Straightening a pig’s tail
Genetically Engineering Pigs to Grow Organs for People
Scientists announce the birth of 37 pigs gene-edited to be better for human transplant.
The idea of transplanting organs from pigs into humans has been around for a long time. And for a long time, xenotransplants—or putting organs from one species into another—has come up against two seemingly insurmountable problems.
The first problem is fairly intuitive: Pig organs provoke a massive and destructive immune response in humans—far more so than an organ from another person. The second problem is less obvious: Pig genomes are rife with DNA sequences of viruses that can infect human cells. In the 1990s, the pharmaceutical giant Novartis planned to throw as much $1 billion at animal-to-human transplant research, only to shutter its research unit after several years of failed experiments.
Quite suddenly, however, solving these two problems has become much easier and much faster thanks to the gene-editing technology CRISPR. With CRISPR, scientists can knock out the pig genes that trigger the human immune response. And they can inactivate the viruses—called porcine endogenous retroviruses, or PERVs—that lurk in the pig genome.
On Thursday, scientists working for a startup called eGenesis reported the birth of 37 PERV-free baby pigs in China, 15 of them still surviving. The black-and-white piglets are now several months old, and they belong to a breed of miniature pigs that will grow no bigger than 150 pounds—with organs just the right size for transplant into adult humans.
eGenesis spun out of the lab of the Harvard geneticist George Church, who previously reported inactivating 62 copies of PERV from pig cells in 2015. But the jump from specialized pig cells that grow well in labs to living PERV-free piglets wasn’t easy.
“We didn’t even know we could have viable pigs,” says Luhan Yang, a former graduate student in Church’s lab and co-founder of eGenesis. When her team first tried to edit all 62 copies in pig cells that they wanted to turn into embryos, the cells died. They were more sensitive than the specialized cell lines. Eventually Yang and her team figured out a chemical cocktail that could keep these cells alive through the gene-editing process. This technique could be useful in large-scale gene-editing projects unrelated to xenotransplants, too.
When Yang and her team first inactivated PERV from cells in a lab, my colleague Ed Yong suggested that the work was an example of CRISPR’s power rather than a huge breakthrough in pig-to-human transplants, given the challenges of immune compatibility. And true, Yang and Church come at this research as CRISPR pioneers, but not experts in transplantation. At a gathering of organ-transplantation researchers last Friday, Church said that his team had identified about 45 genes to make pig organs more compatible with humans, though he was open to more suggestions. “I would bet we are not as sophisticated as we should be because we’ve only been recently invited [to meetings like this],” he said. It’s an active area of research for eGenesis, though Yang declined to disclose what the company has accomplished so far.
“It’s great genetic-engineering work. It’s an accomplishment to inactivate that many genes,” says Joseph Tector, a xenotransplant researcher at the University of Alabama at Birmingham.
Researchers like Tector, who is also a transplant surgeon, have been chipping away at the problem of immune incompatibility for years, though. CRISPR has sped up that research, too. The first pig gene implicated in the human immune response as one involved in making a molecule called alpha-gal. Making a pig that lacked alpha-gal via older genetic-engineering methods took three years. “Now from concept to pig on the ground, it’s probably six months,” says Tector.
“It’s going to make such a huge difference that I don’t think it’s possible to conceive of it.”
Using CRISPR, his team has created a triple-knockout pig that lacks alpha-gal as well as two other genes involved in molecules that that provoke the human immune system’s immediate “hyperacute rejection” of pig organs. For about 30 percent of people, the organs from these triple-knockout pigs should not cause hyperacute rejection. Tector thinks the patients who receive these pig organs could then be treated with the same immunosuppressant drugs that recipients take after an ordinary human-to-human transplant.
Tector and David Cooper, another transplant pioneer, were both recently recruited to the University of Alabama at Birmingham for a xenotransplant program funded by United Therapeutics, a Maryland biotech company that wants to manufacture transplantable organs.
Cooper has transplanted kidneys from pigs engineered by United Therapeutics to have six mutations, which lasted over 200 days in baboons. The result is promising enough that he says human trials could begin soon. These pigs were not created using CRISPR and they are not PERV-free, though recent research has suggested that PERV may not be that harmful to humans. It will be up to the FDA to decide whether pig organs with PERV are safe enough to transplant into people.
If it happens, routine pig-to-human transplants could truly transform healthcare beyond simply increasing the supply. Organs would go from a product of chance—someone young and healthy dying, unexpectedly—to the product of a standardized manufacturing process. “It’s going to make such a huge difference that I don’t think it’s possible to conceive of it,” says Cooper. Organ transplants would no longer have to be emergency surgeries, requiring planes to deliver organs and surgical teams to scramble at any hour. Organs from pigs can be harvested on a schedule, and surgeries planned for exact times during the day. A patient that comes in with kidney failure could get a kidney the next day—eliminating the need for large dialysis centers. Hospital ICU beds will no longer be taken up by patients waiting for a heart transplant.
