A baboon has survived for over two years with dual hearts beating inside its abdomen: the baboon's own heart, and one from a genetically modified pig. The finding, published today in Nature Communications, is an important step toward using pig organs to replace ailing human parts.
The feat was made possible by genetic engineering — and a ton of drugs. Scientists at the US National Institutes of Health were able to keep pig hearts alive inside five baboons for a median of 298 days. The procedure involves connecting a pig's heart to a baboon's circulatory system inside its abdomen, and then keeping the heart alive with a drug cocktail tailored specifically for cross-species transplants. The donor pigs were also genetically modified so that their organs would be more compatible with the biology of humans. The same group had previously reported a maximum survival of 500 days. Today's study extends that number to 945 days.
Baboons with two hearts
Now, the researchers say they will use their fine-tuned drug cocktail to fully replace a baboon's heart with that of a genetically altered pig within the next year. If successful, this experiment will be the most significant step scientists have ever taken toward performing a pig-to-human heart transplant — a procedure that doctors say would counteract the ongoing shortage of human transplant organs.
About 8,000 people die every year while waiting for a transplant. Because of the high demand for donor organs, scientists have long wanted to use organs from animals, a procedure that is broadly referred to as a "xenotransplant." But early attempts at these surgeries didn't go well. In the 1960s, many patients died after receiving organs from baboons and chimps that their bodies rejected. To address this problem, researchers have been working on producing pigs whose biology is compatible with ours. (The pig is thought to be an ideal candidate for animal-to-human transplants because of its size, its short breeding cycle and its DNA, which has been researched extensively.) In 2002, that work began to pay off; two biotechnology companies announced that they had produced pigs whose organs wouldn’t prompt an immediate rejection when placed in the human body.
But even with these modifications, baboons that received organs from these pigs ended up rejecting them over time. That's why today's study is a big deal for researchers who hope xenotransplants will solve the current organ shortage.
In the study, researchers used organs belonging to pigs that were genetically altered to prevent rejection and blood clotting. They sewed pig hearts into the abdomens of five baboons, while conserving the baboons' own heart in its rightful place. The researchers did this so they could focus on the perfecting the drug cocktail and keep the animals alive when the pig hearts were eventually removed. Once the graft was complete, the scientists gave the baboons regular doses of the same anti-rejection drugs that human receive, in addition to antibodies tailored to prevent rejection of an organ belonging to another species.
"These hearts could have gone even longer"
The animals fared well following the graft, although one had to be euthanized about five months later because of an antibiotic-resistant infection. Because the other animals were healthy, the researchers started to wonder around the one year point if the pig hearts might be able to survive without the antibodies. "These hearts could have gone even longer, but we wanted to test to see if the animals had developed some kind of tolerance to the organs," says Muhammad Mohiuddin, a transplant surgeon at the National Heart, Lung, and Blood Institute, and a co-author of the study. But the researchers quickly realized that the hearts' survival was dependent on those drugs; when the scientists stopped administering the antibodies, the baboons slowly started to reject them, Mohiuddin says. So, the researchers removed the pig organs, leaving the baboons intact; the four remaining animals were alive at the end of the experiment.
The study shows that the hearts can survive for two years, and presumably longer, if the baboons stay on the drugs, says Peter Cowan, director of the immunology research center at St Vincent’s Hospital in Melbourne, who didn't work on the study. Because of this, Cowan thinks the study is an important step toward achieving clinical pig-to-human heart xenotransplantation.
The hearts' survival was dependent on the antibodies
The results are promising, but there's still a lot that scientists don't know. Some researchers worry, for instance, that it might too difficult to find a combination of drugs and genetic alterations that prevents rejection in humans. Others think the work is too dangerous because human recipients could become infected with animal viruses, says Mohiuddin. But Arthur Caplan, a bioethicist at New York University, thinks each of those objections will be addressed in time. "We have new gene editing techniques that will lets us focus on their immune system, so it should be possible to do it," he says. In addition, scientists might be able to kill off porcine viruses through genetic engineering or vaccines, he says. Cowan, for his part, thinks today's study provides some reassurance regarding the procedure's safety because "none of the long-surviving recipients showed any evidence of infection by an exotic pig virus."
Now that the researchers have figured out how to keep the pig hearts alive, they will attempt a complete pig-to-baboon heart replacement — a procedure that hasn’t been very successful in the past. The team also wants to perfect the pigs used in these transplants, Mohiuddin says. "As we go along, we are finding new genetic targets that we can suppress and modify, so we are hopeful that the better the pig is, the better will be the survival of these transplants will be." And that's a good thing for humanity; with this technique, "you can get unlimited supply of organs," he says.