How Death Becomes Life

by Joshua Mezrich

  The progression of heart transplantation after Barnard’s first was similar to the explosion in flight after the Wright brothers proved its potential in 1903. Before their success, few people could imagine it being done, but within a year, more than 100 flights had been completed by numerous pilots. So, too, with heart transplantation. In 1968, 101 transplants were performed in 26 countries. Every major hospital wanted a program, and prominent heart surgeons around the world jumped on the bandwagon.

  One great example was Denton Cooley in Houston, possibly one of the most technically gifted heart surgeons in the world. When he heard about Barnard’s first successful transplant, he sent the following cable: “Congratulations on your first transplant, Chris. I will be reporting on my first hundred soon.” He wasn’t kidding. A few months later, in April 1968, he did his first, which took him thirty-five minutes to sew in. His patient made it out of the hospital and back to work (although he died after seven months). Cooley completed seventeen by the end of 1968, but only two of the patients lived longer than six months. Cooley was a master surgeon, but he was not a transplant surgeon. Few heart surgeons were then. By mid-1969, he shut down his heart transplant program, as did the head of almost every other program in the country. Due to the miserable outcomes, physicians were loath to refer patients as donors and donor consent rates were low.

  Roy Calne described the phenomenon this way:

  In the eyes of the media, the drama of the operation seems to be more important than the long-term well-being of the patient, which is what transplantation is really about . . . The surgical results were usually satisfactory but most of the cardiac surgeons had no experience of transplantation immunology or immunosuppression and the infrastructure needed to prevent or control destructive rejection. Virtually all of these poor patients perished, having satisfied the macho aspirations of their surgeons. This series of failures had an extremely bad effect on the image of transplantation and resulted in a self-imposed moratorium on heart transplantation, except in a few centers where the procedure could be done with the appropriate infrastructure.

  In 1971, just seventeen heart transplants were performed in the world.

  In the end, outcomes wouldn’t really improve until the discovery of cyclosporine. As was the case for all transplants, the 1970s were the tough years, when the believers toiled on, despite mediocre results, until better immunosuppression became available. And the main believer was Shumway. A true transplant surgeon, he carried the torch through the wasteland of the ’70s and into eventual success in the ’80s. Without a doubt, although Christiaan Barnard was the first, Norman Shumway was clearly the father of cardiac transplantation.

  KIDNEY TRANSPLANT LED to a Nobel Prize, with a handful of famous surgeons involved and the most prominent hospital in the world at center stage; heart transplant generated international excitement and chaos; and liver transplant (which I’ll discuss in chapter 9) was championed by the biggest name in transplant, perhaps the most recognizable personality in our field, Thomas Starzl. But does anyone know who performed the first lung transplant? For most, the answer is no.

  Actually, the man who performed the first lung transplant in humans was the same one who did the first heart transplant in humans. No, not Christiaan Barnard. It was James Hardy, at the University of Mississippi Medical Center, in Jackson. While Barnard performed the first heart transplant between two humans, three years earlier, in 1964, Hardy had performed the first heart transplant between a chimp and a human. He took an incredibly ill sixty-eight-year-old man with a failing heart and dying limbs, truly hours from death, and sewed a chimpanzee heart into him. The surgery itself went well, and the heart did start beating immediately, but Hardy couldn’t get the patient off the bypass pump. The tiny chimp heart just couldn’t beat strongly enough to sustain the recipient’s blood pressure. Ultimately, it proved too small for the patient, and he died in the operating room. Hardy was demolished in the press and the transplant community.

  This horrible day may have overshadowed a major accomplishment for Hardy of just seven months prior. The year was 1963. Hardy had performed almost four hundred lung transplants in dogs. He had the operation down, but given the quality of immunosuppressive therapies at the time, the vast majority of recipients were dead by four weeks post-op. Nevertheless, Hardy thought it was time to try the procedure on a human.

