Transplantation (medicine)

• 1. Introduction

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  Transplantation is the medical procedure that lets a heart beat in a stranger's chest. An organ, tissue, or cluster of cells is removed from one body and placed in another, usually to replace a damaged or missing function. The donor and the recipient might lie in adjacent rooms, or an organ might travel from one site to a distant operating table. Sometimes the donor and recipient are the same person. Sometimes they are identical twins. Sometimes, in the strangest version of all, the donor is a pig.

  Kidneys are the organ moved most often around the world, followed by the liver and the heart. Yet for every person who receives one, many more wait. Global analyses suggest available transplants meet only a minority of worldwide need. How did surgeons learn to move a living organ from one body to another and have it survive? Why does the recipient's own immune system treat a gift of life as an enemy? And how did a field built on saving lives become tangled with prisons, black markets, and questions about when a person is truly dead?

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• 2. The Body Says No

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  Gasparo Tagliacozzi noticed something that would not be explained for centuries. The Italian surgeon performed successful skin grafts using a person's own tissue, yet he failed consistently when he tried to graft skin from one person to another. In his 1596 work De Curtorum Chirurgia per Insitionem, he blamed the failure on the force and power of individuality. He had stumbled onto rejection long before anyone could understand it.

  Rejection is the central problem of the whole field. Because of the genetic difference between a transplanted organ and its recipient, the recipient's immune system identifies the new organ as foreign and tries to destroy it. This can lead to transplant failure and the urgent need to remove the organ. The risk can be estimated by measuring the panel-reactive antibody level. It can be reduced by serotyping to find the best donor-recipient match, and by immunosuppressant drugs.

  The vocabulary of transplantation is really a vocabulary of how much the body will tolerate. An autograft moves tissue within a single person, so it needs no immunosuppression because the tissue is genetically identical. An allograft moves an organ or tissue between two genetically non-identical members of the same species, and most human transplants are allografts. An isograft is the rare exception that fools the immune system completely: organs moved between identical twins, anatomically like an allograft but provoking no immune response. That distinction would decide the outcome of the very first successful organ transplant.

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• 3. First Successes

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  Theodor Kocher had perfected something dangerous: the total removal of the thyroid gland. The Swiss surgeon could take out the whole organ without the patient dying from the operation. But by 1883 he noticed that patients left without a thyroid developed a strange complex of symptoms, the signs we now associate with a lack of thyroid hormone. So Kocher implanted thyroid tissue back into these people and reversed the symptoms. That implantation, meant to replace an organ's function, was the first transplant in the modern sense. Kocher won the Nobel Prize in 1909 for discovering the function of the thyroid gland, and his procedure became the model for transplanting adrenal glands, parathyroids, pancreas, ovary, testicles, and kidney.

  The French surgeon Alexis Carrel built the next foundation. Working with Charles Guthrie in the early 1900s, he developed the suturing techniques to join arteries and veins, the anastomosis operations that later transplant surgery would depend on. From 1902 he performed transplant experiments on dogs, successfully moving kidneys, hearts, and spleens. He was among the first to recognize the problem of rejection, which would block progress for decades. Carrel won the 1912 Nobel Prize in Physiology or Medicine.

  The breakthrough finally came in 1954 at the Brigham and Women's Hospital in Boston. Dr. Joseph Murray performed the first successful kidney transplant, and he too would receive the Nobel Prize. The success rested on a family bond. The recipient, Richard Herrick of Maine, was in the Navy and had fallen severely ill with acute renal failure. His donor was his identical twin brother Ronald. Because the brothers were genetically identical, no anti-rejection medication was needed, and Richard lived another eight years. Before this case, transplant recipients had not survived more than thirty days. J. Hartwell Harrison performed the organ removal that made it possible.

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• 4. The Heart Race

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  The heart deteriorates within minutes of death, so any transplant would have to be performed at great speed, and it also required the heart-lung machine. James Hardy, the lung pioneer, was ready to attempt a human heart transplant in 1964. But when the heart of his comatose patient Boyd Rush failed prematurely and no human donor was available, Hardy used a chimpanzee heart. It beat in his patient's chest for about an hour, then stopped.

  The first partial success came on the 3rd of December 1967, when Christiaan Barnard of Cape Town, South Africa, performed the world's first human-to-human heart transplant. The recipient was Louis Washkansky, who survived for eighteen days amid what many saw as a distasteful publicity circus. A recent study suggests the donor, Denise Darvall, was not brain-dead, and that her heart was arrested artificially, resembling a non-voluntary active euthanasia. The media interest set off a wave of operations. More than a hundred heart transplants were performed in 1968-69, yet almost every patient died within sixty days. Barnard's second patient, Philip Blaiberg, lived for nineteen months.

  The drug cyclosporine turned transplantation from research surgery into life-saving treatment. Discovered in 1970, it followed earlier work by British surgeon Peter Medawar, who identified the immune reactions behind rejection in 1951 and suggested immunosuppressive drugs. By 1984 two-thirds of all heart transplant patients survived five years or more. On the 9th of March 1981, the first successful heart-lung transplant took place at Stanford University Hospital, and head surgeon Bruce Reitz credited the recovery to cyclosporine.

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• 5. Crossing The Species Line

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  A porcine heart valve transplant is quite common and successful, a routine example of moving tissue from one species to another. This is xenotransplantation, and it is often extremely dangerous because of the increased risk of non-functional compatibility, rejection, and disease carried in the tissue. In the early 1960s, before long-term dialysis existed, Keith Reemtsma and his colleagues at Tulane University in New Orleans transplanted chimpanzee kidneys into thirteen human patients. Most lived only one to two months. But in 1964 a 23-year-old woman lived for nine months and even returned to her job as a school teacher, until she suddenly collapsed and died, her kidneys showing no sign of rejection.

