Nuland, S.B., Doctors: The Biography of Medicine. New York, Vintage Books, 1988.
IntroductionAs the story is often told, William Harvey (1578-1657), the English physician who discovered the circulation of the blood, single-handedly dismantled ancient medicine and ushered in a new era of modern medicine. It is as though he appeared out of thin air, centuries ahead of his time, to set biomedical research on its rightful path. Yet, Harvey was no less a product of his time than his contemporaries, and analysis of his writings on the blood itself—as distinct from the mechanics of blood circulation—reveals a man caught between two worlds. On one hand, Harvey combined theretofore unimaginable experimental prowess, powers of observation, hypothetico-deductive skills, and a willingness to defy authority to set the record straight on the true motion of blood. On the other hand, he held on to antiquated notions of vitalism, innate heat, and spirits because there was no obvious alternative. As the Harveian scholar Walter Pagel, wrote: “Indeed Harvey did not live and work in a vacuum, however much he followed his own bent and built up his own world.” In the tradition of Aristotle and Galen, Harvey appealed repeatedly to teleological principles (especially the idea that nature does nothing in vain). And like his predecessors, he was seemingly obsessed with organ hierarchies, one moment ranking the heart, the next moment the blood, as the principal body part in generating and maintaining life. This peculiarly Harveian hybrid of modern and ancient thought style was captured by Thomas Fuchs in his book The Mechanization of the Heart and Descartes:
Elsewhere, Walter Pagel wrote:
We often idealize our scientific heroes, and Harvey is no exception. There is so much about Harvey’s discovery of blood circulation to cherish and celebrate, and that will be the case of centuries to come. But we should resist efforts to see Harvey as “one of us.” To compare him to the great physicians and scientists of the 19th and 20th century is to devalue the truly revolutionary nature of his accomplishments. Moreover, such comparisons provide a convenient cover to conceal or ignore the shakier aspects of his natural philosophy that place him squarely in his time, on his own terms. The Harveian biographer Gwyneth Whitteridge wrote: “It must not, however, be forgotten that [Harvey’s philosophical notions] do underlie De motu cordis and that by divorcing them in this manner is creating an artificial division in Harvey’s thought.” Consider that Harvey lived over 400 years ago. There was no electricity at the time. People moved around on foot and horseback. Cars would not be invented for another three centuries. He wrote in Latin with a pen and quill by candlelight. He experimented alone in the research chamber of his London home, carrying out scores of dissections of human and animal corpses and “putting thousands of living animals to his subtle knife.” He had an extensive medical practice in London that included all strata of the population and included such specialties as obstetrics and neurology. He was a staunch royalist, swearing fealty to the king, and was caught between the monarchy and the parliamentarians during the English Civil War. He served as Physician Extraordinary to two kings, initially James I, then Charles I, attending to every medical need of the royal family. When Charles I was dethroned, the aging Harvey retired into exile at his country home. He suffered debilitating gout until the end of his life. These were not easy times, and the challenges they posed for Harvey make his accomplishments even more impressive. Harvey became part of what was later called the Scientific Revolution, in which observers looked closely at nature to see it for themselves. Harvey did not have a microscope, nor did he know biochemistry, but he had his imagination and his keen interest in dissecting and looking closely at the body. He also made quantitative measurements to assess (albeit crudely) the amount of blood pumped by the heart. And his observations led him to the idea that blood is not produced in the liver and then used up by the tissues, as his predecessors had thought. Rather, he decided, blood must circulate throughout the body. Yet this decidedly new idea came packaged in traditional assumptions. Aristotle had emphasized the perfection of circles, and so Harvey’s blood moved in a circle. And as others pointed to various different substances as the fluid or force that made living things alive, Harvey looked to the blood to play that role. The goal here is to explore Harvey’s thinking about blood, looking beyond just the idea of circulation. What is blood? Where does it come from? What function does it perform? We will see that Harvey ultimately favored—against the Ancients—the priority and supremacy of blood above all body parts. The heart may impress with its relentless clock-like propulsive activities, but its very existence and motion depend upon the blood from which it derives. Indeed, the heart is formed merely to serve the blood’s need to spread its inherent qualities—innate heat, spirits, and nutriment—to all recesses of the body. It is central and instrumental only in so far as it mediates the mechanical distribution of blood’s life-giving forces. In other words, it is the vital that drives the mechanical, not the other way around. Galen’s cardiovascular systemA discussion of Harvey’s work needs to begin with a consideration of his predecessors. Today, if we were to write about a famous clinician scientist, say a Nobel laureate in Physiology or Medicine, we might contextualize their discovery by highlighting what others had contributed to the field over the past 25-50 years. When writing about Harvey, it is necessary to reach back 2000 years, because, remarkably, it is ancient doctrine that dominated the medical landscape in his day. What Hippocrates wrote still mattered. What Galen declared was near sacrosanct. And, for Harvey, what Aristotle taught was a most important starting point. Harvey’s discovery that blood circulates was anathema to Galenic doctrine, which held that blood is made in the liver and distributed by veins to all parts of the body, replacing tissue lost through normal wear and tear (Fig. 1). In this scheme, blood moves centrifugally from the center of the body (more precisely, from the liver) towards the periphery. A small portion of venous blood reaches the right ventricle, and from there moves through the pulmonary artery to feed the lungs. Fig. 1. Schematic of the cardiovascular system according to Galen. Galen demonstrated that arteries normally contain blood (red color), not air. Arterial blood is derived from the passage of venous blood through invisible pores in the interventricular septum (shown as interrupted septal wall). From Aird WC. J Thromb Haemost. 