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Editing of Pig DNA May Lead to More Organs for People
New York Times, October 15, 2015

This month, scientists gathered at the National Academy of Sciences in Washington to talk about Crispr, a new method for editing genes. In the past couple of years, the technique has become so powerful and accessible that many experts are calling for limits on its potential uses — especially altering human embryos with changes that could be inherited by future generations.

Among the scientists describing recent advances was one of Crispr’s pioneers, George Church of Harvard Medical School. In the midst of his presentation, packed with the fine details of biochemistry and genetics, Dr. Church dropped a bombshell.

In a typical experiment, scientists use Crispr to alter a single gene. But in recent work with pig cells, Dr. Church and his colleagues used Crispr to alter 62 genes at once. The researchers hope that this achievement may someday make it possible to use pig organs for transplantation into humans.

But the experiment also raises a deeper question: Could scientists someday alter complicated human traits by manipulating many genes at once?

“It’s obviously pretty impressive,” said Ron Weiss, a synthetic biologist at M.I.T. who was not involved in the new study. But despite the large number of genes involved, Dr. Weiss and other experts cautioned that the new work doesn’t mean that we’ve suddenly gained the power to bypass evolution. Crispr does not allow scientists to manipulate genes on a huge scale — yet.

Dr. Church’s experiment had its origins in the shortage of organs for transplants. Thousands of people die each year waiting for hearts, lungs and livers.

“It’s a cruel situation currently, that someone who needs a heart transplant has to pin their chance for a healthy life on the untimely death of another person,” said David A. Dunn, an expert on transplantation at the State University of New York at Oswego.

In the 1990s, researchers explored the possibility of using pig organs in humans, a technique known as xenotransplantation. Scientists hoped that pig organs could be cleansed of viruses and other pathogens that might harm their human hosts.

But that work stalled in 1998, when Jay Fishman and his colleagues discovered a bizarre new risk. Lurking in the pig’s DNA are viral genes.

They’re called endogenous retroviruses — humans have them, it turns out. The porcine versions (called PERVs, unfortunately) can produce full-blown viruses able to infect other pig cells. When researchers mixed pig and human cells in a petri dish, they found the pig viruses infected human cells, as well.

It seemed impossible to rid pig cells of PERVs. “They were part of these animals’ genomes,” said Dr. Fishman, associate director of the transplant center at Massachusetts General Hospital.

Dr. Fishman and other researchers have been looking for ways to overcome this hurdle, without much success. In 2013 they asked Dr. Church if he would be game to edit the genes of PERVs, making them harmless to pig cells, and thus to humans.

Dr. Church agreed to give it a shot, although he didn’t think it would work. Other attempts to disable PERVs had failed, mangling DNA so badly that the cells died. But Crispr, it turned out, is well suited to the task.

In the latest experiment, Dr. Church and his colleagues first examined pig cells to figure out exactly how many PERVs were contained in the genome. The researchers found 62. Had they found thousands, the experiment might not have worked.

The scientists then caught a second lucky break: The DNA was nearly identical from virus to virus, because all of them descended from a single ancestor that invaded the pig genome long ago.

To eradicate these viruses, Dr. Church and his team engineered a new set of genes and inserted them into pig cells. The genes produced enzymes that hunted for PERVs and snipped out bits of the viral DNA. After two weeks, the modified pig cells had altered all of their own viral DNA.

After the experiment, the viruses in the pig genome exhibited little activity. And despite the drastic genomic surgery, the chromosomes showed no abnormalities and the cells grew normally.

“This work brings us closer to a realization of a limitless supply of safe, dependable pig organs for transplant,” Dr. Dunn said. He predicted that future research might lead to PERV-free pig clones, which could found an entirely new line of pigs whose organs would be safer for human transplantation.

Importantly, Dr. Church and his colleagues didn’t alter 62 genes with 62 different Crispr molecules. There was no need: One molecule did the whole job. So far, scientists juggling multiple molecules have managed to alter fewer than six genes simultaneously.

We are certainly free to imagine a world in which parents have hundreds of genes in their designer babies edited to alter everything from the color of their eyes to their scores on intelligence tests. This experiment on pigs is a far cry from that scenario.

But that doesn’t mean that scientists won’t learn how to alter many genes in one fell swoop.

Dr. Church and his colleagues have begun experimenting with Crispr to reduce the risk that patients will reject transplanted pig organs, tinkering with 25 genes involved in producing molecules on the surface of pig cells that alert the immune system. The results are not yet published.

We should get expect scientists to swiftly expand their gene editing powers in the years to come, Dr. Weiss said. “Will we be able to to change 12 genes in 12 seconds? That’s not going to happen.”

“But if you say 12 days, that’s pretty likely.”

Copyright 2015 The New York Times Company. Reproduced with permission.
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