Full Reviews:

BRAIN, OCTOBER 2004

VINDICATING WILLIS
By William Feindel

For more than a century, admirers of the life and work of Thomas Willis (1621–1675) have tried to retrieve him from the penumbra cast by the historical limelight of his famous Oxford compatriots—Harvey, Sydenham,Boyle, Wren and Lower—and his brilliant students Hooke and Locke. Their sustained efforts have had some success. Charles Sherrington (1951) put it unequivocally. ‘Thomas Willis practically refounded the anatomy and physiology of the brain and nerves.... He collated bedside observation with anatomical fact. He, as had Fernel, a century before him, shifted the seat of the anima from the chambers of the brain to the actual substance of the brain itself.... Willis put the brain and the nervous system on their modern footing so far as that could be then done.’ Charles Symonds (1955) was one of the first to point out the clinical significance of observations by Willis and his team on the anatomy and physiology of the cerebral circulation and to emphasize the innovative role of Willis as a physician who combined a busy medical practice with his role as head of a team of neurological investigators. Symonds (1960) sampled earlier protagonists of Willis by quoting Soury (1899). ‘Que l'on considère la structure, les fonctions ou les maladies de cerveau, surtout les grands névroses, telles que l'épilepsie et l'hystérie, il n'est pas un point de fait ou de doctrine dans lequel on ne puisse encore démêler aujourd'hui l'influence de Willis, et l'on se persuade sans peine en réalisant les oeuvres du vieux maitre que la force vive de son génie n'est pas encore épuisée.’ And Symonds concluded about Thomas Willis, ‘As a man he was not a courtier but a pious industrious person whose medical practice was informed by the search for truth and whose success as a doctor must be attributed as much—perhaps more—to the honesty and warmth of his character as to his skill.’

Willisian sites

Some geographic sites in England associated with Willis provide provenance to various stages of his career. In 1961, the memorial floor stone for Willis in Westminster Abbey was identified, renewed and rededicated, an event sponsored by British and Canadian neurologists: its lapidary inscription had been ablated unknowingly by the footsteps of a million visitors on their way to the Royal Chapels (Feindel, 1962a). A few years later, a charming thatched brick cottage in Great Bedwin was rediscovered as the birthplace of Willis (Symonds and Feindel, 1969); it was marked by a heritage plaque in 1994 under the auspices of the World Federation of Neurology through the efforts of F. Clifford Rose and others (Feindel, 1996). The houses that Willis leased in Oxford, from about 1657—Beam Hall and Number 3 Merton Street—were depicted (Feindel, 1962a). The Willis family home, Ferry Cottage near Oxford, was pictured by Hughes in 1991. These and other sites identified with Willis were recently described in a ‘neuroarchitectural tour’ (Feindel, 1999).

Distinct among medical memorials is the ‘Patronal Festival’, held each year since 1734 at Fenny-Stratford, mid-way between Oxford and Cambridge, to celebrate the life of Thomas Willis in St Martin's Church (Willis died on November 11, 1675, St. Martin's Day) where a fine chapel was dedicated by Browne Willis, the grandson and heir of the famous doctor. Three times during the day, six ‘Fenny-Poppers’—cast iron mugs stuffed with gunpowder—are set off in mortar trenches to give satisfactory bangs (Viets, 1917; Feindel, 1969). This is followed by a convivial supper in ‘The Bull’, the pub next door to the church. A celebratory church service includes a sermon, often by a prominent medical person, who in 1916 was Sir William Osler, then Regius Professor of Medicine at Oxford and a member of Willis' college, Christ Church. Osler praised Willis as ‘a good scientific man and a first class physician’—a testimonial with which the immortal soul of Thomas Willis no doubt would be content.

The founding of neurology

From the early 1960s, a series of publications began to catalogue the astonishingly able contributions of Thomas Willis and his Oxford circle to the anatomy, physiology, pathology and clinical disorders of the nervous system. For these observations and for coining the term ‘neurology’ (as he is credited in the Oxford English Dictionary), Willis was substantially claimed as ‘The founder of neurology’ (Feindel, 1962a). To commemorate the 300th Anniversary of the publication in 1664 of his celebrated Cerebri Anatome, the 1681 edition of ‘The Anatomy of the Brain and Nerves’, as ‘Englished’ by Samuel Pordage (Willis, 1681), was published in folio facsimile (Feindel, 1965a). A companion volume of commentary included the first biography of Willis and his friends, as well as a bibliographic survey of the 23 editions of this famous book (they appeared as separate editions or as part of Willis's Opera Omnia published in London, Amsterdam, Geneva, Lyon and Venice) which was created by the expertise of Howard Denham (1965) of the Wellcome Historical Medical Library. This tercentenary set was dedicated to Sir Charles Sherrington and Sir Charles Symonds and graced with a Foreword by Wilder Penfield. In designing this special edition, the two volumes were printed on Spanish hand-moulded paper, watermarked with the family arms of Dr Willis; the splendid anatomical figures from the first quarto edition of brain dissections drawn by Christopher Wren and of the spinal and autonomic nerves by Richard Lower, as well as portraits of Willis and his Oxford colleagues were reproduced by top lithographers and printers. Keele (1967), in a scholarly essay on this tercentenary edition, historically situated Willis in the context of the 17th century ‘instauratio’, with its strong political, religious and scientific undercurrents to which the group in Oxford were central.

Among others, Paul Cranefield (1961) wrote about the clinical and pathological correlations of Willis in relation to mental deficiency and psychiatric disorders. Meanwhile, Kenneth Dewhurst (1963a), a psychiatrist with a keen interest in 17th century medicine at Oxford, published a seminar on ‘Thomas Willis as a Physician’ (1964), a monograph on the Oxford lectures of Willis copied by Richard Lower and John Locke (1980), as well as biographies of Locke (1963b, 1984) and Sydenham (1966). Dewhurst (1981) also unearthed original documents and details having to do with Willis's life and medical practice—his case-book, details of his income (said to be the highest of anyone in Oxford), his clinic at the Angel Inn on the High Street in Oxford that served the London–Bristol carriage trade, and his acquisition of large estates in London and near Fenny-Stratford.

During this same time, Alfred Meyer and Raymond Hierons (1962, 1965, 1967) published important detailed analyses on Thomas Willis's concepts of neuro-anatomy and neurophysiology. In his definitive History of Cerebral Anatomy, Meyer (1971) also attributed to Willis the discovery and naming of many structures in the brain. Spillane (1981) devoted a major part of his book on The Doctrine of the Nerves to Willis and his works. He neatly wound up the controversy that stemmed from derogatory but unfounded strictures about Willis by his contemporaries that were uncritically repeated by Foster, Mettler and others.

Two full-length biographies about Willis have appeared, the first by Hansruedi Isler of Zurich, published in 1965 and translated into English in 1968, followed in 1999 by a generously illustrated volume by J. Trevor Hughes from Oxford.

Over the past two decades, another generation of scholars added substantially to Willisian studies. These include Robert Frank's authoritative biographical entry (1976) and his comprehensive monograph (1980) on ‘Harvey and the Oxford Physiologists’ and essays by Robert Martensen (1999) on the cultural influence of Willis, by James O'Connor (2003) on the religious views of Willis as displayed in his anatomical writings and by Zoltán Molnár's (2004) recent perspective that summarizes the evidence for Willis as the founder of clinical neuroscience. Christine Kenny (1998) gave a historical review of illustrations depicting aspects of the arterial circle before Willis compared with its anatomical and clinical definition in Cerebri Anatome (Feindel, 1962a, 1965b). In a thorough examination of the clinical neurology of Willis, Eadie (2003) discusses at length the role that ‘animal spirits’ and ‘nervous juice’ played in the Willisian neuropathology of brain disorders. Willis's attempt, Eadie concludes, ‘to record and interpret all nervous system disease on the basis of disorder of function of a single underlying mechanism represents a formidable synthetic intellectual endeavour on the part of a very busy physician.’

Wren's intravenous invention

In regard to the findings of Willis and his circle, an important point to emphasize is that much of their ‘new’ cerebral anatomy would have been impossible from inspection of brains ravaged by the usual post-mortem disintegration. It was here that Christopher Wren's ingenuity came into play. He invented a technique for intravenous injection which he applied to examine the effects of wine and ale, opium and other drugs in dogs (Gibson, 1970). Wren's technique eventually led to one of the earliest examples of blood transfusion in dog and in man by Lower and King, a demonstration enthusiastically observed by some members of the Royal Society. Robert Boyle had helped Wren to carry out his intravenous procedure in the dog. Boyle himself had used ‘spirit of wine’ to preserve anatomical specimens, ‘for this liquor being very limpid, and not greasy, leaves a clear prospect of the bodies immers'd in it’. Soaked in alcohol, specimens held their original shape and could be sliced open for study. We know also from the letters of Richard Lower to Robert Boyle, in London, that Willis and Lower injected coloured dyes into the carotid arteries and observed their widespread distribution throughout the brain (Symonds, 1954; Feindel, 1962b). These first ‘angiograms’ established the principle of collateral circulation so crucial to our present understanding and treatment of stroke. It seems quite probable that they would also have injected alcoholic liquids through the carotid arteries to preserve the brain. Indeed, the excellent copperplate ‘Figura Ia’ by Wren that illustrates the arterial circle on the base of the brain shows many anatomical details which strongly suggest it was thus preserved. The fullness of the convolutions and narrowness of the sulci represent an appearance familiar to neuropathologists who have perfused formaldehyde through the carotid arteries to fix the brain. In contrast, the brains illustrated in the atlases of Vesalius, Casserius and Veslingius show distortion of the basal structures, especially of the mesial parts of the temporal lobe and upper brainstem, that obscures the configuration of arterial vessels and the origins of the cranial nerves (Feindel, 1962a, 1965b).

The brain figures

This series of handsome anatomical figures by Wren and Lower has been interleaved in Carl Zimmer's book titled, Soul Made Flesh. Thomas Willis, The English Civil War and Mapping of the Mind. They add pictorial lustre to his lively and readable account that focuses largely on the fabulous work of Thomas Willis and his Oxford circle—the prototype of the modern research team in clinical neurosciences. Zimmer narrates the wide sweep of the events in England and in the middle third of the 17th century—a bloody civil war, the beheading of an English king, a plague that wiped out 300 000 Londoners followed by the Great Fire which burnt out the core of the city. He situates Willis in the broader context of the natural and religious philosophy that preceded and then surrounded him.

Though artistically decorative, the anatomical figures could have been more informative by adding their original legends to explain the lettered parts. For example, for Wren's notable ‘Figura Ia’, the original captions indicate the famous arterial ‘circle of Willis’ (or polygon as it is called in French and Spanish). This would help the average reader, even though this term is known to every medical student and used daily by neurologists, neurosurgeons and neuroradiologists. The legends also point out details of the cranial nerves for which the numbering and classification by Willis held sway for a century or more in anatomical teaching. Rarely mentioned is the first precise delineation in this brain figure of the temporal lobes, especially the uncus that comprises part of the amygdala, the forward part of the hippocampus and some of the entorhinal cortex, all of which feature so prominently today in the neurology of temporal lobe seizures, Alzheimer's disease and memory functions.

In ‘Preface to the Reader’ of The Anatomy of the Brain and Nerves, Willis stated, ‘Wherefore to explicate the uses of the Brain seems as difficult a task as to paint the Soul, of which it is commonly said, that it understands all things but itself....’ His use of the term ‘explicate’, from the verb ‘explicare’, meaning to ‘unfold’, was particularly apt, because his new method of dissection revealed insights into brain anatomy by ‘unfolding’ the occipital lobes forward to reveal the ‘brain's innermost regions’ and then by judicious dissection ‘to unlock the secret places of man's mind’ that previous anatomists had not examined as clearly.

This mode of dissection gave Willis and his friends a field day to display accurately (and sometimes to name for the first time) parts of the brain such as the corpus callosum, the thalamus, anterior commissure, corpus striatum, fornix, internal capsule and corpora quadrigemina (see Figura VIIa).

Beam Hall

Zimmer opens his story with an imaginative olfactory tour of Oxford that gives the reader a strong whiff of the grisly dissection room where Willis and his friends presumably performed their anatomizing in Beam Hall. This 15th century gabled stone house on Merton Street was leased by Willis in 1657 at the time of his marriage to Mary, sister to the authoritative Bishop John Fell. Willis lived there until he moved to London in 1667. We know from several sources that regular Anglican services were held illegally at Beam Hall during the Cromwellian regime. Willis also lived here when he was carrying out the programme of brain dissection with his group in the early 1660s. It is tempting to think that it was in Beam Hall where they met ‘to confer and reason about the uses of the Parts’ and then wrote up their findings; thus Willis's dwelling can be claimed as the first ‘Neurological Institute’ (Feindel, 1996). Zimmer takes up this claim enthusiastically. His elaborate description of the dissection room derives from the fine frontispiece in the Dutch edition of Cerebri Anatome by Schagen in 1665, which appears at the start of his Chapter Eight (Feindel, 1999). However, Zimmer's description of ‘Three hundred notorious royalists crowding everyday into this same small house’ for Anglican services seems somewhat exaggerated.

Cromwell and Canterbury

Willis eventually fared surprisingly well, despite the political and religious upheaval of the Civil War in the 1640s, during which time the university at Oxford languished, both his parents died and his medical studies were interrupted. After serving in the army of Charles I, he finished his brief medical course and began a medical practice at the age of 25. He attached himself to William Petty, a man of many parts and Professor of Music as well as Professor of Anatomy. Petty and Willis gained some notoriety in 1650 from the strange case of Anne Green, who caused a certain frisson locally when she was resuscitated after being hanged in December—possibly one of the rare examples of the benefit of Oxford's hypothermia (Feindel, 1962a).

During the next decade of the Cromwellian period, Willis diligently continued his medical practice. At the restoration in 1660, he fell into good fortune, partly because of his strong royalist and Anglican connections, when at the age of 39 he was appointed Sedleian Professor of Natural Philosophy and granted his MD from Oxford on the recommendation of Charles II. For this position he was sponsored by Gilbert Sheldon, one time Warden of All Souls, who then was Bishop of Oxford (1660) and eventually became Archbishop of Canterbury (1663) and Chancellor of Oxford (1667). Willis dedicated his three groundbreaking books on the anatomy, pathology and clinical aspects of the nervous system to his patron, friend and patient, Archbishop Sheldon—surely a unique medical and ecclesiastical connection (Willis, 1664, 1667, 1672).

