Implications of the first pig-to-human transplants
Xenotransplantation could shorten the waitlist
Caption: The surgical team that transplanted a genetically engineered pig heart into a man in January 2022 included Pitt’s David Kaczorowski. The procedure took place at the University of Maryland Medical Center. Xenotransplantation was an interest of Pitt transplant giant Thomas Starzl, who conducted studies in transgenic pigs in the years before his death in 2017.
Demand for life-saving organ transplantation is at an all-time high. Last year, a record 41,000-plus organ transplants were performed in the United States, with top numbers for kidney, liver and heart transplants.
But a limited supply of donor organs continues to be a problem. Currently, transplant waitlists in this country exceed 100,000, with many patients unable to get on the list because of eligibility requirements and racial disparities in access.
As a cardiac transplant surgeon, I’ve witnessed the tragedy of this donor-organ shortage. But I’m also aware of a solution: xenotransplantation, which is transplantation of organs from one species into another.
In September 2021, researchers transplanted two genetically engineered pig kidneys into a brain-dead patient. And, in January 2022, I was part of the surgical team, with Bartley Griffith (Res ’81), that conducted the first pig-to-human heart transplant in a living patient at the University of Maryland Medical Center. I worked with members of the team at Maryland to perform the donor portion of the operation. Sadly, the patient died two months later; but the initial success of the procedure shows how far science has come toward making species-to-species transplants a reality.
Animal-to-human transplants aren’t new. In the 1960s, Keith Reemtsma, at Tulane University, performed 12 kidney transplants using chimpanzees as donors. While most of the transplanted organs—and ultimately the patients—survived for only a few weeks, one patient survived for nine months. Infection was the major issue in half of the patients, while irreversible organ rejection occurred in the other half.
Around that time, Thomas Starzl, then at the University of Colorado, also performed similar animal-to-human kidney transplants using baboons as donors, with the organs surviving up to two months. He’s most known for his liver transplants, with three attempts using chimpanzee livers from 1966 to 1974 that lasted from 24 hours to about two weeks. In the early 1990s, his two baboon-liver transplanted patients lasted for 26 and 70 days. Although one of the baboon livers functioned well, that patient died from infection.
Doctors have also made attempts to transplant animal hearts, the first of which predated the first human-to-human heart transplant. In 1964, a chimpanzee heart transplanted by James Hardy, at the University of Mississippi Medical Center, survived for a few hours.
Len Bailey’s 1983 attempt, at Loma Linda Health, at transplanting a baboon heart into an infant known as Baby Fae prolonged her life for 20 days, a record at the time.
While these early results may seem poor at first glance, a number of these transplants actually lasted longer than many early human-to-human kidney transplants. The first patient to receive a donated human kidney lasted for only four days in 1933, and later attempts in the 1940s and 1950s yielded similar results. Also, immunosuppressing drugs that prevent the immune system from attacking donor organs weren’t available during the early attempts at xenotransplantation.
Certainly, transplanting organs across species faces obstacles, the most integral being evolution. As species grow apart, increasing differences in their molecular makeup can result in incompatibilities that make cross-species transplant difficult or impossible. Among the most problematic are differences in immunity, inflammation and blood clotting that damage both the transplanted organs and the host’s body.
So, while pig-to-human transplants had been attempted in the past, 80 million years of evolution stood in the way. Pigs have molecules on the surfaces of their cells that humans don’t. If these molecules are introduced into a person’s body, the human immune system will register them as foreign and mount an attack. This process, hyperacute rejection, is a central reason many transplanted animal organs fail.
There have been advances in thwarting hyperacute rejection, such as using genetically engineered pigs that don’t carry the genes that produce the foreign molecules triggering rejection. The pig heart my team transplanted this year was genetically engineered, as were the pig kidneys from late 2021. There have also been improvements in medications that suppress the immune system of the recipient so it’s less likely the organ is attacked.
With more of these kinds of medical advances, I’m optimistic xenotransplantation will become a sensible option for all who need an organ.
Editor’s Note: David Kaczorowski (Res ’10) is a Pitt associate professor of cardiothoracic surgery. A longer version of this essay appeared in The Conversation.