Genetically modified organisms appear to be active for more than two days but some researchers doubt that the test was beneficial.Kidney transplants from genes that were genetically modified for human-like immune function were successfully implanted in two recently deceased patients, the research team reported1. Some researchers question the validity of the study and argue that clinical trials in living individuals are the only way to determine if transplantation from pigs can help alleviate the deficiency of human organs found in people who need them.
Researchers have successfully implanted pig organs in non-humans: one baboon lived for more than two years and a genetically modified pig heart2. But monkey antibodies and metabolic processes are different from humans, and certain antibodies commonly used in implants do not work in non-human monkeys, says Robert Montgomery, a rehabilitation surgeon at New York University (NYU) in New York. The city that led the trials. People who have recently died, he says, “are the closest thing we will ever find in a living person without the risk of injury”.
A pair of an organ
In their transplant tests, conducted in September and November 2021, Montgomery and his colleagues used genetically modified pigs to defy an alpha-1,3-galactosyltransferase (αGal) gene. The swine version of αGal triggers the human immune system to reject xenotransplants (organs transmitted from a different type). With each kidney researchers have implanted a pig thymus, a pigment that produces cells that help the body absorb foreign organs.
They tested the “thymokidneys” in two people who were pronounced dead one day or two earlier because they had no brain function. The researchers did not remove the patients ‘kidneys, but they were implanted in the pig’s kidneys with arteries that carry blood to and from the recipients’ legs. They then monitored kidney function and immune responses in patients for 54 hours – a limit set by the NYU ethics board and based on the time required to harvest human organs for transplantation.
Genetic modification
Some researchers, however, are skeptical of the results. Among other things, the pigs used in the study were deficient in only one gene, despite studies showing that mutating three or more genes helps the human immune system to accept an organ3. “It’s a pig that doesn’t fit what we need to know,” said David Cooper, a surgeon at Massachusetts General Hospital in Boston.
In addition, it is difficult to say whether swine kidneys were active or that urine and creatinine were actually leaking from patients’ kidneys. “You can’t explain the results,” said Paige Porrett, an orthopedic surgeon at the University of Alabama in Birmingham. After testing the patient’s immune system to attack the pig’s limb, they implanted two kidneys in a pig with 10 genes and monitored the patient for 74 hours.
Like Montgomery’s team, Porrett’s team saw little response to the immune system. But even though the pig’s kidneys produced some urine, they did not process creatinine, indicating that they were not functioning properly. He says his team has implanted pig kidney in some people who were said to have brain damage, and plans to publish the results soon.
Cooper is not surprised by the findings of either group: studies in monkeys and human serum have already shown5 that animal antibodies will not immediately reject a pig-free pig αGal. Montgomery and Porrett say that it may be medically possible to extend the test, since some patients may live for months after the brain has died. For example, doctors have sometimes kept pregnant women supporting life so that the fetus can stop growing.But doing this for research purposes creates behavioral problems, says Rebecca Pentz, a biologist at Emory University in Atlanta, Georgia, because patients’ bodies should be removed from their families as soon as possible.However, Petz says the NYU study followed the guidelines set by the researchers’ ethics board. He says: “It is a wise use of the dead. “I think xenotransplantation – if we can work on science – will be a moral development because it can save many lives.”
Heart transplant
In part because of such restrictions, Cooper and others argued that it was time to start transplanting animals into living humans – something that has been relatively successful. In January, researchers at the University of Maryland obtained a special permit from the US Food and Drug Administration (FDA) to perform an emergency transplant into a man with a genetically engineered pig in a man who should have died otherwise.The man died two months later. In an April 20 webinar hosted by the American Society of Transplantation, researchers after the study said they thought he had been killed by porcine cytomegalovirus – an animal virus that is harmless to humans but has caused its immune system to weaken.
Porrett points out that the virus has not yet been found in live pigs, and it is still unknown whether some of the more subtle viruses may be infecting humans long after transplantation took place. “We will not be able to answer that until we have patients we can follow for months or years,” he said.Porrett and Cooper’s teams applied to the FDA to initiate small clinical trials that could implant genetically modified pig kidneys in humans. The kidneys are the right organ to start with, Cooper says, because, unlike the heart, they can be removed if problems arise and the patient can be put on dialysis. “It should be done cautiously,” he says.
Source Journal Reference: Sara Reardon, First pig kidneys transplanted into people: what scientists think, Nature news (2022) doi: https://doi.org/10.1038/d41586-022-01418-3,https://www.nature.com/articles/d41586-022-01418-3
