The life and work of William Harvey Kenneth D. Keele This year marks the four hundredth anniversary of the birth of William Harvey, discoverer of the circulation of the blood. His enunciation of this in his elegant De Motu Cordis et Sanguinis in Animalibus (1628) is of interest because it appeals not merely to anatomical and clinical observation but to quantitative methods. Although this is the work for which Harvey is best remembered he also did important work on the formation of the embryo and expounded the theory of epigenesis. William Harvey was the eldest son of a Kentish farmer, Thomas Harvey. Born on 1st April 1578, Wiiam was the oldest of seven brothers, five of whom eventually became Turkey merchants. Two of these, Eliab and Daniel, played so important a supportive role to William throughout his life that, with their father Thomas, they constituted a veritable Harveian team. William Harvey received his early education in Folkestone. In the autumn of 1588 he entered the King’s School, Canterbury. Here, in the oldest school in England, founded by St Augsutine, he was well grounded in Latin and Greek prose and verse. Enjoyment of the Latin writers, particuhuly Virgil and Cicero, remained with him for the rest of his life. In 1593, at the age of sixteen, he entered Gonville and Caius College, Cambridge. Soon after he was awarded a Matthew Parker scholarship in medicine. He obtained his BA degree in 1597, at& which date he was repeatedly absent because of illness. By 1600 Harvey was in Padua. Here signs of the calibre both of his intellect and character became evident, for in this same year he was elected by his fellow students as Councillor of the English Nation, a position which in a ‘student’ university like Padua meant that he played an executive role in the selection of teachers as well as in student organisation. Academically, his career at Padua was promising, not only as regards his rapid graduation as a doctor of medicine in 1602, but also in the life-long stimulus for research that he received from Fabricius of Aquapendente, his teacher in anatomy. For it was from Fabricius’s thorough work on the formation of the foetus and the development of the chick in the egg that Harvey’s lifelong researches on generation stemmed. Moreover, Fabricius was the first to make a clear, systematic investigation of the valves of the veins accompanied by accurate illustrations. This gave Harvey his Brst ideas on the possible circulatory nature of the movement of the blood. Back in London in 1602, Harvey set about creating for himself a career in medicine. Having obtained recognition as a Candidate of the College of Physicians in London, he married Elizabeth Browne, daughter of Lancelot Browne, physician to Queen Elizabeth, and settled in Ludgate. In 1605 Thomas Harvey, William’s father, following the death of his wife, Joan, came to live in London in order to be close to all his five sons now living in that city (figure 1). Here he acted as treasurer to the Harvey family, an outstanding feature of which was the mutual devotion they bestowed on one another. Eliab and Daniel, for example, as they prospered and acquired property out of town, allotted rooms in all their houses for the accommodation of William when he so required. Eliab in particular took on the responsibility of handling William’s financial affairs. The whole Harvey family were well aware of the practical advantages of combined action in attacking life’s problems. One of the strongest reasons why William Harvey attracted so much trust and confidence throughout his life was that he constantly endeavoured to extend this principle beyond his own family circle to friends, colleagues, and his own countrymen. Harvey’s career in London went from strength to strength. Kenneth
Has long had an interest in the history of medicine and is +? Past President of the Section of the History of Medicine of the Royal Society of Medicine. He was Visiting Professor in the History of Medicine, Yale University (1958); Visiting Professor to the Brain Research Institute (University of California, Los Angeles (1966): and Fitzpatrick Lecturer, Royal College of Physicians (196&61). 104
Within a decade he was appointed Physician to St Bartholomew’s Hospital and Fellow of the College of Physicians; in 16 18 he was appointed Physician Extraordinary to James I. His attachment to the Court became closer when Charles I succeeded his father, for Charles made available to Harvey the deer in Windsor Forest and Hampton Court for his experimental work on generation. Harvey’s successful progress in the College of Physicians was signalled by his election as Censor in 16 13 and Lumleian Lecturer in 16 16. It was when he was demonstrating the anatomy of the thorax that Harvey first described his views on the circulation of the blood to his fellow physicians. The Lumleian Lectures were designed to cover the subject of human anatomy and physiology in a series of six annual lectures. For these Harvey