As a scientist, Harvey demonstrated admirable skepticism towards dogma and superstition, but he was not especially innovative as a prac- titioner and he does not seem to have considered the possibility of ther- apeutic blood transfusions. His disciples, however, were soon busily injecting 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 the standard therapeutic arsenal for many years, but seventeenth-century experimentalists did raise intriguing possibilities. Interest in transfusion was high from 1660 until about 1680, when various countries began to outlaw this dan- gerous, experimental practice. Many of the early therapeutic experiments based on the theory of circulation appear as paradoxical as the continued enthusiasm for bloodletting. Although the ﬁrst transfusion experiments generated great expec- tations, blood transfusion did not begin to satisfy the four cardinal vir- tues of a successful medical technique—simplicity, certainty, safety, and efﬁcacy—until after World War I.
The immunological mechanisms that guard the body against foreign invaders and distinguish between self and nonself provided the major obstacles to successful blood transfusion. Of course, unlike twentieth-century transplant surgeons, seventeenth-century physicians had no reason to suspect the existence of immunological barriers between different individuals and species. Why should they expect incompatibilities between blood donors and recipients when most wise men believed that four elements and four humors were sufﬁcient to explain the macrocosm and the microcosm? The avalanche of experiments on blood transfusion that followed acceptance of Harvey’s theory led to competing claims for priority.
The ﬁrst signiﬁcant studies of blood transfusion were performed by Christopher Wren, Richard Lower, and Robert Boyle in England, and by Jean Denis 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 materials into the veins of animals. During experiments exhibited at meetings of the Royal Society, animals were purged, 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 has been removed from the living body, 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 ran to its master, apparently none the worse for its bizarre experience. These remarkable experiments led observers to speculate that someday blood transfusions would cure the sick by correcting bad blood with blood from a more robust donor.
This approach might even be used to improve temperament, perhaps by injecting the blood of a Quaker into an Archbishop. At about the same time that Lower was engaged in blood trans- fusion experiments in animals, Jean Baptiste Denis (or Denys, ca. 1625–1704), Professor of Philosophy and Mathematics at Montpellier and physician to Louis XIV, was already crossing the species barrier in preparation for therapeutic experiments on humans. In March 1667, after 19 successful transfusions from dog to dog, Denis transfused 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 suggested that animal blood might be a better remedy than human blood, because animal blood would not be corrupted by passion, vice, and other immoral human traits. Humans were well nourished by the ﬂesh of animals; thus, it was reasonable to assume that animal blood could also be well assimilated by human beings. As a practical matter, animal blood could be transfused directly from an artery.
With the help of Paul Emmerez, a surgeon and teacher of anat- omy, Denis tested his methods on a 15-year-old boy who had suffered from a stubborn fever. To reduce excessive heat, his doctors had per- formed twenty therapeutic bleedings in two months. Dull, drowsy, and lethargic from the combined effects of illness and medical attention, the patient had been pronounced incredibly stupid and unﬁt for any- thing. On June 15, 1667, Emmerez drew off about 3 ounces of blood from a vein in the boy’s arm and Denis injected about 10 ounces of arterial blood from a lamb. The operation caused a marvelous trans- formation: the boy regained his former wit, cheerfulness, and appetite. The only adverse effect was a sensation of great heat in his arm.
After this happy outcome, Denis injected about 20 ounces of lamb’s blood into a healthy 45-year-old paid volunteer. Again, except for a sensation of warmth in the arm, no ill effects were reported. In another experiment, a patient suffering from a frenzy was given a large transfusion of calf’s blood. Though cured of his frenzy, the patient experienced pains in the arm and back, rapid and irregular pulse, sweat- ing, vomiting, diarrhea, and bloody urine. Given the poor man’s state of health and previous treatments, Denis saw no compelling reason to blame the patient’s physical problems on the transfusion. However, the death of another patient effectively ended the ﬁrst phase of experimental blood transfusions. A 34-year-old man who had been suffering attacks of insanity for about 8 years improved after 2 transfusions of calf’s blood. When the madness reappeared, treatment was resumed, and the patient died. Certainly the death of a patient following the ministrations of a ﬂock of physicians was not without precedent, but this case precipitated a vio- lent controversy and an avalanche of pamphlets.
