You Bet Your Life

PART I

RISK

BY THE END OF 2020, SEVERAL FORCES WERE AT PLAY: IN THE UNITED States alone, SARS-CoV-2 was killing one thousand people every day. Several companies had launched large-scale tests of their coronavirus vaccines, during which tens of thousands of people were injected with either the vaccine or saltwater (placebo) to determine whether the vaccines worked and were safe. Most of the strategies used to make these vaccines had never been used before. They were chosen because they were the easiest to construct and the fastest to mass-produce, not because they were necessarily going to be the best. Dr. Anthony Fauci, head of the National Institute of Allergy and Infectious Diseases at NIH, predicted that a coronavirus vaccine could be available by the end of the year, certainly no later than early 2021. Typically, it takes fifteen to twenty years to develop a vaccine, but, if Fauci was right, these COVID-19 vaccines would be developed in a year. By spending more than $20 billion on large clinical tests and mass production, the US government had taken the risk out of making vaccines for pharmaceutical companies, dramatically compressing time lines.

Additionally, none of these new vaccines would be subjected to the typical licensing procedures required by the FDA, which usually take about a year. Rather, they would be approved through emergency use authorization, which would allow vaccines to be injected into the arms of Americans within moments of rolling off the assembly lines. People would soon be forced to decide between the risk of getting COVID-19 and the risk of getting a vaccine that had not been subjected to the typical research, development, testing, and licensure processes.

Americans making these decisions can’t have been comforted by the past. As has been true for virtually every vaccine ever made, the first vaccines aren’t always the best, safest, and last. For example, a live, weakened polio vaccine introduced in 1963 was replaced by an inactivated polio vaccine in 2000, when it became clear that the former actually caused polio in eight to ten US children every year. The first measles vaccine in 1963—which caused a high rate of fever and rash—was replaced by a safer, better vaccine in 1968. Another measles vaccine, which was also introduced in 1963, was taken off the market when it was found to actually increase the risk of pneumonia. The first rubella (German measles) vaccine in 1969, which caused arthritis in small joints like fingers and wrists, was replaced by a safer vaccine in 1979. The Haemophilus influenzae type b (Hib) vaccine in 1985, a bacterial vaccine that wasn’t particularly effective in young children, was replaced by a far more effective one in 1987. And the first shingles vaccine in 2011, designed to prevent one of the most debilitatingly painful diseases, was replaced by a much better one in 2017.

In the next three chapters, we’ll examine the human stories behind heart transplants, blood transfusions, and anesthesia. In each instance, we’ll also discuss when during the evolution of these technologies it was worth taking the risk and when it wasn’t. Although it’s always easy to judge in retrospect, lessons can be found in each of these stories that might shed light on similar decisions today.

CHAPTER 1

LOUIS WASHKANSKY

Heart Transplants

A CHIMERA, ACCORDING TO GREEK MYTHOLOGY, HAS A LION’S HEAD, A goat’s body, and a serpent’s tail. The Minotaur, who roamed the island of Crete, was half human and half bull. Centaurs were half man, half horse. We are at once fascinated and horrified by mythical beasts that combine one animal part with another. The world’s first heart transplant evoked the same reaction—for the same reason.

Boyd Rush was in bad shape. For years, the sixty-eight-year-old retired upholsterer, who was deaf and mute, had lived alone in the Laurel Trailer Park on the outskirts of Jackson, Mississippi. High blood pressure had taken a toll on his heart, which was failing. As a result of inadequate circulation, his left leg was black with gangrene and his face was dotted with blood clots. On January 21, 1964, after suffering another heart attack, Rush was taken to the University of Mississippi Medical Center. Comatose and with a faint pulse, doctors inserted a breathing tube into his windpipe and attached it to a mechanical ventilator. On January 22, one day after he arrived at the hospital, his left leg was amputated. (Boyd Rush would never be a candidate for a heart transplant today.)

Dr. James Hardy, a heart surgeon at the medical center, had been waiting for this moment. A native of Newala, Alabama, and a graduate of the University of Pennsylvania School of Medicine, Hardy was the first person in the United States to successfully transplant a human lung. After having transplanted hearts into more than two hundred experimental animals, he was ready to perform the first human heart transplant in history. The problem was finding a donor. “At the outset,” said Hardy, “it was expected that months, or perhaps even years, might elapse before an acceptable donor and recipient died simultaneously.”

