William Harvey and the Discovery of the Blood's Circulation

NEW INSIGHTS ON WILLIAM HARVEY'S DISCOVERY

(About 22 double-spaced pages)

ABSTRACT

William Harvey (1578-1657) had rejected the old explanations of the blood's motion before 1617. He did it by observing the orientation of the valves in the veins and their similarity to the cardiac valves, and by reasoning that the abundance of the valves in the veins was anomalous. Harvey then conceived of a replacement paradigm that the blood circulates. This analysis also reconciles Robert Boyle's accounts of Harvey's discovery.

INTRODUCTION

The new insights on William Harvey's discovery that the blood circulates concern the keys to the discovery, Harvey's methodology, and the timeframe of the discovery. The keys which led to Harvey's discovery have been strongly debated.⁽¹⁾ A popular view centers around the blood's quantity.⁽²⁾

No one, however, considered that an important factor was the relative abundance of venous valves. Yet support for the venous valves as key to the discovery can be found in Harvey's earliest works.

Opinions vary widely as to exactly what was Harvey's methodology. One opinion is that he used an approach based on function and the hypo-deductive method.⁽³⁾ This article describes a reject-replace process in which Harvey used both purpose (defined as God's design and intentions) and reasoned anomalies (defined as interpreting phenomena so they contribute to rejecting a received view).

The timeframe in which Harvey made his discovery also has been debated.⁽⁴⁾ Recent estimates fall between 1619 and 1628. This article presents evidence that the discovery process began before 1617. Subsequently, Harvey developed his full hypothesis by 1619 since he wrote in 1628 that he had confirmed it "nine years and more" earlier,⁽⁵⁾ and that his "little book" was "complete some years ago."⁽⁶⁾ Additional support for this surprisingly early date comes from his reference to a 1615 book as "recently published" and his writing about a person being alive who died in May, 1619.⁽⁷⁾

HARVEY'S METHODOLOGY

Harvey's methodology involved purpose, a great deal of practical experience, reasoned anomalies, and paradigms. Purpose and reasoned anomalies have already been defined. `Paradigm' stands for guiding assumptions,⁽⁸⁾ or a received view. Harvey's approach to doing science demonstrates how these concepts interrelate.

Purpose and Experience

In 1616, Harvey began a series of anatomical lectures at the Royal College of Physicians in London. One source for these lectures was Andreas Laurentius' Historia anatomica (1602). Laurentius favored a methodology using doctrine (purpose) and inspection (experience). Harvey followed this approach,⁽⁹⁾ but took purpose and experience to new heights of refinement. Harvey's method generated purpose-based anomalies which led him to reject accepted physiology.⁽¹⁰⁾ Subsequently, Harvey used purpose and other tools to develop his replacement hypothesis that the blood circulates.⁽¹¹⁾

Harvey reports how he used purpose and experience to hypothesize the blood's circulation in Exercitatio anatomica de motu cordis et sanguinis animalibus (1628).⁽¹²⁾ From this treatise's introduction, to its last sentence, Harvey speaks of ends, final cause, or purpose. These terms are so typical of his writings that he has been called the lifelong thinker on the purpose of circulation.⁽¹³⁾ More accurately, he was a lifelong thinker on purpose in anatomy and physiology. Harvey was a Christian who believed that purpose in nature reflected God's design and intentions.⁽¹⁴⁾ He asked the purpose-based question "why?" more than the function-based "how?"

Anomalies

Harvey's method utilized anomalies, of which there are at least three types: recognized, retrorecognized, and reasoned. An example of a recognized anomaly is the absence of passages through the heart's septum. By publishing this discovery in 1536, Niccolo Massa cast doubts on some of the physiology of Galen of Pergamum (129-199). Galen's physiology was the received view leading up to Harvey's time.

Retrorecognized anomalies are not recognized as anomalous under the existing paradigm. Only later, under a new paradigm, do scientists realize that they were anomalous.⁽¹⁵⁾

Hieronymus Fabricius (1533?-1619), Harvey's most influential teacher, provides a relevant example.⁽¹⁶⁾ In 1574, he rediscovered in the veins what we call `valves,' but what he called `ostiola' (`little doors').⁽¹⁷⁾ Others had already known about them, but Fabricius published the definitive work, De venarum ostiolis (1603).

