WHILLIS, THOMAS

(b. Great Bedwyn, Wiltshire, England, 27 January 1621; d. London, England, 11 November 1675)

anatomy, medicine.

Thomas was the eldest of three sons of Rachel Howell and Thomas Willis, the steward of the manor at Great Bedwyn. Before his mother’s death in 1631, the family moved to North Hinksey, Berkshire, where the mother had property. The Proximity to Oxford (a mile and a half) enabled young Willis to be schooled there with Edward Sylvester, who numbered John Wilkins among his former pupils. He matriculated in the university from Christ Church on 3 March 1637, and worked as a servitor to one of the cathedral canons while proceeding B.A. (19 June 1639)and M.A. (18 June 1642). His father’s death in 1643 left Thomas head of the family, and his own partisan military service in the losing royalist cause during the siege of Oxford forestalled his career in the church. He turned to medicine, taking his B.Med. and license to practice on 8 December 1646.

Almost from the beginning of his medical career, Willis evinced an interest in science, first in mathematics but increasingly in chemistry and anatomy. He and two Trinity fellows, Ralph Bathurst and John Lydall, carried out chemical experiments in Willis’ Christ Church rooms in the late 1640’s. When other eminent scientists–Wilkins. William Petty, John Wallis, Seth Ward, and Jonathan Goddard–were appointed to Oxford positions during the years 1648–1651. Willis and his friends joined them and others in forming a philosophical “Clubb” to meet weekly and perform experiments in rota. By the mid-1650’s the club had grown to include Robert Boyle, Christopher Wren, Thomas Millington, and Robert Hooke, the last of whom Willis hired out of Christ Church as a chemical assistant, later recommending him for the same position with Boyle.

Willis and his friends also did anatomical dissections. A clinical notebook kept by Willis (ca. 1651) recorded not only his careful case notes, but also the results of occasional postmortems. In the famous case of Anne Green, convicted and hanged at Oxford for infanticide in late 1650, Willis, Petty, Bathurst, and others assembled for a dissection, only to find the cadaver still very much alive.

Working within this milieu, Willis completed by 1656 his first scientific work, De fermentatione. During th late 1650’s he supplemented this with a major work on fevers, De febribus, and a shorter piece on urine, Dissertatio epistolica de urinis, written to Bathurst; they were published in 1659 as Diatribae duae medico-philosophicae

In De fermentatione Willis argued that all bodies are composed of five kinds of particles: those of spirit, sulfur, salt, water, and earth, in order of decreasing activity. Any body containing a mixture of these particles is capable of fermentation, which Willis defined as an intestine (internal) motion of a body’s chemical particles leading to the perfection or transformation of that body. According to this process must becomes wine and wort becomes beer; liquids coagulate, or solids precipitate from them; food is converted into chyme, and thence into blood. Animals and plants grow by the process of fermentation, just as they are corrupted by it after their deaths.

But for the physician, the most important kinds of fermentation take place in the fluids of the human body, most especially the blood. Accepting Harvey’s theory, he proposed a reason for the circulation: as the blood and its dissolved food pass through the heart, a ferment implanted there excities a fermentation, or “accension,” by which heat is generated and the food converted into nutrient blood.

Willis’ theories were new versions of ideas widely discussed on the Continent during the 1640’s and 1650’s, but with the important difference that Willis cast his explanations into the atomistic and chemical terms that Boyle had made so popular among his Oxford friends. Helmont had proposed that numerous physiological processes are carried out by fermentation, but had used that term to denote an animistic function of the soul. Descartes and the Dutch Cartesian Hogelande had written of a ferment in the heart, but not in such chemical and corpuscular detail.

