THENEWYORKER,JANUARY18, 2021 37
the San Diego researchers, along with
some colleagues from the University of
California, Irvine, announced that they
had created a gene drive in Anopheles
mosquitoes, which carry malaria.
If CRISPR confers the power to “re-
write the very molecules of life,” a syn-
thetic gene drive increases that power
exponentially. Suppose the researchers
in San Diego had released their yellow
fruit flies. Assuming that those flies had
found mates, swarming around some
campus dumpster, their offspring, too,
would have been yellow. And assuming
that those offspring survived and also
successfully mated, their progeny would,
in turn, have been yellow. The trait would
have continued to spread, ineluctably,
from the redwood forest to the Gulf
Stream waters, until yellow ruled.
And there’s nothing special about
color in fruit flies. Just about any gene
in any plant or animal can—in princi-
ple, at least—be programmed to load
the inheritance dice in its own favor.
This includes genes that have them-
selves been modified, or borrowed from
other species. It should be possible, for
example, to engineer a drive that would
spread a broken toxin gene among cane
toads. It may also be possible one day
to create a drive for corals that would
push a gene for heat tolerance, to help
them survive global warming.
In a world of synthetic gene drives,
the border between the human and the
natural, between the laboratory and the
wild, already deeply blurred, all but dis-
solves. In such a world, not only do
people determine the conditions under
which evolution is taking place, people
can—again, in principle—determine
the outcome.
T
he first mammal to be fitted out
with a CRISPR-assisted gene drive
will almost certainly be a mouse. Mice
are what’s known as a “model organism.”
They breed quickly, are easy to raise, and
their genome has been intensively studied.
Paul Thomas is a pioneer in mouse
research. His lab is in Adelaide, at the
South Australian Health and Medical
Research Institute, a sinuous building
covered in pointy metal plates. (Adelaide-
ans refer to the building as “the cheese
grater”; when I went to visit, I thought
it looked more like an ankylosaurus.) As
soon as the first paper on CRISPR as a
gene-editing tool was published, in 2012,
Thomas recognized it as a game changer.
“We jumped on it straightaway,” he told
me. Within a year, his lab had used CRISPR
to engineer a mouse afflicted with epilepsy.
When the first papers on synthetic
gene drives came out, Thomas once again
plunged in. “Being interested in CRISPR
and being interested in mouse genetics,
I couldn’t resist the opportunity to try to
develop the technology,” he said. Initially,
his goal was just to see if he could get
the technology to work: “We didn’t re-
ally have much funding—we were doing
it on the smell of an oily rag—and these
experiments, they’re quite expensive.”
While Thomas was still, in his words,
“just dabbling,” he was contacted by a
group that calls itself GBIRd. The acro-
nym, pronounced “gee-bird,” stands for
Genetic Biocontrol of Invasive Rodents,
and the group’s ethos might be described
as Dr. Moreau joins Friends of the Earth.
“Like you, we want to preserve our world
for generations to come,” GBIRd’s Web
site says. “There is hope.” The site fea-
tures a picture of an albatross chick gaz-
ing lovingly at its mother.
GBIRd wanted Thomas’s help design-
ing a very particular kind of mouse gene
drive—a so-called suppression drive, in-
tended to defeat natural selection en-
tirely. Its purpose is to spread a trait sodeleterious that it can wipe out a pop-
ulation. Researchers in Britain have al-
ready engineered a suppression drive for
Anopheles gambiae mosquitoes. Their goal
is to eventually release the modified mos-
quitoes in Africa.
Thomas told me that there were var-
ious ways to go about designing a self-sup-
pressing mouse, most having to do with
sex. He was particularly keen on the idea
of an X-shredder mouse. Mice, like other
mammals, have two sex-determining
chromosomes—XXs are female, XYs
male. Sperm carry a single chromosome,
either an X or a Y. An X-shredder mouse
is a mouse who has been gene-edited so
that all of his X-bearing sperm are de-
fective. “Half the sperm drop out of the
sperm pool, if you like,” Thomas explained.
“They can’t develop any more. That leaves
you with just Y-bearing sperm, so you get
all male progeny.” Put the shredding in-
structions on the Y chromosome and the
mouse’s offspring will, in turn, produce
only sons, and so on. With each genera-
tion, the sex imbalance will grow, until
there are no females left to reproduce.
Thomas said that work on a gene-
drive mouse was going more slowly than
he’d hoped. Still, he thought that by the
end of the decade someone would de-
velop one. It might be an X-shredder,
or it might use a design scheme that’s“This next piece is also allegro.”