A virus may have driven the death of the first patient to receive a genetically modified pig heart
Doctors may be closing in on an answer for why the first human transplanted with a genetically modified pig heart died last month, around 60 days after the procedure. If accurate, it may amount to an unforced error at one of the most sensitive moments in modern medical history.
At a webinar last month, Bartley Griffith, the surgeon who performed the procedure, revealed that the heart patient, 57-year-old David Bennett, was infected with a pig virus called porcine cytomegalovirus, or pCMV.
MIT Technology Review first reported late Wednesday on the webinar and the debate it set off among transplant experts.
Although the virus is common in pigs and generally only triggers symptoms in very young pigs, it has previously been linked to poor outcomes when researchers transplanted pig hearts with the infection into baboons.
Griffith emphasized they still aren’t sure that the porcine virus contributed to Bennett’s death, but he presented evidence that it set off an ultimately fatal cascade. It’s particularly notable because pigs developed for human transplants are supposed to be kept in completely pathogen-free facilities and tested for the presence of such infections.
When they first noticed low levels of the virus in the heart after transplant, Griffith said, they thought it might be an error.
“We thought maybe that little bit didn’t mean anything, that it was probably an error,” he said. “Our donor heart was allegedly free of CMV.”
Jay Fishman, a transplant specialist at Mass General, told Technology Review that it appeared the virus drove his death. And Joachim Denner of the Institute of Virology at the Free University of Berlin, who led the baboon study showing the risk of pCMV in pig-to-human transplants, told the outlet the same.
Denner added that, although CMV is hard to detect, it could have been found prior to the transplant with better testing. He argued, however, that the virus was not solely to blame — Bennett was very ill — and the procedure was still a success. Early attempts at animal-to-human transplants lasted mere hours.
The virus is not considered to be transmissible to humans.
Technology Review said Revivicor, the biotech that developed Bennett’s heart, declined to comment. The company, a subsidiary of United Therapeutics, has remained largely quiet even as organs from its pigs have been used in a series of headline-grabbing procedures.
Griffith also pointed to other issues that could have impacted Bennett’s survival, including missteps from the transplant team. They gave him antibodies from donor blood twice that were later shown to contain anti-pig antibodies and may have damaged his heart.
The doctor’s attempts to treat the infection with an old AIDS drug failed, but Griffith argued that, if pCMV indeed drove his death, it bodes well for the future of xenotransplantation, as Revivicor, a Harvard spinout called eGenesis and other companies push to launch the world’s first pig-to-human clinical trials.
If Bennett’s immune system had rejected the heart as foreign, it would be unclear to researchers how to proceed and whether the pigs might need additional genetic modifications to make them compatible. Viruses, though, can be detected.
“If this was an infection, we can likely prevent it in the future,” Griffith said.