  He met the perfect recipient on April 15, 1963. John Richard Russell, a fifty-eight-year-old white male, was extremely ill and just what Hardy had been looking for, absolutely perfect, presenting no red flags whatsoever—except maybe just a couple: He was a heavy smoker and had a massive tumor completely obstructing his left main-stem bronchus, with pus around it, and a diseased lung on the other side. He was also in chronic renal failure and was approaching dialysis. Oh, and one other little thing: he had been convicted of murdering a fourteen-year-old boy in 1957 and was serving a life sentence. In his defense, Russell had maintained that the murder was accidental, but he had still been convicted.

  At the very least, it was clear that Russell was dying. Hardy approached him about the possibility of a lung transplant. When writing about the case after its conclusion, Hardy clarified how the decision was made: “Although the patient was serving a life sentence for a capital offense, there was no discussion with him regarding the possibility of a change in his prison sentence. However, authorities of the state government were contacted privately, and they indicated that a very favorable attitude might be adopted if the patient were to contribute to human progress in this way.”

  Six weeks later, a man was brought into the hospital with a massive intracranial hemorrhage. He was undergoing CPR, and when it became clear that he would not survive, his family was asked to consent to organ donation. Hardy removed Russell’s left lung and then sewed in the donor’s left lung, hooking up the blood supply and the airway just as he had hundreds of times in dogs in the lab. The surgery went smoothly, and the lung functioned right away. Unfortunately, after the operation, Russell’s kidneys failed. While he was dying, a major press release announced his pardon by Governor Ross Barnett of Mississippi, who thanked him for his courage in trying to help mankind. At least he died a free man, nineteen days after the world’s first lung transplant.

  Hardy’s poor outcome with a prisoner, followed by his poor reception after the chimpanzee transplant, convinced him to lie low and let others battle through all the bad outcomes that would accompany transplantation in the 1970s. And so, the discipline of lung transplant limped along almost imperceptibly, with no real success for almost twenty years.

  Between 1963 and 1981, roughly forty single lung transplants were performed, with virtually all recipients dying from infection or technical complications. The biggest challenge was the connection to the airway, which would invariably leak into the patient’s chest, causing massive infection and death. This likely was due to inadequate immunosuppression, which led to early rejection. In all those years, there was only one success: a twenty-three-year-old patient in Belgium who received a single lung in 1968 for the diagnosis of advanced pulmonary silicosis. (He was a sandblaster.) Despite some early rejection episodes, he survived for ten months before dying of pneumonia. His autopsy revealed a healthy-looking lung transplant with no evidence of rejection.

  While Hardy falls into the long list of surgeons who wanted to be first, Norm Shumway wanted to be right. By the late 1970s, having established himself as the premier heart transplant surgeon in the world, he was bothered by the subset of patients he couldn’t help: those who needed a heart transplant but also had severe lung disease. Many of these patients had congenital heart disease that had gone untreated and, over time, had damaged the lungs. Why couldn’t he take the heart and lungs en bloc and sew them in together? But first, he needed to know that he had a reasonable chance for success.

  The timing couldn’t have been better for Bruce Reitz. While an undergraduate at Stanford, Reitz became interested in the heart when he studied the immunologic reactions
of the heart as a physiology major. He worked in Shumway’s lab as a medical student (eighteen months after Shumway’s team performed the first heart transplant in man) and returned there after his residency and cardiothoracic fellowship at Stanford. Shumway asked Reitz to focus on combining heart transplant with bilateral lung transplant, and Reitz began by performing autotransplants in monkeys, removing their hearts and lungs while they were on bypass and then sewing them back in. In this way, Reitz and his team could perfect the technique without having to deal with rejection. Once they had done so, they moved on to allotransplant, removing the same organs from donor monkeys and placing them into recipients. But the outcomes were not adequate. Immunosuppressive therapies just weren’t good enough yet.

