Blood Work (4 page)

While the early medical world still clung to Galenic humoral
ism and bloodletting, a number of discoveries set off a chain of questioning about how blood was made and how it moved through the body. In the sixteenth century a little-known anatomist named Amatus Lusitanus speculated that valves in the veins—which he called
ostiola
(little doors)—may in some way direct blood flow, preventing its reflux. This hypothesis, now known to be correct, was promptly dismissed by Andreas Vesalius, one of history's most celebrated dissectionists.
¹⁰
Vesalius argued instead that the main purpose of valves was to strengthen the walls of the veins. With Vesalius serving as something of a last word, interest in valves lay dormant until 1603, when the Italian physician Hieronymus Fabricius rejected the Vesalian idea that valves worked merely as architectural reinforcements and returned to the idea of “little doors.” He likened them to floodgates, which help control flow volume. Without valves blood would stream unchecked into the lower portions of the body, leaving the upper body parts malnourished. In light of these conflicting theories, valves raised more questions than they answered for the seventeenth-century Harvey. There were so many valves, and in so many places in the body, that he wondered why it was that they “were so placed that they gave free passage to the blood towards the heart, but opposed the passage of the venal blood the contrary way.” Surely, he speculated, “nature had not plac'd so many valves without design.”
¹¹

Harvey knew that the only way he could explore his hypotheses on the valves was to perform surgical experiments on live creatures. For as fascinating as human anatomy was and remained for natural philosophers, cadavers presented an intractable problem: They were dead. Dissections had been useful, but Harvey knew that he needed to
see
the blood in motion, to trace its flow through the body, through the valves, and to feel the pulsations of a beating heart. This could only be accomplished through vivisection, by putting living animals under his knife.

Scores of dogs, cats, and pigs roamed the streets and were easily lured with a handful of food; and Harvey kept himself busy with the bounty. Surgery after surgery, he tried to move quickly enough to catch the heart and blood in action. But the animals' writhing was difficult to control, and their heartbeats were too fast. Harvey then turned his attention to cold-blooded creatures. Their slow-beating hearts made eels, snakes, and squid more cooperative subjects. With each heartbeat he plotted the heart's contractions and relaxations; its diastolic and systolic motion. He watched as the heart reddened ever so slightly as it tensed, filled with blood, and then blanched as it forced out its contents. The vivisectionist stared in fascination as his cold-blooded subjects slipped toward death.

Integrating dissection with his observations during live experiments, Harvey was able to quantify for the first time in history
the amount of blood that coursed through a body. He emptied out all the blood in the chamber of a dissected human heart and determined that he had collected about two ounces of blood. From this he estimated the total fluid that pushed in and out of the heart with every contraction. He multiplied this amount by the number of heartbeats per every half-hour, which allowed him to calculate that nearly 540 pounds of blood would have to be produced and burned off in a Galenic physiological model.
¹²
This was entirely impossible. Another explanation had to be found. For Harvey it was soon clear that blood did not make a one-way trip to the heart to be incinerated. Instead blood was pumped through the body by the heart in a circular fashion, with the valves helping to direct the flow.

FIGURE 2:
William Harvey's illustration demonstrating the action of the valves in
De Motu cordis
(1628).

I
n the decades that followed, many of England's most promising minds spared no effort as they worked to confirm Harvey's claims. For young men like Christopher Wren, Harvey's ideas on blood circulation fitted nicely into what was a much larger fascination with novelty and invention. Even as a teenager Wren had made a name for himself for being as clever with his hands as he was with his mind. Working with fellow inventor William Petty, he devised a machine that easily sowed seeds by drilling a hole in the soil. Wren also ingeniously developed a prototype of a double-writing machine in which two pens were mounted on a frame and could be moved simultaneously to produce duplicate copies of a single document. In this age when letters were the primary form of written communication, such a device promised to be invaluably useful. But to Wren's dismay Petty took full credit when it was presented to Oliver Cromwell—now at the helm of the so-called Commonwealth, following the trial and execution of Charles I—at the end of 1650 or the beginning of the following year.
¹³

In 1656 the twenty-four-year-old Wren made a seat for himself at the dissection table and decided to test Harvey's description of the ultimate machine—the circulatory system. In the sixteenth chapter of
De motu cordis,
Harvey had listed other facts that supported experimental evidence for his arguments on the circulation of blood. The most compelling, Harvey argued, was the work of poisons and medications. How was it that a wound from a mad dog could be healed, he asked, but “a fever and other horrible symptoms” could still persist? He concluded that the contagion is carried through the bloodstream to the heart and from there the poison circulates through the rest of the body.
¹⁴
With this in mind Wren injected the veins of a dog with wine and ale. The dog soon became noticeably drunk. In an effort to reverse the effects of the alcohol, the precocious Oxford student injected two ounces of an emetic (
crocus metallorum
). The dog “immediately fell a vomitting, & so vomited till he died.”
¹⁵

