Wide-eyed piglets rush to check out visitors to the unusual cage that can only represent the future of organ transplantation – and no rolling around in the mud here.
At the first genetically modified pig organ which was once transplanted to a person from an animal born on this special research farm in the Blue Ridge mountains – behind a locked gate, where entering must wash the vehicle, change clothes for medical scrubs and enter the disinfectant tub to clean the shoes between each air . – cage conditions.
“These are precious animals,” said David Ayares of Revivicor Inc., which has spent decades studying pig cloning with the right genetic changes to allow it. the first audacious experiment.
Biosecurity is getting tighter just a few miles away in Christiansburg, Virginia, where a new herd is being bred — pigs expected to provide organs for a formal animal-to-human transplant study as soon as next year.
Shelby Lum / AP
This huge first building doesn’t look like a farm. More like a pharmaceutical plant. And the section is closed to all carefully selected employees who shower on time, wear clothes and shoes provided by the company, and then enter the enclave where the piglets grow.
Behind that protective barrier are some of the cleanest pigs in the world. They breathe air and drink water that is better filtered from impurities than is necessary for humans. Even the feed is disinfected – all to prevent infections that could infect transplant recipients.
Shelby Lum / AP
“We designed this facility to protect pigs from contamination from the environment and from people,” said Matthew VonEsch of United Therapeutics, Revivicor’s parent company. “Anyone who enters this building could be at risk of pathogens.”
The Associated Press takes a look at what it takes to clone and raise designer pigs for organs — including a $75 million “pathogen-free facility” built to meet Food and Drug Administration safety standards for xenotransplantation.
Create pigs to reduce the shortage of human organs
Thousands of Americans every year die waiting for transplants, and many experts admit there won’t be enough human donors to meet the need.
Animals offer the comforting promise of a ready supply. After decades of failed attempts, companies including Revivicor, eGenesis and Makana Therapeutics is engineering pigs to become more human-like.
So far in the US, there have been four “compassionate” transplants, the last experimental ones to dying patients – two livers and two kidneys. Revivicor supplies two liver and one kidney. When four patients died within a few months, they provided valuable lessons for researchers who were ready to try again in healthy people.
Now the FDA is evaluating the promising results of experiments on donated human bodies and is awaiting the results of additional studies on pig organs in baboons before deciding on the next step.
Shelby Lum / AP
It’s a semi-custom organ — “we’re growing these pigs for recipient size,” Ayares notes — that won’t show the wear-and-tear of aging or chronic disease like most human donor organs.
Transplant surgeons who have taken organs at the Revivicor farm “go, ‘Oh my God, this is the best kidney I’ve ever seen,'” Ayares added. “Equally when you get a heart, a healthy heart is pink from a young animal.”
Shelby Lum / AP
The main challenge: how not to be rejected and whether the animal can carry some unknown risk of infection.
The process begins by modifying genes in pig skin cells in the laboratory. Revivicor initially removes the gene that produces its namesake sugar alpha-gal, which causes direct damage to the human immune system. Next came the three gene “knockouts”, to remove the other immunity-inducing red flags. Now the company is focusing on 10 gene edits – pig genes that have been deleted and added to humans that simultaneously reduce the risk of rejection and blood clots as well as limit the size of the organ.
He cloned a pig with these changes, similar to how he created Dolly the sheep.
Twice a week, the slaughterhouse sends Revivicor hundreds of eggs taken from the sow’s ovaries. Working in the dark with light-sensitive eggs, scientists look under a microscope as they inhale the mother’s DNA. Then they went into genetic modification.
“Tuck in nice and smooth,” murmurs senior researcher Lori Sorrells, pushing for just the right place without breaking the egg. A mild electric shock binds to the new DNA and activates the growth of the embryo.
Ayares, the molecular geneticist who led Revivicor and helped create the world’s first cloned pig in 2000, said the technique is “like playing two video games at the same time,” holding the egg with one hand and manipulating it with the other. The company’s first modified pig, missing a single GalSafe gene, is now bred instead of cloned. If xenotransplantation eventually works, other pigs with the desired gene combination will too.
Shelby Lum / AP
Hours later, the embryos are brought to the research farm in a handheld incubator and implanted into waiting sows.
Luxury accommodation for important pigs
At the research farm, Tom Petty “Free Fallin” provides a pig cage, where music educates young children with the human voice. In the air-conditioned cages, the animals grunted happy greetings until it was clear that the visitors had brought no treats. The 3-week-old cubs were returned to the safety of their mother. At the front, the older siblings are sleeping or checking balls and other toys.
“It’s a luxury for a pig,” Ayares said. “But it’s a very valuable animal. It’s a very smart animal. I’ve watched pigs play football like soccer.”
About 300 pigs of different ages live in this farm, located in the hills, the exact location is not disclosed for security reasons. Ear tags identify genetics.
Shelby Lum / AP
“There are a few things I can tell you,” said Suyapa Ball, Revivicor’s head of pig technology and farm operations, as he rubbed the back of one pig. “You have to give him a good life. He gave us his life.”
The subset of pigs used for the most critical experiments — the initial efforts with humans and the FDA-required baboon studies — are housed in more restricted, even cleaner barns.
But in neighboring Christiansburg is the clearest signal yet that xenotransplantation has entered a new phase — the 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, enough to supply clinical trials.
The company’s video shows a pig walking behind a protective barrier, chewing toys and repeatedly nosing.
They are born in a pig birthing center connected to the facility, weaned a day or two later and moved to the cleanest barn to be raised. In addition to on-site showers, keepers must wear new protective coats and masks before entering each pig pen – another precaution against germs.
The pig zone is surrounded on all sides by security and mechanical systems that protect the animals. Outside air enters through various filtration systems. Giant barrels contain a supply of drinking water. Standing above the pigsty, VonEsch showed how the pipes and vents were installed to allow maintenance and repairs without animal contact.
It will take years of clinical trials to prove that xenotransplantation really works. But if successful, United Therapeutics plans for a much larger facility, capable of producing up to 2,000 organs a year, at multiple sites across the country.
The field is at a point where various studies “tell us that there is no train wreck, that there is no direct rejection,” Ayares said. “The next two or three years will be very exciting.”
