Weymouth man is world’s first living person to receive genetically edited pig kidney transplant

To make the kidney suitable for human use, researchers executed a series of ‘knockouts’ to reduce or eliminate antigen-based rejection. Human transgenes were inserted. And retroviruses endogenous to pig genomes were deactivated.

“Upon restoration of blood flow into the kidneys, the (porcine) kidney picked up immediately and started to make urine,” Kawai said. “When we saw the fast urine output, everyone in the operating room burst into applause.”

It was a long road to last Saturday’s surgery. Over the last five years, MGH researchers tested pig organs with various gene edits in non-human primates.

Officials said this successful procedure in a living recipient is “a historic milestone” in the emerging field of xenotransplantation – the transplantation of organs or tissues from one species to another – as a potential solution to the worldwide organ shortage.

“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. Our hope is that this transplant approach will offer a lifeline to millions of patients worldwide who are suffering from kidney failure,” Kawai said.

Elias added, “This seminal transplant could not be possible without collaboration and effort from multiple teams and specialists at MGH including physicians, surgeons, scientists, anesthesiologists, and nurses. They participated in coordinating the patient’s care in preparation for the transplant, seeing him through the surgery, and caring for him post-operatively.”

During a four-hour procedure on March 16, surgeons connected the pig kidney’s blood vessels and ureter with those of Slayman, who is living with end-stage kidney disease, hospital officials said.

The procedure was performed under a single FDA Expanded Access Protocol – known as compassionate use – granted to a single patient or group of patients with serious, life-threatening illnesses or conditions to gain access to experimental treatments or trials when no comparable treatment options or therapies exist, officials said. Slayman also received an infusion of novel immunosuppressant drugs, tegoprubart, provided by Eledon Pharmaceuticals Inc., and ravulizumab, provided by Alexion Pharmaceuticals Inc.

The procedure “marks a major milestone in the quest to provide more readily available organs to patients,” officials said.

Mass General Brigham has a notable history in organ transplant procedures.

The world’s first successful human organ transplant, a kidney transplant, was performed at Brigham and Women’s Hospital in 1954. The nation’s first penile transplant was performed at Mass General in 2016.

“Mass General Brigham researchers and clinicians are constantly pushing the boundaries of science to transform medicine and solve significant health issues facing our patients in their daily lives,” Dr. Anne Klibanski, president and CEO of Mass General Brigham, said in a statement Thursday. “Nearly seven decades after the first successful kidney transplant, our clinicians have once again demonstrated our commitment to provide innovative treatments and help ease the burden of disease for our patients and others around the world.”

“The tireless commitment of our clinicians, researchers and scientists to improving the lives of our transplant patients – both current and future – is at the very heart and soul of academic medicine and what it means to work and provide care at Mass General Brigham,” Dr. David F. M. Brown, president of Academic Medical Centers at Mass General Brigham, said in a statement. “We are so thankful to the incredible staff throughout our hospitals who helped make this surgery a success, and to the patient for his bravery and courage.”

The pig kidney was provided by eGenesis of Cambridge, from a pig donor that was genetically-edited using CRISPR-Cas9 technology to remove harmful pig genes and add certain human genes to improve its compatibility with humans, officials said. Additionally, scientists inactivated porcine endogenous retroviruses in the pig donor to eliminate any risk of infection in humans.

Over the past five years, MGH and eGenesis have conducted extensive collaborative research, with the findings published in Nature in 2023.

“We are grateful for the courageous contribution of the patient and to the advancement of transplantation science,” Mike Curtis, chief executive officer of eGenesis, said in a statement. “We congratulate our collaborators at MGH on this historic milestone. We also recognize the work and dedication of the eGenesis team that made this achievement possible. This represents a new frontier in medicine and demonstrates the potential of genome engineering to change the lives of millions of patients globally suffering from kidney failure.”

According to the United Network for Organ Sharing, more than 100,000 people in the U.S. await an organ for transplant and 17 people die each day waiting for an organ. A kidney is the most common organ needed for transplant, and end-stage kidney disease rates are estimated to increase 29-68 percent in the U.S. by 2030, according to literature published in the Journal of the American Society of Nephrology.

“The real hero today is the patient, Mr. Slayman, as the success of this pioneering surgery, once deemed unimaginable, would not have been possible without his courage and willingness to embark on a journey into uncharted medical territory. As the global medical community celebrates this monumental achievement, Mr. Slayman becomes a beacon of hope for countless individuals suffering from end-stage renal disease and opens a new frontier in organ transplantation,” Dr. Joren Madsen, director of the MGH Transplant Center, said in a statement.

In a statement, Slayman said he has been a Mass General Transplant Center patient for 11 years.

“When my transplanted kidney began failing in 2023, I again trusted my care team at MGH to meet my goals of not just improving my quality of life but extending it,” Slayman said. “My nephrologist, Dr. Winfred Williams, MD and the Transplant Center team suggested a pig kidney transplant, carefully explaining the pros and cons of this procedure. I saw it not only as a way to help me, but a way to provide hope for the thousands of people who need a transplant to survive.”

“I want to thank everyone at MGH who has cared for me, especially Dr. Williams, Dr. Kawai, the surgeon who performed my first kidney transplant and now this one, and Dr. Riella, who has orchestrated the logistics behind this new transplant. They have supported me during every step of the journey, and I have faith they will continue to do so,” Slayman said.

Slayman, who has been living with Type 2 diabetes and hypertension for years, previously received a kidney transplant from a dead human donor in December 2018, a procedure performed by Kawai, after being on dialysis seven years before that, officials said.

The transplanted kidney showed signs of failure about five years later and Slayman resumed dialysis in May 2023.

Since resuming dialysis, he encountered recurrent dialysis vascular access complications requiring visits to the hospital every two weeks for de-clotting and surgical revisions, significantly impacting his quality of life and a common problem among dialysis patients, officials said.

Riella led the group of Mass General Transplant Center physicians in applying for the Expanded Access Protocol, which was rigorously reviewed by the FDA before its approval in late February, officials said. Combined, MGH transplant clinicians and surgeons have nearly 30 years of experience with xenotransplantation research.

“Seventy years after the first kidney transplant and six decades following the advent of immunosuppressive medications, we stand on the brink of a monumental breakthrough in transplantation. At MGH alone, there are over 1,400 patients on the waiting list for a kidney transplant. Some of these patients will unfortunately die or get too sick to be transplanted due to the long waiting time on dialysis. I am firmly convinced that xenotransplantation represents a promising solution to the organ shortage crisis,” Riella said.

This is a developing story. Check back for updates as more information becomes available.

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