lisa Jardine

Suppose you were to ask the person in the street which 17th-century discovery was more important -finding the form of the regular orbits of the planets around the sun, or discovering the structure of the human brain and nervous system. Which would the intelligent and scientifically curious man or woman choose? I suspect that it would be the brain. Crucial as the mathematical science of astronomy has been for progress, the greater understanding of the brain and its functions feels more urgently of importance, enabling us to come closer to understanding, literally, who we are and why we are that way. Biology has come out from under the shadow of the physical sciences in the 21st century. Indeed, since Francis Crick and James Watson's breakthrough with the structure of DNA in the 1950s, and the completion of the human genetic sequence by the Human Genome Project in 2003, progress in biology and biotechnology has leapt to the forefront of the public's scientific imagination.

By and large, however, historians of science continue to celebrate the heroes of the physical sciences above their equally talented contemporaries whose interests lay in the biological ones. While Galileo, Halley, Kepler, Leibnitz and Newton are household names, Grew, Lister, Lower, Ray, Ruysch, Sloane and Willis are not. This biography by Carl Zimmer of Thomas Willis (a pioneer in the dissection and observation of the brain, and the author of three important books on the structure of the brain and the nervous system, the medical theory of fevers and the physiological basis for feeling) is one of several recent attempts to redress that balance.

The modernity of Willis's ground-breaking work with the brain, and his account of the role of the nerves in bodily functions, including the emotions, will astonish many general readers. Zimmer himself is engagingly frank about his surprise at the quality of the research and deductions that he uncovered in the course of his research. His thorough, informed reading of Willis's published and unpublished work provides him with a wealth of compelling material. Wherever the author turns his attention to the detail of Willis's achievements (particularly his virtuoso work on the dissecting table), his enthusiasm is infectious.

Zimmer also moves elegantly between Willis's discoveries and equivalent work today, which he argues persuasively would be unthinkable without Willis's innovative initiatives. So the reader not only gets a clear picture of the fundamental advances made by Willis, but also of the current state of play in brain research, particularly the studies being done on the connections, which fascinated Willis, between the "explosions" in the nervous system (Willis thought they were like gunpowder) and the sentiments and emotions that they trigger. Like Willis, Zimmer argues, neurological scientists are still in search of the material foundation of the human soul and what makes our thought processes distinctively human.

Sadly, it is when Zimmer tackles the historical backdrop to his scientific hero's life and work that the pace flags. This is a problem common to a number of recent general history books (it may well be the result of editorial intervention urging the author to help general readers with "background"). Slabs of second-hand recapitulation of earlier theories of the soul and the brain stop Zimmer's otherwise attractively smooth narrative dead in its tracks. So, too, do derivative summaries of the history of the English civil war, or William Harvey 's special relationship with the Stuarts. The voice of the author is drowned out by "factual material"; at times, we are in danger of losing sight of Willis altogether.

Nevertheless, this is a much-needed book on an extraordinary 17th-century figure, who did landmark work that deserves to be brought to everyone's attention.

"History has had a difficult time taking in the full scope" of the works of people such as Willis, Zimmer writes. "It's as if there isn't room in our historical memory." Thanks to Zimmer, there will in future be a place within that memory for Thomas Willis.

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BRITISH MEDICAL JOURNAL, NOVEMBER 6, 2004

By Ian McClure

We take for granted some fundamental principles in medicine—for example, that anatomy underpins pathology and that pathology reveals the causes of clinical disorders. On reading Soul Made Flesh I was amazed to discover that such basic notions were developed only as recently as 350 years ago and that, before this revelation, physicians had been practising on their patients with a mindset of arrogant ignorance. This was a time when medicine was tethered to a set of principles first set out by Plato and Aristotle, 2000 years earlier. These principles were later embellished by medieval theologian physicians but never fundamentally challenged, because the penalties for questioning religious orthodoxy were simply too high.

Then, in London in 1649 an extraordinary event occurred that crushed this medieval permafrost: Charles I, God's anointed representative on earth, had his head chopped off. The social and religious upheaval that led to and ensued from Charles's execution is grippingly described in this outstanding book.

Paradoxically, the protagonist of the medical revolution that attended the mental and physical trauma of the English civil war was a staunch royalist: Thomas Willis (as in the circle of Willis). It was he, along with a remarkable, Oxford based circle of self styled "virtuosi" (which included such geniuses as Robert Boyle and Christopher Wren), who painstakingly debunked the medical myths that had adhered to the proclamations of the ancient Greeks.

