On March 8, 2022, David Bennett died, two months after a team at the University of Maryland Baltimore transplanted a pig heart into his body. Such “xenotransplantation” has long occupied the public imagination, with one of the earliest examples being the myth of Icarus where the father-son duo grafted bird wings onto their bodies. Bennett’s operation has helped reify the “groundbreaking” potential of xenotransplantation: how an unlimited supply of animal organs could render the transplant list, where 17 people die every day waiting for a donor, obsolete. This promise is enticingly attractive, but what is being lost in all the hype and triumphalism it has elicited?
For one, there’s much we still don’t know about xenotransplantation, according to Dr. Richard Pierson, Director of the Center for Transplantation Sciences at Massachusetts General Hospital. The Virginia-based company Revivicor used the CRISPR-Cas9 system to add in six genes and knock out four from the pig used for Bennett’s operation, but “we don’t know precisely what the right pig is that we ought to be using,” Pierson said. Perhaps the right one is the 3-gene pig from the German team, or maybe it’s a hypothetical pig with manifold other genetic modifications. To manage the threat of transplant rejection, doctors say they’ll need to do more genetic tinkering with the pig heart, as well as more tinkering with the immunosuppressive regimen undergone by the patient. “What is the safest way to immunosuppress someone who’s had a xenotransplant?” Pierson said. “We don’t know.” The transplant protocol for Bennett was probably good enough, but nobody knows if it was the best.
There’s also the open question of whether xenotransplantation might enable “zoonoses,” or the jumping of pathogens across the species divide. Revivicor took extensive steps to ensure a “clean pig,” from performing a cesarean section of the pregnant sow, to not allowing the piglets to suckle their mother, to maintaining a hermetically sealed “pig-in-the-bubble” environment. But, despite all this external control, there are porcine endogenous retroviruses that remain and “might be a problem” according to Pierson. He’s quick to clarify that the existing evidence suggests these endogenous retroviruses don’t get into actual humans in any productive way. “We don’t think that’s going to be a major barrier, but it remains unknown,” Pierson said.
These are all known unknowns, but Pierson’s main unanswered question is the unknown. “Is there some pathogen out there? How will we know it’s there? How will we respond if we see it?” he asked rhetorically. Revivicor can do all the testing it wants to ensure a clean pig, but how can they test for something they don’t even know to look for? “There’s going to be a tremendous amount to learn before all these questions are answered,” Pierson said. But this does not mean we should abandon ship. For Pierson, it just means we should take cautious steps forward.
Bennett’s operation inevitably draws historical comparisons to that of Baby Fae, a case that many agree was catastrophically premature. Baby Fae was a 12-day-old infant who, diagnosed with hypoplastic left heart syndrome, received a walnut-sized baboon heart at Loma Linda University in 1984. Baby Fae died 21 days after the operation because of transplant rejection, and her story became an ethical lightning rod, eliciting accusations of inadequate informed consent, medical hubris, and human experimentation. Of course, animal rights activists also raised the issue of exploiting nonhuman primates. Dr. Leonard Bailey, the surgeon behind the operation, dismissed these concerns, saying, “When it gets down to a human living or dying, there shouldn’t be any question.”
But maybe there should be. “These animals are very close to us. They’re experiencing pain, friendship, and love. How can you experiment on them and use them for parts?” asked Dr. Sharon Kaufman, Chair of the Department of Anthropology, History, and Social Medicine at the University of California San Francisco. It’s the central question that has haunted animal experimentation since its inception: How are animals similar enough to be our model organisms yet different enough to be exploited for our ends?
According to Kaufman, xenotransplantation is an expression of our manifest destiny to expand the limits of human life beyond what was previously imaginable. It’s the tyranny of potential whereby progress can march triumphantly, unimpeded by calls for reflection and pause. “There used to be no potential. Now it’s all potential,” Kaufman said. “That’s what’s changed in medicine over the past 50 to 60 years.” If something is available, no matter how experimental, no matter how far-fetched, no matter if it even works, “it becomes ethically appropriate, necessary, and standard.”
Norman Shumway, the father of heart transplantation, once said “xenotransplantation is the future of transplantation, and always will be.” But, with science fiction now becoming our reality, we have to confront renewed questions about our relationship with animals and how we should navigate the interface between our species and others. As Pierson makes it clear, xenotransplantation isn’t quite ready for showtime, but it’s speeding down to realize its potential, whether we like it or not. By cutting past the hype and triumphalism though, animal rights activists, anthropologists, and the public at large can help shape the path xenotransplantation takes, paving a way that is more informed, cautious, and as humane as possible.
Simar Bajaj is an undergraduate student at Harvard University and a research fellow in the Department of Cardiothoracic Surgery at Stanford University. He is passionate about medical education and health equity, hosting That Medic Podcast, leading the World Pre-Health Conference, and directing policy for the American Lung Cancer Screening Initiative. Simar has previously written essays for The New England Journal of Medicine, The Lancet, Nature Medicine, British Medical Journal, and Tarbell.