COURSE TITLE: “Origins of Experimental Medicine: William Harvey’s 1628 masterpiece Exercitatio Anatomica de Motu Cordis et Sanguinis in Animalibus.”
CODIFICATION:NUMBER OF CREDITS/HOURS: 3 credits/ 72 hours
NAME OF COORDINATORS: Angel A. Roman-Franco MD, Raul Mayo-Santana PhDCOORDINATOR’S OFFICE: Department of Pathology; A359
COORDINATOR OFFICE AND CONTACT PHONES: 758-2525, ext 1526
MEETING PLACE: Dept. of Pathology meeting room
HOSPITALS: None
PRE-REQUISITES: None
CO-REQUISITES: None

William Harvey
William Harvey

COURSE OBJECTIVE

The objective of this course is to survey the history of William Harvey (1578-1657) and through the experimental and analytic work compiled in his Exercitatio Anatomica de Motu Cordis et Sanguinis in Animalibus, (An Anatomical Exercise on the Motion of the Heart and Blood in Living Beings) published in Frankfurt in 1628, in the development of Renaissance, modern and contemporary medicine. The course will initiate with a survey of Harvey’s antecedents in Classical Greek and Roman, primarily Galenic, and in Arabic Medicine and the emergence of the epistemological tools that gave course to Harvey’s work. The objective is to be accomplished by addressing through focused lectures and textual analysis of De Motu Cordis and germane literature of several key topics, among which are: the role of Aristotelian, Galenic and Medieval science and medicine on the ideas and methods employed by Harvey; the philosophical background of the experimental and anatomical dissection tradition; the origin, development and application of quantitative methods employed by Harvey and their novelty in Western medicine; and the response by the medical culture of the time to the blood circulation discovery including its detractors as well as supporters. Emphasis will be placed on the contributions to the evolution of Harvey’s thought of Paduan Aristotelianism and its adherents as well as the influence of the coeval experimental philosophy developed by Galileo Galilei. A subsidiary objective is to acquaint the student the techniques of hermeneutics employed in the interpretation and analysis of Harvey’s De Motu Cordis as an instrument through which to understand the creation and development of scientific medicine.

COURSE JUSTIFICATION:

This course is intended for science students of all scientific disciplines. The course provides a guideline and platform upon which the student can pursue further studies on Renaissance history and philosophy of science as seen through the work of William Harvey. This is a field of knowledge not generally offered to science students at the baccalaureate level. It lays the groundwork for understanding the emergence of modern anatomy and physiology.

William Harvey, working within the combined tradition of the experimental anatomy and physiology of Galen[1],[2],[3] as well as the newly developed quantitative and experimental methods of Galileo[4],[5],[6] and the Aristotelian Paduas,[7] as well as the comparable analytic traditions emerging in the University of Oxford,[8] led him to the elucidation of the circulation of the blood on the strength of which he is recognized as the creator of the modern field of experimental physiology and medicine. Emphasis will be also placed on the way his work concerning the circulation of the blood presages the present concept of systems biology. Systems biology has numerous descriptors already presaged in Harvey’s work, for systems biology entails the application of mathematics to the different levels of description and analysis. Firstly, this analysis may begin from the bottom, i.e., the level of facts (exemplified by the clinical method);[9] secondly, it may begin from the top via the use of models or as a third methodology, a combination of the two. Harvey’s De motu cordis exemplifies the effective integrated use of these heuristic tools. Because his work is pivotal in the origin of modern biological analysis as applied to a historically cardinal issue in physiology and medicine it is important for the student of the history of medicine not to neglect the insights inherent to it. In that sense Harvey’s work belongs in the same genus as Claude Bernard’s Introduction à l’étude de la Médicine Expérimental (Introduction to the Study of Experimental Medicine)[10] and Gregor Mendel’s Versuche über Pflanzen-Hybride (Experiments on Plant Hybridization)[11] as it embodies the essence of scientific medicine.