What gave Willis the confidence to challenge these entrenched ideas was his dogged pursuit of detailed anatomical and physiological research. Like nearly all doctors working before the development of modern medical treatments, Willis's cures were essentially useless. Undeterred, he sought to establish the causes of the diseases and death that were routine in 17th century life. Thus, Willis became the first doctor ever to dissect the numerous cadavers obtained from his caseload and, crucially, then to match his pathological findings to his clinical observations. He was also the first to dissect deceased priests and aristocrats. The fact that the bodies of God's chosen few shared anatomical defects with the common masses proved to be a social leveller of enormous significance.

Willis predicted the fundamental neurological concepts of cerebral localisation and of neurotransmitter function, hundreds of years before being proved correct. His other discoveries paved the way for modern neurology and psychiatry. Most importantly, he diplomatically challenged the pervading metaphysical notion that the soul was separate from the body. Remarkably, given his academic and commercial success in his lifetime, his flame dwindled rapidly after his death. In this scholarly yet eminently readable book Zimmer has raised Willis from the ashes. For anyone interested in the history of medicine it is a must read.

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NATURAL HISTORY, JUNE 2004

The Fate of the Soul

Centuries of “experimental philosophy” and cognitive neuroscience have led to a revolutionary understanding of how the brain makes the mind.

By William H. Calvin

IF ANY ORGAN COULD CLAIM to be the seat of feeling and intellect, surely it was the heart. Until three centuries ago, that seemed a fact too obvious to contest. Unlike other organs, you can feel your heart pounding away inside you. If you start thinking exciting thoughts, it beats even faster. If it stops beating, you are animated no more. And so the heart seemed to be the seat of the soul.

“Soul” was the name for what animated something, what gave it goals and the ability to make things happen. Just as people now distinguish hardware from software, anatomy from physiology, brain from mind, nouns from verbs, and form from function, it was once commonplace to distinguish body from soul. Besides The Soul, philosophers also believed in various “little souls,” which made the bodily organs into something more than meat. The stomach’s soul, for instance, was said to attract food down from the mouth. Once seventeenth-century science began to realize the heart is just a humble pump, it was as if the soul had suddenly fled the chest like a restless ghost to lodge itself in the head.

Today we physiologists would point out that the “little soul” animating an organ is simply its function, which arises from the emergent properties of a “committee” of cells. And we would suggest that the big, catchall Soul is one of the brain’s higher functions.

Only forty years ago, it also seemed obvious that the world was divided into animated stuff and nonanimated stuff. But now, instead of a sharp boundary between the living and the inert, there is a gray zone at the level of molecular biology. The still-useful distinction is expressed by the special word we employ for the formerly animated: “dead.”

What really counts, physiologists now know, is “brain dead.” Even though some ancient philosophers knew the brain plays a role in paralysis, seizures, and behavioral derangement, that knowledge was regularly overlooked for the following 2,000 years. The Delphic oracle’s reputed advice to “know thyself” has had a rocky road. No one understood what was inside the brain. No one was able to imagine how all that fatty stuff could animate us, enabling us to think complex thoughts and communicate them to others. Soul, mind, and brain all overlap—but how much? Can we do without one category entirely?

Two new books now provide important perspectives on that question for the general reader. Carl Zimmer’s Soul Made Flesh traces the rise in England of experimental philosophy through the lives of the so-called virtuosi—anatomists, physicians, and philosophers—in the dozen years before they banded together to form the Royal Society in London in 1660. It was the virtuosi who began to re-place Aristotle’s theory of the soul with knowledge about the body and the brain gleaned for the first time through the scientific method. In The Birth of the Mind, Gary Marcus writes from the twenty-first-century perspective of how the brain makes mind (“soul” has now been dropped from the scientific vocabulary). He describes the biological basis for higher mental processes, and explains how the gene-controlled process of wiring up the brain leads to behavioral differences between individuals—the inborn source of the unique individuality of every mind.