The soulful brain

Once Willis took over his Chair, which mandated him to give weekly lectures on Aristotle and Galen, he soon became dissatisfied with the state of knowledge of the ‘offices of the senses’ and the ‘Faculties and Affections of the Soul’. So with ‘all delay being layed aside’ he determined to take himself ‘wholly to the study of anatomy and did chiefly inquire into the offices and uses of the Brain and its nervous Appendix.’ He attracted for this project, Richard Lower, a skillful and tireless prosector, Christopher Wren, then Professor of Astronomy who had superb artistic talent, and Thomas Millington, a ‘most learned’ Cambridge physician.

Even before Cerebri Anatome was published, Willis had already programmed another work on the pathology of the brain (Willis, 1667). Following that, perhaps his most interesting book, De Anima Brutorum (The Souls of Brutes), was largely devoted to comparative neuro-anatomy and clinical neurology (Willis, 1672). In this latter work, Willis again expostulates his views on an immaterial rational soul separate from the brain and a sensitive material soul that was based on a collection of spirits that travelled through the nervous networks which could become diseased like any other part of the body.

Zimmer presents an erudite and highly attractive account of the intricate highways and byways involving these medical and philosophical debates that involve Willis' former student, John Locke and many other luminaries. His colourful comments and references to many interesting characters are supported by back notes, a Dramatis Personae, an extensive bibliography and a useful index. He sometimes takes a certain artistic licence and fills in fact with fiction to keep the story moving.

His copy editors might have forestalled a few minor errors—such as referring to the Greek work ‘neurologia’ as Latin (p. 6). Not all of the brain drawings of Descartes were ‘woefully crude’ (p. 36)—his figures of the cerebellum and cerebral convolutions were as accurate as those of Wren.

In his final chapter entitled ‘The Soul's Microscope’, Zimmer makes a giant temporal and technological leap from the Willisian era in Oxford to a Princeton research laboratory of brain imaging and the revolutionary exploration of brain action now carried on by neuroscientists using functional magnetic resonance. The radio signals recorded in a high magnetic field for specific tasks given to the subject's brain depend on small changes of blood flow that are associated with brain cell activation—a local blushing of the brain—which one can take as an extension of the observations by Willis, Wren and Lower on the cerebral circulation over 300 years ago. Thomas Willis would have been astounded that so much of the brain's work can now be examined without, as he wrote, ‘the opening of Heads especially, and of every kind, and to inspect as much as I was able frequently and seriously the contents.’

The problem of neurology

Carl Zimmer has faithfully recounted the long saga of the problem of explicating the brain and how it became more scientifically based as a result of the studies of Willis and his colleagues that still stand out as enlightening landmarks in the transition from medieval to modern views of the brain (Feindel, 1989). However, as Lawrence Kruger (2004) has commented recently, ‘Perhaps discoveries of the brain shall change the world, but for the neurobiologist who may aspire to change the world, the glass might seem half empty until more significant strides are made in reversing the irreparable ravages of neurological disease, deciphering the mechanism of memory storage and retrieval, or understanding the penchant for violence in our species.’ Wilder Penfield (1965) summed it up in his Foreward to the tercentenary edition of The Anatomy of the Brain and Nerves of Thomas Willis when he wrote, ‘The problem of neurology is to understand man himself’.

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JOURNAL OF CLINICAL INVESTIGATION, SEPTEMBER 1, 2004

By H. Richard Tyler

The soul was once thought to be an ethereal thing with an interface between the macrocosm — stars and planets — and the microcosm — the individual. Its home in the body was the heart and liver, and from there it was distilled from the blood via the rete mirabile at the base of the brain into the ventricles. The brain itself was believed to be unimportant except in its support of the ventricular system.

In his book Soul Made Flesh: the discovery of the brain — and how it changed the world, Carl Zimmer concentrates on the development of ideas throughout history that eventually established a role for the brain in the modern world. The focus of his study is an examination of the ideas that developed in late 17th-century England, but concepts that were popular in earlier periods, going back to the time of Aristotle, are also introduced. Many historical books focus on individuals’ lives, but it is often difficult to understand why or how their theories developed. By providing historical background and focusing on ideas, Zimmer makes a number of disparate individuals (alchemists, anatomists, astronomers, and physicians) seem almost to interact. He develops the connections among them and the weaknesses and strengths of their views on the role of the brain against the background of the time in which they lived.

In its beginning chapters, Soul Made Flesh describes in detail the theories of early philosophers and anatomists as well as alchemists and astronomers and discusses how each set the stage for the next scientific advance. Having provided this historical platform, Zimmer then focuses on events in 17th-century England.

These were difficult times for the original thinker. The world was unstable; new thoughts and ideas were often in conflict with religious beliefs and nationalistic convictions and were a challenge to church doctrine and accepted Aristotelian views.

England was in turmoil for much of the 17th century, and this influenced individuals like William Harvey, Thomas Willis, and their contemporaries at Oxford. Willis was a royalist when it was dangerous to be one, yet he managed to be productive despite the difficulties his beliefs fostered. Zimmer has a superb grasp of these factors and shows how ideas that would appear unusual in this century seemed reasonable in an earlier time.

Zimmer reviews ideas about the brain that were in vogue until challenged by the anatomist Andreas Vesalius in 1537, who corrected many errors in Galen’s writings that had been accepted for centuries. Descartes was the first to put the soul in a cerebral structure — the pineal gland, which was situated in a place that controlled the movement of fluid in the ventricles just above the cerebral aqueduct and which received bilateral fibers. After Harvey’s discovery of the circulation of the blood in 1628, at Oxford, his contemporaries and successors continued his experimental approach. By combining clinical observation, postmortem examination of patients, and experimental data, members of this Oxford circle, primarily Willis, came to realize that the brain itself was an organ with a defined structure and function.

Willis performed many postmortem examinations and began concentrating on the brain and its structures. Using the techniques of Robert Boyle, who had discovered that putting the brain in "spirits of wine" changed its consistency from that of butter to that of boiled egg, allowed Willis to study the fine anatomy. Working with Richard Lower, Willis injected the cerebral arteries with a variety of substances and then traced their paths deep into the brain. The two soon recognized that the ventricles were not as important as had been thought.

Willis published three books primarily related to the nervous system. The first, Cerebri Anatome, was a unified study of the nervous system both centrally and peripherally and set the nervous system up as the center of the individual, dispensing with the concept of the humors of antiquity. In the second, Pathologiae cerebri et nervosi generis specimen, he discussed epilepsy, convulsions, and hysteria as coming from the brain. His third book, De Anima Brutorum, located the soul itself in the brain. This had to be carefully written because of its conflict with centuries of church doctrine. It established the new field of "neurology," a term Willis coined, and ushered in the neurocentric age, which is still flourishing today.

Each chapter of Zimmer’s book is preceded by an engraving, most of which were done by Christopher Wren, Willis’ colleague. These engravings beautifully detail the fine anatomy of the brain, including the structure at the base that now bears Willis’ name. Willis and his colleagues firmly established the brain as the organ whose function was to house the soul and act as the seat of emotion and thought. This concept paved the way for the next major advance, which came a century later with the phrenologists and the development of ideas concerning the localization of brain function to particular areas of the brain.

