CRISPR Containment

DARPA wants to prevent genetic engineering from destroying the world


This week, news broke that Jennifer Lopez has signed on to produce a futuristic new series titled “C.R.I.S.P.R.” which is, of course, also the name of the hip and cutting-edge genetic engineering technique. The series will depict a world of bioterror, where the president is threatened with a genetic assassination attempt and an unborn child is framed for murder. (We have a feeling scientists won’t love it.)

New genetic engineering techniques allow us to imagine curing disease, saving the environment and solving hunger, but it seems some people are also already wondering how they might be used for evil—including Jenny from the Block and the Pentagon’s science lab.

A new program from the Defense Advanced Research Projects Agency (DARPA) seeks to develop a sort of Ctrl Z function for gene editing that would allow scientists to undo their genetic work should they make an unfortunate mistake.

Right now, for example, scientists are investigating ways of using CRISPR to snip out the mutation that causes sickle-cell anemia in blood cells. So far, the treatment has only been tested in mice, but what if it proves to be effective in some people, but causes devastating side effects for others? Or what if scientists use a technique called gene drive to eradicate an invasive species, as right now scientists are considering with mosquitos in Hawaii, but it causes unforeseen environmental damage? DARPA wants researchers to develop a way to control and contain their mess, should anything go awry.

The Safe Genes program, which is currently accepting research proposals, aims to build a “biosafety and biosecurity toolkit” that could respond to different kinds of situations.

CRISPR, said program manager Renee Wegrzyn, has quickly made possible many amazing feats of genetic engineering. “But we really don’t have a sense of what the off-target effects are or the potential consequences,” she said.

Traditional biosafety and biosecurity measures like physical containment no longer work for technologies that are meant to exist in the world we inhabit, solving the problems of our bodies and our environment. CRISPR has made gene editing accessible not just to scientists, but to students and random guys from Mississippi trying to genetically engineer their dog. These facts combined make CRISPR not only dazzling, but potentially very, very dangerous.

The DARPA program, Wegrzyn said, is a “realization” of the technology’s “opportunity costs.”

If, for example, researchers could develop a tool to correct a gene that’s malfunctioning, but for one unlucky person that “cure” had severe side effects, right now there’s nothing that anyone could do about it.

With a drug, if you see adverse side effects, you can stop taking the drug and eventually it will clear from the system,” said Wegrzyn. “With gene-editing you are actually changing the genome.”

Wegrzyn would like researchers to develop drugs that could turn off the gene editor.

We want ways to develop ways to control [gene edits], to turn them off and to actually remove them from the system,” she said.

Some scientists have already begun thinking about these problems. After developing what’s known as a gene drive to circumvent the traditional rules of genetic inheritance, MIT scientist Kevin Esvelt was concerned about what might happen should it be accidentally released into the wild. It could spread a mutation through an entire population as it’s designed to overcome the restrictions of normal genetic inheritance. A possible use case is killing off a local population of mosquitos that threaten to spread Zika, but the very big catch is that such a move could theoretically cause a global mosquito extinction.

So after developing gene drive, Esvelt also proposed a way to limit it. Instead of allowing the traits to be passed down to every generation for eternity, Esvelt has suggested a method of limiting how many generations of offspring wind up receiving the genetically engineered traits.

But for now Esvelt’s solution is just hypothetical. DARPA would like researchers to come up with other ideas like it, and then figure out whether they will actually work. In the end, said Wegrzyn, it’s possible that the scientific community may wind up feeling that some of these technologies are not yet safe to use in the wild after all.

“We want to make sure scientists are thinking about that,” she told me. “This is part of a first step to think of safety first when it comes to these technologies. Every good scientist should be thinking about this anyway.”

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