The version used in Maryland comes from a pig with 10 genetic modifications developed by Revivicor, a subsidiary of United Therapeutics.
After promising tests of such pig organs in baboons, three US transplant teams launched the first human studies beginning in late 2021. Surgeons at New York University and the University of Alabama attached pig kidneys to people with brain death, but the University of Maryland went a step further when Griffith sewed a pig’s heart into Bennett’s chest in early January.
The transmission of swine viruses to humans is a concern – some fear that xenotransplantation could cause a pandemic if the virus adapts to the patient’s body and then spreads to doctors and nurses. The concern may be serious enough to require lifelong patient monitoring.
However, the specific type of virus found in Bennett’s donor heart is not thought to infect human cells, said Jay Fishman, a transplant specialist at Massachusetts General Hospital. Fishman believes that “there is no real risk to humans” from its further spread.
Instead, the problem is that porcine cytomegalovirus is associated with reactions that can damage the organ and the patient – with disastrous results. Two years ago, e.g. German researchers reported that baboon-transplanted pig hearts survived only a few weeks if the virus was present, while infection-free organs could survive for more than half a year.
These researchers said they found “surprisingly high” levels of the virus in the hearts of pigs taken from baboons. They believe that the virus may be confused not only because the baboon’s immune system has been suppressed by drugs, but also because the pig’s immune system was no longer there to keep the virus under control. “It seems very likely that the same thing will happen to humans,” they warned at the time.
Joachim Dener of the Institute of Virology at the Free University of Berlin, who is leading the study, says the solution is more accurate testing. The American team seems to have tested the pig’s snout for the virus, but it often hides deeper in the tissues.
“It’s a latent virus and it’s hard to detect,” Denner said. “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 good analysis and did not detect the virus and this is the reason. The donor pig was infected and the virus was transmitted through transplantation.
Denner says he still thinks the experiment was a “great success.” For example, the first human-to-human heart transplant in 1967 lasted only 18 days, and two years later one in Germany lasted only 27 hours.
Denner says Bennett’s death cannot be blamed on the virus alone. “This patient was very, very, very ill. Don’t forget that, “he says.” The virus may have contributed, but that’s not the only reason. “
Cause of death?
The cause of Bennett’s death is important because if his heart fails as a result of immune rejection, researchers may have to return to the drawing board. Instead, companies such as United Therapeutics and eGenesis or scientists working with them are now expected to begin clinical trials of their pig organs within a year or two.
Bennett was offered a pig’s heart after Griffith applied to the US Food and Drug Administration for special permission to test an animal organ for a single transplant. He was considered a good candidate for the daring experience because he was close to dying of heart failure and did not qualify for a scarce human heart for transplantation due to a history of neglect of medical advice.