2011 Jul;9 Suppl 1:118-29. Arteries arise from the left side of the heart and are responsible for delivering pneuma, derived from the lungs, to the rest of the body. Against Erasistratus, Galen admitted that arteries also contain blood and famously proposed that some blood percolates through invisible holes in the interventricular wall in the heart, moving from the right (venous) to left (arterial) side of the vasculature. Harvey was not shy about dismissing Galen’s claim based on his own observations: “But, by Hercules, no such pores can be demonstrated, nor in fact do any such exist.” In addition to the interventricular passage of blood in the heart, Galen had envisioned small amounts of blood transferring between peripheral arteries and veins through invisible anastomoses. According to Galen, veins and arteries are distinct open-ended systems, with veins nourishing the body with blood and arteries providing vitality through a mixture of spirits and pneuma admixed with blood. Movement of blood, according to Galen, is mediated not by a propelling organ or force pump, like the heart, but rather by the attractive forces of hungry tissues. Through the wisdom of Nature, the attractive faculty does not attract more than is necessary. The quantity of venous and arterial blood delivered to parts of the body is perfectly matched to the needs of the local tissues. In this decentralized model, blood and pneuma are not recycled, but rather consumed at their final destination. The arteries and veins are busy multilane highways, with some substances moving in one direction and others moving in the opposite direction, with the speed and direction of traffic under the governing control of the peripheral tissues. The extent to which the various contents of blood vessels—nutriment, air/pneuma, spirits, and waste products—are physically separated or combined remained a mystery. Harvey’s discovery of blood circulationHarvey studied medicine at Padua in Italy, the greatest medical school of the time. The curriculum at the time revolved around Galen’s physiology and anatomy and Aristotle’s physiology. Importantly, Harvey became familiar with the works of Andreas Vesalius (1514–1564), a Flemish professor of anatomy at Padua, who carried out his own dissections (unlike Galen, he had access to human corpses) and began to point out errors in Galen’s work. In particular, he was the first to question the existence of pores in the interventricular septum. Harvey was also exposed to Girolamo Fabrizio (also known as Fabricius, 1537–1619), professor of anatomy at Padua, who identified venous valves in 1574 and published a description of them in 1603. Though Fabricius misunderstood the function of the valves, Harvey drew on their anatomical arrangement to correctly infer the direction of blood flow. Through a series of brilliant experiments, dissections, vivisections, ocular demonstrations, and calculations, combined with hypothetical-deductive reasoning, Harvey argued that blood travels around the body in a circle, propelled by the motions of the heart (Fig. 2). The mechanical force of the heart replaced Galen’s elusive attractive powers. Harvey published his findings in 1628 in his book titled De motu cordis, an 86-page masterpiece (referred to by Harvey as his “little book”) that remains one of the greatest works in the history of medicine. The work comprises two separate topics: the motion of the heart and the motion of the blood. Fig. 2. Schematic of the cardiovascular system according to Harvey. Harvey discovered that blood circulates not only through the lung, but also around the whole body. An important clue was the presence of valves in the veins (two of them are shown in white). The liver is no longer the source of veins. Rather, the system is driven by the mechanics of the heart (now shown in black). Transfer of blood from arteries to veins in the lung and periphery may occur through direct connections or anastomoses (as shown) or through porosities in the flesh (the latter mechanism being favored by Harvey). From Aird WC. J Thromb Haemost. 2011 Jul;9 Suppl 1:118-29. Harvey’s discovery has been detailed and analyzed ad infinitum. Because we are focusing on the non-hydrodynamical, vital aspect of Harvey’s work in this essay, we will recapitulate only its essentials here:
It is impossible to overestimate the revolutionary implications of Harvey’s discovery. If blood is not converted to tissues in an open-ended system of blood vessels, then perhaps we are more than what we eat. If blood moves in veins towards the heart and not in the other direction, then surely, they are not really the purveyors of nutrition as was claimed for so long. If blood is not consumed, but rather conserved, then maybe it is not such a good idea to phlebotomize patients who are bleeding. The newly appreciated interconnectedness of the vascular system suddenly rendered the traditional boundaries between different body compartments and organs “permeable or wholly invalid.” Moreover, the existence of a circulation implied that arterial and venous blood were essentially identical—a foreign concept in ancient medicine. Harvey emphasized the forceful, rapid movement of blood. There was no time for slow Galenic processes. This was a point of contention for Harvey’s critics, who argued that such violence and rapidity would cause “mixing and confusion of the humors.” Finally, that blood circulates in a closed system of blood vessels, from veins to heart to arteries, and then back to veins, predicted that drugs and poisons, once introduced into the circulation, would diffuse throughout the body, no matter where the entry point. At a time when the entire therapeutic armamentarium was aimed towards coaxing and manipulating the humors, the therapeutic implications of Harvey’s discovery were profound. Finally, Harvey’s findings represented the first serious crack in the foundation of ancient medicine, paving the way for a new worldview of the human body. Robert Frank, writing about 17th century scientific ideas in England, noted: “[Harvey’s] book began the overthrow of a medical and physiological system – concepts of man’s functioning and dysfunctioning—that had endured largely unchanged for almost a millennium and a half.” Harvey’s courageGalen’s system of physiology had gone largely unchallenged for 1600 years. It was codified in Arabic medicine, inculcated by the Catholic Church, incorporated in the curricula of all medical schools (including at Padua, where Harvey studied) and celebrated by intellectuals of all stripes. Acquisition of medical knowledge was limited to the customary study and paraphrasing of early books and the interpretation of traditional texts. To defy Galen amounted to medical blasphemy. This was perhaps Harvey’s greatest achievement, to escape from the clutches of ancient medicine and dare to replace a flawed—yet fiercely guarded—system with a new, evidence-based model of blood circulation. While deferential to his predecessors, Harvey trusted his senses and reason above all else: “The works of nature bow to no antiquity. For indeed there is nothing either more ancient or of higher authority than nature.” Harvey was well aware of the intense opposition his discovery would incite:
