Introduction
Working in transplantation brings pleasures and disappointments. The greatest reward has been seeing the patients, who without transplantation would have been dead, be alive, thrive, and so many times exceed all expectations. Yet, there is also a professional side, marked with struggles and disappointments but also by moments so extraordinary that they eclipsed every hardship. We had a great mentor…. We met new friends…. We traveled in new places…. We lived some great moments. There have also been some moments that defined our lives. In my surgical life, 3 such moments stand apart as milestones in my life in transplantation.

A Telephone Call
The first one was a phone call. I was about to finish the surgical residency at the State University of New York at Stony Brook. After 6 years of training, my surgical experience was as broad and comprehensive as any of my peers. I was now qualified to sit the Surgical Boards. And then what? I could start a private practice or take a junior faculty post in general surgery, but neither felt like my path. I needed more training. Cardiac, thoracic, vascular, and colorectal surgery all offered promising prospects—but I was not attracted to them. My mind was set on the liver. My training there was incomplete; like most general surgeons, I could do cholecystectomies and bile duct explorations but little more. This was the usual surgical repertoire. Few surgeons had broader experience—there was no formal training or certification in liver surgery. The liver, the body’s largest solid organ, was complex, hidden beneath layers of bleeding tissue. At the time, only three centers performed high-volume liver surgery: (1) Sloan-Kettering in New York, under Dr. Joseph Fortner, specializing in hepatic resections for cancer; (2)Emory University in Atlanta, led by Dr. W. Dean Warren, pioneer of the distal splenorenal shunt for portal hypertension; and (3) the University of Pittsburgh, where Dr. Thomas Starzl—who had performed the first successful liver transplant—had recently arrived from Denver. I wrote to all three. Sloan-Kettering and Emory replied quickly: positions were long filled. Starzl, who was my first choice, took longer—but finally invited me for an interview. I had studied his work and admired his life’s story—the depth, the vision, the sheer scope of what he had accomplished. I first saw Dr. Thomas Starzl with Dr. John Najarian at the American College of Surgeons meeting in Chicago, while I was still a trainee. Najarian, a former offensive tackle at Berkeley, was known for his size, strength, and toughness — yet he was performing kidney transplants in the smallest infants with remarkable success. Starzl was his opposite: tall, lean, composed. He used language as deliberately as a scalpel. That day, the two discussed one of the gravest hazards of early transplantation—hepatitis B transmission to staff. There was no vaccine, no effective treatment. Many of their colleagues fell ill; some died. They described how they both nearly lost their lives and how they returned to work as soon as their eyes were no longer jaundiced. I wanted to be like them…. When his letter came, I was on the next plane to Pittsburgh! I had 2 highly complementary letters of recommendation: from my chairman at the University of Stone Brook, Dr. Harry Soroff—a pioneering cardiac surgeon—and Dr. Fabio Giron—a well-known vascular surgeon. I arrived in Pittsburgh on a frigid day in November. The steps to Dr. Starzl’s office in the basement of the Falk Clinic were frozen. Inside, there was controlled chaos; the space was the command center for the entire program. Only one surgeon was there: Dr. Shunzaburo (“Shun”) Iwatsuki, the sole member of the Denver team who had followed Starzl to Pittsburgh. He reminded me of a Samurai: few words, cut and dry. After a brief discussion, he sent me off to wait for Starzl, saying, “He makes the decisions. It doesn’t matter what I think.” I took a seat and waited. Nancy Hartman, Starzl’s assistant—a pleasant, slightly chubby, Midwesterner—told me he had been operating all night and might be a bit late. Nearby, Johny, another assistant, was typing furiously, thrilled with her word processor because she no longer had to retype entire manuscripts every time Starzl made revisions, which he did a lot of times. Then Starzl appeared—ski jacket on, bag of M&Ms in hand. “Hi Andy … you want some?” “No, thank you, Dr. Starzl.” He asked why I was there and what interested me. When I mentioned liver surgery, he replied that they did some of that in Pittsburgh—but the real focus was liver transplantation. He asked about my training; I listed the operations I had done. He was not impressed. “Those procedures were performed only as part of transplant care.” He read my recommendation letters, praised their tone, but added that he didn’t know the authors. He wanted a letter from Felix Rappaport—the only surgeon he knew at Stony Brook. I explained that I had never worked with him. Starzl was unmoved. He wanted a letter from Felix. Dr. Felix Rappaport was a Transplant pioneer. He established a Kidney Transplant Program at Stony Brook, at the sunset of his surgical career, working with junior staff surgeons he had hired. One of them had