I was assigned to be Miller’s number two at the VA and co-chief of vascular surgery at Stanford. Of course, I still picked up as many regular cardiac and transplant cases at Stanford as I could. These were usually the night cases. Everyone else preferred to operate in the daytime, and after the sun went down, they were happy to let me take over. I got to be known as the midnight cowboy. My appetite for heart surgery was never satisfied. I was so hungry for work that one evening when I’d just arrived back in California after an exhausting trip to Europe, where I had been lecturing, I said yes when the chief resident met me at the airport to ask if I could assist on a heart transplant that night. Phil Oyer was on call but said he was sure I’d want the operation. I did. In retrospect, I don’t know how I managed to work nonstop all those years. I guess at the time it didn’t seem like work.
I made time to keep in touch with the lab, which was close to the office I shared with Miller. We had found that the monkeys with heart transplants did well when we treated them with reduced doses of steroids, coupled with cyclosporin but no ATG. When we tried heart-and-lung transplants, we didn’t use steroids at all for the first two weeks, to speed the healing of the airway. The monkeys did fine. The evidence for the effectiveness of cyclosporin continued to mount. Toward the end of the year, we were ready to use it in the patients.
The Food and Drug Administration (FDA) and the Stanford Institutional Review Board gave approval for a preliminary trial of cyclosporin in human heart transplantation. And we had a candidate in mind. In December, a young man in the intensive care unit was dying of a cardiomyopathy, a class of diseases that attack the heart muscle. There was little we could do. He needed a transplant. While we searched desperately for a donor, we tried treating him with a balloon pump, a device that is threaded up the leg artery, in an attempt to augment the heart’s output. A few days later, a young girl in another state had an accident that resulted in irreversible head trauma and was declared brain-dead. Although she was smaller than our patient, we decided to take a chance that her heart would work. Phil Oyer was the attending on call, and he asked me to retrieve the donor heart while he started on our patient with John Wallwork. I flew to the donor’s hospital and opened the chest. The heart was tiny, almost certainly too small to keep an adult man alive. I called Oyer to discuss the situation. There really wasn’t a decision to make—our patient would die unless we did something. We decided to go ahead.
Back at Stanford in the operating room, I scrubbed in to help Phil. When we saw how small the donor heart really was, we knew it wouldn’t work on its own. On the spot we decided to sew it in and leave the old heart in place. The donor heart would serve as an auxiliary pump, and the output from the old heart would remain, at least temporarily. Barnard had used this method. His reasoning was that if the donor heart was rejected, there still would be some underlying circulation provided from the native heart. This operation, called a heterotopic transplant, or “piggy-back operation,” had not been used before at Stanford. Our focus had been on the prevention and treatment of rejection, not in dealing with its consequences. Leaving the old heart in place, where it would continue to fail and become a source of potential infection or blood clot, did not seem optimal.
But in this case, we really had no choice. As we got the donor heart sutured in alongside the patient’s own heart, the new heart took over about half of the cardiac output. In the days and weeks that followed, the donor heart got stronger and progressively provided more of the circulation until the patient’s own heart was doing nothing. The man recovered, was discharged from hospital, and lived a normal life for many years with two hearts in his chest. He was the only patient to have a heterotopic heart transplant at Stanford and was the first patient in the world to be treated with cyclosporin for a heart transplant, that December in 1980.
From then on, cyclosporin was the mainstay of antirejection treatment in all the heart transplants at Stanford. We did not change the treatment regimens of the patients who had previously been transplanted and were doing well. In one of the few papers on transplantation that he published, Christiaan Barnard credited Stanford’s development of heart tissue biopsies and the introduction of cyclosporin as the primary reasons that heart transplantation came into widespread use.
