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illustrations and text of an anatomy book that

TIMELINE
was published more than 300 years ago is a
rather humbling experience.
These books take us back to the sixteenth
Thomas Willis (1621–1675), and seventeenth centuries, around the time of
the English Civil War, the Protectorate and
the founder of clinical neuroscience Commonwealth, and the Restoration. This
was a period of enormous development in
many disciplines, and extremely important
Zoltán Molnár scientific and anatomical books were written
by Nicholas Copernicus and Andreas Vesalius,
Thomas Willis is considered to be one of the neuroanatomical terms that they will among others. This was also a time of progress
greatest neuroanatomists of all time. His encounter during the year, and to help them for the medical schools of Padua, Leiden,
name is usually associated with ‘the circle of to understand their meaning. Reflecting on Paris, Montpellier, Utrecht and Basel. The
Willis’, an anastomotic circle at the base of historical context helps students to demystify recording of human dissections became more
the brain, but his work also formed the terms such as vermis (worm), hippocampus precise, and long-standing dogmas of medi-
foundation of basic neuroanatomical (seahorse), pons (bridge), pulvinar (cushion), cine were overturned. Anatomy teaching was
description and nomenclature, and colliculus (little hill) and thalamus (bed in turmoil. The new generation of anatomists
comparative neuroanatomy. By combining chamber). It was through this practical teach- began to refuse to see things through the eyes
his insightful clinical observations with his ing that I became interested in the period of of others — they wished to examine the
original pathological studies, his enquiring the seventeenth century during which many of anatomical specimen themselves rather than
mind established links that are still these names were allocated, and in particular continue to read Hippocrates and Galen11.
astonishing 300 years on. For these in the seminal work of Thomas Willis This led to original and revolutionary obser-
reasons, Willis’ name and achievements (1621–1675) (TIMELINE). In this article, my vations. Medical students visited various
should be proclaimed to every new goal is to stimulate the new generation of schools on the continent before returning to
generation of neuroscientists. neuroscientists to explore the inspirational England to practice. Among them was
work of this great man. The primary sources
Anatomists are often criticized for using of information on Willis’ era2–5 are very
old-fashioned Latin or Greek nomenclature interesting but relatively difficult to access,
to indicate directions and planes of sections, and excellent studies6–10 from the twentieth
and to refer to gross structures. Knowledge of century provide valuable insights. For this
Latin and Greek was common among edu- review, I used the work of Trevor Hughes
cated persons in the seventeenth century, and extensively10.
these terms would not have posed any serious Oxford made a unique contribution to the
challenge to scholars at that time, but today neuroanatomical nomenclature through
they often seem to be a hindrance to learning the works of Willis. He lived in Oxford for
rather than a help. The Latin and Greek most of his life, with the exception of the last
terminology for the anatomy of the body has nine years, which he spent in London. Our
been much reduced. By contrast, most of students are encouraged to walk down Merton
the original terms for the brain are still used1, Street and look at Beam Hall, where Willis
perhaps because of their accuracy and beauty, lived from 1657 to 1667 (FIG. 1). They are also
which can be appreciated when the initial advised to visit our own College Library, open
difficulties of comprehension are overcome. one of the books from that period and imagine
I have been organizing neuroanatomy the circumstances in which neuroanatomical
practicals since I joined the Department of terms were allocated. Many Oxford colleges,
Human Anatomy and Genetics in Oxford. including Christ Church, Merton and St
The purpose of my first practical and lecture John’s, have extensive collections of his publi- Figure 1 | Beam Hall on Merton Street, Oxford.
is to introduce students to many of the cations. For the modern reader, looking at the The home of Thomas Willis from 1657 to 1667.

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Timeline | The life and work of Thomas Willis*

Elected Sedleian
Together with William Professor of Natural Publication of Cerebri
Born 27 January at Enlisted in Dover’s Petty, Willis ‘revived’ Philosophy, Oxford, UK. Anatome. Elected Publication of Affectionum
Great Bedwyn, Awarded Bachelor of Arts regiment in the Anne Green — a turning Doctor of Medicine, by Fellow of the Royal Quae Dicuntur Hystericae
Wiltshire, UK. degree, Oxford, UK. service of Charles I. point in his clinical career. request of Charles II. College of Physicians. et Hypochondriacae.