But Willis was a practitioner as well as a theorist, and the second tract of 1659, De fe bribus, exemplifies what was to be the enduring characteristic of his published works: the concern to use anatomy, physiology, and chemistry to explain clinical findings. Harvey’s discovery of the circulation, Willis said, necessitated a new theory of fevers based upon knowledge of fermentation. Fever was nothing but the natural exothermic fermentation of the heart, excited to a preternatural degree by foreign materials introduced into the blood. After speculations on the mechanisms that might be involved in this derangement, Willis filled the remainder of the tract with detailed descriptions of fevers drawn from his own casebooks. His characterizations of epidemics were particularly acute, reporting in detail the first English outbreak of war-typhus, among the Oxford troops in 1643, cases of plague in 1645, measles and smallpox in 1649 and 1654, and influenza in 1657 and 1658. He also recorded what seems to be the first reliable clinical description of typhoid fever. To a great degree he, rather than Sydenham or Morton, began the tradition of English epidemiology.

Willis’ life changed radically after the restoration of Charles II in 1660. Wilkins and other friends moved to London and founded the Royal Society. Willis remained in Oxford, and both his growing scientific reputation, and his unswerving loyalty to king and church, were rewarded by his appointment at the university at Sedleian professor of natural philosophy. He graduated D.Med. On 30 October 1660, and began regular lectures on natural philosophy and medicine, which attracted a large audience.

The notes for some of these lectures were copied out by Willis’ assistant from Christ Church, Richard Lower, and later extracted by Lower’s friend John Locke. They show the degree to which Willis ignored the statutory injunction to teach only from Aristotle. Rather, he lectured on neurological topics: sense and motion, the cerebellum, sleeping and waking, pleasure and pain, as well as the clinical effects of neurological changes in diseases such as convulsions, epilepsy, hysteria, vertigo, lethargy, and paralysis.

But, as he remarked later in the preface to Cerebri anatome, he was dissatisfied with excessively speculative nature of these lectures, and in late 1661 he and Lower began a series of dissections of the brain with a view toward clarifying such questions. Lower wrote to Boyle in early 1662 that Willis found “most parts of the brain imperfectly described,” and intended “to make a whole new draught thereof, with the several uses of the distinct parts.” Thomas Millington contributed to the discussions, and just before the completion of the book in July 1663, Wren executed a magnificent series of drawings to illustrate the text.

The Cerebri anatome, published early in 1664, is the foundation document of the anatomy of the central and autonomic nervous systems. It greatly surpassed, in the detail and precision of its descriptions, the fragmentary treatments of the brain that had preceded it. As a text it continued to be used until the late eighteenth century, and was mandatory background reading for neuroanatomists until the mid-nineteenth century.

Willis’ description and classification of the pairs of cranial nerves superseded those of Falloppio (1561), and remained in widespread use until those of Sömmering (1778) replaced them in the late eighteenth century. Willis recognized ten such nerves. His first six are those used today: olfactory, optic, oculomotor, trochlear, trigeminal, and abducens. His seventh cranial nerve included both the facial and auditory (VII and VIII), while his eighth combined the glossopharyngeal and vagus (IX and X) with the cranial root of the spinal accessory (XI). Willis’ ninth cranial nerve is the hypoglossal (XII), and his tenth is the modern first cervical. He described and delineaated the spinal root of the accessory (XI)nerve, not numbering it separately, but pointing out how it accompanies and then diverges from the vagus. The distribution of all cranial nerves is described in great detail.

Willis’ aim in tracing out the cranial nerves was rather more physiological than anatomical: they fitted closely into his ideas of cerebral and cerebellar localization. Most classical and Renaissance anatomists had believed that the three commonly recognized mental functions, sense, imagination, and memory, were carried out by animal sprits inhabiting the cerebrospinal fluid that filled the system of cerebral ventricles. While he accepted the action of animal spirits, Willis rejected ventricular localization on the grounds that distinctions of function could better be maintained by animal spirits acting within the solid portions of the brain.

Willis believed that voluntary functions are localized in the cerebrum. Animal spirits intended for these functions are generated in the grey cerebral cortex from the arterial blood, which continually bathed the cerebrum. These spirits pass inward into the white medullary matter, where they are differentiated and distributed into tracts for separate kinds of voluntary action. Those concerned with sense are localized in the corpora striata, those with imagination (intelligence) in the corpus callosum, and those with memory distribute back outward into the cerebral cortex.

