The Body, page 14
Far more personally noble than Forssmann, and no less stoic in his capacity for experimental discomfort, was Dr. John H. Gibbon of the University of Pennsylvania. In the early 1930s, Gibbon began a long and patient quest to build a machine that could oxygenate blood artificially, to make open-heart surgery possible. To test the capacity of blood vessels deep within the body to dilate or constrict, Gibbon stuck a thermometer up his rectum, swallowed a stomach tube, and then had icy water poured down it to determine its effect on his internal body temperature. After twenty years of refinements, and much heroic swallowing of iced water, Gibbon unveiled the world’s first heart-lung machine at the Jefferson College Hospital in Philadelphia in 1953 and successfully patched a hole in the heart of an eighteen-year-old woman who would otherwise have died. Thanks to his efforts, the woman lived another thirty years.
Unfortunately, the next four patients died, and Gibbon gave up on the machine. It then fell to a surgeon in Minneapolis, Walton Lillehei, to improve both the technology and the surgical techniques. Lillehei introduced a refinement known as controlled cross-circulation in which the patient was hooked up to a temporary donor (usually a close family member) whose blood was circulated through the patient during the period of surgery. The technique worked so well that Lillehei became widely known as the father of open-heart surgery and enjoyed a great deal of acclaim and financial success. Unfortunately, he wasn’t quite as impeccable in his private affairs as he might have been. In 1973, he was convicted of five counts of tax evasion and a great deal of very imaginative bookkeeping. Among much else, he had claimed a $100 payment to a prostitute as a charitable tax deduction.
Although open-heart surgery allowed surgeons to correct many faults they previously couldn’t get at, it couldn’t solve the problem of a heart that wouldn’t beat right. That required the device now universally known as a pacemaker. In 1958, a Swedish engineer named Rune Elmqvist, working in collaboration with the surgeon Åke Senning of the Karolinska Institute in Stockholm, built a pair of experimental cardiac pacemakers at his kitchen table. The first was inserted into the chest of Arne Larsson, a forty-three-year-old patient (and himself an engineer) who was very near death from a heart arrhythmia as a result of a viral infection. The device failed after just a few hours. The backup was inserted and it lasted for three years, though it kept breaking down and the batteries had to be recharged every few hours. As technology improved, Larsson was routinely fitted with new pacemakers and lived another forty-three years. When he died in 2002 at the age of eighty-six, he was on his twenty-sixth pacemaker and had outlived both his surgeon Senning and his fellow engineer Elmqvist. The first pacemaker was about the size of a pack of cigarettes. Today’s are no bigger than one American quarter and can last up to ten years.
The coronary bypass, which involved taking a length of healthy vein from a person’s leg and transplanting it to direct blood flow around a diseased coronary artery, was devised in 1967 by René Favaloro at the Cleveland Clinic in Ohio. Favaloro’s was a story at once inspiring and tragic. He grew up poor in Argentina and became the first member of his family to attain a higher education. Upon qualifying as a doctor, he spent twelve years working among the poor but came to the United States in the 1960s to improve his skills. At the Cleveland Clinic, he was little more than a trainee at first but quickly proved himself adept at heart surgery and in 1967 invented the bypass. It was a comparatively simple but ingenious procedure, and it worked brilliantly. Favaloro’s first patient, a man too ill to walk up a flight of stairs, recovered completely and lived another thirty years. Favaloro grew wealthy and celebrated and in the twilight of his career decided to return home to Argentina to build a heart clinic and teaching hospital, where doctors could be trained and needy people treated whether they could afford payment or not. All of this he achieved, but because of challenging economic conditions in Argentina, the hospital got into financial difficulties. Unable to see a way out, in 2000 he killed himself.
The great dream was to transplant a heart, but in many places it faced a seemingly insuperable obstacle: a person could not be declared dead until his heart had been stopped for a specified period, but that was all but certain to render the heart unusable for transplant. To remove a beating heart, no matter how far gone the owner was in all other respects, was to risk prosecution for murder. One place where that law did not apply was South Africa. In 1967, at exactly the time that René Favaloro was perfecting bypass surgery in Cleveland, Christiaan Barnard, a surgeon in Cape Town, attracted far more of the world’s attention by transplanting the heart of a young woman fatally injured in a car accident into the chest of a fifty-four-year-old man named Louis Washkansky. It was hailed as a great medical breakthrough, though in fact Washkansky died after just eighteen days. Barnard had much better luck with his second transplant patient, a retired dentist named Philip Blaiberg, who survived for nineteen months.*1
Following Barnard, other nations moved to let brain death be used as an alternative measure of irreversible lifelessness, and soon heart transplants were being attempted all over, though nearly always with discouraging results. The main issue was an absence of a wholly reliable immunosuppressive drug to deal with rejection. A drug called azathioprine worked sometimes but couldn’t be relied on. Then, in 1969, an employee of the Swiss pharmaceutical company Sandoz named H. P. Frey, while on holiday in Norway, collected soil samples to take back to the Sandoz labs. The company had asked employees to do so when traveling in the hope that they would find potential new antibiotics. Frey’s sample contained a fungus, Tolypocladium inflatum, which had no useful antibiotic properties but proved excellent at suppressing immune responses—just the thing needed to make organ transplants possible. Sandoz converted Herr Frey’s little bag of dirt, and a similar sample subsequently found in Wisconsin, into a best-selling medicine called cyclosporine. Thanks to it and some associated technical improvements, by the early 1980s heart transplant surgeons were managing success rates of 80 percent, an extraordinary achievement in a decade and a half. Today some four to five thousand heart transplants are performed globally each year, with an average survival time of fifteen years. The longest-surviving transplant patient so far was the Briton John McCafferty, who lived thirty-three years with a transplanted heart before dying in 2016 aged seventy-three.
