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Articles in PresS. J Appl Physiol (April 4, 2013). doi:10.1152/japplphysiol.00216.2013
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Harvey’s epoch-making discovery of the Circulation, its historical
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antecedents, and some initial consequences on medical practice
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An Historical Perspective Article
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Ares Pasipoularides MD, PhD, FACC
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Consulting Professor of Surgery,
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Duke University School of Medicine.
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Formerly, Director of Cardiac Function,
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Duke/NSF Center for Emerging
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Cardiovascular Technologies
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Durham, N.C. 27710, USA
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828-254-0279
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[email protected]
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Address for correspondence:
12 Cogswood Rd.
Asheville, NC 28804
Copyright © 2013 by the American Physiological Society.
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Pasipoularides: Harvey’s discovery of the Circulation
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Abstract
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In Harvey’s Exercitatio Anatomica de Motu Cordis et Sanguinis in Animalibus of 1628, we see
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the mechanisms of the Circulation worked out more or less in full from the results of
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experimental demonstration, virtually complete but for the direct visual evidence of a link
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between the minute final terminations and initial branches of the arterial and venous systems,
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respectively. This would only become available when the capillaries could be seen under the
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microscope, by Malpighi. Harvey’s amazingly modern order of magnitude analysis of volumetric
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circulatory flow and appreciation of the principle of continuity (mass conservation), his adroit
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investigational uses of ligatures of varying tightness in elegant flow experiments, and his
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insightful deductions truly explain the movement of the blood in animals. His end was
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accomplished. So radical was his discovery, that early in the eighteenth century the illustrious
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Hermann Boerhaave, professor of medicine at Leyden, declared that nothing that had been
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written before Harvey was worthy of consideration any more. The conclusions of De Motu
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Cordis are unassailable and beautiful in their simplicity. Harvey’s genius and tireless
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determination have served physiology and medicine well.
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Key words
Aristotle and circular motions; Galen’s De Usu Partium; William Harvey’s De
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Motu Cordis; William Harvey’s order of magnitude analysis of volumetric
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circulatory flow; blood circulation
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All truths are easy to understand once they are discovered;
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the point is to discover them—attributed to Galileo Galilei
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THE CIRCULATION OF BLOOD and the physiologic function of the heart as a pump were
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established by the English physician-physiologist William Harvey (1578-1657) (44), who is
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considered to be the father of modern experimental physiology. Harvey studied medicine at
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Padua (now, Padova), near Venice, which at the time had the most prestigious medical
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university in Europe. It was also one of the most Aristotelian, but Paduan Aristotelianism differed
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from the genre taught elsewhere: at Padua, they taught Aristotle as a preliminary to medicine,
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not theology (44). Since the early fifteenth century, Padua had been ruled by Venice, which
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fostered freedom of thought. At Padua, Harvey was a pupil of Casserius and, most notably, of
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the great anatomist Hieronymus Fabricius of Aquapendente who, after Aristotle (60), became
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known as a “Father of Embryology" (28). Besides Harvey, the intellectual climate attracted many
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of the ablest minds of the time—among them Vesalius, Copernicus, and Galileo (7,51).
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Ancient knowledge, in nuce, about blood motions predating Harvey’s discovery
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That the blood is moved by heart contractions was known since ancient times;
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specifically since the anatomical and physiological studies of the Greek physician Aelius
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Galenus, or Claudius Galen of Pergamos (ca. 130-ca. 200), next to Hippocrates the most
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celebrated physician the world ever produced (15). He performed extensive dissections and
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vivisections on animals, as well as human dissections. At Harvey’s time, physicians in Europe
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had followed Galen’s teachings for 15 centuries. In fact, the enormous influence of Galen's
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works, encompassing all aspects of the practice and theory of medicine, extended well into the
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nineteenth century, as is demonstrated by the highly abridged English-version epitome of them,
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prepared by Coxe and published in 1846 as a teaching text (11,44,50).
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A sizeable number of Galen’s works are lost, and yet at least 122 medical treatises,
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more or less complete, survive and are in print (33); there is reason to believe that they
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constitute not more than a third or a quarter of his works. Harvey read the Latin, and not the
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original Greek text of Galen’s works. The eminent scholar Frederick Kilgour of Yale has
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concluded that Harvey found Galen's results useful to him in developing his global concept of
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the Circulation. He states that Harvey specifically refers to or discusses Galen's findings and
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views on 33 occasions (32): of these 33 references, Harvey employs 20 to support his own
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reasoning and 13 times he disagrees with Galen's findings or views.
Galen maintained that the ultimate branches of the arteries and veins communicated by
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fine tubes that he called “anastomoses,” and that anastomoses existed in both the body and the
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lungs (34,44). He believed that the two varieties of blood, dark red flowing in veins and bright
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red in arteries, originated in different organs—venous blood in the liver, and arterial blood in the
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heart, as is shown in Fig. 2. Blood was propelled inside the vessels by attraction from peripheral
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tissues needing nutrition. Carried in an ebb-and-flow to various parts of the body (consider the
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apparent ebb-and-flow in the veins of the hand, as it is raised up and lowered down), blood was
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constantly consumed by tissues, as nutrient or as matter transformed into flesh, like irrigating
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water in the fields. Thus intravascular blood was not conserved. Galen believed that the heart
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contained a distinctive muscle that was capable of exerting a “vis a fronte” (force from the front)
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capable of spreading the ventricular walls apart, after each systole (44). Interestingly, Harvey
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introduced the concept of a “vis a tergo” (the force from behind, carried out by the blood
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expelled from the left ventricle).
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Galen, the astute observer that he was, must have watched routinely the apparent ebb-
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and-flow in the veins of the limbs, as they are raised up and lowered down, or with transition
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from supine to upright posture and vice-versa, or from prolonged relaxed standing to walking
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with activation of the “muscle-pump,” assuming normal venous valves. Indeed, it can become a
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veritable ebb-and-flood in many common (then and now) disease states; they include varicose
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veins of varying severity, pronounced tricuspid valvular incompetence or stenosis, right sided
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heart failure, pericardial disease and constrictive pericarditis limiting diastolic right ventricular
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compliance, pleural effusion, emphysema, increased intraabdominal pressure, etc. However, he
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misconstrued it as intravascular blood sloshing back and forth—an efflux and reflux of blood to
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and fro, between the centrally placed heart and liver and the periphery. The composite picture
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reproduced in present-day textbooks, which encompasses Figura 1 – Figura 4 of Chapter XIII of
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De Motu Cordis (25,26) depicting Harvey's demonstration of the unidirectionality of venous
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blood flow in the forearm, is the one that revoked this sloshing concept.