Like most brain scientists, I am inconsistent in using the term “mind” (and I haven’t heard a serious discussion about the soul’s interface with the brain for thirty years). Some say “Mind is what brains do,” but most of what the brain does is routine and no different from what all other animal brains do: controlling the search for food and mates, analyzing the sensory inputs, and deciding what to do next. What are so obviously mindlike are the higher intellectual functions involving structured thought. And despite the accomplishments of centuries of science, which are celebrated in these two books, scientific knowledge of how and why our remote ancestors first developed these higher capacities is still anything but complete.

Some 50,000 years ago a burst of technological and artistic activity erupted in Africa and soon became a great profusion of art, trading, body decoration, and new tools. The material evidence of that creative explosion is taken as an indicator of the mind’s “big bang”: the time after which Homo sapiens did things from which we infer that, for the first time, people could think long, complicated thoughts, much as we do today.

What triggered that “modernity”? Was it an enhanced ability to imitate? Planning ability? The use of symbolism, even words? Many suspect that the spark 50,000 years ago may have come from the development of structured language.

A protolanguage made of nothing more complex than short sentences, similar to the ones uttered by two-year-olds, could have been around for a long time, slowly building vocabulary without lengthening sentences. Without longer sentences, though, our ancestors probably lacked long and complex thoughts. That most likely restricted them to a mental life in the here-and-now. They would have been unable to see themselves as the narrators of a life story, always (as we are today) at a crossroads between alternative interpretations of the past and various paths projected into possible futures. (They might not have worried much, either. Although they saw death every day, without the ability to speculate about the future they could not conceive of their own mortality.)

Yet there is a major barrier to creating longer sentences. As the number of words increases, there are so many ways they could relate to one another that you drown in ambiguity. Short sentences—at least in context—are seldom ambiguous, so structuring is optional. But long sentences—the kind that children today are beginning to figure out at age three—are possible only through structuring language with syntax. It works like this: I can have a model in my mind of who did what to whom, where, when, and why. If you and I share a knowledge of how to place words and phrases around a verb to tell a little story, and of how phrases and clauses can be nested inside one another, you can correctly guess the novel set of relationships I’m thinking about, just from the clues in the short string of sounds I utter. You thus recreate my model of events in your mind. This everyday exercise in structured speech, even if its only use was to gossip about who did what to whom, likely facilitated logic, narrative, and contingent planning—perhaps even structured music.

Nevertheless, you may ask, weren’t our ancestors gradually getting smarter, as the brain enlarged threefold in the past several million years? Bigger is smarter, is better—why, it seems obvious.

That common assumption, however, is challenged by what archaeologists have been finding in the past few decades. There were two early periods of human history, each lasting a million years, without obvious signs of toolmaking progress, despite all of the brain enlargement going on at the same time. The increases in brain size must have been driven by something that has not been preserved for the archaeologists to find—perhaps protolanguage, imitation, expanding cooperation, or more accurate throwing. Perhaps cleverness was a by-product? But if the brain-size increase resulted in gradually increasing cleverness (again, the common assumption), note that it didn’t gradually improve their toolmaking. Oops. Even more to the point, by the time of the mind’s “big bang,” people who looked like us, big brain and all, had been running around Africa for more than 100,000 years without showing signs of modern behaviors like fine toolmaking. Oops again. The big brain may (or may not) turn out to be necessary for our kind of intelligence, but it sure isn’t sufficient for modernity.

Once writing was invented, around 3200 B.C., knowledge could not be lost as easily as before; you could actually learn from dead people, and even reanimate their ideas. Indeed, as Zimmer’s historical account makes clear, the ideas about the soul expounded first by Aristotle and then by Galen, the Greek philosopher-physician of second-century Rome, kept popping up—and preventing progress—for two millennia. Beginning in the sixteenth century, as standards improved for what constituted an adequate explanation, many traditional concepts about human bodily and mental animation began to seem simplistic, or even erroneous. In the seventeenth century, as Zimmer recounts, the English physician William Harvey figured out that the “soul” of the heart seemed to be all about pumping endlessly. The organ just didn’t seem to have the right stuff for all those other functions ascribed to it.

