Opinion: Ending animal testing could set back xenotransplantation just as the field is poised for a breakthrough

OpinionFirst Opinion Ending animal testing could set back xenotransplantation just as the field is poised for a breakthrough Transplanting pig organs into humans is going to change lives — if the science can continue Manage alerts for this article Email this article Share this article By Joshua MezrichJune 9, 2026 Mezrich is professor of surgery at the University of Wisconsin and holds the Mark A. Fischer Chair in Transplantation. Health secretary Robert F. Kennedy Jr. seeks to end all federally funded animal testing after concluding that “the predictivity of animal models is very, very poor for human health outcomes.” In November 2025, Centers for Disease Control and Prevention staff were told that the agency would be required to phase out primate studies, and they are in the process of transferring their animals to a primate sanctuary. The National Institutes of Health, the largest funder of biological sciences in the U.S., has stopped issuing funding opportunities exclusively for animal models, sending a clear message that basic science conducted in animals small and large will no longer be a priority. Of the eight NIH-funded National Primate Research Centers in the U.S., one has been shuttered, and a second is exploring the possibility of converting to an animal sanctuary.Advertisement The desire to move away from animal experimentation is based on ethical concerns and a claim that animal trials are unreliable in predicting what will happen in humans. This has been accompanied by an assertion that “new approach methodologies” — including organs on chips, 3D tissue cultures (organoids), and artificial-intelligence-powered computational models — can be better predictors than animal studies. As a transplant surgeon, when I hear debates on this topic, I think about a revolution in health care we are witnessing right now. The field is xenotransplantation, or transplantation of pig organs into humans. And it’s going to change our lives — if changes to animal-testing policy don’t get in the way. In the 1980s, scientists recognized that if a pig organ was placed in a primate (as a model for a human), it would be rejected within minutes. Old world monkeys and humans harbor a natural antibody to a carbohydrate found on all the cells of pigs and other animals below primates on the evolutionary ladder. Multiple researchers futilely attempted to devise strategies to work around this antibody, to no avail.Advertisement Then, in 1996, along came the cloning of Dolly the sheep. This breakthrough represented the first quantum advance in the history of xenotransplantation, making it possible to eventually generate a pig without this carbohydrate (termed knockout pig). This spurred an influx of money from industry, with multiple companies looking for investment opportunities that would take advantage of cloning in both the U.K. and the U.S. Expectations were high, with predictions that xenotransplantation would become a reality in just a few years. But it wasn’t to be. By 2004 the industry money was gone because of three challenges. First, significant protests by animal rights activists, including the vandalizing of investigators’ homes and laboratories, drove efforts at xenotransplantation out of the U.K. Second, the discovery of an endogenous retrovirus in the genome of pig cells raised concerns about a potential xenovirus that could become active after transplanting pig organs into immunosuppressed humans. Third, the outcomes of the transplantation of pig organs into primates, the only model where it was/is possible to test how long a pig xenotransplant could be expected to survive in a human, weren’t improving quickly enough to achieve the companies’ aggressive timelines. Despite successfully utilizing gene therapy and cloning technology to knock the offending carbohydrate out of pig cells in 2003, kidneys and hearts could last only a few months when transplanted into primates before they were rejected. If it weren’t for government investment in continued animal research, xenotransplantation might have ended in 2004. But a handful of committed researchers refused to give up on the field. They secured enough funding with government grants to continue the incremental advances in gene editing and identification of targets that might eventually make it worthwhile to reengage with industry, doing their work in mice and rats, pigs, and primates. Gene editing improved significantly with the development of new techniques. Novel carbohydrates on the cells of pigs were identified and deleted, and experiments led to the addition of genes in the pigs that could further modify the rejection response. Outcomes of transplants into primates slowly began to improve.Advertisement Then in 2012, the second quantum advance in the history of xenotransplantation was realized when CRISPR-Cas9 was demonstrated as a gene-editing tool. This revolutionary discovery simplified gene-editing and made it realistic to generate complex gene-edited animals rapidly and efficiently. Once again industry money came looking for innovations that would utilize this earth-shattering technology, and xenotransplantation fit the bill. Shortly thereafter multiple animals were generated, including the United Therapeutics pig with 10 gene edits, and the eGenesis pig with 69 gene edits, the most edited large animal ever created. In the 1990s survival of xenografts transplanted from pigs to primates could be measured in hours or days. In the 2000s survival of kidney and heart xenografts was measured in weeks to months. Now we are now seeing life-sustaining kidney and heart xenografts lasting years in primates. It was this milestone, a year survival of a life-saving graft, that convinced researchers, clinicians, and regulatory bodies that it was time to consider xenotransplants in humans. Initially small trials were conducted transplanting these organs into brain dead humans, to ensure the organs would not be rapidly rejected and could sustain normal human physiology for a short period. Then, from January 2022 until January 2025 clinicians performed the transplantation of two pig hearts and four kidneys into living humans under the FDA-sanctioned Expanded Access pathway, with one kidney from eGenesis surviving nine months, bridging the recipient struggling on dialysis to an eventual human kidney. Just last year two clinical multicenter pig-to-human kidney transplant trials began, and more than 70 patients will receive life-sustaining pig kidneys in the next year. It is reasonable to assume that genetically modified pig organs will be available to save the lives of patients on the kidney and heart waitlist in the next five years. None of this could have happened without the use of animals for experiments. With each new iteration of transgenic pig, testing was required to assess the potential for graft survival and best use of immunosuppression. While numerous in vitro, cellular, and perfusion assays were used to predict how a novel graft might fare, ultimately the experimental transplants from pig to primate had to be performed to ensure the organs would survive and sustain life in the complex physiologic system that a transplanted organ is faced with.Advertisement While the current transgenic animals represent a massive medical breakthrough, novel iterations will be critical to generate pigs that rival and ultimately surpass outcomes of human organs. These iterations will require testing in primates prior to human trials, and it is only with these critical experiments that xenotransplantation can become a life-saving tool for millions of patients around the world. Perhaps some drug toxicity experiments can be replaced by new approach methodologies, although it is important to note that there is still so much we don’t know about how this will equate to outcomes and toxicity in humans. But it’s more hubris than expertise to claim that animal research no longer plays a role in advancement of medical science and can be replaced without any loss of progress. It is one thing if we decide as a society that we no longer want to fund animal research due to ethical objections, but we need to be realistic about what we will lose from a research standpoint. Innovations like xenotransplantation would never have reached clinical trials without animal experimentation. The U.K. forfeited its role in the field when it stopped supporting the animal work required to make it a reality. The entire field of human transplantation depended on animal research and wouldn’t exist without it. Heart surgery wouldn’t exist without this work, including cardiopulmonary bypass, valve replacements, and mechanical assist devices. The same can be said for the majority of medical innovations in the last 50 years. There are countless other medical innovations that will be lost without continued commitment to animal research. Are we willing to sacrifice breakthroughs we haven’t yet thought of? Joshua Mezrich, M.D., is professor of surgery at the University of Wisconsin and holds the Mark A. Fischer Chair in Transplantation. His second book, “Every Living Creature: How Xenotransplantation Will Change Our Lives,” was published in April. Letter to the editor Have an opinion on this essay? 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