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Authors: Bill Schutt

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Oh yes, before I forget, some plasma cell precursors called memory T cells stick around the circulatory system once things quiet down. Generally, they're dormant, but memory T cells are quite capable of jacking up the immune response at a moment's notice—should the same foolhardy antigen bearer show up again.
*62

And one more thing: inoculations for childhood diseases (like mumps) and regional diseases (like yellow fever) work on this principle as well. In many cases, dead or harmless versions of specific pathogens are injected into the body, which manufactures antibodies to combat the perceived threat. Additionally, memory cells stick around to quickly crank up the immune response should the real pathogen ever show up.

Unfortunately, much of what we know about blood was determined only within the past hundred years or so. Sometimes, though, it was a lack of technology, and not blind devotion to old views, that constrained early researchers. Although the concept of humors would not be extinguished completely for nearly four hundred years, soon after the 1628 publication of William Harvey's landmark book on circulation,
Anatomical Studies on the Motion of the Heart and Blood,
some physicians began to wonder if the benefits of getting someone else's blood into a patient's circulatory system might be greater than draining blood from that person—especially in cases where there had already been significant blood loss.

Dr. Richard Lower performed what is generally considered the first successful blood transfusion in 1666. Using tubing constructed out of goose quills, he connected the carotid artery of one dog (the donor) to the jugular vein of another (the recipient) that he had bled previously to near death. Reportedly, the recipient was resuscitated in a nearly miraculous fashion.

A year later, encouraged by Lower's results, a Parisian, Jean-Baptiste Denis, used a similar device to infuse about eight ounces of calf blood into the arm of a mentally disturbed man by the name of Antoine Mauroy. Denis, like other researchers of his day, believed that blood carried in it the essence of its owner's personality. The rationale for the infusion, therefore, was that the “mildness” of the calf's blood might mellow out Mssr. Mauroy, who police thought was spending a bit too much time running around naked, setting house fires, and beating his wife.
*63

Tied to a chair, Mauroy was first bled (presumably to eliminate bad blood while freeing up a little space). Then he received about six ounces of calf's blood, which was introduced through a metal tube. Mauroy complained about some initial burning in his arm but otherwise showed no serious effects. After a short nap, the patient began singing and whistling—which many of the onlookers who had gathered to watch the procedure actually preferred to getting beaten up by Mauroy or having him torch their houses.

Two days later, encouraged by the results, Dr. Denis injected even more calf blood into Mauroy, but this time the results were quite a bit more dramatic. Reportedly, the patient began sweating, and soon after, he complained of severe pain in his lower back (near his kidneys, claimed Denis). Nearly choking to death, Mauroy vomited his lunch and soon after began urinating gobs of black fluid.

Today, physicians would have immediately recognized that Mauroy had suffered a serious reaction because of the extreme incompatibility of the nonhuman blood he had received. The unfortunate man's immune system had in fact mounted a multi-pronged attack against the foreign blood and the results had nearly killed him. This being 1667, however, the interpretation was somewhat different. To Dr. Denis, surely the vomiting and coal-colored liquid Mauroy continued to urinate for days were proof that the man's madness had been eliminated. After all, the feverish and bedridden patient wasn't nearly as manic as he'd been previously—in fact, he wasn't speaking or moving much at all.
*64

Several months later, any enthusiasm over the potential benefits of blood transfusion was shattered when one of Denis' patients died. The English, who believed that Denis had not only stolen their transfusion techniques but also their limelight, went out of their way to discredit the Frenchman—as did some of his own rival countrymen. Denis tried to defend himself, but the roof fell in when his highest-profile patient, Antoine Mauroy, also died. After a brief respite, the man had reportedly resumed his wild and brutal ways, and this (as it was later discovered) prompted his wife to employ a bit of creative chemistry. Madame Mauroy began adding arsenic to her husband's diet, but for some reason she failed to mention this fact when she and her husband approached Dr. Denis, asking him to perform a third transfusion. Shaken by his former patient's appearance, Denis declined, but when Mauroy dropped dead several days later, the physician found himself charged with murder. Denis was eventually exonerated, but the uproar surrounding the case (as well as transfusion-related deaths elsewhere) sounded the death knell for human blood transfusions and any related experiments. Two years later, the procedure was banned in France and soon after in England. Additionally, a pair of transfusion-related fatalities in Italy led to a denouncement of the procedure by the pope. Public outcry, capped with a papal denouncement, resulted in a silence that would last for the next 150 years.
*65

In 1818 gynecologist James Blundell, in an attempt to reduce the large number of deaths associated with postpartum hemorrhaging, performed what is considered to be the first human-to-human transfusion. He withdrew blood from a donor and injected it into a blood vessel in the arm of the donor's wife. From his earlier work on animals, Blundell recognized the importance of eliminating air from the syringe before injecting the blood and also the necessity of performing the transfusion quickly, before the blood had a chance to clot. Survival was a hit or miss affair, and Blundell's first four patients died, not only because they were in a weakened state already but because the well-meaning physician had no knowledge of blood typing or modern anticlotting agents (like heparin). The use of crude, nonsterilized tools only added to the problem.