Hardy knew that a trauma victim was in the intensive-care unit of his hospital. He also knew that, although this patient was brain dead, his heart was still beating. Hardy’s only option would have been to remove life support and wait for the heart to stop. Believing this was unethical, he refused to do it. (Four years would pass before the diagnosis of brain death allowed doctors to turn off breathing machines in patients whose hearts were still beating.) “Since we were not willing to stop the ventilator,” said Hardy, “we had concluded that a situation might arise in which the only heart available for transplantation would be that of a lower primate.” Hardy had prepared a large chimpanzee named Bino in the operating room next to Rush’s. At the time, the sale of monkeys and chimps in the United States was unregulated.

On January 23, 1964, James Hardy sutured Bino’s heart into Boyd Rush’s chest. After shocking it with a defibrillator, Bino’s heart jumped back to life. Unfortunately, Bino weighed only ninety-six pounds; the chimp’s heart was too small to effectively pump the large amount of blood in Rush’s body. Two hours later, Boyd Rush was dead. He never regained consciousness.

Hardy had originally planned to tell the world what he had done two weeks later at a medical conference. But twenty-five people had crammed into Hardy’s operating room to witness what they believed was about to be history. One, apparently, leaked the news to the press, which carried the story incorrectly as a human-to-human, not chimp-to-human, heart transplant. The hospital had to issue a correction. Now, news outlets across the nation knew exactly what had happened in that operating room in Jackson, Mississippi.

On February 8, 1964, at the Sixth International Transplantation Conference in New York City’s luxurious Waldorf Astoria hotel, James Hardy stood in front of an audience of his peers and described the operation. “It was as if there had been a recent bereavement in my family,” recalled Hardy. “There was not a single hand of applause thereafter. It was a dismal day.”

Also in attendance at that New York City conference was Dr. Norman Shumway, the surgeon who would later be known as the “father of heart transplantation.” Shumway urged restraint. He argued that surgeons needed to improve the preservation of donor hearts and, most important, figure out how to avoid rejection of the donor heart by the recipient’s immune system. When answering a question about Hardy’s choice to use a chimpanzee heart, Shumway was tactful. “Perhaps the cardiac surgeon should pause,” he argued, “while society becomes accustomed to resurrection of the mythological Chimera.”

Despite Norman Shumway’s warning, between 1964 and 1977 at least four people received hearts from sheep, baboons, or chimps; all died within a few days. The procedure that finally put an end to animal-to-human transplants was performed in a small hospital in Southern California in the 1980s, almost twenty years after the first successful human-to-human heart transplant.

Early in the morning of October 26, 1984, Dr. Leonard Bailey of the Loma Linda Medical Center transplanted a baby baboon’s heart into Stephanie Fae Beauclair, a twelve-day-old girl with a severe heart defect. The public knew her as Baby Fae. Bailey had extensive experience transplanting sheep hearts into newborn goats, so he was used to working with small hearts. The operation was a success. At 11:35 a.m. the new heart was beating rapidly in Baby Fae’s little body. Although the baboon’s heart was the size of a walnut, it did what Stephanie’s abnormal heart couldn’t do: supply her body with the oxygenated blood needed to keep her alive.

On November 15, 1984, twenty days after the transplant, Stephanie Beauclair was dead. Bailey had hoped that her immune system would be too immature to recognize the baboon’s heart as foreign and reject it. It didn’t work out that way. Her body sent white blood cells called lymphocytes to the new heart and destroyed it, ending her life. Any hope that surgeons had placed in animal-to-human heart transplants died with Baby Fae.

Animal-rights activists targeted Leonard Bailey. “My family suffered immensely,” he recalled. “We had to have police live in our home. Our personal mail was opened by the police department for over a year. I wasn’t allowed to appear in public without a bullet-proof vest under my clothing.” Although the ethics committee at Loma Linda Medical Center had given Bailey permission to do four more transplants using baboon hearts—and seven baboons were currently housed on site—he never performed another transplant.

The Baby Fae experiment became a cultural icon. Ten years later, in a 1993 episode of The Simpsons titled “I Love Lisa,” the school cafeteria serves beef hearts in honor of Valentine’s Day. Bart puts one under his shirt and declares, “My baboon heart! I’m rejecting it,” before throwing it back on the table. And in Paul Simon’s Graceland album, the song “The Boy in the Bubble” contains the lyric “Medicine is magical and magical is art / Thinking of the boy in the bubble / And the baby with the baboon heart.”

When James Hardy stood at the podium of the Sixth International Transplantation Conference in New York City in 1964, successful heart transplantation centered on three challenges, two of which had been solved. One has never been solved completely.