Incidentally, brain death turned out to be not as straightforward as originally thought. Some peripheral parts of the brain, we now know, may live on after all the rest has grown still. At the time of this writing, that is the issue at the center of a long-running case involving a young woman in the United States who was declared brain-dead in 2013 but who has continued to menstruate, a process that requires a functioning hypothalamus—very much a key part of the brain. The young woman’s parents argue that anyone with even part of the brain functioning cannot reasonably be declared brain-dead.
As for Christiaan Barnard, the man who began it all, success rather went to his head. He traveled the world, dated movie stars (Sophia Loren and Gina Lollobrigida notably), and became, in the words of someone who knew him well, “one of the world’s great womanizers.” Even worse for his reputation, he made a fortune claiming rejuvenative benefits for a range of cosmetics that he most assuredly knew were bogus. He died in 2001, aged seventy-eight, of a heart attack while enjoying himself in Cyprus. His reputation was never again quite what it had been.
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Remarkably, even with all the improvements in care, you are 70 percent more likely to die from heart disease today than you were in 1900. That’s partly because other things used to kill people first, and partly because a hundred years ago people didn’t spend five or six hours an evening in front of a television with a big spoon and a tub of ice cream. Heart disease is far and away the Western world’s number one killer. As Michael Kinch has written, “Heart disease kills about the same number of Americans each year as cancer, influenza, pneumonia, and accidents combined. One in three Americans dies of heart disease and more than 1.5 million suffer a heart attack or stroke each year.”
Today the problem is as likely to be overtreatment as under, according to some authorities. Balloon angioplasties as a treatment for angina (or chest pains) are a case in point, it seems. With an angioplasty, a balloon is inflated inside a constricted coronary blood vessel to widen it, and a stent, or piece of tubular scaffolding, is left behind to keep the vessel permanently open.*2 The operation is unquestionably a lifesaver in emergencies, but it has also proven highly popular as an elective procedure. By 2000, a million precautionary angioplasties were being undertaken in the United States every year, but without any proof that they saved lives. When clinical trials were finally undertaken, the results were sobering. According to The New England Journal of Medicine, for every one thousand nonemergency angioplasties in America, two patients died on the operating table, twenty-eight suffered heart attacks brought on by the procedure, between sixty and ninety experienced a “transient” improvement in their health, and the rest—about eight hundred people—experienced neither benefit nor harm (unless of course you count the cost, the loss of time, and the anxiety of surgery as harm, in which case there was plenty).
Despite this, angioplasties remain extremely popular. In 2013, the former president George W. Bush had an angioplasty at the age of sixty-seven, even though he was in good shape and had no sign of heart problems. Surgeons don’t usually publicly criticize colleagues, but Dr. Steve Nissen, head of cardiology at the Cleveland Clinic, was scathing. “This is really American medicine at its worst,” he said. “It’s one of the reasons we spend so much on medicine and don’t get a lot for it.”
II
HOW MUCH BLOOD you have depends, as you might suppose, on how big you are. A newborn baby contains only about eight ounces, whereas a fully grown man will have more like five quarts. What is certain is that you are suffused with the stuff. Prick your skin anywhere and you will draw blood. Within your modest frame are some twenty-five thousand miles of blood vessels (mostly in the form of tiny capillaries), so no part of you is ever far from the refreshment of hemoglobin, the molecule that transports oxygen throughout your body.
We all know that blood carries oxygen to our cells—it is one of the few facts about the human body that everyone does seem to know—but it also does a whole lot more. It transports hormones and other vital chemicals, carries off wastes, tracks down and kills pathogens, makes sure oxygen is directed to the parts of the body where it is most needed, signals our emotions (as when we blush from embarrassment or grow red with fury), helps to regulate body temperature, and even enables the complicated hydraulics of the male erection. It is, in short, a complex material. By one estimate, a single drop of blood may contain four thousand different types of molecules. That’s why doctors are so fond of blood tests: your blood is positively packed with information.
