Instead of Killing Mosquitoes, Why Don’t We Edit the Viruses Out of Them?

In the fight against zika—the mosquito-spread virus recently declared an international public health emergency due to its potential link with a brain deformity in infants—there are those who argue we should wipe out the insect entirely. But there are many questions about what the ecological impacts of destroying an entire population—or even an entire species—of mosquitoes might be. What if instead of modifying the mosquitoes to wipe out the insects, we modified them to wipe out the virus?

"We are definitely looking at adding zika resistance to the traits that we would have the option of driving through the mosquitoes," said Kevin Esvelt, a molecular biologist at MIT.

Esvelt and his colleagues work on a specific kind of genetic modification called gene drives, which they believe could provide solutions to ending the spread of mosquito-borne diseases without having to eradicate mosquitoes themselves.

"A gene drive is when a gene can spread through a population even though it doesn't help organisms to survive and reproduce," Esvelt said. "Gene drive elements are exceedingly common in nature. What's new now is that we finally have a tool for harnessing gene drives for our own purposes, such as to spread disease resistance to mosquitoes."

That tool is CRISPR/Cas9, the much-discussed genome editing technique that works like a "DNA scalpel," as Esvelt put it. It allows bioengineers to create custom gene drives in species: modifying certain traits and having them spread throughout the species. In simplest terms, you make an organism (like a mosquito) with an edited version of a gene (making it resistant to a virus, for example) and encode the CRISPR system next to that gene, Esvelt said. When that mosquito mates with a wild, non-genetically-modified mosquito, its offspring will get the unedited version of the gene, the edited version, and CRISPR.

"CRISPR will cut the original gene and it will then be repaired using the edited version and the CRISPR system," Esvelt said. "A CRISPR gene drive is really a way of making genome editing happen every generation down through the generations."

This technique has already been proven in yeast and fruit flies, and Esvelt is on a team currently working on a version that would create mosquitoes resistant to viruses that cause strife for humans, like dengue and chikungunya. They're also developing strategies to be able to reverse these gene drives, in case things go awry. Now that zika has emerged as a new, potential threat, Esvelt said they will be looking at incorporating zika resistance as well, though he had some caveats.

"By the time we probably could build a gene drive and certainly before we could get people to agree to whether or not we should use one, the zika outbreak is probably going to be over," Esvelt told me over the phone. "Everyone who is going to get it is likely to have already gotten it by then."

Esvelt pointed out that, until zika arrived in the Americas, it wasn't linked to anything more serious than mild, flu-like aches and fever. There are a lot of theories floating around for why this might be the case—the virus could have mutated or it could be that previous microcephaly links just weren't documented because zika wasn't well monitored—and Esvelt had his own idea. It could be that in areas where the virus was widespread, most women contracted it as children, he suggested. Zika doesn't stay in your system for much more than a week, so by the time those women were of childbearing age, they were already immune and zika posed no threat.

Because the virus descended suddenly on the Americas, a population that had no previous contact with it, pregnant women contracted zika for the first time, which may explain the new link to microcephalic births. Since the virus, as far as we know, poses little risk to anyone other than pregnant women, a more direct solution might be actually trying to spread the disease Esvelt said.

"If women want to get pregnant in the near future, they may well want to set up clinics where you gather people who are zika positive, let mosquitoes feed on them, and then have them bite people who want to be immune," Esvelt said. "Get it when it's harmless to you, and then you're immune forever."

Researchers are currently working on lots of other strategies, including trying to develop a vaccine or treatment. Genetically-modified mosquitoes that produce offspring that die before they mature to the adult stage (effectively wiping out the population) are alreadybeing tested on a small scale in Brazil and theFood and Drug Administration is considering a bid to test the modded skeeters in Florida. Since these mosquitoes aren't using gene drive, it's a little easier to control, and might provide a more immediate solution for controlling the spread of zika.

But for the long term, Esvelt thinks more investment ought to be made in gene drives. There are a lot of ethical questions around the use of this technique, he said, but the time to make those decisions is now, as the threat of viral diseases looms.

"More than 100 million people are infected by dengue every year, and tens of thousands of people actually die from it," Esvelt said. "It's a pretty devastating disease around the world. Anything that gives us the opportunity to talk about whether we should consider using these approaches, like the zika outbreak, at least that could be a little bit of a silver lining out of this tragedy."