1621 1636 1639 1642 1645 1646 1650 1659 1660 1663 1664 1667 1670 1672

Matriculated at Christ Awarded Master Awarded Bachelor of Publication of first Elected Fellow of Publication of Publication of
Church College, Oxford, of Arts degree, Medicine degree, Oxford, UK, book, Diatribae Duae the Royal Society. Pathologiae Cerebri. Anima Brutorum.
UK, and contemplated a Oxford, UK. and began medical practice. Medico–Philosophicae. Moved to London, UK.
career in the church.

*Adapted from ref. 10.

William Harvey (1578–1657), who came to one could understand the three forms of soul Oxford Lectures, which were discovered and
Oxford during the Civil War and was Willis’ — vital, rational and immortal. He thought subsequently published by Dewhurst in 1980
neighbour in Merton Street for a brief period. that the immortal soul was only present in (REF. 9). So, Willis’ teaching duties, combined
Just as Harvey discovered the circulation of the humans, whereas the vital and rational souls with his research and clinical practice, provided
blood, it was Willis who revolutionized the were present in both animals and humans. He a unique opportunity to produce immortal
anatomical description of the brain. studied and compared the nervous systems of publications and disseminate his ideas to a
many different organisms, and this approach readership beyond Oxford. His anatomical
Willis’ unconventional medical training probably contributed to his enormous success. descriptions and clinical case presentations
Anatomical studies of the brain by Andreas Another contributing factor might have were detailed, succinct and well illustrated12.
Vesalius and Johannes Wepfer had been pub- been his teaching duties as the Sedleian Originally contemplating a career in the
lished at least a century before those of Willis, Professor of Natural Philosophy. In this post, church, Willis mastered Latin, which was the
but Willis’ contribution was hugely significant. he constantly exposed his own theories and language of religious authority and political
Willis made wide-ranging original observa- original observations to a thriving intellectual power13,14. The fact that he chose to write
tions in several fields, but focused most of his community. John Locke (1632–1704) took in Latin reflects his deep religious beliefs and
attention on the study of the nervous system. notes on these lectures. These notes, together loyalty to the King.
He believed that by understanding anatomy, with those of Lower, were the basis of Willis’ Willis’ individual contributions made him a
pioneer of his time15,16. Ironically, he probably
owed his originality to the fact that he was
spared classical medical training. At the time,
the course in medicine at Oxford lasted
14 years, during which students were forced to
repeatedly read outdated works by Aristotle,
Hippocrates and Galen11. This was the basis
of all medical learning, and was probably
sufficient to stifle initiative and originality
in most candidates. Turbulent events of
mid-seventeenth century Oxford saved Willis
from this fate. During the Civil War, the Court
and Royalist Troops occupied many Oxford
colleges, so normal academic life must have
been severely disrupted. Willis supported the
King by joining the auxiliary regiment of
the Earl of Dover, but he probably did not par-
ticipate in any battles. Just before the Protestant
takeover, Willis’ loyalty was rewarded with
conferral of his medical degree (Bachelor of
Medicine). This allowed him to start his
medical practice before the Parliamentary
forces and Protectorate transformed Oxford by
Figure 2 | Title page of Cerebri Anatome. This book, in which Willis established the concept of neurology, replacing the Royalist Heads of colleges and
was published in 1664. Reproduced with the permission of the library of St John’s College, Oxford. fellows. In 1646, William Harvey was removed

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Willis’ last book, A Plain and Easie

Publication of Method of Preserving Those That
Pharmaceuticae are Well From the Plague, was
Rationalis (part 1) published, 16 years after his death.

1674 1675 1691

Died on 11 November at home in

St Martin’s Lane, London, UK, buried
in Westminster Abbey, London, UK.