Fueled by excitement about his research, Wren happily bragged to the influential John Wilkins and his friend, the chemist Robert Boyle, that he could easily and quickly convey any liquid poison into the entire bloodstream of an animal. Boyle soon called Wren's bluff by presenting him with a large dog. Unfazed and self-assured, Wren wrangled the dog and strapped it tightly to a table with the help of two colleagues. He exposed a large vein in the dog's hind leg and tied it off. He then made an incision in the blood vessel. Despite the animal's “tortur'd violent strugglings,” Wren slid a small grooved plate, which he had made himself, under the vein to hold it in place. He then inserted a thin pipe into the vein. Boyle described at length Wren's next steps and their marvelous effects: “And accordingly our dexterous Experimenter…conveyed a small Dose of the [opium] Solution or Tincture into the opened vessel…. It was quickly, by the circular of that, carried to the Brain, and the other Parts of the Body: So
that we had scarce untied the Dog…before the opium began to disclose its Narcotick quality.”
¹⁶
Once on its feet, the dog began to “falter and reel.” The animal looked so drugged that, wrote Boyle, spectators offered wagers that the dog would soon expire. But to the surprise of everyone, perhaps even Wren himself, their subject not only survived but also grew fat. The dog, made famous by Wren, was stolen not long after.
¹⁷

FIGURE 3:
Early infusion experiments in animals tested Harvey's theories on circulation and laid the groundwork for the first canine-to-canine blood transfusions. Johann Sigismund Elsholtz,
Clysmatica nova
(1667).

In 1657, the year of William Harvey's death, Wren moved to London to take up the prestigious post of Gresham Professor of Astronomy. His appointment did little to distract him from his medical experiments. Pairing up with Dr. Timothy Clarke, a fellow Oxford anatomist recently transplanted to the capital, Wren continued his work on infusions. Together they tried injecting “many different kinds of waters, beers, milk, whey, broths, wines, alcohol, and even blood itself.”
¹⁸
Wren and Clarke then shifted their trials from dogs to men. In the fall of 1657 the infusionists met at the home of the French ambassador to the Commonwealth, the Duke of Bordeaux. The duke, Wren explained, offered up an “inferior Domestick of his that deserv'd to have been hang'd.”
¹⁹
We have few details on how Clarke and Wren persuaded—or forced—the servant into participating in their experiment. But we do know that Wren in particular was visibly rattled by the outcome. The minute a small amount of the emetic
crocus metallorum
hit the servant's veins, the man fainted. And both Clarke and Wren resolved never again to try “so hazardous an experiment” on humans.
²⁰

The experience must have left a lasting mark on Wren; he did not attempt medical experiments again in any regular way. But circulation would never be far from his mind—or far from those of other experimentalists who were much less reluctant to impose their dangerous procedures on animals, and soon the bodies of fellow humans.

T
he seventeenth century is sometimes referred to as the “Age of Vivisection,” and for good reason. The use of live animal subjects was encouraged by the rise of Cartesian philosophy, which held that human and animal bodies were fundamentally similar—because each functioned essentially like a machine. “It is nature,” wrote Descartes, “which acts in them according to the disposition of their organs, as one sees that a clock, which is made up of only wheels and springs, can count the hours and measure time more exactly than we can.”
¹

As little more than a collection of tubes, pumps, pulleys, and levers, therefore, animals were incapable of language, emotion, and reason. Descartes argued adamantly against critics who claimed that animals found ways to communicate with humans. The philosopher emphasized instead that animals like parrots and magpies may “utter words just like ourselves,” but they “cannot speak as we do, that is, so as to give evidence that they think of what they say.”
²
While animal lovers might think that their pets expressed pleasure and pain, these were only dispas
sionate responses to external stimuli. And because animals do not benefit from this capacity of understanding, Descartes concluded, they cannot feel pain. Descartes' arguments on the beast-machine were taken by some as full license for cruelty. After being accused of kicking a pregnant dog, for example, the late-seventeenth-century French philosopher Nicolas de Malebranche responded cavalierly: “So what? Don't you know that it has no feeling at all?”
³

Vivisection offered new opportunities that many natural philosophers welcomed wholeheartedly, especially members of England's Royal Society. Established in 1660 by order of King Charles II, the Royal Society endeavored to follow the notions set forth in Sir Francis Bacon's
The New Atlantis
decades earlier. It was a state-sponsored “Solomon's House,” after the biblical intellectual leader and builder of temples. The society dedicated itself to “promoting physico-mathematicall experimentall learning.” Meetings took place once a week at Gresham College in Bishopsgate and featured the most renowned natural philosophers of the day, including founding members Wren and Boyle.