Soul Made Flesh belongs in all libraries and would make a superb gift for the neuroscientist or anyone who works with the brain. Zimmer’s knowledge of the period and depiction of the individuals who were responsible for many important scientific theories make for an exciting read. This was a hard book to put down.

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BIOSCIENCE, MARCH 2004

Dissecting Brains?
By Simon Conway Morris

The end of the world is imminent, spiraling out of control to unavoidable disaster. Loudest are the radical fundamentalists, intolerant, bigoted, deaf to all arguments beyond their narrow ken. It is a time of profound antiintellectualism, yet, paradoxically, science is in a ferment of creativity. Longcherished ideas are thrown on furious pyres, leaving worthless ashes to be trampled by careless crowds or blown by meaningless winds. Philosophers no longer discuss abstract precepts in cloistered calm, but engage with the world, questioning every principle, ripping up every foundation. Even the Academy is not immune; the cry goes up to reform radically, once and for all, the ancient universities.

I could, of course, be speaking of today. In fact I am referring to 17th-century England, a country tumbling from the autocracy of the Tudors to the prevarication of the Stuarts,with an interregnum that began with the beheading of a brave but foolish king and ended with the posthumous decapitation of a brave but failed tyrant. The scene of Soul Made Flesh is principally Oxford, and from its shadows of ancient colleges and modern slums step forth both familiar men, notably Christopher Wren,Robert Boyle and William Harvey, and those now poorly remembered, especially Thomas Willis. This was a time of turmoil, of uncertain prospects, when political stars plunged—sometimes to the executioner’s block—or soared to heights of aristocratic excess. The defining years of the English Civil Wars might have resembled a bad-tempered picnic compared with the savagery of the religious wars on the adjacent European mainland, but for England they were the single greatest disaster since the annihilation of the Saxon kingdom 600 years earlier. Add disease, culminating in the Great Plague of 1665, and a ferocious criminal system, not to mention a millenniarian spirit of religious zealotry, and one goes some way toward appreciating the backdrop of Carl Zimmer’s engrossing account of how mechanism replaced spirit, and how the soul was finally banished to the stuff of dreams, or at least so it appears.

Zimmer’s book has many virtues, unsurprisingly given the author’s established reputation as a science writer.The first virtue is that Soul Made Flesh is a wonderful read.Carrying the narrative at a brisk pace, it avoids the tendentious word-spinning of much science writing, where the reader is either left gasping for intellectual oxygen or peering through a fog of verbiage. A second virtue is a sympathy for the time in question and the people caught up in a historical process of which they could have little inkling as to its destination. If only that perspective were more common. So too Zimmer is adept at bringing together the luminaries and other actors of the time:Hobbes on his recalcitrant horse, Wren deftly vivisecting a dog, and Anne Greene mysteriously returning to life after hanging. (Readers of Iain Pears’s fine novel An Instance of the Fingerpost [Penguin, 1999] will be interested to compare the two books’ portrayal of an Oxford far removed from its ongoing Disneyfication and the revival—or was it resurrection?— of the hanged Greene [renamed Sarah Blundy by Pears].)

Zimmer’s book has, however, a very definite purpose: It aims to add one more rung to the ladder that, or so it is widely thought, lifts humanity from the miasmic lowlands of superstition and credulity to the shining uplands of rationality. It is a ladder that defines the Enlightenment, but it has the doom of disenchantment, draining the world not only of magic but also of meaning. From our privileged perspective, the path away from the dictates of Galen and Aristotle, and toward the identification of the brain as the seat of mentality, was painfully crooked as investigators heeded the siren calls of Paracelsus and van Helmont,with their empathetic world of alchemy and mysterious forces that were more easily conjured in cabbalistic scribbling than in the retorts and furnaces of their early laboratories. But the result seems inevitable. In essence, the material world was victorious, hinging on the emergence of a mechanistic paradigm. Spurred on by the materialist manifestos of Hobbes, the Oxford scientists approached the human frame with metaphorical screwdrivers and wrenches. As the levers, pistons, and pumps of the body were identified, so the soul evaporated. To Hobbes, there could be no alternative, and he it was who helped prise open the doors to our modern world (and all its attendant horrors). Perhaps, however, we should remember how Boyle insisted that to understand matter gave no explanation of how “the fabric of the Universe” came to be as it is, what determines its utter contingency.Yet, as Zimmer notes, Boyle was worried. If the deepest secrets of the world were revealed, where might the whole process end?

Despite Zimmer’s empathy with the denizens of the 17th century, it is clear where his sympathies lie. The alchemist Paracelsus was wrong, but Boyle’s notion that “experiments could reveal some of God’s language” (p. 135) appealed to another forlorn hope. Zimmer’s account is also triumphalist as he catapults the reader from the mire of 17th-century England to the clinical austerity of the modern laboratory, where powerful magnets and computers combine to reveal the brain’s cartography,where mind is revealed in (and reduced to) flashing lights. Observing, however, is not necessarily equivalent to understanding. To know that one part of my brain “lights up”when I think of a stiff gin-and-tonic, and another when I write this review, is certainly fascinating. But are we any closer to understanding what makes us sentient?

Zimmer observes that when the hanged Greene returned to life, by whatever route, she began again her gallowsside speech, but otherwise all memory of her terrible ordeal had fled. To say on this basis that memory is mechanical surely misses the point. Think of those memories that surface after decades of absence, returning with an eerie vividness. The simple fact is that we are still as far as ever from understanding how the mush of neurons actually creates and recalls our reality.Even when all parts of the brain are mapped to the nth degree, there is no prospect in sight that mind itself will emerge from the neural shadows. The question is simply different.

So too with the apparently nebulous soul.To talk of banishing it really misses the point, because it presupposes a medieval outlook that was never worth defending. As the philosopher Stephen Clark reminds us, the classic parody of medieval thought, about how many angels can dance on the head of a pin, is answered, “Just as many as they please.” Angels, just in case you had forgotten, are, as Clark writes, “immaterial intellects [that] do not occupy space to the exclusion of any such intellectual substance.” In an analogous way, the same applies to the brain and the soul. The former remains concrete but deeply mysterious, the latter elusive but deeply familiar.

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BOOKPAGE, FEBRUARY 2004

Science is not now, nor has it ever been, a glamour job. It involves patience, focus and the ability to withstand disappointment time and time again. Today's scientists can use modern technology to do many repetitive tasks, and they usually do their work in a clean and safe environment. Not so for men like Thomas Willis. In an environment that would make most modern researchers turn and run, he discovered the basic laws of brain function using tools closer in time to the bronze age than the computer age. Carl Zimmer's new book, Soul Made Flesh: The Discovery of the Brain—and How It Changed the World, is Willis' story, a fascinating look at the medical pioneer who dared to explore the seat of the soul.

The 17th century was a pivot point in history, a time when men began to get past the spiritual in order to explore the purely physical workings of the human body. Only one generation removed from an Italian genius whose explorations triggered a near-excommunication, Willis was more like Edison than Galileo, using tools available to all, and a constantly inquisitive mind, to delve into the mechanics of the brain.