from his Wardenship at Merton College by

Cromwell, who became Chancellor of the
University. Willis probably escaped prosecu-
Figure 4 | Anne Green’s execution and her miraculous resuscitation. Reproduced with the
tion by the Visitors because, although he had a permission of the Bodleian Library, University of Oxford. Original citation: “Title page woodcut of the
room at Christ Church College, he was not execution and resuscitation of Anne Green in 1651 from News from the Dead. Or a true and exact
actually a fellow of the college, and because he narration of the miraculous deliverance of Anne Green, who being executed at Oxford afterwards revived.
studied and practised medicine. Written by a scholler in Oxford. R. Watkins, Oxford 1651, Bliss B 65 (2).”
Willis was in contact with numerous lead-
ing neuroanatomists and scientists from
other disciplines. Although he never left (1632–1723) prepared illustrations for many and the Sheldonian Theatre and All Souls
England, he was influenced by his colleagues of Willis’ books, including Cerebri Anatome College in Oxford, among others. Willis was
in Oxford, many of whom were well travelled (FIG. 2). Wren was an astronomer, but most surrounded by a group of excellent students,
and reported the latest developments from people know him for his architectural work including Richard Lower (1631–1691), who
other universities. Christopher Wren — he designed St Paul’s Cathedral in London, carried out the first successful blood trans-
fusion from the veins of one animal to
another, and John Locke. Willis also had
scientific interactions with Robert Boyle
(1627–1691), who is considered to be the
father of modern chemistry. It was common
at the time for physicians to consult one
another with regard to their patients, and
Willis corresponded with numerous leading
physicians. These letters are good sources for
the investigation of his thinking. St John’s
College Library holds letters that were
exchanged between Willis and Dr Richard
Higges from Coventry, who also corresponded
with John Radcliffe17 (FIG. 3).

Willis as a practising clinician

Willis obtained vast clinical experience during
his career. He had to prove his medical skills
before he could attract patients in Oxford,
where established physicians practised. As a
young doctor, he ran his practice outside
Oxford, visiting markets in neighbouring
villages and offering his services to the general
Figure 3 | Willis’ letter to Dr Richard Higges in Coventry17. In this letter, which is dated 24 March
public. Willis had to compete with quackery,
1665, Willis advises Higges on the appropriate treatment of the foot of a female patient. The letter also refine his skills and build his reputation. To
contains detailed descriptions of how to prepare the medications required during the night and the save money he shared a horse with Richard
morning. Reproduced with the permission of the library of St John’s College, Oxford. Lydall, another struggling physician10.

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Box 1 | Books published by Willis*

Diatribae Duae Medico–Philosophicae (1659)

