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Meet some of the cleanest pigs in the world, raised to grow kidneys and hearts for humans
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Meet some of the cleanest pigs in the world, raised to grow kidneys and hearts for humans

BLACKSBURG, Va. — Wide-eyed piglets that scamper into their unusual barn to check out visitors may be the future of organ transplantation. And there’s no rolling in the mud here.

The first gene-edited pig organs ever transplanted into humans came from animals born on this special research farm in the Blue Ridge Mountains — behind locked gates, where upon entering you must wash your vehicle, change out of your clothes for medical scrubs, and step into tubs of disinfectant to clean your boots between each air-conditioned barn.

“These are precious animals,” said David Ayares of Revivicor Inc., who spent decades learning how to clone pigs with just the right genetic changes to make those first bold experiments possible.

Biosecurity is being tightened even a few miles away in Christiansburg, Virginia, where a new herd is being raised: pigs expected to provide organs next year for formal animal-to-human transplant studies.

This huge, unique building looks nothing like a farm. It looks more like a pharmaceutical factory. And part of it is closed to everyone except for certain carefully selected employees who take a timed shower, put on company-issued clothing and shoes, and then enter an enclave where piglets are raised.

Behind that protective barrier are some of the cleanest pigs in the world. They breathe air and drink water that is more filtered of contaminants than what humans need. Even their feed is sanitized — all to prevent them from picking up potential infections that could ultimately harm a transplant recipient.

“We designed this facility to protect the pigs from contamination from the environment and from people,” said Matthew VonEsch of United Therapeutics, Revivicor’s parent company. “Anyone who enters this building poses a potential pathogen risk.”

The Associated Press got an inside look at what it takes to clone designer pigs and breed them for their organs — including a $75 million “designated pathogen-free facility” built to meet Food and Drug Administration safety standards for xenotransplantation.

Breeding pigs to alleviate human organ shortage

Thousands of Americans die each year waiting for a transplant, and many experts acknowledge that there will never be enough human donors to meet the demand.

Animals offer the tantalizing promise of a ready-made supply. After decades of failed attempts, companies like Revivicor, eGenesis, and Makana Therapeutics are engineering pigs to be more like humans.

So far in the U.S., there have been four “compassionate use” transplants, last-ditch experiments in dying patients — two hearts and two kidneys. Revivicor provided both hearts and one of the kidneys. Although all four patients died within a few months, they offered valuable lessons for researchers ready to try again in people who are not as sick.

Currently, the FDA is evaluating promising results from experiments using donated human bodies and awaiting the results of additional studies using pig organs in baboons before making decisions about next steps.

They are semi-custom organs — “we grow these pigs to the size of the recipient,” Ayares noted — that show no signs of aging or chronic disease, like most organs donated by humans.

Transplant surgeons who have salvaged organs from Revivicor’s farm “say, ‘Oh my God, that’s the most beautiful kidney I’ve ever seen,’” Ayares added. “The same thing happens when they get the heart, a pink, healthy, happy heart from a young animal.”

The biggest challenges: how to prevent rejection and whether the animals may be at unknown risk of infection.

The process begins by modifying genes in pig skin cells in a lab. Revivicor initially removed a gene that produces a sugar called alpha-gal, which causes immediate destruction of the human immune system. Next came three gene knockouts, to remove other immune-triggering red flags. Now the company is focusing on 10 gene edits — deleted pig genes and added human genes that together reduce the risk of rejection and blood clots and reduce organ size.

They clone pigs with those modifications, similar to how Dolly the sheep came into being.

Twice a week, slaughterhouses Revivicor send hundreds of eggs taken from sows’ ovaries. Working in the dark with the light-sensitive eggs, scientists look through a microscope as they vacuum out the mother’s DNA. Then they sneak in the genetic modifications.

“Put it in nice and smooth,” senior researcher Lori Sorrells mutters, pushing in just the right spot without cracking the egg. Mild electric shocks fuse the new DNA and trigger the embryo’s growth.

Ayares, a molecular geneticist who leads Revivicor and helped create the world’s first cloned pigs in 2000, says the technique is “like playing two video games at once,” holding the egg in place with one hand and manipulating it with the other. The company’s first modified pig, the GalSafe single-gene knockout, is now being bred rather than cloned. If xenotransplantation ultimately works, other pigs with the desired gene combinations could do the same.

A few hours later, the embryos are transported to the research farm in a portable incubator and implanted into the waiting sows.

Luxury accommodations for important pigs

At the research farm, Tom Petty’s “Free Fallin'” serenaded a pigsty, where music accustomed the young to human voices. In air-conditioned pens, the animals grunted excited greetings until it became clear their visitors had brought no treats. The 3-week-old babies ran back to the safety of their mothers. Next to them, older siblings lay down for naps or watched balls and other toys.

“It’s a luxury for a pig,” Ayares said. “But these are very valuable animals. They are very smart animals. I’ve seen piglets playing together with balls as if it were football.”

About 300 pigs of various ages live on this farm nestled in rolling hills, the exact location of which has not been disclosed for security reasons. Tags on their ears identify their genetics.

“There are a few that I say hello to,” said Suyapa Ball, Revivicor’s head of swine technology and farm operations, as she rubbed a pig’s back. “You have to give them a good life. They give their lives for us.”

Some of the pigs used in the most crucial experiments—the first attempts with humans and the FDA-required studies with baboons—are housed in more confined but even cleaner barns.

But in neighboring Christiansburg, the clearest sign that xenotransplantation is entering a new phase is the sheer size of United Therapeutics’ new pathogen-free facility. In the 77,000-square-foot building, the company expects to produce about 125 pig organs a year, likely enough to supply clinical trials.

A company video shows piglets running around behind the protective barrier, chewing on toys and dragging balls back and forth.

They were born in a sort of pig birthing center attached to the facility, weaned a day or two later, and moved to their super-clean pens to be hand-raised. In addition to the on-site shower, their caretakers must don a new protective suit and mask before entering each set of pig pens—another precaution against germs.

The pig pen is surrounded on all sides by security and mechanical systems that protect the animals. Outside air is brought in through multiple filtration systems. Large vats contain reserve supplies of drinking water. Standing above the pig pens, VonEsch showed how pipes and vents were placed to allow maintenance and repairs without contact with the animals.

It will take years of clinical trials to prove whether xenotransplantation can really work. But if it does, United Therapeutics plans to build even larger facilities, capable of producing up to 2,000 organs a year, in locations around the country.

The field is at a point where multiple types of studies “are telling us that there are no train wrecks, that there is no immediate rejection,” Ayares said. “The next two or three years are going to be super exciting.”

The Associated Press Health and Science Department receives support from the Howard Hughes Medical Institute’s Science and Educational Media Group. The AP is solely responsible for all content.