Pig Used in Human Heart Transplant Had Virus, Patient 'Looked Infected'

The pig that was used in the first human heart transplant was infected with a porcine virus that may have contributed to the death of the patient, experts have said, with the surgeon that treated him saying David Bennett Sr. "looked infected."

Bennett received a pig heart in a groundbreaking surgery that took place in Maryland in January. The 57-year-old had been suffering from terminal heart disease and the operation was a last ditch attempt at saving his life. Bennett died on March 8, two months after the surgery, the University of Maryland Medical Center (UMMC) confirmed in a statement.

Muhammad M. Mohiuddin, professor of surgery and scientific director of the Cardiac Xenotransplantation Program at UMSOM, said Bennett's surgery had provided "invaluable insights" into how a genetically modified pig heart functions in the human body.

"We remain optimistic and plan on continuing our work in future clinical trials," he said in a statement. At the time, a hospital spokesperson said there was "no obvious cause" for his death.

However, according to a report in the MIT Technology Review, experts have now found that the pig used in the transplant was carrying a porcine virus that may have contributed to Bennett's death.

Presence of a Virus

It said that in a webinar by the American Society of Transplantation on April 20, Bartley Griffith from the University of Maryland School of Medicine, who performed the heart transplant, had described the presence of the virus.

The pig used in the transplant was supposed to be free of all pathogens. Revivicor, the biotech company that raised the pig, hasn't commented on the case. Newsweek has contacted United Therapeutics, Revivicor's parent company, for comment.

According to the MIT Technology Review, Griffith said they noticed a "blip" indicating the presence of porcine cytomegalovirus 20 days after the surgery, but the levels were very low so it was put down as an error. On day 43, Bennett had started to deteriorate: "He looked really funky," Griffith said. "Something happened to him. He looked infected. He lost his attention and wouldn't talk to us."

Doctors tried to treat him for an infection while trying to make sure his immune system continued to accept the donor heart. They treated him and while he appeared to improve, a week later his health went downhill again.

Griffith said a biopsy did not show signs of rejection. Instead the team thinks the virus may have caused the heart to start to fail.

"We are beginning to learn why he passed on," Griffith said in the webinar. He said the virus could have "set this whole thing off."

"If this was an infection, we can likely prevent it in the future."

Jay Fishman, a transplant specialist at Massachusetts General Hospital, told MIT Technology Review the virus found in the pig heart is not thought to be capable of infecting human cells. However, it is known to cause reactions that damage the transplanted organ.

Joachim Denner of the Institute of Virology at the Free University of Berlin, who carried out research into porcine virus on transplant organs, said the virus is latent and difficult to detect. He told MIT Technology Review that the U.S. team appears to have checked the pig's snout, but that the virus was probably present in deeper tissues.

"The virus can be detected and easily removed from pig populations, but unfortunately they didn't use a good assay and didn't detect the virus, and this was the reason," he said. "The donor pig was infected, and the virus was transmitted by the transplant."

However, Denner said the porcine virus wasn't necessarily behind Bennett's death. "This patient was very, very, very ill. Do not forget that. Maybe the virus contributed, but it was not the sole reason."

Christine Tait-Burkard, an expert on coronaviruses and arteriviruses at the University of Edinburgh in the U.K., told Newsweek that in most cases, the porcine cytomegalovirus virus that affected the donor pic is mostly asymptomatic as high herd immunity is present.

"Human cytomegalovirus is known to have the potential to reactivate in organ recipients," she said. "Just like any herpesvirus they integrate into our genome and are mostly dormant until we are exposed to stress or other factors that suppress our immune system. With the drugs given to organ recipients to suppress the immune reaction to not react against the donor organ, this also can suppress the reaction to infectious diseases.

"Whilst the doctors in the U.S. appear to have administered an anti-(human) cytomegalovirus drug cidofovir as well as human herpesvirus drugs, they may have not been suitable to act against the porcine cytomegalovirus.

"This viral infection should have been recognised as a problem for a transplant before the surgery and will need to be taken very seriously for future Xenotransplantations."

UMSM told Newsweek there is currently no evidence that the porcine virus caused an infection in Bennett. "The donor pig was raised in a facility using methods designed to prevent pCMV and other potential pathogens from infecting donor animals," it said. "The healthy donor pig used for the xenotransplant was screened for pathogens multiple times. It was tested just before shipment to Maryland, and just before the transplant a few days later.

"The testing followed protocols that were accepted by the U.S. Food and Drug Administration (FDA). As plans move forward for future clinical trials, more sophisticated testing techniques are being developed and validated to ensure this virus does not go undetected."

This article has been updated to include quotes from Christine Tait-Burkard and the UMSM.