by Rob Dunn
The first opportunity that came to Harvey as a result of his hard work was medical school. He graduated in classics, rhetoric, and philosophy from Gonville and Caius College at Cambridge in 1597, and he could have continued his studies there, but he got word of an opportunity in Padua, at the Bo. Padua offered him the chance to be among the greatest minds of the time, men (and a few clearly remarkable but poorly chronicled women) who gathered to display their knowledge. In the Bo, Fabricius dissected bodies while, in a room in the same building, Galileo wrote about and dissected the skies.
When Harvey arrived in Padua, he found an environment in which progress was more possible than anywhere else in Europe. But where Vesalius drew some influence in Padua from painters, Harvey’s influence would come from another direction, a new generation of astronomers who believed in making predictions and testing them with observations (and even experiments). Galileo was in Padua as a professor while Harvey was there as a student. It is possible Harvey may have taken classes from Galileo, but even if Galileo never directly mentored him, Harvey was influenced by the older man’s approach to science. Galileo achieved many firsts in astronomy, but among the most significant was that he built on Copernicus’s belief that the earth moved around the sun. Copernicus theorized that the earth circled the sun, but Galileo took Copernicus’s work further by generating and then testing a series of hypotheses of the phenomena that would be expected were the sun central. Harvey would come to do something similar for human bodies. He would develop ideas about how they might work and then test, with measurements, observations, and even experiments, the predictions of those ideas.
Harvey thrived in Padua, complaining far less than had Vesalius before him, and he graduated in 1602, having seen by that time, many hearts, dead hearts, hearts as still lifes that he could depict but not quite yet understand. From Padua, he initially took a position as an assistant physician at St. Bartholomew’s Hospital in London. With time, he would be given a lifetime appointment as the Lumleian Lecturer at the Royal College of Physicians. In this post, he was allowed a relatively leisurely schedule. He lectured twice a week on anatomy and surgery. This cushy position afforded him the affluence of time, the same sort of time da Vinci required for the flowering of his own greatness. Harvey had time enough to do his job, healing people, but also to explore ideas too grand to be justifiable to any reasonable (or perhaps even rational) employer—ideas about the heart.
With time, Harvey began to make the sorts of observations of the heart and blood vessels that he thought would lead him to new ideas and, eventually, to tests of those ideas. He used an approach we would now call comparative biology. He looked at the bodies of many animals to understand their differences but also to acknowledge that certain phenomena were easier to study in some organisms than in others. Harvey’s comparative approach allowed him to see phenomena others had missed. He then combined his observations of these phenomena with the findings of his contemporaries and the ideas of his forebears.
By the time Harvey returned to England in the early 1600s, at least one scholar had offered a wild new hypothesis about the workings of the heart. Yet while the hypothesis itself was stimulating to Harvey, the story of that scholar’s life might well have summoned a different emotion—trepidation at the possible consequences of having ideas at odds with the status quo. In Spain, Miguel Serveto (born about 1511), a philosopher-anatomist, had been able to break free of Galen and, in doing so, see the body anew. Between forays into questions about the meaning of life and religion, Serveto discovered a phenomenon everyone else had missed, namely, that the heart pumped blood into the lungs or, as he put it,
The vital spirit is generated by the mixing of the inspired air with blood, which goes from the right to the left ventricle. This blood transfer does not occur through the ventricular septum, as usually believed, but through a long conduit crossing the lungs. The blood is refined and brightened by the lungs, goes from the pulmonary artery to the pulmonary veins, is mixed with the inspired air and eliminates residual fumes. Eventually the whole mixture is sucked by the left ventricle during diastole.
Serveto’s discovery rested on several perceptive observations. He noted that the blood entering the lungs was different in color than that leaving it (due, we know now, to the absence or presence of oxygen). He also noted that the artery leading to the lungs was wide and thick, as though a lot of blood flowed to the lungs, not narrow, as might be expected if it was simply used by the body to supply some form of nutrition to the lungs.