  The appeal of crossing the species line is the shortage of human organs. In the opposite direction, attempts have been made to transplant human fetal hearts and kidneys into animals for future use in patients. Clinical trials with porcine islets of Langerhans have shown promise for treating type 1 diabetes. Genetically modified porcine organs implanted into humans have provided early safety and feasibility data, while identifying important infectious and immunologic risks.

  Those risks proved fatal in 2022, when the first successful heart transplant from a pig to a human patient took place in the United States. The recipient later died after the pig's heart was found to be infected with porcine cytomegalovirus.

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• 6. Closing The Loop

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  For a person with cystic fibrosis, replacing both the heart and lungs together is technically easier and more successful than replacing the lungs alone. Since the recipient's own heart is usually healthy, it can then be transplanted into a second person who needs a heart, turning the cystic fibrosis patient into a living heart donor. This chaining of organs is called a domino transplant. In a 2016 case at Stanford Medical Center, two patients and three surgical teams were involved. A woman with cystic fibrosis received a heart and lungs from a deceased donor, and her own heart went to a woman with right ventricular dysplasia, a condition causing a dangerously abnormal heart rhythm. Both recovered and met six weeks after their simultaneous surgeries.

  The domino logic extends to living kidney donors who cannot match their intended recipient. In a paired exchange, a spouse willing to donate but biologically incompatible gives a kidney to a matching stranger, whose own incompatible partner donates in return. The surgeries are scheduled simultaneously in case a donor backs out, and the couples are kept anonymous until afterward. The first pair exchange transplant in the US took place in 2001 at Johns Hopkins Hospital. The idea reaches back to a 1997 New England Journal of Medicine article by L.F. Ross, and to a 1986 proposal by Felix T. Rapport.

  The chains grew staggeringly long. In February 2009 the first complex multihospital kidney exchange involving twelve people was performed by The Johns Hopkins Hospital, Barnes-Jewish Hospital in St. Louis, and Integris Baptist Medical Center in Oklahoma City. In December 2009 a thirteen-organ, thirteen-recipient exchange was coordinated through Georgetown University Hospital and Washington Hospital Center. In February 2012 the last link in a record sixty-person domino chain of thirty kidney transplants was completed. A single altruistic donor, a good Samaritan kidney, can set such a chain in motion.

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• 7. Who Gets An Organ

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  Less than 3% of all deaths in the United States are the result of brain death, which means the overwhelming majority of deaths are ineligible for organ donation. That scarcity defines everything about how organs are shared. Brain-dead donors are among the most common and ideal sources, since they are often young and healthy. When that pathway is unavailable, donation after circulatory death offers organs with inferior outcomes; liver transplants from such donors show significantly lower graft survival due to biliary complications and primary nonfunction.

  The foundation for national policy in the United States was laid by the National Organ Transplant Act of 1984, which made organ sales illegal and created the Organ Procurement and Transplantation Network. The United Network for Organ Sharing, or UNOS, allocates organs by methods judged most equitable. Liver allocation depends partly on the MELD score, a measure derived from laboratory values that reflect how severe a patient's liver disease has become. By the 9th of September 2022, the United States had reached one million cumulative transplants.

  The rules are tested when people try to bend them. In 2003 at Duke University, a teenage girl received a heart-lung transplant with organs of an incompatible blood type, and after the error she was given priority for a second transplant despite being in such poor condition that she would not normally qualify. Steven Tsui, head of the transplant team at Papworth Hospital in the UK, framed the dilemma plainly in 2008. He said that if a center does thirty heart transplants in an average year, there is no point putting sixty people on the waiting list, because half will die, and it is not right to give them false hope.

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• 8. The Marketplace Of Bodies

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  In Chennai, southern India, poor fishermen sold their kidneys after the Indian Ocean tsunami of the 26th of December 2004 destroyed their livelihoods. About a hundred people, mostly women, sold a kidney for forty thousand to sixty thousand rupees, roughly nine hundred to thirteen hundred and fifty US dollars. Thilakavathy Agatheesh, thirty, who sold her kidney in May 2005 for forty thousand rupees, said she used to earn money selling fish, but post-surgery stomach cramps now keep her from work. Most kidney sellers say selling their kidney was a mistake.

  The prices reveal a stark geography. In the illegal black market a kidney may cost above one hundred and sixty thousand dollars, with middlemen taking most of it, and recipients often catching hepatitis or HIV. In Iran, which has had a legal kidney market since 1988, the donor is paid roughly twelve hundred dollars by the government plus additional funds. Economists Gary Becker and Julio Elias modeled a free market and estimated a price of fifteen thousand dollars for a human kidney and thirty-two thousand for a liver. In Pakistan, Dr. Farhat Moazam reported that in some villages forty to fifty percent of residents have only one kidney, having sold the other.

  The darkest allegations involve organs taken without any consent at all. The World Medical Association holds that prisoners cannot give free and voluntary consent, so their organs must not be used. According to former Chinese Deputy Minister of Health Huang Jiefu, the practice of transplanting organs from executed prisoners is still occurring, and he admitted that roughly 95% of all organs used in China came from executed prisoners. The 2006 Kilgour-Matas report stated that the source of 41,500 transplants between 2000 and 2005 was unexplained, and alleged large-scale organ seizures from unwilling Falun Gong practitioners. China made the selling of organs illegal as of July 2006, requiring that prisoner donors file consent, even as doctors abroad continued to question its high capital punishment rate.

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