Gene drives can force new DNA into subsequent generations at warp speed
Critics worry GMO changes might have unintended consequences
Researchers say they have created fail-safes or can engineer fixes
Editor’s Note: This is part four in a four-part series about the efforts to stop or slow the spread of Zika virus though the use of modified and engineered mosquitoes. See all four pieces here.
University of California-Irvine microbiologist Anthony James says he’s called the “silverback” – the wise old man in the gorilla kingdom – of gene drive researchers, because he’s spent 30 years trying to find a way to genetically engineer an end to malaria, dengue and other mosquito-borne diseases.
“I started my research program in 1986. And it’s hard to convey that to people today, but no genes had been found in mosquitoes, much less the ability to splice, so it was starting from nothing. So I guess that’s why they say I’m the silverback. I started working on it a long time ago and never gave up.”
Today, labs around the world are filled with enterprising researchers using new tools such as CRISPR’s Cas9 to splice a helpful gene into a mosquito’s bloodlin–a gene that might interfere with the mosquito’s ability to live a long life, reproduce or transmit disease
In the case of Zika, it takes 5 to 14 days for a female mosquito to become infected with the virus after biting a human or animal who has an active case of the disease. If a gene can be edited so that it kills or alters the mosquito before she’s infectious, you have effectively solved the problem.
The gene drive takes that one step further by “driving” the new gene into subsequent generations at a much higher rate than the standard genetics you learned in school.
“It’s forcing those genes into the population,” explained molecular biologist Omar S. Akbari. “This is the cutting edge of genetics. Instead of a gene being transferred to 50% of the offspring, now it can transfer to 99%, maybe even 100% of their progeny.”
Gene drives take traditional genetically modified mosquito efforts and put them into overdrive. Take for example the Florida GMO mosquito called OX513A, created by a London company, Oxitec.
“Basically, Oxitec’s technology is a single-generation technology,” explained Akbari. “You mass rear them. You release them. They mate out. They die. You do it again. And if you stop doing it, then they’re all gone. Whereas with gene drive you create them, raise them in mass, then release them and it spreads like wildfire.”
In other words, said Akbari, a gene drive is sort of a poor man’s way of changing an entire population.
“It’s not a good company business model because you’re not going to make money every generation,” said Akbari. “You’re going to release it once and you’re going to solve a world problem. That’s the goal.”
Forget Frankenstein – think ‘Chimera’
Before you can “drive” a beneficial gene into a population, you have to create it. That’s where genetic engineers can get really creative. Take what James and his team did to create a drive against one strain of malaria.
“A long time ago, colleagues of ours were studying human malaria parasites and they put them into mice,” said James. “The mice created antibodies to fight that off. So we went into the mice and got a couple of the antibody genes that are functional and put them in mosquitoes. So we gave the mosquito part of the mouse immune system that allows it to fight off human parasites.”
“Frankenstein’s not a fair comparison,” explains James, “because Frankenstein was made of all human parts. We’re making what’s called a Chimera, an animal that is made from parts of several creatures.”
And it’s just that sort of genetic engineering that has the world of science in shock and awe, and some of the public picturing horror-flick mutant creatures running amok because some scientist didn’t consider all the consequences.
“My argument to that is we know exactly what we put in the mosquito,” said Akbari, “and we can engineer ways of removing those from the mosquito or replacing those mosquitoes.”
“We’ve thought a lot about what could go wrong and this is where the engineering comes back in,” agreed James. “So we just build these with fail-safes so if for some reason the gene got out, it wouldn’t work.”
“I also wouldn’t say, ‘In case we screw something up,’” said Akbari. “I would say, ‘In case evolution does what it’s good at’ and basically the virus evolves and the mosquitoes are no longer able to suppress that virus somehow.”
“So, you’re kind of at an arms race with evolution – who is going to win?” continued Akbari. “And if evolution starts beating you, then the beauty of engineering is that you can go back in with a newer, better version.”
Assuming gene drives make it past their ethical and environmental obstacles and prove themselves safe, how does all of this help fight Zika? That’s still on the drawing board.
“We already have the blueprint,” said James. “We have a box full of parts and we would offer to make probably four or five different things that we would anticipate would work really well.”