The Beginnings of Blood Transfusion
The Beginnings of Blood Transfusion
William Harvey's (1578-1657) discovery of the circulation of the blood, reported in De motu cordis (1628), resulted in attempts to inject various therapeutic agents, including blood itself, into the veins of animals and humans. The first significant experiments on blood transfusion were performed by Richard Lower (1631-1691) in England in 1666 and by Jean-Baptiste Denis (1640-1704) in Paris in 1667. Lower began with a series of experiments on animals in preparation for transfusion of blood into humans, but Denis was the first to perform the experiment on human beings. Interest in blood transfusion was high from 1660 until about 1680, when various countries began to outlaw this dangerous, experimental practice. After the deaths of several patients, this highly experimental form of therapy was abandoned for about 150 years.
Long before 1628 when he assembled his evidence and published De motu cordis (Anatomical Exercises Concerning the Movement of the Heart and Blood in Animals), William Harvey seems to have arrived at an understanding of the motion of the heart and blood. The notes for his first Lumleian Lecture show that by 1616 he was performing demonstrations and conducting experiments to show that blood passes from the arteries into the veins. He concluded that the beat of the heart impels a continuous circular motion to the blood. His discovery that blood continuously circulates in a closed system, was an essential prerequisite to the concept that blood could be transplanted from one animal to another.
With arguments based on dissection, vivisection, clinical experience, and the works of Aristotle and Galen, Harvey proved that in the adult all the blood must go through the lungs to get from the right to the left side of the heart. Harvey proved that it was the beat of the heart that caused a continuous circular motion of the blood from the heart into the arteries and from the veins back to the heart. In support of the novel idea of a continuous circulation of the blood, Harvey turned to quantitative considerations. Although he did experiments aimed at getting an accurate measurement of the quantity of blood put out by the heart with each beat, he emphasized that exact measurement was unnecessary. Even the most cursory calculation proved that the amount of blood pumped out of the heart per hour was so great that it exceeded the weight of the entire body. That is, if the human heart pumps out two ounces of blood with each beat and beats about seventy times per minute, the heart must expel about 600 pounds (272 kg) per hour. Therefore, blood must move in a continuous circle through the body. So the purpose of the motion and contraction of the heart was to impart a continuous circular motion to the blood.
Once this basic principle was grasped, many observations fell neatly into place. Experience gained through phlebotomy and observations on the throbbing of arterial aneurysms, and the pulses of the wrists, temples and necks of patients similarly supported the central thesis of De motu cordis. Knowledge of the continuous circulation of the blood explained many puzzling clinical observations. Circulation explained why poisons or infections at one site could affect the whole system, as could bites from snakes and rabid animals. On the other hand, for traditional medical practice, Harvey's theory seemed to raise more questions than it answered. How could the new system explain how the parts of the body secured their proper nourishment if the blood was not continuously consumed? If the liver did not continuously synthesize the venous blood, what was the function of this organ? How did the body distribute the vital spirits and the innate heat? If the vital spirit was not produced in the lungs or the left ventricle, what was the function of respiration? If all of the blood moved in a circle, what was the difference between the arterial and venous blood? What principles would guide medical practice if the great Galenic synthesis were sacrificed for the theory of the circulation?
Arguing from experimental and quantitative data in biology was a novelty and opponents of Harvey's work presented what seemed to be quite logical alternatives, at least in light of Galenic theory. Harvey's work did not lead to the total rejection of Hippocratic and Galenic principles, or the rejection of venesection as a major therapeutic tool. Harvey's work opened up new fields of research, but not even Harvey seemed to reconsider the relationship between therapeutic bloodletting and a closed, continuous circulation. Indeed, Harvey defended venesection as a major therapeutic tool for the relief of diseases caused by plethora. Long after Harvey's theory had been accepted, physicians believed in the health-promoting virtues of bloodletting.
Paradoxically, while provoking new arguments about the selection of appropriate sites for vene-section, the discovery of the circulation seemed to stimulate interest in bloodletting and other forms of depletion therapy. Bleeding was recommended in the treatment of inflammation, fevers, a multitude of disease states, and hemorrhage. Patients too weak for the lancet were candidates for milder methods, such as cupping and leeching. In addition to prescribing the amount of blood to be taken, physicians had to select the optimum site for bleeding. Arguments about site selection became ever more creative as knowledge of the circulatory system increased. Many physicians insisted on using distant sites on the side opposite the lesion. Others chose a site close to the source of inflammation in order to remove corrupt blood and attract good blood to repair the diseased area. Proper site selection was supposed to determine whether the primary effect of bloodletting would be evacuation (removal of blood), derivation (acceleration of the blood column upstream of the wound), or revulsion (acceleration of the blood column downstream of the wound).