prepared a set of notes caged the Prefectiones, which by good fortune have come down to us. Since they contain entries made over a period of years, they provide invaluable evidence of the growth of Harvey’s thoughts on the two aspects of biology which interested him most, generation and the movement of the heart and blood. In 1628 Harvey published his famous De Motu Cordis et Sanguinis in Animalibus. Having been appointed Physician-in-Ordinary to Charles I, Harvey accompanied him to Scotland in 1633 for his Scottish coronation; and in 1636, as physician to the Earl of Arundel, Harvey set out to travel to Prague and Rome. It was at Altdorfon this journey that Harvey attempted, unsuccessfully, to convince the greatly respected anatomist, Caspar Hofman, of the circulation of the blood. Three years later Harvey was appointed Senior Physician-inOrdinary to the King at a salary of f400 a year with lodgings in Whitehall. When the Kine raised his standard at Nottinaham at the start of the Civil War-in 1642 William Harvey was \;ith him and remained a loyal Royalist throughout. About this time Harvey records that ‘certain rapacious hands not only stripped my house (in Whitehall) of all its furniture, but what is subject of far greater regret to me, my enemies abstracted from my museum the fruits of many years of toil’ Ill. Thus were lost many of his dissections of animals and an unknown quantity of clinical and pathological memoranda. Aubrey reports how Harvey told him that ‘no grief was so crucifying to him as the loss of these papers’. From 1642 to 1646 Harvey pursued his medical and scientific interests in the city of Oxford which during these years was the headquarters of King Charles. After the King surrendered himself to the Scats in 1646 Harvey returned to London and lived with his brother Eliab in St Laurance Poultney, and at Daniel’s house at Coombe in Surrey. In 1650 Sir George Ent visited Harvey in order to obtain from him the manuscript of De Generatione Animalium. published in 165 I. With the execution of King Charles in 1649, Harvey lost the focus of his loyal affection. He now directed his allegiance towards the College of Physicians in Amen Court, which during the Civil War had fallen into a parlous state. Always practical in his demonstrations of affection, Harvey in 165 1 offered to build for the College a new library and museum. Both were completed in 1654, but unhappily, the whole College was destroyed in the Great Fire of 1666. It is not surprising that in 1654 Harvey was offered the Presidency of the College. However, this he did not feel well enough to accept. In 1656 Harvey resigned the Lumleian Lectureship. In the following year, 1657, while staying at his brother Eliab’s house, he died of a cerebral haemorrhage. His body was not buried in
Westminster Abbey, as many felt it should have been, but at Hempstead in Essex where Eliab in 1655 had built a Harvey Chapel. There his body still remains. Harvey’s
Harvey’s three main works, the Preiectiones, De Motu Cordis, and De Generatione, are so interwoven that they may usefully be considered as a trilogy describing three aspects of his creative scientific life. Though these three works are very different in both substanceand form, each contributes vitally to understanding the outlook of the greatestphysiologist England has ever produced.
development. Once the body is formed, the heart is the organ which distributes the blood, which contains all the essential ingredients for preserving the organs of the body. Thus the integration of the two themesof generation and movement of the blood, in Harvey’s mind, are woven into the Prelectiones. De Motu Cordis was undeniably Harvey’s greatest scientific masterpiece.The arrangement of this little book of 72 pages is beautifully logical. In the introduction Harvey shows his appreciation of the work of his predecessors in the field, summarizing their work critically but not maliciously. Harvey’s suppressed excitement over his discovery flashes out when, describing Galen’s assertion that blood oozes through pores in the cardiac septum, he exclaims, ‘But, damme,there are no pores and it is not possibleto show such’l31.
Figure 1 This portrait of William Harvey, aged about 43, wasone of a set of seven oval portraits surrounding a large painting of Thomas Harvey, at Rolls Park. Thus the father, Thomas, was appropriately surrounded by his seven sons. This portrait is now in the National Portrait Gallery.
The paramount interest of the Prelecfiones lies in its revelation of the germinating seedsof Harvey’s thoughts on medicine as a whole, and on the two great problems within that province that interested him throughout his life, the movement of the heart and blood, and the generation of animals. The Prelectiones were compiled at intervals during the years 1615 to 1628. One can see in them Harvey’s early great reliance on Galen’s theory and practice of medicine, and his later growing criticisms of this respected authority.