First, surgeons had to maintain the health of the donor heart for the hour or so between removal and transplantation. In 1952, researchers at Hahnemann Hospital in Philadelphia found that if they dramatically lowered the temperature of a dog before killing it, the dog’s heart didn’t suffer any damage. As a result, cooling the donor and recipient before the transplant became standard procedure.

Second, surgeons had to find the best way to attach the new heart to the major blood vessels of the recipient. By 1960, Norman Shumway and Richard Lower at Stanford University had figured that out.

Third, surgeons had to find a way to prevent the recipient from rejecting the new heart. Before transplanting hearts into people, surgeons had spent decades transplanting them into experimental animals. Shumway and Lower were the most successful. They were the first to show that transplanted dogs could live a normal life for a year. Unfortunately, every successful dog-heart transplant ended the same way: the dog’s immune system rejected the new heart. “If the immunological mechanisms of the host were prevented from destroying the graft,” said Shumway in 1960, “in all likelihood [the heart] would continue to function adequately for the normal life span of the animal.” Scientists and surgeons had to find a better way to prevent immune rejection. Although the first successful heart transplant would be achieved just a few years later, it would be twenty years before doctors came close to truly solving this problem.

Shumway’s observations weren’t new. Surgeons had been trying to conquer the problem of transplant rejection for about four hundred years. In the sixteenth century, an Italian surgeon named Gaspare Tagliacozzi found that he could transplant skin from one body site to another without difficulty. The new skin graft would function perfectly. However, if he took skin from one person and transplanted it onto another, the new skin would turn gray, whither, and die.

In the 1930s, Leo Loeb, working with rodents, found that he could successfully transplant skin from one animal to another, as long as the animals were genetically identical. But if they were genetically dissimilar, the animals would reject the transplant—and the greater the dissimilarity, the more vigorous the rejection. Loeb reasoned that transplants in humans could be successful if the donor organ came from an identical twin. As Loeb had predicted, the first successful kidney transplant, which was performed on December 23, 1954, occurred when Ronald Herrick donated a kidney to his twin brother, Richard. Most people, however, don’t have an identical twin. Therefore, the only way to prevent the body from rejecting the transplanted organ is with drugs that suppress the immune system.

In 1955, the first immune-suppressive drug, prednisone, became commercially available. In 1963, the second, azathioprine, also became available (and won a Nobel Prize for its inventors). Both drugs lessened but didn’t eliminate the possibility of rejection in people with heart transplants. Not surprisingly, both drugs also weakened the body’s ability to fight infections. As a consequence, heart-transplant surgeons are always walking a narrow line between preventing fatal rejections and causing fatal infections. No story shows how difficult this high-wire act was than the first human-to-human heart transplant. It was a procedure that for years afterward made the surgeon who did it the most famous doctor in the world—and, later, one of the most vilified.

Christiaan Barnard was the son of a poor Dutch Reformed Church minister in Beaufort West, part of the vast open spaces of Karoo, the desert heartland of South Africa. It was Barnard’s mother, however, who instilled in Christiaan and his brothers the belief that they could do anything if they just tried hard enough. As a boy, Christiaan set a record for the mile run in his bare feet, won a school tennis championship with cardboard covering the holes in his sneakers, and finished at the top of his class while studying by rural firelight. After graduating from the University of Cape Town in 1945, Barnard won a scholarship to travel to the University of Minnesota, where he became fascinated with heart transplants. (Coincidentally, Norman Shumway, who was the same age as Barnard, trained at the University of Minnesota at the same time.) When Barnard returned to South Africa, he was appointed head of the department of experimental surgery at the Groote Schuur Hospital in Cape Town, eventually establishing the first intensive-care unit in South Africa. In 1967, Barnard spent three months at the Medical College of Virginia to learn more about organ transplantation. When he returned home, he became the first person in South Africa to do a kidney transplant.

Barnard was a man of many contradictions. During apartheid, he ignored the restrictive racial laws in his country, including allowing mixed-race nurses in the operating room to treat white patients. Nonetheless, he was often belligerent to his staff. A colleague described him as “egocentric, hard-working, clever, ambitious, brash, and somewhat arrogant.” “I have a tremendous ego,” Barnard once told an interviewer, “and I must feed it, or I become miserable and unhappy.”

In December 1967, Christiaan Barnard would get his wish—his ego would be fully fed. And it would destroy him.