The search for a better seat of personhood soon began to focus on the brain. Christopher Wren, remembered today mainly for his grand architecture and for rebuilding London after the great fire of 1666, was particularly skillful at illustrating dissected brains. (He also invented intravenous injection—pretty good for an Oxford professor of astronomy.) Wren’s countryman Thomas Willis, an anatomist and physician who plays a central role in Zimmer’s history, “did for the brain and nerves what William Harvey had done for the heart and blood: made them a subject of modern scientific study.” As Zimmer makes clear, however, Wren, Willis, and the other virtuosi were forced not only to invent the practice of science as they went along, but also to navigate the treacherous waters of well-established doctrine regarding the soul.
Willis and the rest of the virtuosi who emerged from the English Civil War pondered how they should go about gathering knowledge through experiments and observations, but only in an ad hoc way. It was [John] Locke who [subsequently] transformed this kind of thinking into a full-blown philosophy, one that would become the heart of the scientific method.

The new science of human nature conflicted with some vested interests concerning the soul. Selling indulgences, for instance, to ensure preferred treatment for your soul in the afterlife, had become a big business, aided by the invention of the printing press. The tortures imposed on dissenters by the inquisitions of the Roman Catholic Church attested to the dangers of thinking differently, and many an early scientist-philosopher was wary and guarded for good reason. The natural philosophers who populate Soul Made Flesh were no exception. “In 1666,” Zimmer writes, “bishops blamed [London’s] fire and plague on [Thomas Hobbes’s] atheism.” Although Hobbes was never formally charged as a heretic, he was “forbidden to write ever again about human nature.”

Even medical men such as Willis had to tread warily through both the religious and the social conventions. Zimmer notes that for most of his working life, Willis was allowed to dissect only the bodies and brains of condemned criminals—his results could thus be ignored because they pertained only to the brains of the “abnormal.” Willis, however, was good at persuading relatives of his aristocratic patients to surrender the bodies of their dead for autopsies.
Because the brains belonged to England’s ruling class, it became hard for his readers to dismiss his observations. The respectability of his success allowed Willis to expand his mechanical, chemical explanations of the brain to include the soul itself without being accused of heresy.

That tactic of Willis’s for gaining scientific acceptance, as Zimmer points out, was a clever bit of social jujitsu.

One might think, in the enlightened present, that holding nonconformist views about the comings and goings of the soul would not be criminalized—but that’s what is happening. The fallacy of “the little person inside” (about which, more in a minute) has long confused matters even for modern psychology students, who expect “a viewer” to be at some location inside the brain. Centuries ago, a little person was imagined to lie within a sperm. (Now the little person is imagined inside the fertilized egg. This is not progress.) The little person or soul causes endless confusion in otherwise responsible reasoning about regulating abortion.

“When life begins” is a phrase that already carries with it the idea that the soul pops out of a starting gate at the moment the sperm enters the egg. Next we see the dubious line of reasoning that concludes that a single cell has achieved legal personhood. It’s only another small leap to claiming that interference with such a one-cell stage of a fertilized human egg is manslaughter or murder.

Few people, however, seem to realize that nature seems rather careless with early embryos; many beginnings are not finished. At least one in four embryos is spontaneously aborted in the first several months. In women who smoke too much (or drink from the wrong water supply), three out of four may be lost. (The usual figures of between 10 and 15 percent for “pregnancy loss” refer to what happens even later, once pregnancy becomes obvious.) Those numbers are, of course, far greater than those of elective abortions.

So when conflicts arise in the early stages of pregnancy, many people have concluded that the beginnings need not be finished—that other considerations (time, place, health, resources, the father, other responsibilities) can reasonably be taken into account by the prospective mother. Many biologists—and some modern theologians, too—would add that, just as a pile of construction materials and some assembly instructions does not constitute a house, neither does a fertilized egg and its genome constitute a person, absent a lot of “value added” over many, many months.

Whatever one thinks about the soul and its connection with the contemporary abortion conflict, the terms in which that issue is argued make it abundantly clear that big ideas still matter. And the soul is one of the big ideas of all time.

Zimmer gives us a history of early concepts of soul and mind, in Soul Made Flesh, and Marcus gives us an overview of contemporary notions of mind, in The Birth of the Mind. In a nutshell, the two books tell the story of how centuries of scientific inquiry have led to new and revolutionary explanations for what animates us.

Many of us, as I mentioned earlier, imagine a little person inside the head watching sensory inputs, then telling the muscles what to do. It took a long time for scientists to realize that ascribing thought to a little person inside the head is the equivalent of asking, “What makes a car move?” and answering, “Another little car inside” rather than “An engine.” But to explain thinking, it is all too easy to argue in a circle. And that classic beginner’s mistake is not always innocuous; it sets you up to view a fertilized egg as also containing a little person inside.

