A complex puzzle realized: US achieves one-millionth organ transplant: Decades of visionary scientists, skilled surgeons, and courageous patients have made this miraculous milestone a reality

Abstract

Key Points•More than 400,000 people alive today have a functioning transplant.•Many, if not all, of the transplant surgeons practicing today can trace their professional lineage through a handful of surgical pioneers.•In the 1980s, science and politics came together to form the US organ transplant system.•Tacrolimus lowered rejection rates, and its discovery accelerated the transition of transplants from an experimental to a clinical procedure. In September 2022, the US reached a momentous milestone, completing its one-millionth organ transplant and rendering organ transplantation almost commonplace. In 2021 alone, >40,000 transplantations took place in this country and >400,000 people now live with a functioning transplant. This achievement has been accomplished thanks to a growing public commitment to organ donation, the collective skill and dedication of thousands of organ donation and transplant professionals, policymakers who embraced a revolutionary way of saving lives, and all the early organ recipients who took that giant leap of faith decades ago. Typically, “The AJT Report” looks forward, examining topics, such as the expansion of more equitable organ allocation policies, the increasing focus on nontraditional donors, and the continuous evolution of organ preservation techniques. However, on this noteworthy occasion, we look back and honor those individuals who did so much to advance the field of transplantation and, in so doing, saved hundreds of thousands of lives. Here are just a few of the pioneers who helped change the thinking and practice of transplantation: Joseph E. Murray, MD: In 1954, Dr. Murray performed the first successful kidney transplant between identical twins at the Peter Bent Brigham Hospital at Harvard Medical School in Boston, Massachusetts; in 1990, he received the Nobel Prize. Thomas E. Starzl, MD, PhD: Dubbed the father of modern transplantation, Dr. Starzl performed the first human liver transplants in 1963. John Najarian, MD: In the 1970s, Dr. Najarian embraced the then-new technique of lymphocyte culture in the creation of anti-lymphocyte globulin therapy and pioneered work in kidney transplantations in children at the University of Minnesota in Minneapolis. Norm Shumway, MD: Considered the father of heart transplantation, Dr. Shumway grew his renowned clinical heart program at Stanford University in Palo Alto, California, in the 1970s. Sir Roy Calne, MD: An early kidney transplant surgeon at Cambridge University in the UK, Dr. Calne was responsible for the world's first combined liver, heart, and lung transplant in 1987, helping to advance transplant science in the US. Many, if not all of the transplant surgeons practicing today, can trace their lineage through one or more of the above pioneers. One such prodigy is John Fung, MD, PhD, chief of the section of transplant surgery and the codirector of the Transplant Institute of the University of Chicago. Dr. Fung joined Dr. Starzl in Pittsburgh in 1984 and managed the first 10 liver recipients who, in 1989, were switched from cyclosporine to tacrolimus. In his book The Puzzle People: Memoirs of a Transplant Surgeon (University of Pittsburgh Press, 1992), Dr. Starzl discusses Dr. Fung. “The surgeon who managed these trials was another new breed whose talents allowed fresh ideas and technologies to force their way into the light as flowers do through cracks in concrete.” According to Dr. Starzl, Dr. Fung had been “a halfway surgeon and a complete immunologist” when he came to Pittsburgh, having been only midway in his residency training in general surgery at the University of Rochester in New York when he chose to take 2 years off for laboratory research.1Eiseman B. The puzzle people: memoirs of a transplant surgeon.Arch Surg. 1992; 127: 1009-1011Google Scholar Dr. Fung was not yet practicing medicine in the early days of transplantation when Dr. Starzl’s generation was working with a 1-year kidney transplant survival rate of 33%. Those were the days when many patients experienced what Dr. Fung describes as “nasty rejections.” Then came tacrolimus. Known then as FK506, tacrolimus lowered rejection rates, and its discovery accelerated the transition of transplantation from an experimental procedure to a clinical one. “When you were part of that era, watching things get better, [you understand that] everybody gets to have credit for it,” reflects Dr. Fung. While science has been critical to the mainstreaming of solid organ transplantation, so too have been policy shifts. Dr. Fung tells a little-known story about how transplant science in its infancy encountered a politician in his professional infancy, and how together, they formed a bond that birthed the US transplant system. The chance meeting occurred at a kitchen table in Chicago in the early 1950s. Loyal Davis, MD, a neurosurgeon, had been the chair of the department of surgery at Northwestern University in Chicago for 16 years when Dr. Starzl arrived for his first day of medical school. Dr. Davis would remain the chair for another 16 years and, most of that time, served as the editor for Surgery, Gynecology, and Obstetrics, the official journal of the American College of Surgeons. According to Dr. Fung, at one time, Dr. Starzl lived with Dr. Davis and thus, was