Louis Washkansky was a fifty-four-year-old Jewish grocer born in Lithuania. When he was twenty-eight years old, Washkansky, a heavy smoker with diabetes, suffered his first heart attack. When he was thirty-eight, he suffered his second; at forty-three, his third. Each left his heart severely damaged: a grotesque, floppy, quivering balloon. His failing heart caused massive amounts of fluid to collect in his legs, which periodically had to be drained. The slightest exertion left him breathless. “I know as soon as I close my eyes,” said his wife, Ann, “that he will take one real long breath and never breathe anymore.” Two-thirds of Washkansky’s left ventricle, which is responsible for pumping oxygen-rich blood to the body, was essentially dead; also, the two arteries that supplied blood to his heart were largely obliterated. Barry Kaplan, Washkansky’s doctor, said it was the largest heart he’d ever seen.

On September 14, 1967, Louis Washkansky was admitted to the Groote Schuur Hospital in Cape Town, breathless and dying. One month later, he suffered kidney and liver failure. The nurse taking care of him said, “He couldn’t breathe. He couldn’t turn around without puffing. He couldn’t do a thing for himself. He was blue. His body was bloated. His legs were draining fluid. He was a very sick man—a very, very sick man indeed.” When Christiaan Barnard looked at the X-ray and saw the size of Washkansky’s heart, he couldn’t believe that he was still alive.

Barnard had his transplant candidate. Now, he had to find a donor.

Twenty-five-year-old Denise Ann Duvall worked at a bank and lived with her parents, Edward and Myrtle. On December 2, 1967, they, along with Denise’s brother, Keith, all got into Denise’s new car to visit friends. First, they stopped at the Wrensch Town Bakery. “My wife wanted a cake for our friends,” recalled Edward, “so we stopped opposite that bakery at Salt River.” At 3:35 p.m. Denise and her mother walked out of the shop, cake in hand. Unfortunately, a large truck parked in front of the store blocked their view of the road. When they stepped out from behind the truck, they didn’t see the white car driven by Frederick Prins, who had been drinking, speeding toward them. “We heard a thud and a bang and a screech of tires,” said Edward. Keith turned around. “Dad!” he shouted. “It’s Mom and Denise!” The two women were knocked across the road. Fifty-two-year-old Myrtle was dead on impact. Denise suffered massive head injuries, with blood pouring out of her nose, ears, and mouth. But she was breathing, and her heart was still beating, when the doctors arrived.

Remarkably, at the same time as the accident, Ann Washkansky and her sister-in-law, Grace, were driving out of the parking lot of Groote Schuur Hospital on their way home. Seeing a crowd gathered on the road in front of the Wrensch Town Bakery, Ann slowed down. “Oh, my God,” she said, “there’s been an accident. There’s a woman on the road.” “Two women,” said Grace.

Denise was brought immediately to Groote Schuur, where she was found to have several large skull fractures. Her pupils were dilated and unreactive to light, evidence of brain death. An electroencephalogram (EEG) showed no brain activity. At the time, South Africa didn’t have laws defining brain death. Every hospital had its own rules. “Our [hospital] lawyers stated that a patient could be considered a donor,” said Barnard, “once two doctors, one being qualified for more than five years, declared that an individual is dead. It did not state what criteria the doctors had to use. They left that to the medical profession.”

Barnard asked Edward Duvall for permission to remove his daughter’s heart. “If you can’t save my daughter,” said Duvall, “you must try to save this man.” Then Barnard spoke with Ann and Louis Washkansky. “There is nothing to think about,” said Louis. “I’ll take the chance as soon as possible.” Barnard remembered the moment: “For a dying man, it is not a difficult decision [to accept a heart transplant] because he knows he is at the end. If a lion chases you to the bank of a river filled with crocodiles, you will leap into the water convinced you have a chance to swim to the other side. But you would never accept such odds if there were no lion.”

Louis Washkansky idolized Christiaan Barnard, calling him “the man with the golden hands.” Ann, on the other hand, didn’t trust him. When she asked Barnard about the risks of the operation, he replied that her husband had an 80 percent chance of survival. Ann wondered how Barnard could possibly have known this, given that the operation had never been done before by him or anyone else.

At 12:50 a.m. on December 3, 1967, Louis Washkansky and Denise Duvall were brought into adjoining operating rooms. “I wanted to turn back, but there was no turning,” said Barnard. “Both of them had living hearts that could not continue to beat for much longer. We were approaching the moment when there would be nothing else to do other than cut out both of their hearts, and place one of them—the girl’s—within an empty chest of the man who would otherwise never leave the operating room alive.”

