DISCOVERY OF THE CIRCULATION OF THE BLOOD

12 May

THE DISCOVERY OF THE CIRCULATION OF THE BLOOD The Scientific Revolution is generally thought of in terms of the physical sciences, but by shifting the focus of concern from physics and astron- omy to medicine and physiology, we can search for new ways of under- standing and integrating science and medicine into the context of the political, religious, and social changes of this period. In the sixteenth century, as we have seen, anatomists and alchemists challenged ancient ideas about the nature of the microcosm, the little world of the human body. In the seventeenth century, William Harvey and the new experi- mental physiology transformed ways of thinking about the meaning of the heartbeat, pulse, and movement of the blood. Revolutionary insights into the microcosm reinforced the shock waves created when Copernicus, Kepler, and Galileo removed the earth from its place at the center of the universe. Blood has always conjured up mysterious associations far removed from the physiological role of this liquid tissue. Blood has been used in religious rituals, fertility rites, charms, and medicines, and no horror film would be complete without buckets of blood. Strength, courage, and youthful vigor were thought to reside in the blood.

Even Renaissance physicians and theologians believed in the medicinal power of youthful blood. The physicians of Pope Innocent VIII (1432–1492) are said to have prescribed human blood as a means of reviving the dying pontiff. How the blood was to be administered is unclear, but the results were predictable. The three young donors died, the Pope died, and his physicians vanished. With philosophers, physicians, and ordinary people sharing a belief in the power of blood, the nearly universal enthusiasm for thera- peutic bloodletting seems paradoxical to modern sensibilities. Never- theless, for hundreds of years, Galenic theory and medical practice demanded and rationalized therapeutic and prophylactic bloodletting as a means of removing corrupt humors from the body. According to the Roman encyclopedist Pliny the Elder (23–79), even wild animals practiced bloodletting. Phlebotomists attacked the sick with arrows, knives, lancets, cupping vessels, and leeches. Indeed, until rather recent times, the surgeon was more commonly employed in spilling blood with leech and lancet than in staunching its flow. Although Renaissance anatomists rejected many Galenic fallacies concerning the structure of the human body, their concepts of function had undergone little change. Ancient dogmas served as a defensive perimeter for physicians confronting professional, political, intellectual, and theological minefields. Even Vesalius avoided a direct attack on Galenic physiology and was rather vague about the whole question of the distribution of the blood and spirits.

When scientific inquiry led to the brink of heresy, Vesalius found it expedient to cite the ancients and marvel at the ingenuity of the Creator. But, despite the delicate issue of the relationship between the movement of the blood and the distribution of the spirits, other sixteenth-century scientists were able to challenge the Galenic shortcut between the right side and the left side of the heart. Michael Servetus (1511–1553), the first European physician to describe the pulmonary circulation, was a man who spent his whole life struggling against the dogmatism and intolerance that permeated the Renaissance world. If any man died twice for his beliefs it was Servetus. His attacks on orthodoxy were so broad and blatant that he was burnt in effigy by the Catholics and in the flesh by the Protestants. While chal- lenging religious dogma, Servetus proved that contemporary anatomical information was sufficient to allow a heretic to elucidate the pathway taken by the blood in the minor, or pulmonary circulation. Servetus left his native Spain to study law, but he soon joined the ranks of wandering scholars and restless spirits destined to spend their lives disturbing the universe. After his first major treatise, On the Errors

Discovery of the minor

of the Trinity (1531), was published, both Catholic and Protestant theo- logians agreed that the author was a heretic of the worst sort. Finding it necessary  to  go  underground, Servetus  established  a  new identity  as ‘‘Michael Villanovanus.’’ Under  this name, he attended  the University of Paris before moving to Lyons,  where he published  a new edition  of the  Geographia  of Ptolemy,  the  Alexandrian  astronomer and  geogra- pher. Even when editing a classic of such great antiquity, Servetus could not resist the opportunity to express dangerous  opinions. While describ- ing France,  Servetus referred  to the ceremony  of the Royal  Touch  in which the king miraculously  cured  victims of scrofula  (tuberculosis  of the lymph nodes of the neck). ‘‘I myself have seen the king touch many attacked  by this ailment,’’ Servetus wrote,  ‘‘but I have never seen any cured.’’ Returning to the University  of Paris  to study  medicine,  Servetus

supported himself by lecturing on mathematics, geography, and astron- omy. When he stepped over the line that  Christian  doctrine  had drawn between acceptable areas of astrology and the forbidden  zone of judicial astrology  (essentially  fortune-telling), he was threatened with  excom- munication. Attacks on judicial astrology can be traced back to the time of St. Augustine  (354–430), but  theological  opposition  and philosoph- ical  skepticism  seem  to  have  intensified  by  the  end  of  the  fifteenth century.  Although  his first impulse was to defend his actions,  the case was hopeless and Servetus returned  to his underground life. The even- tual  separation between  medicine  and  astrology   among  the  learned circles in France  has been attributed to the attack  of the medical faculty of Paris on an astrologer  named  Villanovanus  in 1537. As if looking for more trouble,  Servetus entered into a correspon-dence with  John  Calvin  (1509–1564), the  French  Protestant reformer

