David Bennett, 57, of Baltimore, Maryland, became the first person in the world to get a heart transplant from a genetically engineered pig on January 7. The pig heart was transplanted into Mr. Bennett, who was suffering from terminal heart failure, by surgeons at the University of Maryland Medical Center. Because xenotransplantation, or the transplanting of a pig’s heart into a human, is an experimental procedure, surgeons had to obtain emergency FDA approval (Food and Drug Administration). Mr. Bennett was nearly certain to die as a result of his disease, and he was too sick to qualify for a standard human heart transplant or an artificial ventricular assist device.
Surgeons at the New York University Langone Health medical centre transplanted a kidney from a genetically engineered pig into a brain-dead individual in late September of last year. On November 22, 2021, a person on a ventilator underwent the second similar pig kidney experiment at the same institution. The kidney was genetically modified to fool the human immune system into thinking it was foreign and rejecting it. The transplantation was solely an experiment to see whether an organ from a genetically engineered pig would be compatible, operate correctly, and not be rejected since the patients were already brain-dead.
What crucial genetic changes were made to allow for the transplantation of a pig heart?
Because the human immune system rejects anything unfamiliar, whether it comes from another person who is immunologically matched to the receiver or from a different species like a pig, scientists had to modify the pig DNA to make the organ less likely to be rejected. According to the New Scientist, Revivicor, a US-based business, is producing a small herd of genetically altered pigs. To reduce the risk of rejection, 10 of these pigs’ genes have been genetically changed. Four of the ten genes, including one that promotes an aggressive immune response and another that enables the heart to expand after transplantation, were inactivated. Six human genes were also put into the pig genome to lower the likelihood of rejection even further. In order for the transplanted pig heart to not be rejected, the recipient is also on an experimental drug that suppresses the immune system.
It was discovered in the early 1990s that all human immune responses were aimed towards a single pig antigen—a sugar molecule found on cell surfaces. Knocking down the gene that makes an enzyme, which makes the sugar molecule, lowers the chance of an immunological response that leads to rejection. Pig DNA also includes a large number of retroviruses that may infect human cells. Human recipients are more likely to get infected if such a virus is present in the transplanted organ. To make the organ safer for transplant, dozens of retroviruses have been removed.
Unlike traditional breeding procedures that required knowledge of both copies of a gene, genome-editing technologies like CRISPR/Cas9, which enable exact excision of particular genes, have made gene modification easier, faster, and more accurate. A genetically engineered pig cell is fused with a DNA-depleted pig ovum. The eggs that solely contain the genetically modified DNA begin to divide and develop into pig foetuses. Dolly, the sheep, was cloned using the same method. Surrogate moms have then used to implant the embryos. In contrast to humans, the gestation period is just 114 days. Despite the fact that pigs have a different immune system than humans, they have been chosen as good candidates for xenotransplantation since their organs are physically comparable.
What are the reasons for the increased acceptance of xenotransplantation?
Almost 4,000 patients in the United States received human donor hearts last year, but the demand is far greater. Kidneys are in the greatest demand. According to the health ministry, over 0.18 million individuals in India suffer from renal insufficiency each year, but only about 6,000 kidney transplants are performed each year. In India, between 25,000 and 30,000 liver transplants are required each year, but only approximately 1,500 are done. In the instance of the heart, 50,000 patients are in need of a heart transplant due to heart failure. In India, however, barely 10-15 heart transplants are performed each year. Harvesting organs from genetically modified pigs is being considered as a feasible option for meeting the organ shortage. Aside from technological hurdles, there are also ethical hurdles to surmount before porcine organ xenotransplantation becomes a reality.