From One Pig Heart to 69 Gene Edits: Four Years of Xenotransplantation Progress

On January 7, 2022, a pig heart beat inside a human body for the first time. Four years later, xenotransplantation has reached formal FDA-regulated clinical trials.

Xenotransplantation means transplanting gene-edited pig organs into humans. Since that first heart case in 2022, the field has moved to a regulated FDA trial stage within four years, making it one of the fastest-moving and most closely watched applications of animal models today. Two companies are validating different strategies in parallel, one using 10 gene edits and the other 69, and the field has not converged on a single answer. Hyperacute rejection and viral safety screening, the two central immunological hurdles, now have clear technical solutions. What remains genuinely unresolved is innate immune activation: even after depleting large numbers of T cells before surgery, rejection can still occur within a week. Every documented case so far has survived only weeks to a little over seven months, so durable long-term survival is still a long way off.

Organ shortage is a problem every transplant system in the world shares, and waiting lists are always longer than the supply of usable organs. Xenotransplantation, transplanting gene-edited animal organs into people, spent decades stuck at the animal-experiment and isolated-case stage. In the past four years, though, progress has been fast enough to warrant a fresh look: from the first case that made global headlines to a formally regulated clinical trial framework by 2025, xenotransplantation is turning from "miracle news" into a medical option with a defined technical roadmap.

Four Years, Five Milestones

• January 2022: The world's first living human pig-heart transplant, performed at the University of Maryland on David Bennett Sr. The pig had undergone roughly 10 gene edits, including knocking out the alpha-gal antigen gene that triggers hyperacute rejection and inserting human genes to help regulate immunity and coagulation. He survived about two months. The hospital reported the cause of death as heart failure from complex, multiple factors, with no classic signs of rejection on autopsy, though DNA traces of porcine cytomegalovirus (PCMV) were found in the transplanted heart, underscoring how important pathogen screening is (NBC News, 2022).
• September 2023: The same team performed a second heart xenotransplant on Lawrence Faucette, a 58-year-old veteran who did not qualify for a conventional heart transplant due to other chronic conditions. He was able to get out of bed for rehabilitation for a while, but around six weeks in, his heart showed signs of rejection and he died shortly after (CNN, 2023).
• March 2024: Massachusetts General Hospital (MGH) completed the first living pig-kidney transplant. The pig had undergone 69 gene edits, including inactivating 59 porcine endogenous retrovirus genes, the highest edit count on clinical record so far. The patient died suddenly on day 47 after surgery, but not from direct rejection.
• November 2024: Towana Looney became the longest-surviving pig-kidney recipient on record, living 130 days, four of them without needing dialysis, before the transplanted kidney was removed in April 2025 due to rejection (NYU Langone Health, 2024).
• February 2025: The FDA cleared a clinical trial (EXPRESS) for United Therapeutics' UHeart heart xenotransplant program, initially capped at two patients, marking the first time heart xenotransplantation formally entered an FDA-regulated IND trial (STAT, 2025).
• September 2025: The FDA cleared eGenesis's EGEN-2784 for a formal IND trial (Phase 1/2/3), moving xenotransplantation from expanded compassionate use into a proper clinical trial framework (eGenesis, 2025).
• November 2025: United Therapeutics and NYU Langone's EXPAND trial completed its first transplant (NCT06878560), starting with six participants and room to expand to 50, a turning point from compassionate use to a regular clinical trial (United Therapeutics & NYU Langone Health, 2025).

10 Edits or 69? Two Very Different Technical Approaches

Two distinct strategies have emerged in the field. Revivicor/United Therapeutics focuses on 10 gene edits: knocking out the main rejection-triggering genes and inserting key human genes. eGenesis goes much further, with 69 edits that also inactivate the pig's own retrovirus genes to prevent cross-species viral transmission. Both approaches have reached successful clinical trials, which tells us the field has not converged on a single "correct" answer, it is still testing different technical hypotheses in parallel.

Hyperacute Rejection: The First Hurdle Gene Editing Has to Clear

Human bodies carry large amounts of pre-existing antibodies against the alpha-gal sugar antigen on pig cell surfaces. Contact activates the complement system and can destroy an entire transplanted organ within minutes to hours, a phenomenon known as hyperacute rejection. Knocking out the GGTA1 gene that produces the alpha-gal antigen is the common first step across every xenotransplant program (Boulet et al., 2022), used in both the heart and kidney approaches. Beyond hyperacute rejection, safety screening for porcine endogenous retrovirus (PERV) is the other major immunological hurdle, which is exactly why 59 of eGenesis's 69 gene edits are dedicated to inactivating PERV genes.