Serveto would have been an excellent correspondent for Harvey, a living inspiration. The two might have exchanged insights and built on Serveto’s discovery. But such a relationship was not to be. Decades before the two might have had a chance to meet, Serveto died—of unnatural causes. In addition to studying the heart, Serveto had also been engaged in trying to reform religion (Serveto’s anatomical insights were actually published in a book that focused primarily on religion); he attacked aspects of Catholicism and Protestantism alike, revisiting the standard interpretations of Christianity just as he revisited the standard understanding of the heart. He wrote a series of books, beginning with Errors in the Trinity and culminating in an opus in which he directly attacked Calvin and the idea of predestination (that is, the concept that one’s fate is chosen by God before or at birth). Serveto boldly, some might say too boldly, sent this latter book to Calvin. In response, Calvin wrote to Serveto, “I neither hate you nor despise you; nor do I wish to persecute you; but I would be as hard as iron when I behold you insulting sound doctrine with so great audacity.” Serveto responded to Calvin, and the correspondence continued until Calvin had had enough. He wrote to his friend William Farel on February 13, 1546, “Serveto has just sent me a long volume of his ravings. If I consent he will come here, but… if he comes here, if my authority is worth anything, I will never permit him to depart alive.” Serveto did indeed travel to see Calvin, and on that trip, he was imprisoned by supporters of Calvin. Then, on October 27, 1553, at the age of forty-two, nine months after having published his work on anatomy, he was burned at the stake, surrounded by his heretical writings, including his hypotheses about the workings of the human lungs, arteries, veins, and heart.5
When Harvey discussed the heart with students and did dissections, he mentioned Serveto, but initially as an example of errant thinking rather than insightful progress. Serveto’s ideas were still too radical. But the more Harvey studied hearts, the more he began to think Serveto might have been right. And if the blood indeed flowed into the lungs rather than passing through the wall of the heart, Harvey began to wonder what other bits of the understanding of the heart would have to change. A Paduan anatomist, Realdo Colombo (1510–1559), had written that the valves of the heart seemed to allow blood to move out of the ventricles only (not back in as well, as had long been supposed), implying that there could be just one direction that blood moved in the heart: into atria, out ventricles. Colombo also showed that the veins leaving the lungs contained blood (rather than air), a reality that had begun to be suspected but was not yet well described. With time, Harvey started to teach his students about the ideas of Serveto and Colombo; he also showed them other evidence that seemed to him to suggest Serveto and Colombo were right. In the veins of the legs, there were valves. Vesalius thought the valves kept blood from pooling in the feet, but if the idea that blood flowed out of the heart was right, the function of the valves could be to prevent blood from flowing backward. So Harvey did a test of the kind Galen had done, a test of the function of the valves and of the direction of the flow of blood. He applied a tourniquet to the arm of a volunteer just tight enough to block the flow of blood through the veins (the arteries, being deeper down, were not affected). When he did, the section of arm below the tourniquet (toward the hand) swelled, as would be expected if blood was able to enter that part of the arm but could not leave it. Harvey also showed that if the tourniquet was applied very tightly—tight enough to stop blood flow through both vei
ns and arteries—blood did not build up in the veins (because no blood could get in through the arteries). Finally, he showed that if an artery alone was blocked, blood would build up above the tourniquet, on the side of the artery closest to the heart and the body’s core. It looked as though blood was moving toward the heart through the veins,6 and away from the heart through the arteries. Harvey just didn’t understand how.
Piecing the observations of Serveto, Colombo, and others together, Harvey started to rethink what circulation through the whole body might be like. He imagined new models that might make sense of what he was seeing. As he did, he repeatedly subjected the predictions from these models to real-world challenges, updating the story or shoring up his own confidence with each new test. This approach seems obvious today—creating an idea of how the body might work and then testing it through experiments and observations—but for generations, it had not been used (apart from in the work of da Vinci).