Admittedly William Harvey’s discovery of the circulation of blood is the salient accomplishment of Renaissance biological science. He posited several fundamental questions for which there were available answers grounded on Galenic tradition and the work of his commentators,[12] such as:

  1. What relationship is there between the motions of the auricles and of the ventricles?
  2. Which is the systolic and which the diastolic motion of the heart?
  3. Is arterial pulsation attributable to the propulsive force of the heart?
  4. What is the ultimate function of the cardiac and venous valves?
  5. How does blood course between the right to the left ventricle?
  6. What is the direction of blood flow to and from the heart?
  7. What is the blood volume and how long does it take to circulate?

Despite the fact that he lacked observational knowledge of the capillary circulation to establish the continuity between arteries and veins, as the microscope was yet to be invented, Harvey concluded through inductive reasoning that ‘…blood is driven into a round by a circular motion and that it moves perpetually; and hence does arise the action or function of the heart, which by pulsation it performs.’ His revolutionary concept, first presented to the College of Physicians in 1616 and published in 1628, became accepted in his lifetime. He mentioned early evidence leading to his discovery in his Prelectiones, his lecture notebook,[13] in 1616, coincidentally the year of Robert Cardinale Bellarmine’s admonition to Galileo not to pursue further the Copernican Heliostatic theory, an ironic coincidence given the fact that Harvey’s circulatory theory is deeply intertwined with astronomical circular motion. Needless to say, on April 23rd of the said year Cervantes and Shakespeare died. After rejecting the old Galenic vascular paradigm, Harvey sought the right explanation. He continued making additions about the circulation to his Prelectiones at various times up to at least 1626. Remarkably one of these later additions is a short entry on the discovery of the circulation.

Harvey’s Method.

A contemporary of René Descartes, and as a Paduan student exposed in the emerging Galilean scientific experimental method, Harvey created modern medical physiology and brought the aborning scientific method into Western medicine. He is thus rightly esteemed as the creator of the field of experimental medicine as practiced in the context of the Western scientific canon.   In addition to the new research method Harvey employed research techniques derived from earlier methodologies that antedated him by over 700 years. These methodological prototypes sprang into science with early physicians such as Claudius Galenus.   Galenic medical philosophy was derivative of Hippocratic medical philosophy as taught at the school at Kos. It is upon the work of Hippocrates and the Kosans that Galen builds the edifice of his medical ouvre and adds to that tradition an early version of the experimental method to advance medical physiology and resorts to vivisections of animals for his work on anatomy, including circulatory anatomy and physiology.

The experimental method of Galen’s time waned in the turmoil of Late Antiquity (235-650 CE) but was recovered by Arabic natural philosophers and commentators[14],[15] such as the physician and practical alchemist Jābir ibn Hayyān (721-815)[16] and the philosopher and physician Yaʻqūb ibn Isḥāq al-Kindī [Lat. Alkindus] (801-873)[17], both early Arab exponents of the application of experimentation and quantification in ascertaining the validity of empirical observations and theories. Coeval with these Muhammad ibn Zakariyā Rāzī [Lat. Rhazes or Rasis] (865–925) also expounded the use of experimental methods, in his particular case as a tool in clinical trials. Rhazes designed a clinical trial to discern the relative therapeutic value of bloodletting in cases of meningitis.[18]

These prototypes were expanded upon by the polymath Abū Rayhān al-Bīrūnī (973-1048)[19] and, as example of a scientifically inclined physician closer to the time of Harvey, the Persian Abū ʿAlī al-Ḥusayn ibn ʿAbd Allāh Ibn-Sina [Avicenna] (c. 980-1037)[20], who stipulated “the recognition of the strengths of the characteristics of medicines through experimentation.” Ibn-Sina’s treatise al-Burhân (On Demonstration) of his Kitab al Shifâ’ (the “Book of the Healing”)[21] closely follows Aristotle’s Posterior Analytics, upon which Robert Grosseteste’s (1175-1253) will later expand.[22] These approaches to scientific analysis[23] filtered from the Islamic Empire into the nascent Europe following the re-conquest by the Spaniards of the great learning and translation centers of Toledo (1085) and later on that of Córdoba (1236).

