Genetically Modified Pigs and the Promise of Unlimited Organs

What if your number on a waiting list determined whether you lived or died? Imagine you just learned you needed an organ transplant—a kidney, a heart, a liver, or some other organ—to regain energy to go to work, or attend school, or simply to stay alive and out of the hospital. Unfortunately, because you have Type O blood, you can only receive organs from Type O donors. So you may face a wait of two to five years before you can receive a suitable transplant.

This isn’t a TV or film drama—it’s real life. The severe shortage of organ donors leaves over 100,000 patients in the United States on transplant waiting lists, according to the United Network for Organ Sharing. Many of those people may never receive the life-saving procedures they need. In 2024, more than 48,000 organ transplants were performed, including from more than 7,000 living donors and more than 17,000 deceased donors. While recipients of living-donor transplants typically wait only a few months for the donor to be evaluated, those waiting for organs from deceased donors face much longer waits. The organ donor shortage has cost countless lives. 

There may be a solution in decades to come: genetically modified pigs. By altering the genes of pigs to make their organs more compatible with humans, scientists are creating the possibility of a limitless supply of organs. Transplanting organs from one species to another is called xenotransplantation. Pigs are promising organ donors because their organs are closest in size and function to human ones. And pigs are easy to breed in large numbers. 

However, pig organs have molecules that trigger an immune response in humans, leading to rejection. To overcome this challenge, scientists are using CRISPR-Cas9, a gene-editing technology, to modify specific genes such as GGTA1, which produces a sugar molecule on pig cells that the human immune system attacks. The genetic modifications are made to pig skin cells; then the nuclei of those cells are injected into pig egg cells, which become embryos that are implanted in mother pigs. The mothers give birth to genetically identical pigs with the desired traits, such as reduced risk of organ rejection which makes them reliable for future transplants. These modifications have already been demonstrated successfully in several cases. 

In January 2023, surgeons at the University of Maryland Medical Center successfully transplanted a genetically modified pig heart into a human patient for the first time. Although the patient, David Bennett Sr., only lived for two months following the historic surgery, it marked a significant milestone for xenotransplantation.

“One of the biggest challenges to successful xenotransplantation is overcoming organ rejection,” explains Jeffrey L. Platt, M.D., professor of surgery, microbiology, and immunology, and head of the Transplantation Biology Program at the University of Michigan Medical School. “For xenotransplantation to work on a regular basis, gene manipulation must be combined with immunosuppression to hinder the immune response of the recipient that otherwise would cause rejection of the transplant.” In addition, gene manipulation can be combined “with other methods to lessen incompatibilities and exclude infectious organisms.” 

Platt emphasizes the importance of experience in the field, noting crucial lessons learned from kidney and heart transplants. “We need much more experience in xenotransplantation to achieve success,” he says. “It was experience as much as any drug that helped human-to-human transplantation become a regular part of medical practice and much more experience will be needed to identify and overcome all of the hurdles to success in xenotransplantation.”

Despite the potential to save lives, the use of genetically modified pigs in organ transplants presents other challenges. The primary concern is the risk of disease transmission. Pigs can carry zoonotic diseases—diseases that can be transmitted from animals to humans—which could present serious health risks if not properly controlled. To address this problem, researchers are carefully screening pigs designated as organ sources for harmful bacteria and viruses, and even making genetic changes to make the pigs more resistant to such pathogens.

“Looking to the future, the prospects for xenotransplantation are bright,” says Platt. “As research progresses and new technologies emerge, we may find that xenotransplantation or other technologies will make replacement of organs more accessible and less apt to impose risk and [more likely to] improve outcomes.” Genetically modified pigs could one day transform organ transplants, offering new hope to patients and families.