History of hematology (1500-1800)

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The history of hematology, specifically focusing on the sixteenth to eighteenth centuries, deals with concepts such as humoral theory, bloodletting, transfusions (animal-to-human and, later, human-to-human), early understandings of the circulatory system, and hematological disorders including leukemia, hemophilia, and the hereditary components of hematological disorders. Figures such as William Harvey, Andreas Vesalius, Michael Servetus, William Hewson, and James Blundell laid the groundwork for an understanding of modern hematology; however, their work was possible largely as the result of predecessors such as Galen, Hippocrates, and Aristotle. However, observations in the seventeenth century by William Harvey were slow to break the entrenched influence of Galenic theory that dominated Europe at the time. Galenic theory would not fully disappear from medicine until the middle of the nineteenth century, when germ theory, the brainchild of Louis Pasteur, replaced it. The process by which Western medicine shifted from bloodletting to blood transfusions is a complicated one, as Galenic theory did not suddenly vanish into thin air. The knowledge provided by William Harvey in De Motu Cordis gave his successors the ability to whittle away at Galenic theory and ultimately discredit it.

Galenic Theory

Galenic theory derives from the works of Galen, a Greek physician who lived in the second century CE. Galen was born in the town of Pergamon, located on the Aegean Sea in what is now Turkey. Galen obtained his medical knowledge from dissecting various animals, especially Barbary apes and pigs, and from performing surgery on injured gladiators. Due to his expertise, he eventually became the personal physician to several Roman emperors, including Marcus Aurelius. Galen’s understanding of medicine was directly related to his knowledge of humoral theory, which was the then-current state of medical knowledge in ancient Rome.

Humoral theory

Humoral theory, a critical component of Galenic theory, described how the human body was composed of four humors, or fluids: black bile, yellow bile, blood, and phlegm. If a patient had a dominance of one particular humor, then physicians were led to believe that the humors were imbalanced, therefore making the patient ill. An excess of black bile made the patient melancholic; an excess of yellow bile made them choleric; an excess of phlegm made them phlegmatic, and an excess of blood made them sanguine. Galen’s four humors were used to explain a variety of illnesses. The common cold was explained as an excess of phlegm, owing to the watery secretions expelled through the nose by an infected person. Similarly, jaundice was explained as an excess of yellow bile, even though it is now known to be a symptom of various diseases such as malaria. The humors also could affect one's disposition: a choleric person was typically seen as aggressive and irrational, a sanguine person was optimistic and jovial, a phlegmatic person was sluggish, and a melancholic person was depressed and pessimistic. During the time period of the Scientific Revolution, the four humors were an essential component of understanding someone’s personality.

Bloodletting

Secondary to the four humors, bloodletting, or bleeding, is a pseudoscientific treatment that has been abandoned by modern medicine except as a treatment for a few conditions, such as hemochromatosis. Bloodletting was pervasive in the time period, as people thought it was a treatment for a variety of illnesses as well as a prophylactic. The procedure was performed through the process of opening a vein with a knife or an instrument called a fleam, thus allowing the blood to collect in a bowl under the patient. In the sixteenth century, a patient was most likely to be bled by a barber, who would have done surgery in addition to cutting hair. In England, the barbers and surgeons were merged in 1540 by order of Henry VIII into the Company of Barber-Surgeons. Bloodletting may seem counterintuitive when viewed in a modern context, especially when used for menstrual complaints or illnesses that result in the patient bleeding profusely, such as hemophilia. Physicians at the time did not know about the composition of blood, specifically hemoglobin and hematocrit, and its impact on the bleeding process. Their inability, based on the scientific knowledge of the time, to easily distinguish between an artery and a vein, as inexperienced physicians sometimes cut arteries instead of veins, resulting in the patient bleeding out. Sixteenth-century hospitals also placed bans on the admission of hemorrhaging patients, as well as menstruating and pregnant women. This was because hospitals were run by members of the clergy, and the Fourth Lateran Council forbade priests from operating on patients or bleeding them. Cupping was an alternative to bleeding for patients who were older or physically weaker. The practice of bloodletting maintained popularity throughout the sixteenth century, showing no signs of abating even when anatomists such as Andreas Vesalius published revolutionary works on the human body. Vesalius' book De Humani Corporis Fabrica, often abbreviated as De Fabrica, shows the structures of the body in exquisite detail. However, Galenic theory remained entrenched amongst the medical minds of Europe, leading to no immediate change in the status quo. Eighteenth-century physicians continued to practice bloodletting, although it was performed less frequently over time. Towards the end of the eighteenth century, Benjamin Rush, a physician and signer of the American Declaration of Independence, was an advocate for bloodletting during an epidemic of yellow fever that affected Philadelphia in 1793.