In 1981 we were the only program in the world using cyclosporin in heart transplantation. The results were superior. For many drugs, measuring their levels in the body is an essential tool in maintaining the proper dose. But in the early 1980s, there was no assay for blood levels of cyclosporin. We had to learn by trial and error. We started the patients on twenty-five milligrams per kilogram of body weight per day. We knew the drug could be toxic to the kidneys in larger doses. If we saw the kidneys start to fail, we cut back on the dosage. As so often proved to be the case, the trick was to go to the limit of what should be done—and then stop. It seemed to work.
Our improving results with heart transplantation, plus the gains in immunosuppression we’d achieved with cyclosporin, convinced us that it was time to try a heart-and-lung transplant. Only three heart-and-lung transplants had previously been done in humans. Denton Cooley transplanted a two-month-old baby with an otherwise inoperable heart and lung defect in August 1968. The infant lived for fourteen hours. Walt Lillehei, who had moved from Minnesota to New York, performed the second heart-and-lung transplant on a forty-three-year-old patient with bad heart and lung disease in December 1969. The patient did well at first but died of pneumonia eight days later. Had cyclosporin been available to Lillehei, things might have turned out better. A third operation was performed by Christiaan Barnard in Cape Town in July 1971, on a forty-nine-year-old man with severe lung disease. The patient lived for twenty-three days and died from complications when the airway sutures failed. Barnard, unlike Cooley and Lillehei, had chosen to sew the airways separately for each lung instead of connecting the main airway.
At Stanford, we now had long-term survivors among our monkeys that had undergone heart-and-lung transplants. They seemed to be living life normally. These were also the first long-term survivors of lung transplantation. The immunosuppression regimen was working well. We started making a list of potential human recipients. All the patients we initially considered had pulmonary hypertension—high blood pressure within the lungs. As the heart works harder and harder to pump blood to the lungs, it will begin to fail. This is a fairly common and usually irreversible condition that leaves the patient struggling to breathe and the heart damaged. There was no drug therapy for it at the time. Other patients we looked at as possible candidates had congenital heart defects that had not been repaired when they were children because those techniques hadn’t yet been developed. Now holes in the heart or sometimes abnormal blood vessels were causing excess blood flow to the lungs and damaging fragile lung arteries. Altogether, these patients had both lung and heart disease for which there was no treatment, but they would certainly die unless something could be done for them.
Bruce Reitz had presented the results of the monkey heart-and-lung transplant work at the sixtieth annual meeting of the American Association for Thoracic Surgery in San Francisco in April 1980. During his talk, he reviewed our laboratory results. Twenty-five monkeys had had heart-and-lung transplants. Five of those monkeys had had an auto-transplant—their heart and lungs were taken out and put back in. One of these auto-transplants was still living seven months after the surgery. Twelve monkeys that had been transplanted with other monkeys’ organs but without receiving immunosuppression drugs had lived for at most five days before dying of rejection. Two more had had their own organs taken out and replaced, with the operation done on heart-lung bypass instead of the hypothermia technique. Those animals were still alive. The remainder, also done on bypass, had transplants from other animals and were treated with cyclosporin. The longest survivor (Mom) was still alive nearly four months after the transplant, without rejection, and was doing well. The monkeys who were treated with cyclosporin were the longest-reported survivors after he
art-and-lung transplantation at the time.
Unlike Dick Lower’s presentation on Stanford’s early transplantation research back in 1960, when nobody had showed up to hear him, this new report generated intense interest and some attention from the press. Mary Gohlke, the advertising accounts manager at the Mesa Tribune in Arizona, saw a story about our work and wondered whether we could help her. She had been diagnosed with primary pulmonary hypertension and was getting worse. She’d had to stop working when she became so short of breath that she could barely get around. Gohlke had gone to Houston to see Michael DeBakey, a renowned heart surgeon, who had confirmed her cardiologist’s diagnosis. He told her she could not be treated. Someone on DeBakey’s team mentioned a heart-and-lung transplant but added that such a procedure was still “impossible.”