In 1901, Dr. Carl Landsteiner, an Austrian pathologist, revolutionized the ground rules for blood transfusion after discovering the ABO blood groups.
†66
Simply put, red blood cells (like the foreign microorganisms we saw earlier) have specific surface proteins (antigens) embedded in their cell walls. During transfusions, if the surface proteins on the donor's red blood cells are different from those of the recipient (e.g., antigen A as opposed to antigen B), then the erythrocytes in the donated blood will be attacked by leukocytes (or antibodies) circulating in the recipient's blood. This attack by the recipient's immune system kills the donated erythrocytes through a process called hemolysis—literally, “blood cutting” (a process that resulted in the coal black urine seen in the unfortunate Antoine Mauroy). It also leads to a dangerous form of erythrocyte clumping called agglutination, which can clog small blood vessels, sometimes leading to serious medical problems like strokes.

Basically, then, any human-to-human transfusions performed before the discovery of ABO typing were really just crapshoots. And animal-to-human transfusions (as well as transfusions of alcoholic beverages like wine and beer)—they were just plain weird.

On a related note about blood typing, since erythrocytes in people with type O blood have neither A nor B antigens, in theory, their blood isn't recognized as foreign by any recipient's immune system (no matter what the recipient's blood type may be). Because of this, those with type O blood are sometimes referred to as universal donors.

Likewise, since people with type AB blood (a blood group discovered by Landsteiner's colleagues several years later) have
both
types of antigens, they can theoretically receive blood from any donor. As a result, people with type AB blood are known as universal recipients.

Unfortunately, the labels
universal donor
and
universal recipient
are somewhat misleading since there are other antigens and antibodies in the blood besides those of the ABO system. In modern times, blood is carefully cross-matched and screened for pathogens and toxic substances before any transfusions take place.

The work of Vesalius, Al-Nafis, and Harvey contributed to the less-than-timely discrediting of Hypocrites' humoral system, but by the early twentieth century physicians and researchers knew that bacteria and other pathogenic organisms were the cause of most diseases. Drugs like aspirin appeared in the late nineteenth century and the first antibiotics followed some thirty years later. These new treatments rapidly replaced bloodletting as methods to combat many ailments and to reduce the discomfort from wounds, inflammation, and fever.

Surprisingly, though (or not surprisingly, considering just how long the procedure was employed), therapeutic phlebotomy has shown a positive effect in alleviating some symptoms—especially those tied to elevated blood pressure or increased blood volume.

For example, aneurysms occur when a weakened portion of an artery bulges outward like a blood-filled water balloon. As the heart beats, the aneurysm pulsates (like rhythmically squeezing a baseball-sized water balloon in your hand). In some instances, there is a warning—as the vessel walls stretch, pain receptors connected to the surface of the vessel are stimulated. Unfortunately, in most instances the aneurysm is painless and goes undetected. The real danger from an aneurysm is fairly obvious, and if this “water balloon” pops, the results can be deadly. Many strokes result from ruptured aneurysms in the brain and a burst aortic aneurysm can lead to massive hemorrhaging and death within a matter of minutes.

Aneurysms can occur for any number of reasons including high blood pressure and arteriosclerosis. In the latter, this “hardening of the arteries” reduces blood vessel elasticity and produces weakened regions of the vessel wall that can bulge under the pressure of the blood carried within it.

In the days before the discovery of penicillin, aortic aneurysms were a common side effect of syphilis. Regular bleeding of patients with syphilis-related aneurysms was a way of reducing their blood pressure and thus lessening the chance of having their aneurysms rupture.
*67

Bloodletting was also used to reduce the pain of angina pectoris (literally, “strangled chest”). Angina results from an insufficient supply of blood to the heart musculature (usually because of a blockage or constriction of the coronary arteries). Like the pain from a pulsing aneurysm, angina pectoris is a symptom rather than a disease. It's part of the body's warning system—telling it in no uncertain terms that something is
seriously
wrong. Today, vasodilators like nitrates are used to treat angina. They work primarily by increasing blood flow to the farthest reaches of the body (peripheral blood flow), which reduces blood pressure. Studies on the action of these drugs performed in 1970 indicated that therapeutic phlebotomy also lowered pressure within the resting heart.

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