With what, however, does science replace the little person inside? How does the brain make mind? To begin to address those questions—to do justice to the complexity of human imagination, foresight, and capacity for reflection—you have to come to grips with three basic conceptual features of human mentality.

First, mental life and functionality develop gradually. They occupy no single spot in the brain. And they form a push-and-pull web of influences rather than a falling-domino chain of causation.

Second, human mental life depends, crucially, on structuring to keep concepts from blending together like a summer drink. Structuring makes complex sentences possible, such as “I think I saw him leave to go home,” in which three sentences nest inside a fourth, like Russian dolls. Structuring enables people to test out chains of logic, enjoy complex music, play games with rules, make contingent plans for the weekend.

Third, and probably most difficult, it must be possible for structured mental activity to become qualitatively improved. How do you manage to do something structured that you’ve never done before—say, utter a long sentence about a friend’s hopes and fears? Somehow you start with an incoherent jumble of concepts, then you improve its quality, editing them into a more coherent sentence in a second or two, before you finally decide to go with it.

How did the human animal ever acquire such features of mind? The only relevant process known in nature is Darwin’s variation and selection. Of course, one can see the Darwinian process at work on a grand time scale, in the evolution of new species. But one also sees its results after any flu shot, in the response of the body’s immune system to the challenge of the vaccine, creating better and better antibodies. The Darwinian process is the foundation of biology, without which nothing makes much sense (yet many parents do not wish their children to hear about it). Biologists are just beginning to explore how the brain could apply natural selection to the memories it stores in order to improve the quality of, say, a verbal performance—and do it all in the few instants between an incoherent thought and a structured utterance.

Soul Made Flesh provides an account of the first big steps toward an understanding of how the brain makes mind. Zimmer, a science writer and the author of Evolution: The Triumph of an Idea, the companion volume to the eight-hour PBS television series of the same name, has written a fine intellectual history of early neuroscience. It is full of drama, and it brings to life the struggles for insight that begin in William Harvey’s time with the flowering of physiology.

Most of us regularly fail to distinguish how from why, a process from an object, distributed from pointlike, structured from simple, gradual ramp-ups from sudden beginnings. Scientists, in the course of centuries of investigation, have made all those mistakes; but they also, eventually, corrected them. We still eagerly compete to discover our present misconceptions, one of the things that makes doing science so different from other endeavors.

One long-since-corrected but persistent misconception, at least among nonscientists, is that “science says” genes determine behavior and destiny. If you share that misconception, you probably need to read The Birth of the Mind.

The real story, as Marcus is at pains to emphasize, is about the flexible interactions between genes and the ways the brain is wired up, then subsequently between experiences and how genes are expressed in the brain. What emerges from those interactions are behavioral propensities that allow for an ever-widening set of choices, not “fate.” “A brain built by pure blueprint,” Marcus writes, “would be at a loss if the slightest thing went wrong; a brain that is built by individual cells following self-regulating recipes has the freedom to adapt.”

Marcus, a psychology professor at New York University and the author of The Algebraic Mind: Integrating Connectionism and Cognitive Science, neatly explains why genes are less like blueprints and more like recipes.

A blueprint has point-to-point correspondences between plan and construct. A recipe often shows no such correspondence: indeed, what comes out of the oven is often impossible to reconcile with its list of ingredients. Similarly, Marcus explains, there is seldom a single gene for the variable aspects of the body, such as eye color. Instead a gene is usually part of a committee of genes in which some push while others pull to help control a process.

Marcus also explains how genetic variations change the receptors sticking out from the surface of a so-called pathfinder cell. During embryonic development those variations can give rise to alternative “wiring diagrams” of brain tissue, which, in turn, promote some behaviors more than others. Finally, in considering the prospects for genetically modified humans, Marcus squarely faces the problem of unintended consequences. Soon, he notes, geneticists will be able to synthesize “whatever genes we like.” But, he warns:
For many years it will be difficult, if not impossible, to gauge the potential side effects of a given [gene] manipulation in advance. I can live with a buggy beta-test version of a new software package, but I don’t want to have to restart my child.

