GENES & CELLS
Gene may help elephants avoid cancer
LIF6 tells damaged cells to die before the disease can take hold
BODY & BRAIN
implanted in pigs
Feat brings scientists closer
to transplants on demand
BY AIMEE CUNNINGHAM
Elephants rarely succumb to cancer.
That’s surprising given how large the
animals grow and how long they can live,
which should provide more opportunities for cells to morph into cancer cells.
A newly described gene that was brought
back from the dead may take part in protecting the animals from the disease.
A deep dive into elephants’ evolutionary history revealed a defunct gene called
LIF6 that was somehow reawakened
roughly 59 million years ago, around the
time that elephants’ ancestors began to
develop larger body sizes. Found today
only in elephants, LIF6 is triggered by
another gene, TP53, to put cells out of
commission at the first sign of damage
before they turn cancerous, researchers
report in the Aug. 14 Cell Reports.
Previous work on elephants’ cancer-fighting powers has focused on TP53.
BY MARIA TEMMING
For the first time, researchers have created lungs in the lab and successfully
transplanted them into pigs.
The bioengineered lungs, described in
the Aug. 1 Science Translational Medicine,
developed blood vessels, and the pigs
lived for several weeks after surgery.
That’s a significant improvement from
previous efforts: Lab-grown lungs
implanted in rodents failed within hours.
If the procedure can be adapted
for humans, with lungs grown from a
patient’s own cells, that could reduce
the risk of organ rejection and slash wait
times for transplants.
Immunologist Joan Nichols of the
That gene encodes a protein that detects
DNA damage and signals for a cell to
repair itself or self-destruct, which helps
stop damaged cells from becoming can-
cerous. In 2015, researchers found that
elephants have 20 copies of TP53; other
mammals have one (SN: 11/14/15, p. 5).
“What’s really fascinating to me about
the elephant is that it’s not one mecha-University of Texas Medical Branch at
Galveston and colleagues built lungs for
four pigs by first using sugar and detergent to strip cells from lungs of donor
pigs. That left sterilized, lung-shaped
scaffolds made of intercellular proteins.
(In humans, researchers envision using
donated organs or 3-D–printed scaffolding.) The team then repopulated each
scaffold with blood vessel and lung cells
from the pig destined to receive the organ.
Each lung grew for 30 days inside a
bioreactor tank pumped full of nutrients that helped cells stick to the
scaffold and multiply in the right spots.
The team then replaced the left lung of
each pig with the bioengineered version.
The pigs’ post-op recovery was “pretty
amazing,” says Xi “Charlie” Ren, a biomedical engineer at Carnegie Mellon
University in Pittsburgh. None of the
pigs was given immunosuppressant
drugs, and none of the transplants was
rejected. One pig that Nichols’ team let
live for two months after surgery had
Learning how elephants resist cancer could
lead to improved treatments for humans.
Pigs given lab-grown lungs like this one
showed no signs of rejection after transplant.
nism” that underpins cancer resistance,
says Lisa Abegglen, a cell biologist at the
University of Utah School of Medicine in
Salt Lake City who was part of the 2015
The 2015 study also estimated that just
4.8 percent of elephants die of cancer. For
humans, that number ranges from 11 to
25 percent. Understanding how elephants
resist cancer could provide insights into
treating the disease in people.
In the new experiments, Vincent
Lynch, an evolutionary biologist at the
University of Chicago, and colleagues
chemically damaged the DNA of elephant
connective tissue cells in a dish. LIF6 was
eight times as active in damaged cells
as in undamaged cells. When the team
blocked TP53 from making its protein,
nearly all of LIF6’s activity was wiped out.
More work is needed to figure out
how TP53 and LIF6 potentially help
elephants fight cancer, Abegglen says.
But the animals probably “wouldn’t be
so large and long-lived if these changes
in genes that are unique to the elephant
hadn’t occurred.” s
no breathing problems, and its transplanted lung was colonized by bacteria
that inhabit normal pig lungs.
But the lungs aren’t yet ready for
prime time, says Laura Niklason, a biomedical engineer at Yale University.
While the lungs linked up with the pigs’
circulatory systems, the organs weren’t
connected with the pulmonary artery,
which carries low-oxygen blood for the
lungs to replenish with oxygen. That
left the pigs to rely on their natural right
lungs for air. s