How the kidney of a pig might offer hope for those in need of transplants

Pioneering research builds on groundwork laid in Pittsburgh 

PITTSBURGH, Pa. — In an advance announced this week, surgeons in New York successfully attached a kidney from a genetically modified pig to a deceased person and kept the organ functioning for two days. It is a significant step toward using pigs as organ donors for people who desperately need transplants.

Research carried out by Dr. Thomas E. Starzl, a transplant physician at the University of Pittsburgh Medical Center who died in 2017, helped lay the groundwork for the experimental procedure.

“I would consider this a milestone,” said Dr. Mohamed Ezzelarab, associate professor of surgery at Pitt’s Thomas E. Starzl Institute.

Dr. Starzl carried out the world’s first liver transplant in 1963 while at the University of Colorado. After joining the University of Pittsburgh Medical School in 1981, he went on to establish the city as a leader in organ transplantation. In the early 1990s, Dr. Starzl transplanted livers from baboons into two critically ill patients. One survived 70 days after the procedure.

“Dr. Starzl saw this as a possibility a long time ago,” Dr. Ezzelarab said in an interview on Wednesday. But he cautions that it is likely to be years until pig organs could be used to help living patients in need of transplants.

More than 100,000 people in the United States are on the waitlist to receive an organ — most of them in need of a kidney. An estimated 17 people die every day waiting for an organ, according to the Organ Procurement and Transplantation Network. Animals could provide a virtually unlimited supply, but their organs are not naturally compatible with human bodies.

In recent years, scientists have turned to pigs over baboons as a potential source of organs. Pigs mature much faster than baboons and are already raised for agriculture. But when their organs are transplanted into monkeys, which researchers often use as stand-ins for humans, they’re swiftly rejected.

A main culprit is a sugar known as alpha-gal, which is found on the surface of pig cells and sets off an immediate immune response in the body. Researchers have successfully carried out transplants in monkeys using organs from pigs engineered to lack the gene that makes this sugar. The New York experiment shows that removing this gene may be able to avert immediate immune rejection in humans, too.

This type of immune response, hyper-acute rejection, occurs within minutes after a transplant. “Being able to get past that first hurdle and not have this hyper-acute rejection is very exciting,” Dr. Lynsey Biondi, surgical director of kidney transplant at West Virginia University Medicine, said in an interview. Beyond hyper-acute rejection, there are other types of rejection that can happen weeks or months after a transplant, she said.

In the New York experiment, first reported by USA Today on Oct. 19, surgeons attached a pig kidney to the blood vessels of a brain-dead patient outside of her body. Soon after, the organ started functioning normally, making urine and filtering waste, according to the team that carried out the procedure on Sept. 25. The patient’s family gave consent for the experiment, and researchers observed the kidney’s function for a little over two days.

“It functioned really well and it didn’t reject,” Dr. Robert Montgomery, the surgeon at New York University’s Langone Transplant Institute who oversaw the procedure, said in a video produced by USA Today. The results of the experiment have not yet been peer-reviewed nor published in a scientific journal.

Dr. Muhammad Mohiuddin, a professor of surgery and director of cardiac xenotransplantation — transplants between species — at the University of Maryland School of Medicine, told the Post-Gazette that the experiment is “definitely a step forward” in making pig-to-animal transplants a reality.

But it doesn’t provide any information on how long a kidney from a genetically engineered pig will last in a person who needs a life-sustaining transplant.

Eliminating the gene that produces alpha-gal is likely just the first step. Dr. Mohiuddin and other experts in the field believe additional genetic alterations will be needed in order to make pigs’ organs more suitable for humans. Dr. Mohiuddin’s group is experimenting with pigs that have half a dozen genetic modifications. A Chinese company, Qihan Biotech, has generated pigs with42 modifications across 13 genes.

The pigs used in the NYU experiment, which have just the one genetic modification, were approved by the Food and Drug Administration in December for both human consumption and medical purposes.

Most people are born with two kidneys, and those who are healthy enough can donate one. But Dr. Biondi says there aren’t enough people who are willing to be living donors.

To meet the huge need for donor organs, transplant specialists can now use kidneys from deceased donors with certain infections, like hepatitis C, who were previously ineligible. Doctors are also using specialized machines to preserve kidneys for longer in an effort to use as many as possible. But these steps haven’t been enough to meet the kidney shortage.

“Right now, we’re stuck in this paradigm which is that someone has to die in order for someone else to live,” Dr. Montgomery said in the video. “What we need is a sustainable, renewable source of organs, and that’s what xenotransplantation would provide.”

The animal rights organization People for the Ethical Treatment of Animals, or PETA, issued a statement saying: “Pigs aren’t spare parts and should never be used as such just because humans are too self-centered to donate their bodies to patients desperate for organ transplants.”