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ON THE ROLE OF CLINICAL ANOMALY IN HARVEY'S DISCOVERY OF THE MECHANISM OF THE PULSE BRANDON P. REINES* On the basis of recent scholarship by Whitteridge, Bylebyl, and other historians, the temporal and conceptual evolution of Harvey's research on cardiovascular physiology has become increasingly clear [1, 2]. In the first stage of Harvey's research program, Harvey elucidated the mechanism of the pulse. A coherent account of the pulse allowed him to discover the circulation of the blood and then the cardiovascular system in toto. While a great deal of attention has been focused on the methodology used by Harvey to elucidate the circulation [3, 4], relatively little scholarship has centered on the methodology he used to achieve his first great discovery: the mechanism of the pulse. While Bylebyl does not analyze Harvey's methodology per se, he implies that Harvey elucidated "cardio-arterial physiology" by experiments on animals. Bylebyl certainly does not challenge the notion that Harvey's methodology was essentially vivisectional. The work of scientific philosophers Popper and Humphreys, however, when viewed in linguistic perspective, casts doubt on the significance of animal experiments in Harvey's discovery of the mechanism of the pulse [5, 6]. Humphreys's work in particular reveals the crucial role of clinical anomaly in the discovery. The first clue that Harvey's modus operandi may have been clinicopathologic rather than experimental is contained in his celebrated letter to the physician Vlackveld, in which he wrote: Nature is nowhere accustomed more openly to display her secret mysteries than in cases where she shows traces of her workings apart from the beaten path; nor is there any better way to advance the proper practice of medicine than to give our minds to the discovery of the usual law of nature, by careful investigation of cases of rarer forms of disease. For it has been found in almost all things, that what they contain of useful or of applicable, is hardly perceived unless we are deprived of them, or they become deranged in some way. [7, p. 616] *Associate director, Laboratory Animals Department, Humane Society of the United States, 2100 L Street, NW, Washington, D.C. 20037. <© 1990 by The University of Chicago. All rights reserved. 003 1-5982/91/3401-0703101 .00 128 I Brandon P. Reines ¦ The Mechanism of the Pube That passage constitutes perhaps the clearest account of Harvey's method of physiological discovery. He unequivocally states that "Nature is nowhere accustomed more openly to display her secret mysteries than in cases . . . apart from the beaten path . . ." (emphasis added). In referring to the locus of discovery, Harvey states explicitly that it is not the laboratory but the clinic. It is no coincidence that Harvey's methodology has guided clinical investigators for over 300 years [8]. Understandably, therefore, the few investigators to argue that Harvey 's discovery was largely clinicopathologic are not physiologists but physicians. In the Harveian Oration of October 18, 1895, W. S. Church, then senior physician to St. Bartholomew's Hospital, said: "Harvey, by a chain of close and acute reasoning drawn from direct experiments and from observations on the pulsation in aneurysms and in vessels distal to aneurysmal dilatations and to portions of rigid and calcified arteries, demonstrated once and for all that the motion and contraction of the heart was the main . . . cause of the pulse" [9]. Church's view of Harvey's method clashes with the modern view that it was largely experimental. Even Church, however, does not contend that Harvey's experiments were any more or less important than his observation of clinical anomalies . In fact, Church assigns equal value to Harvey's various experiments and observations. The historical tradition of assigning equal importance to the facts on which a new theory is based has been criticized by philosopher W. Humphreys. Humphreys disputes "the conception of facts as a string of identical pearls" [6, p. 19]. He contends that some facts are of overriding importance in marking the shift from an old theory to a new theory. Humphreys argues that the key event in the discovery of a new theory is the identification of a "natural anomaly": an observation that clearly contradicts existing theory. For example, Humphreys argues that Newton observed and described a natural anomaly that clearly contradicted Snell's law of refraction. Newton had been toying with a prism that projected light through a pinhole onto a far wall. The shape of the image should have been identical with the shape of the pinhole, but it was not. Instead, the image was "in an oblong form" [10, p. 48]. The failure of traditional optics to account for the phenomenon led Newton to discover his new theory of light. A corollary of Humphreys's thesis is that the discovery process is more public than has been suggested by the works of Popper. While Popper focuses on the essential privacy of the discovery process as an imaginative act, Humphreys implies that one aspect of discovery is amenable to empirical investigation: its semantic evolution. Humphreys implies that Newton had fully internalized the semantic structure of Snell's