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Harvey rightly receives credit for ending an era of ignorance of blood circulation and of
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controversy that had lasted for many centuries. It is, however, notable that in his works on the
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heart and the circulation of blood, Galen's name or the attribution “the Divine Galen, father of
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physicians” are encountered numerous times (5,44,70). Galen considered that physiology and
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anatomy formed the critical bases of medical practice and he wrote extensively on both
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subjects. Harvey often refers to Galen as though he were a contemporary. In a sense he was,
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for as an experimental biologist Galen had advanced to positions from which Harvey was the
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first to push on further. Yet the relation between visionary thinkers and the giants they
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supersede is frequently characterized not just by sharp discontinuities, but also by underlying
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connections.
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Thus, although Copernicus and Newton overturned Ptolemaic astronomy and Cartesian
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mechanics, respectively, they owed their precursors significant conceptual and methodological
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acknowledgments. Harvey's relation to Galen reflects a similar pattern; specifically, what seems
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like analogical reasoning inspired by the Galenic tradition underlies several of Harvey's
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arguments about the Circulation. Indeed, Michael Shank of Harvard has identified in Galen's
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discussion of the urinary system, in Book I of On the Natural Faculties, elements that exhibit a
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striking resemblance to several of Harvey's arguments in De Motu Cordis (57). These include
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(see below): Harvey's case against foramina or pores in the septum of the heart, his
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experimental method with its heavy reliance on vivisection, his momentous argument for
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circulation based on quantitative reckoning, and his understanding of the role of the valves in
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the veins. Harvey indubitably had a foothold on Galen's shoulder.
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Some notable scientific forerunners of Harvey
Isaac Newton aptly noted in a letter to his rival Robert Hooke, in 1676: "If I have seen a
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little further, it is by standing on the shoulders of Giants" (44). Even when interrupted by the
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remarkable insights of a genius like William Harvey, the advancement of scientific knowledge is
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a continuum, each step or stride forward always contingent on others that preceded it, as the
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great philosopher Émile Littré has put it (35). Nonetheless, to Harvey it fell, as the Renaissance
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drew to an end, through quantitative thinking with quasi-modern order of magnitude analysis
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and exhaustive experimental work, to conceive, demonstrate, and explain the circulation of the
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blood. By doing so, he took a decisive stride toward a modern physiology.
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Descartes
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Harvey was a contemporary of René Descartes (1596-1650), one of the greatest
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intellects in the history of mankind and the protagonist of the biomedical concept of function,
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which he related to the conceptual metaphor of living organisms as machines that are
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assembled from separate parts (44). The functions of the parts could be reduced to mechanical
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operations, suggesting that organisms were simply automata, akin to the hydraulic-powered
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mechanical statues (or “automata”) that could be found in European royal gardens, which would
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move, assume different poses, and even sing. Descartes said: “I do not recognize any
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difference between machines made by craftsmen and the various bodies that nature alone
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composes” (8). His book De Homine (On Man), published posthumously in 1662, took a
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thoroughly mechanistic view of the human body, based as it was upon his concept of “l'homme
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machine,” the human machine; the representation of the body as a machine still influences
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modern thought. De Homine is arguably the first modern European book on physiology.
Descartes' great legacy to medical science was his philosophical skepticism which
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drives much scientific experimentation. The great triumph of seventeenth-century physiology
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came when Harvey applied this skepticism and the Cartesian mechanistic template to the
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phenomenon of blood circulation and solved what had, since ancient times, been the most
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fundamental and challenging problem in physiology (44). Descartes read De Motu Cordis and in
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his Discours de la Méthode (1637) he gave prominence to Harvey’s discovery, stating
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forthrightly that his own anatomical work had led him too to the conclusion that the blood does
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indeed circulate around the body. He states (12) that Harvey “has the honour of having broken
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the ice on this subject, and of having been the first to teach that there are many small passages
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at the extremities of the arteries, through which the blood received by them from the heart
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passes into the small branches of the veins, whence it again returns to the heart; so that its
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course amounts precisely to a perpetual circulation.”
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Paradoxically, although Descartes expressed flattering remarks about “Heruaeus,” as he
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Franco-Latinized Harvey’s name (13), he also held antagonistic views (48,64) toward some
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portions of De Motu Cordis relating to the functioning of the heart, which seem to have
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emanated from misconceptions that he developed while writing the Discourse on the Method. In
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the latter, he erroneously ascribed the motion of the blood, not to the contraction of the walls of
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the heart, but to the “heat which may be felt with the fingers” (12) and which he infers to be
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generated there. His view was that the heart was able to circulate blood because it could heat
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and so expand the blood that entered it; the visible change in the color of the blood is,
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Descartes assumed, evidence of this expansion.
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Aristotle and Jacopo Zabarella
I believe that Harvey’s own approach to the study of the circulation of blood must have
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been influenced also by the work of Jacopo Zabarella (1533-1589), renowned professor at the
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University of Padua (54), who had died 10 years prior to Harvey’s entrance to the medical
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program. Zabarella was a keen student of Aristotle (384-322 BCE) and his methods (37,49). In
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his treatise De Methodis (On Method) of 1578, Zabarella distinguishes two different methods of
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discovery in which a physician can become acquainted with the parts of the human body
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(38,41). Firstly, he may learn them through empirical knowledge and anatomical observations,
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thus assimilating the matter of his discipline without understanding its rationale. This
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corresponds to the demonstrative method of science, as Aristotle had conceived it. Secondly,
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he can also become familiar with the parts of human body through “philosophy of nature,” where
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he may understand the reasons, which lie behind what he actually observes. This corresponds
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to the analytic or resolutive method of Aristotle, which proceeds from the whole resolving it into
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parts or from the end-effect resolving it into the causes producing it.
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Zabarella deemed that Aristotle made the same distinction in his books the History of
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Animals, in which he relies on sense perception to classify the different parts of animals, and the
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Parts of Animals, in which he offers causal explanations for the observed anatomy. In De Rebus
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Naturalibus (71), Zabarella points out that medicine adopts its physiological component from the
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philosophy of nature. If physicians want to know the anatomy of the human body, they must
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therefore follow Aristotle methodologically. Consequently, they should not study just the History
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of Animals, but in addition the Parts of Animals, which reveals the functions of different parts of
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the body by applying analytical methodology. As Zabarella understood further, in medical
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practice the resolutive method can proceed from knowledge to cure (38).