With the coming of the 12th century and its coeval Renaissance, Aristotelian empiricism,[24] coupled to the experimental methodologies of the aforementioned Islamic natural philosophers, made their way into the mainstream of European thought as attested to by Grosseteste’s commentary on Aristotle’s Posterior Analytics.[25] Upon this foundation the Franciscan friar Roger Bacon (1214-1294) posited his iterating system of observation, hypothesis and experimentation, coupled to independent verification, which embodies the fundamental algorithm of the contemporary scientific method. Following the work of Bacon came that of the Paduan Aristotelian natural philosopher Giacomo Zabarella (1533–1589), a precursor of Galileo and an exponent of the Baconian scientific method.[26]   His work, coupled to that of William of Auvergne (ca.1180/90–1249) in addition to that of Bacon and Grosseteste laid the foundation of the European version of the scientific method.[27] Galileo built upon this tradition employing it to conduct his experiments on motion. However, he presented his findings in a the deeply traditional Euclidean more geometrico[28] instead of the hypothetico-deductive mode of Bacon.[29]   In his written work he scarcely addresses the methodological and epistemological rationale of the method he employed.[30]

Anatomy of the circulatory system from Galen to Harvey and his sources in Renaissance anatomy, medicine and philosophy.

William Harvey was performing his work as the Galenic edifice, at least an anatomical part, was being dismantled. Some key issues concerning Galen’s description of the movement of the blood, particularly his positing of pores that could not be visually resolved connecting the ventricular chambers were being subjected to criticism. Ibn al Nafis (1213–1288) was the first physician to question Galen’s authority in cardiac anatomy and physiology. He is also the first one to posit a pulmonary transit or circulation.[31],[32] It appears that the information did not enter academic or medical discourse, being independently brought to the fore about three centuries later by the Spanish theologian and physician Miguel Servet [Lat., Servetus] (1511–1553),[33] (executed at the stake by John Calvin, in Geneva, on account of his nontrinitarian Christology). Al-Nafis contributions to the knowledge of the pulmonary circulation links the early studies of the school of Galen (130–199) in the 2nd century to that of European Renaissance scholars such as Servetus, Realdus Columbus (1516–1559),[34] Vesalius and Harvey.

In addition to the works of Classical physicians, Harvey was also familiar with the work of many of his immediate predecessors such as the Dutch physician Jacobus Sylvius, discoverer of the homonymous aqueduct (1478-1555); the Italian physician Girolamo Fracastoro (1478-1553) who in 1546 he proposed that epidemic diseases are caused by transferable tiny particles or “spores” that could transmit infection by direct or indirect contact or even without contact over long distances, and sagely wrote “I call fomites such things as clothes, linen, etc., which although not themselves corrupt, can nevertheless foster the essential seeds of the contagion and thus cause infection;”[35] as well as minor ones such as Giulio Cesare della Scala (1484–1558) and Andreas Laurentius Grotte (1605-1664). These authors begin to work around the evident Galenic problems extant in his animal-derived anatomy because such anatomy was not readily transferable to humans.     He was also well acquainted with the work of his immediate contemporaries such as the French philosopher, mathematician and physician Jean François Fernel (Lat., Fernelius) (1497–1558) author of the anatomical treatise De Naturali Parte Medicinae Libri Septem, published in 1542 where he introduced the term “physiology,” and provided the first descriptions of the central canal of the spinal cord and of the peristaltic motion of the intestine;[36] the anatomical works and new pictorial system of representing anatomy of Vesalius,[37] himself noted for his anti-Galenic stance, as well as his coetaneous and also redoubtable challenger of Galen, Bartolomeo Eustachi [Lat., Eustachius](1500 or 1514 –1574); Hieronimus Fabricius ab Aquapendente (1537–1619), pupil of Fallopio, Paduan surgeon and anatomist and Harvey’s teacher and mentor; also Vesalius’ student and fellow anatomist Realdus Columbus (ca. 1516-1559); the vascular anatomist Jul. Cæs. Arantius (1530-1589), discoverer of the separation between the fetal and maternal circulation, a position contrary to that of Hippocrates and Galen; the French physician and anatomist Leonardus Botallus (1519-1587); the Swiss botanist Caspar Bauhin (Gaspard- 1560–1624), precursor of Linnaeus’ binomial classification system; the Dutch osteoloist Volcherus Coiter (1534-1576); Ulysses Aldrovandus (1522-1605) who was a botanist and who revived the interest in Aristotle’s works on biology; the renowned philosopher René Descartes; the Itallian natural philosopher Cæsare Cremonini (1550-1631), infamously remembered Aristotelian who refused to look through Galileo’s telescope; the Italian physician and anatomist Gasparo Aselli (1521-1626), discoverer of the lymphatic lacteals; the also Italian physician and renowned Aristotelian Fortunius Licetus (1577–1657); the Flemish anatomist and fellow Paduan Adrian van der Spieghel (1578-1625) and the German physician Daniel Sennert (1572-1637), another prominent Aristotelian who proposed an intermediate step between corpuscular particle theory and Aristotelian forms. In general all of these physicians and natural philosophers adhered, with varying tenacity, to the philosophy of Aristotle. This in spite of the fact that in the tense religious milieu of the late Renaissance (ca. 1550-1650), traditional charges of impiety directed against Aristotle were wielded with renewed vehemence. Aristotelian philosophy at its first entry into the European universities did not receive a warm welcome in the more ecclesiastically leaning universities, such as Paris. The condemnations of 1277, published by Stephen Tempier, Bishop of Paris,[38] failed in their attempt to prevent Aristotelianism from being included in university curricula. This failure was particularly notable at Padua, where Aristotle was dominant and continued so until well into the Renaissance. Galen was not that warmly received at Padua where Galenism met with a headwind coming from many of Harvey’s contemporaries, otherwise proponents of Aristotle. Several other philosophical and biological (medical) strands interweave to form the knowledge tapestry that would form the backdrop of Harvey’s work, including the natural philosophers of the 14th and early 15th centuries.