Jean Hamburger, who published an interesting portrait of Harvey in the form of an imaginary diary of the physician wrote: “[Harvey] brought to [his discovery] a profound renewal of medical reasoning which up to that time had been the slave of the formidable influence of the traditions of antiquity … Harvey was one of the first, if not the first, to date to question [Aristotle and Galen].” Predictably, Harvey’s discovery was met with mixed reaction. In the initial years after publication of De motu cordis, there was no shortage of detractors. For his part, Harvey remained largely silent, letting the work speak for itself. In 1649, at the ripe old age of 71, Harvey finally broke his silence, publishing two rebuttal letters to the most important opponent of his discovery, Jean Riolan, a leading French physician and strong defender of traditional Galenic doctrine. “Scarcely a day, scarcely an hour, has passed since the birthday of the Circulation of the Blood,” Harvey wrote, “that I have not heard something for good or for evil said of this my discovery. Some abuse it as a feeble infant, and yet unworthy to have seen the light… some oppose it with much ado, others patronize it with abundant commendation.” By the time of Harvey’s death, however, the circulation of blood was widely accepted. But the idea that blood circulates was only part of Harvey’s enduring contribution. He also opened the door for new ways to think about the blood, and it is this innovation we are most concerned with here. Harvey’s use of blood as research toolThough Harvey did not have access to a microscope, he recognized the value of looking as closely as possible to nature and writes about using a magnifying glass to examine the heart and the circulation of insects and chick embryos. Harvey’s observations of blood, then, were limited to those made with the naked eye:
For Harvey, then, blood served as an important, indeed necessary, tool for mapping the movements of the heart and for revealing the circulation. “Blood [courses and revolves] by a new route,” he wrote, “very different from the ancient and beaten pathway trodden for so many ages.” As we shall see, it is when Harvey ventured beyond the mechanics of the circulation that he encountered difficulty in his reasoning. Harvey on the unknownHarvey’s preferred scientific method was to observe, formulate a hypothesis, and then design experiments, which he repeated time after time to test the validity of his hypothesis. While he expressed a preference for the use of sense perception and ocular demonstration, he argued that the perception thus gained must be corroborated or confirmed by reasoning if we are to arrive at scientific knowledge. And not just any reason, but reason that is consistent with the observation. “Harvey insists,” writes Pagel, “in true Aristotelian terms on the harmony between what is observed and reason.” Harvey was more concerned with how things happen, not why, because the former was knowable; the latter was not and relied on theory and speculation. “Our first duty is to inquire whether the thing exists, before asking why it exists,” he wrote. In this respect, Harvey was a modern thinker. Indeed, his new methodology not only led to his discovery that blood circulated but also set a new standard for biomedical research that remains as relevant today as it was in his time. That is not to say Harvey lacked interest in why the circulation—and by extension, the blood—existed. Pagel argues not only that “Harvey was the lifelong thinker of the purpose of the circulation” but that the question of final cause (the final end of perfection for the achievement of which it exists), so essential in Aristotelianism, was a motive that explained much of his life and work. As much as Harvey was confident in his findings that blood circulated, which he presents in a “terse and snappy” style, he wasn’t so clear on the purpose (the “ends and offices”) of the circulation or the nature of blood. “In his philosophical discussions he becomes vague and his sentences grow beyond control.” Harvey lacked any awareness of the microscopic world or biochemical theory. He had no knowledge of blood cells, let alone subcellular elements, and so when considering the question “why”—why do we have blood? why does blood circulate?—he was forced to speculate. Importantly, Harvey was careful to distinguish between experimental proof and conjecture. Consider the following statements (italics are the author’s):
This refreshing candor and transparency stood in stark contrast to the armchair philosophers of the day who blindly followed the ancients in their teachings and promulgated ancient doctrine as fact. In his later writings, for example in his rebuttal letters to Riolan in 1649 and in his book On Generation, published in 1951, Harvey strikes a more confident tone when speculating on matters. And on more than one occasion he promises to settle the matter with a future treatise on the subject (assuring us that he has “a vast number of observations”). Such displays of bravado aside, there is always a sense that Harvey is acutely aware of the boundary between what can and cannot be proven. Harvey on arterial versus venous bloodAs discussed earlier, Galen viewed arteries and veins as separate systems, connected only by invisible, imaginary pores in the interventricular septum and by venous-arterial anastomoses in the periphery. Since there are two types of vessels, there are two kinds of blood: the nutritional blood of the veins and the spirituous blood of the arteries. Veins arise from the liver and deliver aliment to body parts, while arteries originate in the heart and transport vital spirits to the parts. While arteries are primarily instruments of the pneuma, they have their share of thin, pure spirituous blood. The veins, in turn, contain a little mist-like air derived from the arteries. In other words, although veins and arteries contain one single matter, their blood is qualitatively