Leeches

Leeches were used in conjunction with other bloodletting methods, such as cupping and bleeding, to extract blood from patients as part of humoral theory. Beginning in the sixteenth century, prevailing medical theory believed that leeches should be applied in ascending numbers according to the age and sex of the patient. A toddler would require one or two leeches, while a woman would require fifteen, and a grown man would require up to sixty leeches in a single sitting. In the seventeenth and eighteenth centuries, physicians began to prescribe regular hirudotherapy sessions, which came to be known as “leech mania.” European countries such as France depleted their natural leech populations, requiring more leeches from elsewhere in the world, thus creating a vicious cycle that led to the leech becoming an endangered species in Europe. In the middle of “leech mania,” even infants and the elderly could have leeches applied to them, with little regard to the medical history of the patient. “Leech mania” ran counter to Galenic theory, as both Galen and Hippocrates advocated for moderation when bleeding patients.

William Harvey, his predecessors, and his successors

Andreas Vesalius

Andreas Vesalius, or Andre van Wezel, was born in Brussels, then part of the Hapsburg Netherlands, in 1514. He was educated at the Sorbonne and the University of Leuven. It was in Paris that he developed a keen interest in anatomy. He studied Galenic theory under renowned physicians such as Jacques Dubois and Jean Fernel. Vesalius, unlike Galen, was able to dissect human corpses, which gave him a better understanding of how the body worked. Vesalius discovered that the heart lacked a septum, and that it was a four-chambered organ. However, it would take until the seventeenth century for the circulation of the blood to be discovered. Vesalius' student Realdo Colombo discovered the motion of the heart, correctly understanding the systolic and diastolic states of the heart. In Galenic theory, there was no understanding of the pulse, as life was thought to originate in the lungs. The heart was thought to fulfill a function similar to modern medicine’s understanding of the liver. This understanding was rooted in the concept of pneuma, which translates from Greek as "breath," as in the concept of the "breath of life."

Michael Servetus

The first description of the circulation of the blood was not published until 1553, in Christianismi Restitutio, a theological treatise written by Michael Servetus, a physician and humanist thinker from the Spanish city of Tudela. It was Servetus who discovered the motion of the heart, but because his treatise was not a medical or anatomical textbook, it was not taken seriously by his contemporaries.

William Harvey

The most significant figure in the field of seventeenth-century hematology was William Harvey, an English physician from the town of Folkestone. Harvey possessed an awareness of Realdo Colombo's work on the circulation of the blood, however, he was unaware of Michael Servetus' discovery of the heart’s motion, presumably because of Servetus' execution by the Calvinists of Geneva and rejection by the Catholic Church, as his theories were incompatible with the religious fervor of the time period. Harvey began to disprove Galenic theory by dissecting corpses, which gave him a foundation in anatomy that would later provide the basis for his work De Motu Cordis. He was allowed by Charles I to conduct dissections and vivisections on royal deer, which allowed him to understand how the heart worked as a pump, but he found their hearts moved too rapidly for them to be a worthy comparison to the human heart. Instead, he decided to experiment on animals who were dying, so he could watch the heart move at a slower, more observable pace. This inquisitive nature led to a better understanding of the diastolic and systolic motion of the heart, the fact that the heart is a pump, and the fact that blood circulates around the body. Through this knowledge, Harvey was in direct conflict with Galenic theory, which had gone unchallenged for millennia. According to Galenic theory, the liver was thought to produce blood, and the heart was thought of as no more than a filter. Tissues were nourished by the absorption of blood, which did not circulate through the body. Blood passed through the heart by means of a "septum," or pores in the ventricular walls. Galen also surmised that the heart had three chambers, an observation he gleaned from dissecting animals. Harvey, by contrast, discovered that blood is not absorbed by tissues, but instead circulates around the body in a web of arteries, veins, and capillaries. Harvey challenged the established view of Galenic theory, a system that his contemporaries held in high esteem. By doing so, he was seen as a renegade by many at the time.

