On 7 January, David Bennett, a 57-year-old with terminal heart failure, became the first person to receive a genetically modified pig heart. While he died two months later, his surgery still marked a significant step forward.
Several months after Bennett鈥檚 procedure, surgeons at NYU Langone 午夜福利1000集合 in New York transplanted modified pig hearts into two brain-dead people on life support. The hearts pumped blood for three days before the researchers ended the study.
Xenotransplantation, the use of animal organs in another species, had only been done in non-human primates until 2021, when two pig kidneys were transplanted into a brain-dead man on life support. 鈥淭o take that next step towards making [xenotransplantation] a reality, we felt we needed to do this in a human,鈥� says at the University of Alabama at Birmingham, who was involved in that work.
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at the University of Maryland and his team felt the same, hence Bennett鈥檚 transplant.
Since Bennett鈥檚 death, they have been reviewing his tissues to try to understand what went wrong. Like any transplantation, a key threat in xenotransplantation is rejection 鈥� when the immune system attacks the organ. Pigs bred for this purpose undergo genetic modifications to make them more compatible with our immune system. The pig heart Bennett received had 10 mutations introduced. He showed no obvious signs of rejection post-mortem.
Bennett may have died due to complications from a pig virus called porcine cytomegalovirus. During routine tests, doctors detected the virus in Bennett about 20 days after his transplant, despite testing the heart four times pre-surgery. The pathogen was probably lying dormant in the organ and the immunosuppressing drugs Bennett was taking allowed it to reactivate, says Griffith.
When Bennett showed signs of decline, doctors treated him with an antibody serum in the hope this would attack the virus.
We all have antibodies against the antigens found in a range of other animals, which is why Bennett was on specific immunosuppressing drugs, says Griffith. The antibody serum, which came from a human, could, in theory, inadvertently introduce these antibodies into the pig heart. However, there was no evidence of antibody-induced injury in later studies on Bennett鈥檚 pig heart.
In the future, Griffith says they will use more sensitive tests when screening non-human organs and choose antibody treatments with minimal anti-pig antibodies.
It may be more than a decade until xenotransplants are available, but broader trials could begin in the next few years, says Anderson.
鈥淸It] is no longer a fantastic vision,鈥� says Griffith. 鈥淚t鈥檚 actually happened. I think we can just iterate it and make it better.鈥�
