Historic Milestone: First Pig Lung Transplant in Human Shows Promise Despite Challenges
In a groundbreaking medical advancement, scientists have successfully transplanted a genetically engineered pig lung into a human recipient for the first time, marking a significant step forward in the field of xenotransplantation—the process of transplanting organs between different species. This historic procedure, detailed in the August 25 issue of Nature Medicine, represents a potential pathway toward addressing the critical shortage of donor organs worldwide. The procedure was performed on a 39-year-old man who had been declared brain-dead following a brain hemorrhage, providing researchers with a valuable opportunity to study the human immune response to cross-species lung transplantation without putting a living patient at risk.
The genetically modified pig lung remained viable for nine days after transplantation, though researchers observed early signs of inflammation. While this timeframe may seem brief, it represents remarkable progress in an area of medicine that has long faced significant biological barriers. The team specifically engineered the pig lung to reduce the likelihood of rejection by the human immune system—a critical modification that helped the organ to initially integrate with the recipient’s body. This genetic engineering approach builds upon previous successes in xenotransplantation, including the first pig kidney transplant into a human in 2021 and the first pig heart transplant a few months later, demonstrating the rapid advancement of this field in recent years.
Despite the initial success, the transplanted lung began showing signs of the body’s natural rejection process relatively quickly. One day after the operation, researchers observed that the lung had partially filled with fluid and showed evidence of inflammation—early warning signs of potential rejection. By the third day post-operation, antibodies from the recipient’s immune system had begun to attack the foreign tissue, highlighting the persistent challenge of immune rejection that remains the primary obstacle in xenotransplantation. These findings provide valuable insights into how the human immune system responds to pig lung tissue and offer crucial data points for refining future approaches to cross-species lung transplantation.
The urgency driving this research cannot be overstated. In the United States alone, approximately 13 people die each day while waiting for an organ transplant, underscoring the desperate need for alternative solutions to the organ shortage crisis. Lungs represent a particularly challenging organ for xenotransplantation due to their complex structure and constant exposure to the external environment through breathing. The researchers behind this groundbreaking study acknowledge that several limitations still prevent the widespread clinical use of pig lungs in human patients. They suggest that additional genetic modifications to the pig lung or refinements to immunosuppressive medication regimens could potentially help transplanted lungs survive longer and function more effectively in human recipients.
Independent experts viewing this research highlight important questions that remain unanswered. Richard Pierson III, a thoracic transplant surgeon at Massachusetts General Hospital in Boston who was not involved in the research, noted that it remains unclear whether the transplanted lung could have independently supported the recipient without life support. He suggested that temporarily blocking blood flow to the recipient’s remaining human lung shortly after the operation could have demonstrated whether the transplanted organ was functioning adequately on its own and might have provided additional insights into the early immune response. These types of assessments will be crucial in future studies to determine the viability of pig lungs as true functional replacements for human lungs.
Muhammad Mohiuddin, director of the Cardiac Xenotransplantation Program at the University of Maryland School of Medicine, who led the team that performed the first pig-to-human heart transplant in 2022, cautions that lung xenotransplants are unlikely to become part of routine clinical practice in the immediate future. He characterizes xenotransplantation as “a learning process” where progress will be incremental rather than revolutionary. “You will not see survival [times] in years very soon,” he explains, suggesting that researchers must continue to build upon each advancement gradually. Nevertheless, this milestone represents a significant step forward in the quest to develop viable alternatives to human organ donation, potentially offering hope to the thousands of patients worldwide who are desperately waiting for life-saving transplants.