One of the phenomena Harvey tested was how the muscles in the arteries are constructed and work. Galen (at least, as interpreted by his translators) imagined that the flow of blood through the blood vessels was caused not by the contraction of the heart but by muscular contraction of the arteries. Galen and others had felt the arteries pulsing in their patients. The arteries do indeed pulse, but when Harvey studied them in detail, he noted they were reinforced from the inside, not the outside (and blood spurted out from them when they were larger, not smaller). If the arteries squeezed to push blood around the body, then one would expect they would be surrounded by a sheath of muscle. Instead, the muscle—or at least a layer of tough and fibrous cells—was on the inside, as though to protect the vessel against pressure from somewhere else. That somewhere else, Harvey thought, must be the heart. Harvey went on to show not only that the heart beat, but that it did so in two steps, first the atria, then the ventricles. Harvey was able to see these contractions by studying the hearts of fish and frogs, in which the contractions were slow enough to observe.
If the heart pushed the blood through the lungs and then back out to the body, a new question arose: Where did all the blood come from? This was a question that even the combined insights of Servetus and Colombo could not answer. Galen thought that after food was digested in the gut, the result—a sort of magical energy—was transported to the liver, where it was converted into blood. In this model, a person needed to eat food in quantities sufficient to equal the flow of blood through the heart. But there was another possibility that Harvey had begun to contemplate when considering the arteries and veins, namely, that the blood was cycling through the body, being invigorated by the lungs and then used again and again. The difficulty of Harvey’s proposition was that it required blood to move from arteries to veins somehow, somewhere. But the vessels did not connect, not visibly anyway. Harvey believed it had to happen via some invisible pore—not like Galen’s invisible pores in the heart, but maybe another set of invisible pores throughout the body. He could not prove the existence of such pores, but he could, he thought, show the impossibility of their absence by estimating the amount of blood the body would require if blood wasn’t being recycled. Da Vinci had calculated the amount of blood, at minimum, that moved with each tick of the pulse. He then calculated the number of times the pulse beat in a day (not distinguishing yet whether it was the pulse of the heart or the arteries). The two could be multiplied to get a crude lower estimate of the amount of blood a liver would need to produce: thousands of liters of blood a day. The estimate was astonishing (the modern estimate of the volume of blood that goes through the heart each day is even greater, six hundred thousand liters). It was a great pouring of liters of blood, too much for the liver to produce and too much for the average diet to supply food for.7
Pulling all of this together in a book, On the Motion of the Heart and Blood in Animals (1628), Harvey argued that the blood circulated: it was pushed by the heart, went out to the body through the arteries, returned to the heart through the veins, and was pumped to the lungs, where it extracted some vital force; then, with that force, it was pumped back out to the body. He was, of course, right.
Today’s textbooks often emphasize that Harvey discovered circulation, but he did more than that. Until one knew that the heart pumped blood from the lungs out to the body and then back and that blood contained vital stuff, there could be no realistic explanation for the function of the liver, the kidneys, or, really, any other organ of the body. Once Harvey determined what the heart, arteries, and veins did, the rest of the body could finally begin to make sense.
The lungs, for example, the organ for exchange of gas with the environment, suddenly had a job. We know they allow the veins to let go of a toxin (carbon dioxide) and pick up a vital element (oxygen). At the most basic level, the lungs give us invisible, vital succor and let out an invisible and deadly waste.8 As Harvey put it in the paragraph in which he rehung the pieces of the solar system of the body’s organs:
Since all things, both argument and ocular demonstration, show that the blood passes through the lungs and heart by the action of the auricles and ventricles, and is sent for distribution to all the parts of the body, where it makes its way into the veins and pores of the flesh, and then flows by the veins from the circumference on every side to the center, from the lesser to the greater veins, and is by them finally discharged into the vena cava and right auricle of the heart, and this in such a quantity or in such a flux and reflux thither by the arteries, hither by the veins, as cannot possibly be supplied by the ingesta, and in much greater than can be required for mere purposes of nutrition; it is absolutely necessary to conclude that the blood is in a state of ceaseless motion; that this is the act or function which the heart performs by means of its pulse; and that is the sole and only end of the motion and contraction of the heart.
