Posted on 12 January 2022
One could say that the pig has always been man’s best friend when it comes to the heart. Pig hearts are similar in size, structure and function to those of humans, making them the go-to for anatomy studies. In 1965, a human aortic valve was replaced with a pig valve successfully for the first time, and such transplants or ‘xenografts’ are now performed routinely. However, replacing the whole heart with a pig heart has not been feasible. That is, until last Friday, when 57 year-old David Bennett became the first person to undergo the operation, which so far appears to have been successful. How was it done?
The main reason pig to human heart transplants had not previously been attempted was the nature of the immune response that would be produced immediately upon transplantation, called a hyperacute rejection. The human immune system doesn’t tolerate the presence of molecules that aren’t native to the body, including the molecular identifiers called MHC present on the surface of most cells. This means that even when receiving organ transplants from another human, the recipient must take immune system-supressing medication to prevent the organ being attacked and rejected. Transplanting a pig heart into a human poses an additional problem in that pigs hearts express genes for the production of molecules not present in the human heart. These molecules trigger an immediate and aggressive immune response (the hyperacute rejection) in humans, essentially ruining the new heart within minutes.
In the case of David Bennet, the key ingredient to avoiding this immune reaction was gene editing. The pig from which the heart was taken had 4 genes deleted or inactivated, and 6 human genes were added. We don’t know exactly what modifications were made, but it’s likely that they included deleting the gene for α(1,3)galactosyl transferase, the main molecule responsible for hyperacute rejection. The aforementioned MHC molecules may have been modified, and edits were also made to prevent the heart from continuing to grow after transplantation.
This breakthrough is the result of many decades of work. The necessary technology has existed for over 20 years, and has been gradually improving during that time. Pig hearts were successfully transplanted into baboons in 2018, and surgeons successfully transplanted a kidney from a genetically altered pig into a human recipient last year. Attempting a pig heart transplant into humans had previously been prevented by safety concerns.
This surgery demonstrates that it is possible to transplant a pig heart into a human without a hyperacute rejection, which is excellent news. Pigs are easy and quick to raise, and using pigs as a source of organs shouldn’t raise too many ethical concerns given that pigs are already raised and killed for their meat and for other medical purposes. Combined with new cloning technologies, pig hearts and other organs could soon be used to plug the gap in the supply of transplantable organs.
It’s not all plain sailing ahead, though. Mr Bennet still runs the risk of chronic organ rejection later down the line. There’s also the question of how well a pig heart will actually function in a human circulatory system. Since pigs are four legged rather than upright like humans, their hearts don’t usually have to pump as much blood vertically, and so might have a harder time generating the necessary pressure in humans.
expert reaction to pig heart transplant: https://www.sciencemediacentre.org/expert-reaction-to-pig-heart-transplant/