Zimmer paints a vivid picture of the life and times of this stubborn 17th-century trailblazer. Through sheer persistence—and a lot of dissections—Willis and his colleagues managed to discover the workings of the brain and nervous system, and while their theories regarding the mechanisms of its workings were flawed (postulating humors and spirits as the carriers of signals along the nerves—electrochemical reactions being unknown at the time), in principle they were correct.

Soul Made Flesh is a personal story told against an epic backdrop. While highly successful in his own time, Willis left behind a legacy more far-reaching than he could have dreamed. We are in his debt, and in Zimmer's as well for his hugely entertaining portrait of this scientific hero.

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NEWSDAY, FEBRUARY 15, 2004

MIND OVER MATTER

In the middle decades of the 17th century, a group of like-minded English philosophers and medical men came together in the university town of Oxford. Though their country had been turned upside down by civil war and social strife, England's ancient university became something of an intellectual oasis, a place of flourishing scientific inquiry.

The Oxford circle, as they are known, included the young draftsman Christopher Wren, who would later achieve architectural fame for St. Paul's Cathedral in London, and the pioneer of the microscope, Robert Hooke. But perhaps the most influential member was a short, ungainly physician named Thomas Willis. The focus of his research was the mass of gray, mushy stuff that most scientists at the time thought was of little consequence: the brain.

Willis' home, Beam Hall, became a bloody site of investigation into the mysteries of the brain, both animal and human. Willis and friends probed the construction of this delicate organ, eagerly cracking open skulls and scooping out what was inside. Hooke's microscopes allowed them finely detailed glimpses of the brain's delicate configurations, while Wren drew breathtakingly artful sketches of its regions. In the process, the Oxford circle transformed the study of the human body.

Their story is the subject of Carl Zimmer's instructive and engaging account, "Soul Made Flesh: The Discovery of the Brain - and How It Changed the World." Like "The Lunar Men," Jenny Uglow's recent tour de force history of 18th century British scientists, Zimmer's book is a study in intellectual comradeship and cooperation, and how thinkers are shaped by their milieu. Willis, Wren and their collaborators "ushered in a new age," Zimmer writes, "one in which we still live - call it the Neurocentric Age - in which the brain is central not only to our body but to our conception of ourselves." Willis "showed how the brain's intricate structures could form memories, hatch imaginations, experience dreams." He was a detective of the nervous system, not to mention a primitive psychopharmacologist; Willis also wrote what is arguably the first case study of manic-depressive psychosis.

In our age of Prozac and high-powered neurological research, the centrality of the brain seems commonplace, but it was a revolutionary notion in Willis' time. For millennia, the brain was written off as an unfitting site for the location of the soul and the faculties of reason. Aristotle enshrined the heart as the ruling organ of the human body; others located the soul in the liver. Medical thinking in Willis' day focused on the careful maintenance of "humors," fluids thought to control a person's physical and mental qualities. In making diagnoses, doctors little considered the brain. Willis' contemporary, the English philosopher Henry More, could speak for many thinkers of the age: "This lax pith or marrow in man's head," he contended, "shows no more capacity for thought than a cake of suet or a bowl of curds."

But scientific advances and competing theories began to undermine such notions. The philosophies of René Descartes and Thomas Hobbes grounded thought in matter and the material, not in otherworldly spirit. Zimmer patiently fills in the scientific and philosophic background with authority, providing us with refresher courses on ancient thinkers and philosophers, as well as such figures as William Harvey, a 17th century physician who discovered the circulation of the blood. (Harvey's belief in direct observation and anatomy, not philosophic speculation - which then dominated the practice of medicine - influenced Willis enormously.)

Zimmer also rightfully emphasizes the historical and social context of the times. This is not simply a story of medical discovery; it is a chronicle of political and intellectual upheaval. The English Civil War (1642-51) had divided the country into polarized camps - Puritans, under the lead of Oliver Cromwell, were pitted against Anglican royalists loyal to King Charles I. The country was divided, but the Oxford circle, which included both Anglicans and Puritans (Willis was a devout royalist), were united under the banner of science.

Still, they were caught up in the political tensions and intellectual cross-currents of their era. Radical Puritans, who came to power with Cromwell in the 1650s, scorned the inquiries of Willis and Co. Jibed one critic: They "were good at two things, at diminishing a Commonwealth and at Multiplying a Louse." Others accused them of heresy. Yet Willis and his comrades were religious men - "they did not want to be mistaken for atheists using the new science to dismiss God from the world." They staked out a middle ground (which, of course, pleased no one), mixing their "mechanical philosophy with gentle skepticism and an abiding faith in the spirit world," Zimmer notes. Indeed, Willis was determined to show the workings of God and spirit in the brain, not banish them from his research. Willis thought the madness and disorder of his polarized country could be cured by a better understanding of the brain.

Despite the circle's fraught position, their eclecticism took them far. Willis' fervid inquiries reached their apogee in the mid 1660s, when he published his seminal text (with drawings by Wren), "Anatomy of the Brain," which went through 23 editions. He was in the process, Zimmer writes, "of installing the soul in the brain." His dissections revealed a complex relationship between the brain and its chemistry, a whole "geography of passion, reason and memory." What he called "animal spirits" we now know to be firing synapses and electrical pulses, not the workings of some immaterial force. Willis was not ready to follow the radical implications of his research to their conclusion.

For all of his achievements, Willis has been somewhat buried by history. Zimmer blames John Locke, a philosopher who dismissed neurology and observation of the brain. Yet Locke covertly appropriated Willis, Zimmer contends in a deft bit of phrasing: "Willis' neurology runs through 'An Essay Concerning Human Understanding' like buried steel beams, invisibly bearing the weight of Locke's philosophy."

Contemporary neurology would be nowhere without Willis. Even with all the CAT scans and MRIs available to modern science, Zimmer reminds us that there is yet an enormous amount to be learned about the organ once dismissed as a mere "bowl of curds." "In many ways," he writes, "we are still standing in the circle at Beam Hall, with the odor of discovery in our noses, looking at the brain and wondering what this strange new thing is that Thomas Willis has found."

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NATURE, FEBRUARY 12, 2004

SOUL SEARCHING
By Rina Knoeff

The provocative title of this book alone, Soul Made Flesh, made me want to read it. After all, we live in a time where scientists are doing their best to explain all mental phenomena in terms of matter. Advanced medical technology, such as the magnetic resonance imaging (MRI) scan, makes the processes of the brain visible and gives us the feeling that we are gaining an insight into the nature of the mind and its functions. Even more, we are relieved when psychological disorders can be explained in terms of a malfunctioning brain. It enables us to ascribe our depressions and mania to something alien that is not essentially part of our true selves.

Carl Zimmer's fascinating book shows that what we think of as recent developments began in the seventeenth century, when the English anatomist Thomas Willis began dissecting brains in Beam Hall at Oxford. At the beginning of the seventeenth century, the brain was seen as a 'bowl of curds', functioning as a kind of refrigerator to cool the heat of the blood. By the end of the century, thanks to Willis, the brain was studied as the seat of emotions, perception and memory.