According to Willis, sense impressions are carried inward to the corpora striata, where an inward perception arises, If the impression is carried farther on to the corpus callosum, then imagination results. If the fluctuation of spirits are struck back out to the cortex, memory of the event or idea is created. If impressions are reflected back out to the voluntary muscles directly from the corpora striate, then a “reflex” action could occur without conscious volition-a concept of the reflex considerably more sophisticated than that which Descartes had propounded few years earlier.

In performing these functions the spirits transmit their information as successive wave fronts along predetermined medullary tracts. And just as ripples from several sources in a pond can cross unchanged, so also can the same tracts carry both sensory (afferent) and motor (efferent) impulses.

Involuntary functions are carried out in an analogous way by the cerebellum and its attendant structures, the corpora quadrigemina and the medulla oblongata. Spirits for these functions are generated from the blood in the cerebellar cortex,then flow into the underlying medullary structures, where they interact to regulate heartbeat, respiration, and digestion. Therefore it is proper that four paris of cranial nerves (modern V – X) which have involuntary functions should have their origins near the cerebellum.

These involuntary actions are performed especially by what Willis called the “intercostal” and “vagal” nerves–respectively the modern sympathetic and parasympathetic divisions of the autonomic nervous system. The former Willis believed to have an intracranial origin, arising indirectly from the V and VI nerves, while the latter come directly from the vagus (X). He traced in great detail how these two systems,and their attendant spinal ganglia, innervate all the major organs of the thorax and abdomen. By this pathway the cerebellum and medulla could effect the regulation of involuntary functions and, in turn, the states of the viscera could affect the higher conscious functions of the central cerebrum and the higher brain stem.

Good follower of Harvey that he was, Willis did not neglect to trace how all these structures are bathed and nourished by the circulating blood. In preparing the book, Lower wrote in a letter to Boyle (4 June 1663), Willis had been especially struck by a postmortem in which a man dying of an unrelated disease exhibited a completely occluded right carotid artery. Yet blood continued to flow to both cerebral hemispheres, and the patient had complained only of a headache on the left side, where the carotid artery had been enlarged by the increased blood flow. To account for this, Willis traced out the circle of anastomosed arteries at the base of the brain by which, if any carotid or vertebral arteries were blocked, the remaining ones could maintain full blood flow to all parts of the brain. Willis and Lower confirmed this by tying both carotids in a spaniel, to no ill effect. They further demonstrated it by using a technique of injection developed in Oxford a few years earlier by Wren and Boyle; they syringed ink into one artery, and observed it flowing out from the others. The “circle of Willis,” as it has since been known, is clearly delineated in the Wren drawings in the Cerebri anatome. Although an anatomical description of the circle had been published by Wepfer in 1658, Willis was the first to grasp and demonstrate its physiological and pathological significance.

Many of Willis’ deepest insights derived from an unparalleled knowledge of the comparative anatomy of the nervous system. In writing Cerebri anatome he drew conclusions from dissections of fish, birds, and more than a dozen different mammals. From these he suggested that the convolutional complexity of the human cerebral cortex is correlated with man’s greater intelligence. He observed that the cerebellum has a uniformity of appearance in mammals that accords well with its function as a source of animal spirits for involuntary actions. He rejected the Cartesian suggestion that the pineal gland is the seat of the soul because he saw its presence not just in man, but also in other quadrupeds, birds, and fish.

The Cerebri anatome, and to a lesser degree the Diatribae duae, established the lines of research with which Willis occupied the remainder of his scientific life. The action of the nervous system and the composition and function of the blood were his two primary foci. He explored anatomical structures (usually with the assistance of a junior collaborator such as Lower, or his successors Edmund King and John Masters), postulated a series of conclusions about their functions, deduced from them his explanations of malfunction in the course of disease, and illustrated his conclusions with case histories and postmortems.