In the first four years of the Royal Society at least ninety experiments were performed on live animals.
⁴
This figure does not take into account, of course, the many other experiments that were also performed ad hoc on tables in members' homes. One of England's most aggressive vivisectionists was Robert Hooke, known for his observational prowess with the microscope as well as for being the first to use the term “cell” in biology. In their younger years, Hooke and Robert Boyle—two founding members of the society along with Wren—invented a “pneumatick engine” that could be used to create a vacuum chamber. Curious about the conditions within the vacuum, they subjected larks, sparrows, mice, cheese mites, ducks, and cats to the airless horrors of the vacuum.
⁵
Each of the animals was taken just to, or
well past, the point of death before air was once again allowed to fill the chamber. Justifying his research in a Christian context, Boyle brushed off criticisms about the cruelties of animal experimentation in his studies of air pressure: “It is no great presumption to conceive that the rest of the creatures were made for man, since he alone of the visible world is able to enjoy, use, and relish many of the other creatures, and to discern the omniscience, almightiness, and goodness of the author in them.”
⁶

These early air-pump experiments led to the more gruesome vivisections that Hooke conducted on the lungs of living animals. In 1664 the Royal Society dispassionately recorded that the experimentalist wielded his knife on a dog “and by means of a pair of bellows, and a certain pipe thrust into the wind-pipe of the creature, the heart continued beating for a very long while after all the thorax and the belly had been opened.” But mechanistic theories of physiology notwithstanding, even Hooke found this experiment too troubling to repeat. In a letter to Boyle, his partner in research, Hooke described in painful detail the bellows procedure and the “torture of the creature” on which he was experimenting:

Cartesian arguments that animals were little more than soulless machines had been convenient for late-seventeenth-century natural philosophers and vivisectionists who were clamoring to understand the mystery of the body. But as the reaction of the normally cold-blooded Hooke suggests, Descartes' arguments could go only so far in justifying the obvious suffering that animals experienced while being held hostage to man's scalpels. First articulated in the 1630s, not long after Harvey's game-changing discovery of circulation, Cartesianism represented a radical departure from long-standing Aristotelian ideas regarding the body and the soul. According to Aristotle, the lowest entity on the “Great Chain of Being” was plant life, which possessed a corporeal “vegetative soul” endowed with only the basic faculties necessary for life: nutrition, growth, and reproduction. Higher up, animals enjoyed both this vegetative soul and a “sensitive soul,” which allowed for sensation, movement, and—at least to some degree—emotion. Humans alone possessed an “intellective soul,” along with the vegetative and sensitive faculties. The intellective soul provided the faculties of knowledge, memory, will, and reason. In a word, humans had minds (
mens
).
⁸

For most, mind and soul were embodied. According to the Old Testament the soul was part of the blood itself. For Galen it resided in the liver, which was believed to be the seat of blood production. In later Christian doctrine the soul moved from the blood to the ventricles of the brain, where it was better protected from corrupt, earthly forces. Floating in the dark and empty spaces of the brain, the soul thus inhabited the body but was not
of
the body.

When Descartes evicted the soul from the body, he was the target of hostile critiques from nearly all corners of Europe. Yet the philosopher himself struggled to counteract the objection
that thought and emotion can be manifested physically: The act of thinking makes brows furrow, anger tightens the chest, sadness brings tears, desire warms the body. In his later writings Descartes asserted that the pineal gland, nestled (as he understood it) in the center of the brain, served as a way for a disembodied soul to communicate with the body. The movement of the mind on the pineal gland excited the “animal spirits,” which then communicated messages to other parts of the body. “The soul has its principal seat,” wrote Descartes, “in the middle of the brain. From there it radiates through the rest of the body by means of animal spirits, the nerves, and even the blood.”
⁹
Descartes concluded that, while having no material existence itself, the soul radiates through the body via the pineal gland in the brain.

As vivisectionists continued to perform blood experiments,
they were forced to lay their cards openly on the table. Was the soul corporeal? Did it reside in the blood? What if both animals and humans had souls? And most troubling of all, what if animal and human blood were to be mixed? Over the short span of four years, between 1665 and 1669, precisely these questions would determine the French transfusionist Denis' fate—as well as that of blood transfusion more generally—in both England and France.

