New Scientist - 15.02.2020

12 | New Scientist | 15 February 2020

Gene editing

A SPECIES of fish known for its

unusual ability to climb trees has

now been spotted hopping across

water. The team that made the find

says it seems to be a previously

unknown form of fish locomotion.

“We already considered this fish

to be very special since it was so

adept at climbing trees and rock

faces,” says Parvez Alam at the

University of Edinburgh, UK. “But

the hopping was even more bizarre

a finding than we had expected.”

Mudskippers are amphibious

fish that can breathe out of water

and use their pectoral fins to move

about on land. They could be living

examples of how organisms may

have transitioned from water to

land 350 to 400 million years ago.

Alam and his colleagues

originally went to the Indonesian

island of Java to study how

the dusky-gilled mudskipper

(Periophthalmus variabilis)

climbs inclined surfaces such

as trees, rocks and mangrove

roots. But when the researchers

approached the mudskippers,

the fish leapt from trees or rocks

onto the neighbouring water and

hopped across the surface.

An analysis of footage revealed

that the hopping was made possible

by short, rapid bursts of tail-beating.

These movements accelerate each

fish across the water’s surface and

propel it into the air. The fish briefly

remains airborne before landing

back onto the water to repeat

the process for a subsequent

hop (Zoology, doi.org/dk8s).

“This observation highlights

how well adapted mudskippers

are to life on land, where returning

to the water appears to be actively

avoided, even when danger is

imminent,” says Alice Gibb at

Northern Arizona University. ❚

IMMUNE cells altered with CRISPR

gene-editing technology to fight

cancer have been injected into

people without any serious side

effects, the first US trial of its kind.

It is also the first CRISPR cancer

trial in the world to publish its

findings, and the positive results

will pave the way for more trials.

“It’s an important milestone,”

says Waseem Qasim at the UCL

Great Ormond Street Institute

of Child Health in the UK, who is

carrying out a similar trial there.

The US test was only to assess

safety. The three participants

had advanced cancer that hadn’t

responded to other treatments,

and were given only one dose of

gene-edited cells. “Is it safe and

feasible?” says Edward Stadtmauer

at the University of Pennsylvania,

one of the researchers. “I think

that’s what we demonstrated.”

At the moment, blood cancers

can be treated by removing

immune cells from individuals,

adding a gene that makes them

target cancer cells and putting

them back in the body.

But this treatment doesn’t work

for everyone, says Stadtmauer.

And in some, it works at first

but they later relapse.

The hope is that using CRISPR

technology to delete genes that

weaken the response of immune

cells to cancer, in addition to

adding the tumour-targeting

gene, will make this approach

even more effective. For instance,

immune cells have a safety switch,

called PD-1, that other cells can

flip to say “don’t hurt me”. Many

cancers exploit this to avoid attack.

In the US trial, immune cells

were removed from three people

who had tumours with the same

protein on their surface. A virus

was used to add a gene to make the

immune cells target this protein.

Next, three genes, including

that for PD-1, were deleted using

CRISPR. After six weeks, the cells

were put back in the individuals,

where they survived for at least

9 months (Science, doi.org/dk8f).

There were two big safety

concerns. Firstly, CRISPR can cause

unintended changes to genomes

that could turn cells cancerous.

Deleting three genes means

cutting around each one in three

spots in the genome, for instance,

and the wrong ends can be joined

up. This did happen in some cells,

but there was no sign of any of

them turning cancerous.

The second worry was that

lingering traces of the protein

used for CRISPR gene editing

might trigger an immune

reaction, since it is of bacterial

origin. There was no sign of this.

The trial won’t continue

because the gene-editing

technology used is already

outdated, says Carl June, also at

the University of Pennsylvania.

A new form of CRISPR called base

editing now exists that can be

used to inactivate genes without

cutting DNA, which should reduce

the cancer risk even further.

There are “limitless” other

ways to edit immune cells to

make them more effective, says

Stadtmauer. In particular, he

wants to create “off-the-shelf ”

cells that could be given to

anyone, rather than modifying

each person’s own cells. This

would speed up treatments

and reduce costs. ❚

“ Mudskippers appear to

actively avoid returning

to the water, even when

danger is imminent”

Zoology

Gene editing may one

day replace some forms

of cancer treatment

Michael Le Page

E R I C K I TAYA M A /G E T T Y I M AG E S

News

CRISPR shows promise in cancer

First trial of this form of gene editing for people with tumours passes safety test

Tree-climbing fish

can also hop across

water’s surface

James Urquhart