It is interesting to note that Galen’s influence in Europe declined after the collapse of the Roman Empire and the discord of the early medieval period disrupted scientific study and education. However, by the 1300s, with the rediscovery of Classical learning Galen again became a primary figure amongst contemporary physicians. The Church favored his works as they we understood to be harmonious with Christian doctrine, and put a great deal of effort into defending Galen. [39] For nearly two centuries physicians, academic as well as non-academic ones, believed his ideas were correct and that it was nearly impossible to improve on his work. Despite this fairly dogmatic background Vesalius became a pioneer in questioning Galenism as a result of his empirical observations. So successful was he that by the 1500’s serious and strong critiques of Galenism were being made, at least by minds that were more experimentally inclined. Aristotle, however, did not suffer the same fate among physicians, though he was severely questioned by the likes of Galileo.

The concept of circularity, its symbolism and its impact on Harvey.

Harvey was a devoted follower of Aristotle, and thus felt in harmony with the prevailing Aristotelianism of the Paduans. As such he adhered to the underlying unity between various circular motions in the universe – the planets in the heavens, air and rain in the sky, a view he eventually extended to the movement of blood inside bodies. As he put it, the heart ‘deserves to be styled the starting point of life and the sun of our microcosm just as much as the sun deserves to be styled the heart of the world.’[40] Harvey far from being a radical reformer was an Aristotelian and Galenic traditionalist who, despite all his experiments, adhered firmly to Aristotelian dynamics and kinematics.[41] John Aubrey states: Harvey ‘bid me goe to the fountain head and read Aristotle … and did call the neoteriques shitt-breeches.’[42]

Harvey considered rest and motion as different things and motion as a superadded quality. He did not envision motion as a property of the heart but of the blood, attributing it to its “innate heat,” which is as far as his Aristotelianism would have led him. Furthermore, by way of explanation he further asserted that the blood’s innate heat is not fire, nor derived from it; and that the blood is a spirit, not occupied by one; it is also “celestial, for in nature, (that is, the soul) that which answers to the essence of the stars, is something analogous to heaven, the instrument of heaven.”[43] In denying that a spirit descends and stows itself in the blood or elsewhere, as an “extraneous inmate,” he bravely says: “I cannot discover this spirit with my senses, or any seat of it.”[44]