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Although he is celebrated as a scientific revolutionary, in the genre of Galileo, Harvey
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was a devoted Aristotelian who saw an underlying unity between various circular motions in the
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Pasipoularides: Harvey’s discovery of the Circulation
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universe—the planets in the heavens, air and rain in the sky, blood inside animal bodies—see
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Fig. 1. Indeed, he was a life-long theorizer on the purpose and the enigma of circular
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phenomena: the circulation of the blood (De Motu Cordis) and the cycle of generation
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(Exercitationes de Generatione Animalium, see later), both forming the microscopic copy of a
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cosmological pattern. As he put it metaphorically, the heart “deserves to be styled the starting
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point of life and the sun of our microcosm just as much as the sun deserves to be styled the
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heart of the world” (26,44). In some ways, Harvey was not a radical reformer but a traditionalist
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who maintained many Aristotelian ideas and he remained till the end of his momentous life a
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staunch Peripatetic. According to the 17th century natural philosopher and diarist-biographer
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John Aubrey, Harvey “bid me goe to the fountain head and read Aristotle... and did call the
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neoteriques [upstart (“modern”) philosophers] shitt-breeches” (3,20,44).
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Erasistratus and Galen
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Erasistratus (304-250 BCE) was a Greek anatomist and physician who around the year
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300 BCE made a great discovery, that of the valves of the heart (14,17). Around the opening by
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which the venae cavae and right auricle communicate with the right ventricle, he found three
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membranous folds (tricuspid valve), disposed in such a manner as to allow any fluid coming
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from the veins to pass into the ventricle, but not to go backward. The opening of the vena
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arteriosa (pulmonary artery) into the right ventricle is quite different from the tricuspid valve, as
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Erasistratus observed; it is provided with three pouch-like, ∑-shaped (sigmoidal, or semilunar)
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valves the arrangement of which is such that a fluid can pass out of the right ventricle into the
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vena arteriosa, but not back again. He found a similar sigmoidal valve at the origin of the arteria
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aorta from the left ventricle. The arteria venosa (pulmonary vein[s]) and left auricle had a
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distinct opening into the left ventricle, and this was provided with triangular membranous valves,
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akin to those on the right side but only two in number. Thus the two ventricles had four
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openings, two each; and there were altogether eleven valve leaflets, arranged in such a manner
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as to permit fluids to only enter the ventricles from the auricles, and to only pass out of the
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ventricles by the vena arteriosa and the aorta, but not to go the other way. He also concluded
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that the heart functioned as a pump.
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Thus, Erasistratus implicitly laid the foundations of the theory of the motion of the blood.
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Unfortunately, all his works are lost; they were probably destroyed when the Great Library of
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Alexandria was burned down by the fanatic mob. We have, therefore, only indirect accounts of
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his work through the fragmentary references to him in the works of his successors (31),
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primarily Galen.
Galen's theory of the motions of the blood in the heart and lungs may be synopsized as
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follows (see Fig. 2), based on a remarkable passage (27) at the end of the tenth chapter of the
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sixth book of his ΠΕΡΙ ΧΡΕΙΑΣ ΜΟΡΙΩΝ (De Usu Partium) [Harvey too gives extensive
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discussion to Galen’s text, in Chapter VII of De Motu Cordis (25)]: Οn entering the right
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ventricle, blood must pass by a one-way valve opening inward, so that only an insignificant
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portion can regress into the vena cava from which it is discharged. Some of the blood passes
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directly from right to left ventricle through “foramina” or “pores” in the interventricular septum.
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But much, and apparently most, of the blood moves into the vena arteriosa (pulmonary artery)
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through a one-way semilunar valve that opens outward from the right ventricle. On contraction
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of the thorax, the blood in the vena arteriosa, having its backflow cut off from behind by the
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semilunar valve, can only flow forward into the arterial system of the lungs (in modern usage,
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venous). Whether Galen's arteria venosa (pulmonary vein[s]) then carries blood to the left
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ventricle is in question. He almost certainly thought of the arteria venosa as conveying the
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inspired air, or at least some quality derived from it, from the lungs to the left ventricle. In the
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opposite direction smoky wastes were borne from the left ventricle to the lungs via the arteria
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venosa; this process was made possible by the comparative insufficiency (a remarkable
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functional attribute) of the mitral valve opening into the left ventricle.
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Yet one other essential point about the views of Galen: he was among the first to
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recognize the heart as a pump. He thought that both the contractions and the dilatations of the
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heart—what we call systole and diastole—were equally active movements. The heart actively
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dilated, so that it had a kind of sucking action (the above-mentioned “vis a fronte”) upon the
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fluids which had access to it, a strikingly modern conception (6,43-46,61). The blood in the left
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ventricle passed into the aorta through an orifice guarded by a one-way semilunar valve
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opening outward. With respect to the arterial pulse, Galen was of the opinion that the walls of
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the arteries partook of that which he reasoned to be the nature of the heart walls, and that they
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had the power of alternately actively contracting and actively dilating (44).
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To the vexing question, why the teachings of Galen have come to be misunderstood by
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scholars of great distinction, no definitive answer can be given. However, substantially correct
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accounts of Galen's dogmata have been provided by several authors and essayists, including
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William Harvey himself (25,32,47,52,53,69). He states [p. 51 in Chap VII in the Keynes
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Translation (25)]: “But seeing there are some such persons which admit of nothing, unless there
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be an authority alleged for it, let them know, that the very same truth may be proved from
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Galen's own words, that is to say, not only that the blood may be transfused out of the vena
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arteriosa, into the arteria venosa, and thence into the left ventricle of the heart, and afterwards
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transmitted into the arteries, but also that this is done by a continued pulse of the heart, and
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motion of the lungs, whilst we breath. There are in the orifice of the vena arteriosa three shuts,
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or doors, made like a ∑ or half-Moon (sigmoidal or semilunar), which altogether hinder the blood
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sent into the vena arteriosa to return to the heart, which all know.”
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Ibn al-Nafis
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Guesses about a pulmonary passageway for blood had been voiced in the Proto-
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Renaissance by the Arab physician Ibn al-Nafis (1213–1288) of Damascus, who understood
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that all the blood that reached the left ventricle had passed through the lungs (65). Andrea
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Alpago, an Italian physician who had lived in the Islamic Orient before moving to Padova, made
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a Latin translation of Ibn al-Nafis’ work that was published in 1547 (1,40). Al-Nafis observed that
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the wall of the interventricular septum is not porous, as was believed by all scholars and
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physicians adhering to Galen’s works. Blood was channeled from the right heart via the
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pulmonary artery to the lungs, to be “mixed with air,” and emptied back to the left side of the
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heart through the pulmonary veins. Whether he had known or not of Galen’s words regarding
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the passage of blood through the lungs (cf. above) has not been ascertained. He also stated
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that there must be small communications or pores between the pulmonary artery and vein, an
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expectation which could be interpreted as a reference to capillary vessels that preceded by
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about 400 years their discovery by Marcello Malpighi (65,68) and also followed Galen’s
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analogous inference by about 11 centuries (34,44).