Pig Pancake Art
greffedufois: When I was waiting for a liver I often would be at the grocery store staring at pig livers thinking ‘why can’t I just use one of these dammit!?’
Luckily I got my transplant from my aunt after 2 years on the waiting list. Now I’m 8 years out and doing great!
If my kidneys burn out from the anti rejection meds (unfortunately not uncommon in transplant recipients) you bet your ass I’ll take a porcine kidney.
TheScribe86: …and with each passing day mankind draws closer to bringing about its own destruction by the menace that will be known as manbearpig
anonomatopoet: This is not kosher, is it?
Bourbonchild: God, I sure hope they have cleared all the retroviruses out of the pig genome, or some apocalyptic cross-species virus could emerge.
awesomemofo75: If we eat the pigs…are we cannibals?
DesireOfTheEndless: Oryx and Crake anyone?
J4CKR4BB1TSL1MS: David Cameron is eagerly following new developments.
Astark: Would it be considered immoral to eat the rest of the pig? ‘Cause nobody’s getting a pork chop transplant.
MisidentifiesAnimals: That thumbnail has some of the cutest goats I’ve ever seen!
panzerkampfwagen: It doesn’t say it’ll prevent rejection, just that the rejection won’t be so bad that it can’t be overcome with drugs. If you get an organ now from a human donor your body will reject it if you don’t take drugs to overcome that.
Edit – edited a word
Baron_Ultimax: As a side effect the pigs develop human like intelligence the new race of hyperpigs becomes a new slave race
hiscapa-is-detated: “And I know you won the race but you’re not gonna live forever.”
“I’m not stupid, Lucius. No one lives forever. No one. But with advances in modern science and my high level of income… I mean it’s not crazy to think I can’t live to be 245, maybe 300. Heck I just read the newspaper, they put a pig heart in some guy from Russia. I mean, do you know what that means??”
“No I don’t know what that means, I guess longer life?”
“Well no, he didn’t live.”
Sapibear: Expected to come in and see Margaret Atwood all over this.
This is literally out of her trilogy.
TheUplist: Jesus that took a LONG time. I first heard about this process in 1996. The year I graduated high school. From here on out… Godspeed.
DrSmirnoffe: 20 years ago, Malorie Blackman wrote a story along similar lines. And now, Pig Heart Boy could potentially become a reality.
Jerktionary: Oryx and Crake type shit
Cat6racer: I’m getting my pigoons at Healthwizer
Hawkmoona_Matata: Holy shit! I did a Biology Project on this very topic during November! They use CRISPR and it’s the bridge to genetically modified organs!
#Edit: [Found the stupid pun-ridden slideshow I made for it!](https://drive.google.com/file/d/1fYBNBJoQN2Csn8ByRw2HhqTq9INjPh1X/view?usp=sharing)
Formatting is messed up through the Google Drive Preview, but should be good otherwise.
WateredDown: Do you want orcs?
Because that’s how you get orcs.
predictablePosts: Nice now we can create a pig with two butts.
RatioVincere: Pigoons from [Oryx and Crake](https://en.wikipedia.org/wiki/Oryx_and_Crake?wprov=sfti1) by Margaret Atwood.
tiaradactyl: But… What about the pigs?
eeu914: Aww why the pigs though? Can’t we genetically engineer a blob of biomass with less feelings?
TVxStrange: I can’t wait to live forever.
amelech: I love how the article keeps referring to them as PERV free pigs
TallHonky: Eat more bacon then switch out your bad heart with a pig`s. Win win… unless you`re the pig.
wisdom_possibly: GMO organs could be dangerous. I only buy organic organs from Oregon. Quality, American-made organs.
Taronar: Mr.nobody anyone?
stirls4382: Poor pigs..
Xendarq: Somehow, some way, Captain Cheeto will try to fuck this up.
sexyagentdingdong: this is the plot of MR. Nobody
SeismicInfluence: Yeah I don’t know what the deal is with people displeased with Netflix movie Bright. At first I hated the racism it portrayed towards the orcs and was ready to turn the movie off but I knew I had to give it a chance. This movie is somewhat avant garde in that someone finally incorporated the idea of a magic world combined with our modern society (more gritty and realistic than Harry Potter), that idea alone is awesome. And then to make it a movie about working together to overcome the hate and ignorance we as society have been sickened with, this movie deserves everyone’s attention! Also, Lucy Fry is so beautiful! And Joel Edgerton is so wholesome and good I just wanted to give him a hug every fucking scene. And Will, well, everything he touches turns fascinating in my opinion
Peace and buds y’all
grimskull1: This is both insane and great news