The concept of circular, uniform motion was central to the mechanics of Greek astronomy and physics as well as philosophy. Aristotle’s exposition of circular motion and its universal symbolism was an elaboration of doctrines first posited by Plato who was the first to visualize the movement of the blood as a homolog in the microcosmos of the motion of the universe.[45] Aristotle, following Plato posited that only circular motion is eternal, since other types of motion have an initiating-point, a mid-point and end-point, whereas circular motion is bounded but unending.[46] This view was essentially unchanged throughout Late Antiquity and the Middle Ages and even up to the time Copernicus was in Padua. Copernicus entered the University of Padua to study medicine in 1501 and he stayed until 1503, but did not acquire a degree in medicine, going on instead to study canon law. Galileo would follow him in this path beginning in 1592, when he too entered the study of medicine (though he obtained his degree and went on to develop medical instruments) and continued on to teach mathematics until 1610.[47] A consummate Aristotelian it was part of Harvey’s intellectual armamentarium to consider the circular motions of the heavens as prefiguring the circular motions in the microcosmos of man. Thus he confidently states: “Coepi egomet mecum cogitare, an motionem quandam quasi in circulo haberet…”[48]

It is of importance to understand the pervasiveness of the concept of circularity to understand that just as in the times of Copernicus the medical curriculum at the University of Padua did not just include medicine, anatomy, and the like when Copernicus, Galileo and Harvey studied it.[49] Siraisi[50] noted that “the reception in twelfth-century western Europe of Greek and Islamic technical astronomy and astrology fostered the development of medical astrology…the actual practice of medical astrology was greatest in the West between the fourteenth and the sixteenth centuries.” Astrology was taught in the medical schools of Italy, including Padua. “The importance attached to the study of the stars in medieval medical education derived from a general and widely held belief that the heavenly bodies play an intermediary role in the creation of things here below and continue to influence them throughout their existence. The actual uses of astrology in medical diagnosis and treatment by learned physicians were many and various. ‘Astrological medicine’[51] is a vague and unsatisfactory term that can embrace any or all of the following: first, to pay attention to the supposed effect of astrological birth signs or signs at conception on the constitution and character of one’s patients; second, to vary treatment according to various celestial conditions…third, to connect the doctrine of critical days in illness with astrological features, usually phases of the moon; and fourth, to predict or explain epidemics with reference to planetary conjunctions, the appearance of comets, or weather conditions”[52] Thus it is to be expected that to obtain a degree in medicine Harvey had to have demonstrated proficiency both in astronomy as well as in astrology, and for the two the principle of circular motion was foundational.

Giordano Bruno (1548-1600), highlights the “circular” pattern of the motion,[53] and makes particular mention of the blood, adding: “The spiritual life-force is effused from the heart into the whole of the body and (flows back) from the latter to the heart, as it were from the centre to the periphery and from the periphery to the centre, following the pattern of a circle…. The material part of all these spirits is a fluid which cannot move on its own account, but by means of its innate spirit. Hence there is no circular or sphaerical motion outside the body, for the blood, which in the animal moves in a circle in order to distribute its motor, the spirit, lies immovable outside the body, is inert and decays, no longer deserving the name of blood…”[54] In later works he adds: “…in us the blood and other fluids are being moved continually and very rapidly in a circle, flow and flow back, are diffused from the centre into the extreme periphery and from there return to the centre-a ovement for which the followers of Aristotle give far-fetched and confused reasons such as an instinct of nature, the necessity of fate, the providence of God…” He again refers to the circular movement of the blood in two of his latter treatises (De immenso et innumerabilibus (Frankfurt 1591), VI, 8; and La Monade, il Numero e gli Innumerevoli, 1591, p. 23).[55] Bruno believed in the perfection of the circle as the fundamental symbol of all life and action in the cosmos (De Triplici Minimo, I, 3; De Monade, I, 2).[56]

Andrea Cesalpino of Arezzo (1524-1603) as thorough an Aristotelian as Harvey, became renowned as a philosopher, botanist, physician and demonologist posited an early possibility of the circulation of the blood also grounding his argument on the concept of circularity and circular motion so pervasive among Renaissance peripatetics. In 1655 and therefore during Harvey’s lifetime, Giovanni Nardi (d. 1655) known as the “Florentine Esculapius,” asserted in his Noctes geniales that Cesalpino had previously described the circulation of the blood. It appears that although Cesalpino did mention that some form of pulmonary circulation existed, he envisioned the pulmonary circulation to be of the nature of a distillation by heat and explained the action of the valves of the heart as conserving the heat either of the blood or the heart. He did not attribute circulation to the motive force of the heart.[57] Others that similarly, resting on the acknowledged concept that circular motion was the natural motion in the microcosmos as well as the microcosmos also alluded to a circulation of some sort of the blood, but without presenting a mechanistic explanation for such motion other than the philosophical one.[58] This will be discussed more thoroughly in the course.

