Xenotransplantation
Xenotransplantation, or heterologous transplant, is the transplantation of living cells, tissues or organs from one species to another. Such cells, tissues or organs are called xenografts or xenotransplants. It is contrasted with allotransplantation, syngeneic transplantation or isotransplantation, and autotransplantation. Xenotransplantation is an artificial method of creating an animal-human chimera, that is, a human with a subset of animal cells. In contrast, an individual where each cell contains genetic material from a human and an animal is called a human–animal hybrid.
Patient derived xenografts are created by xenotransplantation of human tumor cells into immunocompromised mice, and is a research technique frequently used in pre-clinical oncology research.
Human xenotransplantation offers a potential treatment for end-stage organ failure, a significant health problem in parts of the industrialized world. It also raises many novel medical, legal and ethical issues. A continuing concern is that many animals, such as pigs, have a shorter lifespan than humans, meaning that their tissues age at a quicker rate. Disease transmission and permanent alteration to the genetic code of animals are also causes for concern. Similarly to objections to animal testing, animal rights activists have also objected to xenotransplantation on ethical grounds. A few temporarily successful cases of xenotransplantation are published.
Bioprosthetic artificial heart valves are generally pig or bovine-derived, but the cells are killed by glutaraldehyde treatment before insertion, therefore technically not fulfilling the WHO definition of xenotransplantation of being live cells.
History
The first serious attempts at xenotransplantation appeared in the scientific literature in 1905, when slices of rabbit kidney were transplanted into a child with chronic kidney disease. In the first two decades of the 20th century, several subsequent efforts to use organs from lambs, pigs, and primates were published.Scientific interest in xenotransplantation declined when the immunological basis of the organ rejection process was described. The next waves of studies on the topic came with the discovery of immunosuppressive drugs. Even more studies followed Joseph Murray's first successful renal transplantation in 1954 and scientists, facing the ethical questions of organ donation for the first time, accelerated their effort in looking for alternatives to human organs.
Non-human kidney to a human
On February 16, 1963, the first transplant of a non-human animal's organ into a human being took place in Minneapolis when surgeons led by Claude R. Hitchcock and R. Joseph Kiser "tried grafting a baboon kidney" into "a woman in whom previously implanted human kidney was doing poorly", and the kidney "immediately began functioning normally and cleared her blood of wastes". Her body rejected the kidney five days afterward and she died in March, three weeks later.Starting in October 1963, doctors at Tulane University attempted renal transplantations from non-human primates in six people who were near death. The first person, a 32 year old woman with a chronic kidney disease received the kidneys of a rhesus monkey and the kidneys "functioned well for seven days, then failed," and the patient died later from her illness. The first successful attempt with a chimpanzee was performed on November 5 at Charity Hospital in New Orleans by a 12-man team of Tulane physicians, led by Keith Reemtsma, and the patient, a 44-year-old dock worker named Jefferson Davis, left the hospital on December 17 after a six-week recuperation. After this and several subsequent unsuccessful attempts to use primates as organ donors and the development of a working cadaver organ procuring program, interest in xenotransplantation for kidney failure dissipated. Out of 13 such transplants performed by Keith Reemtsma, one kidney recipient lived for nine months.
Non-human heart to a human
An American infant girl known as "Baby Fae" with hypoplastic left heart syndrome was the first infant recipient of a xenotransplantation, when she received a baboon heart on October 26, 1984. The procedure was performed by Leonard Lee Bailey at Loma Linda University Medical Center in Loma Linda, California. Fae died 21 days later, on November 15, due to a humoral-based graft rejection thought to be caused mainly by an ABO blood type mismatch, considered unavoidable due to the rarity of type O baboons. The graft was meant to be temporary, but unfortunately a suitable allograft replacement could not be found in time. While the procedure itself did not advance the progress on xenotransplantation, it did shed a light on the insufficient amount of organs for infants. The story made such an impact that the crisis of infant organ shortage improved for that time.Non-human heart, lungs, and kidneys to a human
The first heart transplant in a human ever performed was by Hardy in 1964, using a chimpanzee heart, but the patient died within 2 hours.The first transplant of a non-genetically modified pig's heart, lungs and kidneys into a human was performed in Sonapur, Assam in mid-December 1996, and was announced in January 1997. The recipient was Purno Saikia, a 32-year-old terminally-ill man; he died of multiple infections shortly after the operation. The Indian cardiothoracic surgeon Dhani Ram Baruah and two of his associates, Jonathan Ho Kei-shing and C.S. James, performed the surgeries. Baruah claimed that Saikia had failed to respond to conventional surgery, and that the patient and his family had consented to the procedure.
All three involved in the surgery were arrested on January 9, 1997, for the alleged violation of the Transplantation of Human Organs and Tissues Act of 1994. Baruah was dismissed in medical circles as a "mad scientist" and the procedure was dubbed a "hoax". Baruah signed a statement saying he had done no transplant, but then alleged that the confession was forced from him. They were found guilty of unethical procedure and culpable homicide and imprisoned for 40 days. Dhani Ram Baruah's surgical institute was also found to be without necessary registration.
Critics said Dhani Bam Baruah's claims and medical procedures were neither taken seriously nor accepted by the scientific community because he never got his findings scientifically peer-reviewed. Past complaints of ethics violations during surgeries in Hong Kong by Baruah and Ho had occurred in 1992, when they had implanted heart valves, developed by Baruah, made of animal tissue. A year later, six patients died. The Asian Medical News reported that "grave concerns" were expressed "over the procedure and ethics of the implementation".
Genetically engineered non-human kidney to a human
In September 2021, surgeons led by Robert Montgomery performed the first genetically engineered pig kidney xenotransplant to a brain-dead human at NYU Langone Health with no sign of immediate rejection. The kidney was procured from a pig with only a single gene modification: the removal of alpha-gal.In July 2023, surgeons from the NYU Langone Transplant Institute completed a transplant of a genetically modified pig kidney into a patient declared brain dead but maintained on a respirator. The patient had previously consented to be an organ donor, but his tissues were not considered suitable for transplant. The kidney came from an animal with a knocked-out gene for the production of alpha gal sugars, which has been implicated in immune response to mammalian tissue. In order to ensure that renal function was only supported by the pig kidney, the team removed both of the patient's kidneys. The team has reported that the kidney has maintained optimal functioning for over a month, as evidenced by routine testing of creatinine and weekly biopsies. The team plans to monitor the patient for another month, pending approval by ethics board and his family.
In March 2024, Richard Slayman, a patient whose transplanted human kidney had failed, received a genetically engineered pig kidney xenotransplant from surgeons at Massachusetts General Hospital. This kidney has 69 genomic edits made by eGenesis, Inc. Slayman died a few months later of unrelated causes, with no apparent rejection of the kidney. Meanwhile, in April 2024, Lisa Pisano became the second person to receive such a kidney transplant. Because of "unique challenges" related to a mechanical heart pump she received along with the kidney, her kidney had to be removed due to "insufficient blood flow" late in May. Medication also deteriorated the kidney, which led to its rejection.
On January 25, 2025 Tim Andrews and on June 14, 2025 Bill Stewart received pig kidneys similar to the one used for Slayman. Leonardo V. Riella Tatsuo Kawai and Nahel Elias were medical and surgical directors for these two transplants both done at Massachusetts General Hospital. Both patents are still successfully off dialysis and the first of these is "the longest known survival time for a gene-edited pig organ to date" in a patient. "Based on lessons from these early cases, the U.S. Food and Drug Administration has granted approval to biotech company eGenesis to launch a clinical trial that will transplant gene-edited pig kidneys into 30 patients who are 50 or older and on dialysis while awaiting a human kidney."
Genetically engineered non-human heart to a human
In January 2022, doctors led by cardiothoracic surgeon Bartley P. Griffith and Muhammad M. Mohiuddin at the University of Maryland Medical Center and University of Maryland School of Medicine performed a heart transplant from a genetically modified pig to a terminally ill patient, David Bennett Sr., who was ineligible for a standard human heart transplant. The pig had undergone specific gene editing to remove enzymes responsible for producing sugar antigens that lead to hyperacute organ rejection in humans. The US medical regulator gave special dispensation to carry out the procedure under compassionate use criteria. The recipient died two months after the transplantation.In June and July 2022, surgeons at NYU Langone Health performed two genetically modified pig heart transplants into recently deceased humans. The hearts were from pigs that had the identical 10 genetic modifications used in the University of Maryland Medical Center heart xenotransplantation in January 2022. All three hearts came from Revivicor, Inc., a facility based in Blacksburg, Va., and a subsidiary of United Therapeutics.
On 20 September 2023, surgeons at the University of Maryland Medical Center in Baltimore performed a heart transplant from a genetically modified pig to Lawrence Faucette, a patient with terminal heart disease who was ineligible for a traditional heart transplant. On 30 October 2023, Faucette died after showing signs of organ rejection.