The fate of the soul, I suspect, is to be reinvented again and again. That’s because one nonessential aspect of it—that little person inside—is a beginner’s error. Even today, when higher education provides a much better explanation for the emergence of persons and their roles and responsibilities toward one another in a society, the old version survives, because it is so easily reinvented by each succeeding generation.

The problem is serious because relying on the “little person” concept may force us to devalue things people might want to retain. Some optional add-ons to the soul (which vary around the world) include: comforting the bereaved or downtrodden, intimidating a misbehaving child, proselytizing, reaching for the greater meaning of self and life. Many are invaluable appeals to kindness or long-term individual responsibility that could readily stand on their own. The ghostly prop (the “little person,” the soul) carries a danger with it: when a historic or scientific analysis casts doubt on “the little person within,” some will throw out the baby with the bathwater and turn away from the valuable teachings.

Yet a stripped-down concept of soul might continue to stand for the uniqueness that different genes, in conjunction with different formative experiences and different personal decisions, confer on each individual. While the term “individual” might suffice, the term “soul” might better connote human foresight, ethics, and sense of responsibility, the personal track record and outlook on life that should matter to each of us. All those ideas are well worth emphasizing, no matter what one’s religious tradition or beliefs about an afterlife.

Once on the right track, science is pretty good at turning the crank. The coming decades will likely see a revolution in our thinking about how one cell slowly becomes a real person, gradually able to comprehend life’s great journey.

William H. Calvin is the author of A Brief History of the Mind: From Apes to Intellect and Beyond (Oxford University Press, 2004). He won the Phi Beta Kappa book prize for his previous book, A Brain for All Seasons. He is a neurobiologist and an affiliate professor of psychiatry and behavioral sciences at the University of Washington in Seattle.

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NATURE MEDICINE, OCTOBER 2004

By Marco Piccolino

With Soul Made Flesh: The Discovery of the Brain—and How It Changed the World, Carl Zimmer (author of Parasite Rex) provides a vivid picture of a colorful phase of scientific development in seventeenth-century England. The book largely centers on the figure of Thomas Willis, a physician and anatomist whom most medical students know indirectly because of the 'circle of Willis,' the arterial structure at base of the brain which insures appropriate blood flow to the 'organ of soul,' the brain.

Willis was the author of a series of studies on brain anatomy, culminating in 1664 with the publication of De Cerebri Anatome, a milestone in the development of what we now call the 'neurosciences'—a word introduced about 30 years ago by Francis O. Schmitt. More than any other, we owe Willis credit for the first modern images of central nervous system anatomy—images magnificently drawn by Christopher Wren, on the way to becoming the major English architect of his time. With Richard Boyle, John Wilkins and others, Wren associated with the circle of 'natural philosophers' that collaborated with Willis in Oxford—a 'circle of Willis' of a different kind. Some of them went on to found the Royal Society (the scientific academy which, for the next centuries, would have a fundamental role in the development of English science).

In contrast to the previous representations of the brain that flourished after the renewal of anatomical studies in the scientific Renaissance—generally more concerned with aesthetics—Willis' work was clearly the expression of a new research attitude, emerging with the scientific revolution of the seventeenth century. Willis and his associates aimed to find the plan of organization of the brain, convinced that the structural aspects of organisms could be explained on the basis of mechanical or chemical operations. This was a breakthrough in the conception of the higher functions of the nervous system, at the time still dominated by the doctrines developed in the Hellenistic period by Galen of Pergamum in Asia Minor. Galen maintained that the hollow parts of the brain, the cerebral ventricles, were the central sites of the circulation of the 'animal spirits,' elusive messengers of the operation of soul. The brain substance itself had only a secondary, protective role (which accounts for the term 'cortex'—rind—used to designate the external part of the brain).

According to Zimmer, it is mainly through Willis' endeavor that "soul was made flesh." Zimmer makes the bold—and in my opinion, perhaps not totally justified—claim that Willis and his associates initiated the 'Neurocentric Age,' an age in which we still live, "in which the brain is central not only to the body but to our conception of ourselves." Throughout the book, Zimmer establishes a link between the investigations of Willis (and of the scientists of his age) and modern achievements in neuroscience based on approaches such as electrophysiology, imaging and cognitive studies.