At ﬁrst, Denis blamed the patient’s death on overindulgence in wine, women, and tobacco, but he later suggested that the widow had deliberately poisoned his patient. Although the courts did not convict Denis of malpractice, to all intents and purposes, blood transfusion was found guilty. Denis and Emmerez abandoned experimental medicine and returned to conventional careers, which presumably included the use of orthodox remedies more revolting and dangerous than calf’s blood. English scientists were quite critical of the experiments performed by Denis, but they too were experiencing mixed success in blood trans- fusions. About six months after Denis’s ﬁrst human transfusion, Richard Lower and his associates hired Arthur Coga, a man described as debauched, frantic, and somewhat cracked in the head, as a test sub- ject. Some of Lower’s colleagues were skeptical, but others believed that the transfusion might cool Coga’s blood and rid him of his frenzy. After the injection of about 12 ounces of sheep’s blood, Coga reported feeling much improved. Unfortunately, after a second transfusion, his con- dition deteriorated.
Rumors circulated that his bad behavior had been deliberately engineered by parties trying to discredit the Royal Society and make the experiment look ridiculous. The learned Fellows of the Royal Society were justiﬁed in their fear of ridicule. Their reports pro- vided satirists like Jonathan Swift (1667–1745) and Thomas Shadwell (1641–1692) with ample raw material. In Shadwell’s comic play The Virtuoso, amateur scientist Sir Nicholas Gimcrack transfuses 64 ounces of sheep’s blood into a maniac. After the operation, the patient becomes so wholly sheepish that he bleats perpetually, chews the cud, and sprouts a magniﬁcent coat of wool, while a sheep’s tail emerges from his ‘‘human fundament.’’ Sir Nicholas plans to transfuse many more lunatics so that he can harvest the wool.
Safe blood transfusions were made possible when the immunol- ogist Karl Landsteiner (1868–1943) demonstrated the existence of dis- tinct human blood group types. In 1930, Landsteiner was awarded the Nobel Prize for his studies of blood group factors. Landsteiner found that all human beings belong to one of four different blood groups, designated O, A, B, and AB. Blood group typing also provided information that was useful in criminal cases, paternity suits, genetics, and anthropology. Indeed, so much information can be gleaned from blood that patients hospitalized for several weeks might begin to think that bloodletting is once again an integral part of medical care. Despite the fact that blood transfusion has become a routine procedure, myths and superstitions continue to ﬂourish in one form or another, making many people reluctant to donate or accept blood. Of course, not all fears about the safety of blood transfusion are unjusti- ﬁed. Unless blood is properly tested, recipients of blood and blood products are at risk for diseases like syphilis, malaria, hepatitis, AIDS, and even West Nile fever.
Infected and contaminated human tissues and organs have caused serious infections in recipients. Many transplants involve soft tissues such as tendons, ligaments, and cartilage obtained from cadavers for use in elective orthopedic surgery. One body can sup- ply enough tissue for thirty orthopedic transplants. Heart valves are also collected and used as replacements. Failure to prevent or detect bac- terial or fungal contamination has led to deaths caused by infections. A new hazard of blood transfusions and organ transplants ﬁrst emerged in 2002 when four patients who received the heart, liver, and kidneys of the same donor were infected with the West Nile virus. This virus is especially dangerous to people with weakened immune systems, such as patients undergoing organ transplants. Inevitably, the need to detect and exclude unhealthy donors creates conﬂicts between public health concerns and individual liberty. Denying a person the right to donate blood may not seem a great infringement of personal liberty, but being labeled as a carrier of the hepatitis virus or the AIDS virus may have very serious consequences.