I went home. It was getting light. I collapsed into bed and had barely closed my eyes when the phone rang. The patient’s mother, who lived on the East Coast, had flown in and just arrived at the hospital. She had left home when we had informed her that we had a donor for her son. She did not know what had happened after that.
I returned to the hospital to break the news, feeling numb. I explained to his mother that despite our best efforts, her son had died on the operating table. I did my best to comfort her. When I finally went home again, it was hard to put one foot in front of the other. I felt like I was carrying a weight that threatened to crush me.
When Shumway got back, he was entirely supportive. But I could not get over what had happened. I kept going over the experience we’d had with the third patient in our heart-and-lung transplant series, who’d been operated on a year earlier. She had also had previous heart surgery and had also died. Had we missed something? In that case the prior surgery had gone in through the front of the chest and there was no extensive scarring. So it was hard to say whether prior chest surgery was a deal breaker, but I didn’t want to take any more chances. I decided not to accept anyone else who’d already had heart surgery. This stayed our policy for many years.
As our transplant list grew, we had to find a way to preserve the lungs out of the body. Bringing a brain-dead patient from far away to Stanford Hospital wasn’t practical in the long term. There were rules against transporting bodies across state lines, which forced us to seek time-consuming exemptions from government officials every time we wanted to move a donor over a border. Our goal in the lab was to find a solution with which to perfuse the lungs and make them cold without injuring the delicate exchange cells that make up the fragile boundary between blood and air. A worker’s strike at Stanford kept our regular technicians away from work. We carried on without them, enlisting the help of two visiting medical students from Germany. One of these, Hermann Reichenspurner, would in due course go on to be an internationally recognized surgeon in his own right, and the president of the International Society for Heart and Lung Transplantation.
We eventually found a preservation solution that worked on lungs. We also modified our surgical technique to preserve the vagus and phrenic nerves, which control the abdominal organs and the diaphragm, both of which had been damaged in Mary Gohlke’s operation. The technique we developed then is still used today.
We still had more people in need of transplants than we had donors. Four months passed as we marked time. Then, in early November, we got word of a donor from out of state. This was going to be a test of our new lung solution. The donor team flew out. When they got to the donor, they flushed the heart as usual and the lungs with the new solution. Everything went perfectly, and lung function after the transplant was normal. The press still followed us closely, and reports of this operation spurred an increase in the numbers of donors we were offered. After a hiatus of four months, we did three heart-and-lung transplants in four days. All the donors were from out of state, and all had their organs removed at the hospitals they were in. All the recipients did well. Lung transplantation had arrived.
I didn’t concentrate on transplantation exclusively. In those early years on the faculty, I was busy building up my practice in regular heart surgery, doing valve replacements, aortic surgery, and bypasses. Shumway often asked me to do his cases, too. I kept an eye on his schedule. Whenever I saw he was still in the operating room at five p.m. and I was free, I would scrub in and stand there until he saw me. Then he would leave. Many years later he told me how grateful he was. Nobody else ever did that for him.
We began to see warning signs that lung transplantation might not be forever. A thirty-two-year-old man from Binghamton, New York, named Charlie had been transplanted on May 1, 1981. He was the second heart-and-lung transplant in the Stanford series, and only the second heart-and-lung patient in the world to have been discharged from hospital. He had done well for three years but now suffered from narrowing of the bronchioles, the small air passages in the lungs. This could only be the result of chronic rejection. We increased Charlie’s cyclosporin dosage, but this had caused kidney failure. Charlie was soon on a ventilator, which required a tracheostomy, a hole in the neck to access the trachea.
In the heart, chronic rejection is manifested by progressive narrowing of the coronary arteries. We now learned that narrowing of the small airways in the lung was a hallmark of rejection in that organ. Charlie’s situation was dire. The only thing that could save him was another heart-and-lung transplant. We doubted this was possible. Charlie’s general condition was poor. A re-transplant of both heart and lungs had never been attempted. And our experience with the scarring adhesions encountered in a patient who’d had previous heart surgery told us that Charlie’s chances of surviving the surgery were remote. How much worse would this be in someone who’d had a complete heart-and-lung transplant? Surely both Charlie’s heart and lungs would be heavily scarred and stuck to the chest wall. The surrounding nerves that supplied the diaphragm and the abdominal organs were sure to be bound up in this same mess. In the end, we decided we could not use a precious donor for Charlie when we had so many other patients waiting for a new set of heart and lungs. It was a horrible decision to have to make, but we felt it was out of our hands.
Charlie had been on the ventilator for about six weeks, clinging to life, when I got a call from Chris McGregor, Shumway’s chief resident. I had begun to wean myself from the unremitting day-and-night hospital schedule I’d kept since my days at St. Mary’s, when the best I could do to get away was to stand on the balcony of the entry hall late at night. McGregor’s call came on a Sunday, and I was at my ranch in San Gregorio, forty-five minutes from the hospital. He told me we had a donor who was the wrong size and blood type for everyone on the list but one.
“What about doing Charlie?” Chris asked.