A top anatomist, Fabricius might have discovered the blood's circulation. According to Galen, blood ebbs and flows in the arteries, distributing the vital spirit. Blood moves similarly in the veins, nourishing the body, but generally in an outward direction from the heart. (Figure 1 depicts the veins in Galenic physiology.) The discovery of ostiola unbalanced the physiological symmetry of Galen's explanation. Further, if ostiola allowed blood to flow only toward the heart, then the body's extremities would starve, in which case Galen's physiology would be obviously incorrect.

Figure 2, from Fabricius' book, shows an arm prepared for bloodletting and ostiola in two veins turned inside out.⁽¹⁸⁾ Fabricius' approach was to depict the structure of the body part (here the ostiola), describe their function, and then explain their purpose in terms of the rest of the body. He argued that the purpose of ostiola was to slow the blood's flow, preventing it from collecting too rapidly in the body's extremities. If the blood flowed too quickly to the hands and feet, other body parts would be undernourished. Fabricius drew an analogy between ostiola and floodgates which hinder water flow in the sluices at a mill. Thus, he apparently explained ostiola in terms of accepted physiology.

Actually Fabricius modified Galen's paradigm. In order to keep the blood from falling down in the venous system, Galen had hypothesized the existence of an "attractive force." Fabricius replaced that notion with his more mechanical explanation. Perhaps this is one reason he ended De venarum ostiolis by saying "such is the wisdom and ingenuity of Nature which by my own efforts I have discovered in this new field." Fabricius realized that the next area for scientific advance was physiology. This is why he referred to the "new field" involving the ostiola in the veins. However, under Harvey's explanation, ostiola became retrorecognized anomalies which he renamed valves.

Paradigms and Anomalies

Harvey learned a "revived-Aristotelian" methodology under Fabricius⁽¹⁹⁾ and inculcated the expectation of making regular and new findings in anatomy and/or physiology. Yet, while Fabricius correctly depicted the structure of ostiola, he was wrong about their function and purpose. Therefore it is not surprising that Harvey had his own ideas about making new findings. He wrote that "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. . . ."⁽²⁰⁾

Of course Harvey did not use the terms anomalies or paradigms, but for didactic purposes we can consider "beaten path" as research under the current paradigm, "traces" as anomalies, and nature's "secret mysteries" as a replacement paradigm. Specifically, Harvey focused on medicine in this letter, but he also applied his approach to anatomy and physiology. Concerning this approach, he made similar statements in more general contexts. One was to a friend:

. . . the examination of the bodies of animals has always been my delight; and I have thought that we might thence not only obtain an insight into the light- er mysteries of nature, but there perceive a kind of image or reflex of the omnipotent Creator himself.⁽²¹⁾

Again, we can consider "the lighter mysteries of nature" a replacement paradigm. Also, we see that Harvey believed that successive paradigms would approach objective truth and that a greater knowledge of God could be obtained through anatomy.⁽²²⁾

Not all `facts' are equal. The trick is discerning which ones are important. Despite numerous dissections and vivisections, Harvey failed to discover significant anomalies. Undeterred, he then generated them by reasoning based on purpose and his experience. Creativity and experience are involved in developing reasoned anomalies. A discovered anomaly may be recognized immediately, but a reasoned anomaly is not so easily interpreted. It is developed in the mind - a mental, rather than a physical, discovery. Reasoned anomalies entail thinking about familiar things in unfamiliar ways. Reasoning out an anomaly not only requires knowledge, but also the ability to break away from some of that same knowledge.

THE KEY TO THE DISCOVERY

Robert Boyle (1627-1691) has been called the `Father of Chemistry,'⁽²³⁾ and is well-known for the physical law which bears his name. What is not so well known is that he was intensely interested in medicine, and was awarded a medical degree in 1665.⁽²⁴⁾

Boyle published medical books, ranging from his important Memoirs for the Natural History of Humane Blood, Especially the Spirit of that Liquor (London: 1684), to several editions of remedies for laymen, Medicinal Experiments: or a Collection of Choice and Safe Remedies, For The most part Simple and easily prepared: Very useful in Families, and fitted for the Service of Country people (London: 3rd ed., 1696).

Scattered throughout Boyle's works are so many medical remembrances relating to a conversation he had with Harvey that some scholars think Boyle had several meetings with Harvey, even though Boyle claimed only one.⁽²⁵⁾

Boyle had interviewed Harvey some thirty years after the discovery of the blood's circulation. Then Boyle delayed publishing the information from this conversation. These circumstances raise concerns about whether Harvey recalled the true details of the discovery, whether Boyle heard rightly what Harvey said, and whether Boyle correctly remembered the interview. All this is compounded by the fact that Boyle's two accounts of Harvey's discovery differ from each other.

