Meet some of the purest pigs in the world, bred to grow kidneys and hearts for the benefit of humans

BLACKSBURG, Va. (AP) – Wide-eyed pigs running to see visitors in their unusual barn can wait the future of transplants – and there’s no mud-slinging here.

The the first genetically engineered pig organs Human transplants come from animals born on this special research farm in the Blue Ridge Mountains – behind locked gates, where entry requires washing your car, exchanging your clothes for letters medical and step into disinfectant baths to clean your shoes between each breath. – a barn with conditions.

“These are valuable animals,” said David Ayares of Revivicor Inc., who has spent decades studying breeding pigs with the right genetic changes to allow them. those first attempts are clever.

Pest control is getting tighter just a few miles from Christiansburg, Virginia, where a new herd is being raised – pigs expected to donate organs for official transplant studies. person to person once in the next year.

This gigantic first-of-its-kind building is nothing like a farm. It is like a medicinal plant. And another part of it is closed to all workers except for some carefully selected ones who take a bath on time, put on the clothes and shoes provided by the company, and then go into the secret place where the puppies are still grow up there.

Behind that protective barrier are some of the cleanest pigs in the world. They breathe air and drink water that is better treated against impurities than is required of humans. Even their food is disinfected – all to prevent them from getting any infection that might end up harming the person who transmits it.

Matthew VonEsch of United Therapeutics, which is the parent company of Revivicor, says: “We created this facility to protect pigs against infection from the environment and people. “Everyone who enters this building is at potential risk of a pathogen.”

The Associated Press has gotten a glimpse of what it takes to assemble and raise pigs for organ transplants — including a $75 million “designated virus-free facility” built to meet safety standards. of the Food and Drug Administration for xenotransplantation.

Making pigs alleviates the shortage of human organs

Thousands of Americans every year die waiting for download, and many experts agree that there will never be enough human donors to meet that demand.

Animals offer a wonderful opportunity to find a ready-made supply. After decades of failed efforts, companies including Revivicor, in Genesis and Makana Therapeutics are engineering pigs like humans.

So far in the United States there have been four “compassionate use” transplants, last-ditch tests on dying patients – two hearts and two kidneys. Revivicor donated two hearts and two kidneys. Although four patients died within a few months, they provided important lessons for researchers willing to try again in less ill people.

The FDA is currently evaluating the promising results from the human trials provided and is awaiting the results of other studies of pig organs in monkeys before taking the next steps.

They’re conventional organs — “we grow these pigs to the size of the recipient,” Ayares noted — that won’t show the wear and tear of aging or chronic disease like many human-donated organs. .

Transplant surgeons at the Revivicor farm “go, ‘Oh my god, that’s the best kidney I’ve ever seen,'” Ayares added. “The same thing when they get a heart, a nice healthy pink heart from a small animal.”

Big issues: how to avoid rejection and how animals can carry other unknowns risk of infection.

The process begins by genetically modifying the pig’s skin cells in the laboratory. Revivicor originally deleted a gene that produces a sugar called alpha-gal, which causes immediate destruction of the immune system. Next came three genetic “tests,” to remove other red flags that challenge the body. Now the company is focusing on 10 genetic changes – pig genes have been deleted and human ones added that reduce the risk of rejection and blood clots as well as organ size.

They transform the pigs in the same way as Dolly the sheep were created.

Twice a week, the slaughterhouse sends Revivicor hundreds of eggs extracted from pig’s eggs. Working in the dark with light-sensitive eggs, scientists peer under a microscope as they absorb the mother’s DNA. Then they slide into genetics.

“Put it in nice and smooth,” murmurs senior researcher Lori Sorrells, pushing into just the right spot without cracking the egg. Light electrical impulses bind into the new DNA and activate the embryo’s growth.

Ayares, a molecular geneticist who leads Revivicor and helped create the world’s first pigs in 2000, says the process is “like playing two video games at the same time, ” to hold the egg in place with one hand and crack it with the other. The company’s first modified pig, yes GalSafe single gene knockout, now constructed in a cloned environment. If xenotransplantation ends up working, other pigs with the desired genes will be too.

Hours later, the embryos are transported to the research farm in a hand-held machine and implanted into waiting females.

Comfortable quarters for precious pigs

On the research farm, Tom Petty’s “Free Fallin'” was a fun pig barn, where music meets people’s voices. In the air-conditioned pens, the animals muttered happy greetings until it became clear that their guests had not brought food. At 3 weeks old the babies returned to the protection of the mother. In the next house, the older brothers were sleeping on the floor or looking at balls and other toys.

Ayares said: “It’s a luxury for a pig. But these are very important animals. They are very intelligent animals. I saw the cubs playing with balls together like a ball.”

About 300 pigs of different ages live on this farm, which is located in the hills, its exact location unknown for security reasons. The tags on their ears identify their genes.

“There are some that I say goodbye to,” said Suyapa Ball, Revivicor’s head of porcine science and farm operations, as he rubbed the back of one pig. “You have to give them a good life. They sacrifice their lives for us.”

A small percentage of the pigs used in the most critical experiments – those early experiments with humans and monkey studies required by the FDA – are kept in restricted, even clean, cages.

But in neighboring Christiansburg it’s a clear sign that xenotransplantation is entering a new phase – the size of United Therapeutics’ new germ-free facility. In the 77,000 square meter facility, the company expects to produce about 125 pig organs per year, possibly enough to provide clinical trials.

The company’s video shows pigs running behind a protective barrier, chewing toys and nose balls back and forth.

Born in a type of piggery that is connected to the facility, they are weaned after a day or two and moved into their very clean pens to be hand-raised. In addition to the on-site shower, their caretakers must wear a new protective suit and mask before entering the pigs’ pens – another measure to protect themselves against germs.

The piggery is surrounded on all sides by security and mechanical systems that protect the animals. Outside air comes in through a number of cleaning methods. Large vats contain potable water storage facilities. Standing above the pig rooms, VonEsch shows how the pipes and windows are positioned to allow maintenance and repair without coming into contact with the animals.

It will take years of clinical trials to prove whether xenotransplantation can work. But if successful, United Therapeutics’ plan is for larger facilities, capable of producing about 2,000 organs per year, in several locations around the country.

The field is in an era where many types of studies “tell us that there is no train wreck, that there is no immediate rejection,” Ayares said. “The next two or three years are going to be very exciting.”

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