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DRIVEN To Extinction
Mary G. Barry, MD
Louisville Medicine Editor
[email protected]
G
ene drives scare me. It is now
technically possible, in a con-
trolled laboratory setting, to re-
move whole mosquito species
from the planet.
The September 24 th issue of Nature Bio-
technology reported work from the team of
Dr. Andrea Crisanti, a molecular parasi-
tologist at Imperial College London, a top
public university that Prince Albert founded
for scientific research. His team has been
studying Anopheles gambiae mosquitoes
and the use of genetic interference in their
reproduction, with the aim of eradicating
malaria. Using the CRISPR-Cas9 technique
(the removal of one gene with the insertion
of another in its place), his team developed
a gene drive that caused the collapse of the
lab mosquitoes in only eight generations.
Per Wikipedia: “A gene drive works by
cutting a chromosome at a specific site that
does not encode the drive. This induces
the cell to repair the damage by copying
the drive sequence onto the damaged chro-
mosome. The cell then has two copies of
the drive sequence. This relies on the fact
that double strand breaks are most often
repaired by homologous recombination,
using a template, instead of end to end.”
A gene drive uses nested elements, a
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homing endonuclease or an RNA-guided
one such as Cas9: these cut out the gene
being removed. The second part of the
drive is the DNA repair template, which
fits exactly into the double-stranded spot
but carries the “kill shot” function. Its sides
are homologous to the surrounding genes.
Thus each organism, having been duped
into repairing its damaged chromosome
with a Trojan horse sequence, will get two
copies of the gene drive. The offspring will
inherit one ‘Kill’ gene and one wild gene.
This method depends on sexual repro-
duction, so it will not work with viruses and
bacteria. But with mosquitoes, once a Kill
gene-equipped parent mates with a non-kill
gene parent, it is only a matter of time before
the successive mating of many mosquitoes
produces the mating of two mosquitoes
carrying the Kill gene. This will produce
an infertile organism, and eventually, no
more mosquito eggs at all.
Dr. Crisanti’s team used 20 cc cages. He
said that did not allow for the naturalistic
behavior of mosquitoes flying around and
seeking mates. He estimated at least five
more years before he could conduct any
field tests on wild mosquito populations.
However, Professor Luke Alphey’s
original team from Oxford first produced
genetically engineered mosquitoes back in
2002. These are male-only insects who have
been reared from the 2002 originals (now in
the second generation of design), who mate
with wild females. Their offspring carry a
gene that produces a protein that females
cannot survive. The males survive it for a
limited time, during which they mate with
more females, but the gene does not persist
for more than 10 generations and is not
passable to any other species. Oxitec (now
part of an American company, Intrexon
Corporation) has conducted field trials in
association with Grand Cayman and claims
an 80-90 percent reduction of the number
of mosquito eggs produced. This number
has been disputed by government officials
in the Cayman office of mosquito control.
Florida, after Zika appeared there, was set to
be a test site as well, but as yet no neighbor-
hood would agree to serve as one. Formerly
the Food and Drug Administration dealt
with this technology in this country, but it
is now being overseen by the Environmental
Protection Agency.
However, a different sort of mosquito
has already been released in Florida. This
technology has been used in Australia to
combat Dengue fever. Males only (males do
not bite, remember) which have been infect-