Michael Servetus

Michael Servetus.

who founded a religious system based on the doctrines of predestination and salvation solely by God’s grace. In addition to criticizing Calvin’s Institutiones, Servetus sent him an advance copy of his radical treatise, On the Restitution of Christianity (1553). Calvin responded by sending pages torn from the Restitution to the Catholic Inquisition with the information that Servetus had printed a book full of scandalous blas- phemies. Servetus was arrested and imprisoned, but managed to escape before he was tried, convicted, and burned in effigy. Four months later, Servetus surfaced in Calvin’s Geneva, where he was arrested and condemned to burn ‘‘without mercy.’’ Attempts to mitigate the sentence to burning ‘‘with mercy’’ (strangulation before immolation) were unsuc- cessful. Almost all the newly printed copies of the Restitution were added to the fire. In 1903, the Calvinist congregation of Geneva expressed regrets and erected a monument to the martyred heretic. Moreover, a review of his case revealed that the death sentence had been illegal, because the proper penalty should have been banishment.

Given the fact that Servetus’ account of the pulmonary circulation is buried within the seven hundred page Restitution, it is clear that his inspiration and motives were primarily religious, not medical or scienti- fic. According to Servetus, to understand the relationship between God and humanity, and to know the Holy Spirit, one must understand the spirit within the human body. Knowledge of the movement of the blood was especially important, for as stated in Leviticus, ‘‘the life of the flesh is in the blood.’’ Disputing Galenic concepts, Servetus argued that the fact that more blood was sent to the lungs than was necessary for their own nourishment indicated that passage of blood through pores in the septum was not the major path by which blood entered the left side of the heart. In Galen’s system, aeration was the function of the left ven- tricle of the heart, but Servetus thought that changes in the color of the blood indicated that aeration took place in the lungs. Then, the bright red blood that had been charged with the vital spirit formed by the mixing of air and blood in the lungs was sent to the left ventricle.

Servetus did not go on to consider the possibility of a systemic blood circulation. Apparently, he was satisfied that he had reconciled physi- ology with his theological convictions concerning the unity of the spirit. What effect did Servetus have on sixteenth-century science? In retrospect, Servetus seems a heroic figure, but if his contemporaries knew of his work, they were unlikely to admit to being in sympathy with the ill-fated heretic. Moreover, historians believe that only three copies of the Restitution survived the flames. It is unlikely that Servetus influ- enced anatomists any more than Ibn an-Nafis, the Egyptian physician who had described the pulmonary circulation in the thirteenth century. However, there are always many uncertainties about the actual dif- fusion of information and ideas—especially those that might be considered heretical, dangerous, and subversive—as opposed to the survival of documentary evidence.

Whatever influence Servetus did or did not have on sixteenth-century science, his career remains a fascinat- ing revelation of the dark underside of the Renaissance and religious intolerance. His Restitution proves that in the sixteenth century, a man with rather limited training in medicine and anatomy could recognize the workings of the pulmonary circulation. While in no way as colorful a figure as Servetus, Realdo Colombo (Renaldus Columbus; ca. 1510–1559) was a more influential scientist and teacher. Colombo, the son of an apothecary, was apprenticed to an eminent Venetian surgeon for seven years before he began his studies of medicine, surgery, and anatomy at the University of Padua. The records of the university refer to him as an outstanding student of surgery. When Vesalius, who had served as professor of anatomy and surgery since 1537, left the university in 1542 to supervise the publication of the Fabrica, Colombo was appointed as his replacement. Colombo was appointed to the professorship on a permanent basis in 1544 after Vesalius resigned. Displaying little reverence for his eminent pre- decessor, Colombo became one of the most vociferous critics of the Fabrica and the former colleagues became bitter enemies. Vesalius described Colombo as a scoundrel and an ignoramus. From the time of his first public anatomical demonstrations to his death, Colombo drew attention to errors in the work of Vesalius and boasted of his own skills in surgery, autopsy, dissection, and vivisection. However, Colombo’s attempt to create an illustrated anatomical treatise that would supercede the Fabrica was unsuccessful.

In 1545, Colombo left Padua to take a professorship at Pisa. Three years later, he settled permanently in Rome. Later, the anatomist Gabriele Fallopio (1523– 1562), who referred to Vesalius as the ‘‘divine Vesalius,’’ accused Colombo of plagiarizing discoveries made by him and other anatomists. Fallopio’s own Observationes anatomicae was primarily a series of com- mentaries on the Fabrica. Colombo might have been demonstrating the pulmonary circu- lation as early as 1545, but his anatomical treatise, De re anatomica, was not published until 1559. Calling on the reader to confirm his obser- vations by dissection and vivisection, Colombo boasted that he alone had discovered the way in which the lungs serve in the preparation and generation of the vital spirits.