Both cases lasted only weeks to a couple of months, far short of long-term survival, but they helped researchers pinpoint exactly where the real obstacles lie: hyperacute rejection can be addressed through gene knockouts, and viral safety screening already has a clear technical path. Neither is currently the biggest barrier facing xenotransplantation.

Rejection Can Still Occur Within a Week, Even After Clearing Out Immune Cells

The core challenge in xenotransplantation isn't surgical technique, it's the immune system. Studies show that even when large numbers of T cells are depleted before surgery, rejection can still appear within a week after transplantation (Boulet et al., 2022). This points to innate immunity, not just the well-known T-cell-mediated adaptive rejection, as the next hurdle to overcome. In the MGH kidney case, the patient's sudden death on day 47 was not caused by direct rejection; immune analysis showed that innate immune activation remains an unresolved problem.

Looking Ahead: Where Will the Organs Come From

If hyperacute rejection and viral safety screening can be further overcome, the central question in xenotransplantation shifts from "can a pig heart or kidney hold up" to "where will the organs come from." Global organ donation has long fallen short of demand, and many patients on waiting lists deteriorate or die before an organ becomes available. Gene-edited pigs with a controlled, traceable origin can, in theory, be bred at scale in controlled environments, free from the constraints of donor willingness and tissue matching. Biotech companies like Revivicor and eGenesis already maintain breeding populations of specific gene-edited pigs as part of their core business, so in a sense, a "pig population as organ source" is already underway, just still limited to a small number of compassionate-use and clinical-trial cases. What will actually determine whether this moves from isolated cases to routine surgery is still whether immune rejection and viral safety can be reliably solved, and that is still a long way from where the technology and clinical evidence currently stand.

Based on the sources checked, no direct reports of human xenotransplantation performed in Taiwan were found, though clinical cases have been reported at Xijing Hospital and Guangxi Medical University in China. Taiwan's pig-model research can be positioned as upstream animal experimentation and organ validation, connecting into these international clinical breakthroughs downstream, which is exactly the role animal-model services play across the whole development chain.

From a pig heart beating inside a human body for 60 days to 69 gene edits and survival past seven months, xenotransplantation hasn't advanced in a straight line, it's been a continuous process of trial and correction. Pigs are worth studying not because they look like us, but because they get sick the way we do, and recover the way we do too. Every correction in xenotransplantation starts with something validated first in an animal model.

Getting Fluent at the Operation Before the Real One

"The hard part of xenotransplantation is the immunology, not the surgical technique" holds on one condition: that the operating team already has the operation down. A heart transplant runs on feel and timing. From the moment the heart comes out to the moment a new one beats again, the patient's circulation and oxygenation are handed entirely to a cardiopulmonary bypass machine, and the order in which the aorta, both venae cavae, the pulmonary artery and the left atrium are anastomosed, the tension on every suture line, when to go on bypass and when to come off it, all of it ends up showing in the ischemic time. None of that can be read out of a paper. It has to be practised.

PigModel operates a cardiopulmonary bypass machine and offers surgeons in Taiwan a service for rehearsing heart transplant surgery in pigs. The pig is not a compromise here: porcine heart size, coronary distribution and hemodynamics are all close to human, the tissue feel under a needle, the vessel calibre and the anastomotic angles sit in the same range, and what a surgeon builds here carries straight back into the operating room. (Our companion piece, A Pig's Heart, a Human's Catheter: The Science of Cardiovascular Device Testing, compares that anatomy and physiology in more detail.)

To be clear about what this is and is not: practising on a pig trains the operation itself, not the immunological barrier this article has spent its length describing. Hyperacute rejection and innate immune activation do not go away because a team has grown fluent. But the reverse holds too. On the day the immunology is finally solved, whether that opening can be taken depends on whether there is a pair of hands that has already done this several dozen times. Taiwan has no clinical xenotransplant case to date, which also means this surgical pathway has no accumulated local experience behind it. Better to walk the learning curve in the animal lab than to begin it on the first real patient, so that when the first one truly happens, it is not the first one for the hands doing it.

Frequently Asked Questions

What is xenotransplantation?

Xenotransplantation means transplanting gene-edited animal organs, such as a pig heart or kidney, into a human body. In January 2022, the University of Maryland Medical Center completed the world's first living human pig-heart transplant, the field's first milestone.