From Harvey’s descriptions of his clinical methods and repeated post-mortem examinations (figure 2) one is brought to realise that he was a pioneer in correlating morbid anatomy with the clinical course of disease. Indeed, on several occasions Harvey mentions his intention of publishing works on Medical Observations and Medical Anatomy, but since these have never been found the Prelectiones contain the only clues we now possessas to the scopeof such works. Perhaps the most interesting of these lecture-notes are those that show Harvey building up the concepts of his two great finished pieces on the movement of the heart and blood, and on generation. It is surprising to find him here so early presenting clear pen-sketchesof both of theseworks. Here too, one seesthat they both sprang from Harvey’s basic theme that the blood is the primary part of the body from which the heart, blood vessels,and all the other organs are formed during its generation and
Figure 2 Folio 3% of William Harvey’s PrelectionesAnatomiae Universalis. On this page Harvey lists 13 post-mortem examinations of the liver. (Reproduced by permission of the British Library Board.)
Harvey presentshis whole casein seventeenshort chapters. In the first he makeshis position quite clear; he is presenting his own observations on the beating heart in animals, not through the authority of books. Straightaway he runs up against difficulties. ‘I kept finding the matter so truly hard and beset with difficulties that I all but thought, with Fracastoro, that the heart’s movement had been understood by God alone. For I could not rightly distinguish how systole and diastole came about’l41, he writes. This difficulty Harvey solved by using cold-blooded animals such as frogs, toads, and serpents,in which the heart rate is slow and more easily observed. In the second chapter he analyses the cardiac movementsinto 105
four components. (1) The heart rises and lifts its apex in such a fashion that its pulsation impinges on the chest wall at the time and can be felt outside it. (2) It appears to contract more in a transverse than in a longitudinal direction. (3) The heart becomes harder and (4) paler during systole. From thesefour observations he deduced that, ‘the movement of the heart was a sort of generalisedcontractionU1. During systole of the ventricles they decreasein volume and expel their content of blood. In the next two chapters Harvey analyses the movements of the atria and the arteries in relation to those of the ventricles, noting that the atria beat before the ventricles and that the arteries expand with ventricular systole, being blown out like ‘the fingers of a glove’ and not sucking in blood like bellows. He then describesthe heart’s movement as a whole. In the sixth chapter he deals with the pulmonary circulation, comparing the course of blood from veins to arteries in lungless animals with that in the human embryo-a fine anatomical feat. He writes, ‘The truth is as manifest in the foetus [as it is in the lungless animal], namely that the heart by its beat transfers blood from the vena cava and discharges it into the aorta’. He then goeson to show that the blood is propelled into the lungs and that in adult animals with lungs it does not passthrough the septumof the heart as it doesin the foetus or animals without lungs. In the eighth chapter Harvey considers the systemic circulation. Here he is almost overwhelmed by what he has to say. He writes, ‘But what remains to be said upon the quantity and source of the blood that passesis of so novel and unheard-of character, that I not only fear injury to myself from the envy of a few, but I tremble lest I have mankind at large for my enemies’i’l]. Finding that the amount of blood passing from the veins to the arteries was more than could possibly be derived from ingested food, he relates how, ‘I began privately to consider if it had a movement, as it were, in a circle. This hypothesis I subsequently verified.. .‘. In the ninth chapter he sets out to show how he verified this hypothesis, He makesthree fundamental postulates. If these are stated, he writes, ‘then I conceive that the truth I contend for will follow necessarily, and appear as a thing obvious to all’[91. These three postulates are (1) that the blood is continuously transmitted by the action of the heart from the vena cava to the arteries in such a quantity that cannot be supplied by the ingesta; (2) that the blood is continuously, evenly and uninterruptedly driven by the beat of the arteries into every member and part, entering each in far greater amount than is sufficient for nutrition or than the whole mass of blood could supply; (3) that the veins in like manner return the blood constantly to the heart from all parts. In demonstrating the first postulate Harvey perforce took the great step of introducing the quantitative method of measurement into animal experiment. ‘In man’, he writes, ‘let us take the amount that is extruded by the individual beats . . . as half an ounce, or three drachms, or at least one drachm. In half an hour the heart makesover a thousand beats. . . on occasion two, three, or four thousand. If you multiply the drachms per beat by the number of beatsyou will seethat in half an hour either a thousand times three drachms, or a thousand times two drachms, or five hundred ounces or other such proportionate quantity of blood has been passedthrough the heart into the arteries, that is, in all casesblood in greater amount than can be found in the whole of the body. . .’ This ‘shows that the beat of the heart is continuously driving through that organ more blood than the ingestedfood can supply’[ 101. In the tenth chapter he comparesthe amount of blood passing per unit of time with the amount of fluid ingested.He finds that the largest yield of milk from a cow is 7-8 gallons per diem. This amount passesthrough the heart in l-2 hours. Finally, in chapter eleven he enters on the well-known seriesof experiments in which he ligatures the veins and arteries of the arm. He writes, ‘Just asin a tight ligature the arteries above the ligature are distended and pulsate, but not those below . . . in a medium tight ligature the veins below the ligature swell up and are resistant, but those above behavequite differently’1 111. 106
In the thirteenth chapter he demonstrates his third postulate (figure 3) that blood flows back to the heart through the veins. He describesthe venousvalves,noting that they facethe heart and that Fabricius, though describing them in detail, did not understand their real function. After describing the venous nodes in the arm he adds, ‘But so that this truth may be more openly manifest, let the arm be ligated above the elbow in a living human subject as if for blood-letting [AA]. At intervals there will appear,especially in country folk and those with varicosis, certain so to speak nodes and swellings [B. C. D. D. E. F.l . . . thesenodes are produced by valves . . . If by milking the vein downwards . . . you try to draw blood away from the node . . . you will seethat none can follow . ..Ifyou... exert a pressuredownwards [on this node1you will seethe blood completely resistant to being forcibly driven beyond
Figure 3 These four figures are the only illustrations contained in Harvey’s De Motu Cordis. The lettering refers to the demonstration of the action of the venous valves in the arm, as described in the thirteenth chapter of the work, part of which is quoted in this article. (Bycourtesyof theWellcomeTrustee4
the valve [Ol . . .’ He assertsthat if the blood is pressedupwards with the finger M to the region above the valve ‘you will seethat part of the vein remaining empty . . . fH.01’. Finally press the blood out of the vein L N into the region abovethe valve, and now take the finger L away and let the vein fill up from below. ‘Do this quickly a thousand times. If after that you make a calculation (by multiplying by a thousand your estimate of the amount which is raised above the valve at each upward stroking of the vein) you will find that so much blood passes in a relatively short time through the one portion of the vein that I believe you will be completely convinced by the speedof the blood’s movement, of the fact that it circulates’i 121.Harvey, in this neat experiment, is again using the quantitative argument which he previously applied.
Harvey’s evidence for the circulation of the blood was almost complete, but not quite. He could not seefor himself the passage of blood from the peripheral arteries to the veins. He had no microscope. He had to postulate ‘pores’ in this postion. His ‘pores’ were revealedby Malpighi in 1661 as the capillaries. Twenty-one years after it was written Harvey published two letters to Riolan which may be looked upon as supplementsto De Motu Cordis, strengthening its weak points by bringing to bear fresh experimental evidence in favour of the circulation and briefly recapitulating the whole theme. Harvey ends these letters with the surprising assertion, ‘Before long, perhaps, I shah have occasion to lay before the world things that are more wonderful than these,and that are calculated to throw still greater light upon natural philosophy. Meanwhile I shah only say . . . that the heart with the veins and arteries and blood they contain, is to be regarded as the beginning and author, the fountain and the original of ah things in the body’[ 131. It may seem surprising to us today to reahse that Harvey himself looked upon his concept of the Generation of Animals as ‘more wonderful’ than his concept ofthe Circulation of the Blood. That he did so is repeatedly stated in the fifty-first to fifty-seventh Exercisesof De Generatione, where one meetssuch assertionsas, ‘Emboldened by what I have observed both in studying the egg and whilst engagedin the dissection of living animals, I maintain against Aristotle that the blood is the prime part that is engendered, and the heart the mere organ destined for its circulation. Blood lives, and the whole body is derived from it. . . The admirable circulation of the blood, originally discovered by me, I have lived to see admitted by almost all . . . wherefore I imagine that I shah perform a task not less new and useful than agreeable to philosphers and medical men if I briefly here discourse of the causes and uses of the circulation’. To understand Harvey, therefore, it is essentialto follow him into his studieson generation. Though a number of anatomists had worked on the