PHOTO ILLUSTRATION BY ALYSE MARKEL/GETTY IMAGES
Editor’s note: In the months since this article first published in the March/April issue of Popular Mechanics, there have been a series of ground-breaking updates in the field of organ transplantation. On January 7, 2022, doctors at the University of Maryland Medical Center transplanted a heart from a genetically modified pig into a 57-year old patient for the first time ever. Just two weeks later, a team of doctors at the University of Alabama at Birmingham announced that they had performed another successful kidney transplant, this time transplanting both kidneys from a genetically modified pig into the body of a brain-dead patient.
In a groundbreaking 2021 experiment, surgeons from NYU’s Langone Health connected a genetically modified pig kidney to the blood vessels of a brain-dead organ donor on life support. The pig’s organ filtered waste from the woman’s blood and produced urine, just like a human kidney, for the entire 54-hour experiment. This first-of-its-kind procedure could signify pig kidneys as a transplant option for more than 90,000 Americans waiting for such an operation.
Transplanting organs is difficult, because our immune system is programmed to destroy anything it doesn’t recognize as native to the body. Animal-to-human transplants are extra challenging because most mammals, including pigs, carry a gene that allows their body to make a sugar found in cell membranes called alpha-gal. But that gene is inactivated in some species of primates, including humans. Our immune system therefore sees alpha-gal as an intruder and produces natural antibodies designed to destroy it. In some people, alpha-gal antibodies cause an allergic reaction after they consume meat and/or dairy products (see sidebar). For transplant patients, the presence of alpha-gal in a transplanted organ can trigger an immune system response that leads to organ failure.
The researchers performing the pig-to-human organ transplant anticipated the possibility of rejection, says Robert Montgomery, M.D., chair of surgery at NYU Langone Health and director of the NYU Langone Transplant Institute. Montgomery and his team connected the woman’s blood vessels to those of the pig kidney, clamping the vessels shut to prevent blood flow until the kidney was in place. “Right before we opened up the clamps, I said to the team, ‘I don’t know what’s going to happen…but we’re going to learn something important,’” Montgomery says.
When the team opened the clamps, the woman’s blood flowed and filtered normally through the pig’s kidney. The organ functioned as well at the end of the experiment as it had in those first few minutes. “I was pretty blown away,” Montgomery says.
To protect the kidney and the host from rejection during the transplant, Montgomery and his team turned to Revivicor, a Virginia-based biotechnology company, which produces and breeds “GalSafe” pigs, animals genetically engineered without the gene needed to make alpha-gal. Revivicor uses a method called homologous recombination to produce the pigs, removing the gene from the nucleus of a nonreproductive cell and then inserting that modified nucleus into a female reproductive cell. Once the reproductive cell develops into an embryo, researchers implant it into a “pseudopregnant” sow, a pig that’s experiencing the physical and behavior changes of pregnancy but is not actually pregnant. The sow will then give birth to a pig that’s missing the alpha-gal gene, and that pig can breed with other GalSafe pigs to produce more pigs without the alpha-gal gene.
🥩 Explained: Alpha-Gal and Meat Allergies
Lone star ticks can transfer alpha-gal sugar molecules through their saliva when they bite you, spurring an immune system response that sends a flood of antibodies to attack the sugar. If your body overproduces those antibodies, your immune system might also attack the alpha-gal found in animal food products such as pork, beef, gelatin, and milk. This can lead to an allergic reaction ranging from hives to nausea to, in extreme cases, anaphylaxis. Alpha-gal syndrome—unique for its immune system response to a sugar (most allergic reactions are triggered by a protein)—has no cure, but sometimes symptoms fade over time. Meanwhile, Revivicor breeds GalSafe pigs for human consumption in addition to creating organs safe for transplants, so meat lovers with an alpha-gal allergy could soon enjoy the occasional slice of bacon. —Jennifer Leman
The surgeons transplanted the pig’s thymus in addition to its kidney. The thymus gland controls the release of mature T-cells, immune system cells that fight foreign invaders in the body. It also deletes T-cells that malfunction and attack the body’s own tissues. In a pig-to-human organ transplant, the pig thymus deletes human T-cells that would otherwise attack the donated pig organs—in this case, the kidney. Including the thymus was an unusual part of the protocol and is not the clinical standard, says Susan Quaggin, M.D., chief nephrologist and professor of medicine at Northwestern University. Typically, surgeons administer immunosuppressive drugs to prevent the organ recipient’s immune system from attacking the new organ. Using the thymus instead is “exciting and innovative,” she says, but this novel approach could slow down this procedure’s path to FDA approval if more testing is required.
The next step will be to test the viability of the GalSafe kidney in a living human, Montgomery says. While this procedure didn’t indicate how long the kidney would keep working in a human, it suggested the pig kidney won’t be immediately rejected, he says. “I think that’s going to give all of us who are involved in this field, and the [government] regulators, some increased confidence that it’s going to be okay, and that we can now make this jump.”
The technology is unlikely to ever fully replace human kidneys, but after clinical trials and plenty of follow-up, Montgomery says, genetically modified pig kidneys will become a viable option for kidney transplant patients in the next five to 10 years.
This content is created and maintained by a third party, and imported onto this page to help users provide their email addresses. You may be able to find more information about this and similar content at piano.io