The response to Harvey’s discovery.

Following the publication of De Motu Cordis, and for a number of years thereafter, there was more opposition to Harvey’s discovery than approval with Robert Fludd being one of the few early natural pphilosophers to recognize the validity of it, as expressed in his Integrum morborum mysterium sive Medicinae Catholicae.[59], [60] However the prevailing position was one of opposition to Harvey, and it set in shortly after publication of his book. The second edition of De motu cordis, Parisanus’ Exercitationes, is an anti-Harveian publication ; it was enlarged by the indefatigable Jacob Primrose 1580 (?)-1659, an early pediatrician reprinted all texts opposed to the idea of the circulation.[61] During the first ten years after the publication, only Francis Glisson[62] and John Wallis had publicly defended Harvey. George Joyliffe (1627-58), M.D. Cantab., Thomas Wharton (1614-73), physician to St. Thomas’s Hospital, Thomas Willis (1621-75), M.D. Oxon, Samuel Collins (1617-85) who studied at Leyden and took his M.D. at Cambridge in 1648, and the other Samuel Collins (1618-1710), the comparative anatomist—all the younger generation of learned doctors, even the famous Thomas Sydenham (1624-8g)—remained mute as far as the great discovery was concerned.[63] Besides Robert Fludd, Kenelm Digby (then an exile in Paris) was the first Englishman to write a favorable comment (1644). The tide, however, had turned by the publication of Descartes’ Discours de la Methode (1637)[64] and this represented the last major challenge to Harvey’s findings.[65] After 1637 Descartes accepted Harvey’s formulation of the circulation of the blood. In I649, in his seventy-first year Harvey allowed himself his first public reply to the many criticisms of his De Motu Cordis. He was stimulated to this by the publication in the previous year of a work by John Riolan of Paris, who made partial concessions to Harvey’s thesis, but held that there were parts of the body in which circulation of the blood did not occur.

The final confirmation of Harvey’s discovery came with the identification of pulmonary capillaries, which had been deduced by Harvey from first principles, by Marcello Malpighi (1628–1694). Malpighi was Professor of anatomy at Bologna, Pisa and Messina. He began to use the microscope, earlier initiated by Robert Hooke in England, Jan Swammerdam in the Netherlands and van Leeuwenhoek of Delft, and was the first to observe the capillary circulation in vivo. The microscope enabled Malpighi to examine and describe the histology of the lungs, kidneys, spleen and liver. This led to his discovery, in 1660, of capillaries. His work De pulmonibus observationes anatomicae published in 1661 therefore completed Harvey’s work showing how the blood gets from the arteries to the veins. It was Malpighi that demonstrated first that the blood did not leak out of its proper vessels into the air spaces, as it was believed, but made its way from artery to vein through the minute structures known as capillaries. This is eloquently reveled in a letter dated 1661which Malpighi write to his friend and fellow iatrophysicist Giovanni Borelli where he recounts the results of his microscopic examination of a living frog’s lung performed in collaboration with Charles Fracassati ((1630–1672),[66] in 1660: “For while the heart is still beating, two movements contrary in direction though accomplished with difficulty are observed in the vessels so that the circulation of blood is clearly laid bare and indeed the same may be even more happily recognized in the mesentery and in other larger veins contained in the abdomen. And thus by this impulse, the blood is showered down in minute streams through the arteries, after the fashion of a flood, into the several cells, one or other conspicuous bronchi, passing right through or leaving off there, and the blood, thus repeatedly divided, loses its red color and carried round in a sinuous manner, is poured out on all sides until it approaches the walls and the angles and the absorbing branches of the veins. The power of the eye could not be carried further in the opened living animal; hence I might have believed that the blood itself escaped into an empty space and was gathered up again by a gaping vessel and by the structure of the walls. But an objection to this view was afforded by the movement of the blood being tortuous and scattered in different directions and by its being united again in a determinate part. My doubt was changed into certainty by the dried lung of the frog which to a very marked extent had preserved the redness of the blood in very minute tracts. By the help of our more perfect glass the vessels joined together in a ring-like fashion. And such is the wandering about of these vessels as they proceed on this side from the vein and on the other side from the artery that the vessels no longer maintain a straight direction but there appear a network made up of the continuation of the two vessels. This network not only occupies the whole but extends to the wall and is attached to the outgoing vessel. Hence it was clear to the senses that the blood flowed away along tortuous vessels and was not poured into spaces but was always contained within tubules and that its dispersion is due to the multiple winding of the vessels. Nor is it a new thing in nature to join to each other the terminal mouths of vessels, since the same obtains in the intestines and other parts and indeed what seems more wonderful she joins together by conspicuous anastomoses the upper and lower termination of veins as the most learned Fallopius has very well observed”[67] Van Leeuwenhoek, unaware of Malpighi’s work, rediscovered the blood corpuscles in 1674[68] and the blood capillaries in late 1683 through the examination of dead specimens [2] .[69] In his observation of 1688 however, Van Leeuwenhoek actually saw the blood streaming through the capillaries.[70] Following these revelations the Harveyan theory gained increasing acceptance.