This work contains descriptions of fermentation and fevers. Willis was searching for
explanations for basic biological and chemical processes (biochemistry) of the body.
His observations on various types of fever are spectacular. He distinguished intermittent,
continuous and putrid fevers, and his descriptions indicate that he described fevers associated
with malaria. He also described and analysed camp fever (febris castrensis).
Cerebri Anatome cui Accessit Nervorum Descriptio et Usus (1664)
The concept of central, peripheral and autonomic nervous systems was established in this
work. The word ‘neurologie’ first appeared in Pordage’s translation19. Cerebri Anatome was
in use for nearly 200 years, and brought international recognition to Willis. It contains
descriptions of the brain, the spinal cord, and the peripheral and autonomic nervous systems.
Willis reclassified Galen’s descriptions of the cranial nerves. The vascular supply to the brain
and spinal cord are described with superb illustrations by Wren. The idea that the cerebral
cortex is the seat of higher human cognitive functions was published in this volume. The
contributions of Dr Richard Lower, Dr Thomas Millington and Dr Christopher Wren are
acknowledged in the preface. The book is dedicated to Willis’ patron, Dr Gilbert Sheldon,
Archbishop of Canterbury.
Pathologiae Cerebri et Nervosi Generis Specimen (1667)
This work contains some of the first descriptions of numerous neurological disorders and other Figure 5 | Thomas Willis aged 45 years. From
the title page of Pathologiae Cerebri, engraved by
diseases, including epilepsy and asthma. Willis was 45 years old at the time of publication, and
Loggan in 1667.
well established.
Affectionum Quae Dicuntur Hystericae et Hypochondriacae (1670)
This book has three parts, which discuss hysteria and hypochondria, blood, and muscular action, In 1636, shortly before Willis started his
respectively. Willis was the first to suggest that the cause of hysteria was located in the brain. His studies at Oxford, the University statutes
thoughts on blood and circulation were advanced and similar to those of William Harvey, but his were revised, and dissection became part of
ideas on muscle action — despite the suggestion of reflex action — were less clear. medical training. Through the 1636 charter,
De Anima Brutorum Quae Hominis Vitalis ac Sensitiva Est (1672) Charles I granted that the Tomlins Reader in
This book is considered to be one of Willis’ most influential works. It is the continuation of his Anatomy could claim the body of anyone
anatomical and pathological observations that were described in Cerebri Anatome and who was executed within 21 miles of Oxford.
Pathologiae Cerebri. Willis deals with the soul and with pathological states that affect the soul Medical students had to participate in
and brain, and speculates on brain function and functional disorders. He provides a comparative two public dissections in addition to anatom-
neurological overview of different nervous systems. His description of the state of paracusis ical lectures and dissections to obtain a
(the ability of patients with hearing loss to hear better in noisy environments) and myasthenia Bachelor of Medicine degree. William Petty
gravis, and his ideas on sleep, headache and vertigo, are still relevant today. (1623–1687) was the Tomlins Reader in
Pharmaceuticae Rationalis (1674–1675) Anatomy at Oxford and a long-standing
In the first volume, available medicines are described, together with Willis’ anatomical, medical colleague and mentor of Willis. They
pathological and clinical observations. It was in this book that Willis described his scientific often performed dissections together at
approach to rational pharmacology. He provides his spectacular description of the different Petty’s residence in Bulkley Hall, a building
forms of polyuria, including diabetes mellitus, although he could not possibly have off High Street in Oxford that is the site of a
understood its pathogenetic mechanism. This volume also contains experimental Thai restaurant today. These dissections were
observations of dogs and cats. The second volume was published just after Willis’ death, and it done in private, and often under very strange
explores various respiratory, gastrointestinal and dermatological diseases. It describes the circumstances.
contemporary medical treatments, with bleeding, purgation, blistering, branding and Willis’ fortunes as a clinician changed
vomiting as therapies. when, on 14 December 1650, along with
A Plain and Easie Method of Preserving Those That are Well From the Plague (1691) Petty, he revived a prisoner named Anne
A posthumous edition of Willis’ work written around 1666, and his only book to be written in Green. Green had been charged with murder
English. It contains numerous prescriptions that were edited by his pharmacist John Hemmings. for killing her newborn baby, and was hanged
on the Cattle Yard in Oxford. Descriptions
*Based on REF. 10
note that she hung for half an hour, was then
pronounced dead and placed into a coffin
Willis’ way of observing and treating others, probably because of their different (FIG. 4). By the time that Willis and Petty
patients was different to that of many of his sugar contents. This led him to propose that opened the coffin to start her dissection at
contemporaries, owing to his original observa- the sweetness of the urine enables doctors to Petty’s residence, a strange noise was emitted
tions and critical views. His approach is illus- distinguish this particular form of polyuria from her throat and she started to breathe. A
trated by his observations on urine samples from other forms of increased urine produc- contemporary description mentions that
supplied by his patients for diagnostic pur- tion, including chronic kidney disease. The tes- Willis and Petty poured some hot cordial into
poses — a common practice at the time. Willis timony of his sharp observations is that we still her mouth and tickled her throat with a
stored these samples at his home, and noticed refer to diabetes subtypes as mellitus (‘sugar feather to provoke more coughing. They
that flies preferred particular samples over diabetes’) and insipidus (‘water diabetes’). rubbed her arms and legs until she opened

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her eyes, then bled her of five ounces of