different. Galen held that blood in veins is moist in texture and red in color, while arterial blood is thinner, lighter, yellower in color, hotter, and more vaporous and spirituous compared with venous blood. Robert Frank, another Harveian biographer, wrote of the ancients: “Color—the visible difference between bright red arterial blood and dark red venous blood—was merely one of a number of natural and essential differences between the contents and functions of the two systems [the arteries and veins].” Yet in isolation, neither vapor, nor air, nor ether, nor any pneuma whatever is seen to be contained in them. Harvey’s discovery that arteries and veins are continuous led him to conclude that arterial and venous blood must be the same. He filled basins with blood from arteries and veins and observed them for differences and similarities. In either basin you find blood “nearly” of the same color, he explained, not of very different consistency in the coagulated state, forcing out serum in the same manner, and filling cups to the same height when cold or hot. Harvey writes:
This last passage illustrates Harvey’s scientific method at work: observation of blood in arteries and veins in multiple, repetitive experiments on dead and living specimens combined with reason to conclude identity of blood between the two sets of blood vessels. But arterial blood is redder than venous blood. That is plain to any observer. Even Galen described the redder hue of arterial blood. So, what was Harvey thinking? A clue lies in a single passage in De motu cordis, in which he notes that as blood is withdrawn from an artery or vein, the arterial sample indeed has a brighter hue, but then attributes the dissimilarity in color to an in vitro artifact based on differences in the size of the orifices from which the blood is withdrawn. So the problem was not so much with his sense perception as it was with his line of reasoning. Harvey was taken to task by many of his critics for overlooking the differences in color between arterial and venous blood. Whitteridge wrote: “The assertion by Harvey of the identity of the venous with arterial blood was to prove a stumbling block to several anatomists who had indeed observed the difference in colour between the two.” She cites as one example a passage from a letter written in 1643 by an opponent of Harvey, Ole Worm of Copenhagen, to Thomas Bartholin:
Though Harvey claimed that venous and arterial blood are identical to the naked eye, he posited invisible differences between the two types of blood. He writes repeatedly about how arterial blood is more spirituous and possessed of higher vital force. It is warmer, more perfect, vaporous, and alimentive. It supplies the body parts with nutrition, heat, and spirits, while veins, which drain these parts, contain blood that is cool, effete (Harvey’s term), and poorly nutritive. We now know that aside from the difference in color, there really is no way to distinguish between venous and arterial blood with the naked eye. Harvey was obviously wrong in claiming that arterial blood is hotter and more spirituous than venous blood. However, he correctly captured the novel concept that arteries deliver and offload substances in the tissues (replace spirits with oxygen, and he’s on the right track). Without a biochemical framework and toolkit, he simply had no way of knowing the nature of the cargo. Harvey on humorsIn medical school at Padua, Harvey was taught that the body parts of all animals were governed by the primary qualities (moisture, dryness, coldness, and warmth), which in turn were embodied in or associated with the four essential humors of the body. Hippocrates (or more precisely his followers) had first proposed the theory of humors. And Galen, some four centuries later, codified and solidified the theory with such flare, self-confidence, and persuasion that it persevered as the predominant physiological framework until Harvey made his discovery in the 1600s. There are 4 such humors: black bile, cold and dry; yellow bile, hot and dry; phlegm, cold and damp; and blood, hot and damp. They arise from elaboration of food in the stomach, liver, and veins. Blood as humor is distinguished from blood, the fluid that emerges when a vein is cut. Humors are derived from the diet, and each possesses its own power and nature. For example, blood and phlegm are moist and flourishing, while yellow bile and black bile are dry and effete. Galen tried to relate the properties of food to the humors and their qualities. For example, some foods are heating, others cooling, moistening, or drying. Some thicken the humors, others thin them. Blood always has some admixture of the four humors. The relative amounts of humors depend on body type, diet, and time of year. The four humors march to their own tune, being variously attracted or discarded according to the underlying needs of the tissue. As a result, they flow in multiple directions within the veins, nonchalantly passing one another like ships in the night. Health is manifested by a balance of humors, disease by an imbalance. Each individual has their own natural mixture, and it is this particular combination that shapes their physical well-being and mental state. Medical therapy was designed to recalibrate and restore humoral balance. If the patient was too hot, they were treated by cooling; if too dry, by dampening and so on. One reason the humoral theory fared so well over the millennia is that it provided a plausible explanatory framework, while at the same time precluding refutation based on anatomical dissection. In a book on the history of the humors, Noga Arikha wrote: “’Folk beliefs that had always informed humoural theory survived this onslaught from on high, simply because there was no better explanation for our passions was available, and because humours were surely being secreted somehow, somewhere. Perhaps they did not take the pathways that had been imagined until now, but there had to be more to the story than blood.”