Researchers implant genetically altered pig kidneys into a brain dead man

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, marks another major step forward in the use of animal organs to replace failing ones in humans. Earlier this month, doctors at the University of Maryland transplanted a genetically altered pig's heart into a living man with terminal heart disease.

The UAB kidney transplant took place in September, less than a week after surgeons at NYU Langone performed a similar surgery on a deceased woman.

All three surgeries reflect advances in the accelerating field of xenotransplantation - the process of implanting organs from one species into another.

Gene-editing technology

In an interview Thursday, Jayme Locke, director of UAB's Incompatible Kidney Transplant Program, said that the advances are made possible by new technologies, including CRISPR, the gene-editing technology 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 could 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 a donor organ. 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.

The possibility of using animal organs has intrigued scientists for more than a century. In 1905, French surgeon M. Princeteau grafted slices of rabbit kidney into a child, declaring the immediate results "excellent." The child died two weeks later.

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 biotechnology company United Therapeutics Corporation. Its subsidiary Revivicor, Inc., provided the pig. UAB now 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 later this year - usually the first phase for testing safety in people.

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 going ahead.

At a news conference Thursday, Julie O'Hara, the ex-wife of recipient Jim Parsons, who was declared brain dead following 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 wanted it. UAB plans to call the preclinical human model the Parsons Model.