blood18. They also used some heating plasters
on her body and subsequently placed her into
a bed with another woman to keep her warm
(FIG. 4). She could speak in twelve hours,
answer questions in a day, and eat solid food
in four days. Within a month she had recov-
ered completely, and went on to marry and
bear three more children18.
After this incident, Willis’ medical practice
took off, and his life became more comfort-
able. He left his accommodation at Christ
Church, married Mary Fell (daughter of
the Dean of Christ Church) and moved to
Beam Hall on Merton Street (FIG. 1). He was
appointed as the Sedleian Professor of
Natural Philosophy in Oxford by Gilbert
Sheldon (1598–1677), who supported Willis
throughout his career. This patronage is Figure 6 | Illustrations from Cerebri Anatome (1). The illustration shows a normal brain (left) and a
acknowledged in the dedications of several of brain from a case of congenital idiocy (right). Reproduced with the permission of the library of St John’s
Willis’ books. In 1663, Willis was elected College, Oxford.
a Fellow of the Royal Society. He published
Cerebri Anatome in 1664. This book remained
the most significant contribution to neuro- material, including his rigorous pathological had his own apothecary, John Hemmings,
anatomy for almost 200 years. Willis pub- observations and correlations of patholo- who lived within his household for a period.
lished seven books, all in Latin except for the gical and clinical findings. He recognized that It might be argued that the remedies offered
last, Method of Preserving Those That are Well “meningitis and purulent states of the brain by Paracelsus, Helmont, Sylvius and Willis
from the Plague (BOX 1). Cerebri Anatome was do not cause phrenzy, but lethargy and coma. were just as strange as the medications that
translated into English by Samuel Pordage Mania is a delirium without fever but with are offered by contemporary unqualified
and published in 1681. This translation of fury and boldness”10. He described morpho- practitioners. However, unlike many of these
The Anatomy of the Brain was subsequently logical abnormalities of the brain in cases practitioners, Willis was genuinely trying to
reprinted in 1971 (REF. 19). Pordage had no of congenital mental retardation (FIG. 6). understand the disease and find a rational
medical training and probably did not He also noted the unilateral degeneration of treatment.
understand much of the text that he was the cerebral peduncle (the main output Willis gave a clear description of the symp-
translating. Nevertheless, some parts of his pathway towards the spinal cord) in a case of toms of myasthenia gravis, malaria, typhoid
translation of Cerebri Anatome could almost long-standing one-sided paralysis. These fever, puerperal fever and diabetes mellitus.
be used today as a standard anatomy text. findings show just how far ahead of his time He made pioneering observations of various
Willis established the concept of neurology in he was, and how his approaches differed neural structures, and his system of nomen-
Cerebri Anatome, and it is believed that the from those of other eminent contemporary clature is still used. He identified the spinal
word ‘neurology’, which featured in Pordage’s physicians. accessory nerve, claustrum, medullary pyra-
translation, can be attributed to him. Willis Iatrochemistry — the use of chemistry in mids, anterior commissure, inferior olives,
was 45 years old when Pathologiae Cerebri medical practice — was pioneered by corpus striatum, optic thalamus, vagus nerve,
was published (FIG. 5). He became one of the Paracelsus, and Willis was influenced by this nervus ophthalmicus, internal capsule and
most trusted physicians in Oxford, and later trend through the work of Helmont. Willis cerebellar peduncles10 (BOX 2). The terminology
London. He charged the highest sums for his
services from his wealthy patients and treated
the poor for free 2. Box 2 | Willis’ lasting contributions*
Neuroanatomical terms coined by Willis
Founder of neuropathology Anterior commissure | Cerebellar peduncles | Claustrum | Corpus striatum | Inferior olives
Why did Willis become one of the greatest (corpora teretia) | Internal capsule | Medullary pyramids | Nervus ophthalmicus | The word
neuroanatomists of all time? Dissecting ‘neurology’ | Optic thalamus | Spinal accessory nerve | Stria terminalis (taenia cornua) |
his own clinical cases must have been a key Striatum | Vagus nerve
element that contributed to his success.
Pathologies recognized by Willis
He often followed his patients for years, Achalasia of the cardia (achalasia of the oesophagus) | Akathisia (restless legs syndrome,
and dissected them after their death. He Ekbom’s syndrome) | Symptoms of myasthenia gravis | Paracusis Willisii. Occurs in deaf
was therefore in a position to relate altered patients whose hearing improves in the presence of noise, indicating osteosclerosis | Diabetes
behaviour to abnormalities of the brain. He mellitus | Abnormalities of the brains of patients with congenital mental retardation | Unilateral
recognized the pathological basis of several degeneration of the cerebral peduncle in a case of long-standing unilateral paralysis | Symptoms
diseases, and his anatomical descriptions and of malaria | Distinctions between typhoid and puerperal fevers
case histories are still valid (BOX 2). He became
*Based on REF. 10.
well known because he published much of his

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recognized that the medulla oblongata of the

