Meet some of the world’s cleanest pigs, raised to produce kidneys and hearts for humans
BLACKSBURG, Virginia — The wide-eyed piglets rushing to observe visitors to their unusual barn may well represent the future of organ transplantation – and there is no question of rolling around in the mud here.
THE First genetically modified pig organs All viruses transplanted into humans come from animals born on this special research farm in the Blue Ridge Mountains — behind locked gates, where entry requires washing your vehicle, swapping your clothes for scrubs, and stepping into vats of disinfectant to clean your boots between each air-conditioned barn.
“These are valuable animals,” said David Ayares of Revivicor Inc., who has spent decades learning how to clone pigs with the right genetic modifications to enable these first daring experiments.
Biosecurity is getting even tighter a few miles away, in Christiansburg, Virginia, where a new herd is being raised — pigs that are expected to provide organs for formal animal-to-human transplant studies as early as next year.
The massive building, the first of its kind, looks nothing like a farm. It looks more like a pharmaceutical factory. And part of it is off-limits to all but a select few employees who take a scheduled shower, put on company-issued clothes and shoes, and then enter an enclave where piglets are raised.
Behind this protective barrier are some of the cleanest pigs in the world. They breathe air and drink water that is better filtered for contaminants than that required for humans. Even their food is disinfected – all to prevent them from contracting infections that could harm the transplant recipient.
“We designed this facility to protect pigs from contamination from the environment and people,” said Matthew VonEsch of United Therapeutics, Revivicor’s parent company. “Anyone who enters this building is a potential pathogen risk.”
The Associated Press got a glimpse of what it takes to clone and breed designer pigs for their organs — including a $75 million “designated pathogen-free facility” built to meet Food and Drug Administration safety standards for xenotransplantation.
Thousands of Americans every year die waiting for transplantation, and many experts acknowledge that there will never be enough human donors to meet the need.
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 human-like.
So far in the United States, there have been four “compassionate use” transplants, last-minute experiments on dying patients — two hearts and two kidneys. Revivicor provided both hearts and one of the kidneys. Although all four patients died within months, they offered valuable lessons for researchers willing to try again in less sick people.
The FDA is currently evaluating promising results from experiments on donated human bodies and awaiting results from additional studies on pig organs in baboons before deciding on next steps.
These are semi-customized organs — “we grow these pigs to the size of the recipient,” Ayares noted — that won’t show wear and tear from aging or chronic disease like most organs donated by people.
Surgeons who have harvested organs from Revivicor’s farm “are like, ‘Oh my God, this is the most beautiful kidney I’ve ever seen,’” Ayares added. “It’s the same thing when they harvest the heart, a healthy pink heart from a young animal.”
The main challenges: how to avoid rejection and whether the animals could be carrying an unknown disease risk of infection.
The process begins by editing genes in pig skin cells in the lab. Revivicor initially deleted a gene that produces a sugar called alpha-galthat triggers an immediate destruction of the human immune system. Then came the deletion of three genes, to eliminate other alarm signals that trigger the immune system. The company is now focusing on 10 genetic modifications: deleted pig genes and added human genes that together reduce the risk of rejection and blood clots and limit the size of organs.
They cloned pigs with these alterations, much in the same way that Dolly the sheep was created.
Twice a week, slaughterhouses ship hundreds of eggs from sows’ ovaries to Revivicor. Working in the dark, scientists examine the light-sensitive eggs under a microscope while sucking out the maternal DNA. Then they insert the genetic modifications.
“Take it in gently,” lead researcher Lori Sorrells whispers, pushing into the right spot without rupturing the egg. Gentle electrical shocks fuse the new DNA together and activate the embryo’s growth.
Ayares, a molecular geneticist who runs 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 engineered pig, the GalSafe The single knockout gene is now reproduced instead of cloned. If the xenotransplantation eventually works, other pigs with the desired gene combinations will too.
A few hours later, the embryos are transported to the research farm in a portable incubator and implanted into waiting sows.
At the research farm, Tom Petty’s “Free Fallin’” serenaded a pigsty where young piglets were being accustomed to the human voice through music. In climate-controlled pens, the animals grunted enthusiastic greetings until it was obvious their visitors weren’t bringing any treats. Three-week-old babies scurried to the safety of their mothers. Nearby, older siblings lay down for naps or played with balls and other toys.
“It’s a luxury for a pig,” Ayares said. “But they are very valuable animals. They are very intelligent animals. I’ve seen piglets playing with balls together like soccer.”
Nestled among rolling hills, the exact location of which has not been revealed for security reasons, is home to about 300 pigs of varying ages. Ear tags identify their genetics.
“There are some I salute,” said Suyapa Ball, head of swine technology and farm operations at Revivicor, as he rubbed a pig’s back. “We have to give them a good life. They give their lives for us.”
A subset of pigs used for the most critical experiments — early attempts with humans and FDA-required baboon studies — are housed in smaller, even cleaner barns.
But it’s in nearby Christiansburg that the new phase of xenotransplantation is most clearly visible: the sheer size of United Therapeutics’ new pathogen-free facility. In the 77,000-square-foot building, the company plans to produce about 125 pig organs a year, likely enough to fuel clinical trials.
The company’s video shows piglets running behind the protective barrier, chewing on toys and sniffing balls back and forth.
The pigs are born in a sort of pig farrowing center attached to the facility, weaned a day or two later, and transferred to their ultra-clean pens to be hand-raised. In addition to the on-site shower, their caretakers must don new hazmat suits and masks before entering each pig pen — another precaution against germs.
The pig area is surrounded on all sides by safety and mechanical systems that protect the animals. Outside air enters through several filtration systems. Giant tanks hold reserves of drinking water. Standing above the pig pens, VonEsch showed how pipes and vents were placed to allow maintenance and repairs without any contact with the animals.
It will take years of clinical trials to prove that xenotransplantation is truly effective. But if it succeeds, United Therapeutics plans to build even larger facilities, capable of producing up to 2,000 organs a year, in multiple locations across the country.
The field is at a point where many types of studies “tell us that there is no catastrophe, that there is no immediate rejection,” Ayares said. “The next two or three years are going to be extremely 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.