been my chief resident a couple of years earlier. As soon as the interview concluded, I ran out and found a pay phone. Fortunately, I had enough quarters to make the long-distance call. It was freezing cold. I called Linda Brochhousen, the omnipresent and omnipotent assistant at the surgery office at Stony Brook and asked if she could arrange for Dr. Rappaport to see me as soon as possible. Linda delivered: I had an appointment with him the following day. Dr. Rappaport was kind but firm. He could not write me a letter because he did not know me. I asked if, having been at Stony Brook for 4 years, he might inquire about me and send his impression to Dr. Starzl. He reluctantly agreed. Two days later, he called me to his office. He showed me a copy of the letter he had already sent to Dr. Starzl. In it, he wrote that he had asked many members of the faculty about me. Several told him I was the best resident they had ever trained; others warned him to stay away from me—that I was not a good person. I told him that, with such a letter, my chances were probably over. He replied that it was already “water under the bridge.” In retrospect, I believe the source of that mortal judgment was my former chief resident, recently recruited by Dr. Rappaport. During our time together, I had done all his work, including the surgeries and rounds he was supposed to perform. He was fundamentally lazy. At the time, he didn’t seem to mind—but I think he was waiting for an opportunity to get back at me. At the same time, my wife, Patricia was completing her internal medicine specialty training at the Einstein/Montefiore-North Central Bronx Hospital Program. She passed the board exams and quickly distinguished herself among her peers. She wasn’t just my favorite—she was admired and respected by everyone she worked with. Out of 20 graduating residents, she was one of only 2 chosen for an additional year as Chief Resident. During her “Chief” year, she chose to specialize in endocrinology, with a particular focus on diabetes. While I was still searching for my path, she was accepted to a prestigious fellowship at Harvard’s Joslin Clinic, renowned for its work in childhood diabetes. We agreed she should accept and see where it would lead. If we had to, we could live apart—my parents had done so for years—my father was a chief engineer in the Greek Merchant Marine, yet they remained close and thrived together. My prospects for a fellowship in Pittsburgh seemed slim, so I looked to Boston. I had a tentative offer for a 1-year fellowship in parenteral nutrition at Massachusetts General Hospital—the main Harvard teaching hospital. It wasn’t the path I had envisioned, but we would be in the same city and I would have a foothold until the right opportunity appeared. It was a late evening in May 1983, on the Surgical Ward of the Northport VA Hospital on Long Island, New York. The day had been long—and for many of us it followed a long night. The scheduled operations were behind us and now came the final sign-out rounds. When rounds ended, those on call would remain in the hospital; the rest would head home. I was the Chief. I was always on. I was leading the way with the team, the surgical residents, medical students, and the head nurse. Then out of the blue the overhead speakers came to life—an incoming call for me. We all used pagers those days—the old “Bell Boys”—for most calls. But when it came over the overhead speakers, sounding the alarm throughout the hospital, it meant urgency—a trauma or an emergency. I handed the rounds to the senior resident and ran to the nursing station to pick up the call. It was Nancy Hartman. “Please hold for Dr. Starzl.” Then his voice, could not be mistaken for anyone else. “Andy, are you still interested in that job?” “Absolutely, Dr. Starzl,” I said aloud. Inside my head, I was shouting: Am I interested in that job? Are you kidding me? I had given up hope of ever hearing from him. After Dr. Rappaport’s letter, I was certain Pittsburgh was closed to me. The program was the best in the country. Competition was brutal. I doubted Starzl would take anyone with questionable recommendations. And yet here was Dr. Starzl—inviting me to join him. “Yes, Dr. Starzl. Thank you for your call. I’ll be there July 1.” I called Patricia the moment I hung up. The call transformed everything. We were both elated. Linda Brockhousen was still finishing her work; my news was a most joyous ending to her long day. It was one of the happiest days of my life…. That night, I learned something about Starzl that would stay with me: he valued straight talk. He despised lies. I am the same way. The truth is the only way forward. Felix Rappaport had done me a service. He always spoke the truth, the brutal truth. He would not have it any other way. I called him the next morning; he was delighted. We met several times at transplant meetings, and we stayed friends until his death in 2001. His obituary in the JAMA (Journal of the American Medical Association) was written by Starzl himself. Reading it, one can see the respect between them—and why Starzl insisted that he wanted to see a letter from him. As for the junior faculty member who, I suspect, gave the unfavorable report, I have not seen him.

