SCIENCE science.org 10 DECEMBER 2021 • VOL 374 ISSUE 6573 1307two of his funding agencies, the Department
of Defense (DOD) and the National Institutes
of Health (NIH). Harvard didn’t learn about
the deals until 2015, the government says.
In April 2018, according to prosecutors,
Lieber told DOD that “he had never been
asked to participate” in the foreign talents
program. Several months later, prosecu-
tors say Harvard told NIH that Lieber “has
represented that he is not and has never
been a participant” in a Chinese talents
program. The government says both asser-
tions were false.
Lieber has pleaded not guilty to all the
charges, and his lawyers declined to com-
ment. “We will do our talking in the court-
room,” says Marc Mukasey of Mukasey
Frenchman LLP, a New York City law firm.
So far, Lieber’s attorneys have been largely
unsuccessful in attacking the government’s
case. U.S. District Court Judge Rya Zobel,
who will preside, denied a request to sup-
press statements from Lieber’s 3-hour inter-
rogation after his arrest, ruling that he had
not been coerced. A different judge threw out
Lieber’s request to clarify what it means to
“participate” in a foreign talents program,
part of his assertion that federal disclosure
rules are ambiguous and confusing.
For Lieber to be found guilty of lying to
DOD and NIH, the prosecution must prove
he knew his statements were false and that
the information was germane to his grants
from those agencies. (In Hu’s case, U.S. Dis-
trict Judge Thomas Varlan found that Hu did
not intentionally mislead NASA, that univer-
sity officials had assured Hu that NASA rules
restricting work with China didn’t apply to
his research project, and that Hu had done
the work he promised to NASA.)
The tax and banking charges against
Lieber—which were added several months
after his arrest—are less open to interpreta-
tion. “You either check the box or you don’t”
on the relevant paperwork, said one lawyer
familiar with the case who requested ano-
nymity. The lawyer speculates that prosecu-
tors added the charges to induce Lieber to
make a plea deal. “You don’t always crimi-
nalize [those violations],” the attorney says,
“but it increases the pressure ... to plead
guilty to something.”
One common thread in the pending cases
is their staggering cost. Chen and Lieber
are the only two defendants still receiving a
salary from their universities. Several have
launched fundraising campaigns to cover
legal fees that could exceed $1 million, with
varying success. Just one defendant, Massa-
chusetts Institute of Technology engineer-
ing professor Gang Chen, has an employer
willing to pay for his defense. Harvard has
refused, saying Lieber violated his contract
by not fully disclosing his WUT ties. j
I
n some farmers’ ideal world, cows would
birth only females, sows would bear no
boars, and chicks would all grow up to
be hens. There would be no need to kill
millions of male animals, which don’t
produce eggs or milk.
Now, scientists are a step closer to this re-
ality. Researchers have harnessed the gene
editor CRISPR to produce litters of mice of
all one sex. That’s a potential boon to ag-
riculture and may offer a more immediate
advantage in research. “The paper shows
a state-of-the-art solution to producing
single-sex species” with “impressive re-
sults,” says Ehud Qimron, a CRISPR expert
at Tel Aviv University who was not involved
with the work.
The impact for lab animals may be huge.
“In the past 5 years around 25,000 papers
were published using mice in sex-specific re-
search studies,” says co-author James Turner,
a molecular geneticist at the Francis Crick
Institute. “If we could prevent the generation
of the unstudied sex, the number [saved]
would be in the hundreds of thousands.”
Other methods exist to skew the male/
female ratio of newborn animals. Scien-
tists can sort sperm by the weight of the
sex chromosome (the Y is lighter than the
X), or cause embryos of one sex to die be-
fore birth. In a study published 2 years ago,
researchers using CRISPR managed to pro-
duce altered mice in which four of five lit-
ters were all female.
In the current work, that efficiency jumps
to 100%, a welcome gain. The authors also
target a gene that is conserved in many ani-
mals, so the technique may prove useful for
more than just mice. “The approach seems
generalizable to other animal species,” in-
cluding birds and fish, says Michael Wiles, a
molecular geneticist at the Jackson Labora-
tory who was not involved with the study.
It could even help with the recovery of en-
dangered species, Wiles says, depending on
which sex was in short supply.
Many kinds of research studies require
animals of a particular sex. Scientists engi-
neering new lines of genetically modified
mice prefer males, which can father new lit-
ters every few days, whereas females require6 to 8 weeks to produce one. Studies of repro-
ductive tissues only need males or females,
as do certain hormone and cancer studies.
“Developing ways to have same-sex litters is
of utmost importance,” Qimron says.
In the new study, Turner and Crick mo-
lecular geneticist Charlotte Douglas and
Peter Ellis from the University of Kent be-
gan by identifying a molecu lar target that
would effectively eliminate embryos. It had
to be “expressed at a high enough level and
at the right time during development to
ensure 100% elimination,” Turner says. The
team picked a gene called Topoisomerase 1
(TOP1) , which is key for cell division; dis-
abling it should lead to the quick demise of
a very early embryo.
The team then separated the two parts
of CRISPR: the enzymatic complex that
physically disrupts a target gene, and
the “guide RNA” that recognizes the gene
and guides the complex to the right spot
in the genome. The researchers put the
guide RNA targeting TOP1 into the mother
mouse’s genome and attached the DNA
encoding CRISPR’s cutting complex to the
father’s Y chromosome. The enzyme and
guide RNA were reunited only when sperm
with the Y chromosome fertilized the fe-
male’s eggs, creating the X/Y combination
that defines a male.
When the developing male embryo was
only a few dozen cells, the effects of gene
editing kicked in, killing that embryo before
it got a chance to implant in the mother’s
womb. And indeed, no male pups were born,
the team reported last week in Nature Com-
munications. The reverse was true when
researchers attached the CRISPR complex
to the male’s X chromosome; in that case,
CRISPR kicked in when the male and fe-
male X chromosomes were united, and all
the female embryos failed to implant.
The modification also made things easier
on the mouse mothers. When targeted em-
bryos die before implantation, the mother
has fewer embryos to sustain, making it
more likely that the other embryos will
thrive. Perhaps that’s why the disappear-
ance of the undesirable embryos resulted
in larger than expected litters of the desired
sex. (The litters should have been half the
usual size, but they were just 30% to 40%Gene editing produces
single-sex litters in mice
CRISPR approach may curb culling of lab animals, chicks
GENETICSBy Elizabeth Pennisi