Researchers reported Thursday the results of a remarkable series of experiments aimed at saving human life using organs from genetically engineered pigs.
This time around, surgeons in Alabama transplanted a pig’s kidneys into a brain-dead man—a step-by-step rehearsal for an operation they hope to try in living patients possibly later 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 newest study and aims to begin a clinical trial of pig kidney transplants.
Recent headlines have focused on similar studies as the research continues into human-animal 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. A heart was also donated by the University of Maryland Medical Center to a man who is currently in his last days.
But scientists still needed to learn more about how to test such transplants without risking a patient’s life. With the help of a family who 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 over three days, until the man’s body was removed from life support, the pair of pig kidneys survived with no sign of immediate rejection, her team reported Thursday in the American Journal of Transplantation.
This was just one of many key discoveries. Locke said it wasn’t clear if delicate pig kidney blood vessels could 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. There were no pig virus infections transmitted to the recipient. Also, there weren’t any pig cells in the bloodstream.
But Locke said the kidney experiment could have more far-reaching impact — because it shows that a brain-dead body can be a much-needed human model to test potential new medical treatments.
This research was done after Jim Parsons of Alabama, aged 57, died in an accident involving dirtbike racing.
After hearing this kind of research “had the potential to save hundreds of thousands of lives, we knew without a doubt that that was something that Jim would have definitely put his seal of approval on,” said Julie O’Hara, Parsons’ ex-wife.
There is a huge need for organ donations: More than 41,000 organ transplants took place in the United States last year. This was a new record. However, there are still more than 100,000 individuals on the waiting list. Many people die each year without ever receiving an organ. And thousands more don’t even make it onto the waiting list.
Animal-to-human transplants, what’s called xenotransplantation, have been attempted without success for decades. People’s immune systems almost instantly attack the foreign tissue. But scientists now 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 testing pig organs in non-human primates that helped pave the way but “there are only things we can learn by transplanting them into humans.”
There are still many hurdles to overcome before testing can begin in humans, such as deciding who is qualified to test an organ from pigs. Karen Maschke, a researcher at the Hastings Center, will assist with the development of ethics and policy recommendations for first clinical trials funded by the National Institutes of Health.
Scientists also still 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.
UAB collaborated with Revivicor (a subsidiary of United Therapeutics) to conduct the latest kidney experiment. Revivicor also donated organs for both the New York heart transplant and UAB’s recent kidney transplant. Company scientists made 10 genetic changes to these pigs, knocking out some genes that trigger a human immune attack and make the animals’ organs grow too large—and adding some human genes so the organs look less foreign to people’s immune systems.
There are also practical issues like how to reduce the time it takes to get pig organs there. UAB placed the affected pigs at Birmingham’s germ-free hospital, complete with an operating area that allows for organ removal and preparation for transplant.
David Ayares is chief scientific officer at Revivicor. He stated future plans included building additional such facilities close to transplant centers.