The book is written in an engaging way and the scientific descriptions are masterfully inserted into the context of a complex and dramatic phase of English history. Zimmer describes how the considerable religious and politic turmoil of the era affected the protagonists of this scientific revolution, but did not tame their intellectual freedom or their hunt for knowledge directly derived from the 'book of Nature' rather than from the tradition of Galen, Aristotle and Hippocrates. The combination of intellectual vivacity and dramatic political conditions reminds us of a famous line spoken by Orson Welles in The Third Man:

"You know what the fellow said: In Italy for 30 years under the Borgias they had warfare, terror, murder and bloodshed, but they produced Michelangelo, Leonardo da Vinci and the Renaissance. In Switzerland they had brotherly love—they had 500 years of democracy and peace, and what did that produce? The cuckoo clock."

Paradoxical as they are, such words might perhaps authorize some intellectual optimism in our present world dominated by political instability, wars, terrorism, and religious and cultural conflicts.

I have greatly enjoyed reading Zimmer's book and I would recommend it to scientists and to members of the general public interested in some of the paths leading to today's understanding of the brain. Nevertheless I have some criticisms, particularly because Zimmer keeps out of the scene many scientists who contributed to the revolution of life sciences in the seventeenth century and to the progress of nervous and muscular physiology (among them outstanding figures such as Francis Glisson, Jan Swammerdan, William Croone and Niels Stensen). I would also not endorse Zimmer's claim that Thomas Hobbes (together with William Harvey, another of the important dramatis personae of this book), by publishing Leviathan, "had essentially invented political science." At the time of Hobbes' masterpiece, political science was already a rather well established discipline, as the Principe of Niccolò Machiavelli had appeared in print more than a century before (not to mention works by Guicciardini, Botero, Bodin and others). In this and other aspects, it seems Zimmer's book is less a systematic historical account of the way "soul was made flesh" in seventeenth-century Europe, and more a fascinating play concentrated on an English scientist and his 'circle.'

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THE GUARDIAN, APRIL 24, 2004

The Soul In A Bowl of Curds
By Steven Rose

We live, the science writer Carl Zimmer tells us in this engagingly written book, in a "neurocentric age". Ask anyone raised in modern western society where their self, their personhood, is situated, and they will unhesitatingly locate it a little behind their eyes. Few neuroscientists would disagree, or doubt the propositions that the mind is the brain, the brain is the mind. But it was not always so, and relics of this past can be found in everyday speech and customs. On Valentine's Day we exchange hearts, not hypothalami, and in distress we grieve from the heart, not the amygdala, all because Greek, along with Chinese, medicine placed the heart at the centre of the self. But football fans whose team loses a match are gutted, and our everyday insights are gut feelings, because the Egyptians and the Hebrews lowered their sights from the heart to the bowels. Aristotle neatly combined the lot by providing us with three sorts of soul, located conveniently in bowels, heart and head, enabling that separation of lust (gut) and emotion (heart) from rationality (head) that has so plagued western philosophy ever since.

So how did we become neurocentric? And why, when neurocentrism seems so self-evident to us, did it take so long for it to triumph? Zimmer locates the transition from heart to brain in mid-17th-century Oxford, and above all to the insights of a short, stammering physician with hair "like a dark red pigge". And as for the delay, it is primarily down to the first-century Greek physician Galen, whose mistaken anatomy and physiology were received as gospel truths for the succeeding 14 centuries. Over this entire period, professors presided over dissections, reciting Galenic truths from the textbooks to their assembled students in flagrant contradiction of the evidence being carved out in front of them. The theatre of such events, long preceding Gunther von Hagens's plastinated displays, is memorably caught in Rembrandt's paintings of anatomy lessons.

Even when the importance of the brain began to be recognised, artists and philosophers alike focused their attention not on the soft greyish "bowl of curds" that we now see as housing its hundred billion nerve cells and their hundred trillion connections, but on the fluid-filled spaces of the brain's interior, the ventricles. Leonardo impregnated them with wax, stripped away the surrounding tissue and superbly illustrated their shape. Descartes saw them as the source of the hydraulic fluids that powered the nerves. Deciding, on somewhat dubious grounds, that the tiny pineal gland deep in the brain was the seat of the soul, the contact point between mind and matter, God and Man, he noted that the fluid from the ventricles washed its sides, and hence could act as a two-way transmission medium between soul and flesh.