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Interestingly, Professor Wilson of Yale has concluded (69) that the three different
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individuals that are generally said to have discovered the pulmonary circuit of the blood, Ibn al-
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Nafis, Miguel Servetus, and Realdo Colombo, made their discoveries almost certainly
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independently of one another. However (69), all three seem to have begun their reasoning from
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the same literary source: the particular passage at the end of the tenth chapter of the sixth book
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of Galen's De Usu Partium, where Galen shows (see earlier discussion) that blood which has
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passed into the pulmonary artery from the right ventricle of the heart must pass through the
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anastomoses between arteries and veins into the pulmonary vein(s) when the lungs shrink in
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expiration.
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Miguel Servetus and Realdo Colombo
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The topic of the pulmonary circulation was tackled again three centuries later by the
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Spanish theologian and physician Miguel Servetus (1511-1553), the guiding life force, though
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not an actual founder, of the Unitarian Church (22), and the Italian physicians Colombo and
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Cesalpino. In that time of fanaticism, Servetus's theological writings were condemned. He
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published his books either under his own name or under the pseudonyms of "Villanobus" or
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"Serveto de Revés." Leibniz, inappropriately in my view (see next, as well as Fig. 1), gave
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Servetus credit for having been the discoverer (22) of the pulmonary “circulation.” Servetus, in
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his Christianismi Restitutio (1553) (56), gave a description of the bountiful (vs. restricted,
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according to Galen) perfusion of blood from the right ventricle through the lungs and from there
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to the left ventricle and the arteries, and particularly to the brain. However, he did not discuss
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the motive function of the heart. His stated objective (56) was to indicate the transfer of the Holy
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Spirit from the inspired air to the brain, the seat of the soul. Being in agreement with Galen that
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blood is consumed by organs and tissues, Servetus did not mention its return to the heart;
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accordingly, he should not be considered as a discoverer of the lesser circulation.
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Realdo Colombo (1516-1559) (62), who had been Vesalius' assistant and succeeded
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him as professor of surgery at the University of Padua, clearly described the pulmonary loop.
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The process, communicated six years earlier in Christianismi Restitutio by Servetus, was
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perfected and demonstrated more completely in Colombo’s work De Re Anatomica, Libri XV
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(1559) (30,39). Colombo clearly outlined the passage of venous blood from the right ventricle,
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through the pulmonary artery to the lungs, from where it emerges bright red after mixture with
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some “spirit” in the air, to return to the left ventricle through the pulmonary veins. Harvey read
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Colombo's writings at Padua, and he acknowledged him repeatedly in De Motu Cordis (25), as
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the discoverer of the pulmonary loop. Notable was also Colombo's description of general
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cardiac action (67), which correctly stated that blood is collected into the ventricles during
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diastole, or relaxation of the ventricular muscles, and expelled from them during systole through
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myocardial contraction; as was mentioned above (6,43-46,61), this view is nowadays rendered
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somewhat controversial by Francisco Torrent-Guasp’s model of the human heart. Colombo
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determined that the main action of the heart was actually contraction, not expansion as had
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been thought until then.
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Andrea Cesalpino
In 1571, Andrea Cesalpino (1524-1603) (21), with whose medical works Harvey must
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have also been acquainted, published Peripateticarum Quaestionum Libri Quinque, a
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systematic book based on the Aristotelian philosophical framework (9). In it, he described (2,10)
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quite accurately the heart valves and the pulmonary vessels connected to the heart, as well as
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the pulmonary circulation. Although Cesalpino had not attained a thorough knowledge, founded
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on anatomical research, of the entire course of the blood, he speculated that the heart is the
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center of the “circulatio sanguinis” (blood circulation), a term that he coined, and specified that
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blood flows in a perpetual movement into the heart from the veins and from the heart to the
329
arteries (2,10). He examined experimentally the difference between the blood flow in veins and
330
that in arteries, and he deduced the presence of “vasa in capillamenta resoluta” (2), the invisible
331
hair-like “capillaries,” as he was the first to name them, between the two vascular networks; he
332
did, however, acknowledge that these connections were “what the Greeks call anastomoses”
333
(9,10). He certainly had a flair for words that ring prescient in our ears!
334
Cesalpino operated on living animals, exposed the pulsating arteries and accompanying
335
veins and investigated what ensued when he cut off the flow through them. He ascertained that
336
when he ligated an artery, it bulged on the cardiac side implying flow toward the periphery; in
337
contrast, when he ligated a vein, the bulge ensued on the peripheral side, implying flow toward
338
the heart (2,9). Moreover, in Quaestio IV of the Peripatetic Problems, the pulmonary circulation
339
is identified unambiguously, although its function is considered to be one of cooling. In
340
Paragraph 11, Cesalpino states (9,10):
341
“From the contact with cold air or water during its passage (through lungs or gills), nature
342
has provided a cooling process. The lung, then, draws warm blood through the vein-like artery
343
(vena arterialis, i.e., pulmonary artery) from the right ventricle of the heart and returns it through
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Pasipoularides: Harvey’s discovery of the Circulation
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anastomoses to the arteria venosa [pulmonary vein(s)], which enters the left heart… Dissection
345
corroborates this ‘circulatio sanguinis’ (circulation of the blood, see above) from the right
346
ventricle of the heart through the lungs and to the left ventricle of the same. For, there are two
347
vessels which connect into the right ventricle and two into the left. Of these two, one introduces
348
blood only, while the other conducts it out with its valves constituted for that purpose. The
349
vessel which leads in is the great vein on the right which is called the vena cava. The one on the
350
left, leading in from the lung, is small, and has a single coat like other veins. The vessel leading
351
out on the left is the great artery and is called the arteria aorta; the vessel on the right is small,
352
however, and leads to the lungs, and has two coats like other arteries.”
353
The preceding excerpt bears upon the question of Cesalpino’s place in history and
354
demonstrates that he had probably penetrated into the enigma of the Circulation further than
355
any other physiologist before Harvey—in Italy, he is regarded as the real discoverer (see Fig. 3).
