Time for a genetic intervention?

Photographer: Saul Martinez/Bloomberg

Fighting Zika Virus With Genetic Engineering

Faye Flam is a Bloomberg View columnist. She was a staff writer for Science magazine and a columnist for the Philadelphia Inquirer, and she is the author of “The Score: How the Quest for Sex Has Shaped the Modern Man.”
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In a handful of labs around the world, scientists have quietly invented a new and powerful biotech weapon against disease-carrying mosquitoes. Called gene drive, it goes far beyond ordinary genetic modification, bending the rules of inheritance to spread modified genes through vast populations of organisms. If it works as expected, it could be used to extinguish the population of mosquitoes rapidly spreading the Zika virus through South America.

An even more consequential deployment would spread an altered gene through the world’s population of malaria-carrying mosquitoes, endowing them with resistance against the parasite that now kills more than 400,000 people every year. 

This is heady stuff to consider for a public that has yet to come to terms with genetic modification. While some scientists allegedly want to “sic” gene drives on Zika-carrying mosquitoes, most biologists involved hope for something less dramatic -- the chance to gradually ramp up testing while encouraging public discussion about the issue. It remains to be seen whether the Zika threat will mushroom into a problem that would justify the risk of rushing a new technology. However, the death and suffering caused by malaria already justifies continued investment in gene drive research, and given enough testing, it might prove safer than spraying insecticides.

The power of the technology comes from the way it breaks the rules of normal reproduction. In most species, animals carry two versions of each gene on two matched sets of chromosomes. Each copy passively accepts a 50/50 chance of getting shuffled into an egg or sperm, and from there, to progeny. But with gene drive, a modified gene carries instructions to attack the opposing chromosome, snip it, and insert a second copy of itself.

In the face of Zika, gene drive might boost the effectiveness of genetic engineering solutions already being explored by the British company Oxitec. The company was originally looking for ways to control the spread of another mosquito-borne disease, dengue fever. It’s experimenting with genetically modified male mosquitoes carrying a gene that’s lethal to larvae. But their field trials have led to tabloid press accusations that they’ve caused the Zika problem.

Beyond the PR hassles, the company faces a hurdle posed by evolution. If the introduced gene is lethal to offspring, natural selection will weed it out, favoring the healthy version of the gene. But there are tricks -- ways the lethal gene could kill only male offspring or only females, while being carried on through the other sex. Gene drives could accelerate the spread of such a gene so that it might cause a population to crash before evolution would weed it out.

Last April, scientists demonstrated an effective gene drive in laboratory fruit flies -- the fast-spreading gene had the striking effect of turning most of the population yellow. They published the results in the journal Science. Last November, the same researchers, collaborating with scientists working on malaria resistance, demonstrated an anti-malaria gene drive could work in mosquitoes.

But moving such a novel and powerful technology into field trials will have to wait for an unprecedented level of public trust and international cooperation.

“The greatest risk is not technological or ecological -- it’s social,” said Kevin Esvelt, who developed one of the most promising versions of gene drive while at Harvard University and is now a professor at MIT’s Media Lab.

Not that we human beings haven’t already made profound global changes in the environment -- we’ve wiped out species, allowed others to take over new islands and continents, and even changed the composition of our planet’s atmosphere. But in most cases, these changes have been both unintended and harmful.

Esvelt’s gene drive uses so-called gene editing, or Crispr, which gives modified genes a particularly efficient toolkit for inserting themselves into their partner chromosomes.

Endowing genes with special equipment to foil the rules of genetics may sound magical, but biologists have simply co-opted tools that other living things invented through evolution. Human DNA is littered with invasive genes that copied themselves into us with natural gene drives.

The question here is what unintended -- and unanticipated -- consequences might arise. Mosquitoes may be hated, but they’re part of ecosystems and provide food for birds, bats and some fish.

Anthony James, a University of California biologist who has been working on gene drive in mosquitoes, said that in their experiments the insects live on, except that they carry antibodies that make them resistant to the malaria parasite.

James said the situation is different with Aedes aegypti, the species that carries Zika. The virus was recently declared an international emergency by the World Health Organization after circumstantial evidence linked it to a spike in birth defects in Brazil. The Zika-carrying mosquitoes spread other serious diseases -- chikungunya, dengue and yellow fever. It makes more sense to tackle all these diseases, he said, by introducing a gene that causes the mosquito offspring to die.

Since these mosquitoes came from Africa and hitchhiked to the Americas on ships, they aren’t part of the normal ecosystem, he said. Wiping them out could be thought of as a bioremediation.

The potential risks and benefits are profound enough that the National Academy of Sciences has begun an evaluation, expected out later this year. Even if the U.S. scientific community gives a gene drive the green light, say, to eradicate our Zika-carrying mosquitoes, the consequences can’t be easily confined to one country. Flying insects don’t respect international borders.

“We have not faced a challenge that requires so many people in so many countries to agree to something,” said MIT’s Esvelt. But he suggests that we should factor in the dangers of existing technology -- insecticides -- known to harm beneficial insects and other wildlife, adding, “This is much more eco-friendly than using sprays.”

The Mosquitoes Taking on the Zika Virus

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To contact the author of this story:
Faye Flam at fayeflam@gmail.com

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Tracy Walsh at twalsh67@bloomberg.net