Surprisingly enough, Willis is largely unknown. Some might remember him as the discoverer of the so-called 'circle of Willis', a ring of blood vessels at the base of the brain, but it is not widely known that his descriptions of the brain and nerves are at the root of modern neurology. According to Zimmer, this is because John Locke's ideas eclipsed those of Willis. Locke argued that we cannot know much about the inner working of the mind, so we should restrict ourselves to the ideas themselves and how they are confirmed by everyday experience. Willis, on the other hand, showed that the anatomy and chemistry of the brain could reveal the working of the mind — an idea that was dangerous at the time because it smacked of atheism.

Yet, Willis managed to keep out of theological trouble by strictly separating the immortal, rational soul from its bodily counterpart, the sensitive soul. The latter, Willis argued, consists of tiny particles that function as messengers, conveying sense and motion from the brain via the nerves to the rest of the body, and vice versa. Illness is caused by miscommunication and damage to the brain. Most notably, Willis was able to explain psychological illnesses and disabilities resulting from brain damage.

Zimmer's book is fascinating, not least because it provides a vivid picture of the world of which Willis was a part. Not only does he describe the smells of seventeenth-century Oxford in a way that transports you right there, but he also convincingly explains Willis's work in its political and religious contexts. We meet Oliver Cromwell and his puritan followers as well as King Charles II and his curiosity for the new experimental natural philosophy. Thomas Hobbes and Lady Anne Conway also figure in the story. Last, but not least, the reader is made part of the audience watching the often outrageous and crazy experiments of the so-called Oxford experimental circle — a group of natural philosophers busy with topics as diverse as submarines, blood transfusions, spacecraft and vacuum pumps.

Historians of science have written extensively about seventeenth-century English natural philosophy. Yet making sense of the diverse experiments of the Royal Society and its forerunners remains a tricky enterprise. Historians usually focus on one or two philosophers, a series of experiments or a particular philosophical movement. Zimmer's book is remarkable in that it offers a multifaceted picture of the world and work of Willis. In so doing he has managed to make sense of Willis's ideas in turbulent times of revolution, plague and fire.

In the final chapter, Zimmer moves from the dissection room in seventeenth-century Oxford to a present-day MRI investigation at Princeton University. He introduces us to the philosopher Joshua Green, who is interrogating someone in the machine while he looks at depictions of the brain on his computer screen. The aim of his research is to establish a better understanding of the nature of moral judgements. The soul made flesh — it is an eerie reality of modern neurological and philosophical research. To my taste, Zimmer does not sufficiently distinguish Willis's concept of soul from its twentieth-century counterpart. For Willis, the concept of soul referred to the processes of life at large, whereas nowadays we associate the soul with mental functions.

In the seventeenth century, people tried to cure diseases of the mind by manipulating the brain and nervous system. It is this continuity of concern that makes Zimmer's book such a fascinating read.

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LIBRARY JOURNAL, DECEMBER 15, 2003

With an enthusiasm normally reserved for today's discoveries, Zimmer, a regular columnist for Natural History, brings alive the science of 350 years ago, telling the story of the "discovery" of the human brain by physician Thomas Willis. Exploring the effects of this breakthrough on 17th-century Oxford, the author traces and investigates the subsequent discoveries and theories in neurology and medicine that flowed from Willis and others (e.g., Harvey, Hobbes, Descartes, Boyle, and Locke) in Oxford and on the continent. It was a time of adventure, with discoveries in science often overshadowed by successive wars in England and further complicated by inefficient means of communication, limited equipment for experiments, plagues, religious affiliations, education, power, and politics. Zimmer's elegant writing combines these multiple perspectives to produce a fascinating tour de-force of a man, a time, and a place that readers will greatly enjoy.

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BOOKLIST, DECEMBER 1, 2003, STARRED REVIEW

Every Renaissance history tells how seventeenth-century pioneer William Harvey finally solved the riddle of the heart. Yet even among anatomists, few know how one of Harvey's students--Thomas Willis--first systematically dissected an even more mysterious human organ: the brain. A gifted science writer, Zimmer recounts Willis' singular achievement in a narrative that illuminates not only the scientific revolution in medicine but also the cross-grained personality of one of the chief revolutionaries. Readers may marvel that Willis learned enough science to lead a revolution during an Oxford education disrupted by civil war and religious zealotry. But Zimmer recognizes how a few Oxfordians (including Christopher Wren, Robert Boyle, and Robert Hooke) instilled in Willis a deep skepticism toward inherited dogmas and a lively receptivity toward new ideas. Eventually, Willis turned one of those new ideas (a mere glimmer in the rationalist philosophy Rene Descartes) into a fledgling new science: neurology. In language accessible to general readers (supplemented with illustrator Wren's wonderful drawings from Willis' original work), Zimmer details the groundbreaking research through which Willis mapped the brain and diagnosed its disorders. And beyond Willis' science, Zimmer adumbrates its radical metaphyiscal implications, which undercut moral and religious doctrines tied to the immaterial soul (doctrines in which, ironically, Willis himself fervently believed).
A remarkable fusion of scientific history and cultural analysis.

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PUBLISHER’S WEEKLY, NOVEMBER 24, 2003, STARRED REVIEW

The subtitle doesn’t do justice to this illuminating book, which transcends the “history of X and how X changed the world” genre with a deep and contextualized exploration of two millennia’s worth of human theories about consciousness and the soul. Zimmer, a columnist for Natural History and author of the highly praised Evolution: The Triumph of an Idea, is interested in how philosophers and scientists moved from a view of the human soul as immaterial and residing in the hear to the common explanation of thought as having a material grounding in the brain and nervous system. His wide-ranging narrative reaches from the days of Aristotle to a 21st-century lab in the basement of a Princeton University lab in the basement of a Princeton University building. The central figure in Zimmer’s tale is the oft-overlooked 17th-century scientist Thomas Willis, a member of the British Royal Society and colleagues of Boyle and Hooke. Willis, a figure of fascinating contradictions, was a conservative, religious royalist raised on a farm outside Oxford, who wound up working on the frontiers of science, as physician to the highest strata of London society and as an experimenter who helped found a new science of the brain. In the end, however, this book is less about Willis in particular than about the evolving metaphysics of the soul in general, and the reader is left with a better picture of the roots of the modern understanding of the self as well as a familiarity with one of the unsung heroes of the scientific revolution.

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KIRKUS REVIEWS, NOVEMBER 1, 2003

Seventeenth-century England forms the tumultuous backdrop for science journalist Zimmer's account of the handful of thinkers who established that the brain, not the heart, was the seat of the soul. The author singles out as his hero Thomas Willis, a name best known today among anatomy students for the "circle of Willis," a ring of blood vessels at the base of the brain. A poor boy educated in medicine at Oxford, Willis eventually removed to London to become a rich and famous society physician. But it was his Oxford days, at the center of a circle of scholars that included Christopher Wren, Robert Hooke, and Robert Boyle that marked the revolution that dethroned Aristotle and Galen. Meticulous autopsies of Willis's patients and multiple experiments on animals dead and living (PETA would weep) established that it was the brain and the system of nerves carrying "spirits" to and fro that accounted for thoughts, emotions, and actions. Moreover, the dissections were also able to point to brain specialization, linking diseased parts to symptoms suffered by the deceased. Willis and his peers were not ready to surrender all to a mechanistic view. They posited a dual soul: a sensitive, material soul subject to disease and a "rational" soul deep in the brain that was immaterial and immortal. And for all Willis's acute observations of patients' signs and symptoms, his treatments stuck to the potions, purges, emetics, and bloodletting that were standard care at the time. Zimmer details all of these developments, along with brief bios of the principals, against the chaos and calamities of the English civil war, the beheading of Charles I, the rise of Cromwell, the Restoration, the Irish rebellion, the devastating plague of 1664-5, the great London fire of 1666, and enough bloody religious battles to satisfy the Taliban. Indeed, the many parallels that can be drawn between politics, religion, science, and human behavior then and now add unexpected dividends to this engaging narrative.
Absorbing and thought-provoking.

