Reviewing the case of David Bennett

In January, US surgeons and scientists achieved a breakthrough in transplantation surgery: they gave a man dying of heart failure the heart of a pig that had been specifically developed, and altered genetically, to produce organs compatible with humans. The recipient, David Bennett, survived for two months; he passed away in March. Now the doctors looking into his case have announced that a pig virus might have been partly to blame. They’ve detected low levels of an agent called porcine cytomegalovirus. This can’t infect human cells but it might have begun to spread through the pig heart cells, causing the donor organ to fail. Nevertheless, it’s very early days and was present at only very low levels meaning it may just have been a red herring. Chris Smith caught up with the surgeon who carried out the transplant, Muhammad Mohiuddin, to discuss what happened in this case, and what we’ve learned about the potential of using pig organs in this way…

Muhammad - We performed the first ever pig to human heart transplant in a patient for whom we have exhausted all other means to save his life. It took place on January 7th, 2022.

Chris - Now the patient has unfortunately passed away. Why did he not make it?

Muhammad - For that I'll have to give you a little background. This patient came in a very bad condition with heart failure and he was put on a heart lung machine. So he was kept alive by these means. He was deemed ineligible for human heart because of his non-compliance issues and several other factors. So, we offered him this pig heart, which was genetically modified to make it more acceptable to humans. And in our non-human primate studies, we proved this heart can sustain life of a baboon for up to nine months. For the first 50 days, his heart functioned very well, but then it was contracting very well, but it was not relaxing. And for that reason, you know, we had to put him back on that heart lung ECMO machine for the last 10 days to see if we can rescue this heart. But unfortunately it did not happen.

Chris - In summary, this gentleman received this genetically modified pig heart, which you had preliminary data from non-human animals, primates, baboons for example, that it could sustain an animal of human sort of size for an extended period of time. He was initially doing well. Then something caused him to decompensate. Things went wrong. Do you have any insight into why you ended up back on that machine and why he just didn't make it?

Muhammad - There are several factors, just after the transplant and the heart was beating well we found that he had a dissection, so we had to stop the heart again, fix that. And from that, we thought that his kidneys and the bowel got affected a little bit because his kidney did not function throughout his survival. And we had to put him on dialysis. He had multiple infection issues, and now we found that the heart had DNA from aporcine virus. We are investigating whether this virus played any role. And we so far have no evidence that this virus caused any disease. This is an ongoing investigation and this virus is just one piece of the puzzle.

Chris - Have you got plans in the near term to do this again? Or are you now in learning phase? Let's see what happens? Let's evaluate and then see where we find ourselves?

Muhammad - Yeah, there is a lot to be learned and we are very grateful to Mr. Bennett for allowing us to learn from his participation in this process. We are excited that, you know, this heart did not reject within few days until day 50. It looked like that there was no signs of rejection. So this provides a lot of hope that this is a viable option.