The death of a man who received a gene-edited pig heart in a landmark transplant operation earlier this year may have had an unexpectedly routine cause: a common and preventable infection in the donor heart, reports MIT Technology Review.
In January of this year, a man named David Bennett made history: After an eight-hour operation at the University of Maryland Medical Center, he became the first human on Earth whose heart came from a member of a species different: a pig, to be specific.
It was a highly experimental surgery, and Bennett knew it was the last resort: “It was either die or do this transplant,” he said at the time. “I want to live.”
And live it did, at first: Bennett began physical therapy to regain strength, was able to spend time with his family, and there was no sign of the heart being rejected. In fact, she performed like a “rock star,” according to her transplant surgeon, Bartley Griffith of the University of Maryland School of Medicine.
But after about six weeks, things took a turn for the worse, and in early March, Bennett died.
Initially, his doctors were stumped. “No obvious cause was identified at the time of his death,” a hospital spokeswoman told the New York Times, and any further comment would have to wait until a full medical investigation was conducted.
Now, the culprit in Bennett’s death may have been found: The heart used in the transplant was infected with porcine cytomegalovirus.
“It was amazing. That pig is supposed to be clean of all porcine pathogens, and this is important,” said Mike Curtis, CEO of eGenesis, a competitor company that also breeds pigs for organ transplants.
“Without the virus, would Mr. Bennett have lived? We don’t know, but the infection didn’t help. It probably contributed to the failure.”
Speaking at a recent webinar for the American Society of Transplantation, Griffith said the virus “maybe was the actor, or could be the actor, that triggered all of this.” If so, he sees reason for optimism: “If this were an infection, we can probably prevent it in the future,” he said during the presentation.
But the presence of this virus in the transplanted organ highlights a concern that experts have long held about xenotransplantation: the transfer of animal pathogens to human hosts.
In the age of coronavirus, the most immediate thing that comes to mind when we think of zoonotic diseases is probably the fear of accidentally starting a new pandemic. In this case, however, “there is no real risk to humans,” Jay Fishman, a specialist in transplant infections at Massachusetts General Hospital, told MIT Technology Review.
But evidence suggests that porcine cytomegalovirus can have devastating effects on transplant recipients. A 2020 study found that the presence of the virus reduced the survival time of baboons given pig hearts from up to 28 weeks to just one or two.
The researchers behind that paper, a German team led by virologist Joachim Denner, said at the time that they thought “the same thing is very likely to happen in humans,” and the Bennett case may have proved them right. In introducing him, Griffith noted that the damage caused by the disease was similar to that seen in baboons, adding that he “personally suspects[s] [Bennett] He developed a capillary leak in response to his inflammatory burst, and that filled his heart with edema, the edema turned into fibrotic tissue, and he went into severe, nonreversible diastolic heart failure.”
It may be tempting to pass this off as a case of extreme and inexplicable bad luck for Bennett, but the case raises some real and important questions surrounding the field of xenotransplantation.
“It’s a big red flag,” Arthur Caplan, a bioethicist at New York University, told the MIT Technology Review. If infections cannot be ruled out, he said, “then such experiments are hard to justify.”
But for Denner, the solution is simple: more precise tests.
“It is a latent virus and difficult to detect,” he explained. “But if you test the animal better, it won’t happen. The virus can be easily detected and eliminated from pig populations, but unfortunately they did not use a good assay and did not detect the virus, and this was the reason. The donor pig was infected and the virus was transmitted by the transplant.”
But even if the virus is what was behind Bennett’s death, and it should be noted that it’s still too early to know a conclusive cause of death, Denner says the experiment was a “great success.”
“This patient was very, very, very sick. Don’t forget about it,” he told the MIT Technology Review. “Maybe the virus contributed, but it wasn’t the only reason.”