brainstem is essential for the regulation of
the functions of the heart, lungs and intestines.
Like Descartes, Willis was aware of the
concept of reflex action. He believed that
nerve impulses journeyed to and from the
brain, and that ‘animal spirits’ were
‘reflected’ back towards the periphery from
the striatum10,19. His theories about the pas-
sage of nerve impulses are all the more
remarkable when one considers that they
antedate the discovery of electric current by
hundreds of years.
It is not often recognized that Willis was
also the first person to propose that the
higher cognitive function of the human brain
comes from the convolutions of the cerebral
cortex19. At the time, the dominant view was
that of the Greek physician Galen (130–200
Figure 7 | Illustrations from Cerebri Anatome (2). The base of a human brain (left) and a sheep brain
AD). Galen held that the fluid-filled cavities
(right) with the circle of Willis (the anastomotic arterial circle). The spectacular differences between the
cerebral cortex of humans and other animals led Willis to argue that “the cerebrum is the primary seat of of the brain contained the final product of
the rational soul in man, and of the sensitive soul in animals. It is the source of movements and ideas.” ‘perfect distillation’, called animal spirit.
Reproduced with the permission of the library of St John’s College, Oxford. Animal spirit could be animated and was
the source of all intellect. It was generally
believed that there are three cells (ventricles)
was probably established according to the Willis’ legacy involved in cognitive functions. The first, sen-
shape, consistency, location and colour of these Willis’ name has survived largely because of his sus communis, received signals from the eyes,
structures in the brain and brain sections. The description of the circle of Willis — the arte- ears, tongue, nose and skin. These signals were
names do not reflect their function, which was riosus circle at the base of the brain. He thought to mix before passing to the middle
not known at that time. serendipitously came across the idea of a ventricle, the seat of reason (ratio), thought
circle during a post mortem of a man who died (cognition) and judgement (aestimatio)20. The
Father of comparative neuroanatomy of stomach cancer, and he demonstrated its final step was memory itself (memoria),
In his search for specific human abilities in functional significance by tracing the course of which was formed in the last ventricle. This
cognitive functions, Willis compared the a post-mortem injection of ink. Others, dogma was rarely questioned until Leonardo
peripheral and central nervous systems of including Fallopius (1523–1562), Casserio da Vinci (1452–1519) found that most sen-
various species with the equivalent systems in (1561–1616),Vesling (1598–1649) and Wepfer sory nerves target the area around the third
humans. In Cerebri Anatome, he described the (1620–1695), had mentioned this structure ventricle (the region now called the thala-
significantly larger size of the human cerebral previously10. However, Willis provided the best mus), indicating that sensus communis was
cortex compared with that of other species. In illustrations, and he also described and empha- located at the third ventricle rather than at the
Anima Brutorum, Willis extended his work to sized the anastomotic nature of the circle’s lateral ventricles. René Descartes (1596–1650)
an even wider range of species, including silk- arrangement (FIG. 7). So, the structure has retained elements of these ancient ideas when
worms, oysters, lobsters and earthworms. remained associated with him. explaining the behaviour of animals, but for
Dissection of these specimens would have Willis’ achievements are particularly him the human mind was a separate entity
required a high degree of surgical dexterity, impressive when one considers that he made that communicated with the brain through
and the elaborate illustrations demanded con- his observations by dissecting unfixed brains, the pineal gland.
siderable artistic skills. Willis was surrounded some of which must have been in extremely Willis based his proposal for the role of the
by students whom he trained and inspired. In poor condition. Paraformaldehyde fixation cerebral cortex in higher cognitive functions
his comparative anatomical work, he was was not used for another 250 years. By study- on his observations of the sheer size of the
probably helped by Edmund King and John ing these unfixed brains, Willis reclassified cortex in humans compared with that of other
Masters, as he shared his practice and research the cranial nerves, superseding Galen’s descrip- animals (FIG. 7). He noted that the convolutions
with them around this time. The nervous sys- tion. He recognized the first to the sixth cranial are larger and more numerous in the human
tems of various animals had not previously nerves as we know them today. His seventh cortex, and related this to the superior intellect
been examined in great detail, and because of nerve was the auditory nerve with two of humans. He argued that, in birds and fish,
his pioneering discoveries, Willis is considered branches. His eighth nerve was the vagus, and the flat and even surface of the brain is
to be the father of comparative anatomy. He he recognized its branches to the heart. completely devoid of gyri and bends, and this
also carried out numerous experiments on Together with Richard Lower, he demonstrated is why such animals have an inferior capacity
animals to understand the mechanism of their functions by ligating them in dogs. Willis for understanding and learning19 (BOX 3).
nerve action, and he sought to relate these discovered the spinal accessory nerve, and his Willis believed that only humans possessed
experiments to the origin of the clinical symp- illustrations show the glossopharyngeal and ‘immortal soul’.
toms observed in his patients. These were hypoglossal nerves, although with the opposite Willis associated several physiological states
revolutionary concepts at the time. nomenclature to what is used today. He also with the function or dysfunction of the brain.

