The death of the first human transplanted from a pig’s heart is believed to be due to a pig virus

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The first human pig heart transplant died last March. The medical team had provided no further information, except that his condition had worsened within a few weeks. Recently, the surgeon who performed this first xenograft announced that the heart was a carrier of a porcine virus that contributed, to some extent, to the patient’s premature death. A look back at this medical enterprise and the reasons for its failure.

David Bennett Sr., who was on the verge of death in January, later received a genetically engineered pig heart in a pioneering cross-species transplant, which was hailed as a success. A few days after the operation, David Bennett showed no signs of rejection. His surgeon, Bartley Griffith of the University of Maryland School of Medicine, pointed out that ” his new heart was beating wonderfully and [que] [David] he acted like a rock star “. He had even been able to watch the world-famous NFL football championship final game, the Super Bowl. But about 40 days later, Bennett, 57, conditions worsened. After two months, he died. In one statement released by the university in March, a spokesman said there was “no no obvious cause identified at the time of death and that a full report was pending.

However, during a webinar hosted by the American Society of Transplantation on April 20, B. Griffith explained that Bennett’s heart had been affected by porcine cytomegalovirus, a preventable infection but linked to devastating effects on transplants. . The matter is now widely discussed among specialists, who believe the infection was a potential contributor to Bennett’s death and a possible reason why the heart stopped.

A virus hidden in the pig’s heart

This transplant is an important step for xenografts, i.e. organ or tissue transplants between two different species. In order for this type of intervention to be successful, the pigs are specially bred and selected. In fact, the biggest obstacle to organ transplants in animals is the human immune system, which attacks foreign cells in a process called rejection. To avoid rejection, companies genetically modify pigs by removing and / or adding certain genes to give their tissues a profile that protects them from immune attack. In David Bennett’s case, the pig had undergone 10 genetic modifications, carried out by Revivicor, a subsidiary of United Therapeutics. Additionally, these pigs, bred specifically to provide organs, should be virus-free.

Unfortunately here it seems that the experience has been compromised by a mistake of this level. Revivicor has not made any public statements regarding the virus, which could compromise future evidence.

In fact, Griffith said during his presentation: ” If it’s an infection, we can probably prevent it in the future mainly because this type of virus can be easily detected and eliminated by pig populations. If the porcine virus really played a significant role in this premature death, it could mean that a virus-free heart xenograft could last much longer. Some surgeons believe that genetically modified organs could, in theory, continue to beat for several years and stricter procedures should allow for greater “filtering” of viruses.

But in fact, porcine cytomegalovirus is linked to harmful reactions to organs and patients. In 2020, a team of German researchers led by Joachim Denner of the Robert Koch Institute in Berlin found that pig hearts transplanted into baboons lasted only a few weeks if the virus was present, while the infection-free organs could survive for longer. six months.

Finally, a fear raised by this type of transplant is that it could trigger a pandemic if a swine virus like the one hidden in the transplanted heart adapts to the human body. However, experts believe that the specific type of virus present in Bennett’s heart is unable to infect human cells. They are therefore reluctant to fully attribute Bennett’s death to the virus. But what would be the real cause of death?

An inevitable death?

It was the United States Food and Drug Administration (FDA) that issued a special permit to test an animal organ in a one-time transplant, on Bennett, at Griffith’s request. He seemed like a good candidate, because not eligible for a human heart transplant, he was sentenced to death. The operation went very well. But despite an encouraging recovery, Bennett’s condition remained fragile all along, as his surgeon points out in his online presentation. He decompensated very quickly, with all the signs of an infection that, until then, had gone unnoticed. A 34-day biopsy also revealed nothing abnormal.

His doctors monitored his health with great rigor, running a battery of advanced blood tests, looking for traces of various viruses and bacteria. However, a very low level of this virus was found during an analysis, but it was supposed to come from an error, so the figures were so low. The test to clarify this point takes 10 days, effectively preventing doctors from knowing if the virus has already multiplied and therefore from intervening early enough to contain it.

The probable cause of Bennett’s death is therefore not necessarily attributable entirely to the virus, but was at least the trigger of an immune storm, which Bennett’s general health could not stem. Faced with signs of infection, doctors were faced with a dilemma, well known in transplants: how to fight infections by controlling the patient’s immune system. Eventually, doctors gave Bennett a drug of last resort called Cidofovir, sometimes used in AIDS patients, along with intravenous immunoglobulin. But that wasn’t enough to keep him alive.

Despite this premature conclusion, the experiment allowed to accumulate a great deal of valuable knowledge about xenografts and the mandatory conditions to be met – such as a more sensitive screening of animals for the virus – so that this type of operation can be repeated with more safety and success. The latter bring some hope to combat the shortage of transplantable human organs.

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