Malaria, carried by Anopheles mosquitoes, infects up to 500 million people each year
and kills 1 million, most of them children in sub-Saharan Africa. Dengue fever, a
viral disease transmitted by Aedes mosquitoes, is now endemic in more than 100 countries
and strikes an estimated 50 million people per year. Major international efforts to
control, prevent, or eradicate these diseases are in place, but traditional methods
such as vaccines and insecticides have met with limited success. Now scientists are
exploring the use of so-called selfish DNA to bioengineer mosquitoes that will take
over vector populations, eventually suppressing the diseases altogether.
Selfish DNA is defined as a segment of the genome with no apparent function other
than to ensure its own replication. Such elements—which include transposons and homing
endonuclease genes—are unique in that they can replicate themselves within a genome
and are not necessary for the reproductive success (or “fitness,” in evolutionary
terms) of the host organism. Selfish genes may be the ideal vehicles to deliver knockout
blows to vector-borne diseases.
“You can do this in two ways,” says Fred Gould, a professor of entomology at North
Carolina State University. “One is to have the selfish DNA element be neutral—that
is, it just inserts itself into the population and doesn’t actually lower the fitness
of the organism, but it carries with it . . . an antipathogen gene. So you wind up
with a population that looks the same and has the same fitness, but can’t transmit
the disease. The other approach is to actually have these selfish genes drive through
a [vector] population and decrease its fitness, so that their density goes down.”
Some of these methods have shown success in the laboratory, but they are all still
many years away from field deployment. Hoping to accelerate that process, Gould and
2 colleagues organized a conference held 5–7 December 2007 at the National Evolutionary
Synthesis Center (NESCent) in Durham, North Carolina. Part of NESCent’s mission is
to host “catalysis meetings”—intensive interactive sessions that bring together diverse
groups to spark new ideas and new collaborations in emerging fields.
“Selfish DNA and the Genetic Control of Vector-Borne Diseases” gathered approximately
30 researchers whose work ranges from basic to applied science, and whose focus ranges
from the molecular to the population level. “Having people with really specific expertise
in the basic sciences talking to people who are trying to apply these things gave
good insights,” says Gould. “There was a deep interdisciplinary interaction, and it
wasn’t just superficial or lip service.”
Participants discussed some of the enormous challenges that remain to be overcome
before any of these strategies will be ready for large-scale deployment. Among these
are perfecting the models and determining the optimal combination of gene drive systems
(i.e., methods of effectively introducing the desired gene into the population) and
effector genes (which encode the antipathogenic element) to maximize vector control
and minimize the development of resistance by the pathogens.
So when might we realistically expect to see mosquitoes modified with selfish DNA
deployed in the field? “We’ve been saying ten years for the last ten years,” says
Anthony James, a professor of microbiology and molecular genetics at the University
of California, Irvine, and principal investigator for a large, multicenter research
project into several of the applications being developed for genetic control of dengue
virus transmission. “It’s such an adjustable horizon because as we get closer to something
actually working, the size and scope of the challenges actually change.” The risk,
says Gould, is that a prematurely deployed system would fail to control the disease,
resulting in a rebound effect by resistant disease strains and perhaps permanently
closing the window on all genetic control strategies.
Another question is whether the public can—or indeed should—accept the idea of releasing
genetically modified organisms into the environment, let alone insects that are encouraged
to spread, invade, and supersede native populations. Says Gould, “I think it’s important
to stress that there are a million children a year dying of malaria, and preventing
that is a much bigger benefit than the risk of a single gene moving into another Anopheles
species—the risks of genes moving and disrupting habitats are small.”