Gohlke was going downhill. She had two teenage sons, and she wasn’t ready to die and leave them behind. After reading about our work, she phoned in the summer of 1980 and asked to speak to Reitz. Bruce was polite but noncommittal. He told her about what we had learned with the monkeys, but emphasized that everything was still experimental. He said that heart-and-lung transplantation might be able to help her in the future. He didn’t say it, but he must have known her future was going to be a short one.
Gohlke called back several months later. She said her condition had worsened. She wanted to know if we would consider her for a transplant. In October, Mary and her husband, Karl, came to Stanford to meet with Bruce and the heart transplant team. She was an excellent candidate—and we were her only hope. But we weren’t ready. We hadn’t yet tested cyclosporin in a human heart transplant. That would have to come first. In early 1981, after several heart transplant patients had received cyclosporin and were doing well, the Institutional Review Board at Stanford gave approval for a combined heart-and-lung transplant in an initial patient. Even though the FDA had approved cyclosporin at Stanford for initial trials in heart transplantation, they had still not approved it for heart-and-lung transplantation. This seemed like a technicality, but without the FDA’s approval, we couldn’t proceed. Mary continued to get sicker. When she heard that we were waiting on the FDA, she called the editor of her newspaper, who had friends in the Arizona congressional delegation. Arizona senator Dennis DeConcini intervened, and suddenly we had a green light from the FDA. Gohlke moved to Palo Alto to be nearby until a donor could be found. We didn’t know how long that would take or how much time we had. When she arrived, Gohlke weighed only seventy-six pounds.
We had not yet done much work on lung preservation for transplantation in the laboratory, because we’d been focused on the operative technique and the subsequent prevention of rejection. We decided to transport any potential donor to Stanford, so that the organs could be removed in room 12 and the transplant done in room 13. This would minimize the time the lungs were out of the body.
Six weeks went by. Mary was fading. Then a nineteen-year-old man was killed in a traffic accident in Southern California. His body was flown to Stanford. Bruce called me that evening with the news that our first heart-and-lung transplant was a go. There was much preparation. John Wallwork was busy getting the consent forms in order, making sure enough blood was available, and calling in the anesthesia and the heart-lung bypass team. Like any team, a surgical crew is only as strong as the weakest link. We were lucky at Stanford that Shumway had gathered an outstanding group of people over the years, and not just the surgeons, but everyone who contributed to an operation, from the anesthetists to the nurses to the intensive-care recovery unit. We were ready now.
The operation began shortly after midnight on March 9, 1981. Ed Stinson and Phil Oyer were in room 12 with the donor. Shumway and Reitz began on Mary Gohlke in room 13. Mary was put on bypass, and her worn-out, failing heart and lungs were carefully removed. We were accustomed to the sight of a totally empty chest in monkeys, but seeing one in a human was different. The heart and lungs were so much bigger. Looking into the empty space where the vital organs should be made us all pause for a second. The heart-lung machine hummed. Mary Gohlke, with no heart and no lungs, was alive.
Stinson and Oyer had removed the donor’s heart and lungs so that they would be ready when room 13 sent for them. Shumway was there to take the blame if anything went wrong. This was how he worked, taking responsibility for bad outcomes and giving all the credit to his colleagues when things went well. He set an example I hoped to follow someday. The mood in the OR was relaxed. The surgical procedures had been practiced many times. We were confident it would go well and believed that no amount of additional research could have made us any better prepared.
Phil Oyer brought the donor heart and lungs into the OR where Gohlke was. They’d been flushed and cooled in a bowl of saline exactly as we had done it in the lab. Reitz and Shumway started to sew them in. First the trachea, the main airway, and then the entrance chamber of the heart, carrying the venous blood, and finally the aorta, the lifeline to the body. When all the air had been purged, the flow of blood to the heart was restored. Slowly, it began to beat. Then the lungs were inflated. The heart-lung machine was disconnected. Mary Gohlke was on her own again. Behind our masks, everyone was smiling.