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He suggested that headaches are related to a

Box 3 | Willis on the increased size of the cerebral cortex in human
sudden increase of blood flow to the brain, and
he believed that the cause of the pain was the From REF. 19, a reprint of the 1681 translation of Cerebri Anatome to English by Samuel Pordage,
compression of nerves adjacent to the bulging chapter 9, 59–60.
blood vessels. These ideas were so powerful “But a reason and necessity of the turnings about in the brain, and not of lesser moment that
that they were widely believed until recently 21. the other, is fetched from the dispensation of the animal Spirits. For as the animal Spirits, for the
Willis had pioneering thoughts on sleep, various acts of Imagination and Memory, ought to be moved within certain and distinct limited
sleepwalking, insomnia, narcosis, lethargy and or bounded places, and those motions to be often iterated or repeated through the same tracts or
coma. He related lethargy to obstructive paths: for that reason, these manifold convolutions and infoldings of the brain are required for
these divers manners of ordinations of the animal Spirits, to wit, that in these Cells or
hydrocephalus, brain tumour and stroke.
Storehouses severally placed, might be kept the species of sensible things, and as occasion serves,
When he dissected his own patients, he tried to
may be taken from thence. Hence these folds or rollings about are far more and greater in man
relate the symptoms of different psychiatric
than in any other living Creature, to wit, for the various and manifold actings of the superior
diseases, including mania, melancholia and Faculties; but they are garnished with an uncertain, and as it were fortuitous series, that the
hysteria, to brain pathology. Many of his con- exercises of the animal Function might be free and changeable, and not determined to one.
temporaries were looking for the causes of Those Gyrations or Turnings about in four-footed beasts are fewer, and in some, as in a Cat, they
these disorders in other organs, such as the are found to be in a certain figure and order: wherefore this Brute thinks on, or remembers
uterus, lungs and spleen. Willis’ approach — to scarce any thing but what the instincts and needs of Nature suggest. In the lesser four-footed
exclude these organs and indicate different beasts, also in Fowls and Fishes, the superficies of the brain being plain and even, wants all
parts of the brain — was rational and based on crankling and turning about: wherefore these sort of Animals comprehend or learn by imitation
careful and accurate observations. He noticed fewer things, and those almost only of one kind; for that in such, distinct Cells, and parted one
abnormalities of cortical morphology in the from another, are wanting, in which the divers Species and Ideas of things are kept apart.
brains of patients with mental retardation But that in more perfect Animals, all the turnings about are made of a twoford substance, viz.
(FIG. 6). Willis’ ideas and work on cerebral cor- Cortical and Medullary; the reason seems to be, that one part may serve for the production of
tical function continue to inspire us, as we try the animal Spirits, and the other for their exercise and dispensation. For we may well think, that
to exploit functional brain imaging in the the animal Spirits are wholly or for the most part procreated in the Cortical substance of the
search for higher cognitive functions and brain; for this severs and receives immediately from the blood the subtil liquor, and imbuing it
for understanding neurological and mental with a volatile Salt, exalts it into very pure Spirits.”
disorders22,23.
Living in Oxford helps one to imagine
this historical period. One of my favourite Zoltán Molnár is in the Department of Human 15. Dewhurst, K. in Historical Aspects of the Neurosciences
Anatomy and Genetics, University of Oxford, (eds Rose, F. C. & Bynum, W. F.) 327–344 (Raven, New
novels is An Instance of the Fingerpost by Iain York, 1982).
South Parks Road, Oxford OX1 3QX, UK
Pears24, in which the author transports us and St John’s College, St Giles Street,
16. Viets, H. R. A Patronal Festival for Thomas Willis
(1621–1675) with Remarks by Sir William Osler, Bart.
to the seventeenth century world of Willis. Oxford OX1 3JP, UK. FRS. Ann. Med. Hist. 1, 118–124 (1917).
Many of the characters are based on real e-mail: zoltan.molnar@human- 17. Willis, T. Letter to Richard Higges, ms 296, St John’s
College Library, Oxford (1665).
Oxford figures, and when reading this novel, anatomy.oxford.ac.uk 18. Hughes, J. T. Miraculous deliverance of Anne Green: an
one feels that one is present when these fun- doi:1038/nrn1369 Oxford case of resuscitation in the seventeenth century.
BMJ 285, 1792–1793 (1982).
damental discoveries of medicine were made. 19. Willis, T. The Anatomy of the Brain (Tuckhoe, New York,
1. Butler, A. B. & Hodos, W. Comparative Vertebrate
It is an overwhelming experience for today’s Neuroanatomy, Evolution and Adaptation (Wiley & Sons
1971).
20. Blakemore, C. in The Oxford Companion to the Body
neuroanatomists to examine a book written Ltd, Chichester, 1996).
(eds Blakemore, C. & Jennett, S.) 602–603 (Oxford Univ.
2. Wood, A. Historia et Antiquitates Universitatis Oxoniensis
by Willis and realize just how advanced his (Oxon, 1674).
Press, 2001).
21. Gorman, C. & Park, A. The new science of headaches.
work was. He had an inquisitive mind and 3. Fell, J. Postscript to Willis’ Pharmaceutice Rationalis part
Time 160, 54–60 (2002).
2 (T. Ding, London, 1684).
was very creative in his work, developing new 4. Aubrey, J. Brief Lives Chiefly of Contemporaries Vol. 2
22. Hughes, J. T. in Neuroscience Across the Centuries
(ed. Rose, F. C.) 93–94 (Smith-Gordon, London, 1989).
methodologies and terms that have stood the (ed. Clark, A.) 302–304 (Clarendon, Oxford, 1898).
23. Zimmer, C. Soul Made Flesh: The Discovery of the Brain
5. Willis, B. Letter to Bishop Kennet (7 March 1725).
test of time. Willis is still at the centre of Reproduced in Wood, A. Athenae Oxoniensis Vol. 3
and How it Changed the World (Heinemann, Portsmouth,
New Hampshire, 2004).
debates about higher intelligence and the (eds Wood, A. & Bliss, P.) 1048–1053 (London,
24. Pears, I. An Instance of the Fingerpost (Random House,
1813).
nature of the soul that have been repeatedly 6. Feindel, W. Thomas Willis: The Anatomy of the Brain
London, 1997).