law. In a sense, Newton was intellectually primed to identify an anomaly to traditional optics. While others might have ignored the oblong image, to Newton it stood out like a cuckoo in a robin's nest. Hence, Perspectives in Biology and Medicine, 34, 1 ¦ Autumn 1990 \ 129 Newton's discovery process consisted of three successive semantic steps: (1) internalization of the semantic structure of traditional optical theory, including Snell's law ofrefraction; (2) identification ofa natural anomaly that contradicts Snell's law and traditional optics; and (3) discovery of a new linguistic structure that accounts for the anomaly, which became known as Newtonian optics. Like Newton, Harvey was fully versed in traditional theory. Harvey had internalized all of Galenic physiology, including Galen's theory of the pulse. In line with the modern view, Galen held that the pulse is caused by the expansion of the arteries. Likening the heart and arteries to a bellows, however, Galen claimed that they actively expand, drawing in "spirit" through invisible pores in the skin. The heart had power over the arteries only to an extent: in Galen's view, the heart wall sends an instantaneous shock wave to the arteries. Galen's narrative of his theory of the pulse is open to interpretation (as are all qualitative theories). In the narrative, Galen uses analogy to explain his theory of the action of the arteries: "You might grasp the difference between being expanded through being filled and being filled through being expanded still better with the help of examples. Wineskins and bags are expanded through being filled; bronzesmiths' bellows are filled through being expanded" [1 1, p. 177]. The argumenter analogium helps the reader grasp Galen's conception intuitively by painting a mental image, but it does not clarify the two key elements of his theory of the pulse: (1) the nature of the viz pulsifica, the power communicated from the heart to the arteries; and (2) the role of the arteries in the production of the pulse. In an effort to test his theory of the pulse, Galen performed an animal experiment that ostensibly confirmed it. Arguing that the pulse wave would be blocked if the tunics of the artery were immobilized, Galen described an experiment in which a hollow reed was slipped into the artery of an animal's limb. He then described tying the arterial walls to the reed inside. Galen insisted that the experimenter would be unable to feel the pulse below the reed, though blood could pass freely through it: If you will expose any one of the large and obvious arteries, freeing it first from the skin and then from the matter that lies over it and around it, so as to be able to put a ligature round it; then open it along its length and insert a hollow reed or small bronze tube into the artery through the opening, so as to mend the wound with it and prevent hemorrhage; then so long as you study it in this condition, you will see the whole artery pulsadng. But when you put a ligature round and press the coat ofthe artery against the reed, you will no longer see the part beyond the ligature pulsating, although the passage of the blood and pneuma through the hollow ofthe reed proceeds as before to the end ofartery. If the arteries got their pulsation in this way, then even now pulsation would be continuing in the parts beyond the ligature near their ends. Since this does not 130 I Brandon P. Reines ¦ The Mechanism of the Puke happen, it is clear that the faculty that causes the movement of the arteries/is transmitted to them from the heart through their coats. [11, p. 179] For nearly 2,000 years, the hollow reed experiment stood as the main proof of Galen's theory of the pulse. Harvey doubted that Galen had actually performed the experiment since, in his own hands, "the effusion of blood from the wound confuses everything, and renders the whole experiment unsatisfactory and nugatory, so that nothing certain can be shown" [12]. The widely divergent results it has produced in the laboratories of experienced physiologists over several centuries testify to its cumbersomeness [13, pp. 378-389]. Judging from his many published works, Galen did attempt to perform the experiment many times on many different species [13, p. 380]. For Harvey's purposes, however, it was irrelevant whether or not Galen had actually performed the experiment. Galen's description of the reed experiment constitutes the most precise linguistic form of his theory of the pulse. Galen provided his successors with a formal linguistic structure that is sufficiently precise to be rejected, by couching his theory in the language of experiment. In describing the hollow reed experiment , Galen clarifies the two key elements of his theory of the pulse. His "experiment" really constitutes a linguistic clarification that (1) the power that produces the pulse is such that it will be interrupted by immobilization of the arteries, and (2) the role of the arteries in the pulse is such that it will be deleted by immobilizing their walls. Harvey was in a position to reject the ancient theory of the pulse because he had internalized the language ofthe hollow reed experiment. He knew that it was not necessary for him to actually perform the experiment. He needed only to feel