One account of Harvey's discovery is in Boyle's Some Considerations touching the Usefulness of Experimental Natural Philosophy,⁽²⁶⁾ dictated around 1650 (seven years before Harvey's death) but not published until 1663.⁽²⁷⁾In this treatise, Boyle reported that "the structure of the valves of the heart and veins" first influenced Harvey (pp. 34-45). Boyle did not say what it was about this structure that led Harvey to conceive of the blood's circulation. Somehow, the structure of the venous valves was linked to those in the heart. What was that link, and how did it come about?

The link involving Harvey's discovery was that heart valves allow one-way flow only, and their structure, particularly the aortic and pulmonary valves, is similar to that of venous valves. Harvey may have learned of this similarity from Fabricius. In De venarum ostiolis, Fabricius pointed out how the aortic valve (the three cusps of the valve are each marked "F"in Figure 3) is like the venous valves (as seen in Figures 2 and 4).⁽²⁸⁾

The only obvious difference besides size is that the aortic valve has three cusps, while the venous valves have one or two. This comparison suggests that the venous valves are one-way, like the heart's. Harvey knew Fabricius' work well. For example, the similarity between the muscular arms pictured in Figures 2 and 5 is no accident: the only pictures in De motu cordis are nearly identical to the one in Fabricius' book.⁽²⁹⁾

Harvey meant it when he wrote that from among ancients he followed Aristotle, but from among contemporaries, he followed Fabricius.⁽³⁰⁾

Boyle dictated Disquisition to clarify and extend his earlier comments on purpose. However, Boyle stated that he never consulted his previous writings. Therefore, when he came to his Harveian example, he did not check what he had dictated earlier. Instead, he recalled the conversation with Harvey from memory. This recollection differs from what he dictated before:

And I remember that when I asked our famous Harvey, in the only discourse I had with him, (which was but a while before he died), what were the things that in- duced him to think of a circulation of the Blood? He answered me, that when he took notice that the valves in the veins of so many several parts of the body, were so placed that they gave free passage to the blood towards the heart, but opposed the passage of the venal blood the contrary way: he was invited to imagine, that so provident a cause asnature had not plac'd so many valves without design: and no design seemed more probable, than that, since the blood could not well, because of the interposing valves, be sent by the veins to the limbs, it should be sent through the arteries, and return through the veins, whose valves did not oppose its course that way.⁽³²⁾

In this account, Harvey initially made his discovery by observing the orientation of the valves, and by asking in effect, why so many venous valves?

Since not all veins have valves, one could argue that the valves are not that abundant. Harvey does not share this perception; he is struck by their quantity. He mentions twice the abundance of these valves in this account. The presence of "so many valves" in the veins leads to the implied question of why there are none in the arteries. Harvey uses purpose, not to ask about the venous valves or their structure, but to generate a reasoned anomaly about their relative abundance. In Harvey's reasoning process, there should not be so many of these valves.

Harvey's stress on both the orientation and abundance of the venous valves undercuts the idea that later emphasis on their structure influenced Boyle's or Harvey's memory. This observation of the orientation and abundance of venous valves is a unique remembrance of the discovery.⁽³³⁾

There was no earlier emphasis on the valves' direction and abundance which could have affected Harvey's or Boyle's recollection. This fact alone should make scholars cautious about discounting Boyle's report. The best explanation is that Boyle did not contradict himself, but remembered part of the conversation in one treatise and part in another. This interpretation is supported by references to the orientation and number of venous valves in Harvey's earliest, as well as later, works. For example, Harvey discussed the number and competence of venous valves in De motu cordis: Where a valve might be "contrived more negligently," or, where there is but a single valve, such situations are compensated for by the abundance of valves.⁽³⁴⁾

A few single or defective valves might not completely stop the blood's reverse flux, but so many valves result in one-way flow, causing Harvey to reason that there is an anomaly here.

