The pig heart that was transplanted to a human was infected with a pig virus

Investigations following the patient's death have raised many questions that need to be addressed.
Ameya Paleja
The heart surgery in progressUniversity of Maryland Medical Center

Earlier this year, 57-year-old David Bennet made history when he became the first human to receive a pig's heart in a transplant. While the procedure was successful, Bennet did not survive very long and passed away after two months. Now, investigations into the cause of his death have revealed that the transplanted heart had a pig virus infection, which could have led to bennet's death, MIT Technology Review reported.  

Bennet's story should ideally have been the success story that heralded a new age of xenotransplants - where donor and recipient belong to different species. What is has now done instead is raised a series of questions ranging from procedural to ethical ones that need some deep-digging to find the correct answers. 

How was the virus not detected? 

The company behind the technology, Revivicor, has gone to great lengths to ensure that the donor organ is not rejected by the host's immune system. Its procedure includes editing over 10 genes that remove traces of its porcine origin and adding elements that make it look more human to the immune cells. 

However, amidst all these details, the company apparently did not test thoroughly for porcine cytomegalovirus. Joachin Denner at the Free University of Berlin, who was part of the transplant told MIT Tech Review that the virus is latent and can be hard to detect but a thorough test would have been able to detect it, prior to the transplant. What Revivicor did test was the donor's pig snout. But since the virus lurks deep in the tissues, it was likely transmitted during the transplant.

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After the transplant, Bennet was kept under observation at the hospital and underwent a series of tests to determine to monitor the transplant. One of these tests scanned his blood for hundreds of bacteria and viruses and it was here that the cytomegalovirus was first detected. The detected levels were low enough not to cause an alarm but it took 10 days to carry out the test. 

Why did the patient die? 

One day, Bennet woke up with what looked like obvious signs of an infection that the doctors did not know which. The immune system of transplant patients is tuned down to reduce the chances of organ rejections, but this also makes it harder to fight infections.

At this point, doctors did not know the true extent of the infection, and nobody had treated the pig virus in a human patient before. Handicapped by a comprised immune system, the doctors used cidofovir, usually the last resort anti-viral, and antibodies sourced from blood donors. 24 hours later, Bennet's condition had improved but his heart had begun to fail. 

Previous research has shown that xenotransplants have lasted only a few weeks in baboons if the virus was present while lasting almost half a year when it was not. Researchers think that the virus multiplies unchecked since the host immunity is compromised and at sufficiently high levels causing a cytokine explosion, a hyperactive immune response. 

Bartley Griffith, the surgeon who performed the transplant, told MIT Tech review that the elevated immune response may have led to edema - a swelling, in the transplanted heart, which would have eventually led to a heart failure. 

While this is a plausible explanation, there are many other questions that still need to be answered. Should these transplants be allowed when we know so little about their ill effects? Did the patient have enough options, when he made his choice to undergo the transplant? How can companies improve their protocols to avoid such events in the future?

This is the slow grind of science. 

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