The operation was finished a little before dawn. Security guards were posted at the entrance to the intensive care unit to discourage interlopers from the press. There was a lot of press interest, as this was an operation that had never turned out well before. I don’t know what they hoped to report—but I was pretty sure I knew what they expected to report.
Gohlke made slow but steady progress. She was weak from her prolonged illness. She had a lot of ground to make up. Some of the nerves to her stomach had been affected by the operation, and she subsequently needed an additional abdominal operation. Yet she was cheerful. Day by day, she got better. Three months after the surgery, Mary Gohlke—the world’s first successful heart-and-lung transplant—was discharged from the hospital. She stayed in the Stanford area for some time to ensure that everything was okay before going home to Arizona, where she went back to work at the Mesa Tribune. Gohlke and Max Jennings, the executive editor of the paper, coauthored a book about her experience titled I’ll Take Tomorrow. Gohlke became an informal ambassador for the Stanford program and took up the cause of organ donation.
We did four more heart-and-lung transplants that year. Two of the patients did not leave the hospital because of postoperative complications. But a new era had begun. The lungs could now be transplanted in a human, bringing hope to thousands of patients with otherwise untreatable lung conditions. Mary Gohlke lived for five more years with her new heart and lungs. She died of complications from a fall. Her heart and lungs showed little signs of rejection.
In the spring of 1982, one year after the Gohlke operation, Bruce Reitz left to become chief of cardiac surgery at Johns Hopkins Hospital. Shumway appointed me the director of heart and lung transplantation and director of the research lab. I was thirty-four years old.
Now that I was in charge of the laboratory, I wanted to concentrate on what I thought was important to advance the program. If we were going to expand the numbers of heart-and-lung transplants we were doing, we would have to find a way to preserve the lungs for an extended period of time when they were out of the body, just as we could do with the heart. We had a grant from the National Institutes of Health (NIH), which we supplemented with money from the clinical program. Dr. Shumway never restricted our use of these funds, which were plentiful in those days. Nowadays university hospitals are often better at counting their money than spending it.
Director of heart-lung transplantation and the experimental laboratories at Stanford. I was thirty-four.
The lungs present a unique challenge. Unlike the other organs, they are exposed to the outside air. Indeed, that is central to their function. They have to transfer oxygen from the air to the blood. The cells that make up that interface are fragile, and their blood supply is unusual. The pulmonary artery, the artery from the heart to the lungs, does not car
ry oxygenated red blood as arteries do for every other organ. The pulmonary artery carries deoxygenated blue blood—to which the lungs add oxygen. But the lungs themselves also need oxygen, and so in addition to the pulmonary artery they are supplied by the bronchial arteries, which come directly off the aorta and carry oxygenated blood.
I did my first human heart-and-lung transplant in June 1982. This was Stanford’s sixth and the world’s ninth. The recipient was a young man who had had a previous thoracic operation for a congenital condition. He now had irreversible lung disease and a severely damaged heart. Shumway, who had been present for all the previous heart-and-lung transplants, was out of town. We started the operation in the early evening. Phil Oyer was in the next room with the donor. We were about to learn a terrible lesson.
When I opened the chest, I found that the patient’s lungs were embedded in a dense matrix of scar tissue from the previous surgery, which had gone in through the side. It was as if they were cemented in. I wasn’t sure I could get them out. New arterial vessels had formed in the scar tissue to supply more blood to the dying lungs. Everything I touched started to bleed. But there was no going back. The patient would die if we stopped. It took forever to get the lungs and heart out, and it was bloody. In the early hours of the morning, I started to sew in the new heart and lungs. That was the easy part. The bleeding from all the raw surfaces continued, and the new lungs were damaged by the repeated blood transfusions we had to give. We worked through the night, but it was hopeless. After twelve hours in the OR, there was nothing more we could do. I was devastated, and so exhausted I could barely stand.
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