Business & Tech

Gene editing spurs hope for transplanting pig organs into humans

Piglets whose genes were edited to remove a retrovirus. The advance, reported on Aug. 10, 2017, in the journal Science, may make it possible one day to transplant livers, hearts and other organs from pigs into humans, a hope that experts had all but given up.
eGenesis via The New York Times
Piglets whose genes were edited to remove a retrovirus. The advance, reported on Aug. 10, 2017, in the journal Science, may make it possible one day to transplant livers, hearts and other organs from pigs into humans, a hope that experts had all but given up.

In a bold scientific step that helps open the door to organ transplants from animals, researchers at Harvard and a private company have created gene-edited piglets cleansed of viruses that might cause disease in humans.

The advance, reported Thursday in the journal Science, may make it possible one day to transplant livers, hearts, and other organs from pigs into humans, a hope that experts had all but given up.

There were 33,600 organ transplants last year, and 116,800 patients on waiting lists, according to Dr. David Klassen, chief medical officer at the United Network for Organ Sharing, a private, nonprofit organization that manages the nation’s transplant system.

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If pig organs were shown to be safe and effective, “they could be a real game changer,” said Klassen, who was not involved in the new study. Dr. George Church of the Harvard group now says the first pig-to-human transplants could occur within two years.

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The new research combines two great achievements in recent years — gene editing and cloning — and is unfolding quickly. But the work is novel and its course unpredictable, Klassen noted. It may be years before enough is known about the safety of pig organ transplants to allow them to be used widely.

Major religious groups have already weighed in on the ethical questions, however, generally concluding that pig organs are acceptable for lifesaving transplants, noted Dr. Jay Fishman, codirector of the transplant program at Massachusetts General Hospital. Pig heart valves already are routinely transplanted into patients. The idea of using pigs as organ factories has tantalized investigators for decades. Porcine organs can be the right size for human transplantation, and in theory, similar enough to function in patients.

In the 1990s, scientists began pursuing the idea in earnest. But in 1998, Fishman and his colleagues discovered that hidden in pig DNA were genes for viruses that resembled those causing leukemia in monkeys.

When researchers grew pig cells next to human embryonic kidney cells in the laboratory, these viruses — known as retroviruses — spread to the human cells. Once infected, the human cells were able to infect other human cells.

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Fears that pig organs would infect humans with bizarre retroviruses brought the research to a halt. But it was never clear how great this threat really was, and as years have gone by, many experts, including Fishman, have become less concerned.

Some patients with diabetes have received pig pancreas cells, hidden in a sort of sheath so the immune system will not reject them. And burn patients sometimes get grafts made of pig skin. The pig skin is eventually rejected by the body, but it was never meant to be permanent anyway.

There is no evidence that any of these patients were infected with porcine retroviruses. In any event, said Dr. A. Joseph Tector, a transplant surgeon at the University of Alabama Birmingham, pig retroviruses are very sensitive to the drugs used to treat HIV.

“We don’t know that if we transplant pig organs with the viruses that they will transmit infections, and we don’t know that the infections are dangerous,” Fishman said. “I think the risk to society is very low.”

Church and his colleagues thought the retrovirus question could be resolved with Crispr, the new gene-editing technology. They took cells from pigs and snipped the viral DNA from their genomes. Then the scientists cloned the edited cells.

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Each pig cell was brought back to its earliest developmental stage and then slipped into an egg, giving it the genetic material to allow the egg to develop into an embryo. The embryos were implanted in sows and grew into piglets that were genetically identical to the pig that supplied the initial cell.

Cloning often fails; most of the embryos and fetuses died before birth, and some piglets died soon after they were born. But Church and his colleagues ended up with 15 living piglets, the oldest now 4 months old. None have the retroviruses.

Church founded a company, eGenesis, in hopes of selling the genetically altered pig organs. Eventually, Church says, the company wants to engineer pigs with organs so compatible with humans that patients will not need to take anti-rejection drugs.

Part of the organ rejection problem is already being solved with gene editing and cloning. It is an issue that emerged in the early 1980s when surgeons put a pig heart into a baboon. To their shock, the baboon died in minutes.

Researchers soon discovered that pig organs are covered with carbohydrate molecules that mark the organs for immediate destruction by human antibodies.

Dr. David Cooper, at UAB, and his colleagues, including Tector, have used gene editing and cloning to make pigs without the carbohydrates on the surfaces of their organs.

They successfully transplanted hearts and kidneys from those pigs into monkeys and baboons. So far, the animals have lived more than a year with no problems, Tector said.

To some, the idea of growing pigs to be organ factories is distasteful, if not unethical.

But, Cooper noted, the few thousand pigs grown for their organs would be a small fraction of the 100 million pigs a year that are killed for food in the United States. And, he said, the pigs would be anesthetized and killed humanely.

Many patients may prefer a human organ, Cooper acknowledged, but that is not always possible.

“About 22 people a day die waiting for a transplant,” he said. “If you could help them with a pig organ, wouldn’t that be wonderful?”