The first-ever transplant of a pig heart into a human marked a profound shift in medical science. This extraordinary achievement represents a significant step forward in addressing the persistent global organ shortage. The procedure opened new avenues for xenotransplantation, offering a potential lifeline for countless patients awaiting life-saving organs.
The Historic Procedure
The groundbreaking surgery took place in January 2022 at the University of Maryland Medical Center in Baltimore. The patient, 57-year-old David Bennett Sr., suffered from terminal heart disease and was ineligible for a traditional human heart transplant. Bedridden for weeks and relying on an extracorporeal membrane oxygenation (ECMO) machine, Mr. Bennett agreed to the experimental procedure as his only option.
Dr. Bartley Griffith, the clinical director of the Cardiac Xenotransplantation Program at the University of Maryland School of Medicine, performed the transplant surgery. The U.S. Food and Drug Administration (FDA) granted emergency authorization for the surgery in late December 2021 under its compassionate use provision, recognizing Mr. Bennett’s dire condition.
Why Consider Pig Organs?
Xenotransplantation, the use of animal organs, stems from a severe shortage of human donor organs. Thousands of patients globally are on transplant waiting lists, with many dying before a suitable organ becomes available. This approach offers a potentially unlimited supply of organs.
Pigs have emerged as the most suitable donor animals due to their physiological and anatomical similarities to humans, including comparable organ size. Pigs also have a high breeding potential and are widely available, making them a practical source for organs.
Historically, a major hurdle has been hyperacute rejection, an immediate and severe immune response where the human body rapidly rejects the animal organ. This occurs because the human immune system recognizes certain sugar molecules on the surface of pig cells as foreign, triggering organ failure.
Enabling the Transplant
The success of Mr. Bennett’s transplant was largely attributed to significant advancements in genetic modification, specifically using CRISPR technology. The donor pig underwent ten genetic modifications to reduce the likelihood of rejection and ensure compatibility with the human recipient.
Four pig genes were inactivated; three of these were responsible for producing antibodies that trigger hyperacute rejection, while the fourth controlled the growth of the pig heart tissue to prevent it from becoming too large for a human. Additionally, six human genes were inserted into the pig’s genome. These introduced human genes were designed to help the human immune system accept the new organ by mimicking necessary surface signals, thereby preventing antibody binding and blood clots.
To further manage the patient’s immune response, a specialized regimen of immunosuppressive drugs was administered, including an experimental drug developed in conjunction with conventional anti-rejection medications. Measures were also taken to prevent zoonotic disease transmission.
The Patient’s Journey and Medical Impact
Following the transplant, David Bennett Sr. showed initial signs of recovery, with the genetically modified pig heart functioning well and no immediate signs of acute rejection for nearly seven weeks. He was able to come off the ECMO machine, and his new heart was pumping effectively. However, approximately 40 days after the transplant, his condition began to deteriorate, and he passed away on March 8, 2022, two months after the surgery.
Post-mortem analysis and subsequent studies provided unprecedented medical insights. Researchers found evidence of porcine cytomegalovirus (PCMV) DNA in Mr. Bennett’s system, which may have contributed to the heart’s decline and his eventual death. While the donor pig had been screened for pathogens, this latent virus was difficult to detect in initial tests.
The case also revealed challenges related to his severely immunocompromised state before the transplant, which limited the effectiveness of certain anti-rejection regimens. Despite the patient’s passing, the transplant provided invaluable data on the viability of a genetically modified pig heart in a human, the complexities of immune suppression, and the importance of stringent viral screening, all of which will inform future xenotransplantation efforts.