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Making a FRIENDLIER Mosquito
Bioengineered
insects could help defeat malaria ~ or they could turn out to be
Frankenbugs and wreak havoc on our ecosystem, writes Bhaskar Dutta
IN 1897, British scientist Ronald Ross discovered that malaria was
spread, or “vectored” by mosquitoes. He was also the first to propose
reducing or eliminating the world’s mosquito population as a way of
controlling the disease. But it wasn’t until the discovery of
insecticides, ferocious enough to take on the insects, that such an
idea became truly feasible.
Ever since then, the fight against mosquito-vectored diseases has been a
chemical combat. Scientists developed drugs that were very useful
against the diseases, and insecticides that were very useful against
the mosquitoes that transmitted these diseases. And for a time it
looked as though we were winning the fight.
Unfortunately, over the past 30 years the rules of our chemical battle
have changed. Mother Nature intervened and evolution occurred. The
insects are now resistant to the pesticides, and the diseases are now
resistant to the drugs. A number of these diseases are considered the
deadliest on earth.
To address these concerns, scientists have for the past 15 years been
trying to move beyond the chemical paradigm to a genetic one. The dream
has been to build a genetically modified insect, a transgenic mosquito
that is unable to transmit such diseases. The approach, if successful,
could provide entirely new ways of combating the transmission of
malaria, African sleeping sickness, Chagas diseases, and other
devastating insect-borne infections.
The successful creation of a mosquito modified to be unable to transmit
disease occurred in May 2002. Working in a laboratory with a version of
malaria that infects mice, geneticist Marcelo Jacobs-Lorena (then at
Case Western Reserve University and now at Johns Hopkins) found a way
to inhibit the disease’s transmission. In recent months, Jacobs-Lorena
and other scientists building on his work have taken the process
further. They feel that a transgenic mosquito that is immune to malaria
and able to live in the wild is at hand.
Researchers are seeking to apply genetic engineering to two different
approaches: population reduction and population replacement. In
population reduction, a gene is introduced that diminishes the
reproductive capability of an insect. For example, researchers at
Oxitec Ltd, a biotechnology company in Oxford, UK, are focusing on ways
to reduce the population of Aedes aegypti, the mosquito that transmits
dengue fever.
Oxitec researchers have developed a genetic control system called
Release of Insects with a Dominant Lethal. With this RIDL technique, a
gene is introduced into the insect that is fatal even if only a single
allele is present, a “dominant lethal”.
During breeding, the “factory stock” of these insects could be protected
from the effect of the dominant lethal by supplying an antidote in
their food that would not be available in the environment. To be
effective, however, the dominant lethal must not kill the released
adults immediately, since they must live long enough to mate with the
wild population. All progeny of such mating, however, would inherit one
copy of the lethal gene and so die.
Population replacement is a more complex approach. This calls for
changing the genetic make-up of insects so they are either incapable of
being infected by a parasite or incapable of passing along the
parasite. Anthony James, professor of molecular biology and
biochemistry at the University of California, Irvine, is one researcher
working on this approach. James and his colleagues have been working on
creating mosquitoes that produce a modified mouse monoclonal antibody
that binds to the circumsporozoite protein, the predominant surface
antigen of the parasite stage that infects the mosquito’s salivary
glands.
Studies with genes targeting human malaria are underway, but James
suspects that while creating insects refractory to certain human
pathogens will happen soon, developing a system where this trait can be
spread safely and efficiently throughout a wild population is seven to
10 years down the road.
In yet another approach, scientists at the University of
California-Davis have proposed controlling malaria by releasing
genetically engineered mosquitoes into the wild to resist malaria. If
the resistant mosquitoes breed and spread their genes through the
population, malaria transmission should be shut down.
To put genes into an insect, these scientists use a mobile piece of DNA
called a transposon. Transposons are essentially a mobile piece of DNA
that snip themselves in or out of the genome under the right
circumstances. Scientists can add a new gene into a transposon and use
it to carry that DNA into the insect genome.
But according to postdoctoral researcher Matthew Hahn and Sergey
Nuzhdin, a professor of evolution and ecology at UC Davis, the plan
faces two problems. First, the malaria resistance genes available are
not very effective. Second, there’s no way to reliably push the genes
through the population.
So, Hahn and Nuzhdin propose an alternative strategy. They suggest
designing a transposon that gives an advantage to mosquitoes that
already carry genes to block malaria so that those genes spread through
the population by natural selection. The work is published in the 6
April issue of the journal Current Biology.
Although many scientists agree that using genetically modified insects
could have a dramatic effect on disease prevention, much work still
needs to be done and many concerns need to be addressed. For one, there
are no clear regulatory guidelines for the release of such insects.
Also, uncertainties abound when it comes to understanding the effect
these insects could have on other insects and perhaps entire ecosystems.
Finally, both microbes and insects evolve rapidly and in the past have
always managed to devise strategies to beat the weapons we have created
to attack them, such as insecticides and drugs. The fear is that
genetic engineering of insects and their symbionts could spur the
evolution of new, even more efficient vectors of disease.
“The chances that we're going to end up making a Frankenstein mosquito
are pretty remote,” says Frank Collins, a molecular parasitologist at
University of Notre Dame, but even he agrees that the possibility
exists.
One thing is certain: The bioengineered mosquito hangs precariously off
the cutting edge of genetic research. How we proceed is likely to set
standards for how we mould our world at a time when such mouldings are
both probable and perhaps practical.
(The author is an R&D biotechnologist with Dr Reddy’s Laboratories Ltd., Hyderabad.)
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