FIGURE 4:
For Descartes, the pineal gland (H) helped mediate communication between the corporeal body and the noncorporeal intellect and soul.
De homine
(1662).

 

B
lood experiments were not only a matter of philosophy; they were also a performance that showcased a surgeon's skill in unpacking nature's mysteries. With nimble hands and unbreakable concentration, the surgeon Richard Lower became legendary for his perfectly choreographed surgical displays. It was through his work that blood—and later, blood transfusion—would rise to take medicine's center stage both in England and, not long after, in France. Born three years after Harvey published
De motu cordis,
the sunken-eyed and impassive Dick Lower had earned a name for himself through the dexterity and care he took in his anatomical and physiological experiments. Unlike many surgeons who were known to carve up cadavers—both human and animal—with about the same art as a local butcher, Lower worked slowly and patiently as he chiseled, like a sculptor, through the mysterious flesh of his subjects. He was a dedicated, even obsessive, anatomist who seemed incapable of separating himself from his work. The antiquarian Anthony Wood claimed that Lower often skipped Mass in favor of dissection; indeed, Wood had seen him hard at work on a calf's head on a Sunday morning, in his dissection rooms adjacent to Christ Church college.
¹⁰
Even Lower's pets were unable to escape his knife. Another contemporary, John Ward, noted in his diary that Lower owned “a dog which they call Spleen because his spleen was taken out.” The dog was, of course, promptly dissected when it finally died about a year later.
¹¹

Lower's gifts as a vivisectionist surgeon were lauded by Thomas Willis, his professor at Oxford, who acknowledged his student and assistant Lower in
Cerebri anatome
(1664) as “a doctor of outstanding learning and an anatomist of supreme skill. The sharpness of his scalpel and of his intellect…enabled me to investigate better both the structure and functions of bodies, whose secrets were previously concealed.” Not a day passed without Willis and Lower undertaking “some anatomical administration” on the brains and bodies of a whole bestiary of creatures: “horses, sheep, calves, goats, hogs, dogs, cats, foxes, hares, geese, turkeys, fishes, and even a monkey.”
¹²
Credited with the discovery of the circle of arteries that supply blood to the brain (the circle of Willis), Willis enlisted Lower to help him perform a wide range of infusion experiments in order to track the path of the blood from the brain through the rest of the body and back. A fellow student at Oxford with Wren, Lower injected milk into the veins of dogs and ink into their brains as well as other “kinds of liquors, tinctured with saffron, or other colours…to try how the blood moves, and how the tincture may be separated in the brain.”
¹³
A nimble and creative thinker, Lower explored the implications of his teacher's work. Building on Willis's discovery of the arterial circle, Lower established that cerebral circulation could be maintained even if one or more parts of the circle became blocked or narrowed.

Cartesian dualism of mind and body did not sit well with Willis. His many dissections had shown that both humans and animals had pineal glands. This in itself had given Willis plenty of reason to doubt the French philosopher's already tenuous claims of mind-body dualism. Following along the lines of one of Descartes' main detractors, Pierre Gassendi, Willis instead made the case that man was a “two-soul'd animal.” Like animals, man had an embodied “sensitive soul,” which was responsible for lesser
faculties such as growth and sensation and was present in all parts of the body, including the blood. The rational soul, on the other hand—the soul that thinks, feels emotion, and reasons—was also embodied, and located exclusively in the brain. In contrast to Descartes as well, Willis believed that animals did have souls. They showed evidence of memory, decision-making ability, and emotion—which meant that they must have some soul, albeit a primitive one. Yet it was humans alone who benefited from the much-more-complex rational soul.

For Lower debates and questions surrounding the exact nature of the soul were interesting but apparently not of immediate concern. Moving from the brain to the blood, Lower continued Wren's earlier infusion experiments and focused on the possibilities of intravenous feeding. Lower wondered whether he might keep a dog alive “without meat, by syringing into a vein a due quality of good broth, made pretty sharp with nitre, as usually the chyle tastes.” Perhaps he could even implant permanently a tube into the animal, so that he would not need to make a fresh incision every time. With this in mind he injected a dog with warm milk; the dog died one hour later. When he later dissected the animal, he found that its blood had mixed with the milk “as if both had curdled together.” Like oil and water, there were some things that just did not mix well with blood, he concluded.
¹⁴
Not one to shy from a challenge, he wondered aloud in a letter to Boyle if the problem of intravenous feeding might be solved by mixing blood with blood. “As soon as I can get two dogs of equal bigness,” he wrote, he would bleed an artery of one dog into the vein of the other “for an hour's time, till they have whole changed their blood.”
¹⁵