The version used in Maryland came from a pig with… 10 gene modifications developed by Revvicor, a subsidiary of United Therapeutics.
After promising tests of such pig organs in baboons, three US transplant teams launched the first human studies in late 2021. Surgeons at New York University and the University of Alabama each attached pig kidneys to brain-dead people, but the University of Maryland went a step further when Griffith stitched a pig heart into Bennett’s chest in early January.
The transmission of pig viruses to humans has been a concern – some feared that xenotransplantation could trigger a pandemic if a virus adapted in a patient’s body and then spread to doctors and nurses. The concern may be severe enough to require lifelong monitoring of patients.
However, the specific type of virus found in Bennett’s donor heart is not believed to infect human cells, says Jay Fishman, a transplant infections specialist at Massachusetts General Hospital. Fishman thinks there is “no real risk to humans” from further spreading.
Instead, the problem is that porcine cytomegalovirus has been linked to reactions that can damage the organ and the patient, with catastrophic consequences. For example, two years ago German researchers reported that pig hearts transplanted into baboons only lasted a few weeks if the virus was present, while organs free of the infection could survive for more than half a year.
Those researchers said they found “astonishingly high” levels of virus in pig hearts removed from baboons. They think the virus may be confused not only because the baboons’ immune systems were suppressed with drugs, but also because the pig’s immune system was no longer there to control the virus. It “seems very likely that the same thing could happen to humans,” they warned at the time.
UNIVERSITY OF MARYLAND SCHOOL OF MEDICINE
Joachim Denner of the Institute of Virology at the Free University of Berlin, which led the study, says the solution to the problem is more accurate testing. The US team appears to have tested the pig’s snout for the virus, but often it lurks deeper in the tissues.
“It’s a latent virus and difficult to detect,” Denner says. “But if you test the animal better, it won’t happen. The virus can be detected and easily removed from pig populations, but unfortunately they did not use a proper test and did not detect the virus, and this was the reason. The donor pig was infected and the virus was transmitted through the transplant.”
Denner says he still thinks the experiment was a “huge success.” For example, the first human-to-human heart transplant, in 1967, lasted just 18 days, and two years later, one in Germany lasted just 27 hours.
Denner says Bennett’s death cannot be attributed to the virus alone. “This patient was very, very, very sick. Don’t forget,” he says. “Maybe the virus contributed to this, but it wasn’t the only reason.”
cause of death†
Bennett’s cause of death matters, because if his heart fails due to immune system rejection, researchers may have to go back to the drawing board. Instead, companies like United Therapeutics and eGenesis, or academics working with them, are now expected to start clinical trials on their pig organs within a year or two.
Bennett was offered a pig heart after Griffith applied to the US Food and Drug Administration for special permission to try an animal organ in a one-time transplant. He was considered a good candidate for the daring attempt as he was approaching death from heart failure and was ineligible for a scarce human heart for transplant due to a history of ignoring medical advice.