Much earlier, Leonardo da Vinci (1489–1515), in his dissections, injected the blood vessels with wax for preservation and thereby discovered and named the capillaries, although he did not display their role in linking the arterioles and venules.[71] His biographer Paolo Giovi, a pupil of Marcantonio della Torre during the years when he was collaborating with Leonardo, wrote in 1520: ‘In the medical faculty he learned to dissect the cadavers of criminals under inhuman, disgusting conditions … because he wanted [to examine and] to draw the different deflections and reflections of limbs and their dependence upon the nerves and the joints. This is why he paid attention to the forms of even very small organs, capillaries and hidden parts of the skeleton.’

Despite the overwhelming amount of evidence favoring a circulation of the blood, the experimentus cruxis demonstrating the connection between the arteries and veins had yet to be performed. In fact, in 1651 Harvey had to admit he conceded the possibility of some form of Galenic porosity as the mechanism:[72] “I confess, I say, nay, I even pointedly assert, that I have never found any visible anastomoses… – anastomoses in the way the word is commonly understood, and as the meaning has come down to us from Galen, viz., a direct conjunction between the orifices of the arteries and veins – I still admit…that I have found what is equivalent …in three places, namely, in the plexus of the brain, in the spermatic or preparing arteries and veins, and in the umbilical arteries and veins. I shall now, therefore, for your sake, my learned friend, enter somewhat more at large into my reasons for rejecting the vulgar notion of the anastomoses, and explain my own conjectures concerning the mode of transition of the blood from the minute arteries into the finest veins…. I imagined that the transference from the extremities of the arteries into those of the veins could not be effected without some other admirable artifice, at least wherever there was no transudation through the pores of the flesh. I therefore held the anastomoses of the ancients as fairly open to suspicion, both as they nowhere presented themselves to our eyes, and as no sufficient reason was alleged for anything of the kind. But you will ask, what is this artifice? What these ducts? viz. the small arteries, which are always much smaller – twice, even three times smaller – than the veins which they accompany, which they approach continually more and more, and within the tunics of which they are finally lost. I have been therefore led to conceive that the blood brought thus between the coats of the veins advanced for a certain way along them, and that the same thing took place here.”

In 1661 Malpighi made his first observation of functional capillaries. He was able to observe and identify them while examining the network of microscopic blood vessels of the lungs and the urinary bladder of frogs.   He went on to speculate that capillaries were the connection between arteries and veins that allowed blood to flow back to the heart, which completed the chain of the circulation of the blood first asserted by William Harvey. His most famed publication was De Viscerum Structura Exercitatio Anatomica. The first edition appeared in 1666, the year of the Great Fire of London, and was followed by a second edition, London, Joseph Martyn, 1669. [73] His discovery of the capillary circulation was published in the form of two letters, ‘De Pulmonibus’, addressed to Borelli, published at Bologna in 1661 and subsequently reprinted at Leiden and elsewhere (vide supra). These letters also contained the first account of the vesicular structure of the human lung, and for the first time they made possible a theory of respiration. With the discovery of the capillary bed Harvey’s circulation became fact.