Early blood transfusions

Xenotransfusions would have been impossible without Harvey’s discovery of the circulation of the blood. Xenotransfusions, or transfusions between animals and humans, or between two different species of non-human animals, began in earnest in the seventeenth century. In 1667, a surgeon named Griffoni successfully transfused his deaf pet spaniel, who was failing to thrive, with lamb's blood. Most of the animals transfused were dogs, animals whom Harvey had experimented on to find out how the heart worked. In June of 1667, the first successful animal-to-human blood transfusion was carried out by Jean-Baptiste Denis, when blood from a young sheep was transfused into a fifteen-year-old boy. However, in his next transfusion attempt, it failed miserably. The patient was a thirty-four-year-old mentally ill man, and Denis thought that the man’s neurological condition could be cured or alleviated via the transfusion of blood from a calf. The patient began to display symptoms of transfusion incompatibility; however, his symptoms also matched those of arsenic poisoning. Denis, as the physician responsible for the transfusion, was accused of poisoning his own patient, as there was no notion of how blood from a calf would be rejected by the immune system, causing the patient to react adversely. As a result, the royal court at Versailles intervened and demanded an end to transfusions involving humans, placing transfusions on pause for over 150 years. While influenced by Harvey, the physicians carrying out these transfusions were not immune to the influence of Galenic theory, which stated that an animal's character was carried in the blood. The Galenic philosophy behind xenotransfusion’s use as a "cure" for mental illness was that young animals, especially lambs and calves, were seen as calm and docile.

William Hewson

William Hewson was Harvey’s successor, and built upon concepts that Harvey had discovered in the seventeenth century. Hewson was born in Hexham in the eighteenth century, and his contributions centered around demonstrating the existence of the lymphatic system in humans, as well as correctly identifying the shape of red blood cells. Antonie Van Leeuwenhoek had previously identified red blood cells as spherical, but through Hewson’s work, he correctly recognized them as discoid. The significance of discovering the shape of red blood cells was that medicine, especially hematology, drifted further away from its foundations in Galenic theory. Through his scientific discovery, Hewson produced evidence for the existence of a cell membrane in red blood cells and also isolated fibrin from the coagulation process, which was an integral breakthrough in hematology in order to understand the coagulation process. He wrongly identified the dark cores of red blood cells as their nuclei, which was rectified by later scientists. Ironically, Hewson’s cause of death was sepsis, which he contracted while dissecting a corpse. In 1774, precautions were not taken to ensure the protection of the physician or the patient. Physicians often probed open wounds with their fingers, allowing pathogens to jump from their hands to the wound.

Human-to-human blood transfusions

Human-to-human blood transfusions should be addressed, even though they fall outside of the scope of the Scientific Revolution. However, they are adjacent to the Scientific Revolution and many of the same themes can be applied from xenotransfusions to human-to-human transfusions, which did not start until the beginning of the nineteenth century, when James Blundell, a British obstetrician, carried out the first successful transfusion between two humans to treat postpartum hemorrhage in 1818. The donor was the patient's husband, and four ounces of blood were extracted from his arm to save his wife. Blood types had yet to be discovered, however, a potential explanation for the success of this transfusion is that the patient had Type AB blood, known as the "universal recipient.”