Before leaving Oxford in late 1667 to set up a large and lucrative practice in London. Willis brought out his Pathologiae cerebri et nerrosi generis Specimen, the clinical study that he had promised as a companion volume to the Cerebri anatome. He based his analysis of convulsive diseases upon the belief that muscle contraction results from the explosive mixing of two types of particles : saline-spirituous particles from the nerves, and nitrosulfurous particles from arterial blood. When spirits of too heterogeneous a nature are supplied by the nervous system, the muscle contraction is too powerful and uncontrolled, thus causing convulsive symptoms. Thus, he argued, epilepsy originates in the central cerebrum, not in the meninges. Or too few particles could be supplied by the nerves, resulting in weak contractions, a condition he illustrated with the first clinical description of myasthenia gravis. Convulsive coughs and asthma, hysterical and hypochondriacal disorders, even scurvy, he saw as nervous afflictions.

In 1670 he published another set of tracts elaborating his earlier ideas on metabolic heat and muscular contraction. He accepted Lower’s contention, advanced in the Tractatas de corde (1669), that the heart is merely a muscle and does not have an innate ferment. Therefore, the body’s heat must come from an “accension” or fermentative process lodged in the blood itself. This process demands both a sulfurous fuel, derived from food, and nitrous particles derived from the air. It is exactly analogous to inorganic combustion. Here Willis was both elaborating his and Bathurst’s earlier ideas on the metabolic function of air, and adding to them ideas about aerial “nitrous particles” published by his Oxford confreres Boyle, Hooke, Lower, and John Mayow, during the 1660’s.

These same themes, joined to other also adumbrated in the Cerebri anatome, were the core of his anatomical and clinical study De anima brutorum, published in 1672. Man, he said, has two souls: a corporeal, mortal soul which he shares with animals, and a rational, immortal one which is uniquely human. The Corporeal, or “brutish,” soul consists of two parts: one lodged in the blood is responsible for vital function, the other located in the nervous system is responsible for functions of action and sensation. The vital soul in the blood performs nourishment by taking up and distributing food particles, and produces heat and vitality by “burning” some of these with the nitrous particles derived from the air. In explaining the functions of the sensitive soul, he recapitulated many of the neurophysiological concepts first introduced in Cerebri anatome, especially those of localization, and extended these to invertebrates with some of the first detailed dissections of the earthworm, oyster, and lobster, He traced in detail how vibratory impressions from the five senses are transmitted through the plenum of animal spirits which inhabit the nervous system, and how these impulses are interpreted, processed, and stored in specialized parts of the cerebrum and medulla oblongata.

As in previous books, Willis was not satisfied with anatomical investigation and speculative interpretation. He goes on to argue, with the aid of extensive case histories and numerous postmortems, how a broad range of disorders are due to derangement of the neural portion of the corporeal soul. Sleeping and waking, headache, lethargy, narcolepsy, coma, nightmare, vertigo, apoplexy, delirium, frenzy, and paralysis-all are of neurological, rather than supernatural or humoral, origins.

Willis’last work, the Pharmaceutice rationalis, was cast from the same mold. In its two parts, brought out in 1674 and 1675, he summarized the anatomy and physiology of the thoracic and abdominal organs, hypothesized mechanisms of their pathology, and filled pages with case histories, therapies, and postmortems. Many observations testify to his acute clinical judgment. He discovered the superficial lymphatics of the lungs, distinguished acute tuberculosis from the chronic fibroid type, and gave the first clinical and pathological account of emphysema. He described extrasystoles of the heart, aortic stenosis, heart failure in chronic bronchitis, and emboli lodging in the pulmonary artery. He was the first European to note the sweet taste of the urine in diabetes mellitus, and described the pains and weakness of diabetic poluyneritis. He made original observations on the muscle layers of the stomach wall, and devised the use of a whalebone probang to treat achalasia of the cardia.