356
However, it is highly unlikely that this is a valid allegation. Consider the following: De Venarum
357
Ostiolis (19), the treatise of the illustrious teacher of Harvey, Fabricius of Aquapendente, was
358
published in 1603, over 30 years after Cesalpino’s own Peripateticarum Quaestionum Libri
359
Quinque, and a year after Harvey left Padua.
360
Fabricius’ and indirect consequential evidence of Cesalpino’s total ignorance of the simple
361
hydraulics of blood in the systemic loop.
It provides undeniable direct evidence of
362
In it, Fabricius writes that the purpose of the valves in the veins was not to ensure the
363
unidirectional flow to the right heart, but to prevent overdistension of the veins by blood passing
364
through the venous trunks to their tributaries, and also to retard the progress of the venous
365
current so as to afford each part, or organ, time to procure its proper nutriment (in agreement
366
with the Galenic concept). Fabricius also noted that arteries do not need valves because they
367
are not liable to overdistension, given the strength and thickness of their coats. Neither are
368
valves needed to retard the blood stream, because in the arteries there is perpetual flux and
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Pasipoularides: Harvey’s discovery of the Circulation
16
369
reflux of blood [quod sanguinis fluxus refluxusque in arteriis perpetuo fiat]. Such, then, was the
370
state of understanding of the systemic loop taught by Harvey’s teacher over 30 years after the
371
publication of Cesalpino’s Peripateticarum Quaestionum Libri Quinque.
The understanding as to the function of the valves was, in nuce, that they were present
373
to sustain the column of venous blood and thus prevent blood from stagnating at the extremities
374
of the limbs with a consequent unequal distribution of nutriment—a view that was the only
375
conceivable one without the complete refutation of the then current and universally accepted
376
Galenic notions on the movements of the blood.
377
Harvey’s epoch-making discovery and posthumous vindication
378
Indeed, it was reserved for Harvey, from all the known fragmented anatomical facts to
379
devise a coherent, comprehensive, hydraulically consistent theory of the cyclic, incessant,
380
coupled and concurrent passages of blood through a greater systemic and a lesser pulmonary
381
loop (see Fig. 1). To this end he arrived through the application of, paraphrasing Galileo, easy to
382
understand once they had been applied mathematical methods (the point was to apply them!)
383
and exhaustive, meticulous animal studies.
384
In this context, we need to ask what led Harvey to see mechanisms completely
385
differently than other researchers, thinkers and experimentalists. It was not simply a matter of
386
his using his eyes better, nor the fact that he used experiment, because his rivals did so too.
387
Indeed, with respect to using one’s eyes, the Circulation is not something that is visible. It is the
388
deduction of a quantitative argument about anatomical pathways, the capacity of the chambers
389
of the heart, its rate of pulsation, and the implicit recognition of the continuity principle of fluid
390
dynamics. The latter was enunciated first by Aristotle (44), whose devoted follower Harvey was
391
throughout his life, and embodies the law of mass conservation, as applied to blood in the
392
Circulation.
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Pasipoularides: Harvey’s discovery of the Circulation
17
393
394
Application of the resolutive or analytic method of Aristotle,
395
with mass conservation considerations
Through mass conservation arguments, Harvey rebuked the Galenic view of continual
397
formation of blood by the liver from digested food brought to it via the portal vein, with
398
subsequent passage through the systemic veins to the periphery (Fig. 2), there to be
399
continuously consumed as nutrient or transformed into flesh. He started by measuring the
400
quantity of blood in the body of an animal (he took an animal and cut a vein in order to extract
401
“all” the blood) and saw that its quantity was limited. He also ascertained that by cutting a single
402
artery “all” the blood may be easily drained from the whole body in half an hour's time.
403
Therefore, the blood content is not continually formed, in the Galenic notion, but must be preset.
404
He went on to describe, in Chapter IX of De Motu Cordis, how the blood that is put out
405
by the heart in less than half an hour would amount to a multiple of the total weight of a man. It
406
is instructive to consider his reckoning as he presents it [in Chapter IX, in the Keynes translation
407
(25)], albeit somewhat abridged here for brevity. In an approach somewhat reminiscent of a
408
thought experiment, in Ernst Mach’s Gedankenexperiment sense, he reasoned that with every
409
successive systolic contraction, the heart pumped, say, two fluid ounces of blood out through
410
the aorta, “which by reason of the hindrance of the portals (aortic valve cusps) cannot return to
411
the heart.” He could count the heart beats in a minute—about 72—so he could estimate the
412
heart's nominal hourly output, 8,640 ounces of blood. Since that much blood would weigh three
413
times as much as an average man (more than 240 kg), Harvey realized that the same blood
414
must be pumped around-and-around the system: “But grant that it be not done in half an hour,
415
but in a whole hour, or in a day, be it as you will, it is manifest that more blood is continually
416
transmitted through the heart, than either the food which we receive can furnish, or is possible
417
to be contain'd in the veins.” What a neat example of a modern engineering order of magnitude
418
analysis, perfectly suited to the question at hand! Today's accurate calculations or assessments
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396
Pasipoularides: Harvey’s discovery of the Circulation
18
419
of cardiac output would not change Harvey's conclusion that the blood circulates. Indeed,
420
Harvey’s invocation of incontrovertible quantitative reasoning in physiology may be just as
421
important as his momentous discovery of the Circulation!
As a result of the above illuminating quantitative arguments, Harvey came to discuss the
423
concept of a closed-loop circulation (25), as is depicted in Fig. 1. Recapitulating now, through
424
his simple but powerful mathematical calculations of the amount of blood that traverses each
425
side of the heart per unit time and with every systole, Harvey deduced that the amount of blood
426
that passes through the heart even in only one-half hour should be more than the total
427
contained in the body. Bear in mind that all of Harvey’s estimates were intentionally low, so that
428
he could unquestionably indicate the vast amount of blood Galen's theory required the liver to
429
produce. He states [Keynes translation, from (25)]: “But howsoever, though the blood pass
430
through the heart and lungs in the least quantitie that may be, it is convey'd in far greater
431
abundance into the arteries, and the whole body, than it is possible that it could be supplyed by
432
juice of nourishment which we receive, unless there were a regress (return) made by its
433
circuition.”
434
Thus, through his unassailable quantitative reasoning, Harvey argued that the incessant
435
blood motion is readily compatible only with a circulatory system! Quod erat demonstrandum, or
436
περ
δει δε ξαι, as Euclid, or Archimedes himself would note. This was accomplished
437
through deceptively simple arithmetic considerations. We remember, however, the likewise
438
straightforward and deeply insightful dictum attributed to Galileo: “All truths are easy to
439
understand once they are discovered; the point is to discover them.” The point in Harvey’s case
440
was to conceive the powerfully insightful deduction that emanated, quite naturally, from his
441
order of magnitude analysis.