. Roger French wrote: “The educated doctor had an impressive story to tell the patient about the way he understood the patient’s body and its diseases.” The true constituents of blood would remain elusive until the introduction of the microscope. The finding that blood circulated did not, in itself, rule out the presence of humors. For all anyone knew, the heart propelled blood imbibed with black bile, yellow bile, and phlegm around the body in a circle. However, Harvey pays little attention to humoral theory. After all, the violent, rapid motion of blood as it moves around the body would not provide time for the slow, meandering, drop-by-drop, ebb-and-flow movement of the humors as envisioned by the ancients. In one of the few references to humors in De motu cordis, Harvey writes “how the circulation may be established through the whole body, and each of its individual parts… without confusion and disturbance of humors.” In On Generation, Harvey endorses Aristotle’s view that blood is “the only humour that is distributed to every part of the animal.” Elsewhere, he writes “I do not believe that the excrementitious fluids or bad humors when once separated… necessarily circulate with the blood.” For the longest time, human emotions and personality types were mapped to individual humors. For example, someone may be described as “sanguine,” “choleric,” “melancholic,” or “phlegmatic” depending on which humor was produced in excess. In On Generation, Harvey endorses Aristotle’s view that blood causes many things among animals, including their “tempers [for example, timid, courageous, passionate, furious] and capacities.” However, instead of ascribing emotions to individual humors, he saw the mark of the blood itself, and of its spirits, in “the way in which our body reacts differently in every affection, appetite, hope, or fear.” Not only that, but blood is the cause of sleep or wakefulness, tenuity and purity, genius or aptitude. Blood (with its innate heat and spirits) had now replaced individual humors. Harvey on spiritsHow do we explain the corruption of blood when it is removed from the body? At one moment, it is a warm fluid in motion, the next it is a cold, motionless multicomponent substance that bears no resemblance to its in vivo counterpart. Harvey implicated two vital constituents in living blood: spirits and innate heat. Both entities had held an important place in physiology since antiquity. Today, we think of spirits as a non-corporeal essence of a being: “Cancer destroyed her body but not her spirit” or “Her spirit lives on.” However, for the ancients, the term spirit was used more agnostically to describe a faculty or function of an organ. Spirits were conceived to be a form of subtle matter, for example, fiery or airy, that had the capacity to dwell in both liquids and solids, and which were the instrument of a faculty within the body. While they were considered to be quasi-metaphysical in nature, they were subject to physical laws such as retention by the thick walls of arteries and motion with flowing blood. According to Galen, nature rules the body from three centers: the liver, heart, and brain. The liver distributes blood through the veins, the heart distributes vital spirit through the arteries, and the brain distributes psychic (animal) spirit through the nerves.
While Harvey believed that blood carries spirits (“… no one denies that the blood [from arteries and veins] is imbued with spirits”), he doubted that they exist as independent entities. After all, when he cut through an artery or the pulmonary vein, he saw no evidence of air, spirits, or fuliginous vapors escaping or entering. Blood in arteries is not frothy or fermenting, as you might expect if the spirits were aerial. The spirits, then, are innate to blood, flowing in the arteries not separately and disjoined, but as one body “like whey and butter in milk or heat in hot water.” They signify one and the same thing, though different—like generous wine and its spirit. Just as wine becomes corrupt when it loses its spirits, so too does blood. In this sense, spirits were in fact quite real. They continued to make all the difference between blood and gore, indeed between life and death. Harvey preferred the notion of a single species of spirits, which most closely resembles the vital spirit of the ancients. They are present in both venous and arterial blood, but they are in much greater supply in arteries, which distribute them to the body parts (Fig. 3). Arterial blood, he wrote, is more spirituous and possessed of higher vital force. Harvey equates the spirit in arteries, the vital spirit, to “the vital principle,” whose presence is a requisite for “proper blood.” If we did not know any better, we might ascribe these comments to Galen himself. Harvey’s position on the spirits evolved over time. He does not show his hand in De motu cordis, which of course was more concerned with establishing the fact of the circulation. In his second disquisition to Jean Riolan, Harvey “digresses into a discussion of these spirits, a topic which he had carefully avoided in De motu cordis.” He writes with some trepidation: “There is nothing more uncertain and questionable, then, than the doctrine of spirits.” “The nature of spirits is wholly ambiguous,” he declared. “There is still a question of what the spirits are,” he wrote, “how they exist in the body, of what consistency, whether separate and distinct from the blood and solids or mingled with these.” That blood circulates is incontrovertible, he writes, while the purpose of the circulation and the contents of blood are for the time being unknowable. Again, it is hard not to admire how Harvey drew boundaries between what he knew and what he did not. By the time On Generation was published, Harvey seems to have gained confidence in his standing as a philosopher. A primordial drop of blood in the chick embryo, he writes, contains a vital principle and provides spirits to all body parts as they develop and grow. Vital principle has its first and chief seat in the blood. In the adult, body parts are sustained and actuated by the inflowing heat and vital spirits. Blood, the dwelling place for vital principle, swells in consequence of containing an inherent spirit and it is this motion that triggers diastole of the atria. Blood distributes spirits to the heart by way of the coronary arteries. The spirit (or certain force) is inherent in the blood, acting superiorly to the powers of the elements. What is more, the spirit and blood contain a soul, which is identical to the essence of the stars. Heavy words from the investigator who had so methodically uncovered the circulation of blood. Fig. 3. Gradient of spirits across the vasculature. Blood is propelled from the left ventricle (LV) of the heart into arteries, where it is distributed to the tissues of the body. Blood leaves the arteries, presumably through tiny holes in their walls or open ends, and percolates through porosities (interstitium) of the body parts (indicated by gap between red artery and blue vein). Blood then returns to the right atrium (RA) of the heart, forced by the propelling action of the heart and compression of veins by surrounding muscle. Blood in the right atrium is then sent into the right ventricle (RV), and from there propelled into the pulmonary artery, lungs and left atrium (LA). Arterial