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5-Animals: Transgenic mosquitoes unfit for duty

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TITLE:  Transgenic mosquitoes unfit for duty
        Malaria-resistant insects must be bred for success
SOURCE: Nature, UK, by Tom Clarke
DATE:   Feb 21, 2003

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Transgenic mosquitoes unfit for duty
Malaria-resistant insects must be bred for success

Mosquitoes genetically engineered to be immune to malaria - a hope for
ridding the world of the disease - won't get off the ground without
serious help, new research warns (1). Cloned from a single ancestral
insect and reared in the laboratory for years, transgenic mosquitoes are
so inbred that they can't cut it in the wild, find Andrea Crisanti and
colleagues at Imperial College in London. "They wouldn't stand a chance
out there," says Crisanti. Natural, malaria-carrying insects seem to beat
these genetic couch potatoes to mates and resources every time, his new
study confirms. The findings indicate that countless millions of
mosquitoes would need to be released in a particular place to give them a
hope of replacing the wild, parasite-riddled varieties. The scale and
cost of such an exercise could make transgenic mosquitoes a practical
impossibility. "Releases would have to be massive and probably
continuous," says mosquito ecologist Willem Takken at Wageningen
University in the Netherlands.

Stop and go

The GM strategy involves engineering lab mosquitoes to contain a gene
that stops the malaria parasite from completing its life cycle in their
guts and salivary glands. The malaria-proof insects would then be set free.

To help the gene spread during mating, another gene - a transposon - is
inserted alongside. Researchers hoped that this would drive the anti-
malaria gene through the wild mosquito population. In theory, after
several generations, all wild mosquitoes would have inherited the gene.
With no insect to carry it, the disease that kills more than one million
people a year - most of them children - would be eradicated for good. But
in practice, a supplementary gene and its driver seem to act like a
molecular ball and chain. "Even natural mutant mosquitoes disappear in
the field," Takken points out. Moreover, wild mosquitoes' genetic
diversity already gives them the evolutionary edge over seriously inbred
lab-reared mosquitoes.

Glow up

To study how trangenic mosquitoes might fare, Crisanti's team, creators
of the first malaria-proof mosquito (2) , created four different strains
of mosquito containing genes coding for green or red glowing proteins (to
represent anti-malaria genes) and transposons. Wild mosquitoes swamped
these insects. After only four generations - equivalent to just one
summer in many parts of Africa - none of the inserted genes could be
detected. "None of this looks particularly encouraging," laments Peter
Billingsley, who works on the mosquito's lifecycle at the University of
Aberdeen, UK. But it is possible, he concedes, that genes for producing
glowing pigment are more costly to mosquitoes than anti-malaria genes
would be. One solution might be to mate transgenic mosquitoes with wild
ones and select those that retain the malaria-resistance genes in the
lab, before releasing the insects into the wild. This might make the
manipulated insects tough enough to dominate their wild cousins, suggests

1) Catteruccia, F., Godfray, C. J. & Crisanti, A. Impact of genetic
manipulation on the fitness of Anopheles stephensi mosquitoes. Science,
299, 1225 - 1227, (2003).
2) Catteruccia, F. et al. Stable germline transformation of the malaria
mosquito Anopheles stephensi. Nature, 405, 959 - 962, (2003).