442
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422
Pasipoularides: Harvey’s discovery of the Circulation
443
Application of the demonstrative method of Aristotle,
444
with functional anatomical observations
19
Starting in his first Lumleian lecture to the (later to become “Royal”) College of
446
Physicians in London, in April 1616 (58), Harvey presented in homilies the broad outlines of his
447
ideas about the blood circulation. He proceeded with their publication, however, only in 1628;
448
after more than another decade of further comprehensive animal research to perfect an
449
assiduous experimental validation of his grand idea of the Circulation. Clearly, he followed
450
determinedly the Horatian admonition: Nonumque prematur in annum (Horace, Ars Poetica 388)
451
—“…Then put your manuscript, Away till the ninth year: you can always destroy, What you
452
haven’t published: once out, there’s no recall.”
453
In studying the cardiovascular system, Harvey became a pioneer also in the study of
454
embryology, having examined the development of the chick in the egg and having performed
455
many dissections of mammalian embryos at various stages. In the course of his tireless
456
functional anatomic cardiovascular studies of scores of species and many embryonic
457
preparations (see below) he formulated his understanding of comparative anatomy and
458
embryology, which formed a leg of his edifice of the Circulation of the Blood. From these
459
experiments, he was also able to formulate his theory of animal generation, which he published
460
in 1651 in Exercitationes de Generatione Animalium (24). In this work he propositioned that,
461
rather than existing preformed as a homunculus in the ovum, as believed by his
462
contemporaries, the embryo is formed gradually from its parts, as Aristotle had demonstrated
463
many centuries earlier in formulating his theory of epigenesis.
464
Harvey labored incessantly; alongside his medical practice, he examined thoroughly
465
more than 80 species in various animal classes, including mammals, birds, reptiles, amphibians,
466
fishes, crustaceans, and insects! Of the essence is that he not only compared their
467
cardiovascular organs, but he also manipulated them in dead and in living animals. In all of
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445
Pasipoularides: Harvey’s discovery of the Circulation
20
468
these endeavors, he followed the paradigm set by Galen (25). He isolated various parts of the
469
heart; he ligated and divided arteries; he famously compressed veins on either side of
470
interposed valves. His observations showed that the cardiac valves allowed only unidirectional
471
blood flow. He thus arrived at the conclusion that the heart valves subserve essentially the
472
same function as the venous valves, i.e., they guard against refluxes of blood, and identified the
473
systolic contraction as the active working phase of the heart muscles.
Harvey arrived at the global kinematics conclusion that the blood from the right ventricle
475
flows through the lungs to the left side of the heart, from there to be distributed to the whole
476
body by the arterial vasculature. Subsequently, blood flows centripetally through the systemic
477
veins to return back into the right heart, completing the circle (25). Only the during-his-time still
478
unknown pulmonary and systemic capillaries and adjoining microvasculatures formed
479
unidentified gaps in Harvey’s overall circulatory system paradigm (see Fig. 1). Without a
480
microscope, Harvey could not see what connected the arteries and veins, but he perceived that
481
a connection had to exist between the arteries and the veins. Accordingly he conjectured,
482
following Galen, the discovery of small arteriovenous inosculations or “anastomoses,” and pores
483
or “porosities” of the flesh through which the blood seeped from arteries to veins (25).
484
Furthermore, from his meticulous measurements of blood vessel sizes and the timing of
485
the pulse and the contractions in the heart's big ventricles and smaller auricles, Harvey correctly
486
advocated that the heart beat originates in the auricles and that the powerful contraction ensues
487
in the ventricles only after they have been filled-up with blood from the chambers above them.
488
He likewise deduced that the pulse beat in the arteries was a delayed consequence of the left
489
ventricular contraction.
490
At this juncture, the question arises: from where did Harvey get the idea of the
491
experimental method? He had two primary foundations: one was the codified work of Galen,
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474
Pasipoularides: Harvey’s discovery of the Circulation
21
who was perhaps the greatest experimentalist in biology and medicine; the other, was the new
493
tradition of experimental science which was blossoming in the seventeenth century in Padua.
494
Galileo was teaching at the University of Padua during Harvey’s student years there, and it
495
seems highly unlikely that Harvey could have avoided at least some acquaintance with his
496
measurement principles and methods. In turn, Harvey’s experimental paradigm influenced many
497
figures rising to influence in British “natural philosophy,” such as Robert Hooke, Robert Boyle,
498
John Wallis, and especially Christopher Wren (see below). Members of this group worked
499
toward founding the Royal Society of London for the Improving of Natural Knowledge. Its motto,
500
shown in its Coat-of-Arms in Fig. 4, seems to be inspired by or, at least, in harmony with the
501
paradigm of Harvey and declares “Nullius in verba,” (take no-one's word for it). It is an
502
expression of the resolve of Fellows to withstand any sort of domination by any authority and to
503
verify all statements by an appeal only to facts determined by experiment.
504
Microscopic demonstration of the “missing link” and
505
Harvey’s posthumous vindication by Marcello Malpighi
506
The capstone of Harvey’s splendid physiologic construct was contributed by Galileo’s
507
student Marcello Malpighi (1628-1694), who provided microscopic evidence of the “missing
508
link,” represented by the capillaries, in 1661, four years after Harvey’s death (44,66). That was
509
also fifteen centuries after Galen surmised that the veins communicate with the arteries by fine
510
tubular anastomoses. Malpighi is arguably the father of microscopic anatomy, or histology,
511
because of his many important discoveries, including the red corpuscles, to which he correctly
512
attributed the color of blood, and fibra, today’s fibrin (44).
513
Cold-blooded amphibians, including the frog, have capillaries and red corpuscles that
514
are 3-4 times the size of those of warm-blooded animals (44). Conveniently, Malpighi saw the
515
capillaries first in the lungs and the mesentery of a frog, and the discovery was announced in
516
the second of two letters, Epistolae duae de Pulmonibus, addressed to his good friend the
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492
Pasipoularides: Harvey’s discovery of the Circulation
22
517
iatrophysicist Borelli, and dated 1661 (44). “I could clearly see that the blood is divided and
518
flows through tortuous vessels,” wrote Malpighi, “and that it is not poured into spaces, but is
519
always driven through tubules and distributed by the manifold headings of the vessels...” In
520
extrapolating his findings to humans, Marcello Malpighi vindicated Harvey, if only posthumously.