Hematological disorders

Neither Galen nor William Harvey delved into hematological disorders, but their works provided the structural foundation for later generations of scientists to explore these disorders. By knowing about the circulation of the blood, scientists have realized that hemophilia is a disorder pertaining to the coagulation process, and that leukemia is recognizable by an excessive amount of white blood cells, which gives the blood a milky appearance. William Hewson stands out as a founding father in the field of hematological disorders. His discovery of fibrin paved the way for the discovery of hemophilia as a deficiency in Factor VIII, a coagulating compound in the blood. Similarly, his discovery of cell membranes in red blood cells led to the discovery of blood types, and his discovery of the shape of red blood cells led to the later discovery of a hematological disorder unknown to eighteenth-century medicine: sickle-cell anemia. One of the better-known hematological disorders discovered by eighteenth-century physicians was hemophilia. The existence of hemophilia has been known since the Bronze Age, but eighteenth-century physicians gained more insight and understanding of it largely in part due to the frequent intermarriages of European royals in the periods up to the eighteenth century. This led to the discovery of the hemophilia gene being carried in the female line, yet only men were symptomatic. In retrospect, a notable carrier of the hemophilia gene was Queen Victoria, whose daughters unknowingly spread it into the Spanish and Russian royal families. Historians can chart the progress of hemophilia in Queen Victoria’s family; however, the knowledge that she carried the hemophilia gene was unknown at the time. Leukemia was another hematological disorder known to eighteenth-century physicians, representing the time of discovery when hematological disorders were found to exist. When physicians placed a blood sample from a leukemia patient under a microscope, they could see that the patient had milky blood, caused by the abnormally high levels of white blood cells in their bloodstream. Iron-deficiency anemia was also discovered in the seventeenth century, during which revolutionary treatments began to emerge. Thomas Sydenham, a physician known as "the English Hippocrates", administered iron supplements orally as a definitive treatment for iron-deficiency anemia. The eighteenth century possessed a sense of discovery in regards to disease progress.

In consideration of the current historical consensus, one benefits from a conceptual grounding in medical works to foster an understanding. Although Williams Manual of Hematology is clinical in nature, thus not offering any interpretation of the facts, this clinical knowledge would have been unknown without Harvey’s discovery. Furthering the clinical perspective, Dr. Gerald Hart’s “Descriptions of Blood and Blood Disorders” uses clinical information to gain a better understanding of Galenic theory. His strength is in the statement of the facts of what constituted Galenic theory and its placement in the worldview of the sixteenth through eighteenth centuries. He did not address William Harvey directly, although the clinical groundwork addresses both Galenic theory and William Harvey. With these two clinically focused works, contrasting Dr. Dhun Sethna’s The Wine-Dark Sea Within allows for a more critical approach, faulting Galen for the stagnation of medicine that would last until the nineteenth century. As a cardiologist, Dr. Sethna does not hold back in his criticisms of Galen, stating that medicine would have advanced by leaps and bounds had the West not grown so attached to Galen and his theory. His acknowledgement of the significance of William Harvey’s discovery of circulation was one of the book’s greatest strengths. Rose George’s Nine Pints takes a similar approach, written from the perspective of a journalist with personal hematological experience. Her stance is that Galenic theory was ineffective at worst and a placebo at best, yet, in an abrupt shift, she looked at William Harvey through the lens of seventeenth-century English politics. Christiane Fabbri’s article “Treating Medieval Plague: The Wonderful Virtues of Theriac” shows Galenic theory in a less critical light, as it is placed in the context of the sixteenth through eighteenth centuries. Fabbri expresses that Galenic theory worked in conjunction with the worldview of the sixteenth through eighteenth centuries, which saw diseases as poisons that could be cured via methods such as bloodletting. The article did not focus on Harvey, as plague was more sporadic in Harvey’s day. Shaun McCann’s A History of Hematology: From Herodotus to HIV took a neutral stance on Galenic theory. He stated that the only thing Galen did was maintain the medical status quo. McCann depicts Harvey’s discovery as a clean break from Galenic theory. In Anita Guerrini’s The Courtiers’ Anatomists: Animals and Humans in Louis XIV’s Paris, she discussed the intersection of Galenic theory and William Harvey’s discovery of the circulation in terms of Harvey’s endorsement of bloodletting as ironic, as Harvey’s discovery should have eradicated Galenic theory, but instead Harvey’s stance, in her expression, only prolonged the existence of Galenic theory. In Heather Webb’s “The Lake of My Heart,” part of a larger book titled Blood Matters: Studies in European Literature and Thought, 1400-1700, she has a unique perspective, as she writes about blood through the lens of Dante’s Divine Comedy, showing how literature could incorporate medical theories, which helped to understand her point. In Margaret Healy’s “Was the Heart ‘Dethroned?’,” which is a chapter within Blood Matters, she describes Harvey’s theory from the perspective of seventeenth-century English politics, especially in regard to the king, an abrupt shift from the usual depictions of Harvey’s theory. In examination of these sources in total, one can see a definitive historical path of hematological advancement through their works.

References

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