Reengineering Life is a column from Future Human about the ways humans are using biology to reprogram our bodies and the world around us.
Every day in the United States, 17 people die waiting for a lifesaving organ transplant. To address this crisis, one biotech company is turning to an unlikely source: pigs. Maryland-based United Therapeutics says it plans to begin transplanting organs from genetically modified pigs into people as soon as this year.
“We’re right on that cusp. We’re looking to get into humans within the next year or two,” said David Ayares, PhD, in an exclusive interview with Future Human. Ayares is the chief scientific officer of Revivicor, a subsidiary of United Therapeutics that’s developing the pigs. “We think we have the pig that is going to be what we bring forward into humans in 2021 or 2022.”
For decades, scientists have been hopeful that organs from other species could be used to replace faulty ones in humans, known as xenotransplantation. But animal organs trigger immediate and severe immune reactions when transplanted into humans. In one famous case in 1984, a newborn in California known as “Baby Fae” received a heart from a baboon but died less than a month later when her body rejected the organ.
Scientists at Revivicor took the first steps to curb this immune rejection in 2003, when they knocked out a gene in pigs that makes a sugar known as alpha-gal. This sugar, which is found on the surface of pig cells, is believed to be a cause of rejection in patients. “Most of the early rejection, called hyperacute rejection, that you would see in a heart or a kidney xenotransplant is due to the human immune reaction to that alpha-gal sugar,” Ayares explained.
Years later, researchers discovered that this sugar, which is found in other animals that people eat, is also responsible for an uncommon allergy to red meat. Known as alpha-gal syndrome, the condition most often begins when a Lone Star tick bites someone and transmits alpha-gal into the person’s body. This triggers an immune response that later produces an allergic reaction to red meat like beef, pork, and lamb.
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Revivicor’s modification eliminates the sugar from the surface of pig cells. In December, the Food and Drug Administration (FDA) deemed the pigs safe for human consumption. Known as GalSafe pigs, they are the first genetically modified animal to be approved both for human food consumption and as a source for potential therapeutic uses, according to the FDA.
But Ayares said United Therapeutics doesn’t plan to start producing allergy-free pork anytime soon. Instead, he sees the FDA approval as a step toward more extensively genetically modified pigs that could be used as human organ donors.
“Our ultimate goal is to essentially have an unlimited supply of organs,” he said.
While the number of U.S. organ transplants hit an all-time high in 2019, many people still don’t get one on time. More than 109,000 patients in the United States are currently waiting to receive an organ, according to the Department of Health and Human Services.
The single alpha-gal alteration won’t be enough to make pig organs compatible with human bodies though. Over the past decade, Revivicor has been tinkering with other genes that could prevent an immune response and other potential complications like blood clotting. The company’s current pig has total of 10 genomic modifications—four disabled pig genes and the addition of six human genes. These highly modified pigs will be the ones used in human clinical trials. The company thinks these multiple alterations will make the pig organs comparable to human donor organs.
It’s unknown how long these pig organs will last in human patients. Revivicor, along with researchers from the National Institutes of Health, reported in 2016 that they were able to keep pig hearts alive in baboons for two and a half years. The baboons kept their original hearts, however — the pig hearts were transplanted to the baboons’ abdomens. Kidneys from Revivicor’s pigs have survived for more than six months in monkeys.
The hope is that the organs could last for the rest of a person’s life, but they’ve also been envisioned as a bridge to keep a transplant patient alive until a healthy human organ becomes available.
United Therapeutics and Revivicor plan to begin a trial for pig-to-human kidney transplants first, and then move on to heart transplants. More patients are waiting on kidneys than any other organ, with the wait time ranging from three to five years, according to the National Kidney Foundation. Ayares said the ideal participant for these trials would “definitely be somebody that’s on an organ transplant list” but didn’t elaborate on how the company plans to choose patients for the trial.
Revivicor isn’t the only company seeking to transplant genetically engineered pig organs into people. Boston-based eGenesis and its Chinese partner Qihan Biotech are using the gene-editing tool CRISPR to modify pigs in hopes of someday using their organs in human patients as well. Last year, Luhan Yang, PhD, CEO of Qihan Biotech, told me the company has bred thousands of edited pigs with multiple genomic alterations. Meanwhile, XenoTherapeutics of Boston is currently testing pig skin from Revivicor’s GalSafe pigs in a clinical trial to treat burn wounds. The pig skin grafts are meant to be temporary until the patients’ own skin grows back.
Pig heart valves are already routinely used to replace damaged ones in people, but the tissue is treated with chemicals that kill off its cells.
As for people with alpha-gal syndrome, they might have to wait a little longer for allergy-free pork. Ayares said United Therapeutics won’t be directly involved in developing and marketing pork from the GalSafe pigs, but it is interested in finding a third-party distributor to bring the meat to customers.
Transplanting pig organs into people will no doubt be risky, but if it works, it could end the years-long wait for transplant patients — and potentially save lives.