Spin a test tube of blood in a centrifuge and it will separate into four layers: red cells, white cells, platelets, and plasma. Plasma is the most abundant, constituting a little over half of blood’s volume. It is more than 90 percent water with some salts, fats, and other chemicals suspended in it. That isn’t to say plasma is unimportant, however. It is anything but. Antibodies, clotting factors, and other constituent parts can be separated out and used in concentrated form to treat autoimmune diseases or hemophilia—and that is a huge business. In the United States, plasma sales make up 1.6 percent of all goods exported, more than America earns from the sale of airplanes.
Red blood cells (formally called erythrocytes) are the next most plentiful component, constituting about 44 percent of the total volume of the blood. Red blood cells are exquisitely designed to do one job: deliver oxygen. They are very small but superabundant. A teaspoon of human blood contains about twenty-five billion red blood cells, and each one of those twenty-five billion contains 250,000 molecules of hemoglobin, the protein to which oxygen willingly clings. Red blood cells are biconcave in shape—that is, disk shaped but pinched in the middle on both sides—which gives them the largest possible surface area. To make themselves maximally efficient, they have jettisoned virtually all the components of a conventional cell—DNA, RNA, mitochondria, Golgi apparatus, enzymes of every description. A full red blood cell is almost entirely hemoglobin. It is essentially a shipping container. A notable paradox of red blood cells is that although they carry oxygen to all the other cells of the body, they don’t use oxygen themselves. They use glucose for their own energy needs.
Hemoglobin has one strange and dangerous quirk: it vastly prefers carbon monoxide to oxygen. If carbon monoxide is present, hemoglobin will pack it in, like passengers on a rush-hour train, and leave the oxygen on the platform. That’s why it kills people. (About 430 of them a year in the United States unintentionally, and a similar number by suicide.)
Each red corpuscle survives for about four months, which is pretty good going considering what a jostling and busy existence it leads. Each will be shot around your body about 150,000 times, logging a hundred miles or so of travel before it is too battered to go on. Then these corpuscles are collected by scavenger cells and sent to the spleen for disposal. You discard about a hundred billion red blood cells every day. They are a big component of what makes your stools brown. (Bilirubin, a by-product of the same process, is responsible for the golden glow of urine as well as the yellow blush of fading bruises.)
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White blood cells (or leukocytes) are vital for fighting off infections. In fact, they are so important that we will treat them separately in chapter 12, on the immune system. For the moment, it is enough to know that they are much less numerous than their red siblings. You have seven hundred times as many red blood cells as white ones, which constitute less than 1 percent of the total.*3
Platelets (or thrombocytes), the final part of the blood quartet, also account for less than 1 percent of blood’s volume. Platelets were for a long time a mystery to anatomists. They were first seen under a microscope in 1841 by a British anatomist named George Gulliver, but they weren’t named or properly understood until 1910 when James Homer Wright, chief pathologist at the Massachusetts General Hospital in Boston, deduced their central role in clotting. Clotting is a tricky business. The blood must be perpetually on alert to clot at a moment’s notice, but equally mustn’t clot unnecessarily. As soon as a bleed starts, millions of platelets begin to cluster around the wound and are joined by similarly vast numbers of proteins, which deposit a material called fibrin. This agglomerates with the platelets to make a plug. To try to avoid errors, no fewer than twelve fail-safe mechanisms are built into the process. Clotting doesn’t work in the principal arteries, because the flow of blood is too fierce; any clot would be swept away, which is why major bleeds must be stopped with the pressure of a tourniquet. In severe bleeding, the body does all it can to keep blood flowing to the vital organs and diverts it away from secondary outposts like muscles and surface tissues. That’s why patients who are bleeding heavily turn a cadaverous white and are cold to the touch. Platelets live for only about a week, so must be constantly replenished. In the last decade or so, scientists have realized that platelets do more than just manage the clotting process. They also play important roles in immune response and in tissue regeneration.
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For the longest time, almost nothing was known about the purpose of blood beyond that it was somehow vital to life. The prevailing theory, dating since the time of the venerable but frequently mistaken Greek physician Galen (ca. 129—ca. 210), was that blood was manufactured continuously in the liver and used up by the body as fast as it was made. As you will doubtless recall from your school days, the English physician William Harvey (1578–1657) realized that blood is not endlessly consumed, but rather circulates in a closed system. In a landmark work called Exercitatio anatomica de motu cordis et sanguinis in animalibus (On the Motion of the Heart and Blood in Animals), Harvey outlined all the details of how the heart and circulatory system work, in more or less the terms we understand today. When I was a schoolboy, this was always presented as one of those eureka moments that changed the world. In fact, in Harvey’s day the theory was almost universally ridiculed and rejected. Nearly all Harvey’s peers thought him “crack-brained,” in the words of the diarist John Aubrey. Harvey was abandoned by most of his clients and died a bitter man.
