The New Yorker - USA (2021-01-18)

(Antfer) #1

36 THENEWYORKER,JANUARY18, 2021


hundredfold. Using CRISPR, Cooper ed-
ited a second batch of embryos to de-
lete a section of the gene that codes for
bufotoxin hydrolase. The result was a
batch of less toxic toadlets.
After we’d talked for a while, Coo-
per offered to show me her toads. This
entailed penetrating deeper into the
A.C.D.P., through more air-lock doors
and layers of security. We all put scrubs
on over our clothes and booties over
our shoes. Cooper spritzed my tape re-
corder with some kind of cleaning fluid.
“Quarantine Area,” a sign said. “Heavy
Penalties Apply.” I decided it would be
better not to mention the Odin and
my own rather less secure gene-edit-
ing adventures.
Beyond the doors was a sort of anti-
septic barnyard, filled with animals in
variously sized enclosures. The smell was
a cross between a hospital and a petting
zoo. Near a bloc of mouse cages, the de-
toxed toadlets were hopping around a
plastic tank. There were a dozen of them,
about ten weeks old and each about three
inches long. “They’re very lively, as you
can see,” Cooper said. The tank had been
outfitted with everything a person could
imagine a toad would want: fake plants,
a tub of water, a sunlamp. I thought of
Toad Hall, “replete with every modern
convenience.” One of the toads stuck out
its tongue and nabbed a cricket. “They
will eat literally anything,” Tizard said.
“They’ll eat each other. If a big one en-
counters a small one, it’s lunch.” Let loose
in the Australian countryside, a knot of
detoxed toads presumably wouldn’t last
long. Some would become lunch, for ei-
ther freshies or lizards or death adders,
and the rest would be outbred by the
hundreds of millions of toxic toads al-
ready hopping across the landscape.
What Tizard had in mind for them
was a career in education. Research on
quolls suggests that the marsupials can
be trained to steer clear of cane toads.
Feed them toad legs laced with an
emetic, and they will associate toads
with nausea and learn to avoid them.
Detoxed toads, according to Tizard,
would make an even better training tool:
“If they’re eaten by a predator, the pred-
ator will get sick, but not die, and it will
go, ‘I’m never eating a toad again.’”
Before they could be used for teach-
ing quolls—or for any other purpose—
the detoxed toads would need a variety


of government permits. When I visited,
Cooper and Tizard hadn’t started in on
the paperwork, but they were already
contemplating other ways to tinker.
Cooper thought it might be possible to
fiddle with one of the genes that pro-
duce the gel coat on the toads’ eggs and
to do so in such a way that the eggs
couldn’t be fertilized.
“When she described the idea to me,
I was, like, ‘Brilliant!’ ” Tizard said. “If
we can take steps to knock down their
fecundity, that’s absolute gold.”
A few feet away from the detoxed
toads, Spot and Blondie were sitting in
their own tank, an even more elaborate
affair, with a picture of a tropical scene
propped in front for their enjoyment.
They were almost a year old and fully
grown, with thick rolls of flesh around
their midsections, like sumo wrestlers.
Spot was mostly brown, with one yel-
lowish hind leg; Blondie was more richly
variegated, with whitish hind legs and
light patches on his forelimbs and chest.
Cooper reached a gloved hand into the
tank and pulled out Blondie, whom she’d
described to me as “beautiful.” He im-
mediately peed on her. He appeared to
be smiling malevolently. He had, it
seemed to me, a face only a genetic en-
gineer could love.

A


ccording to the standard version of
genetics that kids learn in school,
inheritance is a roll of the dice. Let’s say
a person (or a toad) has received one ver-
sion of a gene from his mother—call it
A—and a rival version of this gene—
A1—from his father. Then any child of
his will have even odds of inheriting an
A or an A1, and so on. With each new
generation, A and A1 will be passed down
according to the laws of probability.
Like much else that’s taught in school,
this account is only partly true. There
are genes that play by the rules and there
are renegades that don’t. Outlaw genes
fix the game in their own favor and do
so in a variety of devious ways. Some in-
terfere with the replication of a rival gene;
others make extra copies of themselves
to increase their odds of being passed
down; and still others manipulate the
process of meiosis, by which eggs and
sperm are formed. Such rule-breaking
genes are said to “drive.” Even if they
confer no fitness advantage—indeed,
even if they impose a fitness cost—they’re

passed on more than half of the time.
Some particularly self-serving genes are
passed on more than ninety per cent of
the time. Driving genes have been dis-
covered lurking in a great many crea-
tures, including mosquitoes, flour bee-
tles, and lemmings, and it’s believed that
they could be found in a great many
more, if anyone took the trouble to look
for them. The most successful driving
genes are hard to detect, because they’ve
driven other variants to oblivion.
Since the nineteen-sixties, it’s been
a dream of biologists to exploit the power
of gene drives—to drive the drive, as it
were. Thanks to CRISPR, this dream has
now been realized, and then some. In
bacteria, which might be said to hold
the original patent on the technology,
CRISPR functions as an immune system.
Bacteria that possess a “CRISPR locus”
can incorporate snippets of DNA from
viruses into their own genomes. They
use these snippets, like mug shots, to
recognize potential assailants. Then they
dispatch CRISPR-associated, or Cas, en-
zymes, which work like tiny knives. The
enzymes slice the invaders’ DNA at crit-
ical locations, thus disabling them.
Genetic engineers have adapted the
CRISPR-Cas system to cut pretty much
any DNA sequence they wish. They’ve
also figured out how to induce a dam-
aged sequence to stitch into itself a thread
of foreign DNA it’s been supplied with.
(This is how my E. coli were fooled into
replacing an adenine with a cytosine.)
Since the CRISPR-Cas system is a bio-
logical construct, it, too, is encoded in
DNA. This turns out to be key to cre-
ating a gene drive. Insert the CRISPR-Cas
genes into an organism and the organ-
ism can be programmed to perform the
task of genetic reprogramming on itself.
In 2015, a group of scientists at Har-
vard announced that they’d used this
self-reflexive trick to create a synthetic
gene drive in yeast. (Starting with some
cream-colored yeast and some red yeast,
they produced colonies that, after a few
generations, were all red.) This was fol-
lowed three months later by an announce-
ment from researchers at the University
of California, San Diego, that they’d used
much the same trick to create a synthetic
gene drive in fruit flies. (Fruit flies are
normally brown; the drive, pushing a gene
for a kind of albinism, yielded offspring
that were yellow.) Seven months later,
Free download pdf