Air entered the lungs, where it mixed with blood brought in by the pulmonary artery from the right ventricle of the heart. Blood and air were taken up by the branches of the pulmonary vein and carried to the left ventricle of the heart to be distri- buted to all parts of the body. Although Ibn an-Nafis and Michael Servetus had also described the pulmonary circulation, Colombo appar- ently had no knowledge of their work and made the discovery through his own dissections and vivisection experiments. Moreover, because Colombo’s formal training was inferior to that of Vesalius, he was apparently less familiar with certain aspects of Galen’s writings on the lungs, heart, and blood. Despite his declarations of originality and dar- ing, Colombo was rather conservative in his discussion of the functions of the heart, blood, and respiration. In any case, Galenic dogma was still too firmly entrenched for relatively modest inconsistencies and cor- rections to cause a significant breach in its defenses.

The difficulty of establishing the relationship between a scientific discovery, or a specific observation, and the conversion of physicians to a new theory is very well illustrated in the case of Andrea Cesalpino (Andreas Cesalpinus; 1519–1603). Celebrated as the discoverer of both the minor and major circulation by certain admirers, Cesalpino, Professor of Medicine and Botany at the University of Pisa, was a learned man who combined a great reverence for Aristotle with an appreciation of Renaissance innovations. His medical doctrines were based on the Aristotelian philosophical framework established in his Quaestionum peripateticarum (1571). While he also wrote several books on practical medicine, his major area of interest was botany. Certainly, Cesalpino had a gift for choosing words like circulation and capillary vessels that ring with remarkable prescience in the ears of posterity, at least in translation. His descriptions of the valves of the heart, the blood vessels that link the heart and lungs, and the pathways of the pulmonary circulation were well defined. Cesalpino also spoke of the heart in very lyrical terms as the fountain from which four great blood vessels irrigated the body ‘‘like the four rivers that flow out from Paradise.’’ While his contemporaries generally ignored Cesalpino’s ideas about the heart, modern champions of Cesalpino have devoted much effort to finding his references to the circulation and arranging these gems into patterns that escape the notice of less devoted readers. Like Servetus, Cesalpino is worth studying as a reflection of the range of ideas available to anatomists in the sixteenth century. Cesalpino was preoccupied with Aristotelian ideas about the primacy of the heart and the movement of innate heat.

As Aristotle’s champion, Cesalpino attacked Galenic concepts with philosophic arguments and anatomical evidence. For this work, Cesalpino deserves a place in the history of physiology, but not the place properly occupied by William Harvey. Because William Harvey suggested that the demonstration of the venous valves by Girolamo Fabrici (Hieronymus Fabricius; 1533–1619), his teacher at the University of Padua, had been a major factor in making him think the blood might travel in a circle, the dis- covery of these structures occupies an important place in the story of the circulation. Many other anatomists described the venous valves at about the same time, but we shall examine only the work of the man who directly inspired Harvey. After earning his doctorate at the University of Padua, Fabrici established a lucrative private practice and gave lessons in anatomy. Eventually he replaced Gabriele Fallopio as professor of surgery and anatomy. Teaching anatomy was a difficult and unpleasant task and Fabrici, like Fallopio, seems to have evaded this responsibility whenever possible. Sometimes he disappeared before completing the course, angering students who had come to Padua to learn from the great anat- omist.

Fabrici saw teaching as drudgery that conflicted with his research and private practice. Students complained that he was obviously bored and indifferent when teaching. Presumably, they thought it more natural for the teacher to be enthusiastic and the students to be bored and indifferent. On the Valves of the Veins was not published until 1603, but Fabrici noted that he had been studying the structure, distribution, and function of the venous valves since 1574. Fabrici assumed that Nature had formed the valves to retard the flow of blood from the heart to the periphery so that all parts of the body could obtain their fair share of nutrients.

Arteries did not need valves because the continuous pulsations of their thick walls prevented distention, swelling, and pool- ing. Calling attention to a common procedure, Fabrici noted that when a ligature was tied around the arm of a living person, in preparation for bloodletting, little knots could be seen along the course of the veins. Careful dissection reveals that these swellings correspond to the location of the valves in the veins. Intrigued by Fabrici’s demonstrations of the venous valves, Harvey repeated his simple experiments and observed that when the ligature was in place, it was not possible to push blood past the valves. Fabrici believed that the little structures in the veins acted like the floodgates of a millpond, which regulate volume, rather than valves that regulate direction. Unlike Fabrici, Harvey realized that the venous blood was directed to the heart, not to the periphery.

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