eGenesis, a biotech company in Cambridge, Massachusetts, is experimenting in the field of xenotransplantation by transplanting gene-edited pig hearts into infant baboons. The company’s goal is to pave the way for similar transplants in human babies, offering a potential temporary solution for infants with serious heart defects while they wait for a human donor heart. However, the path forward carries ethical dilemmas and technical challenges.
Xenotransplantation and the Potential of Pig Organs
Xenotransplantation, the transplantation of organs and tissues from animals to humans, has been explored as a possible solution to the critical shortage of human donor organs for decades. Pigs emerged as the preferred donor candidates due to their reproductive efficiency, organ size compatibility, and well-established farming practices. However, transferring organs between different species is complicated, as the recipient’s immune system may reject the organ. In addition, even an organ from an uninfected animal could cause an infection in the recipient. “There’s a risk that viruses that are endemic to animals evolve in a human and become deadly,” said Chris Gyngell, a bioethicist at Murdoch Children’s Research Institute in Melbourne, Australia.
Gene Editing with CRISPR
eGenesis uses the gene-editing tool CRISPR to address the risks of viral transmission associated with pig organs. “You can use CRISPR-Cas9 to inactivate the 50 to 70 copies of retrovirus in the genome,” said Mike Curtis, president and chief executive officer at eGenesis. Additionally, they “knock out” pig genes that could lead to harmful immune responses in humans and insert human genes to reduce the likelihood of organ rejection. With these precautions, the team introduces over 70 gene edits to produce pig donor organs that might be suitable for human transplantation.
Transplanting Pig Hearts Into Infant Baboons
Before attempting human transplants, eGenesis is testing the effectiveness of the gene-edited pig hearts by conducting transplants with infant baboons. Although two surgeries have been performed, both baboons died within days due to surgical complications. Despite the outcomes, the team remains optimistic. In both cases, “the heart itself was beating well,” said Mike Curtis, president and chief executive officer at eGenesis. “So far, the first two are very encouraging from cardiac performance … the hearts look good.” The team is hopeful that the complications will be avoidable in future surgeries, he says.
Ethical Considerations and Challenges
Infants with serious heart defects face a high mortality rate due to the limited availability of suitable human hearts. Nevertheless, critics caution that transplanting gene-edited pig organs in human recipients has serious risks as well as ethical concerns. For instance, the lack of informed consent for infants necessitates decisions to be made by caregivers, who may be desperate to save their child’s life. Additionally, xenotransplantation remains experimental, with unknown long-term risks. “The desire to do something to save these babies [with heart conditions] is obviously very strong for everyone who is involved,” said Syd Johnson, a bioethicist at Upstate Medical University in Syracuse, New York. “But we still need to be honest and transparent about what the risks are.” Johnson added that “one hundred percent of the patients who’ve been transplanted with an animal organ have died [soon after the procedure]—that’s just an inescapable fact.” In 2022, David Bennet Sr. became the first living person to receive a gene-edited pig heart and died two months later.
Next Steps
eGenesis is planning to continue its baboon trials, with at least one operation per month until 12 animals have undergone the procedure. The team hopes to refine the surgical technique and extend baboon survival with the goal of eventually offering the engineered pig hearts to help infants who have very few treatment options.
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