- The Observer
28 25.08.19 News
Mutant sheep bred
in lab to fi ght lethal
child brain disease
Scientists create fl ock
to mimic gene that
causes Batten disorderScientists have created a flock of
sheep that carry the gene for a lethal
inherited brain disorder in humans.
The condition, Batten disease , usu-
ally starts in childhood and is invari-
ably fatal, often within a few years of
diagnosis.
The project, which is designed
to test treatments for the disease,
is based at Edinburgh University’s
Roslin Institute, where cloning tech-
niques were used to create Dolly
the sheep in 1996. The scientists
acknowledge that the approach could
be controversial as it involves creat-
ing animals programmed to die, but
stress that their aim is to alleviate
human suffering.
“We have deliberately re-cre-
ated the condition in a large mam-
mal because sheep have a brain of a
similar size and complexity to th at
of a child,” said Tom Wishart , pro-
ject leader. “That means treatments
we test on them are much more likely
to be relevant to humans than those
tested only on cell cultures or mice
and rats.”
In the UK, Batten disease affects
between 100 and 150 children and
young adults. It is inherited from two
symptomless parents who each carry
a rare recessive gene mutation. That
mutation interferes with the opera-
tion of lysosomes , which act as the
waste disposal systems for cells.
Children who carry two copies of
the faulty gene begin to suffer loss of
vision, impaired cognition and mobil-
ity problems. Seizures and early death
follow. “It is devastating for families,”
Wishart said.
There are several types of Batten
disease, he added. “One of the more
rapid types is CLN1 , and that’s what
we have recreated in our sheep.”
The Roslin scientists used the
gene-editing technique Crispr-
Cas9 to create the faulty CLN1 genein the sheep. “We collected sheep
embryos from the abattoir,” Wishart
said. “Then we fertilised them and
added Crispr reagents to alter their
genetic structure before implanting
the embryos into a surrogate sheep’s
uterus.”
Three sheep were born that each
possessed two copies of the CLN1
gene with the same mutation found
in affected humans. They began to
show many symptoms of Batten dis-
ease, including changes in behav-
iour and brain size. “The progress of
the disease in sheep closely resem-
bled its development in children,” said
Wishart.
Other sheep were engineered to
carry only a single copy of the gene.
“These are symptomless carriers, like
the parents of Batten disease chil-
dren,” said Wishart. “From these we
can breed sheep that have two faulty
copies of the CLN1 gene. These will
go on to develop a disease like thoseRobin McKie
Science Editorchildren, and will be the ones to test
our therapies.”
Researchers are working on several
treatments , including gene therapy
in which healthy genes are delivered
by viruses to replace mutated ver-
sions. Many of these techniques are
being developed using cell culture
and research on mice and rats.
“These studies are crucial in mak-
ing basic discoveries,” said Wishart.
“But if we do not use these few larger
animals in refi ning those discoveries,
all that early work could be wasted.
“It is a terrible necessity – to repro-
duce such a condition. However, we
are talking about using maybe only
10 or so animals for this research with
the ultimate aim of finding treat-
ments that could add years to the lives
of young patients.
“Unlike humans, we can study
sheep before their outward symp-
toms develop to gain new under-
standing of how the disease unfolds. ”Dolly the sheep in 1997,
the year after she was
cloned by the Roslin
Institute in Edinburgh.Free Nazanin
or I fear she
will take her
life, pleads
husband
The husband of Nazanin Zaghari-
Ratcliffe , the British-Iranian woman
detained in Iran, fears she may try to
take her own life if she is not given her
freedom soon.
Richard Ratcliffe told the Observer
he was afraid the harsh new jail con-
ditions imposed last week could
lead to a deterioration in her men-
tal health and might trigger a sui-
cide attempt.
She is no longer permitted
to call him in the UK andDonna Ferguson has been told she can only see their
fi ve-year-old daughter Gabriella once
a month. Previously she had been
allowed to see her twice a week.
“The next escalation I would worry
about is a more severe hunger strike
or a suicide attempt. I know she’s
despairing and that’s what she’s been
saying would happen next,” he said.
Nazanin has been having suicidal
thoughts since her second hunger
strike failed to secure her release in
February, he added. “She has regu-
larly been talking about how she can’t
go on. In my phone calls, I would try
to give her reassurance that there arereasons to be hopeful. T he worry is if
she’s stopped from being given rea-
sons to hope, it will affect her morale
and what she then decides to do.”
Ratcliffe said he thought Nazanin
would fi nd the separation from her
daughter particularly hard. In the
past, he has been able to persuade
her to promise not to attempt suicide.
But his wife’s mental health suffered
when she was handcuffed to a bed
and held in solitary confi nement in a
mental health ward for six days, and
then returned to prison. “After that,
she told me she wasn’t sure she’d be
able to keep her promise to me.”Last week, Ratcliffe revealed he had
not been offered a meeting with either
the prime minister Boris Johnson or
the foreign secretary Dominic Raab
since they took offi ce. Raab has sub-
sequently invited Ratcliffe to meet
him in early September. The Foreign
Offi ce is very cagey about its strategy,
Ratcliffe said, and has a tendency to
wait for things to calm down before
deciding what to do. “ There just isn’t
time to wait, for us.”The Samaritans can be contacted in the
UK on 116 123. International helplines
can be found at befrienders.orgkke her
aads
nnnd
take her own life
freedom soon.
Richard Ratcliii
he was afraid thhh
ditions imposss
lead to a deterrr
tal health anddd
cide attemmpp
She is
to call