521
Early medical squabbling around Harvey’s discovery
As Claude Bernard (1813-1878), the great French physiologist-physician, has
523
remarked—epigraph to Chapter 15 of Flesch R, The art of clear thinking, New York, 1951: “In
524
science the important thing is to modify and change one's ideas as science advances.” De Motu
525
Cordis, Harvey’s monumental treatise presenting the greatest generalization in the history of
526
physiology, the Circulation of the blood, received heavy criticism from his contemporaries, and
527
because of public criticism he even lost many patients from his private practice. Some questions
528
were, admittedly, legitimate; the ultimate purpose of the circulation of the blood, and the
529
difference in color between arterial and venous blood, remained as two vexing unresolved
530
questions in Harvey's scheme. His discovery attained wide acceptance only gradually and
531
stingily by the medical establishment, which was accustomed to and comfortable with the
532
ostensibly sensible Galenic texts and doctrines, and found it hard to modify and change their
533
ideas. Some even ridiculed the patently foolish concept of grounding scientific understanding on
534
observation, given that the real world was filled with distortions and exceptions.
535
Indicative of his difficulties in this regard is that he continued passionately his
536
experiments for decades after the publication of De Motu Cordis. A well-designed experiment on
537
the pulmonary circulation is described, quite vehemently, in a letter written to his friend, Paul
538
Slegel of Hamburg in 1651 (23): "In a strangled human body, the pulmonary artery and aorta
539
are ligated, the left ventricle opened, and a cannula placed in the vena cava, and water forced
540
in. What happens? [Quid fit?] The right ventricle is greatly swollen [vehementer intumuit].
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522
Pasipoularides: Harvey’s discovery of the Circulation
23
Through the opening in the left ventricle, however, not a drop of water or blood escapes. So
542
now (the solution having been predicted), the syringe is introduced into the pulmonary artery,
543
with a ligature around it lest water regurgitate into the right ventricle. We force the water in the
544
syringe against the lungs and immediately water with copious amounts of blood [cum copioso
545
sanguine] leaps out of the cleft in the left ventricle, so that, as much water as is expressed into
546
the lungs, so much flows out of the hiatus mentioned. You can experiment as often as you like,
547
and know for certain that this is so. By this one experiment, I have easily butchered all the
548
arguments of Riolan on this question [Hoc uno experimento, facile omnes Riolani circa hanc
549
rem altercationes jugulaveris]."
550
The above excerpt from Harvey’s letter to his friend is illuminating in at least two
551
respects: It attests to his utter impatience with his adversaries, some of whom are obviously still
552
going strong in opposing his Message, nearly a quarter of a century after its publication; and it
553
gives in nuce a self-contained, first-hand account of his incredibly modern approach to
554
physiological investigation, for us to admire! It also emphasizes that the experimental
555
demonstration of the Circulation rested not only on the calculation of the volumetric flow rate of
556
blood passing through the heart with every beat but also on Harvey’s deep understanding of the
557
uses of ligatures of varying tightness in investigating circulatory flows.
558
Happily, our brains are not physiologically static organs, and they and our convictions
559
can change throughout life and with the passage of time (42). Increasingly, Harvey’s
560
momentous discovery diffused through the ranks of the scientific community and the medical
561
profession, and of other curious minds. Increasingly in the 1630s, Harvey's system gained
562
ground as the general public began to see it as a paradigm for a new approach to the human
563
body and to medicine. Exploring the human anatomy became fashionable and engendered
564
fascination matching the exploration of the skies. In Amsterdam, the physician Nicolaes Tulp
565
gave public anatomy demonstrations, using cadavers of executed criminals. He was
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541
Pasipoularides: Harvey’s discovery of the Circulation
24
566
immortalized in Rembrandt’s painting “The anatomy lesson of Dr. Tulp” in which, using a
567
forceps, he lifts up a muscle of the left forearm of a cadaver using his right hand. According to
568
an orthopedic surgeon who has studied the painting exhaustively (36), Dr. Tulp is holding his left
569
hand in such a way as to reproduce the movement brought about by this particular muscle—the
570
flexor digitorum superficialis—with his own left hand.
571
Initial ricochet effects of Harvey’s grand “billiard ball strike” and
572
early medical applications
Before too long, Harvey’s discovery of the Circulation became the source of enduring
574
repercussions on medical practice that were natural, rather than imposed by the medical
575
establishment, since the medical profession organizes itself to support and further develop a
576
medical scientific advance and new understanding, once it has been accepted. Solid
577
understanding of the circulation of blood acted as a "billiard ball" producing a series of ricochet
578
effects on medical practice. Elaborated in De Motu Cordis in 1628, it marked the birth of modern
579
circulatory physiology and had far-reaching repercussions on the practice of medicine. It led to
580
the first attempts at blood volume replenishment by transfusions after heavy hemorrhage, and to
581
the administration of solutions of medicinal substances as intravenous injections or infusions.
582
By 1657, the year that Harvey died, the first direct animal transfusions were conducted
583
by the English anatomist and physiologist Richard Lower (1631-1691). Collaborating with
584
Robert Hooke, he also followed the movement of blood as it passes across the lungs and
585
observed that it changes color when exposed to air. Lower refined and supplemented Harvey's
586
circulatory concept in his work De Corde, which he published in 1669 (18); he attributed
587
arterialization to air actually entering the blood in the lungs—Antoine Lavoisier (1743-1794)
588
eventually showed that arterialization involves O2 uptake and CO2 release in the passage of
589
blood through the pulmonary capillaries (29).
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573
Pasipoularides: Harvey’s discovery of the Circulation
25
Following the publication of De Motu Cordis, several individuals in different European
591
countries would start thinking along similar lines; this resulted in conflicting priority claims as to
592
the first human blood transfusion. The first fully-authenticated human blood transfusion was
593
probably accomplished by Jean-Baptiste Denis (1625-1704), eminent physician to King Louis
594
XIV of France, on June 15, 1667 (63). He transfused the blood of a sheep into a 15-year old
595
boy, who actually recovered. Denis was, of course, totally unaware of the serological and
596
immunological conditions that impinge on such technically simple undertakings. Having been
597
recognized not to be generally successful, such endeavors were soon outlawed. Conversely,
598
the practice of bloodletting, which had been common since ancient times, seemed to take an
599
upswing in the aftermath of Harvey’s momentous discovery.
