Transplant specialists believe that the pig heart transplanted into a US patient earlier this year in a landmark operation carried a porcine virus that may have contributed to his death two months reports MIT Technology Review.
The virus is a well known and avoidable risk, said the Review.
As reported in MedicalBrief on 12 January, David Bennett was near death when he received a genetically edited pig heart in a pioneering between-species transplant initially hailed as a success.
A few days later, Bennett’s new heart was pumping well, said his transplant surgeon, Bartley Griffith of the University of Maryland School of Medicine.
But about 40 days later Bennett’s condition deteriorated and two months later he died. A university statement said there was “no obvious cause identified at the time of his death” and that a full report was pending.
Now MIT Technology Review has learned that Bennett’s heart was affected by porcine cytomegalovirus, a preventable infection linked to devastating effects on transplants.
The issue has become a subject of wide discussion among specialists, who think the infection was a potential contributor to Bennett’s death and a possible reason why the heart did not last longer.
The heart swop was a major test of xenotransplantation, the process of moving tissues between species. But because the special pigs raised to provide organs are supposed to be virus-free, it now appears the experiment was compromised by an unforced error. The biotechnology company that raised and engineered the pigs, Revivicor, has made no public statement about the virus.
Not all bad
The detection of the pig virus in Bennett’s heart is not necessarily all bad news for xenotransplantation. If a pig virus played a role, it could mean a virus-free heart xenotransplant could last much longer. Some surgeons think the latest gene-modified organs could in theory keep beating for years – and more rigorous procedures should be able to screen out the virus, writes MIT Technology Review.
Joachim Denner of the Institute of Virology at the Free University of Berlin said the US team appeared to have tested the pig’s snout for the virus, but often it lurks deeper in the tissues.
“It’s a latent virus and hard to detect,” he said. “But if you test the animal better, it will not happen. 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. The donor pig was infected, and the virus was transmitted by the transplant.”
Denner says Bennett’s death cannot be blamed on the virus alone. “This patient was very ill,” he said. “Maybe the virus contributed, but it was not the sole reason.”
Cause of death?
Bennett’s cause of death matters, because if his heart failed as the result of immune rejection, researchers might need to return to the drawing board.
He was offered a pig heart after Griffith applied to the US Food and Drug Administration (FDA) for special permission to try an animal organ in a one-off transplant. Bennett was considered a good candidate because he was nearing death from heart failure and was ineligible for a scarce human heart for transplant owing to a history of disregarding medical advice.
His condition remained fragile all along. Still, after the operation, his new pig heart was squeezing powerfully and looking normal, said Griffith.
The team constantly checked him with cutting-edge blood tests. They used a DNA sequencer to scan his blood for floating fragments of pig genes – any increase would be a sign that heart cells were dying. Another novel test screened Bennett’s blood for traces of hundreds of bacteria and viruses.
It was that test, run on a blood draw taken from Bennett 20 days after his surgery, that first returned “a little blip” indicating the presence of porcine cytomegalovirus. But the levels were so low the team thought the result could be in error, Griffith said, especially since the pigs were supposedly guaranteed free of the germ.
The doctors faced another problem. The special blood test took about 10 days to carry out. So they couldn’t yet know that inside Bennett’s new heart, the pig virus was starting to multiply fast and setting off what Griffith now believes was a possible “cytokine explosion” – a storm of immune-system molecules.
A serious problem became apparent around day 43 when Bennett woke up feverish and breathing hard. They gave him a last-resort drug called cidofovir, sometimes used in Aids patients. And since his immune system was so weak, they also gave him intravenous immunoglobulin, antibodies collected from blood donors.
Bennett looked better 24 hours later but a week later his heart started to fail and then he died.
It’s too soon to say for sure why he died and researchers are still sifting through complex clues. The doctors also worry they made a mistake by giving him human antibodies, which they did twice. Later tests showed those blood products had contained some anti-pig antibodies and might have damaged the organ too.
Griffith said a biopsy of Bennett’s pig heart late in the experiment did not show telltale signs it had been rejected by his immune system, which had always been the biggest fear, and what the special gene-edited pigs were designed to avoid in the first place.
“I believe he developed a capillary leak in response to his inflammatory explosion, which filled his heart with oedema, which turned into fibrotic tissue, and he went into severe and unreversing diastolic heart failure,” said Griffith. However, the presence of the virus could now factor into some people’s questions over whether the experiment should have taken place at all.
“It’s a big red flag,” says Arthur Caplan, a bioethicist at New York University. If doctors can’t prevent or control infection, “then such experiments are tough to justify.”
See more from MedicalBrief archives:
World first: Transplant of pig heart on terminal US patient
First pig-to-human kidney transplant
Gene-edited piglets opening door to animal organ transplants