Wide-eyed piglets rushing to check out the visitors to their unusual barn just might represent the future of organ transplantation 香蕉视频直播� and there香蕉视频直播檚 no rolling around in the mud here.
The first gene-edited pig organs ever transplanted into people came from animals born on this special research farm in the Blue Ridge mountains 香蕉视频直播� behind locked gates, where entry requires washing down your vehicle, swapping your clothes for medical scrubs and stepping into tubs of disinfectant to clean your boots between each air-conditioned barn.
香蕉视频直播淭hese are precious animals,香蕉视频直播� said David Ayares of Revivicor Inc., who spent decades learning to clone pigs with just the right genetic changes to allow those first audacious experiments.
The biosecurity gets even tighter just a few miles away in Christiansburg, Virginia, where a new herd is being raised 香蕉视频直播� pigs expected to supply organs for formal studies of animal-to-human transplantation as soon as next year.
This massive first-of-its-kind building bears no resemblance to a farm. It香蕉视频直播檚 more like a pharmaceutical plant. And part of it is closed to all but certain carefully chosen employees who take a timed shower, don company-provided clothes and shoes, and then enter an enclave where piglets are growing up.
Behind that protective barrier are some of the world香蕉视频直播檚 cleanest pigs. They breathe air and drink water that香蕉视频直播檚 better filtered against contaminants than what香蕉视频直播檚 required for people. Even their feed gets disinfected 香蕉视频直播� all to prevent them from picking up any possible infections that might ultimately harm a transplant recipient.
香蕉视频直播淲e designed this facility to protect the pigs against contamination from the environment and from people,香蕉视频直播� said Matthew VonEsch of United Therapeutics, Revivicor香蕉视频直播檚 parent company. 香蕉视频直播淓very person that enters this building is a possible pathogen risk.香蕉视频直播�
The Associated Press got a peek at what it takes to clone and raise designer pigs for their organs 香蕉视频直播� including a $75 million 香蕉视频直播渄esignated pathogen-free facility香蕉视频直播� built to meet Food and Drug Administration safety standards for xenotransplantation.
Creating pigs to ease the shortage of human organs
Thousands of Americans each year die waiting for a transplant, and many experts acknowledge there never will be enough human donors to meet the need.
Animals offer the tantalizing promise of a ready-made supply. After decades of failed attempts, companies including Revivicor, eGenesis and Makana Therapeutics are engineering pigs to be more humanlike.
So far in the U.S. there have been four 香蕉视频直播渃ompassionate use香蕉视频直播� transplants, last-ditch experiments into dying patients 香蕉视频直播� two hearts and two kidneys. Revivicor provided both hearts and one of the kidneys. While the four patients died within a few months, they offered valuable lessons for researchers ready to try again in people who aren香蕉视频直播檛 quite as sick.
Now the FDA is evaluating promising results from experiments in donated human bodies and awaiting results of additional studies of pig organs in baboons before deciding next steps.
They香蕉视频直播檙e semi-custom organs 香蕉视频直播� 香蕉视频直播渨e香蕉视频直播檙e growing these pigs to the size of the recipient,香蕉视频直播� Ayares noted 香蕉视频直播� that won香蕉视频直播檛 show the wear-and-tear of aging or chronic disease like most organs donated by people.
Transplant surgeons who香蕉视频直播檝e retrieved organs on Revivicor香蕉视频直播檚 farm 香蕉视频直播済o, 香蕉视频直播極h my god that香蕉视频直播檚 the most beautiful kidney I香蕉视频直播檝e ever seen,香蕉视频直播櫹憬妒悠抵辈 Ayares added. 香蕉视频直播淪ame thing when they get the heart, a pink healthy happy heart from a young animal.香蕉视频直播�
The main challenges: how to avoid rejection and whether the animals might carry some unknown infection risk.
The process starts with modifying genes in pig skin cells in a lab. Revivicor initially deleted a gene that produces a sugar named alpha-gal, which triggers immediate destruction from the human immune system. Next came three-gene 香蕉视频直播渒nockouts,香蕉视频直播� to remove other immune-triggering red flags. Now the company is focusing on 10 gene edits 香蕉视频直播� deleted pig genes and added human ones that together lessen risk of rejection and blood clots plus limit organ size.
