A history-making experiment ended two weeks ago when dozens of doctors and nurses silently lined the hospital hallway in tribute. A pig’s kidney worked normally inside the brain-dead man on the gurney, rolling past them for two months. The experiment ended as surgeons at NYU Langone Health removed the pig kidney and returned the donated body of Maurice “Mo” Miller to his family for cremation.
It was the longest time a genetically modified pig kidney functioned inside a deceased human. Although the research involved functionally dead, it pushed the boundaries and taught scientists critical lessons they plan to share with the Food and Drug Administration. They hope to conduct tests with pig kidneys on the living eventually.
“It’s a combination of excitement and relief,” Dr. Robert Montgomery, the transplant surgeon who led the experiment, told The Associated Press. “Two months is a lot to have a pig kidney in this good a condition. That gives you a lot of confidence” for the next attempts.
Montgomery, a heart transplant recipient himself, sees animal-to-human transplants as pivotal to easing the nation’s organ shortage. More than 100,000 people are on the national waiting list, most needing a kidney, and thousands will die waiting.
So-called xenotransplantation, defined as “any procedure that involves the transplantation, implantation, or infusion into a human recipient of live cells, tissues, or organs from a nonhuman animal source, ” has failed for decades. The human immune system immediately destroys foreign animal tissue. The latest thing they’re trying is genetically modifying pigs so their organs are more human-like.
Some short experiments in dead bodies avoided an immediate immune attack but shed no light on a more common form of rejection that can take a month to form. Last year, University of Maryland surgeons tried to save a dying man with a pig heart, but he survived only two months as the organ failed for reasons that aren’t completely clear. The FDA gave Montgomery’s team a list of questions about how pig organs perform their jobs compared to humans. Montgomery ventured that preserving Miller’s body on a ventilator for two months to see how the pig kidney worked could answer some of those questions.
Unfortunately, Miller had been declared brain-dead and unable to donate his organs due to cancer. After wrestling with the choice, his sister, Mary Miller-Duffy donated the Newburgh, New York, man’s body for the pig experiment. She recently got a card from a stranger in California who’s awaiting a kidney transplant, thanking her for helping to move forward desperately needed research.
Shortly before what would have been his 58th birthday, on July 14th, surgeons replaced Miller’s kidneys with one pig kidney plus the animal’s thymus, a gland that trains immune cells. For the first month, the kidney worked fine with no signs of trouble. But soon, doctors measured a slight decrease in urine produced. A biopsy confirmed a subtle sign that rejection was beginning –- allowing doctors to tell if it was treatable.
“We are learning that this is actually doable,” said NYU transplant immunologist Massimo Mangiola.
The researchers checked off other FDA questions, including seeing no differences in how the pig kidney reacted to human hormones, excreted antibiotics, or experienced medicine-related side effects.
“It looks beautiful, it’s exactly the way normal kidneys look,” Dr. Jeffrey Stern said after removing the pig kidney at the 61-day mark for closer examination.
Researchers took about 180 different tissue samples from every major organ, lymph nodes, the digestive tract to scour for any hints of problems due to the xenotransplant.
Karen Maschke, a research scholar at the Hastings Center who is helping develop Ethics and Policy Recommendations for Xenotransplant Clinical Trials, cautioned that experiments in the deceased can’t predict that the organs will work the same in the living. But they can provide other valuable information, she said. That includes helping to tease out differences between pigs with up to 10 genetics changes that some research teams prefer — and those like Montgomery uses that have just a single change, removal of a gene that triggers an immediate immune attack.
“Why we’re doing this is because there are a lot of people that unfortunately die before having the opportunity of a second chance at life,” said Mangiola, the immunologist. “And we need to do something about it.”
If faced with the choice between a xenotransplant and death, would you hesitate?
Sources:
https://www.nbcnews.com/health/health-news/organ-transplant-work-us-revamps-organ-donation-system-rcna76103
https://www.sciencedirect.com/topics/medicine-and-dentistry/xenotransplantation
https://www.cbsnews.com/baltimore/news/maryland-surgeons-perform-second-pig-heart-transplant-trying-to-save-a-dying-man/
https://nyulangone.org/news/pig-kidney-xenotransplantation-performing-optimally-after-32-days-human-body