A Cardiac Arrest
The second greatest moment followed a cardiac arrest. My career in transplantation began on the wrong foot. July 1, 1983, my first day as a transplant fellow, should have been a day of celebration…. I was part of one of the finest training programs in the world. The reality was different. Far from being celebrated, the program was viewed with suspicion and even contempt within the hospital in Pittsburgh. A White Paper was signed by 54 residents and interns of the Department of Medicine and denounced liver transplantation as unrealistic, possibly unethical. They refused to care for the liver transplant patients before or after the transplant. There were notable exceptions among the Faculty: David Van Thiel in hepatology, Åke Grenvik in the surgical intensive care unit (ICU), and Yugoo Kang in anesthesia. But, beyond these few allies, the atmosphere ranged from indifference to open hostility. For all practical purposes, Pittsburgh was the only active liver transplant program in the United States. As a result, the sickest liver patients from across the country came to the University of Pittsburgh Presbyterian Medical Center—the UPMC. Because the hospital house staff declined responsibility, the entire burden of care fell upon the “Clinical Transplant Team”—3 transplant fellows and 2 surgical residents. On July 1, one of the 3 fellows, Ira Fox, went to Kathmandu to clear his mind in the pure Himalayan air before beginning his fellowship, he was not there…. Walt Andrews, an excellent pediatric surgeon, began his training with a planned kidney transplant rotation. That left me, Andy, with the two residents, one of whom started with a vacation, as was customary for residents rotating on the transplant service. The other, Mary Mancini, was a hardworking chief resident and also a devoted Catholic nun who shared my burden. She eventually became a cardiac surgeon. Together, we managed the sickest patients imaginable, coordinated the operating room, and timed each liver transplant with precision. This was critical because permissible cold ischemia was short and could not be extended with delays. Things got smoother with time, but criticism was constant. I ended up taking care of a lot of the patients, a lot of the time. This gave me great experience with the patients but not much time in the operating room. Even when I was there, I had to respond to urgent calls. I finished my 2-year training having done kidneys but only one liver transplant start to finish. Rob Gordon was the person—the only one—who allowed me to do it and supervised me. Dr. Starzl openly questioned whether I would ever be capable of doing liver transplants. He said of me in his book that “no one worked so hard and achieved so little.” In reality, I had achieved something very important—I learned more about the patients than anybody else. This all changed in Dallas. Dr. Starzl, on the invitation of Dr. John Fordtran, recruited Göran Klintmalm to head a sister program at Baylor University Hospital in Dallas, Texas in 1985. I was asked to go help him—and I did. Göran was very gracious and very supportive. I was doing the recoveries of the livers, and then he assisted me to do the liver transplants. I never failed. Dr. Starzl took note and asked me to stay in Pittsburgh as junior staff. I was still not totally trusted. He called me to his office one day together with Satoru Todo. Todo was in charge of the animal lab and was an exceptionally good surgeon but was not allowed to have any responsible position in the hospital. So Starzl told us that from now on we would be allowed to operate independently, but only together—never by ourselves. And I have to say, that was great. We were like Siamese twins, alternating the surgeon and first assistant positions. Then one day I was operating on a 50-some-year-old man from Connecticut. The liver transplant was progressing well until I unclamped the inflow. The patient had a cardiac arrest. We could not reverse it. Not by indirect massage. Not by direct massage of the heart after we opened the diaphragm. We worked more than an hour. The anesthesiologist, Judy Freeman—an excellent anesthesiologist, by the way—advised us to stop. The patient would be brain dead even if we restored circulation because of ischemia of the brain. We refused. We kept working. She called Dr. Starzl. It was probably 3:00 or 4:00 in the morning. He appeared at the door of the operating room, in his ski jacket. He asked me if I wanted to stop. I said no. He said okay and left. We kept working. Then suddenly, the heart kicked in. I was able to finish the transplant. The liver seemed to be working. I stayed with the patient. As we were transporting the patient from the operating table to the stretcher to move him to the ICU, he woke up and started communicating with me. He wanted to have the endotracheal tube removed because it was bothering him. He was extubated very quickly in the ICU and seemed totally normal. In fact, he was totally normal. He did not have any damage. It was one of the happiest moments of my life. So I called Dr. Starzl. He said that was fine and to go to work. What I didn’t know—and none of us knew—was that he was in the amphitheater of the operating room and had observed the whole drama. We found that out when we read his book The Puzzle People. He described that day, saying that “I started the day as a trainee and finished it as a professor.” In retrospect, the patient was probably severely hypothermic and that was the reason he had the cardiac arrest—and also the reason his brain was protected until the heart function was restored.

