Surgery & Anesthesia · 2021
Genetically Modified Pig-to-Human Kidney Xenotransplant
The organ transplant waiting list has grown steadily for decades, and kidney disease sits at its center. Fewer than 25,000 renal transplants are performed annually in the United States against a waiting list that has exceeded 90,000 patients. Xenotransplantation, using animal organs as a source, had been attempted sporadically since the 1960s, but every attempt foundered on hyperacute rejection: the human complement system recognized alpha-1,3-galactose residues on pig endothelial cells and destroyed the graft within minutes to hours. Genetic modification offered a theoretical escape from that barrier, but the step from preclinical primate work to a human recipient had not been taken.
In September 2021, Robert Montgomery and colleagues at NYU Langone surgically attached the kidney of an alpha-1,3-galactosyltransferase (GGTA1) knockout pig to the femoral vessels of a brain-dead human recipient being maintained on life support, with consent from the family. The organ was positioned outside the abdominal cavity to allow direct observation. Over 54 hours it produced urine, serum creatinine fell appropriately, and no signs of hyperacute rejection appeared. The result was notable not only for what happened but for what did not: the complement cascade did not fire, and the graft remained viable.
The donor pig carried a single gene knockout, the simplest genetic modification available at that stage. Within months, teams at NYU, the University of Alabama at Birmingham under Jayme Locke, and Massachusetts General Hospital were working with pigs carrying up to 10 genetic edits, including removal of additional pig antigens and insertion of human complement-regulatory, coagulation, and immune-modulatory genes. A separate 2021 experiment at UAB attached a similar pig kidney to a brain-dead patient for 74 hours without rejection. The field moved from proof-of-concept to iterative refinement within a single year.
Subsequent years brought more challenging tests. In 2022 a pig heart was transplanted into a living patient at the University of Maryland; it functioned for nearly two months before failure. The cause involved both immune factors and a porcine virus (porcine cytomegalovirus) that highlighted the need for comprehensive pathogen screening of donor animals. Chronic kidney disease affects roughly 37 million Americans, and xenotransplantation remains one of the few approaches that could increase the absolute supply of transplantable organs rather than optimizing allocation of an unchanged supply. Regulatory frameworks for first-in-human trials with genetically modified animal organs were under active development at the FDA as of 2024.
Key People
- Robert Montgomery — Transplant surgeon and NYU team lead
- Jayme Locke — UAB xenotransplant surgeon, subsequent pig kidney trials
- Mehmet Toner — Biomedical engineer, MGH
N Engl J Med, 2022
Related landmarks
- 2024 · First gene-edited pig kidney transplanted into a living person (Surgery & Anesthesia)
- 2009 · WHO Surgical Safety Checklist (Surgery & Anesthesia)
- 2000 · FDA Clearance of the da Vinci Surgical System (Surgery & Anesthesia)
- 1985 · First Laparoscopic Cholecystectomy (Surgery & Anesthesia)