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THE SCOTSMAN, MARCH 28, 2004

The brains behind the operation
By John Freeman

ALTHOUGH neurologists have much to learn about the brain, the 17th century was a dark age by comparison. Back when bleeding was the main cure, scientists believed wisdom originated in the heart. The brain, they figured, was just a bellows pumping ‘spirits’ to various parts of the body.

In his engaging study, Carl Zimmer shines a searchlight on this tumultuous era, when England was in chaos, the cosmos was being reconfigured to Galileo’s design and the whereabouts of the soul was in hot debate. At the centre of this last issue was an overlooked Oxford-born physician, Thomas Willis, who spent his life studying the body and the brain. Along the way he put to rest a 2,000-year-old idea about the soul.

To help readers appreciate Willis’s breakthrough, Zimmer plunges us elbow deep into 17th-century medicine. Willis, like many physicians, earned his silver as a ‘pisse prophet’, swirling urine in a flask, examining its colour and then prescribing a remedy. His research was performed on the side, in unimaginable conditions. Without formaldehyde or freezers, brains taken out of the body "had the look and feel of custard".

The state of England made scientific study difficult, too. After the fall of Charles I, Cromwell purged Oxford University of royalists, forcing Willis to work in secret. Along with fellow sympathisers Christopher Wren - then a student prodigy - and John Wilkins, Willis formed a club that gathered weekly to do experiments and ponder their meaning.

What these men accomplished from mucking around in the craniums of dead convicts was an intellectual coup d’etat. Until the late 1600s, medical professionals were taught the ideas of the ancient Roman physician Galen, who learned anatomy during gladiator contests. In this fashion, Galen came to believe that the body ran on a balance of spirits and that the soul rested in a variety of organs. The "vegetative soul" rested in the liver, the "vital soul" came from the heart, whereas the "rational soul" came from the head.

Zimmer reveals how these medical beliefs dovetailed with political philosophy. Hobbes, for example, thought the state was like a body; it needed a rational soul to rule it - a monarch - and laws to govern it. The greatest overlap in this arena came in the form of William Petty, a doctor who trained with Willis and tutored with Hobbes, and went on to map Ireland. "He saw souls as cogs in a nation’s economic machine," writes Zimmer, and a map was a way to study a nation’s anatomy.

In this context, Willis’s discovery that wisdom, memory and feeling originated in the brain had immense political and theological ramifications. Soul Made Flesh opens in 1662 with a description of Willis, Wren and company taking a brain out of a corpse’s skull.

It was not the first time, since Egyptians had fished brains out with a hook prior to burial. By the time this scene recurs, Zimmer has given readers such a thorough background on the time that we feel Willis’s disgust, fear and awe as he gently peels back the outer membrane to grasp the seat of the soul.

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DENVER POST, FEBRUARY 8, 2004

Although modern doctors still have a lot to learn about the brain, the 17th century was a dark age by comparison. Back when bleeding was the "take-two-of-these-and- call-me-in-the-morning" cure, scientists universally believed that wisdom originated in the heart. The brain, they figured, was just a bellows that pumped "spirits" along to various parts of the body. Even Thomas Hobbes, that man ahead of his time, argued that nerves extended from the heart and sent feeling to the limbs.

In his wry and engaging study, Soul Made Flesh, Carl Zimmer sends the searchlight of his curiosity into this tumultuous era, when England was in chaos, the cosmos was being reconfigured to Galileo's design and the whereabouts of the soul was a topic of hot debate. At the center of this last issue was an unlikely man named Thomas Willis, an overlooked Oxford-born physician who spent his lifetime studying the body and the brain. Along the way he put to rest a 2-millennia-old idea about the soul.

To help readers appreciate the marvel of Willis' breakthrough, Zimmer plunges us elbow deep into the messy realities of 17th-century medicine. Needless to say, things weren't pretty. "If you needed a broken bone set, a locksmith on Cat Street could do it for you."

Willis, like many physicians, earned his silver as a "pisse prophet," swirling urine around in a flask, examining its color, and then prescribing a remedy. Whatever research Willis performed, he did on the side, and in conditions that are unimaginable. Without formaldehyde or freezers, brains taken out of the body "often had the look and feel of custard."

The state of England made serious scientific study difficult, too. After the fall of Charles I, the countryside languished in chaos with Cromwell imposing religious rule over subjects. Parliament had been disbanded. Oxford University was purged of loyalists, and Protestants frequently stormed classrooms questioning by what right professors taught students the inner workings of the body. A loyalist to the crown, Willis was forced to work in secret. And so, along with fellow sympathizers Christopher Wren - then a prodigy student - and John Wilkins, he formed the Oxford Experimental Philosophy Club, which gathered every Thursday to watch experiments and noodle about their meaning.

What these men accomplished mucking around in the craniums of dead convicts was nothing less than an intellectual coup d'etat. Until the late 1600s, medical professionals, if they could be called that, were taught from a 2nd-century doctor named Galen, who learned anatomy by working as a doctor during gladiator contests. What Galen couldn't glean there, he extrapolated from animals. In this fashion, Galen came to believe that the body ran on a balance of spirits and that the soul rested in a variety of organs. The "vegetative soul" rested in the liver, the "vital soul" came from the heart, whereas the "rational soul" came from the head.

In Soul Made Flesh, Zimmer adeptly reveals how these medical beliefs dovetailed with political philosophy at the time. Hobbes, for example, thought the state was much like a body; it needed a rational soul to rule it - a monarch - and laws to govern it. The greatest overlap in this arena came in the form of William Petty, a doctor who trained with Willis and tutored with Hobbes and went on to map the entirety of Ireland. "He saw souls as cogs in a nation's economic machine," writes Zimmer, and a map was a way to study a nation's anatomy.

In light of this context, Willis' discovery that wisdom, memory, thought and feeling all originated from the brain had immense political and theological ramifications. Soul Made Flesh opens in 1662 with a brisk description of Willis, Wren and company taking a brain out of a corpse's skull. It wasn't the first time, after all, since Egyptians used to fish it out with a hook prior to burial. By the time this scene recurs much later, though, Zimmer has given readers such a thorough background on the time that we feel Willis' disgust, fear and awe as he gently peeled back the outer membrane to grasp what was once thought to be the seat of the soul.

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METAPSYCHOLOGY, MAY 28, 2004

By Maura Pilotti

In Soul Made Flesh, Carl Zimmer cleverly and elegantly recounts the events that led to the acknowledgment of the brain as the physical substrate of our perceptual and cognitive functions. The book provides a historical context that allows readers to better understand contemporary neuroscience and its struggle to uncover how brain matter can potentially account for diverse human abilities, from those shared with other animals (e.g., perception of environmental patterns) to those that make us most unique (e.g., language and consciousness).