Valen and Uterus Transplantation:A Pro-Vital Transplant
The stage for what became the third happiest moment of my surgical career was set after the completion of a multivisceral transplant. We had replaced the liver, stomach, pancreas, and small intestine of a young woman and hopefully restored her health — except she could never have a baby because she had previously undergone a hysterectomy. I found myself wondering, could we have also done a uterus transplant as well? The team in Gothenburg had already shown that transplantation of the uterus was not only possible, but, in small animals, it produced normal offspring. We needed proof in large mammals, so we went to work. Our team at the University of Miami obtained animals from the mini-swine colony maintained by Dr. David Sachs in Boston. For years, these animals had served as a critical translational bridge between rodent models and human trials. With my associates, Drs. Akin Tekin, Takis Tryfonopoulos, and Tom de Faria, we performed heterotopic uterus transplants in these animals. We needed to know whether uterine grafts were highly immunogenic, like intestines, or more tolerant, like livers. We used a heterotopic model. Vascular anastomoses were between the donor aorta and inferior vena cava and the recipient iliac vessels. The donor vagina was exteriorized, allowing easy access for observation and biopsies. We showed that the transplant could be done safely, with long-term survival. This model allowed us to study the biological behavior of the uterine graft—its rejections and responses to treatment. Briefly, they proved to be something in between livers and intestines, behaving much like kidney allografts. From this, we were able to plan what we thought was a perfect immunosuppressive regimen. I was at the University of Gothenburg receiving an honorary PhD when my good friend Michael Olausson, then chief of transplantation, introduced me to Mats Brännström and his team. We decided to collaborate and together performed uterus transplants in baboons. It was an intercontinental effort—carried out at the Mannheimer Institute in Florida and at a WHO-approved facility in Nairobi, because experiments with primates were virtually impossible in Sweden. In Florida, we performed orthotopic uterus transplants. All animals survived the surgery and immediate postoperative course. Long-term survival was very difficult because adequate immunosuppression had to be given parenterally. Nevertheless, it was clear that the animals that survived long term behaved like the mini-swine. Mats invited us to participate in the first clinical trial, which was about to start in Gothenburg. While we were awaiting approvals, Ömer Özkan and his team in Antalya performed a uterus transplant from a deceased donor in August 2011—this was the first successful human uterus transplant in the world! The Gothenburg trial, the first series from living donors in the world, began in September 2012. Of the 9 initial procedures, 7 were successful. Yet trepidation hung over us—because, until then, no baby had ever been born after a uterus transplant in humans, not even in a large mammal. Would the tiny uterine vessels get big enough to support the pregnancy and a baby? Would the baby be normal? The only other successful transplant, Ömer’s, had not yet produced a birth. That changed forever on September 4, 2014, when hope became reality. Vincent was born—a healthy baby boy. Vincent’s birth was the proof of principle: a living, healthy child. It had been said that uterus transplants are not “vital” transplants. They are not vital for the mother. Vincent showed that, although this may be true for the mother, uterus transplantation is vital for the baby. It is a new type of transplant, not vital per se but a pro-vital transplant. In Cleveland, we had powerful team of OB-GYN and transplant surgeons but also had a very complex approval process before we could start. Our first transplant, which took place in February 2016, had to be removed 2 weeks after implantation due disruption of the left arterial anastomosis from a Candida albicans infection. Our second transplant gave a perfectly healthy baby girl—Valen. She was born 19 months after the transplant by Cesarean section. The amniotic sac was intact. Hearing Valen’s healthy, loud cry was the third happiest moment of my surgical career. She is now 6 years old and goes to school. Six of our seven subsequent uterus transplants, all from deceased donors, were successful and have resulted in 5 healthy babies—and 1 more is on the way. Transplantation gave us moments of joy that cannot be measured. They are not written in our papers—but they happened, they filled our lives, and they cannot be ignored….