Author: Yi Xuan Goh
Artist: Yi Xuan Goh
Editor: Altay Shaw
In the US, 5,600 people die each year while waiting for a transplant. Every 8 minutes, another patient is added to the list. Although organ donation consents increase yearly, it still cannot meet the growing demand. To mitigate the organ shortage, researchers are exploring possible alternatives. One of the most prominent current studies is xenotransplantation using pig organs, which involves transplanting cells, tissues, or organs from pigs to humans.Why pigs? Many people find it puzzling that pigs are considered the most suitable animal source, despite non-human primates being more similar to humans in many ways. However, pigs are not chosen randomly. They are regarded as the best candidates for organ xenografts because of the similarities in their organ size, physiological metabolism, and immune system to humans. On the other hand, non-human primates do not have a sufficient population to support clinical trials and potentially carry uncharacterised viruses.
In the past few years, significant strides have been made with the use of genetically modified pig organs for xenotransplantation in living humans. In 2022 and 2023, the University of Maryland Medicine Faculty achieved a groundbreaking feat by performing the world’s first and second successful pig heart transplants into human patients. With FDA approval, 57-year-old David Bennett and 58-year-old Lawrence Faucette, who were suffering from terminal heart disease and did not qualify for a traditional heart transplant, received a modified pig heart with several immunity-triggering genes removed. With no initial signs of rejection, both surgeries were deemed a success.
In March, the field witnessed another remarkable milestone: the first pig kidney transplant in a living human performed by Massachusetts General Hospital (MGH). Facing end-stage renal disease, 62-year-old Richard Slayman was the first to receive the pioneering surgery. The special pig kidney, provided by eGenesis of Cambridge, Massachusetts, was from a donor that had been genetically edited 69 times using CRISPR-Cas9 technology to remove genes responsible for rejection, a significantly more intense edit than the 10 edits in the previous pig-heart transplants. Richard’s bravery and the success of the surgery are a testament to the potential of xenotransplantation. “At MGH alone, there are over 1,400 patients on the waiting list for a kidney transplant. Some of these patients will unfortunately die or get too sick to be transplanted due to the long waiting time on dialysis,” said Leonardo V. Riella, MGH Medical Director for Kidney Transplantation. “I am firmly convinced that xenotransplantation represents a promising solution to the organ shortage crisis.”
Despite these groundbreaking advancements, there are remaining safety concerns. Both pig heart transplant recipients passed away within two months after their respective surgeries due to heart failure thought to be influenced by several factors. A major concern of xenotransplantation is zoonosis, the transmission of pathogens between species. The heart transplanted to David Bennett was later found to contain a pig latent virus known as porcine cytomegalovirus, which was believed to have contributed to his heart failure. On May 12, much earlier than expected, Richard Slayman passed away two months post-procedure. Although the hospital stated there was “no indication” that his death was related to the transplant, Slayman’s death is undoubtedly a significant setback for xenotransplantation. “Rick said that one of the reasons he underwent this procedure was to provide hope for the thousands of people who need a transplant to survive,” they said. “Rick accomplished that goal and his hope and optimism will endure forever.”
Another pressing concern among the public regarding xenotransplantation is the welfare of the animals. While representing a significant technical advancement, xenotransplantation has ignited ethical debates about animal rights. Critics argue against the practice of slaughtering animals to harvest xenografts for human use, contending that it is unethical to kill animals for their organs, as it reduces them to mere tools for human benefit. Conversely, some argue that the primary animal welfare issue for most people is not the killing of animals per se. They note that if society condones the slaughter of billions of pigs for food, the notion of using them to save human lives should not be inherently disturbing. Instead, public concern often focuses on the treatment of these animals. Like many laboratory animals, pigs raised for xenografts are typically kept in confined, sterile environments to minimise the risk of pathogen transmission. This practice conflicts with the animals’ physiological and psychological needs. Nonetheless, there is hope that technological advancements will eventually improve these donor animals’ living conditions.
Nevertheless, The progress of xenotransplantation continues to advance rapidly. In April, NYU Langone Health performed the world’s second gene-edited pig kidney transplant into a living human. Following that, on May 24, Chinese researchers announced the successful transplantation of the first genetically modified pig liver into a living human patient. These recent xenotransplants have provided scientists with invaluable insights, far surpassing the knowledge gained from previous clinical trials on non-human primates. Despite these significant strides, there remains a considerable journey ahead before xenotransplantation can become an approved method to address the critical organ shortage crisis.
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