They clone pigs with those alterations, similar to how Dolly the sheep was created.
Twice a week, slaughterhouses ship Revivicor hundreds of eggs retrieved from sow ovaries. Working in the dark with the light-sensitive eggs, scientists peer through a microscope while suctioning out the maternal DNA. Then they slip in the genetic modifications.
香蕉视频直播淭uck it in nice and smooth,香蕉视频直播� murmurs senior researcher Lori Sorrells, pushing to just the right spot without rupturing the egg. Mild electric shocks fuse in the new DNA and activate embryo growth.
Ayares, a molecular geneticist who heads Revivicor and helped create the world香蕉视频直播檚 first cloned pigs in 2000, says the technique is 香蕉视频直播渓ike playing two video games at the same time,香蕉视频直播� holding the egg in place with one hand and manipulating it with the other. The company香蕉视频直播檚 first modified pig, the GalSafe single gene knockout, now is bred instead of cloned. If xenotransplantation eventually works, other pigs with the desired gene combinations would be, too.
Hours later, embryos are carried to the research farm in a handheld incubator and implanted into waiting sows.
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Luxury accomodations for important pigs
On the research farm, Tom Petty香蕉视频直播檚 香蕉视频直播淔ree Fallin香蕉视频直播櫹憬妒悠抵辈 was serenading a piglet barn, where music acclimates the youngsters to human voices. In air-conditioned pens, the animals grunted excited greetings until it香蕉视频直播檚 obvious their visitors brought no treats. The 3-week-olds darted back to the security of mom. Next door, older siblings laid down for a nap or checked out balls and other toys.
香蕉视频直播淚t is luxury for a pig,香蕉视频直播� Ayares said. 香蕉视频直播淏ut these are very valuable animals. They香蕉视频直播檙e very smart animals. I香蕉视频直播檝e watched piglets play with balls together like soccer.香蕉视频直播�
About 300 pigs of different ages live on this farm, nestled in rolling hills, its exact location undisclosed for security reasons. Tags on their ears identify their genetics.
香蕉视频直播淭here are certain ones I say hi to,香蕉视频直播� said Suyapa Ball, Revivicor香蕉视频直播檚 head of porcine technology and farm operations, as she rubbed one pig香蕉视频直播檚 back. 香蕉视频直播淵ou have to give them a good life. They香蕉视频直播檙e giving their lives for us.香蕉视频直播�
A subset of pigs used for the most critical experiments 香蕉视频直播� those early attempts with people and the FDA-required baboon studies 香蕉视频直播� are housed in more restricted, even cleaner barns.
But in neighboring Christiansburg is the clearest signal that xenotransplantation is entering a new phase 香蕉视频直播� the sheer size of United Therapeutics香蕉视频直播� new pathogen-free facility. Inside the 77,000-square-foot building, the company expects to produce about 125 pig organs a year, likely enough to supply clinical trials.
Company video shows piglets running around behind the protective barrier, chewing on toys and nosing balls back and forth.
They were born in sort of a porcine birthing center connected to the facility, weaned a day or two later and moved into their super-clean pens to be hand-raised. In addition to the on-site shower, their caretakers must put on a new protective suit and mask before entering each suite of pig pens 香蕉视频直播� another precaution against germs.
The pig zone is surrounded on all sides by security and mechanical systems that shield the animals. Outside air enters through multiple filtration systems. Giant vats hold backup supplies of drinking water. Standing over the pig rooms, VonEsch showed how pipes and vents were placed to allow maintenance and repair without any animal contact.
It will take years of clinical trials to prove whether xenotransplantation really could work. But if it succeeds, United Therapeutics香蕉视频直播� plan is for even larger facilities, capable of producing up to 2,000 organs a year, in several places around the country.
The field is at a point where multiple kinds of studies 香蕉视频直播渁re telling us that there香蕉视频直播檚 no train wrecks, that there香蕉视频直播檚 no immediate rejection,香蕉视频直播� Ayares said. 香蕉视频直播淭he next two or three years are going to be super exciting.香蕉视频直播�
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The Associated Press Health and Science Department receives support from the Howard Hughes Medical Institute香蕉视频直播檚 Science and Educational Media Group. The AP is solely responsible for all content.
Lauran Neergaard, The Associated Press