Harvey also rejected Fabricius' explanation because of a recognized anomaly. He wrote that the discoverers of the valves "did not rightly understand" their purpose, and specifically cited the orientation of the jugular vein valves:

. . . for their office is by no means explained when we are told that it is to hinder the blood, by its weight, from all flowing into inferior parts; for the edges of the valves in the jugular veins hang downwards and are so contrived that they prevent the blood from rising upwards. . . . ⁽³⁵⁾

Harvey understood Fabricius' position, but saw no support for it. In the above passage, Harvey used the Latin term `valvulas' (or a form of it) and not Fabricius' `ostiola' to identify the cusps in the veins. This difference in nomenclature accurately reflects the different role of these cusps in Fabricius' physiology compared to their role in Harvey's. When and why did Harvey realize Fabricius was wrong?

THE EARLY EVIDENCE

While giving recognition to Fabricius, Salomon Alberti, a German anatomist, described the one-way nature of the valves in the veins in 1585. Immediately following the section on the venous valves, he described the ileocecal valve located between the small and large intestines. Harvey read this section, and in his lecture notebook, Prelectiones Anatomiae Universalis (1616), compared the function of the ileocecal valve to that of the valves in the veins: "Those who say as Sal[omon] Alb[erti] that there is within [the bowel] a membrane which closes the passage as in the veins."⁽³⁶⁾

Without getting into its construction,⁽³⁷⁾ the important function of the ileocecal valve is that it stops reverse flow. Similarly, preventing reverse flow is what the valves in the veins do also. Of interest to us is the fact that Harvey treated the one-way nature of the venous valves as a given. He compared the ileocecal valve to the venous valves, and not vice-versa. Also, he used `valvulas,' not `ostiola.' Why? He did not use Fabricius' nomenclature because he had already rejected his old teacher's interpretation concerning the function of the venous valves. He knew the valves are one-way and therefore the old explanations of the blood's motion had to be incorrect.

Additionally, Harvey mentioned the orientation and abundance of the venous valves later in his Prelectiones. Writing before he hypothesized the blood's circulation, Harvey remarked that "Wherefore there are many valves in the veins opposed to the heart; the arteries have none except at the exit from the heart."⁽³⁸⁾ This important early observation has a lot packed in it. Analyzing these observations, we find that it encapsulates what we know from Boyle's reports about the discovery and what Harvey later wrote about the venous valves in De motu cordis:

1. There is more emphasis on the valves' abundance

than on their structure.

2. There is a link to the heart, (the aortic valve "at

the exit from the heart.")⁽³⁹⁾

3. There is a contrast between the venous system and

the arterial.⁽⁴⁰⁾

4. All valves have the same orientation ("opposed to

the heart").

5. The comparison of the veins and arteries has

the form of a reasoned anomaly.

The broader context of the above passage from Prelectiones involves the heart's pulse, not the blood's circulation. Again, what is important here is Harvey's nomenclature. He wrote `valvulas,' not Fabricius' `ostiola' for the valves in the veins. Harvey used Fabricius' picture, but not his terminology because even at this early date he already doubts Fabricius' explanation.

ANALYSIS OF THE REJECTION

There are several possible ways Harvey could have come to realize Fabricius was wrong about the venous valves. One was through the influence of Alberti, who said they were one-way. Another was the similarity of venous valves to the one-way heart valves. Harvey knew this either from his own dissections, or from Alberti, or from Fabricius' pictures (Figures 2 and 3). Other reasons originate with Fabricius' De venarum ostiolis: Fabricius observed that ostiola could hold back venous blood and thought thick blood could be held back for a long time. He also explained that anyone pushing "the blood down through the veins would feel the resistance and power of the ostiola." Finally, Fabricius reported that triple ostiola had been found in veins of oxen. Yet, in his own words, the triple cusps in the heart "prevented reflux of blood."⁽⁴¹⁾

Therefore, Harvey made no great conceptual leap to reason that even if they were not 100% efficient, the abundance of ostiola effectively stopped reverse flow. By 1617 he had made that leap.⁽⁴²⁾ He had rejected Galen's and Fabricius' explanations, but had no replacement paradigm. Thus he was not yet ready to publicize his doubts.

Years later, when Boyle asked Harvey what first induced him to think that the blood circulates, Harvey remembered correctly. His answer, in Disquisition, "that so Provident a Cause as Nature had not so Plac'd so many Valves without Design," and "were so placed that they gave free passage to the blood toward the heart" expanded on Harvey's statement in his 1616 Prelectiones. Also in this statement is the link between the structure of the venous and cardiac valves referred to in Considerations. Both reports Boyle dictated about Harvey have their genesis in Harvey's Prelectiones. Thus, we have reconciled Boyle's accounts of Harvey's discovery. The keys to rejecting the current paradigm were the abundance of venous valves, their orientation, and their similarity to the one-way heart valves.