subject of the generation of animals since Aristotle wrote his great work on the subject, they had not surpassed his achievement in any essential feature. Indeed, Fabricius of Aquapendente, Harvey’s teacher, had unhappily imposed a number of errors on to Aristotle’s account of the development of the chick in the egg. Harvey divides his own study on the generation of animals into three parts: (1) the order of the development of the parts of the embryo; (2) the primary matter of origin and the efficient causeof generation; (3) the developmentofthe soul in man and animals. The first part was a scientific problem involving observation and experiment, to which Harvey made important contributions both in identifying the part of the egg in which the embryo develops, and in establishing the macroscopic sequential order of organ development-epigenesis. The secondtheme was in the 17th century beyond the reach of the macroscopic methods of observation used by Harvey. It became for him, therefore, hugely a philosophical problem. However, Harvey’s approach to it shows remarkable insights, among which his comparison of conception and contagion is full of interest. However, philosophical speculation dominates the discussion and Harvey concludes with a deist solution to his problem. It is Harvey, the deist, who concludes that, ‘there is not lessof skill and presciencemanifested in the structure of the chick than in the creation of man and the universe’i 141. The third part is concerned with the origin of the soul. Harvey locates this in the blood whence all vital force emerges.From the blood with its innate heat and powers of nutrition Harvey derives the heart, blood vessels,and all the organs of the body built up with their aid. In this part of his treatise Harvey fits the movement of the heart and blood into his deeperphilosophical and religious convictions. It is apparent from the design of the book that Harvey in the De Generatione reveals himself as scientist,
philosopher, and deist. In ah these aspectshis genius is powerful enough to bridge centuries and bring him into sensitive contact with aspectsof 20th century thought. Harvey’s De Generatione Animalium did not create the furor that his De Motu Cordis produced. Nevertheless one must be careful not to underrate the importance of De Generatione Animalium. Harvey himself was particularly enthuiastic over his discovery of the cicatricular site of development of the chick embryo, for all previous workers, including Fabricius, had missed this. And how could anyone describe the early stages of the development of the chick embryo unless they knew where to look for it? His observation and description of the serial formation of organs out of undifferentiated tissuesconfirmed Aristotle’s theory of epigenesisand expandedit. Though Harvey describes the use of lenses in making his observations, there is no evidence that he used the microscope. Malpighi, by doing so in 1673 and focusing on the cicatricula, revealed the formation of the embryo in earlier stages than Harvey had seen it. Even so, Malpighi did not see the undifferentiated morula and gastrula stagesof development, but found many organs already formed. This led him to affirm the pre-formation view of embryogenesisand to deny epigenesis.Not until Caspar Wolff brought out his Theory of Generation in 1759 did epigenesisbegin to come back into its own. Wolff observed the emergenceof plant buds by growth and differentiation and this led to similar observations on the emergenceof the organs of the chick from undifferentiated tissue. Thus at last microscopic observation in the hands of Wolff came to confirm the macroscopic observations of Harvey and Aristotle. When about 1830 von Baer found the ovum itself floating in the fluid of a Graahan follicle and observedits development into the germ layers of ectoderm, mesoderm, and endoderm, the fundamental pattern of epigenesis came into view and Harvey was amply vindicated. References
[ll R. Willis, The Works of William Harvey, M.D. translatedfrom the Latin by RobertWillis, London, 1847,p. 48I. [21 A. Clark, Aubrey’s Brief Lives, editedfrom the author’sMS.%by AndrewClark,Oxford.Vol. I, p. 297. I31 K. J. Franklin, Movement of the Heart and Blood in Animals, translated from the original Latin by Kenneth Franklin, BlackwellScientificPublications,Oxford, 1957,p. 19. Ibid. p. 23. Ibid. p. 27. Ibid. p. 49. Willis, op,cit., p. 45. Franklin,op. cit., p. 58. Willis, op. cit., p. 48. Franklin,op. cit., pp.62,63. Ibid. p. 73. Ibid. pp.84-86 (abbreviatedquotation). Willis, op. cit., p. 137. Ibid. p. 368.
GeoffreyKeynes,The Life of William Harvey, Oxford, 1966. GeoffreyKeynes,The Portraiture of William Harvey, London,1949. Kenneth Keele, William Harvey, the Man, the Physician and the Scientist, LondonandEdinburgh,1965. C. D. O’Malley, F. N. L. Poynterand K. F. Russell,William Harvey: Lectures on the Whole of Anatomy. An annotatedtranslation of Prelectiones Anatomiae Universalis. LOSAngeles,1961. Gweneth Whitteridge,The Anatomical Lectures of William Harvey. Prelectiones Anatomiae Universalis. De Musculis, edited, with an introduction,translationandnotes by GwenethWhitteridge,Edinburgh andLondon, 1964.
Suios, Volunn 2, No. 3,1979 Ltd. Ptintod in Onmt Btitain)