acquainted with his daughter, Nancy. One day, while working at the kitchen table at Dr. Davis’ house, Dr. Starzl met Ms Davis’ beau, a young man named Ronald Reagan. Over time, the 2 men got to know each other well. Fast forward to 1981. The transplant community had established the quality and safety of antirejection treatment with a combination of cyclosporine and prednisone. Unfortunately, because of administrative roadblocks, there was no way to systematically apply this advance to organs other than the kidney because transplantation of the liver, heart, lungs, pancreas—and all organs other than the kidney—were classified as “experimental.” Government agencies had used this designation for more than a decade, ostensibly because liver and heart transplantation results were too poor to be considered a “service.” The procedures were expensive, and payors were reluctant to underwrite the hospital bills. The US president at the time was the newly elected Mr. Reagan. Later that year, he would nominate C. Everett Koop, MD, as Surgeon General of the United States. Dr. Koop had recently retired as surgeon-in-chief of the Children’s Hospital of Philadelphia. President Reagan assigned Dr. Koop the job of reviewing liver transplantation results. In so doing, he met with Dr. Starzl to discuss the problem of the experimental label. Dr. Koop had set aside most of the morning for the conversation about liver transplants and listened intently. Surgeon General Koop was sworn into office in January 1982. With his earlier conversation with Dr. Starzl in mind, he held a Consensus Development Conference on liver transplantation. Here, Dr. Starzl presented his research and the results of his operations. He explained how Medicare, the government’s most powerful and pervasive health care provider, had determined the operations to be experimental and nonreimbursable for costs and how insurance companies had cited this determination to avoid covering the procedure. Convinced by Dr. Starzl’s argument, Surgeon General Koop declared that liver transplantation would no longer be deemed an experimental procedure but rather a “clinical service.” In addition to paving the way for that critical determination, the President and Mrs Reagan provided powerful and highly public support for transplantation. Starting in 1983, the President campaigned actively to increase public awareness of the organ shortage. “President Reagan’s attention to the problem had a greater positive impact on organ donation than any other single factor in the 1980s,” Dr. Starzl noted in his book. In 1984, in signing the National Organ Transplant Act, the President stated, “Over the last 3 years, I have urged the American people to remember that many lives could be saved through generous donations of lifesaving organs. I have been encouraged by the response of the media and the public to this compassionate cause, and this act will serve to support this ongoing work.” 2Reagan R. Statement on Signing the National Organ Transplant Act. Ronald Reagan Presidential Library & Museum, 1984https://www.reaganlibrary.gov/archives/speech/statement-signing-national-organ-transplant-actDate accessed: November 18, 2022Google Scholar That same year, National Organ Transplant Act established the Organ Procurement and Transplantation Network to maintain a national registry for organ matching. Is it safe to say that the seeds of the Organ Procurement and Transplantation Network were planted at that kitchen table in Chicago in the early 1950s? After all, the first transplant was performed that same year at Little Company of Mary Hospital in Evergreen Park on the south side of Chicago by surgeons Richard Lawler, MD, James West, MD, and Raymond Murphy, MD. Without an immunosuppressive protocol, the patient, Ruth Tucker rejected her new kidney which had to be removed 10 months after the surgery. Thanks to the vision and skill of such practitioners and the bold risk-taking of all Ruth Tuckers, we can celebrate 1 million transplants performed today. A transplant team at Duke Health in Durham, North Carolina, has used the living arteries and valves from a freshly donated heart to perform the world’s first partial heart transplant on a 5-pound newborn, Owen Monroe. Owen was born with his 2 main heart arteries fused—a condition called truncus arteriosis. His one vessel also had a leaky valve, making it unlikely that he would survive the wait for a full heart transplant. A child with Owen’s condition would typically receive the 2 preserved cadaver arteries with valves. Instead, Joseph W. Turek, MD, PhD, Duke’s chief of pediatric cardiac surgery, used living tissue and valves taken from a donor’s heart with strong valves but weak muscles, precluding its eligibility for a full transplant. The surgery was able to use a donated heart that would otherwise have been discarded. The team at Duke anticipates that the novel transplant will eliminate the need for the multiple open-heart surgeries that typically occur every time a child outgrows an old valve. The innovative surgery, which occurred on April 22, 2022, appears to be a success, as evidenced by Owen’s remarkable growth and improvements. Experts at Duke have expressed hope that a similar approach could be used to treat common valve replacements in children, providing them with donated tissue that grows as they grow. Lara C. Pullen, PhD, is a cofounder of OrphanCures, a company that helps bring drugs with potential for treating rare disease to market.