blood is imbued with spirits, just as wine is. The spirits dissipate in the peripheral tissue, so the blood returning to the heart is like wine deprived of its spirit (i.e., vinegar). The red-blue gradient represents the degree to which the blood is spirituous. Harvey on innate heatAn important principle underlying ancient medicine is the concept of innate heat. It was long appreciated that heat is necessary for life. Aristotle proposed that because death is cold and life is warm, all living things are possessed of a source of innate heat from which warmth and life are dispensed or communicated to the parts. He held that innate heat is the originator of everything in the body and that the heart is the source of this heat, which it imparts to all parts of the body. Galen agreed that the heat of the body is innate and is inexorably linked to life and the soul. It is present in the body from its creation (it is most abundant at birth) and helps to sustain all parts of the body. Innate heat is required for alterative processes and thus is indispensable for digestion, nutrition, and the generation of humors. According to Galen, nourishment from the blood is necessary for continuance of the innate heat, just as the burning of suitable logs is necessary for the fire on the hearth. The innate heat is a special kind of heat that is not derived from any outside source but comes from the heart (especially the left ventricle) and is distributed throughout the body by way of the arteries. The blood is the matter, or fuel, of the innate heat. The innate heat needs moderation by the cooling action of air drawn into the body through the lungs and skin. Like his predecessors, Harvey also subscribes to the vital role of innate heat. Innate heat is not fire, but rather a nonphysical divine heat that does not need anything from the outside. Heat distinguishes what is living from what is dead. It is the principle of life, while death is corruption through deficiency of heat. Innate heat is the source of the vitality and self-motion of living things “mirroring within themselves, as it were, the sun as principle of all cosmic movement.” Heat is also necessary for sensation and digestion. Indeed, this innate heat is the common instrument of every function and the prime cause of the pulse. Different body parts have different degrees of heat. Blood is the hottest entity in the body. It is by its very essence hot: when it ceases to be hot it ceases to be blood. What is the source of the heat? In De motu cordis, Harvey seems to waver. At times, he favors the heart, which he describes as the seat and fountain, a kind of home and hearth, where the cherisher of nature, the original of the native fire, is stored and preserved. The heart is a fountainhead that dispenses heat and life to all parts, from which sustenance may be derived, and upon which concoction, nutrition, and all vegetative energy may depend. Elsewhere, Harvey is not so sure: “blood receives infusion of natural heat, impregnated with spirits in heart… whether or not the heart, besides propelling blood, giving it motion locally, and distributing it to the body, adds anything else to it—heat, spirit, perfect—must be inquired into by and by.” In On Generation, Harvey pivots and declares blood as the definitive source of heat. Blood is the only innate heat, the first engendered natural heat. Blood is the hearth, the household divinity, the sun of the microcosm, the fire of Plato. When an artery is tied off, the limb becomes cold, pale, torpid (Harvey’s word, meaning having lost motion or the power of exertion or feeling). Therefore, Harvey concludes, arteries must carry warmth. Indeed, arteries carry fresh, warm, and vivified blood, which cherishes and warms the body parts and restores to them sense and motion. Arterial blood replaces chilled blood in the extremities that has lost its heat and spirits. The chilled blood returns to the heart by way of the veins, where it renews its warmth. Cold parts can only be saved by the internal warmth. They cannot be salvaged by a fire or other types of external warmth any more than those of a dead body could be recovered. The picture that emerges, then, is one of repeated cycles of warming and cooling as blood makes its way from arteries to veins. Blood returning to the heart in the vena cava gradually increases in temperature by its internal heat and swells and rises in the manner of fermentation. This causes the right atrium to undergo diastole, triggering the cardiac cycle. Harvey agreed that the heat is dampened by its passage through the lungs (he had no idea about the existence of oxygen), so that it reaches a perfect temperature by the time it arrives at the left ventricle (Fig. 4). The heart itself receives its heat only from the blood of the coronary arteries. Fig. 4. Gradient of innate heat across the vasculature. Blood is propelled from the left ventricle (LV) of the heart into arteries, where it is distributed to the tissues of the body. Blood leaves the arteries, presumably through tiny holes in their walls or open ends, and percolates through porosities (interstitium) of the body parts (indicated by gap between red artery and blue vein). Blood then returns to the right atrium (RA) of the heart, forced by the propelling action of the heart and compression of veins by surrounding muscle. Blood in the right atrium is then sent into the right ventricle (RV), and from there propelled into the pulmonary artery, lungs and left atrium (LA). Innate heat is highest in arterial blood. The heats dissipates in the peripheral tissue, so the blood returning to the heart is cold and effete. The red-blue gradient represents the temperature of the blood (red=hotter, blue=less hot). Harvey on nutritionAccording to Galen’s system of physiology, food is converted to blood in the liver and blood is then distributed to all body parts, centrifugally through the veins, where it is consumed. The amount and direction of nutrient flow in the veins are mediated by attractive forces of hungry tissues, not by any forceful action of the heart. After crude calculations of cardiac output, Harvey concluded that it is impossible for the liver to furnish such high quantities of blood, and, besides, no tissue needs this much feeding. The whole of the ingested juices percolates through the liver, Harvey explains, where it undergoes “additional change (concoction, transmutation and sanguification), lest arriving prematurely and crude at the heart, it should oppress the vital principle.” Aliment is further processed in the heart, where it receives its perfection (including its innate heat and spirits) for distribution by the arteries to all body