a pulse in a limb distal to a site of arterial immobilization in a living animal or human being. Given that he did not believe it possible to effectively perform the experiment in animals for technical reasons, he had likely been searching for a natural equivalent of Galen's animal experiment. Harvey must have felt a pulse in an animal or human limb distal to a site of natural arterial immobilization before his formal lectures on the pulse in 1616 [14]. On purely linguistic grounds, therefore, Harvey must have seen the case described in his second letter to Riolan before 1616. In addition, there is historical evidence that the second letter to Riolan was written decades before the first in the 1610s [15, p. 33]. The case of the nobleman with the calcified aorta constitutes the only "experiment" ever described by Harvey that unambiguously conflicts with Galen's theory of the pulse. Wrote Harvey: I beg here to refer to a portion of the descending aorta, about a span in length, . . . which I removed from the body of a nobleman, and which is converted into a Perspectives in Biology and Medicine, 34, 1 ¦ Autumn 1990 | 131 bony tube; by this hollow tube, nevertheless, did the arterial blood reach the lower extremities of this nobleman during his life, and cause the arteries in these to beat; and yet the trunk was precisely in the same condition as is the artery in the experiment of Galen, when it is tied upon a hollow tube; where it was converted into bone it could neither difate nor contract like a bellows, nor transmit the pulsific powerfrom the heart to the inferior vesseh; it could not convey force which it was incapable of receiving through the solid matter of bone. In spite of all, however, I well remember to have frequently noted the pulse in the legs and feet of this patient whilst he lived, for I was myself his most attentive physician, and he my very particular friend. The arteries in the inferior extremities of this nobleman must therefore of necessity have been dilated by the impulse of the blood like flaccid sacs, and not have expanded in the manner of bellows through the action of their tunics. It is obvious, that whether an artery be tied over a hollow tube, or its tunics be converted into a bony and unyielding canal, the interruption to the pulsine power in the inferior part of the vessel must be the same. [12, p. 15; emphasis added] Harvey reported yet another identical case in his letter, although he need not have. Nature knows no artifact: the natural experiment was more persuasive than any animal experiment because of the seamlessness of its performance. Therein lies the beauty of the clinicopathologic method. Like the oblong image on the wall of Newton's laboratory, the nobleman with the calcified aorta constitutes the natural anomaly that allowed Harvey to reject Galen's theory of the pulse. It allowed Harvey to take the first semantic step in the evolution of his theory of the cardiovascular system. REFERENCES 1.Whitteridge, G. Growth of Harvey's ideas on the circulation of the blood. Br. Med. J. 2:7-12, 1966. 2.Bylebyl, J. The growth of Harvey's De Motu Cordis. Bull. Hist. Med. 47(5):427-470, 1973. 3.Peller, S. Harvey's and Cesalpino's role in the history of medicine. Bull. ??. Med. 23(3):213-235, 1949. 4.Jucovy, P. M. Circle and circulation: the language and imagery of William Harvey's discovery. Perspect. Biol. Med. 20(1):92-107, 1976. 5.Popper, K. The Logic of Scientific Discovery. New York: Basic, 1960. 6.Humphreys, W. Anomalies and Scientific Theories. San Francisco: Freeman, Cooper, 1968. 7.Willis, R. (ed.). The Works of William Harvey. London: Sydenham Society, 1847. 8.Bearn, A. G. The contribution of clinical medicine to biochemical genetics. In Dwease and the Advancement of Basic Science, edited by H. K. Beecher. Cambridge, Mass.: Harvard Univ. Press, 1960. 9.Church, W. S. Harvey and the rise of physiology in England. Lancet 2:1023-1028, 1895. 10. Cohen, I. Isaac Newton's Papers and Letters on Natural Philosophy. Cambridge, Mass.: Harvard Univ. Press, 1958. 132 I Brandon P. Reines ¦ The Mechanism of the Puke 1 1. Furley, D., and Wilkie, J. (eds.). Galen on Respiration and the Arteries. Princeton , N.J.: Princeton Univ. Press, 1984. 12.Harvey, W. Exercitationes Duae Anatomicae de Circulatione Sanguinis ad Riolanum Filium. Rotterdam: Leers, 1649. 13.Harris, C. The Heart and the Vascular System in Ancient Greek Medicine from Alcmaeon to Galen. Oxford: Clarendon, 1973. 14.Whitteridge, G. The Anatomical Lectures of William Harvey. Edinburgh: Livingstone , 1964. 15.Frank, R. Harvey and the Oxford Physiologists. Berkeley: Univ. California Press, 1980. TRIAGE I was medical student. By what authority did I not leave the E.R. that night, run upstairs, and wheedle from the OB nurses a heated blanket for that shivering old woman slipping without us into death as surely as the baby inside the sick woman upstairs slipped with our attention safely into life? (It's against the rules; already I'd been graded down for kindness.) When I gave birth and got my own warm blanket, I remembered her shivering. Ten years have passed. I still have no answer. Pem Kahler Perspectives in Biology and Medicine, 34, 1 ¦ Autumn 1990 \ 133 ...


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