Can Cloned Pigs Save Dying Humans?
Why replacement organs will come from a farm.
This year’s Nobel Prize in Literature went to Kazuo Ishiguro, whose 2005 book Never Let Me Go described a dystopian world where (spoiler alert!) human clones are raised for their organs. The prize was timely in a way, since a version of this idea is now just around the corner — with pigs instead of humans.
Today, there are more than 116,000 people on the U.S. transplant waiting list, and 20 of them die every day. The need for organs vastly exceeds the supply. Researchers are getting closer to putting donor organs into deep cold storage, building new organs from scratch, or even growing replacements inside a patient’s body. But the technological advance you will likely see the soonest is the one that sounds most like science fiction: genetically engineered pigs will be cloned to provide human organs.
Donated organs have a brief window of usability and have to be rushed to recipients on helicopters and jets. “As soon as you remove the organ from the body, the clock is on,” says Gloria Elliott, a bioengineer at the University of North Carolina-Charlotte and director of the Charlotte Banks Initiative. That’s a group of researchers working toward “banking” human organs — cryopreserving them and stopping the clock indefinitely. This would help ensure usable organs reach people who need them. Embryos are already cryopreserved — but bigger, more complex tissues are a challenge.
Elliott’s lab is developing solutions to pump into fresh organs that will let them chill to a solid without forming harmful ice crystals. But, she says, “I think we’re still a long ways away from having a full suite of organs in the freezer ready for use.”
Other scientists are trying to build organs to order. Researchers such as Harald Ott at Harvard University have a way to strip the cells from existing organs, leaving behind a ghostly white scaffold; they’re working on covering these scaffolds with new cells to create whole new organs. Luis Alvarez directs the organ manufacturing group at United Therapeutics, where researchers are developing a platform to 3-D print human organ scaffolds, starting with lungs. The team is creating biological “inks” that will mimic the makeup of real organ scaffolds. “What you end up printing has the same feeling as, like, a liver and onions before you cook it,” Alvarez says, unappetizingly.
Alvarez says typical 3-D printers don’t have high enough resolution to recreate an organ scaffold’s intricacies. In fact, the resolution needs to be about three orders of magnitude smaller. United Therapeutics is developing that technology, but Alvarez thinks the first animal studies are still three or four years away. The organ transplant technology that’s furthest along, he thinks, is xenotransplantation — engineering animals to be organ donors for humans.
As for which animals would be ideal, pigs have a physiological likeness to humans, ready availability, and large litters. That’s why Harvard University’s George Church cofounded the company eGenesis with Luhan Yang: to engineer donor pigs. Church also does research in organ cryopreservation and 3-D organ printing. But, he says, “based on my first-hand, direct observations, xenotransplantation is way ahead of the other ones.”
The characters in Never Let Me Go are all cloned from different “models,” which works well for populating the novel with different characters but less well as a scientific premise. If doctors really planned to ease the organ shortage with human clones, wouldn’t they find (or create) one genetically ideal donor and clone that person over and over?
Church’s group is trying to build one ideal pig. So are researchers at the University of Alabama at Birmingham, where Joseph Tector directs the xenotransplant program. Tector says he and his colleagues want to engineer “the very simplest pig” that will be compatible with humans. In fact, they’ve already engineered it. In 2015 they created a pig with edits to three genes, removing sugars on the outsides of cells that would flag the human immune system. Now the researchers are evaluating the health of those animals and testing their organs in primates.
“Things switch from being unethical to being very ethical as you eat away at all the uncertainties and objections.”
Tector’s group believes editing so few genes lowers the risk of unintended DNA changes — at least for now. “Maybe in 20 years we won’t think anything of chopping the genome up like you’d cut up a steak,” Tector says.
But the researchers at eGenesis are making more edits. Close to 70 genes may be altered in their final pig, Church says.Among other changes, they’ve been working to remove retroviruses that are part of the pig genome. These viruses incorporate themselves in host DNA, like HIV in humans. Earlier this year, the eGenesis team announced it had used the gene-editing technology CRISPR to take all 25 retroviruses out of its pigs.
Scientists disagree about whether these retroviruses are really a problem. Tector points out that they’ve never been proven to cause disease in humans. “We’ve considered it very carefully,” Tector says, but decided it’s not worthwhile to try to remove pig retroviruses. Church, though, says he wouldn’t feel comfortable running a human trial with the viruses still in the pigs.
Tector’s group has already transplanted kidneys from its engineered pigs into monkeys, which have survived for more than a year. He thinks clinical trials could start within three years. Scientists at Revivicor (part of United Therapeutics) have also had success putting engineered pig hearts and kidneys into baboons. George Church estimates his group is less than two years away from starting animal trials, though he won’t say which organs they plan to test first.
Kazuo Ishiguro imagined human clones raised in isolated, fenced-in facilities. The book’s main characters attend an experimental school that’s gentler than the rest, where they even take art classes. But they later learn their artwork was made for evidence in an outside debate about whether clones have souls.
Cloned pigs are less ethically fraught than cloned humans; no one is giving paintbrushes to Tector’s or Church’s animals. But some people may still feel uneasy about xenotransplantation. “I think the pigs are further along technically” than advances such as cryopreservation or organ manufacturing, Elliott says, “but the public acceptance of it may be a little harder.”
“Maybe in 20 years we won’t think anything of chopping the genome up like you’d cut up a steak.”
Church, on the other hand, doesn’t think public sentiment against cloned pig organs will be a problem. Pig tissue is already used in surgeries such as heart-valve replacements, and he imagines that the facilities where pigs are kept could be expanded to house porcine organ donors. “Things switch from being unethical to being very ethical as you eat away at all the uncertainties and objections,” he says.
As an example, he points to in-vitro fertilization, which many scientists found alarming and unethical before the first “test-tube baby” was born in 1978. And although both Jewish and Islamic dietary laws forbid eating pork, theologians who discussed xenotransplantation at a 2013 symposium argued that these laws wouldn’t apply to life-saving transplants of pig parts.
Tector says he doesn’t expect the public will have any trouble accepting xenotransplantation “if it works well and it’s done right.” The next chapter in medicine may resemble fiction, but it doesn’t have to be dystopian.