  Things changed in the summer of 1978, when Reitz and his team were able to obtain cyclosporine for their research. This new wonder drug changed everything. With cyclosporine part of the antirejection regimen in their monkeys, the tracheal (airway) anastomosis healed and the monkeys survived.

  By the fall of 1980, Reitz and Shumway thought their results in the lab good enough for them to consider a heart-lung transplant in a human. Enter Mary Gohlke, a forty-five-year-old woman whose pulmonary hypertension had led to a failing heart and lungs. Gohlke knew she couldn’t wait much longer, and was able to reach her senator in Arizona, who pushed the FDA to give Stanford approval to use cyclosporine in combined heart-lung transplants. On March 9, 1981, Reitz and Shumway removed Gohlke’s heart and lungs. In Reitz’s own words, “The appearance of Mary Gohlke’s totally empty chest was indeed a dramatic moment. I wondered, ‘Is this really going to work out?’ But the implantation went smoothly, the heart resuscitated quickly, and lung function was adequate immediately. ” Gohlke went on to live five more years, and when she died, her organs were still functioning, with no rejection noted during her autopsy.

  TWO YEARS AFTER Gohlke’s transplant, in 1983, the first successful lung transplant alone was performed by Joel Cooper at the University of Toronto. The patient was Tom Hall, a fifty-eight-year-old with pulmonary fibrosis (scarring of the lung tissue). Cooper had previously taken part in the forty-fourth failed attempt, in the late 1970s, and realized that doing more in humans at that point would have been fruitless. So, in the tradition of all great pioneers, he went back to the lab. Knowing that the factor killing all their patients was the airway’s inability to heal, he focused on wound healing, and found that high-dose steroids were most to blame. Like Shumway and Reitz, he realized he’d need something different. By the time cyclosporine was available for use in humans, Cooper had perfected a novel technique for sewing the airway and bolstering it with omentum, vascularized tissue found in the belly. Although he now thought it time to resume human transplantation, he was not sure what kind of outcome he could expect. He recalled his conversation with Tom Hall before the surgery: “I said, ‘Tom, there have been about 44 attempts thus far and no one has survived. Are you sure you want to go ahead with it?’ He said, ‘I am grateful to be number 45. ’ ” Hall lived more than six years, truly returning to a normal life.

  Cooper went on to conduct the first successful double lung transplant in 1986 as well. Lung transplant (like pancreas transplant, discussed in chapter 8) has some particular challenges. Unlike with heart, liver, and kidney transplantation, which became relatively safe after the introduction of cyclosporine, lung patients, even as recently as the early 1990s, had only a fifty-fifty shot at leaving the hospital alive. Infection has always been one major hurdle. In 1990, 290 cases were reported, with 65 percent survival at one year and 54 percent at two. But due to the commitment of pioneers such as Reitz and Cooper, the likelihood of leaving the hospital today is close to 97 percent. The current one-year survival rate is roughly 80 percent, with five-year survival just better than 50 percent. For unclear reasons, lungs seem to be susceptible to a unique type of chronic rejection that limits long-term outcomes. Numerous investigators are trying to understand this better. It is hoped that outcomes will continue to improve.

  8

  Sympathy for the Pancreas

  Curing Diabetes

  When a child is diagnosed with type 1 diabetes, an entire family is diagnosed with type 1 diabetes.

  — TYPE1MOMS (WWW.TYPE1MOMS.ORG)

  Insulin is not a cure for diabetes; it is a treatment. It enables the diabetic to burn sufficient carbohydrates so that proteins and fats may be added to the diet in sufficient quantities to provide energy for the economic burdens of life.