If we didn’t use the heart and lungs, they would be wasted. Charlie was just waiting to die. I didn’t have to think. I told McGregor I was on my way.
We spent the rest of the day doing Charlie’s operation. It was the first redo heart-and-lung transplant in the world, and I suspect that even now no more than a handful have been tried. If any. The operation was challenging, but not as difficult as we’d feared. In the earlier case, twenty-five years had allowed the scar tissue and vascularity to build up within the chest. Charlie’s chest surgery was much more recent. Everything in his chest was stuck and scarred, but it was manageable. Shumway came in for a while but did not scrub. He just chatted with the nurses and let us know he was around even though it was a Sunday.
The world’s first redo heart-lung operation. I am being assisted by Chris McGregor (in the dark cap). Dr. Shumway (in the white cap) is observing.
One problem we had was that the previous donor’s trachea was hardened in place, and Charlie’s own trachea had been compromised by the tracheostomy that had been done to put him on the ventilator. It was impossible to get back to the original suture line to sew the new donor trachea to Charlie’s. So I cut the previous donor trachea and sewed the new one to that. Charlie now had segments of three tracheas—his own, and two from different donors. This worried me. It seemed like a perfect setup for everything coming undone. But there was nothing else for it. I decided that if Charlie’s airway didn’t fall apart, I would never worry about the sutures of the trachea again. It didn’t, and I didn’t.
There was another thing I’ll never forget about that operation. The day before it, I’d been clearing brush at my ranch and had gotten covered in poison ivy. When McGregor called me on Sunday morning, I was coming out in a rash all over my body. It was driving me crazy. Operating for many, many hours, standing there under the hot operating-room lights as I itched everywhere and could do nothing about it, was torture. As soon as we were done late that afternoon, I tore off my gown and asked the anesthesiologist to give me a shot of steroids. He did, and the relief was almost instantaneous.
Unbeknownst
to me, there was a surgeon visiting from Brazil that day who observed the operation. I had friends in Brazil. Soon, I heard from one of them.
“Stuart, is everything all right?” he asked.
I assured him that it was.
“Are you sure?” he persisted. This went on for a while. “You would tell me if anything was wrong, wouldn’t you?”
Of course, I said. Finally I asked him what it was all about. He said he’d heard from someone who’d seen me operate that when I finished I desperately needed an injection. He thought I must be a drug addict.
A few days later, when I was in the intensive care unit, Shumway came up to me, put his arm on my shoulder, and said, “That was a terrific job. I don’t know anybody else who could have pulled it off.”
Charlie recovered, left the hospital, and wrote a book. Chris McGregor later joined the faculty at the Mayo Clinic and became the head of transplantation there.
We were still learning. We continued to monitor rejection of the lungs by doing heart biopsies. We still thought it was likely that since the heart and the lungs came from the same donor, both organs would reject together. But as we’d seen earlier in monkeys, the lungs seemed more prone to rejection. In 1983, we learned that was the case in humans as well. Our thirteenth patient did well for the first two weeks before changes in his lungs showed up on an X-ray. His heart biopsies were negative, so we initially assumed this was infection and not rejection. We gave him antibiotics. After a few days with no response, he was having difficulty breathing. I took the risk of treating for rejection. If I was wrong, any infection would quickly get out of control because of the increased immunosuppression.
It was the right decision, but it was too late. The patient died of rejection of the lungs. The heart showed no signs of rejection. We later were able to show in the laboratory that the lungs could reject independently of the heart. It was another important lesson that had been learned at terrible cost.
Our program kept expanding. For the next year, I headed the only team in the world doing heart-and-lung transplants. We had a big waiting list and were doing an average of one operation a month. Then, in November 1983, cyclosporin was released for general use by the Sandoz company under the trade name Sandimmune. This launched or restarted heart-transplant programs around the world.
In January 1984, I presented a paper on our experience with heart-and-lung transplantation at the opening of the annual Society of Thoracic Surgeons meeting in San Antonio, Texas. The paper was judged to be the most significant of the meeting, and was subsequently published in the Annals of Thoracic Surgery. Reviewing our findings for the society, Dick Lower wrote:
Dr. Jamieson and colleagues report one of the most extraordinary clinical studies of this decade and perhaps of this century. Total heart and lung transplantation combines in one procedure impressive technical expertise with an understanding of complex anatomical, physiological, and immunological principles, a combination perhaps unparalleled in the surgical literature.
That same year, more than fifty centers worldwide started doing heart transplantation, and by 1985 there were more than a hundred. Ten years later there were more than 250. Cyclosporin is still the most widely prescribed immunosuppressant for organ transplants. Shumway’s persistence and our determined work in the lab meant that many thousands of people who otherwise would have died of heart or lung disease were given a new chance at a normal and healthy life.
Despite the new enthusiasm for heart transplantation in adults, nothing was happening with transplants in babies and children. Adrian Kantrowitz in New York had done the first transplant in a baby in December 1967, commencing the operation at the same time that Christiaan Barnard was finishing up his landmark transplant in an adult in Cape Town. The infant lived only a few hours. Almost seventeen years later, even with the huge advances in heart transplantation that had taken place, nobody else had transplanted a baby, largely because infant donor hearts were unavailable.