To move forward, what was needed was a conceptual flip, to turn the brain inside out, recognise the "bowl of curds" as the home of thinking stuff and the fluid of the vesicles as merely the repository for its waste - not so obvious at a time before microscopes made it possible to see structure, cells and nerves within the brain-goo. This, Zimmer claims, was the achievement of the group of virtuosi - highly talented polymaths -more or less trapped in Oxford during the civil war and the Cromwellian republic of the mid-17th century. The group, inspired by the physician William Harvey, discoverer of the circulation of the blood and the role of the heart, included Christopher Wren in his pre-architect days, Robert Boyle, Irish aristocrat and formulator of the laws relating to pressure and temperature of gases, and Robert Hooke, who first used the term "cell" to describe the biological equivalents of atoms. And, central among them, was the upwardly mobile son of a local farmer, Thomas Willis.

With the restoration of the monarchy, many of this group would relocate to London and establish the Royal Society as Britain's first scientific academy. Yet this was before the days of scientific specialisations, of the fragmentation of culture and the location of "science" on the far side of the snow-line. The interests of the virtuosi ranged across the entire terrain of the natural and social sciences, from physics and physiology to architecture and the arts. Wren's drawings of nerves illustrate Willis's textbook (and are reproduced by Zimmer). William Petty began as a physician and ended as a pioneer social statistician. Keen natural observers, they also invented a new technique for acquiring knowledge of the world - they experimented.

This, above all, is why Willis's dissecting rooms, across the road from Merton College, take centre stage in Zimmer's account. It is here that human corpses were dissected with increasing delicacy, that the great nerve tracts to and from the brain began to be mapped, and where Willis made the one discovery that formal accounts of the history of neuroanatomy recognise - the rich blood supply to the brain and the "circle of Willis" at the base of the brain, crucial to ensuring that supply. But it is also where the experimenters strapped living dogs to their dissecting table and opened them up to explore the beating of the heart, the effects of removing a variety of internal organs (some of which, astonishingly, the dogs survived) and the possibility of transfusing blood.

But nobody can entirely break the chains of the past. To transcend Galen, Willis turned to the writing of the mystical 16th-century alchemist Paracelsus and his successors. Where Galen approached life through anatomy, Paracelsus did so through chemistry. What was important to health in the Paracelsian tradition was the balance of chemicals in the body. So to the traditional medical approaches of bleeding sick patients nearly to death to rid them of undesirable "humours" Willis added unsavoury concoctions of semi-toxic metal salts. This seems greatly to have increased his fame as a physician after the Restoration, though it is puzzling to see why, as Zimmer cites no evidence of his medical successes and a fair number of distinct failures.

Although Willis is ostensibly Zimmer's central theme, the book ranges widely. Not only does he provide a good account of the state of medico-physiological knowledge during the post-Galenic period leading up to the birth of modern neuroscience, but Willis's own story becomes almost submerged in a racy history of the civil war, the Cromwellian revolution and the subsequent restoration of the monarchy. The great theological debates of the time provide the conceptual framework within which the new sciences were born, especially the Protestant (and above all Puritanical) refusal to accept the authority of the church's interpretation of scripture. Despite many of them being royalists, the virtuosi shared this scepticism, symbolised in the motto of the Royal Society - Nullius in verba .

Despite Willis's achievements, he remains today a relatively unknown figure, certainly by comparison with his great contemporaries. Zimmer argues that this is largely the fault of the man who was briefly Willis's pupil, the great John Locke. Willis was a materialist who saw in materialism the revelation of the works of God. The charge of atheism, thrown by the church at all who dared to confront scripture with empirical evidence or logical reason, was almost as serious a threat to livelihood, if not life, in the Protestant north of Europe as it was in the Catholic south, and the virtuosi picked their way carefully through this minefield. Locke, a generation later, felt free to discuss the mind and its functions without the need to refer either upward, to scriptural authority, or downward, to the materiality of the body. The English tradition of empiricist philosophy was born, creating a fresh severance between the studies of mind and of brain, which was to last virtually until the last couple of decades.

In his final chapter, Zimmer fast-forwards his story somewhat uncritically to the modern triumphs of (American) neuroscience, with its commitment to reducing the soul to nothing more than flesh powered by information theory. I suspect that the virtuosi, marvelling at the extraordinary windows into the brain provided by the latest imaging techniques, would nonetheless have resisted such a simplistic interpretation. I share that scepticism.

Guardian Unlimited © Guardian Newspapers Limited 2004.

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