As a scientist, Harvey demonstrated admirable skepticism towards dogma and superstition, but he was not especially innovative as a practitioner and he does not seem to have considered the possibility of therapeutic blood transfusions. Harvey's methods stimulated his disciples to work out the medical and physiological implications of his discovery. The questions raised by his work provided the Oxford physiologists—scientists such as Robert Boyle (1627-1691), Christopher Wren (1632-1723), Robert Hooke (1635-1703), John Mayow (1640-1679), and Richard Lower (1631-1691)—with a new research program, that is, the exploration of the systemic effects of injecting various drugs and fluids into the veins of animals and human beings. By the 1660s, British physiologists were performing ingenious experiments involving the injection of drugs, poisons, nutrients, pigments, and blood itself into animal and human veins. The transfusion and infusion of medicinal substances into the bloodstream did not become part of routine medical practice for many years, but seventeenth century experimentalists did raise many intriguing possibilities.
Competing claims for priority have created some confusion in the history of blood transfusion, but the body of evidence indicates that the first significant studies of blood transfusion were performed by Christopher Wren, Richard Lower, and Robert Boyle in England, and by Jean-Baptiste Denis (1640-1704) in Paris. According to Thomas Sprat's History of the Royal Society (1667), Christopher Wren was the first to carry out experiments on the injection of various fluids into the veins of animals. During experiments exhibited at meetings of the Royal Society, experimental animals were purged, vomited, intoxicated, killed, or revived by the intravenous injection of various fluids and drugs. Dogs, birds, and other animals were bled almost to death and sometimes revived by the injection of blood from another animal.
Reasoning that the nature of blood must change after it was removed from the living body, the English physician and physiologist Richard Lower decided to transfer blood between living animals by connecting the artery of the donor to the vein of the recipient. During a demonstration performed at Oxford in February 1666, Lower removed blood from a medium sized dog until it was close to death. Blood taken via the cervical artery of a larger dog revived the experimental animal. Using additional donors, Lower was able to repeat this procedure several times. When the recipient's jugular vein was sewn up, it appeared to be in good condition. These experiments led observers to speculate that someday blood transfusions could cure the sick by replacing bad blood with healthy blood.
After learning about Lower's experiments performing a series of transfusions from dog to dog, Jean-Baptiste Denis, professor of philosophy and mathematics at Montpellier and physician to Louis XIV, conducted a series of experiments on the transfusion of blood from dog to dog. In March 1667, he transferred blood from a calf into a dog. Observing no immediate adverse effect, Denis concluded that animal blood could be used to treat human diseases. Denis argued that humans were able to assimilate the flesh of animals and that animal blood might be a better remedy than human blood, because animal blood would not be corrupted by human vices. Moreover, as a practical matter, animal blood could be transfused directly from the artery of the donor to the vein of the human recipient.
On June 15, 1667, with the help of Paul Emmerez, a surgeon and anatomist, Denis tested his methods on a fifteen-year-old boy who had suffered from a chronic fever and had endured numerous therapeutic bleedings. Emmerez drew off about three ounces of blood from a vein in the boy's arm and Denis injected about ten ounces of arterial blood from a lamb. The operation seemed to be a great success, except for the boy's complaint about the sensation of great heat in his arm. In another experiment, Denis injected about twenty ounces of lamb's blood into a healthy forty-five-year-old paid volunteer. Again, except for a sensation of warmth in the arm, no ill effects were reported. A man suffering from "frenzy" seemed to improve after a transfusion of calf's blood, but the patient experienced pains in the arm and back, rapid and irregular pulse, sweating, vomiting, diarrhea, and bloody urine. Given the patient's poor state of health and previous treatments, Denis saw no compelling reason to blame these problems on the transfusion. Thus, although Denis reported several apparently successful transfusions, his experiments also resulted in what was probably the first recorded account of the signs and symptoms of a hemolytic transfusion reaction. The death of a patient who had been given two injections of calf's blood as a treatment for recurring attacks of insanity precipitated a violent controversy, an avalanche of pamphlets, a lawsuit, and the arrest of Denis.
Although not found guilty of malpractice, Denis and Emmerez discontinued their experiments and returned to conventional careers. In 1668, the Chamber of Deputies declared that the transfusion of blood from animals into humans was prohibited, unless specifically approved by the Faculty of Medicine of Paris. Then years later, the British Parliament also prohibited blood transfusion. Little progress was made in the field in the next 150 years.
English scientists had been very critical of the experiments performed by Denis, but they too experienced mixed success in blood transfusions. About six months after Denis's first human transfusion, Richard Lower hired a "lunatic" named Arthur Coga, to serve as a test subject. Coga's condition seemed to improve after an injection of sheep's blood, but his condition deteriorated rapidly when he was given a second transfusion. The first transfusion experiments had briefly stimulated great expectations, but blood transfusion did not become routinely safe and effective until after World War I. Seventeenth century physiologists, who explained their world in terms of four elements and four humors, could not appreciate the immunological barriers between different species and individuals. Safe blood transfusions were made possible when the immunologist Karl Landsteiner (1868-1943) demonstrated the existence of distinct blood group types.
LOIS N. MAGNER
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