Rejecting a reigning paradigm is a first step in advancing science. Yet, this does not necessarily give the investigator a new paradigm.⁽⁴³⁾ So it was with Harvey. He knew the correct structure and function of the valves, but not their purpose. The search for purpose resulted in the conception of a replacement paradigm.

HARVEY'S HYPOTHESIS

In Chapter VIII of De motu cordis, Harvey reported several reasoned anomalies and wrote about how he hypothesized that the blood circulates:

In truth, when, from a variety of investigations through dissection of the living in order to experiment and through the opening of arteries, from the symmetry and magnitude of the ventricles of the heart and of the vessels entering and leaving (since Nature, who does nothing in vain, would not have needlessly given these vessels such relatively large size), from the skillful and careful craftsmanship of the valves and fibres and the rest of the fabric of the heart, and from many other things, I had very often and seriously thought about, and had long turned over in my mind, how great an amount there was, that is to say how great the amount of transmitted blood would be [and] in how short a time that transmission would be effected, . . . I began privately to think that it might rather have a certain movement, as it were, in a circle, . . . .⁽⁴⁴⁾

While there is much in this passage,⁽⁴⁵⁾ we will focus on the purpose for the comparatively large size of the heart vessels. Researchers discovered the ventricles long ago, and nothing appeared abnormal about them. Nevertheless, Harvey generated an anomaly by judging that they were too large for their role in the current paradigm. Since he thought that nature does nothing in vain, he had to find a different explanation for this anomaly.

For Harvey, it followed that the "relatively large size" of the ventricles and their conduits made it likely that blood was abundant in the body.⁽⁴⁶⁾ Nevertheless, it appears that this abundance was a derivative factor from his prior consideration of their large size. If the blood's quantity initially led to the circulation hypothesis, then this quantity would explain the vessels' large size. In which case, Harvey would have said so - but he did not. Instead, he wrote that "since Nature, who does nothing in vain, would not have needlessly given these vessels such relatively large size." The ventricles and their conduits have been designed large and the question is why so large?

Only now is Harvey ready to address the blood's quantity. Quantity is important, but of the many factors involved, there is no justification to say it was prior. If anything, quantity was one of the last factors Harvey considered, after which the hypothesis started to come into focus. Also, Harvey does not calculate amounts of blood.⁽⁴⁷⁾ It is the comparatively large size of the vessels which suggests the abundance of blood involved.⁽⁴⁸⁾ This abundance does become important and poses questions of its own. One is the purpose-based question, why is there so much blood passing through the heart in so short a time?⁽⁴⁹⁾ (This is another reasoned anomaly.) Other inferences include the heart's symmetry and related vessels, and "many other things." These "other things" included the number of venous valves, and their orientation.⁽⁵⁰⁾ Just the same, the real importance of the venous valves involved Harvey's earlier rejection of Galen's paradigm.

DISCUSSION

Harvey sought to solve nature's mysteries. He dissected and vivisected. He studied the slowed-down heartbeats of dying animals. He experimented with tourniquets both loosely and tightly applied. He examined simple and compound hearts. If Harvey had discovered the capillaries, then he would have recognized an anomaly. However, this discovery was made later, with an improved microscope. Instead, Harvey joined his mass of accumulated data with the idea of purpose to generate reasoned anomalies. The reasoned anomaly of the abundance of the venous valves, their orientation, and their similarity to the cardiac valves led Harvey to reject Galen's and Fabricius' physiology. Harvey had previously mentioned these keys to his discovery in his Prelectiones (1616), so he had to have rejected the other explanations by that time.

Harvey's next step was paradigm replacement. From De motu cordis, we can see that Harvey meditated on many factors. The factors included:

1. Reasoned anomalies based on his experience (includ-

ing the venous valves).

2. The symmetry and magnitude of the heart ventricles

and associated vessels.

3. The skillful and careful craftsmanship of the heart

valves as well as other parts of the heart.

