Scientists Are Working on an 'Undo Button' For Genetic Experiments Gone Wrong

The solution to GMOs that go wrong could be more gene editing.

Eradicating malaria and dengue has been a dream for quite some time, and there are plenty of humans who wouldn't mind if mosquitoes disappeared along with those diseases. A new genetic editing technique may make that future possible. But what if playing God over nature goes wrong? Well, then we can engineer new organisms that can reverse any damage we've done—and so on, and so on.

CRISPR/Cas9, a bioengineering technique that uses RNA to target and edit specific regions of genetic code, has been everywhere lately, and for good reason: It's more powerful, cheaper, and easier to work with than previous genome editing techniques. The technology also enables a technique proposed in 2003 called a "gene drive" to become a reality.

A gene drive uses CRISPR to force a genetically modified trait onto a wild population, by hacking that trait to be inherited more readily than a wild-type trait. In practice, this would mean that you could make a mosquito's immunity to malaria more dominant than the non-immune gene. You'd then release these genetically modified mosquitoes into the wild and, within a couple generations, have an entire population of malaria-immune mosquitoes.

This is how a gene drive works. Image: Emb Reports/Arthur Caplan

There are numerous potential uses for the technique. Mice, a necessary vector for lyme disease's transfer to humans, could be made immune from the disease; locusts could have their swarming gene switched off; invasive species could be eradicated within a few generations using gene drives that code for sterility.

As you can imagine, the ability to purposefully push a trait upon a wild population has a number of people worried. Eliminating an invasive species sounds like a great idea, but ecosystems may have already evolved to rely on that invasive species, for instance.

"If you took the mosquitoes out of an ecosystem, it might change everything," Hank Greely, a bioethicist at USC, said at the New Yorker Festival earlier this month. "You don't ever put your foot in the same river twice."

And so, scientists are also working on a "reverse" gene drive: Essentially, an "undo" button that requires more CRISPR to change things back to normal.

"They have the potential to decimate an entire species"

"The ability to undo something if things don't look like they're going right is tremendously important. You can program a CRISPR scalpel to overwrite a gene drive with a new version," Kevin Esvelt, a Harvard researcher working on gene drives said at the festival. "To undo a change, you have to drive your update through the population with CRISPR as well."

Esvelt was part of the team that conducted the world's first-ever successful gene drive at George Church's Harvard laboratory earlier this year. The team changed the natural inheritable dominance of yeast traits. Since then, it has been demonstrated that gene drives work in fruit flies as well.

Around the world, biotech companies and scientists are prepared to release millions of genetically modified mosquitoes into areas plagued with disease—but without a gene drive, there's no guarantee the strategy would work. With a gene drive, there's no guarantee that eradicating mosquitoes wouldn't wreak unpredictable havoc on the entire ecosystem.

"There are costs to doing nothing as well"

"The use of gene drives poses a much larger risk to the environment, as they have the potential to decimate an entire species, eliminate a food source for other species, or promote the proliferation of invasive pests," Arthur Caplan, a bioethicist at New York University, wrote in a paper published last week.

Caplan doesn't dismiss the potential for gene drives to do good in the world—they're so compelling precisely because they could eradicate disease or otherwise solve problems that have plagued humans for centuries—but he, too, believes that reverse gene drives need to be tested before we push these things into the wild.

"Regulations should require the development of methods to halt the effects of edited insects or animals should they prove harmful to other organisms, the environment, or humans," he wrote.

When the gene drive were first proposed a decade ago, the potential problems it might cause seemed theoretical. Now, we've got the technology and its efficacy has been demonstrated in a laboratory. There is a biotech company waiting for FDA approval to release genetically modified mosquitoes in Florida in an attempt to eradicate dengue there. With a gene drive, it'd theoretically have a better chance of succeeding. The question is quickly becoming how and where will we use this technology, not if we'll use it at all.

Esvelt says that CRISPR is another tool we can use to change nature, and, used correctly, it has the opportunity to be a more environmentally friendly one than the massive pesticide and bulldozing campaigns we used to eradicate malaria in the United States.

"We have technology that might be used to solve some of the world's problems, and they might cause other problems," Esvelt said. "Doing nothing is a choice. But there are costs to doing nothing as well. CRISPR allows us to speak nature's language to hopefully more elegantly solve problems."