The EconomistJuly 22nd 2017 61For daily analysis and debate on science and
technology, visit
Economist.com/science1I
T IS life’s lottery, blessing some and curs-
ing others in equal number: the chance
of a sexually reproducing organism’s off-
spring inheriting a particular version of a
gene from a particular parent is 50%. Usual-
ly. But there are exceptions. Gene drives are
stretches ofDNAthat change those odds to
favour one parent’s version of a gene over
the other’s. That version will thus tend to
spread through a population. If the odds
are stacked sufficiently in its favour it can
do so fast and, within a few generations,
become the only version of the gene in
question that remains in circulation.
Researchers realised, soon after the dis-
covery of gene drives half a century ago,
that they might be forged into tools for
eradicating diseases and pests. For exam-
ple, a drive promulgating a genetic variant
that made mosquitoes unable to host the
parasite that causes malaria could be used
to help eliminate the disease. If the propa-
gating variant made female mosquitoes
sterile, it might provide a means to elimi-
nate the troublesome insects themselves.
Engineering gene drives to do human-
ity’s biddingin this way proved, however,
devilishly difficult. The idea therefore lan-
guished until 2015, when Valentino Gantz
and Ethan Bier of the University of Califor-
nia, San Diego, used CRISPR-Cas9, a recent-
ly discovered gene-editing tool, to make a
gene drive that could be inserted any-genes, and a piece ofRNA, a chemical akin
to DNAthat is made up of similar genetic
letters. This “guide”RNAwill stick only to a
section ofDNAwith a letter-sequence
complementary to its own. The enzyme is
bound to the guide RNA. The guide RNAis
bound to the DNA. Hence the enzyme re-
cognises the DNAit has to cut, and snips it
at the correct location. By inserting the
gene for Cas9 into an organism, together
with genetic material that instructs a cell to
produce the correct guide RNA, biologists
can therefore use CRISPR-Cas9 to sever a
genome at a specific point.
They can then insert at that point what-
ever payload of other genes they might
like—to modify mosquitoes so they cannot
transmit diseases, say—knowing that the
cell’sDNA-repair mechanismswill subse-
quently kick in to repair the incision
around the newly inserted genes.
Handily, the system works in any or-
ganism, not justthe bacteria in which Cas9
is found naturally. To use it as a gene drive,
all that is required is to include in the pay-
load the genes for the CRISPR-Cas9 system
itself, and to ensure that some copies get in-
serted into an organism’s germ cells—those
that develop into sperm or eggs. This will
mean that the gene drive is passed on to all
of that organism’s offspring.
CRISPR-Cas9 gene drives have, though,
a significant drawback. When the drive
cuts the genome but fails, forsome reason,
to insert itself into the incision, the cell in-
stead inserts new genetic letters to replace
those cut away by the enzyme before it re-
joins the severed DNAstrands. This pro-
cess often changes the letter sequence at
the site. That means the guide RNAcan no
longer recognise it. And that, in turn,
means the organism (and its progeny) are
now resistant to the drive.where in a target genome that they chose.
Those findings sparked concerns about
the effects gene-drive-carrying organisms
could have if they were ever to be released
into the world. For example, a gene drive
that somehow hopped from a target spe-
cies into the genomes of other animals
might wipe them out before anything
could be done about it. A study published
in PLOSGenetics, by Philipp Messer of Cor-
nell University and his colleagues sug-
gests, however, that those who would de-
ploy gene drives against scourges such as
malaria face a more immediate hurdle:
such drives simply may not work. Just as
insects and pathogens evolve resistance to
new pesticides and antibiotics, so gene
drives, too, may provoke resistance—and
may do so far faster than many suspected.Life finds a way
In nature, elements of the CRISPR-Cas9
system help bacteria to ward off viral infec-
tions. Some viruses replicate themselves
by inserting theirDNAinto the genomes of
their hosts. This hijacks a cell’s protein-
making machinery, causing itto turn out
components for new viruses. CRISPR-Cas9
selectively excises such foreign DNA, elim-
inating the invaders.
The excision mechanism consists of
two molecules: an enzyme (Cas9) derived
from a bacterium called Streptococcus pyo-Gene drivesResistance is inevitable
A promising tool for dealing with pests and pathogens runs into an old enemyScience and technology
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