4. The amount and transmission time of the blood

transmitted by the heart.⁽⁵¹⁾

These led him to hypothesize that the blood circulates. This conception had to occur before the middle of 1619, since the evidence is that he had written De motu cordis by then. The blood's quantity was not a consideration in rejecting the old physiology, and was just one of many factors in hypothesizing the replacement paradigm. We can say that, with his discovery of the blood's circulation, Harvey also became the discoverer of the real purpose of the venous valves. First the valves appeared to fit the old paradigm; then Harvey made them reasoned anomalies; now they are retrorecognized anomalies as well. These valves are not floodgates slowing blood flow, but are check valves aiding the blood returning to the heart. Harvey, by his way of thinking, had finally determined God's intentions in the design of the venous valves and, with the discovery of the circulation, he also had found one of nature's secret mysteries.⁽⁵²⁾

ACKNOWLEDGEMENTS

Portions of the research for this paper were funded under a grant from The Pascal Centre, Redeemer College, Ancaster, Ontario. Opinions expressed in this article are not necessarily those of The Pascal Centre or Redeemer College. I thank R.S. Westfall, T. Whelan, C. Briggs, and anonymous reviewers for their comments. I am especially indebted to S. Wykstra for his comments. Figure 1 is from Tabulae anatomicae sex, 1874 ed., National Library of Medicine. Figures 2-4 are from Hieronymus Fabricius' De venarum ostiolis, 1603 (C.C. Thomas Co., facsimile, 1933). Figure 5 is from W.R. Lefanu, Notable Medical Books (1976) and is by permission of Eli Lilly and Co.

NOTES AND REFERENCES

1. Lord Cohen of Birkenhead argues for the idea of the sameness of the blood. Lord Cohen of Birkenhead: The germ of an idea, or what put Harvey on the scent? J His Med 12:102-105,1957. W. Hunter thinks it was an overripe plum ready for anyone to pick. Banyon HP: The significance of the demonstration of the Harveian circulation by experimental tests. Ann Sci 3, 4:444, 1938, 1939. Banyon says it could have been Harvey's intelligent experimental method. Ibid, p453. Gweneth Whitteridge contends for the venous valves, Isis, 71:503, 1980.

2. Pagel W: "William Harvey's Biological Ideas." New York: Hafner Publishing Co., Inc., 1967, p53. See also Bylebyl JJ: The medical side of Harvey's discovery: the normal and the abnormal. In William Harvey and His Age (Bylebyl, Ed) Baltimore: The Johns Hopkins University Press, 1979, pp28-102. In the 1980's, Bylebyl and Whitteridge debated what first led to Harvey's discovery in the pages of Bul His Med.

3. M. Ghiselin, "William Harvey's Methodology in De motu cordis from the Standpoint of Comparative Anatomy," Bul His Med 40:314-327, 1966

4. R. Willis, in an older study, thinks Harvey wrote De motu cordis before 1619. Willis R: The life of William Harvey. In The Works of William Harvey. London: 1847, pxl (hereafter called "Works." Whitteridge supposes Harvey began hypothesizing blood circulation in 1619 and cautiously guesses 1625 for the full discovery. Whitteridge G: "William Harvey and the Circulation of the Blood." New York: American Elsevier, Inc., 1971, p105. Pagel dates Harvey's conception in 1626-1627. Pagel W: "New Light on William Harvey." Basel: S. Karger, 1976, pp9 and 12; earlier it was `the latter part of the first half of the 1620's.' Pagel W: "William Harvey's Biological Ideas." New York: Hafner Publishing Co., 1967, p341. G. Keynes thinks the mental discovery was not as early as 1616 and places it between 1619 and 1628. Keynes G: "The Life of William Harvey." Oxford: The Clarendon Press, 1966/1978, pp108-109.

5. Harvey W: "An Anatomical Disputation concerning the Movement of the Heart and Blood in Living Creatures." (Whitteridge Trans) London: Blackwell Scientific Publications, 1976, p5.

6. Ibid, p6. This early date could explain hints that some of the medical community on the continent heard rumors of Harvey's discovery by 1622. Ferrario EV: William Harvey's debate with Caspar Hofmann on the circulation of the blood. His Med 15:7-21, 1960.

7. Ibid, pp10 and 100 respectively.

8. See Laudan L et. al: Testing theories of scientific change. Synthese 69:154, 163, 1986. `Paradigm' should not be tightly defined - it could even be considered as a habit of the mind. See Margolis H: "Paradigms and Barriers, How Habits of Mind Govern Scientific Beliefs." Chicago: University of Chicago Press, 1993, p2.

