More tests with pig organs
U.S. researchers hope to save human lives with xenotransplants
Researchers have reported the latest in a string of experiments in the quest to save human lives with organs from genetically modified pigs.
This time, surgeons in Alabama transplanted a pig’s kidneys into a braindead man — a step-by-step rehearsal for an operation they hope to try in living patients possibly this year.
“The organ shortage is, in fact, an unmitigated crisis, and we’ve never had a real solution to it,” said Dr. Jayme Locke of the University of Alabama at Birmingham, who led the study and aims to begin a clinical trial of pig kidney transplants.
Similar experiments have made headlines in recent months as research heats up into animal-to-human transplants.
Twice this fall, surgeons at New York University temporarily attached a pig’s kidney to blood vessels outside the body of a deceased recipient to watch them work. This month, surgeons at the University of Maryland Medical Center gave a dying man a heart from a gene-edited pig that so far is keeping him alive.
But scientists needed to learn more about how to test such transplants without risking a patient’s life. With the help of a family that donated a loved one’s body for science, Locke mimicked the way human organ transplants are done — from removing the pig “donor” kidneys to sewing them inside the deceased man’s abdomen.
For a little more than three days, until the man’s body was removed from life support, the pair of pig kidneys survived with no sign of rejection, her team reported Thursday in the American Journal of Transplantation.
That was only one of several key findings. Locke said it was unclear whether delicate blood vessels in pig kidneys would withstand the pounding force of human blood pressure, but they did. One kidney was damaged during removal from the pig and didn’t work properly, but the other rapidly started producing urine, as a kidney should. No pig viruses were transmitted to the recipient, and no pig cells were found in his bloodstream.
Locke said the kidney experiment could have more far-reaching impact, because it shows that a braindead body can be a muchneeded human model to test potential medical treatments.
The research was conducted in September after Jim Parsons, a 57-year-old Alabama man, was declared brain-dead following a dirtbike racing accident.
After hearing that this kind of research “had the potential to save hundreds of thousands of lives,” said Julie O’Hara, Parsons’ exwife, “we knew without a doubt that that was something that Jim would have definitely put his seal of approval on.”
The need for a source of organs is huge: While more than 41,000 transplants were performed in the U.S. last year — a record — more than 100,000 people remain on the national waiting list. Thousands die every year before getting an organ, and thousands more never even get added to the list, considered too much of a long shot.
Animal-to-human transplantation — or xenotransplantation — has been attempted without success for decades. Human immune systems almost instantly attack the foreign tissue. But scientists have new techniques to edit pig genes so their organs are more human-like, and some are anxious to try again.
The recent string of pig experiments “is a big step forward,” said Dr. David Kaczorowski of the University of Pittsburgh Medical Center. Moving on to first-stage trials in potentially dozens of people is “becoming more and more feasible.”
A heart transplant surgeon, Kaczorowski has done experiments with pig organs in nonhuman primates that helped pave the way, but “there are only things we can learn by transplanting them into humans.”
Hurdles remain before formal testing begins in humans, including deciding who would qualify to test a pig organ, said Karen Maschke, a research scholar at the Hastings Center who will help develop ethics and policy recommendations for the first clinical trials under a grant from the National Institutes of Health.
Scientists have much to learn about how long pig organs survive and how best to genetically alter them, cautioned Dr. Robert Montgomery of NYU Langone Health, who led that center’s kidney experiments in the fall.
“I think different organs will require different genetic modifications,” he said in an email.
For the newest kidney experiment, UAB teamed with Revivicor, the subsidiary of United Therapeutics that also provided organs for the recent heart transplant in Maryland and the kidney experiment in New York. Company scientists made 10 genetic changes to the pigs, knocking out some genes that trigger a human immune attack and making the animals’ organs grow too large — and adding human genes so the organs appear less foreign to people’s immune systems.
Then there are practical questions such as how to minimize the time spent getting pig organs to their destination. UAB housed the altered pigs in a germfree facility in Birmingham, complete with an operatingroom-like space to remove the organs and ready them for transplant.
Revivicor chief scientific officer David Ayares said the company plans to build more such facilities near transplant centers.