The first reported person in the world has received a genetically modified pig kidney. A transplant surgeon at Massachusetts General Hospital successfully performed the groundbreaking, four-hour procedure on Richard Slayman, a 62-year-old manager at the Massachusetts Department of Transportation, on March 16. His doctors report he is doing well and expect him to leave the hospital soon.
The surgery was the culmination of years of work transplanting kidneys from a specially bred group of pigs—which had been genetically modified to more closely resemble those of humans—into primates. Encouraged by those results, the team at Mass General Brigham—the health system to which the hospital belongs—was confident it was time to test the pig organs in the first patient.
Slayman had received a human kidney transplant five years ago, but like so many people with kidney disease, the organ began to fail and he continued to need dialysis. Even those frequent efforts to replenish his kidney function weren’t enough, however, and his health progressively worsened. “At one point, he literally said, I just cannot go on like this,” said Dr. Winfred Williams, Slayman’s physician and associate chair of nephrology at Massachusetts General Hospital, during a March 21 briefing.
Dr. Tatsuo Kawai, director of the Massachusetts General Hospital’s Legorreta Center for Clinical Transplant Tolerance, was Slayman’s kidney transplant surgeon five years ago, and he also performed the pig-kidney surgery. While more than a dozen people in the operating room watched, Kawai carefully connected the pig kidney to Slayman’s circulatory system—not an easy task, given the patient’s history of diabetes and hypertension, which had weakened his blood vessels. “The size of the pig kidney was exactly the same as the human kidney,” Kawai said during the briefing. “Upon restoration of blood flow into the kidney, the kidney pinked up immediately and started to make urine. When we saw the first urine output, everyone in the operating room burst into applause. It was truly the most beautiful kidney I have ever seen.”
The pig donor
The kidney came from a special group of pigs bred to produce human-like kidneys. eGenesis, a biotech company that has been studying ways to make animal tissues as human as possible, worked closely with the research team at Mass General Brigham to come up with the right genetic animal donors that would make their organs safe enough to transplant into people, and effective enough to take over their kidney function.
Several genetic innovations over the past few decades made such a feat possible. The pigs’ cells were treated with the gene-editing technology CRISPR, which allows scientists to make very precise genetic changes in cells. These CRISPR-ed cells were then used to create pig clones so the pigs would have identical and consistent genetic changes. Their kidneys were then transplanted first into primates, and finally into Slayman.
All told, the pig kidneys contained 69 genetic changes in three major categories. The scientists knocked out or eliminated three pig genes that trigger immediate rejection by the human immune system, added seven human genes to make the pig tissue appear more human to the immune cells, and inactivated viral genes in pig cells that could cause infections. They also used a unique cocktail of antibody treatments to further dampen the immune reaction and give the transplanted kidney the best chance of surviving in the patient.
Next steps
eGenesis is working on other pig organs as well. In January, the company partnered with researchers at the University of Pennsylvania to transplant a genetically modified pig liver into a brain-dead patient. That work, along with Slayman’s experience, is making a strong case for the role of pig organs in addressing the shortage of organs for thousands of patients on waiting lists. More than 100,000 people are placed on the kidney transplant waiting list in the U.S. each year, while only 20,000 kidneys are available.
The Mass General Brigham team hopes to perform more of these transplants to get a better idea of how long the pig kidneys can function and whether they can meaningfully extend the length and quality of patients’ lives. For now, says Williams, patients on the waiting list or dialysis could potentially benefit from receiving a pig kidney temporarily as they wait for a human one. Even such bridging can be critical for patients like Slayman; while he had been on dialysis, he experienced clotting issues that compromised the blood flow required to make it effective and required dozens of surgeries to improve his circulation. Pig kidneys could become a realistic option for people like him for whom dialysis becomes too challenging.
The long-term hope is that pig kidneys may even become a substitute for human organs if they prove up to the task. “We never anticipated dialysis would become a lifelong solution for kidney failure,” said Dr. Leonardo Riella, medial director of kidney transplantation at Mass General Brigham and lead investigator of the trial. “Yet this is the stark reality for over 600,000 patients in the U.S.; dialysis has sadly become their last resort for managing their disease. Now picture a different narrative, one where healthy kidneys are readily available for transplantation. Today we are offering a glimmer of hope that may one day be possible for many more patients.”