Gutting It Out
Treating the human gut has always
been difficult — the tools used to
measure its health are imprecise and
usually highly invasive.
In a capsule endoscopy, for example,
doctors take snapshots with ingestible
cameras, but the devices don’t measure
chemical composition, a more revealing
barometer of gut health. Stool tests are
limited in what they can detect, and
surgical biopsies are disruptive.
New directions in research, however,
are revealing potentially more
accurate and less invasive ways to
determine gut health. These
methods could revolutionize
early detection of
gastrointestinal diseases
such as Crohn’s disease,
colon cancer and irritable
bowel syndrome.
Several teams are
working on biosensor
capsules that are
swallowed. Unlike camera
pills that merely take images,
the capsules carry genetically
engineered bacteria programmed to
detect biological signals in the gut, such
as inflammation. The data can be sent
to smartphones or other devices to relay
information in real time.
A paper published in May in Science
described a biosensor capsule, nearly
as long as one AAA battery, that
successfully detected gastric bleeding
in pigs. Lead author Mark Mimee, a
postdoc at MIT, says he plans to shrink
the capsule for an easier swallow. In
addition, Mimee is developing sensors to
measure a broad range of gut chemical
signals to detect the presence of diseasessuch as cancer and liver disease. Human
trials remain several years away.
Biosensors could also potentially be
used to heal the gut by neutralizing
toxins or balancing the microbiome, says
the paper’s senior author Timothy Lu, a
biological and electrical engineer at MIT.
Gastroenterologists know that gut
gases tell a tale of intestinal health,
but they also are hard to measure, and
typically require invasive methods. In
2018, a team of researchers in Australia
organized the first human trials of an
ingestible sensor that measures
gas production from inside
the intestines. In one study,
for example, published in
September in Alimentary
Pharmacology and
Therapeutics, the capsule
accurately measured
hydrogen production
in real time during food
fermentation in the guts
of 12 people. A larger
human trial is planned.
Stephanie Hansel, a
gastroenterologist at Mayo Clinic
in Rochester, Minnesota, likes what
she sees in the burgeoning field. She
regularly treats people with Crohn’s,
a debilitating disease that causes
inflammation in the digestive tract.
Testing for it involves both a capsule
endoscopy and a colonoscopy, in
which a camera on a flexible tube is
passed through the rectum and into
the intestine.
“If a less-invasive test could offer the
same or better information, patients
and [medical] providers would be
thrilled,” says Hansel.January/February 2019^ DISCOVER^61
TOP: LILLIE PAQUETTE/MIT. BOTTOM: RMIT UNIVERSITY/PETER CLARKE
of the paper. They also ine-
tuned the cell transfer process to
minimize damage to the eggs.
Because clones are identical,
they are useful as animal models,
eliminating the genetic variation
that can skew results between a
test group and a control group.
Monkey clones could be used for
testing potential treatments for
human diseases, from cancer to
Alzheimer’s. Researchers could
also genetically edit cells of
cloned monkeys to model disease
progression, says Poo.As for creating human clones,
Poo says the research shows
it can be done, but he and his
team have no interest. “Besides
many technical dificulties that
remain to be overcome, we see
no justiiable reason to pursue
human cloning,” says Poo, “nor
would the societies around the
world permit such an attempt.”
While human cells may be
cloned experimentally, for
example to research tissue
regeneration, the cloning of an
entire human is illegal in more
than 70 countries, according
to the Center for Genetics and
Society. U.S. law does not ban it,
but over a dozen states do.
As for Zhong Zhong and Hua
Hua, closing in on their irst
birthdays, they are healthy and
living with other lab monkeys
their age. “We have not seen any
behavioral abnormality,” says Poo.Rather than use
adult cells in the
DNA transfer,
they used fetal
cells, which
react better to
chemical stimuli
for embryo
development.
Biosensor capsules
could detect bleeding...... or even heal
the gut.