Doctors in New York have managed to keep a brain-dead man in a state of sort of suspended animation for more than a month after removing his kidneys and replacing them with one from a pig.
A ventilator has kept 57-year-old Maurice Miller’s heart beating and other organs functioning while the pig kidney produces urine and other normal byproducts.
The experiment marks by far the longest time an animal’s organ has been functional inside a person, albeit one who is clinically dead. One gene in the pig was deleted to prevent the human body from immediately mounting an immune response to the foreign organ.
Dr. Robert Montgomery, who directs the NYU Langone Transplant Institute, said he hopes that by showing the kidney can function successfully in a brain-dead person, it will clear the way for the Food and Drug Administration to approve clinical trials in living people.
“We’ve really gotten a much better sense for what it looks like (for) the pig kidney to replace all of the functions of the human kidney,” he said. “It’s always something the FDA has asked about.”
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Addressing a desperate need for replacement organs
Researchers at the University of Alabama at Birmingham coincidently published a paper Wednesday in the journal “JAMA Surgery” showing that a pig kidney could function well for a week in a brain-dead human subject.
A third team, at the University of Maryland Medicine, used a pig’s heart to keep alive a Maryland man for two extra months in 2022, before he succumbed, likely to a virus caught from the pig.
All three efforts and a handful of others around the world are designed to address the desperate need for replacement organs.
More than 100,000 Americans are waiting for a new kidney, heart or lung at any time and thousands never qualify for a wait list or die before someone else’s tragedy makes an organ available. Compatible pig organs could provide another option.
Miller suffered from an aggressive brain tumor, which meant his own organs were not considered eligible for donation to a living person. After he was declared brain dead his family agreed to let his body be used for the procedure, which took place on July 14. LiveOnNY, a nonprofit that facilitates organ and tissue donation, was involved in informing and obtaining consent from his family.
Mary Miller-Duffy said her brother, whom she called “Mo,” would have wanted to participate in the research.
“I can say with confidence that he would be proud of the fact that in the tragedy of his death his legacy will be helping many people live,” she said at a Tuesday news conference. “Mo was a kind, giving brother who loved life and always lent a helping hand. It is only fitting that in his final act, he will be helping so many in need through this innovative medical advancement.”
Montgomery led the operation, his fifth experimental transplant using a pig organ at NYU Langone, including the world’s first on a brain-dead person.
One of the pig’s genes was deleted to prevent what’s called “hyperacute rejection” in which the body immediately responds to being connected to the foreign organ and renders it useless. In December 2020, the Food and Drug Administration approved the use of pigs with this specific gene edit as a food source for people with alpha-gal syndrome, a meat allergy caused by a tick bite, as well as a potential source for human therapeutics.
GalSafe pigs are engineered by Revivicor, Inc., a subsidiary of United Therapeutics Corporation of Maryland.
The NYU transplant also included the pig’s thymus, a gland that educates the immune system and seems to delay immune rejection and preserve kidney function.
Other research teams, including the University of Alabama at Birmingham’s, use UKidney pigs with 10 gene edits, also engineered by Revivicor.
In their case, the family of a 52-year-old man with hypertension and stage 2 chronic kidney disease agreed to participate in the research on the condition that his name not be made public.
That man’s own kidneys were removed and replaced with a UKidney pig’s, which functioned well for the weeklong procedure, according to the publication. In their case, the family of a 52-year-old man with hypertension and stage 2 chronic kidney disease agreed to participate in the research on the condition that his name not be made public. That man’s own kidneys were removed and replaced with a UKidney pig’s, which functioned well for the weeklong procedure, according to the publication.
More work ahead of convincing FDA to approve a clinical trial
Montgomery said he prefers single-gene-edited pigs for kidney transplants, convinced that one is enough, along with the thymus transplant and a conventional transplant drug regimen.
“We’ve now gathered more evidence to show that, at least in kidneys, just eliminating the gene that triggers a hyperacute rejection may be enough along with clinically approved immunosuppressive drugs to successfully manage the transplant in a human for optimal performance − potentially in the long-term,” he said in a statement.
To make sure the pig kidney was truly functioning in both the NYU and UAB experiments, the man’s own kidneys were both removed during the initial surgery. Once transplanted, the pig kidney began to produce urine immediately. Over the next month, the man’s body was maintained on life support while the kidney’s function was monitored. Levels of creatinine, an indicator of kidney function, have remained normal and there has been no indication of rejection.
An autopsy on David Bennett, the man who lived with a pig heart for two months, revealed that his heart was infected with a pig cytomegalovirus, though it may not have caused his death.
Transplant teams stepped up their testing to ensure the pigs used in so-called xenotransplants from animals to people are not infected with pig viruses. Studies have shown that the current patient is not infected with porcine cytomegalovirus or any other common pig viruses.
Montgomery, a heart transplant patient himself, has said he thinks transplant patients will feel better about receiving organs from pigs if they see that the organs have not triggered rejections or other problems in brain-dead subjects.
He plans to continue the current experiment for another month, if possible.
By keeping a pig kidney in a brain-dead person for such a long-time, Montgomery said, it will help address questions raised by similar experiments in non-human primates. Researchers have had trouble keeping primates alive for several months after a transplant because of a longer-term immune response in which antibodies begin attacking the new organ.
It is extremely difficult to keep a brain-dead person on life-support for longer than a month or two, Montgomery said. But a biopsy done Friday on the pig kidney showed no antibodies have yet developed, which should help convince the FDA that the procedure is safe to test in living people, he said.
The team at University of Maryland, led by Dr. Muhammad Mohiuddin, is hoping to find a second living person, healthier than Bennett was, willing to test a pig heart. Although Mohiuddin said he cannot promise how long the person will live, he thinks someone who starts out healthier will fare better with a pig heart.
To convince the FDA to approve clinical trials for pig organs, he said, “we firmly believe that a live patient is the best way to go.”