How long can a patient survive after a pig heart transplant?

Neither of the two publicly documented heart xenotransplant cases has survived long. The first patient, David Bennett Sr., died about two months after surgery, mainly from heart failure caused by multiple complex factors (NBC News, 2022). The second patient, Lawrence Faucette, died about six weeks after surgery following signs of rejection (CNN, 2023).

What's the survival record for pig kidney transplants?

Towana Looney holds the longest survival record so far, at 130 days, including four months without needing dialysis, before the transplanted kidney was removed in April 2025 due to rejection (NYU Langone Health, 2024). Massachusetts General Hospital's first pig-kidney recipient died suddenly on day 47, though not from direct rejection (Ribas et al., 2026).

How many gene edits does a pig need before it can be transplanted into a human?

There are currently two main technical approaches. Revivicor/United Therapeutics uses about 10 gene edits focused on knocking out the main rejection-triggering genes. eGenesis goes further with 69 edits, including inactivating the pig's own retrovirus genes. Both approaches have reached clinical trials, showing the field hasn't converged on a single correct answer.

Why does the alpha-gal gene need to be knocked out in pigs?

Human bodies carry large amounts of pre-existing antibodies against the alpha-gal sugar antigen on pig cell surfaces. Contact activates the complement system and can destroy an entire transplanted organ within minutes to hours, known as hyperacute rejection. Knocking out the GGTA1 gene that produces alpha-gal is the common first step in every xenotransplant program (Boulet et al., 2022).

Once hyperacute rejection is solved, is xenotransplantation problem-free?

No. Studies show that rejection can still occur within a week after surgery even when large numbers of T cells are depleted beforehand, which points to innate immunity, not just the well-known T-cell-mediated adaptive rejection, as the next hurdle (Boulet et al., 2022). This remains a widely acknowledged unsolved problem in the field.

What stage has xenotransplantation reached now?

In September 2025, the FDA cleared eGenesis's EGEN-2784 for a formal IND clinical trial (Phase 1/2/3). That November, United Therapeutics and NYU Langone's EXPAND trial completed its first pig-kidney transplant under a formal regulatory framework, starting with six participants and room to expand to 50. Xenotransplantation is moving from expanded individual use toward standardized clinical trials.

Are there any clinical xenotransplantation cases in Taiwan?

Based on the sources checked, no direct reports of human xenotransplantation performed in Taiwan were found, though clinical cases have been reported at Xijing Hospital and Guangxi Medical University in China.

Does PigModel offer a heart transplant rehearsal service?

Yes. PigModel operates a cardiopulmonary bypass machine and offers surgeons in Taiwan a service for rehearsing heart transplant surgery in pigs. To be clear about the scope: what this trains is the surgical technique itself, going on and off bypass, the great-vessel anastomoses, and control of ischemic time. It does not address the immunological barrier in xenotransplantation, and it does not represent human xenotransplantation carried out by our company.

References

Boulet, J., Cunningham, J. W., & Mehra, M. R. (2022). Cardiac xenotransplantation: Challenges, evolution, and advances. JACC: Basic to Translational Science, 7(7), 716–729. https://doi.org/10.1016/j.jacbts.2022.05.003

CNN. (2023, October 31). Second person to receive experimental pig heart transplant dies nearly six weeks after procedure. https://www.cnn.com/2023/10/31/health/lawrence-faucette-second-pig-heart-transplant-dies

eGenesis. (2025). FDA clears EGEN-2784 for clinical trial (IND) [Press release]. https://egenesisbio.com/news-media/press-releases/

NBC News. (2022, July 8). First man to receive a transplanted pig heart died of heart failure, not rejection, encouraging doctors. https://www.nbcnews.com/health/heart-health/first-man-receive-transplanted-pig-heart-died-heart-failure-not-reject-rcna37078

NYU Langone Health. (2024). Towana Looney, longest-surviving pig-kidney transplant recipient [Press release].

Ribas, G. T., et al. (2026). Immune profiling in a living human recipient of a gene-edited pig kidney. Nature Medicine. https://doi.org/10.1038/s41591-025-04053-3

STAT. (2025, February 3). FDA approves first xenotransplantation clinical trial, as United Therapeutics forges ahead. https://www.statnews.com/2025/02/03/united-therapeutics-xenotransplantation-clinical-trial/

United Therapeutics, & NYU Langone Health. (2025). First transplant in the EXPAND clinical trial (ClinicalTrials.gov Identifier NCT06878560).