  — FREDERICK BANTING, “DIABETES AND INSULIN,” NOBEL LECTURE, SEPTEMBER 15, 1925

  There’s an old saying in surgery. “Eat when you can, sleep when you can, and don’t mess with the pancreas.” I think every surgeon has at least one experience related to a leaking pancreas, and it likely involves multiple drains, an open wound, and a miserable patient. Yet there is a certain amount of celebrity associated with surgeons who operate on this organ. The Whipple, in which the head of the pancreas is removed because of cancer or benign lesions, is one of the most fabled operations, and those who do it are considered high priests of abdominal surgery. The irony is that along with the complexity of the operation and the high rate of complications (two things that frighten off the most courageous surgeons), the operation doesn’t even work very well. While some surgeons report a five-year survival rate of 20 percent, most patients who live are found not to have had cancer in the first place, but rather, inflammation or a precancerous lesion. I understand that patients are trying their best to survive, but with the most famous surgical operation, the one that is like slaying the dragon, patients usually end up getting eaten by the dragon anyway.

  In organ transplant, we don’t just mess with the pancreas; we roll it up, squeeze it out, and transplant the whole thing for patients afflicted with diabetes.

  As I finished my residency in Chicago, I wanted to continue my training at a top-notch transplant center. I was interested in learning liver transplantation (the Super Bowl of the abdomen), but I also wanted to have the opportunity to mess with the pancreas. I got that chance at the University of Wisconsin—and it didn’t disappoint.

  In my first two months in Madison, I performed sixteen pancreas transplants. Most of them were with Hans Sollinger, perhaps the premier pancreas transplant surgeon in the United States. Hans started in pancreas transplant in the early 1980s, when outcomes were dismal, mostly because the connection between the pancreas and the bowel kept falling apart. Across the country, programs were giving up on the operation. Some surgeons were letting the pancreatic duct drain freely into the abdomen or were bringing it out through the skin and collecting the fluids in a bag. Around that time, Dr. Folkert Belzer, the chairman of surgery at the University of Wisconsin, told Hans he’d better figure out how to make pancreas transplant work or he’d shut the program down. In a fit of frustration, Sollinger yelled out, “How ’bout I sew the pancreas to the fucking bladder!” Though Sollinger said this in desperation, both he and Belzer realized it was a good idea, and that’s what saved the pancreas program at Madison.

  This was in 1983, and for the next fifteen years, Sollinger’s idea (which he first tested in dogs) became the primary technique used by surgeons across the globe. Around the mid-1990s, after documenting that patients were suffering long-term urinary tract complications due to the drainage of pancreatic juices (and given the improved immunosuppression, which allowed for better healing), Sollinger switched back to drainage into the bowels. I still see this as one of his finest moments—even though he had popularized bladder drainage, which played a huge role in the success of the entire discipline, he was one of the first to publish and lecture on its problems, and he encouraged surgeons to switch back to bowel drainage. That took guts!

  I’M NOT ONE to judge the patients I evaluate, but I accept that many diseases are caused at least in part by the choices we make. If we got everyone to stop smoking and abusing alcohol and drugs, to eat better, and to clean up the environment, we doctors probably would have very li
ttle to do.

  None of this applies to patients with type 1 diabetes of course. People develop this horrible disease through no fault of their own, typically at a young age, when they are supposed to be enjoying the world around them without thinking about consequences. And the consequences of diabetes are brutal: amputated limbs, blindness, heart disease, kidney failure, and perhaps most cruelly, impotence. Patients diagnosed with type 1 diabetes are usually kids, tend to be thin, and in general look quite healthy. They are often active, play sports, and do well in school. What we don’t see is how different their lives are from those of other kids. Anytime they eat, they have to think about how much insulin they should take. Their fingers become hardened from all the needle pricks. In many cases, the disease plays a major role in defining their personalities. When all the other kids at a birthday party run over to eat cake and ice cream, the kids with type 1 diabetes run over to their parents to ask if they can, knowing that they will be told no. Kids with type 1 are awakened a couple of times every night so their blood sugar level can be checked, to make sure they don’t dip too low or soar too high while they’re sleeping. These kids are forced to be organized, prepared, and detail-oriented. When you evaluate them in the clinic, they always ask dozens of questions, write everything down, and think through every detail (or their parents do).