Unfortunately, Willis was scarcely able to enjoy the acclaim that greeted his later works. Tending a busy London practice, he was unable–and perhaps disinclined–to participate in the activities of the Royal Society and the Royal College of Physicians. His personal life was touched with tregedy: six of his eight children died before adolescence: his first wife, the sister of John Fell, dean of Christ Church, died in 1670 : and both of his brothers predeceased him. Willis died of pneumonia on I I November 1675, and was buried in the north transept of Westminster Abbey. He was survived by his second wife.

Willis has often been castigated for the unremittingly speculative nature of much of his writings, but that is to judge him by the scientific taste of the present century. He saw himself as a physician whose lasting contribution would be to formulate a series of corpuscular explanations that would link anatomical fact with clinical practice. A number of these hypotheses were, even if incorrect, extremely fruitful. His notion of animal heat arising from a fermentation in the blood, fed by a nitrous aerial agent, was elaborated by Mayow into a concept of respiration and metabolism that foreshadowed Lavoisier’s discovery of oxygen a century later. Willis’ ideas of cerebral localization were the impetus for a line of experimental work traceable into the early nineteenth century. His notion of the corporeal soul in the nervous system, and the disorders to which it was prone, was both a contribution to comparative psychology and the beginning of modern concepts of neurology. His speculations on the involuntary functions of the “intercostal” and “vagal” nerves provided the foundation of our knowledge of the autonomic nervous system. Yet if these ideas were more subject to correction than his easily verifiable conclusions on cerebral and cerebellar structure, cerebral circulation, and the cranial. nerves, they were no less important a part of his oeuvre. Willis accomplished much, not in spite of his penchant for speculation, but because of it. He attempted, with an energy and insight unsurpassed in the seventeenth century, to construct a medical system that encompassed not only his own anatomical discoveries and acute clinical observations, but set them within the emerging Harveian physiology and the new corpuscular natural philosophy.

BIBLIOGRAPHY

I. Original Works. Willis’ clinical notebook (ca. 1651) in MS 799’^ais MS 799’ in the Wellcome Medical Historical Library, London. Diatribac dune inedico-philosophicae, quarun : prior agit c/c fer,ne ntatione . . . altera de f e hribus (London, 1659) had a 2nd ed., with additions, in 1662. Locke’s extracts from Lower’s transcript of Willis’ lectures are in the Bodleian Library, Oxford, MS Locke f. 19. pp. 1–82, passim. Cerebri anatomy : cui accessit nerrorun descriptio et uses (London, 1664) was published that year first in a quarto and then in an octavo ed. : a t rans. i s available in modern facs. (Montreal, 1964). Pathologiae cerebri, et nervosi generic specimen (Oxford, 1667) contains a frontispiece portrait of Willis, aetatis suae 45, drawn by Loggan. The two tracts De sanguinis accensione and De mote nucsculari were published with Affectionum quae dicuntur hystericae & hypochondriacae pathologic spasmodica s’indicata (London, 1670). De anima brutorum (Oxford, 1672) is available in a facs. of a 17th-century trans. Pharmaceutice rationalis was published in two pts. : I (Oxford, 1674), II (Oxford, 1675), II (Oxford, 1675), published posthumously. Willis” Opera omnia was published immediately after his death (Geneva, 1676) and reprinted several times in the succeeding decades. These often contain tract De ratione motus muscularum which was misattributed to Willis; it was published anonymously by William Croone (London, 1664), All of Willis’ works, with the exception of Affectionum, were translated by Samuel Prodage and published in one volume as Practice of Physick (London, 1684).

II. Secondary Literature. Hansruedi Isler, Thomas Willis, 1621–1675: Doctor and Scientist (New York, 1968), is the only full-length historical treatment of Willis. Audrey B. Davis, Circulation Physiology and Medical Chemistry in England 1650–1680 (Lawrence, Kans., 1973), sheds much light on Willis’ chemical ideas. The fundamental study by Alfred Meyer and Raymond Hierons, “On Thomas Willis’ Concept of Neurophysiology,” in Medical History,9 (1965), 1 – 15, 142 – 155, has an extensive bibliography which provides the best entree into the literature on specialized topics of Willis’ life and work.

Robert G. Frank, Jr.