The first pig heart transplant

First pig heart transplant

"Will I oink?" asks David Bennett, recipient of the pig heart transplant

Seven days into the new year, a ground-breaking operation was carried out in Baltimore, Maryland: the first ever transplant of a pig heart into a human. 57-year-old David Bennett suffered from end-stage cardiac failure. Having been deemed unsuitable for both a human heart transplant and a ventricular assist device (an artificial mechanical pump), he was permitted to receive the xenotransplant under compassionate use, which allows severely ill patients to receive unauthorised medicine as a last resort. Xenotransplantation entails inserting an organ of a different species into humans, an idea that has been around since the 1920s and still remains contentious. While the ethics that come with such a procedure are highly debated, the idea may offer hope to those awaiting transplants. A longstanding concern with all transplants is the risk of rejection from the recipient’s immune system. Using CRISPR, however, the organs can be genetically modified to reduce this risk. These organs typically come from pigs, as they are favoured over primates given they achieve human size in 6 months and are easy to raise. With pigs producing around 8 piglets per litter, many believe utilising their modified organs

Surgeons at the University of Maryland Medical Center transplanted a genetically altered pig heart into David Bennett.Credit: University of Maryland School of Medicine

may solve the urgent problem of organ shortages. The heart was derived from a pig developed by the US firm Revivicor, with 10 modified genes. Alpha-gal is a sugar found on the surface of pig cells which causes an aggressive immune response to flare up in humans. Of the 4 genes scientists inactivated, one coded for the enzyme that attaches this exact sugar. They also inactivated a gene which prevents the heart from continuously growing after transplantation by hindering its response to growth hormones. To boost acceptance, 6 human genes were further inserted into the heart. On 7th January, David Bennett underwent this procedure under immunosuppressants, and the outcome seemed to be optimistic afterwards, with reports of Bennett slowly gaining strength. He was under close monitoring for signs of organ rejection, which could take weeks or longer to manifest. Albeit the low risk at the time, they were also on the lookout for signs of infections. Unfortunately, Bennett passed away in March. Recent news disclosed that a latent virus, compounded with his initial heart condition, may have been contributing factors. However, scientists have noted that the cause of his death may not fall solely on the infection.

David Bennett Sr. (centre) after his heart transplant pictured with his son, David Bennett Jr (left) (Image credit: University of Maryland Medical Center)

Despite this, he survived significantly longer than the recipient of a baboon heart in 1984, and the surgical procedure has provided "invaluable insight" , in the researchers' words. Prior to this, late 2021 additionally saw several successful transplants of modified pig kidneys into brain-dead humans. In one such experiment, the recipient of the kidney was Jim Parsons, a registered organ donor whose family gave permission for the experiment to be carried out. The kidney came from the same line of pigs that Bennett obtained the transplanted organ from. They found that the transplanted kidney managed to produce urine for 77 hours. However, kidney function was not perfectly restored: it was unclear why the kidneys did not remove creatinine from the blood, which is an indicator of normal kidney function. Nonetheless, with 100,000 on the waiting list but less than 25,000 receiving kidney transplants in the US, kidney xenotransplantation may offer hope to many. Even if pig organs do not last as long as human organs might, a xenotransplant could be used while waiting for a compatible human organ to be available in the meantime. Reasonably, hesitancy remains. Worries are not least due to the viral genes that lurk in the genomes of all pigs (porcine endogenous retroviruses). However, fears may have been assuaged by evidence of successful transplants of pig pancreas cells into humans, and efforts to delete viral genes through genetic modification. Concern has also been raised over animal rights and welfare, especially given pigs will have to be reared in strictlymonitored pathogen-free environments to ensure organs are free of disease. And, of course, there is the everlasting question of what effects a xenotransplant may have on a recipient’s sense of identity. Clearly, the technology is not without ethical debate. If a kidney transplant does not go to plan, surgeons can remove the organ and put the patient back on dialysis. If the same happens for a heart transplant, the outlook does not bode so well. So, is experimenting with heart transplant ethical, such as in Bennett’s case? Scientists are eager to start larger trials testing similar heart transplants which can prove useful as attempts at understanding how humans would respond to xenotransplants are limited by animal models. However, some argue such experiments should be done incrementally with kidney transplants rather than heart transplants while others are adamant that the chances of surgical success greatly outweigh the risk of waiting for an available human organ. How would attitudes towards xenotransplantation change if we consider the usage of other animal parts in medicine that has been established for decades, such as that of pig heart valves, or insulin produced by pigs and cattle? Equipped with recent apparent successes in xenotransplantation, this poses many questions to consider when deciding the ethics, regulations and policies of such a technology, and how best to move forward.

Vanessa Yip

The kidney produced urine for 77 hours