First, Barnard turned off Denise’s mechanical ventilator. Standing next to him was his brother, Marius, another heart surgeon. “So, we waited,” said Barnard, “while the heart struggled on—five, ten, fifteen minutes… until it finally revealed itself in a straight green line across the screen—death. ‘Now?’ asked Marius. ‘No’ I said. ‘Let’s make sure there is no heartbeat coming back.” In his account, Barnard didn’t want anyone to accuse him later of killing Denise, something that would soon become a problem for American heart surgeons. What really happened in that operating room that morning, however, was somewhat different. Forty years later, after Christiaan Barnard had passed away, Marius revealed that his brother had injected Denise with a potassium solution designed to stop her heart immediately after removal of life support. Barnard didn’t want Denise’s heart to be damaged from the lack of oxygen that had been supplied by the breathing machine. So, he forced the issue.

Assisted by Marius, Barnard opened Denise’s chest, removed her heart, cooled it to fifty degrees Fahrenheit, and, at 2:20 a.m., opened the chest of Louis Washkansky. Holding Denise’s smaller heart in his hands, Barnard said, “For a moment I stared at it, wondering how it would ever work. It seemed so small and insignificant—too tiny to handle all the demands that would be put upon it.… And the heart of Washkansky had created a cavity [in his chest] twice the normal size. All alone, in so much space, the little heart looked much too small—and very lonely.” Using the technique developed by Norman Shumway and Richard Lower at Stanford, Barnard sutured Denise’s heart into Washkansky’s chest. Initially, the heart lay motionless. So, Barnard gave Washkansky’s new heart an electric shock with a defibrillator. “The heart lay paralyzed, without any sign of life,” said Barnard. “We waited it seemed like hours until… little by little it began to roll with the lovely rhythm of life.” Five hours after the start of the operation, Christiaan Barnard could finally take a breath. “Dit werk,” he said to Marius in Afrikaans: “It works.” Barnard then gave Washkansky medicines to suppress his immune system, hoping to stave off rejection for as long as possible.

At 5:43 a.m., Washkansky was taken back to his room, and at 9 a.m. he woke up. “You promised me a new heart,” he told the nurse. “I assume you kept your promise.” Washkansky’s recovery bordered on the miraculous. “It was amazing to see how he lost all evidence of heart failure,” said Barnard. “The swelling of his legs disappeared; the swelling of his liver disappeared; his lungs became dry; and he was well, mentally well. So, we were very optimistic at the beginning.”

Louis Washkansky, the first heart-transplant recipient to regain consciousness, was immediately the world’s most famous patient. Cabinet ministers, photographers, journalists, and representatives of every major broadcasting organization flooded his room. One particularly low moment came when a BBC interviewer asked Washkansky by phone what it felt like, as a Jew, to have the heart of a gentile. “Well, I never thought of it that way,” he replied. “I don’t know…” One of the doctors in attendance, Dr. Bossie Bosman, cut the connection to London and shouted angrily at a BBC technician, “How do you feel working for a company that asks stupid questions?”

On December 15, 1967, two weeks after the operation, Washkansky worsened. His lungs filled with fluid and he struggled to breathe. Barnard considered two possibilities: either the fluid in Washkansky’s lungs was caused by heart failure from rejection, or it was caused by a bacterial pneumonia. Barnard chose the former, dramatically increasing the quantity of immune-suppressive drugs. Unfortunately, he had made the wrong choice. On December 21, eighteen days after the world’s first human-to-human heart transplant, Louis Washkansky was dead. The autopsy showed only minimal signs of rejection and lungs full of bacteria. Suppressing the immune system of a man fighting serious bacterial pneumonia was the worst possible thing Barnard could have done. “There was at least a part of my daughter that was still alive,” lamented Edward Duvall, “but now she is completely dead.”

Heart surgeons across the globe were surprised that Christiaan Barnard, an unknown surgeon from a country that had only recently opened an intensive-care unit, was now basking in the fame of being the first surgeon in history to transplant a human heart. Everyone had assumed that it would have been Norman Shumway taking the bows. “Shumway did everything by the book,” said James Hardy, “only to have history stolen from him.”

Barnard became an international celebrity. Within two weeks of Washkansky’s operation, the surgeon was on the cover of Time, Life, and Newsweek magazines. But he was dissatisfied with the outcome of the transplant. He wanted to prove that he could do better than prolong someone’s life for only eighteen days. His next chance came one month later.