Posted on 1-6-2002

Gene-Altered Mosquito Latest Trojan Horse
By Rick Weiss, Washington Post Staff Writer, Thursday, May 23, 2002; Page A03

Scientists in Cleveland for the first time have created genetically
engineered mosquitoes that have a reduced capacity to transmit malaria. The
feat points to the possibility of disrupting the scourge by releasing
gene-altered insects in Asia and Africa, where the disease kills an
estimated 2 million people every year, most of them children younger than
5. But that prospect has alarmed some scientists and others who fear that
such a program could trigger ecological disruption and ultimately increase,
rather than decrease, the global burden of disease.

Experts said the advance has also brought renewed attention to the fact
that the United States has yet to promulgate regulations limiting the
environmental release of genetically engineered insects capable of
transmitting human or animal diseases. The new work, published in today's
issue of the journal Nature, is the culmination of 15 years of efforts by
several competing teams trying to gain control over the genetic machinery
of the mosquito. Although scientists had previously managed to insert
various genes into the notoriously irritating insects, none until now had
succeeded in making a mosquito that blocks the development of the malarial
parasite inside the insect's body.

That parasite, a single-celled creature called Plasmodium, must pass
through a mosquito's gut and then be reinjected via mosquito saliva into
humans or other animals to complete its life cycle. Control of the disease
has been difficult because plasmodium has developed resistance to
medicines, mosquitoes have become resistant to insecticides, and efforts to
develop an effective vaccine have so far failed. Taking a novel tack,
Marcelo Jacobs-Lorena of Case Western Reserve University and his colleagues
identified a small protein that binds tightly to a mosquito's gut lining.
The team then engineered mosquitoes with a gene that allows the insects to
produce that protein after ingestion of a blood meal.

In experiments, most plasmodium cells failed to pass through the
mosquitoes' gut lining and could not travel to the insects' salivary
glands. When the team allowed the mosquitoes to feed on malaria-infected
animals and then later bite uninfected ones, disease transmission was about
80 percent less likely than with normal mosquitoes. Jacobs-Lorena suggested
that scientists could knock down wild populations of mosquitoes with
insecticides and then repopulate the area with laboratory-reared
gene-altered ones. But he acknowledged that five to 10 years of work might
be needed first.

Additional genes that block other aspects of plasmodium's life cycle in
mosquitoes ought to be added, he said, to reduce transmission even more.
Moreover, he said, the work so far has been done only with a variety of
plasmodium that infects rodents, not people. And the team has yet to make
engineered mosquitoes of the species that spreads human malaria in Africa,
where most cases occur. The mosquito species used in the experiment spreads
malaria in India.

In addition to technical challenges, Jacobs-Lorena added, funding is
sparse. "It's a poor country's disease. If we had a way to prevent heart
attacks I'm sure there'd be a line of company executives outside my office
ready to write checks." But others expressed relief that the work might
progress slowly, saying recent experiences with gene-altered crops -- many
of which spread their genes through the environment more widely than had
been anticipated -- teach that extreme caution is warranted. "We've had
unexpected results in virtually every area of genetically engineered
organisms," said Andrew Kimbrell, executive director of the International
Center for Technology Assessment, which has filed petitions with the
federal government seeking to block the release of engineered insects until
regulations are drawn.

Andrew Spielman, a professor of tropical public health at Harvard
University, echoed those concerns, saying it would be ecologically unwise
and probably medically useless to release engineered mosquitoes in malarial
areas. "The lure of this kind of quick fix is so great that people tend to
be very sloppy in their thinking," Spielman said.