parts. However, it is the arteries, not the veins, that transmit the digested, perfect, peculiarly nutritive fluid to the tissues. Indeed, tie off arteries, and you will note that the body parts not only become torpid and frigid, and look pale, but at length they cease to be nourished. While Harvey’s new model of blood circulation replaced attractive forces with convective bulk flow, it did not address the question of how the food was ultimately assimilated by and transformed into tissue. It was here that Harvey admitted to a certain type of attraction: “I do not believe that any kind of attraction can be demonstrated in the living body except that of the nutriment, which gradually and incessantly passes on to supply the waste that takes place in the tissues.” In a remarkable foreshadowing of the process of diffusion, Harvey claimed that tissues attract only what they need for sustenance, leaving the rest to continue on in the circulation: “So much of the blood must remain as is appropriated to the nutrition of the tissues; for it cannot nourish unless it be assimilated and become coherent, and form substance in place of that which is lost.” The thinner, more pure and spirituous part permeates more quickly (the nutritive portion, the ultimate aliment of the tissues), and the thicker, more earthy and indifferently concocted portion moves more slowly or is refused admission. How are nutrients physically transferred from the blood vessel to the tissue? No matter how hard Harvey tried to find an answer to this question, he came up empty. Without the benefit of a microscope, which would not be invented until decades later, he could not see the capillary vessels that connected arteries to veins. Harvey proposed that the smaller vessels that penetrate the substance of the tissue must contain tiny pores and that nutrient-rich blood passes through these holes into the interstitium. That which is contained in the porosities, and not assimilated by the tissues, is then urged into the small veins by the force of the pulse and movement of surrounding muscle. This hypothesis is not that surprising given the unlikelihood (at the time) that substances could actually pass through the wall of a microvessel. Harvey on heterogeneity of bloodHarvey argues that blood is blood no matter where it is found in the circulation. But because arteries function to deliver heat, spirits, and nutrients to the tissues, venous blood must be deficient in these properties and therefore qualitatively distinct. Harvey also considered additional nuances across the vascular tree. Intestines Harvey, like Galen, maintained that blood that passes from the intestines to the liver contains chyle, which is incompletely digested matter and the substrate for nutrition of the body parts (Fig. 5). However, whereas Galen invoked 2 way traffic in the mesenteric and portal veins, with chyle traveling from the intestines to the liver and blood (nutriment) moving towards the intestines, Harvey appreciated that chyle and blood travel in one direction towards the liver. Chyle is absorbed from the gut into the mesenteric veins (mesenteric veins suck up the chyle from the intestines), where it is diluted out by the large quantities of blood delivered by the mesenteric arteries. The diluted mixture, which has the same color and consistency as other blood, is taken by the portal vein to the liver where it undergoes additional change, including concoction, transmutation, and sanguification as it flows through meandering channels. Harvey proposed additional vascular-bed specific differences in blood composition in the gastrointestinal tract. For example, blood in veins leading from the stomach is supposedly thin, watery, and not fully chylified, whereas hemorrhoidal veins carry thick and more earthy blood, derived from the feces. Fig. 5. Bidirectional vs. unidirectional model of blood flow in the intestines. Movement of blood in the mesenteric blood vessels. Left, Galen’s vision shows chyle absorbed by mesenteric veins in the intestine moving towards the liver in the the portal vein. At the same time, nutriment concocted from chyle in the liver, is distributed to the intestines through the same passageways (as well as to other body tissues through their respective venous supply). Thus, there is bidirectional passage of chyle and nutriment in the portal and mesenteric veins. Right, Harvey showed that blood (with its nutriment) is delivered to all tissues by way of the arteries (in this case, to the intestines through the mesenteric artery), while chyle moves through the mesenteric and poral vein towards the liver, driven by the hydraulic pressure of the heart and arteries. Movement of substances in the blood is unidirectional. Lungs For Harvey, as for his predecessors, the lungs function to cool the blood: “The blood is sent through the lungs, in order that it may be tempered by the air that is inspired, and prevented from boiling up, and so becoming extinguished.” In addition, lungs perfect the blood (Fig. 6). For example, they expel suffocating fumes which are then cast off during expiration resulting in fanning and purification of the blood. They also make spirits. Lungs provide more perfect nutrition and a larger supply of native heat for full concoction of aliment. All of this happens as blood percolates through the spongy parenchyma of the lungs—its movement in and out of vessel pores being mediated by the mechanics of breathing and the pulse of the pulmonary artery. As a result of these various modifications, blood is thinner in the lungs compared to other parts of the body. Fig. 6. Purification and cooling of blood in the lung. Blood arriving at the right atrium (RA) is sent to the right ventricle (RV) from which it is propelled into the pulmonary artery and lungs. It returns to the left atrium through the pulmonary vein, and is then sent to arteries by way of the left ventricle. Blood is cooled and perfected by the lungs in its transit through the pulmonary circulation. Purpose of the circulation of the bloodAs we have seen, Harvey admitted he did not know the exact purpose of the circulation of the blood. He certainly weighed in with his own hypotheses, but he was careful to couch them as mere speculation. Let’s let him speak for himself:
So, the heart propels perfected blood through the arteries, forcing blood that has lost its perfection in the periphery back to the heart by way of the veins. Harvey equates perfection with heat, spirits, and nutriment. In these particulars, he was incorrect. Yet, as we discussed earlier, Harvey captured the key function of the circulation of the blood in assuming that something—some “stuff”—is delivered by arteries to the tissues, and that the blood returning back to the heart is lesser for it. Harvey on organ hierarchyHave you ever considered what the most important organ in the body is? Is there such a thing? Subspecialists may tend to vote for their organ of interest. Perhaps the priorities of modern-day transplant programs (liver, heart, lung, and kidney) provide a yardstick, though that is hardly fair to the brain. Maybe we should relegate organs we can live without—the appendix, spleen, gallbladder, or colon—to the bottom of the organ pyramid. But tell that to the family of the asplenic patient who perishes from overwhelming sepsis. Does any of this really matter? It mattered to Harvey and all of his predecessors. As vitalists, they believed that while the adult organism is a whole, it includes subordinate wholes, and is itself a subordinate to the whole of organic existence. For Aristotle, the heart reigned supreme. Galen believed in the tripartite supremacy of the heart, brain, and liver. Harvey vacillated between the heart and the blood as the controlling part of the body. In De motu cordis, Harvey refers to the supremacy of the heart. It is the beginning of life, the sun of the microcosm, the household divinity, the foundation of life, the source of all action by nourishing, cherishing, quickening the whole body (see Table in Appendix). The heart is the principle of life, seat and fountain, home and hearth, which stores and preserves heat and dispenses heat and life to all parts as from a fountainhead. Yet, Harvey wavers. Elsewhere in De motu cordis, he writes:
While espousing the central role of the heart in the circulation of blood, Harvey provides hints about his leanings towards the primacy of blood in De motu cordis. Based on his observation of hens’ eggs, for example, he informs us that blood is actually the first part of the embryo to form. A palpitating drop of blood, red and like the point of a pin, makes its appearance in chicks in the first 7 days, from which the auricles (atria) are formed, then the ventricles. Perhaps life begins not with the heart, he muses, but with a pulsating drop of blood. In Exercises on the Generation of Animals, Harvey no longer equivocates. Blood is unquestionably the first body part to exist. He variously describes it as the primary generative particle, the primigenial and principal portion of the body, the first engendered part. It provides nutrients for fetal growth and is the author and preserver of all other organs. The heart and liver do not make blood. Rather, blood fashions them. Indeed, the whole body is added and appended to blood to subserve its very needs. No other part of the body has greater excellence or worth. Here, we see a new allegiance to the blood. Indeed, On the Generation feels like one long ode to this mysterious red fluid. Blood has replaced the heart as the hearth, the household divinity, the innate heat, the sun of the microcosm, the fire of Plato. Because by a vague and incessant motion it preserves, nourishes, and aggrandizes itself. Blood proceeds at all times with such foresight and understanding, and with definite ends in view, as if it employed reasoning in its acts. The blood must exist before the heart, both in the order of generation and of nature and essence. In its infinite wisdom, the blood uses the heart as its instrument for mechanical distribution around the body.
ConclusionAs we have seen, Harvey was a man of his times. At Padua, he was schooled in the tradition of Galen and Aristotle. Yet, he was also exposed to the works of more contemporary physicians, including Vesalius and Fabricius, which provided important clues about the path of blood flow. Harvey came to realize that Galen’s system of human anatomy and physiology was untenable, and that medical progress was not simply a question of reading and understanding the ancients more completely. Rather, he recognized the need for new methods of generating and validating. After his discovery that blood circulated, Roger French wrote: “the whole theory of medicine was destroyed, along with its power to convince.” In contrast to his incontrovertible findings on the mechanics of the blood circulation, Harvey’s theories about its purpose are frequently seen as a nod to the ancients. In other words, Harvey had one foot looking forward, with the other planted in tradition. How fair is this assessment? It is true that Harvey held a vitalistic view that life involves phenomena distinct from the laws of chemistry and physics. But there was little understanding of chemistry and physics at the time, and there were no universal laws to speak of. Just because somebody believes that the four elements and the four humors constitute a law does not make it so. Nor does the reductionist claim that life is explained by make-believe “atoms” floating in a void (a concept that dated back to the ancients) or the random interaction of particles, as the mechanists claimed. Nobody had a clue about microscopic and subcellular basis of life, and whether someone predicted that life would ultimately be explained by laws of nature or by some special, vital laws seems beside the point. In rejecting imaginary “laws” of elements and atoms and replacing them with spirits and innate heat, Harvey earned the title of vitalist. Fine, but in doing so he created a new physiological framework that, while certainly flawed, at least succeeded in promoting the organism as a whole with continuity and connection in its form, properties, and activities. Vital forces were convenient placeholders that would eventually give way to oxygen and other organic molecules. In this way, perhaps Harvey is more modern than we give him credit for. Besides, Harvey was on to something that we can relate to: blood, reigning supreme, is in constant motion, permeating all parts of the body, transporting vital substances to the tissues. It is our lifeline, at once mysterious and fascinating. In the final analysis, Harvey’s own blood project was one his most enduring contributions. AcknowledgementsThe author is grateful to Jane Maienschein and Charles Bardes for their invaluable input and editing, and Marianne Grant for reviewing the final draft of the manuscript. William C. Aird received his MD from University of Western Ontario. He completed a fellowship in Hematology at the Brigham and Women’s Hospital, Harvard Medical School in Boston and is presently a practicing hematologist at the Beth Israel Deaconess Medical Center and Professor of Medicine at Harvard Medical School. He is founder and Executive Director of The Blood Project. Click here to learn more. Appendix
2) Comments on the heart
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