revisited by scientists and anatomists. and Nerves (McGill Univ. Press, Montreal, 1964).
Acknowledgements
7. Frank, R. G. Jr in Dictionary of Scientific Biography
Interestingly, Willis’ education benefited Vol. 14 (ed. Gillispie, C. G.) (Macmillan, New York,
C. Hilliard drew my attention to Willis’ letters to Dr Richard
Higges and helped me with my study of original manuscripts.
from political upheaval, which saved him 1976).
I am grateful to the President and Fellows of St John’s College
8. Isler, H. Thomas Willis 1621–1675: Doctor and Scientist
from the detrimental effects of regurgitating (Hafner, London, 1968).
for their kind permission to take pictures of the original publica-
tions and manuscripts. I would like to thank N. Pollini,
outdated works and freed him to make accu- 9. Dewhurst, K. Thomas Willis’ Oxford Lectures (Sanford,
E. Hurren, R. Hevner, K. Mitchell, C. Blakemore and C. Voelker
Oxford, 1980).
rate and original observations. The academic 10. Hughes, J. T. Thomas Willis 1621–1675, His Life
for useful discussions and B. Riederer for help with the
photography for Figure 1.
climate in Oxford was highly beneficial, and Work (Royal Society of Medicine, London,
1991).
emphasizing the ongoing need for researchers 11. Sinclair, H. M. & Robb-Smith, A. H. T. A Short History of
Competing interests statement
The author declares that he has no competing financial interests.
to work in a unique collegiate academic Anatomical Teaching in Oxford (Oxford Univ. Press,
1950).
atmosphere. Above all, Willis’ life illustrates 12. Dewhurst, K. Willis’ Oxford Casebook (Sanford, Oxford, Online links
the importance of intellectual and research 1981).
13. French, R. K. The languages of William Harvey’s natural FURTHER INFORMATION
freedom. Each generation of medical students philosophy. J. Hist. Med. Allied Sci. 49, 24–51 The Galileo Project: http://es.rice.edu/ES/humsoc/Galileo/
‘rediscovers’ Thomas Willis for itself, and (1994). Thomas Willis
14. O’Connor, J. P. Thomas Willis and the background to Encyclopedia of Life Sciences: http://www.els.net/
reading his works is a humbling yet strong Cerebri Anatome. J. R. Soc. Med. 96, 139–143 Cerebral cortex diseases and cortical localization
stimulus for thought and debate. (2003). Access to this interactive links box is free online.

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