Much of Harvey’s work had been done on dogs, but it was now obvious that within each dog and each human, the heart’s rivers flowed in a circle. Galileo had shown without a doubt that the earth circled the sun, and Harvey had now shown that the blood circled the body. This same circuit can be found in every living bird and mammal species and, with some tweaks, in every reptile, amphibian, and fish too.
One might imagine that, with this knowledge of the heart’s circuit, physicians would begin a great wave of new research, perhaps even attempt surgeries on the heart. None of this occurred. After Harvey offered his revelation, he was lauded. He retired, and then, so it seems, the entire field followed suit. Harvey’s colleagues tried to get him to come back to work, but he stayed in retirement. As he put it,
Would you be the man who should recommend me to quit the peaceful haven where I now pass my life and launch again upon the faithless sea? You know full well what a storm my former lucubrations raised. Much better is it oftentimes to grow wise at home and in private, than by publishing what you have amassed with infinite labour, to stir up tempests that may rob you of peace and quiet for the rest of your days.
Harvey had begun to be believed, but he was tired. He would leave the next steps to others, and there were many steps. Blood itself would not be understood for decades. Harvey never really understood blood. He never saw how it cycled in the body, and he could not see the capillaries that connected the arteries and the veins. It would take another generation before the Italian scientist Marcello Malpighi would use a microscope to observe the connections, a single cell wide, between the narrowest arteries and the narrowest veins. Like Harvey, Malpighi chose to work on those organisms in which he might most easily see the phenomenon he was interested in. He looked at model organisms. When it came to seeing the smallest arteries and veins, frogs were ideal, and it was in them that he observed with his microscope the capillaries that connect the smallest arteries, the arterioles, to the smallest veins, the venules. The walls of these capillaries are a single cell thick—each tunnel just one four-thousandths of an inch wide—but they are everywhere. No cell in your body is more than twenty microns (about a third of a hair) away from
a capillary. Capillaries abut the alveoli of the lungs and pick up oxygen and release carbon dioxide. Capillaries bathe the cells in the body’s sea of blood.
But what did the blood actually carry? Harvey ducked this question and simply moved the magic of the heart to the blood. The blood carried vital spirit, inhaled in the lungs and spread to the body. Harvey thought that the heart required this vital stuff to live. He also imagined that some sort of fermentation occurred in the veins just before the blood coming back from the body reached the heart. Fermentation, he knew, turned grape juice to wine. Perhaps it also turned blood that had been used by the body back into something more vital.
I’ll pause to note the enormous loveliness of the idea that our blood is enlivened by fermentation. Of course, it is wrong. The character of the blood that reenters the heart is determined not by fermentation but by what has happened to the blood throughout the body as it has been carried here and there. The oxygen and sugar are used up by the cells. In their place, the blood receives cellular waste and carbon dioxide (itself a kind of waste). But Harvey was on the right track; although this process is not technically due to fermentation, there were microbes involved.
No less than 3.8 billion years before Harvey suggested that fermentation enlivened the blood, life evolved on Earth.9 We take it for granted now that our cells require oxygen, but this reality was discovered only in the mid-1900s and it might easily have been otherwise. When life began, not only was oxygen not necessary, it scarcely existed at all. Although just how life began is the subject of active, albeit speculative, research, we know that life almost certainly began with a single cell. From that cell, every living thing that has ever lived descends. There are no exceptions on Earth, not even the hint that one might plausibly look for exceptions. That first cell and its early descendants, as near as anyone has been able to determine, could deal with extreme heat and lived off the energy they could derive from chemically transforming inorganic molecules such as hydrogen and sulfur. At least initially, their diet did not include other organisms, for the simple reason that there were none. There was also not yet oxygen, and so they were anaerobic (an-means “without” and aerobic “using oxygen”). They did without, as do many kinds of single-celled organisms living in modern low-oxygen environments, from the muck at the bottoms of swamps to the partially digested food in your colon.