In a Groundbreaking Medical Feat, Genetically Edited Pig Kidney Is Transplanted Into Human

In a groundbreaking medical procedure, surgeons at Massachusetts General Hospital have successfully transplanted a genetically modified pig kidney into a 62-year-old man with end-stage kidney disease. This pioneering operation marks the first time an animal kidney engineered for human compatibility has been successfully transplanted into a living human recipient.

The patient, Richard (Rick) Slayman of Weymouth, Mass., underwent the four-hour surgery on March 16th. Slayman has type 2 diabetes and high blood pressure – the most common causes of chronic kidney disease. He had previously received a human kidney transplant in 2018, but that kidney failed after five years, forcing him back onto dialysis with worsening complications from end-stage renal failure. 

“The success of this transplant is the culmination of efforts by thousands of scientists and physicians over several decades. We are privileged to have played a significant role in this milestone,” said Dr. Tatsuo Kawai, HMS professor of surgery and director of the Legorreta Center for Clinical Transplant Tolerance at Mass General, who helped lead the transplant team. “Our hope is that this transplant approach will offer a lifeline to millions of patients worldwide who are suffering from kidney failure.”

Addressing a Critical Organ Shortage

The ability to safely utilize engineered animal organs addresses a critical shortage of donor organs available for the tens of thousands of patients in need of lifesaving transplants. According to the United Network for Organ Sharing, over 100,000 people in the U.S. are currently on the waitlist for an organ transplant, with 17 people dying each day still waiting. Kidneys are by far the most in demand, with an estimated 800,000 Americans suffering from end-stage kidney disease requiring dialysis or transplant.

“If it were easy, we’d be doing it by now, but it’s not,” said Dr. Joren Madsen, director of the MGH Transplant Center. “The barrier to pig xenotransplantation is formidable. The good news is we’ve been able to overcome that barrier.”

Overcoming Rejection Through Gene Editing  

The key breakthrough allowing for successful cross-species organ transplantation was the gene-editing work done to modify the pig’s kidney to be biologically compatible with the human body. Using CRISPR-Cas9 technology, the kidney received a total of 69 genomic modifications, including:

– Removal of certain pig genes that produce molecular sugars that trigger antibody rejection by the human immune system.

– Addition of specific human genes to improve compatibility and prevent rejection responses.  

– Inactivation of all porcine endogenous retroviruses embedded in the pig’s DNA to eliminate infection risk.

The genetically engineered pig kidney was provided by eGenesis, a company co-founded by HMS geneticist George Church that has partnered with Mass General over the past five years. Their extensive research culminated in a Nature paper published in October 2023 detailing the gene-editing processes.

Long-Term Monitoring Ahead

While Slayman’s body has shown no signs of rejecting the modified pig kidney so far, physicians stress that several years of close monitoring are still needed to evaluate long-term graft function and confirm sustained tolerance without complications. Ethical concerns around cross-species transplantation also remain.

Nevertheless, this breakthrough represents a monumental stride toward a future where a renewable supply of compatible, engineered organs could alleviate the perpetual strain on the limited pool of human donor organs. For the hundreds of thousands of patients ineligible or still waiting for a lifesaving transplant, it offers a powerful new ray of hope.

“We have made a tremendous step forward and confirmed that xenotransplantation is no longer hypothetical,” said Dr. Kawai. “We’re definitely on the road to producing an unlimited supply of organs to meet the staggering need worldwide.”