Traces of a virus known to infect pigs were found in a 57-year-old Maryland man who survived for two months with a transplanted heart from a genetically altered pig, according to the surgeon who performed the procedure, the first of its kind. .
The disclosure highlights one of the most pressing objections to animal-to-human transplants, which is that the widespread use of modified animal organs could facilitate the introduction of new pathogens into the human population.
The presence of the virus’s DNA in the patient may have contributed to his sudden deterioration more than a month after the transplant, said surgeon Dr. Bartley Griffith of the University of Maryland School of Medicine.
But there was no evidence that the patient developed an active infection with the virus, or that his body had rejected the heart, Dr. Griffith added.
The patient, David Bennett Sr., had been very ill prior to surgery and suffered many other complications after the transplant. He died on March 8.
Dr. Griffith’s revelations about viral traces found in the patient, made last month at a meeting of the American Society for Transplantation, were first reported by the MIT Technology Review.
In an interview with The New York Times on Thursday, Dr. Griffith and his colleague, Dr. Muhammad Mohiuddin, scientific director of the cardiac xenotransplantation program at the University of Maryland Medical Center, said they were saddened by the loss of the Mr. Bennett. but that they were not deterred from their goal of using animal organs to save human lives.
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“This really doesn’t scare us about the future of the field, unless for some reason this incident is being interpreted as a total failure,” said Dr. Griffith. “It’s just a learning point. Knowing it was there, we can probably prevent it in the future.”
The pig, which had been genetically modified so that its organs would not trigger rejection by the human immune system, was provided by Revivicor, a Blacksburg, Virginia-based regenerative medicine company.
Company officials declined to comment Thursday, and Food and Drug Administration officials, who gave transplant surgeons emergency clearance for the operation on New Year’s Eve, said they couldn’t answer for sure. immediately to questions.
University officials said that although the pig had been tested several times for the virus, the tests detect only active infections, not latent ones in which the virus can hide silently in the pig’s body. (The tests were done on nasal swabs, but the virus was later detected in the pig’s spleen.)
The latent virus could have “hitchhiked” in the transplanted heart patient, Dr. Griffith said.
Mr. Bennett’s transplant was initially deemed successful. It showed no signs of organ rejection and the pig’s heart continued to function for more than a month, passing a critical milestone for transplant patients.
A test first indicated the presence of porcine cytomegalovirus DNA in Mr. Bennett 20 days after the transplant, but at such a low level that Dr. Griffith said he thought it might have been a laboratory error.
However, about 40 days after the surgery, Mr. Bennett suddenly became seriously ill, and subsequent tests showed a skyrocketing in viral DNA levels, Dr. Griffith said.
“So we started to think that the virus that appeared very early on the 20th as a simple flash started to grow over time, and it could have been the actor, it could have been the actor, that caused all this,” said Dr. Griffith told other transplant scientists at the meeting.
On day 45, Mr. Bennett’s health abruptly deteriorated.
Doctors treated Mr. Bennett with antiviral drugs and intravenous immunoglobulin (IVIG), a product made from antibodies, but the new heart filled with fluid, doubled in size and stopped working, and he was eventually put on a cardiopulmonary bypass machine. .
The heart transplant was one of several groundbreaking transplants in recent months offering hope to the tens of thousands of patients in need of new kidneys, hearts and lungs amid a dire shortage of donated human organs.
In October, surgeons in New York successfully attached a kidney grown from a genetically altered pig to a brain-dead patient and found that the organ functioned normally and produced urine.
In January, surgeons at the University of Alabama at Birmingham reported they had transplanted kidneys from a genetically modified pig into the abdomen of a brain-dead 57-year-old man.
But the prospect of unforeseen consequences, and in particular the possible introduction of animal pathogens into the human population, may dampen enthusiasm for the use of genetically modified organs.
Many scientists believe that the coronavirus that triggered the global Covid pandemic originated with a virus that spread from an unidentified animal to people in China.
Porcine cytomegalovirus hasn’t been a big concern since it’s a herpesvirus, which tends to be species-specific, said Dr. Jay Fishman, associate director of the transplant center at Massachusetts General Hospital, which studies infectious diseases.
“They will replicate only in the host they are associated with,” said Dr. Fishman.
However, the virus could infect the transplanted animal organ, causing a cascade of systemic effects that would ultimately harm the patient.
“Did this contribute to the patient’s death? The answer is, obviously, we don’t know, but it could have contributed to his not doing well overall,” Dr. Fishman said.
Dr. Jamie Locke, a transplant surgeon and director of the Incompatible Kidney Transplant Program at the University of Alabama at Birmingham, said genetically modified pigs whose organs will be used for transplants must be raised in a pathogen-free facility and weaned from your mothers. within 48 hours of birth, to prevent transmission of porcine cytomegalovirus during lactation.
The university has such a facility, and Dr. Locke said she was still planning to start a small Phase 1 clinical trial in which she will transplant kidneys from genetically modified pigs into people with end-stage kidney disease.
More sensitive testing of animals will be required to detect the virus, he added.
“From my perspective, it’s not slowing down what we need to do, but further emphasizing that data showing our herd is free of that virus will be critical” for regulatory clearance to move forward, he said.