Surgeons at the University of Alabama at Birmingham have transplanted genetically modified pig kidneys into a brain-dead man, the university announced Thursday.
The transplantation of the organs, which functioned for more than 70 hours, was another major step forward in the use of animal organs to replace failing human ones. Earlier this month, doctors at the University of Maryland transplanted a genetically altered pig’s heart into a living man with terminal heart disease.
All three surgeries reflect advances in the accelerating field of xenotransplantation — the process of implanting organs from one species into another.
In an interview Thursday, Jayme Locke, the director of UAB’s Incompatible Kidney Transplant Program, said that the advances have been made possible by new technologies, including CRISPR, the gene-editing tool that was recognized with a Nobel Prize in chemistry in 2020.
“The new tools have changed the precision and rapidity,” Locke said. The peer-reviewed research on the transplant was published Thursday in the American Journal of Transplantation.
Locke and other doctors hope the use of genetically altered animals can address the shortage of organs available for transplant.
The need is dire. More than 100,000 patients are on the national transplant waiting list. Seventeen of them die every day waiting for donor organs. For the 37 million Americans with chronic kidney disease, the lack of organs can be a death sentence. Forty percent of wait-listed patients will be dead within five years, she said.
A chief challenge has been to prevent the recipient’s immune system from rejecting the animal organ — a process that is being addressed by disguising the foreignness of the animal organ through genetic modifications.
The UAB work was supported by the biotechnology company United Therapeutics Corp. Its subsidiary Revivicor provided the pig. UAB keeps a breeding herd of genetically modified pigs, Locke said.
The pig kidneys used in the UAB study had been modified with 10 gene edits. The transplantation replicated the process of human-to-human transplantation. After transplantation, the organs filtered blood and produced urine for the duration of the study — 70 hours, until it was stopped.
The use of a brain-dead human allows surgeons to test a preclinical model without harming a living person, rather than relying on other primates as substitutes. Nonetheless, the research at UAB underwent both internal and external ethical reviews. Locke said she hopes to enter phase one clinical trials this year — usually the first phase for testing safety in humans.
Karen Maschke, an expert at the Hastings Center on the ethical, regulatory and policy issues involving the use of new biomedical technologies, described the UAB research as one step in a complex process before pig kidneys could become widely available as substitutes. The fact that this study has been published in a peer-reviewed journal, she said, has “given organ transplant community more details about what happened” that will be important in the future.
PETA Senior Vice President Kathy Guillermo issued a statement in response to news of the transplant. “Ripping organs out of one species and putting them into another is cruel and dangerous — the risk of transmitting unknown viruses with an animal is real, as the current pandemic has taught us,” Guillermo wrote.
UAB said the kidneys were procured from a pig at a clinical-grade, pathogen-free facility. Locke also said no pig cells or pathogens were detected in the blood of the organ recipient.
At a news conference Thursday, Julie O’Hara, the ex-wife of recipient Jim Parsons, who was declared brain dead after a motorbike accident, described her hope that the process would “eliminate the organ shortage crisis.” Parsons’s own kidneys were donated to another person before he received the pig kidneys.
O’Hara said she made the decision with their children and other close family members and felt sure her ex-husband would have approved. UAB plans to call the preclinical human model the Parsons Model.
Source: The Washington Post