An organ is a collection of tissues joined into a structure to serve a common function. Failure of an organ to perform its functions causes serious physiological diseases, and if left untreated, often leads to patient mortality. Unfortunately, organ failure is not uncommon. One of the most prevalent types is kidney failure, affecting approximately 815,000 Americans, most of which have developed from kidney diseases associated with diabetes and high blood pressure. 

Organ transplantation is one approach to treating organ failures. In the United States, more than 260,000 people are living with a kidney transplant.  However, transplantation largely relies on the availability of organ donors. Over 90,000 Americans are on the kidney transplant waiting list, but in 2024, only 1 in 4 patients were able to receive a kidney, forcing the majority to rely on alternative treatments such as dialysis. Ethical problems surrounding organ transplantation remain significant, as the growing demand for organs has led to unethical practices such as illegal organ trading. 

Xenotransplantation, the transplantation of organs or tissues from nonhuman organisms to humans, differs significantly from allotransplantation and autotransplantation, where transplants occur between humans or within the same individual, respectively. Attempts of xenotransplantation date back to the early 1900s. In 1905, French surgeon Laurent Princeteau implanted a rabbit kidney slice into a child suffering from renal insufficiency. 

In 1963, Dr. Keith Reemtsma at Tulane University pioneered the use of non-human primate xenografts (organs from non-human species) for treating kidney failure. Thirteen near-death patients received kidney transplants from Chimpanzees. Most of the patients died within four to eight weeks due to immune rejection or infectious complications. However, one patient survived an additional nine months and returned to work as a schoolteacher before dying from acute electrolyte disturbances, caused by excessive urine production (diuresis) associated with xenotransplantation. 

The first cardiac xenotransplantation was performed by Leonard Bailey, where the heart from a baboon was transplanted to an infant girl, anonymously known as “Baby Fae”. The transplantation was initially meant to be temporary, but unfortunately, a suitable donor was not available at the time, and Baby Fae died 20 days after the transplantation due to graft rejection, likely caused by ABO blood type mismatch. 

These early cases highlight one of the main challenges of xenotransplantation: transplant rejection. The human immune system is designed to attack any foreign substance, including xenografts. If this response is not dealt with, the immune cells destroy the organ immediately after the foreign organ is implanted into the receiver, triggering immune responses that can lead to the death of grafts, even patient death in severe cases. Advancements in immunology and pharmaceutics have equipped doctors with drugs that hold back the immune system from attacking foreign organs. 

In the 21st century, significant progress was made in the field of genetic engineering, which also shed light on xenotransplantation. Knocking out genes related to the production of immune response-triggering epitopes can reduce the likelihood of rejection. Starting in 2021, doctors from NYU Langone Health performed multiple experiments implanting genetically modified pig kidneys in patients recently declared brain dead. The kidney came from a pig donor with the gene encoding for the production of Galactose-α-1,3-galactose, a sugar that has been implicated in the immune response to mammalian tissue, knocked out. Clinical researchers reported that the xenograft maintained optimal function with no sign of immediate rejection. 

These findings paved the way for the first pig kidney xenografts in living patients. In March of last year, patient Richard Slayman received a pig kidney xenograft at the Massachusetts General Hospital. This kidney has 69 genomic edits in total, 3 of which are gene knockouts, and 7 human gene insertions. Mr. Slayman died two months later due to unrelated causes, with the xenograft not showing signs of rejection. In April 2024, patient Lisa Pisano received a pig kidney xenotransplantation at NYU Langone. She died in July of that year, due to multiple complications arising from the process. In November 2024, patient Towana Looney received a pig kidney xenograft at NYU Langone. Looney experienced a swift and successful convalescence, and as of this February, she has lived well for over 60 days post-transplant. 

While xenotransplantation presents a revolutionary approach to addressing organ shortages, further research and ethical considerations of performing medical procedures on non-human subjects must be addressed before it becomes a standard medical practice.