600
One of the earliest attempts at intravenous injection was made in 1656 by (the later to
601
become “Sir,” and President of the Royal Society) Christopher Wren (1632-1723), one of the
602
most accomplished individuals of the Scientific Revolution period and a keen experimentalist in
603
the natural sciences, who was strongly influenced by Harvey's discovery. He is recorded in the
604
historical archives of the Royal Society of London as “…the first author of the noble anatomical
605
experiment of injecting liquor [liquid] into the veins of animals… Hence arose many new
606
experiments and chiefly that of transfusing blood, which the Society has prosecuted in many
607
instances, that will probably end in extraordinary success” (59). His technique did not find
608
immediate therapeutic application, although he succeeded in injecting drugs directly into a dog's
609
veins, with the help of a hollow, slender quill (from a bird’s feather), to which was attached a
610
small animal bladder.
611
Among the physicians who ventured intravenous Injections and infusions of drug
612
solutions was Johann Sigismund Elsholtz (1623-1688), a German naturalist and court physician
613
to the Elector of Brandenburg and Duke of Prussia. He performed early research on blood
614
transfusions and "infusion therapy.” In his 1667 work Clysmatica Nova (16), he investigated the
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590
Pasipoularides: Harvey’s discovery of the Circulation
26
615
possibilities of intravenous injection. Johann Daniel Major (1634-1693) was a professor of
616
theoretical medicine and of botany and chemistry at the Christian-Albrechts-Universität in Kiel,
617
Germany (55). Major thought that illnesses might arise from degraded blood; in such cases,
618
cures could be provoked by either injecting a healing medicament straight into the blood stream,
619
or by transfusing intravenously the blood of a healthy individual directly into the patient. To
620
perform his injections, he used tiny silver pipes (needles) rather than the more common feather
621
quills.
622
Conclusion
In Harvey’s opus majus, his Exercitatio Anatomica de Motu Cordis et Sanguinis in
624
Animalibus (An Anatomical Disquisition on the Motion of the Heart and Blood in Animals), we
625
see the mechanisms of the Circulation worked out more or less in full from the results of
626
experimental demonstration, virtually complete but for the direct visual evidence of a link in the
627
periphery between the minute final terminations and initial branches of the arterial and venous
628
systems, respectively. This would only become available when the capillaries could be seen
629
under the microscope. Harvey’s amazingly modern order of magnitude analysis of volumetric
630
circulatory flow and appreciation of the principle of continuity (mass conservation), his adroit
631
investigational uses of ligatures of varying tightness and in various combinations in elegant flow
632
experiments, and his insightful deductions truly explain the movement of the blood in animals.
633
His end was accomplished. So radical was his discovery, that early in the eighteenth century the
634
illustrious Hermann Boerhaave, professor of medicine at Leyden, declared that nothing that had
635
been written before Harvey was worthy of consideration any more (4). The conclusions of De
636
Motu Cordis are unassailable and beautiful in their simplicity. Harvey’s genius and determination
637
have served physiology and medicine well!
638
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623
Pasipoularides: Harvey’s discovery of the Circulation
27
639
640
Acknowledgment I decided to write this tribute to William Harvey and his Circulation of the
641
Blood on the happy occasion of my friend Peter Damian Richardson, FRS, advising me of his
642
election as Honorary Fellow of the Royal College of Physicians of England.
643
644
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Pasipoularides: Harvey’s discovery of the Circulation
28
Figure legends
646
Fig. 1 Around and around: William Harvey's scheme for the Circulation shows the aorta and
647
subsidiary arteries in white coming out of the left side of the heart, while the vena cava brings
648
dark venous blood back to the right heart from the periphery, organs and tissues. The vena
649
arteriosa (pulmonary artery) carries venous blood to the lungs and the arteria venosa
650
(pulmonary vein[s]) arterialized blood to the left heart. This completes the circle, whereas the
651
lesser (pulmonary) and the greater (systemic) loops cannot do so, taken individually. None of
652
Harvey’s “predecessors” had envisaged a comprehensive hydraulically sound Circulation
653
schema! To come full circle, you have to end at the same point that you started from; hence, the
654
terminology of a “lesser (pulmonary) loop” and a “greater (systemic) loop.” Nobody before
655
Harvey envisaged the Circulation of Blood! Aristotle’s water cycle influenced Harvey’s thinking,
656
as he affirms in Chapter VIII of De Motu Cordis, and is sketched in the center.
657
658
Fig. 2 In Galen’s schema, the venous, arterial, and nervous systems, with the liver, heart, and
659
brain as their respective centers, were separate, and each distributed through the body one of
660
the three pneumata: respectively, the natural, the vital, and the animal spirits. Blood was carried
661
both within the venous system and the arterial system. The most basic kind of pneuma was
662
concerned with nutrition. The liver drew material from the gastrointestinal tract after it had been
663
digested, converted it into blood and infused it with “natural” spirit. This blood from the liver then
664
coursed through the veins throughout the body, to nourish the muscles and all other organs.
665
Some of it passed from the liver through the inferior vena cava, into the heart where it was
666
further refined with another pneuma, the “vital” one. The heart and lungs worked together in this
667
process, some of the blood passing through the pulmonary artery into the lungs; there it
668
nourished the lungs and also mixed with the air breathed in. Some of the blood in the heart
669
passed from right to left through “pores” in the interventricular septum. It was bright red because
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Pasipoularides: Harvey’s discovery of the Circulation
29
670
it had the vital spirit infused within it; from the left heart, it went out via the aorta to warm up the
671
body. Some blood from the heart went to the brain, where it was admixed with the third kind of
672
pneuma, the “animal” spirit. This was the most refined pneuma. It gave the brain its own special
673
functions and also flowed peripherally through the nerves, enabling motion using the muscles
674
and perception using the senses.
675
Fig. 3 Commemorative plaque on the house of Cesalpino in Rome, with the inscription
677
“QUÌ ABITÒ ANDREA CESALPINO, SCOPRITORE DELLA CIRCOLAZIONE DEL SANGUE E IL
678
PRIMO AUTORE DELLA CLASSIFICAZIONE DELLE PIANTE,” (Here resided Cesalpino, discoverer
679
of the circulation of blood and the first author of the classification of plants).
680
681
Fig. 4 “Nullius in verba,” take no-one's word for it: the motto of the Royal Society of London
682
for the Improving of Natural Knowledge is proclaimed on its Coat-of-Arms. It seems to have
683
been inspired by or, at least, in harmony with the paradigm of William Harvey and affirms a
684
resolve to withstand dominance by any authority and to verify all statements by appealing only
685
to facts determined by experiment. The two keen-scented white hounds symbolize the capacity
686
to pursue and sniff-out true knowledge.
687
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Pasipoularides: Harvey’s discovery of the Circulation
30
688
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