The book resembles a dramatic fiction story, which has the same vividness and intensity as only real tragedy unfolding in front of one's mesmerized eyes may have. It focuses on one central character, Thomas Willis, and touches on other, not less interesting, thinkers, among whom there are physicians, alchemists, philosophers, utopians, revolutionaries, etc. Each character, regardless of his centrality, is pictured against a colorful background of historic dramas, including various calamities (e.g., the plague and the great fire of London) and religious and political armed struggles (e.g., the English civil war and the Irish rebellion). The narrative is exciting and the characters as animate and tangible as if they were breathing beings acting their intricate roles right before one's eyes. Thus, it comes as no surprise if readers may be reluctant to take a break from the book and thus interrupt the flow of interconnected events that emerge from its pages. However, upon re-opening the book, those same events are sure to immediately emerge from the fog of memory in the vivid colors they had when they were temporarily interrupted by the exigencies of the readers' mundane lives.

Thomas Willis is depicted as a man of distinguished valor among a considerably remarkable array of thinkers spanning several centuries. Unsurprisingly, some of these thinkers ultimately succeed first in establishing that the brain, not the heart, is the location of the human soul, and then in claiming that the brain is the soul itself (i.e., the engine of perceptual and cognitive functions). The thinkers' investigative techniques and related discoveries, their correct intuitions and false interpretations, and their struggle against obsolete and misleading ideas provide an unequal insight into how scientific inquiry works and progresses. Their personal lives and "scientific" pursuits are exquisitely intertwined so as to provide an engaging narrative where the characters and their paths of actions appear as tangible as those of real life beings. Of course, some of the accounts of discoveries are a bit gruesome and it is difficult not to feel sorry for the animals submitted to unquestionably cruel treatments. Nevertheless, the narrative is engaging, thought-provoking, and not lacking of current appeal. Indeed, the struggles that the book repeatedly depicts between antiquated ideas and novel ones regarding human faculties and their main physical substrate (the brain) will remind readers of more current struggles. For instance, those between the need of researchers to conduct scientific inquiries, which, in an ethically sound manner, can answer daring questions about human nature, and moral and religious dogmas, which tend to prevent such inquiries (see debate about stem cell research or the Bush administration's sudden re-examination of federally founded grants devoted to the study of sexual behavior in its different forms). As a result, the Soul Made Flesh is a book not only about the history of the development of our knowledge of the brain, but also about how independent thinkers have overcome dogmas and improved human life with their newly acquired knowledge, a story that cannot be forgotten in the current politicized arena of clashing interests.

In summary, Soul Made Flesh is an outstanding book, which can be read by virtually anybody who is interested in understanding the historic development of scientific inquiries about human nature and of how the corresponding knowledge that it is bound to generate can ameliorate our existence. It is also a book about the present, which helps readers to comprehend that clashes between scientific pursuits (the need to know) and religious dogmas (the need to believe) are not an anomaly but simply history replicating itself. Among all the books available at libraries or bookstores, Zimmer's work is certainly a must-read.

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TIME OUT NEW YORK, JANUARY 22-29, 2004

Although doctors today barely understand the brain, by comparison, the 17th century was a dark age. Back then, scientists bellieved wisdom and thought originated in the heart; the brain they figured, was just a set of bellows that pumped "spirits" throughout the body. In his wry and engaging study Soul Made Flesh, science journalist Carl Zimmer rediscovers Thomas Willis, the much overlooked physician who spent his lifetime attempting to undo this misperception, thereby founding the modern science of neurology.

To help readers appreciate the resistance Willis faced, Zimmer plunges us elbow-deep into the messy realities of 17th-century medicine. "If you needed a broken bone set, a locksmith on Cat Street could do it for you." Willis, like many physicians, made his living as a "pisse prophet," swirling urine around in a flask, examining its color and then prescribing a remedy. Brain research was only a sideline, conducted under unimaginable conditions. Without formaldehyde or freezers, brains under examination "often had the look and feel of custard."

While much of the action in Soul Made Flesh takes place during this dismal era, the book also ranges over two millennia of theories about conscisouness and the brain. In the process, Zimmer crafts a fabulous story about the shift in ideas that transformed the soul from an ethereal entity to a tangible thing.

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ST. PETERSBURG TIMES (FLORIDA) JANUARY 25, 2004

Most historians adopt the Great Man approach to history. They assume history is propelled by a few exceptional people who guide the destiny of the human race.

The opposite is true, of course - historical forces drive the lives of every human, including those who make it into the history books. The people we deem great may possess exceptional talents, but they get carried along by the waves of change just like everyone else. Their accomplishments usually depend as much on luck as on skill.

In Soul Made Flesh: The Discovery of the Brain - and How It Changed the World, Carl Zimmer shows how historical forces affected the destiny of Thomas Willis, the 17th century English physician who essentially invented the study of the brain. Instead of presenting a close-up of Willis, however, Zimmer places him within a panoramic history of England during a period of political upheaval, civil war, religious ferment, plague and assorted other stresses. Zimmer provides so much historical context that at times Soul Made Flesh resembles Where's Waldo? with Willis, like the title character of those children's books, appearing as one small figure among the teeming masses.

Historical forces altered the arc of Willis' life at every stage. He attended Oxford University, for example, but ended up guarding the city walls against Parliamentary armies during the Civil War. The war also disrupted the traditional curriculum, freeing Willis from Aristotle and other ancient authorities on the natural world. The restoration of the monarchy provided Willis - a loyal Royalist who always supported the king - with the political protection needed to publish works that some religious zealots considered scandalous. And the creation of the Royal Society for Promoting Natural Knowledge in 1660, just as Willis was achieving his greatest insights into the brain, extended the influence of his work.

What influenced Willis even more, however, were the exceptional people who crossed his path.

One of his teachers at Oxford was William Harvey, who discovered that the heart pumped blood through the body in a loop. A good friend, William Petty, introduced Willis to dissection, which aroused the enthusiasm of an artist friend named Christopher Wren, who went on to become England's greatest architect. (Willis used Wren's beautiful drawings of the brain to illustrate The Anatomy of the Brain and Nerves, and Zimmer reproduces a Wren drawing at the front of each chapter.) Robert Boyle, fascinated by alchemy, brought the wonders of chemistry to Willis and the circle of friends they assembled at Oxford.

These friends generated a synergy that pushed Willis toward a modern approach to science based on the logical inferences he drew while dissecting corpses. He noticed, for example, that four arteries converged at the base of the brain, forming what has become known as the Circle of Willis. To test his hypothesis that this circle enabled the four arteries to share blood, he tied off three of the four arteries in a dog, which not only recovered from the operation but behaved normally, with only one artery supplying blood to its brain.

Willis wanted to explain the human body "without recourse to occult qualities, sympathy, or other refuges of ignorance," as he put it. Yet, despite his modern approach to scientific discovery, Willis did not completely transcend the conventional wisdom of his time. To treat lesions caused by the plague, for example, he recommended that "live frogs be apply'd and renew'd as oft as they die."

Such bizarre advice shows that Willis remained firmly rooted in his epoch, but by allowing his curiosity to roam freely - and by receiving a few lucky breaks from the forces of history - he managed to launch an investigation into the brain that neurologists carry on to this day.

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