Giving Malaria a Deadline
With a new genetic tool, scientists move a step closer to eradicating mosquitoes and the deadly diseases they carry.
- Malaria is among the world’s worst scourges. In 2016 the disease, which is caused by a parasite and transmitted by mosquitoes, infected 194 million people in Africa and caused 445,000 deaths.
But
biologists now have developed a way of manipulating mosquito genetics
that forces whole populations of the insect to self-destruct. The
technique has proved so successful in laboratory tests that its authors
envisage malaria could be eliminated from large regions of Africa within
two decades.
A team led by Andrea
Crisanti, a biologist at Imperial College, London, altered a gene that
disrupts the mosquito’s sexual development; the females become infertile
but the males remain able to spread the debilitating gene to an
ever-dwindling number of progeny. Dr. Crisanti found that laboratory
populations of mosquitoes can be driven to extinction within 11
generations, he and colleagues report in Monday’s issue of Nature Biotechnology. Wild populations could be made to crash in about four years, according to computer models.
The
technique involves equipping mosquitoes with a gene drive, a genetic
mechanism that forces a gene of choice into all of an organism’s
offspring. (Normally, sexual reproduction would pass the gene to only
half the progeny.) Genes carried by a gene drive therefore can spread
very rapidly through a population, which makes the technique both
powerful and potentially dangerous. No gene drive has yet been released
in the wild.
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Previous
efforts to reduce mosquito fertility using gene drives have failed
because mutations arise in the stretches of DNA targeted by scientists, nullifying the engineered changes. These mutations are heavily favored by natural selection and permit the mosquitoes to escape the genetic trap.
Dr.
Crisanti and his colleagues instead found a way to target a stretch of
DNA that does not vary from one mosquito to another, presumably because
each DNA unit plays so vital a role that any mutations would kill the
organism. This invariant DNA sequence occurs in a gene called doublesex,
which determines sexual development in the mosquito species Anopheles
gambiae, one of the major carriers of the malaria parasite in Africa.
Dr.
Crisanti’s team disrupted the doublesex gene in a way that affects only
females. These females develop ambiguous sexual features: they cannot
bite because they have male-type mouthparts, and they are infertile. But
the males are unaffected and continue spreading the disruptive gene
until no more eggs are laid.
In the
lab, when males with the doublesex gene drive were placed in cages of
wild mosquitoes, the populations were driven to extinction in as few as
seven to 11 generations. No mutations could be found in the targeted
sequence of DNA.
“We are not saying this is 100 percent resistance-proof,” Dr. Crisanti said. “But it looks very promising.”
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Kevin
Esvelt, who studies the evolution of gene drives at Massachusetts
Institute of Technology, indicated that the biological aspects of
mosquito control may now be close to solution. “With this achievement,
the major barriers to saving lives are arguably no longer mostly
technical, but social and diplomatic,” he said.
Launching
a gene drive into the wild is risky. Once released, it can’t be
recalled or easily disabled should anything go awry. In 2016, the
National Academy of Sciences called for extensive tests and public consultation before any gene drive is released.
The
theory of how gene drives could be used to control pest populations was
laid out in 2003, in an article by Austin Burt, a biologist at Imperial
College, London, and a co-author on the new paper. He hopes that a
small-scale field trial can be started in Africa in five years.
Implementing
such a program would entail releasing just a few hundred drive-carrying
mosquitoes in each village. “We wouldn’t have to hit every village,
maybe as few as one percent,” Dr. Burt said. Complete eradication isn’t
necessary; the malaria parasite can’t maintain its populations once the
number of mosquitoes falls below a certain number.
“If
there are no unexpected technical or regulatory delays,” Dr. Burt said,
“it’s possible to envisage that gene-drive mosquitoes, in combination
with other approaches, could have eliminated malaria in significant
parts of Africa in 15 years.”
Achieving such a goal likely will require a continentwide agreement,
since a gene drive, once released, probably couldn’t be confined to a
single country, and biologists want to avoid any unintended
consequences. All insects analyzed so far rely on the doublesex gene to
direct their sexual development. It could be disastrous if an altered
doublesex gene drive somehow jumped from mosquitoes to another insect
species, such as bees.
“That’s not
possible,” Dr. Crisanti said. He noted that every insect species has its
own version of both the doublesex gene and the gene’s highly conserved
region, so a gene drive aimed at one species wouldn’t work in any other.
For that same reason, the technique potentially could be aimed at a
wide range of noxious insects, each targeted individually.
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“These sequences might be an Achilles heel present in many insect pests,” Dr. Crisanti’s team writes in their paper.
Dr.
Esvelt acknowledged that the new gene drive could possibly spread to
other insects but said that, if it did, the most likely host would be
other Anopheles mosquito species. “The known harm of malaria greatly
outweighs every possible ecological side-effect that has been posited to
date, even if all of them occurred at once,” he said.
From https://nyti.ms/2Q0gdna
From https://nyti.ms/2Q0gdna
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