When plastic surgeon Joseph E. Murray was awarded the Nobel Prize in Physiology or Medicine in 1990 (an honor he shared with physician E. Donnal Thomas), his citation read: “He has given the gift of life to hundreds of thousands of people destined to die young." Murray, who died in 2012, had set out to accomplish what had once been thought impossible, even unethical by the medical community — organ transplantation.
That success, however, did not come easily. Because the human immune system is designed to reject foreign bodies, transplanting organs between people was long deemed impossible. But Murray's successful transplantation of a kidney between two identical twins in 1954 would pave the way for other transplants to follow. And in the decades since, the field of organ donation has grown by leaps and bounds, tackling logistical and ethical challenges along the way.
A Success for Organ Transplants
Murray's first taste of transplantation came during World War Two. After graduating Harvard Medical School, he was inducted into the Medical Corps of the U.S. Army, serving at Valley Forge General Hospital in Pennsylvania. While there, he worked on injured soldiers, repairing disfigured hands and faces.
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After the war, he joined the surgical staff at the Peter Bent Brigham Hospital. There, he led a team which had one goal: human organ transplantation. The issues the team faced were manifold, from identifying the best way to hook up blood vessels to pinpointing where to put the new kidney. Murray went to New York for more training as a plastic surgeon, before returning to Brigham in 1951. More than anything, though, antigens were the biggest recurring problem; at the time, organ transplant recipients inevitably died of rejection.
Just two years later, Murray had a unique opportunity, when 22-year-old Richard Herrick of the U.S Coast Guard fell ill with kidney failure. Herrick, it turns out, had an identical twin, Ronald. On December 24, 1954, Richard Herrick, who had become delirious and hostile as kidney failure affected his faculties, went under the knife alongside his brother.
The procedure was the first successful human organ transplant. Richard ended up marrying one of the nurses he’d berated from his bedside. Ronald, meanwhile, lived for another 56 years.
A Growing Field
But in many ways, Murray's success marked the beginning of a journey, not the end. Most people are not so fortunate as to have an identical twin, and rejection continued to thwart a majority of transplants.
Work by other scientists, particularly Gertrude Elion and George Hitchings, proved pivotal. The pair were pioneers of what’s called rational drug design, where drugs are designed to hit specific biological targets, unlike the ad-hoc methods that had been used previously.
But the pair also designed a drug that would prove pivotal in organ donation — azathioprine, the first-ever immunosuppressant drug, first used in 1961. The discovery transformed the field, as recipients no longer needed to have won the genetic lottery in the form of an identical twin. A flurry of breakthroughs soon followed: first, in 1962, there was the first successful kidney transplant from a cadaver. Then, in 1963, an organ was recovered from a brain-dead donor for the first time. Later that same year, long-term immunosuppression was achieved by combining azathioprine with steroids. And in 1964, tissue antigen matching was found to have the best outcomes for deceased-donor kidney transplants.
Still, these improvements in immunosuppression also raised significant ethical questions. First and foremost was the cost of donation itself, particularly when organs like the heart or lungs were involved; if a donor wasn’t truly dead before the removal of these critical organs, they surely would be afterwards. Though it didn't fully resolve the debate, a 1968 report from Harvard Medical School introduced what would be the basis for the neurological criteria that define modern brain death. It wouldn’t be until 1981, however, that a Congressional commission would round out the definition with the cardiopulmonary criteria, as well.
Leaps and Bounds for Organ Transplants
Over the years, various improvements have been made on both the medical and legislative sides. The National Organ Transplant Act of 1984 made it illegal to sell organs and created the Organ Procurement and Transplantation Network, which works to ensure the fair allocation of donated organs. It also established the Scientific Registry of Transplant Recipients, which evaluates the scientific and clinical status of organ transplantation. A few years later, in 1988, the FDA approved an organ preservation solution that increased the time abdominal organs could be kept in cold storage.
New possibilities emerged alongside these developments. The use of laparoscopic surgery to remove a kidney from a living donor in 1995, for example, made recovery easier and faster for donors. In 1999, the first hand transplant was performed. The first partial face transplant happened in 2005, and the first full transplant came just five years later. In 2014, a baby was born from a transplanted uterus for the first time. And in 2019, a human kidney was flown from one hospital to another by drone for the first time in the history of organ transplantation.
Yet despite the miracles of modern technology, long-term survival rates have not seen vast improvements since the 1980s, according to a study published in the Texas Heart Institute Journal in 2019. The authors of that paper note in their conclusion that if organ transplantation “is to remain an effective treatment option, long-term management methods and approaches must continue to improve.” In the U.S., on average, 17 people die every day while waiting for an organ transplant.
Such improvements will require scientists and physicians to draw from all that we've learned over more than half a century of organ transplantation. Murray knew better than most how advances are built on the shoulders of giants. As he said in his Nobel acceptance speech: “We all have been warmed by fires we did not build. We all have drunk from wells we did not dig.”