9. Wear A: William Harvey and the `way of the anatomists.' His Sci 21:223-249, 1983.

10. The importance of anomalies is discussed by Kuhn TS: "The Structure of Scientific Revolutions." Chicago: The University of Chicago Press, 1962/1970; Humphreys WC: "Anomalies and Scientific Theories." San Francisco: Freeman, Cooper, & Co., 1968; and others such as Reines BP: On the role of clinical anomaly in Harvey's discovery of the mechanism of the pulse. Persp Bio Med 34:128-133, 1990. While Kuhn's ideas on anomalies and paradigms have been criticized, broadly considered, they are still interesting. I prefer to think of a paradigm as the received view which is taught as authoritative.

11. The importance of hypotheses is discussed by Hempel C: "Philosophy of Natural Science." Englewood Cliffs, N.J: Prentice Hall, Inc., 1966, p15.

12. 12.Hereafter called "De motu cordis."

13. Pagel W: "New Light on William Harvey," p14. I second Pagel's statement that "The search for purpose was a mighty motive directing Harvey's research before, during and after the discovery [of the blood's circulation]. It is conspicuous in his account of it and perhaps more so than the modern scientific peruser would like or allow." Ibid, p23.

14. Bumer A: Christian Aristotelianism and atomism in embryology. Science and Religion - Wissencraft und Religion (Buttner and Bumer, Eds) Bochum: Brockmeyer, 1989, pp16-24. Harvey refers to Jesus twice in his scientific writings. In one of them, he could have written "Jesus," but instead intones "our Savior Christ, of men most perfect." "Works," p529.

15. Lightman A and Gingerich O: When do Anomalies Begin? Science 255:690, 1992. This type of anomaly is described, but not named, in "Anomalies and Scientific Theories," p56.

16. H. B. Adelmann is correct in stating that "if ever a man was influenced by his teacher, that man was Harvey." Adelmann HB: "The Embryological Treatises of Hieronymus Fabricius of Aquapendente." New York: Cornell University Press, 1942, p115.

17. Hereafter `ostiola' will be used in place of `little doors.'

18. Fabricius H: "De venarum ostiolis," 1603 (Franklin KJ Trans) Springfield, IL: C.C. Thomas, 1933.

19. Fabricius' method is considered part of the `Aristotle Project' at Padua. Cunningham, A.R: Fabricius and the `Aristotle Project' in anatomical teaching and research in Padua. The Medical Renaissance of the Sixteenth Century (Wear, French and Lenie, Eds) New York, NY: Cambridge University Press, 1985, pp195-222.

20. "Works," p616.

21. Ibid, p146.

22. See also Ibid, p153. This emphasis on finding truth in nature is where Harvey went beyond the `Aristotle Project.' The reasons for this may have been due to the rise of scepticism and different responses to this challenge by Protestants and Catholics. A beginning point for this line of reasoning is Popkin RH: "The History of Scepticism from Erasmus to Spinoza." Los Angeles, CA: University of California Press, 1979.

23. R. Pilkington, Robert Boyle, Father of Chemistry (London: John Murray, 1959).

24. W.R. LeFanu, Notable Medical Books (Indianapolis: The Lilly Research Laboratories, 1976) p. 93.

25. Hunter RA and Macalpine I: William Harvey and Robert Boyle. Notes Records Roy Soc London, 13:115-127, 1958.

26. Hereafter called "Considerations."

27. Frank, Jr RG: "Harvey and the Oxford Physiologists." Los Angeles: The University of California Press, 1980, p316.

28. "De venarum ostiolis," p52. Harvey probably learned earlier about the venous valves as Fabricius' student. Fabricius' `discovery' of them was witnessed by his German students, (Ibid, p45) and he frequently showed them to his students thereafter. "William Harvey and the Circulation of the Blood," p21.

29. Keynes G: "A Bibliography of the Writings of William Harvey, M.D., Discoverer of the Circulation of the Blood." Cambridge, 1928.

30. Harvey's text for the demonstration of the valves in the veins, as shown in Figure 5, also derives from Fabricius. See "De venarum ostiolis," p50. However, there is a deeper way Harvey follows Fabricius. Fabricius criticized Vesalius for not going beyond careful anatomy to physiology. Fabricius and Harvey do go beyond careful anatomy to physiology, but Harvey's physiology was more careful, and therefore more productive, than that of Fabricius.

31. Hereafter called "Disquisition."

32. Boyle R: "A Disquisition about the final causes of natural things: Wherein it is Inquired, Whether, And, (if at all) with what Cautions a Naturalist should admit them?" London, 1688, pp157-158. (The emphasis is mine.) Boyle dictated this in the 1670's for Henry Oldenburg. When Oldenburg died, Boyle delayed finishing it.