The new model of blood circulation also cast doubt on the traditional practice of blood-letting, at that time one of the main treatments available to physicians, questioning the reasoning behind the part of the body where blood was taken, in what quantity, how often, and whether it should be near or distant from the lesion and on the same side of the body or not (16). Nevertheless William Harvey (1578-1657) and even Thomas Sydenham (1624-89) continued to defend the practice of bloodletting either by venisection or leeches. Harvey died on 3 June 1657. He was an Italian-trained Aristotelian and Galenist whose theories had little impact on physicians’ favorite medical treatment of bloodletting: despite Harvey’s demonstration that a healthy heart regularly pumps blood round the body, it was well into the nineteenth century before measuring a patient’s pulse accurately became standard practice in Europe, a technique, sphygmology, that had been in existence since antiquity in Chinese, Hindu, Greek and Arabic medicine.

COURSE CONTENT and TIME DISTRIBUTION:

For course content see above. Course meets weekly at the time and place agreed with the students for a total of 18 sessions. The specific dates and hours for each course component will be established collectively by the instructor and the students.

TEACHING STRATEGIES:

LECTURES

  1. Introduction
  2. The Paduan environment.
  3. The language of Harvey: “more disputatio” vs “ocular proof”
  4. The astronomical and physics antecedents
  5. Harvey’s natural philosophy
  6. On Anatomy: philosophical and medical dimensions
  7. The motion of heart and blood before Harvey
  8. The confirmation of the theory: Malpighi and microscopic anatomy
  9. From rejection to acceptance: the beginnings of modern scientific medicine
  10. The impact of Harvey’s discovery in contemporary science and medicine

TEXT ANALYSIS

  1. Introduction to Renaissance medicine: I
  2. On motion: II-IV
  3. Action, motion function: V-VII
  4. Quantitative analysis: Ch VIII
  5. The First Supposition: IX-X
  6. The second supposition: XI-XII
  7. The Third Supposition Ch XIII-XIV
  8. Confirmation of the Circulation XV-XVII

ASSESSMENT STRATEGIES: Students will be required to attend the lectures, read the assigned text and be prepared to discuss with faculty the issues raised by the lecture and the reading in relation to Renaissance as well as modern anatomy and physiology of the lesser circulation. Emphasis will be placed on the historical context of the discovery and its scientific and historical impact.

GRADING SYSTEM: Letter grade :A-F

RESOURCES:

Text Resources:

GENERAL INSTRUCTIONS AND COURSE REQUIREMENTS:

Students with a health condition or situation that, according to the law, makes them eligible for reasonable accommodation have the right to submit a written application to the professor and the Dean of their Faculty, according to the procedures established in the document, Submittal Process for Reasonable Accommodation of the Medical Sciences Campus. A free copy of this document may be obtained at the Office of the Dean for Student Affairs, second floor of the School of Medicine Pharmacy building. A copy may also be obtained at the Office of the faculty Deans as well as in the MSC web page. The application does not exempt students from complying with the academic requirements pertaining to the programs of the Medical Sciences Campus.

  1. It is a REQUIREMENT to participate and be punctual to all activities. If you will not be able to attend due to a mayor cause (sickness, death in the family, etc.) you are responsible of notifying the course coordinator PRIOR to the activity and to make arrangements for reposition of the missed activity. As a general rule, no excuses will be given unless there is an emergency and each case will be evaluated separately. If you are absent, you MUST present a formal excuse from the Office of the Assistant Dean of Student Affairs of the appropriate faculty prior to the completion of the course.
  2. In case there is a special need to be absent, the procedures of the “Politica Institucional para Excusar Estudiantes de Actividades Evaluativas o Docentes” will be followed.
  3. Students are expected to demonstrate each and every one of the course objectives.
  4. Should knowledge become available that dishonesty regarding any particular examination has occurred; the course faculty reserves the right to cancel the examination before or after it has been administered and to require a repeat exam or completely eliminate the exam from the course evaluation.
  5. Dress code: All students must comply with the UPR School of Medicine Dress code, approved in 1996 and revised in 2007. (Posted at the SOM Web Page)

 

Ángel A Román-Franco MD
Professor Emeritus

Raúl Mayo–Santana
PhD Distinguished Professor

 

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