The New York Times, July 17, 2014
Every year, malaria-carrying mosquitoes kill more than 600,000 people, most of them children. Over the centuries, people have battled those mosquitoes in numerous ways, like draining swamps, spraying insecticides and distributing millions of bed nets. And yet malaria remains a menace across much of the world.
A new technology for editing DNA may allow scientists to render the insects resistant to the malaria parasite, the authors contend. Or it might be possible to engineer infertility into mosquito DNA, driving their populations into oblivion.
The new technology could potentially be used against a wide range of other species that are deemed a threat, like invasive predators,herbicide-resistant weeds and bat-killing fungi.
Although research on this procedure, known as Crispr, is in its infancy, the authors of the new papers say it warrants a public discussion right now. Using the approach to genetically engineer wild species could be a boon to humanity on some fronts, but it could also lead to a broad spectrum of unplanned ecological harm.
“Rather than just running off and immediately let this thing loose, we should start having conversations about this,” said George Church, a Harvard geneticist and a co-author of the new papers.
Crispr is a system of molecules that allows scientists to alter DNA with exquisite precision. Researchers design the molecules so they attach to DNA at a specific location. They then slice out the DNA there — whether an entire gene or a snippet of one — and then prompt a cell to replace it with a new segment designed by the scientists.
Although the technology is just a couple of years old, researchers are already using it to alter the DNA of cells and lab animals. Some experiments also hint that doctors may someday be able to use it to treat genetic disorders. They could replace faulty genes with working versions.
But recently, Dr. Church and other Crispr experts began to wonder if the technology had another possible use: as a weapon against our natural enemies.
Here’s how it might work against malaria. In a lab, scientists would insert a package of genes into mosquitoes. The package would include a gene for a protein that makes the mosquitoes resistant to malaria parasites. The package would also contain genes for Crispr molecules.
The scientists would release these engineered mosquitoes into the wild, where they would mate with their normal counterparts. Each parent would pass down its DNA to its offspring. The Crispr genes would produce their molecules inside the mosquito’s cells. They would then alter the cells from within.
The Crispr molecules would target a gene in the other parent’s DNA passed down to the offspring, which they would replace with the resistance gene. Now the new mosquitoes would carry two copies of the malaria-resistance genes instead of one.
When those mosquitoes mated, they would pass those engineered genes to their own offspring in turn. From one generation to the next, Crispr could spread the resistance genes with remarkable speed.
In theory, it might take just a few years for a whole population of mosquitoes to become resistant. The malaria parasite would be unable to survive in enough mosquitoes to last.
There’s precedent for this approach. Some genes have naturally evolved the ability to spread quickly by making extra copies of themselves. In 2003, Austin Burt of Imperial College London proposed mimicking this biology to fight insect-borne diseases. Since then, several research groups have started testing engineered mosquitoes.
Crispr may drastically accelerate this research. Scientists can quickly synthesize packages of genes, and Crispr ensures they make copies accurately and efficiently.
And unlike previous methods, Crispr can potentially work in just about any species of animal, plant or fungus.
In their eLife paper, Dr. Church and his colleagues explore how they might harness Crispr’s versatility. As farmers use herbicides to kill weeds, for example, some weeds inevitably evolve ways to resist the chemicals. It might be possible to use Crispr to rewrite the weed genes, returning them to their vulnerable state.
Dr. Church and his colleagues have started experiments in his lab with yeast, nematodes, and mosquitoes, to see if Crispr can indeed spread genes through a population.
“In a year or two, we could be doing field trials if there was a general consensus this was a good idea,” he said.
Jennifer A. Doudna, a Crispr expert at the University of California at Berkeley who was not involved in the papers, said she thought Dr. Church might be painting too rosy a picture. “Realistically, it’s not going to go as easily as they make it sound,” she said.
If scientists tried to engineer a species, she said, mutations might remove the stretch of DNA that the Crispr molecules used as their target. They would be unable to make extra copies of their gene.
Alison A. Snow, an ecologist at Ohio State University, also had doubts about how effective some of the methods could be. She said that the idea of making resistant weeds vulnerable “seems naïve to me.”
Dr. Snow said that more than 25 species of weeds are resistant to a single herbicide, known as glyphosate. Even if scientists could introduce Crispr genes into all those species, the weeds might evolve new ways to resist glyphosate. Or they might be replaced with other species that quickly evolve resistance.
But Dr. Doudna said that with enough time, scientists could make the technique work, at least in some species. “On longer time scales, the potential is very real,” she said.
In their Science paper, Dr. Church and his colleagues called for a conversation about how to judge the risks of the technique and what regulations should be put in place.
Dr. Snow agreed, saying, “We need to discuss this now, because it’s right on the horizon.”
Dr. Snow says she worries that engineering wildlife with Crispr could lead to ecological havoc. If scientists attacked an invasive species in a country where it’s causing trouble, the species might deliver the genes to its original habitat. Back home, the species may have an important role in its ecosystem.
Another danger arises from the ability of closely related species to interbreed. A harmful species might pass on Crispr genes to a harmless one, taking it down as well.
“It’s an emerging technology that’s extremely risky,” Dr. Snow said.
Dr. Church and his colleagues don’t deny that Crispr could pose risks to wildlife, but they have come up with ideas about how to defend against those risks. Scientists might be able to reverse a Crispr campaign by releasing a second package of genes. The second package would replace the original one, removing the harmful gene.
In their Science paper, Dr. Church and his colleagues argue that risks can be reduced by coming up with regulations for the technology. They sketch out a series of steps that should be taken before approving each Crispr campaign, like preparing reversal genes and monitoring wild populations for any unplanned spread of the genes.
While Dr. Church is hopeful about the uses of Crispr, he doesn’t see regulations as getting in the way of progress. “The thing that really slows things down,” he said, “is making a big mistake.”
Copyright 2014 The New York Times Company. Reprinted with permission.