33. J.J. Bylebyl completely overlooks the abundance of the venous valves. Rather, he focuses on the structure of the valves. Bylebyl JJ: Boyle and Harvey on the valves in the veins. Bul His Med 56:351-367, 1982. He also sets up a false comparison by asserting that Harvey said the quantity of transmitted blood was what "first led him to conceive of the circulation." Ibid, p352. We will see that there is no direct support for this assertion.>

34. "Works," pp66-67. Harvey's experimental determination that the valves are truly one-way was for justification, not discovery, Ibid, p64.

35. Ibid, p63.

36. Harvey W: "Lectures on the Whole of Anatomy" (O'Malley, Poynter, Russell, Trans) Berkeley: University of California Press, 1961, p77. (Hereafter called "Lectures" in the footnotes and "Prelectiones" in the text.)

37. The ileocecal is a sphincter valve.

38. Harvey W: "Lectures, p191. The date of this lecture notebook is nominally 1616, with some parts added later. Harvey wrote this passage prior to 1617. (However the next page after this quotation is Harvey's famous later addition on the blood's circulation. The handwriting of this addition is different from the main text.) "William Harvey and the Circulation of the Blood," pp87-88.

39. In "De motu cordis," Harvey explains "that the function of the valves in the veins is the same as that of the three sigmoid valves which we find at the commencement of the aorta. . . ." "Works," p66.

40. In "De motu cordis," Harvey, while discussing the valves in the veins, states "Let it be added that there are no valves in the arteries (save at their roots). . . ." "Works," p63.

41. "De venarum ostiolis," pp50-53.

42. This may partially explain a marginal note in the notebook of Henry Power (1623-1668) to the effect that Harvey made his discovery in 1614. Banyon HP: The significance of the demonstration of the Harveian circulation by experimental tests. Ann Sci 3, 4:443-453, 1938, 1939.

43. Braithwaite RB: "Scientific Explanation." New York: Cambridge University Press, 1968, p20.

44. Bates DG: Harvey's account of his `discovery.' Med His 36:361-378, 1992. This is the latest and best researched translation of this important passage.

45. One error in this critical passage is that `copia' (abundance) has no noun in the genitive to define it. Willis' translation is "mass of evidence," "Works," p45; Bylebyl's translation is "amount [of blood]." (See Bylebyl's article on Harvey in the "Dictionary of Scientific Biography," Vol. 6, (Gillispie Ed) New York: Charles Scribner's Sons, 1970, p155.)

46. Galen used this same line of reasoning in his analysis of the kidneys. Temkin O: A Galenic model for quantitative physiological reasoning? Bul His Med 35:470-475, 1961.

47. Later in "De motu cordis," Harvey estimates the quantity of blood by means of a qualitative thought-experiment, but the context is justification, not discovery.

48. In the Introduction of "De motu cordis," Harvey follows this same pattern. He deduces that there is a large amount of blood from the size of the vessels involved. There is no calculation of the amount of blood. "Works," p15.

49. In "De motu cordis," Harvey also addresses the abundance and rapid motion of the blood also in the context of experimenting with the valves in the veins (as seen in Figure 5). "Works," p67. Since Fabricius had his readers similarly experiment with a ligated arm, this could be the initial stimulus for Harvey's meditation on the quantity of blood ("De venarum ostiolis," p50).

50. R. French argues that the orientation of the venous valves "triggered the recognition of the circulation in "William Harvey's Natural Philosophy." New York, NY: Cambridge University Press, 1994, p350. In a footnote, he discounts the notion that consideration of the quantity of blood led to the discovery as a "reading back the characteristics of modern science," p92. >

51. A fifth meditation may have been the general idea of movement in a circle. Pagel W: J His Med 6:116, 1951 and 12:140, 1957. Jucovy PJ: Circle and circulation: the language and imagery of William Harvey's discovery. Pers Bio Med 20: 92-107, 1976. Again, there are no grounds for saying it was what first induced Harvey to conceive of the circulation.

52. There are other illustrations in the Scientific Revolution of the approach which Harvey utilized. Nicholas Copernicus generated reasoned anomalies to challenge Ptolemaic astronomy. John Ray used them in questioning spontaneous generation. Isaac Newton rejected the prevailing theory of colors because of a recognized anomaly. Then he developed a replacement theory.