Then, in London on July 30, 1984, Dr. Magdi Yacoub transplanted a heart from a three-day-old Dutch baby into nine-day-old Hollie Roffey. Roffey suffered from a birth defect called hypoplastic left heart syndrome, in which the main pumping chamber of the heart is underdeveloped. Roffey died eighteen days after surgery.
That fall, on a Sunday morning in October 1984, a baby was born in the high California desert who was to make medical history. The five-pound, nine-ounce girl appeared normal, but her heart had the same defect as Hollie Roffey’s. The little girl’s days were numbered. Her name was Stephanie Fae Beauclair-Drew. Soon the whole world would know her as Baby Fae.
Leonard Bailey at Loma Linda University Medical Center, who headed their cardiac team, specialized in heart surgery in babies. Having seen countless babies die of heart defects that could not be repaired with conventional heart surgery, Bailey had always been interested in heart transplantation in infants. As a medical student, he had visited the Stanford laboratories when that program was just beginning.
Bailey called me in 1983 to ask if I would come to Loma Linda to spend a day with his team. I asked what it was about. He was reluctant to say on the telephone. Curious, I flew to John Wayne airport in Orange County, where Len was waiting for me on the curb. We drove to Loma Linda, about forty-five miles away, through open fields that have long since disappeared beneath California’s endless concrete jungle. During the drive, Bailey told me about the work he had been doing in the laboratory during the past several years. At first I wasn’t sure I was hearing him correctly. Then I realized why he’d been reluctant to tell me what was going on. At the hospital we walked into a conference room filled with people, including doctors, laboratory workers, and nurses.
The team launched into a presentation of seven years of work on cross-species transplantation in newborn animals. Their research was based on the idea that the immune system is not fully functional at birth. It takes time to develop the antibodies that cause the hyperacute form of rejection known to occur in cross-species transplants—and that I’d studied in the lab back in London. Bailey had performed some two hundred same- and cross-species experimental transplants in the neonatal period, mostly using goat, lamb, or piglet hearts transplanted into baby goats. On average, the transplanted goats without immunosuppression survived about two and a half months before beginning a slow rejection. This was totally different from the rapid, hyperacute rejection I’d observed countless times in mature animals. Bailey’s team had a goat named Livingston that had been transplanted with another goat heart as a newborn and grew to six months of age without immunosuppression. It appeared that the immune systems of Bailey’s animals were intact, but they were more accommodating as newborns. When the team used cyclosporin, the animals were far less likely to reject the new hearts. Some had grown up and had their own offspring.
We discussed other work that had been done in cross-species transplantation, particularly the work of Dr. Keith Reemtsma, who had transplanted chimpanzee kidneys into human beings at Tulane in the early sixties. He had some success despite the limited immunosuppression then available. But adult heart transplantation using primates had been a dismal experience. Barnard’s baboon-transplant patient had died hours after the operation. A second attempt, this time with a chimpanzee heart, failed after three and a half days. Barnard gave up cross-species transplantation because of the rejection issue, though he said that he’d try again when better antirejection drugs were developed. But in a 1978 interview, Barnard said that he’d had second thoughts about ever again transplanting a primate heart, “not because I’m so convinced I’m on the wrong track, but because I got emotionally involved with the chimp.”
Among potential animal donors for a human, primates would be best. Chimpanzees were not available, and in any case were so humanlike that nobody wanted to use them. Christiaan Barnard wasn’t always wrong. Orangutans and gorillas were endangered. But baboons were plentiful and controlled as pests in many parts of Africa. They are hardy animals and reproduce easily. Bailey’s te
am decided that their donors would have to be baboons.
After they were done talking, I encouraged them to continue their research. I told the team I thought neonatal heart transplantation across close species might be possible. I returned to Stanford intrigued by Bailey’s work and the careful way that they had conducted their research. The ethical issues were serious, but I was impressed by Bailey’s absolute integrity. And I thought he might well be on the right track.
Sir Peter Medawar, who had won the Nobel Prize in 1960 for his transplant research, and whom I had met when I was working in Ken Porter’s lab, had discovered that the immune system is not preprogrammed to distinguish between self and non-self, but learns to do so as a result of exposure during early development. In other words, if there were no preformed antibodies against an organ from another species, there was a chance such an operation could work. Bailey would be taking a huge chance if he transplanted a baboon heart into a human infant, but he was on solid theoretical ground.
When twenty-four-year-old Teresa Beauclair had delivered her baby at a hospital in Barstow, the infant was promptly transferred to Loma Linda for an assessment of a heart defect. The news could not have been worse. Beauclair was told nothing could be done to save the baby. She had three choices: Leave the baby at Loma Linda to die, take her back to the hospital in Barstow to die, or take her home to die. Furious, Beauclair demanded to know why we could put a man on the moon but couldn’t make her baby well. She took the infant back to Barstow.
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