Those who closely follow research in the field of transplantation have been expecting that someday a genetically edited pig organ would be transplanted into a living human. But when the University of Maryland School of Medicine in Baltimore announced that on Jan. 7 a genetically edited pig heart had been given to a human recipient, the news came as a surprise.
The operation, known as a xenotransplant, was widely described in the media as a "success," but there are many questions that need answers to justify undertaking what is a hugely risky experiment.
Maybe the Maryland team already has good answers, and maybe the case will be reported in detail in peer-reviewed journals so that other medical teams can learn from their pioneering effort. But since this transplant was done as an emergency rescue, not a clinical trial, the data acquired are likely to be only anecdotal and perhaps not fully shared. In some ways, the next attempt will have to start from scratch.
For now, though, several matters bear consideration. For example, what data suggested that it would now be safe enough to try a pig heart in a living human?
True, doctors have used pig parts to make insulin, blood thinners and heart valves for years. Genetically edited pig hearts have been transplanted into baboons, leading to months of survival. Gene-edited pig-to-human skin grafts have shown promise. Edited pig kidneys have produced urine in two deceased human recipients in experiments at our institution and didn't show signs of rejection after a couple of days.
But it is a long technical jump from those developments to a decision to put a genetically edited pig heart, using new immunosuppressive drugs, into a living human. We need to see the preclinical studies that made the Maryland team say, "Now is the time."
Just as important is knowing why this patient was chosen and what he was told. Put aside his newly revealed criminal record, which is not morally relevant in selecting a subject in a dangerous experiment with a high likelihood of failure.
What is relevant is that the Maryland team said he had been deemed ineligible for a standard human heart transplant in part because he did not properly manage his heart failure, thus becoming too sick to survive a human transplant. What sort of support will the team offer to give him the best possible chance to do well with all the needed follow-up care, including a novel immunosuppression regimen that will be tested on him for the rest of his life?
One line of reasoning to give him the first such xenotransplant is that his life depended on it and he had no other options. But patients in that situation are often vulnerable and desperate, and they may not fully understand what they're signing up for. The consent process used in this case - which is crucial in first-of-their-kind experiments - remains unclear.
It makes sense that Maryland's xenotransplant team wanted to pioneer the transplant of a pig heart. It would be interesting to know how conversations went with the chief medical officer or the board of trustees to convince them that this risk - and the expense, because insurance won't go near covering the huge cost yet - would be a success and not a PR nightmare.
Who else signed off? Institutional review boards are required to review studies involving human subjects to make sure the risks aren't too great. But the xenotransplant was not a study - it was treated as a onetime emergency event, so even if the team approached the board, no approval was required. Ironically, this pig-heart transplant was probably easier to do with a human than another one involving a baboon because of requirements imposed by animal care and use committees.
The surgical team did approach the Food and Drug Administration, likely for approval of the edited pig heart as a new biological entity. They were granted an emergency authorization through an expanded access (compassionate use) pathway to permit treatment for a life-threatening situation. But what exactly was the evidence that made the FDA think the benefits outweighed the risks, even for a patient with terminal heart disease? Even if he were dying, planning for a pig-heart transplant would involve weeks of preparation, which seems to stretch the definition of an emergency.
There is no question that using pigs as organ sources is the future. Advancements in gene-editing technology and transplant science have brought several xenotransplant programs to the verge of expanding the organ pool for the many dying for want of an organ. But first efforts often fail. Those brave enough to jump into the unknown need to be especially clear that they went forward at the right time and with the right patient, who fully understood the risks involved.y
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Arthur Caplan, Laura Kimberly, Brendan Parent and Tamar Schiff are members of the transplant ethics and policy working group in the Division of Medical Ethics at NYU Grossman School of Medicine.
The Washington Post