By Dr. Marco Vinicio Benavides Sanchez

In recent years, one of the most revolutionary frontiers in modern medicine has begun to move from the realm of science fiction into clinical reality: xenotransplantation, the transplantation of living cells, tissues, or organs from one species into another. Of particular interest is the use of genetically modified pigs as a source of organs for human patients. This once-taboo idea is now being tested in high-profile clinical trials with encouraging—but cautious—results. So, where do we stand today?

The Organ Shortage Crisis

The driving force behind xenotransplantation is the global organ shortage. Tens of thousands of patients around the world die every year while waiting for an organ transplant. In the United States alone, over 100,000 people are on the transplant waiting list, with many dying before a compatible organ becomes available.

Human organ donation is simply not keeping pace with the demand. The concept of using animal organs to fill this gap is not new—it was first proposed over a century ago. But early attempts, including baboon-to-human transplants, were marred by immunological rejection, ethical concerns, and technical failures.

Why Pigs?

Pigs have emerged as the most promising donor species for several compelling reasons:

• Size compatibility: Pig hearts and kidneys are similar in size and function to human organs.

• Reproductive efficiency: Pigs reproduce quickly and can be bred in controlled environments.

• Genetic modifiability: Advances in gene editing (especially with CRISPR-Cas9) have enabled the creation of pigs whose organs are less likely to be rejected by the human immune system.

Furthermore, pigs are already used in medicine—for example, pig heart valves and insulin—reducing some of the ethical concerns compared to using primates.

A Breakthrough in Heart Transplantation

In January 2022, the world witnessed a historic event: a 57-year-old man with end-stage heart failure received a genetically modified pig heart in a transplant performed at the University of Maryland Medical Center. The patient, David Bennett Sr., survived for two months post-surgery before dying of heart failure, possibly related to porcine cytomegalovirus (a pig virus).

Although the patient did not survive long-term, the procedure marked a watershed moment. It proved that a pig heart could support human life, at least temporarily, without immediate hyperacute rejection.

In September 2023, a second patient, Lawrence Faucette, received a pig heart under even more controlled conditions. He lived for six weeks before succumbing to heart failure, but again, the organ functioned well for a time. Researchers learned valuable lessons about immune suppression, organ preservation, and infection control.

Kidney Transplants Show Even More Promise

In the realm of kidney transplantation, xenotransplantation is making even more rapid progress. In 2021, surgeons at NYU Langone Health transplanted pig kidneys into brain-dead human recipients maintained on life support. The kidneys began producing urine immediately and continued to function for days without rejection.

More recently, in 2023 and 2024, several successful pig-to-human kidney transplants were performed on living recipients with promising results. In March 2024, a 62-year-old man with end-stage renal disease received a pig kidney transplant at Massachusetts General Hospital. The kidney, from a genetically engineered pig, functioned properly, allowing the patient to stop dialysis.

This success demonstrated that xenotransplantation could move from experimental surgery into potential clinical application.

How Are These Pigs Modified?

To prevent the human immune system from attacking the pig organs, the donor pigs are heavily genetically engineered. Most commonly, this involves:

• Knocking out key pig genes that trigger hyperacute rejection (e.g., the gene that produces alpha-gal, a sugar molecule not present in humans).

• Adding human genes to make the organ more “human-like” immunologically (e.g., human complement regulatory proteins).

• Inactivating retroviruses embedded in the pig genome to prevent the risk of cross-species infections.

Some pigs used in recent transplants have had 10 or more genetic modifications, making them bioengineered organ sources rather than ordinary farm animals.

What Are the Risks?

Despite the progress, several major concerns remain:

1. Immune rejection: Even with advanced gene editing, long-term tolerance is not guaranteed. Rejection may occur weeks or months later, often suddenly and severely.

2. Zoonotic infections: Transplanting animal tissue into humans carries the theoretical risk of introducing new pathogens, such as porcine endogenous retroviruses (PERVs).

3. Ethical issues: Questions about animal rights, informed consent, and fairness in access must be addressed as this field grows.

4. Immunosuppression: Like with any transplant, patients require powerful drugs to suppress the immune system, increasing the risk of infections and cancer.

Regulatory and Ethical Perspectives

In the United States, the Food and Drug Administration (FDA) is closely monitoring xenotransplantation studies under its “expanded access” framework, allowing compassionate use in patients with no other options. However, full regulatory approval for widespread clinical use is still years away.

Ethically, the use of pigs—already widely raised for food—may be more acceptable to the public than using primates. Nonetheless, transparency, animal welfare, and patient autonomy remain critical considerations.

The Road Ahead

As of mid-2025, we are standing at the threshold of a new era. Xenotransplantation is no longer a theoretical solution; it is now a real, viable possibility being tested in operating rooms and intensive care units.

However, widespread clinical use will require:

• More robust clinical trials to assess safety and efficacy.

• Standardized protocols for pig breeding, organ harvesting, and transplantation.

• Long-term follow-up data on recipients.

• Global collaboration among regulatory agencies, researchers, and bioethicists.

Several biotech companies, including eGenesis, Revivicor, and Makana Therapeutics, are racing to develop clinical-grade xenografts. Meanwhile, advances in synthetic biology and artificial organs may eventually complement or even replace the need for pig organs altogether.

Conclusion

Xenotransplantation is progressing faster than many had anticipated. What was once considered speculative is now entering the clinic, offering hope to thousands of patients who might otherwise die waiting for a human organ. The road ahead is still filled with scientific, ethical, and logistical challenges, but the first steps have already been taken—and they are monumental.

If successful, pig-to-human transplantation could transform modern medicine and redefine our relationship with biology, technology, and even other species.

Stay tuned. The future is closer than we thought.

References:

1. Yuan, Y., Cui, Y., Zhao, D., et al. (2024). Complement networks in gene-edited pig xenotransplantation: Enhancing transplant success and addressing organ shortage. Journal of Translational Medicine, 22, 324. https://doi.org/10.1186/s12967-024-05136-4

2. Böhmig, G. A., Diebold, M., & Budde, K. (2024). Opinions on the future of clinical pig kidney xenotransplantation. Transplant International, 37, 13475. https://doi.org/10.3389/ti.2024.13475

3. Shirini, K., Ladowski, J. M., & Meier, R. P. H. (2025). Xenotransplantation literature update July–December 2024. Xenotransplantation, 32(1), e70027. https://doi.org/10.1111/xen.70027

4. Cooper, D. K. C., & Pierson, R. N. III. (2023). Milestones on the path to clinical pig organ xenotransplantation. American Journal of Transplantation, 23(3), 326–335. https://doi.org/10.1016/j.ajt.2022.12.023

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