ADVANCES
16 Scientific American, August 2020
ADES SPELEOLOGICAL GROUPIllustrations by Thomas FuchsNEUROBIOLOGY
Building
with Biology
A novel technique turns brain
cells into circuit components
New research could let scientists co-opt
biology’s basic building block—the cell—
to construct materials and structures with-
in organisms. A study, published in March
in Science and led by Stanford University
psychiatrist and bioengineer Karl Deis-
seroth, shows how to make specific cells
produce electricity-carrying (or blocking)
polymers on their surfaces. The work could
someday allow researchers to build large-
scale structures within the body or improve
brain interfaces for prosthetic limbs.
In the medium term, the technique may
be useful in bioelectric medicine, which in-
volves delivering therapeutic electrical
pulses. Researchers in this area have long
been interested in incorporating polymers
that conduct or inhibit electricity without
damaging surrounding tissues. Stimulating
specific cells—to intervene in a seizure, for
instance—is much more precise than
flooding the whole organism with drugs,
which can cause broad side effects. But
current bioelectric methods, such as those
using electrodes, still affect large numbers
of cells indiscriminately.
The new technique uses a virus to deliv-
er genes to desired cell types, instructing
them to produce an enzyme (Apex2) on
their surface. The enzyme sparks a chemical
reaction between precursor molecules and
hydrogen peroxide, infused in the space be-
tween cells; this reaction causes the precur-
sors to fuse into a polymer on the targeted
cells. “What’s new here is the intertwining
of various emerging fields in one applica-
tion,” says University of Florida biomedical
engineer Kevin Otto, who was not involved
in the research but co-authored an accom-
panying commentary in Science. “The use of
conductive polymers assembled [inside liv-ing tissue] through synthetic biology, to en-
able cell-specific interfacing, is very novel.”
The researchers tested the process and
tracked cell function in rodent brain cells,
artificially grown human brain models, and
living worms. They also injected the ingre-
dients into living mice’s brains to show they
were not toxic.
The commentary authors say this work
could pave the way for improved treat-
ments for depression or Parkinson’s dis-
ease by increasing the precision with which
neurons are stimulated. It could also pre-
cisely target cells that carry information to
the brain, potentially giving amputees sen-
sations in a prosthetic limb.
Deisseroth sees the research having even
broader uses. “We’ve been able to build new
structures inside cells we target genetically,
so we have only the cells of interest con-
struct something for us; that’s pretty exciting
and very, very general,” he says. “It’s a basic
science exploration of: What can we do?
What can we build within biological struc-
tures using their structural complexity?”
Obstacles remain, however. “There are
regulatory hurdles associated with gene
therapy in humans,” Otto says. The dura-
bility of changes, as well as viability of the
technique in higher species, also needs to
be demonstrated, he adds. — Simon MakinG E O L O G Y
Study in Red
Stalagmites rich in organic
matter record environments past
Not far from the famously multihued archi-
tecture of Bilbao in northern Spain, an
underground world boasts its own vibrant
display of color. The stalagmites and stalac-
tites of Goi koe txe Cave are not just the usu-
al white; many range from honey to deep
red. New research shows that these forma-
tions, known generally as speleothems, get
their red color from organic compounds
leached from soil and transported by water.
Scientists suggest, in an article published
online in April in Quaternary International,
that Goi koe txe Cave’s speleothems record
environmental conditions such as rainfall.
Virginia Martínez-Pillado, a paleoclima-
tologist at the Atapuerca Research Group
and the UCM-ISCIII Center for Human Evo-
lution and Behavior in Madrid,
hiked and crawled through Goi-
koe txe Cave to reach its sala
roja (“red chamber”). “All
around you is red,” Martínez-
Pillado says of the cavernous
room covered in stalagmites
and stalactites. She and her colleagues col-
lected four stalagmites rising from the cave
floor and brought them back to the labora-
tory. The team analyzed trace elements in
them and ruled out iron oxidation, which
often causes red coloration. (Think Mars.)
A reddish hue can also derive from
organic materials, so the scientists next
checked the stalagmites’ molecular makeup.
By measuring how the speleothems scat-
tered and absorbed light, the researchers
found that they contained humic and fulvic
acids. These complex molecules form from
decomposed plant debris, and the team
concluded they must have been picked up
by water and deposited on the stalagmites
as they grew over thousands of years.The stalagmites could therefore point
to past environmental conditions. Chang-
es in rainfall, for instance, would affect the
amount of organic matter flushed into the
cave, says Alison Blyth, a geochemist at
Curtin University in Perth, Australia, who
was not involved in the study: “If we mea-
sure the chemical signals preserved in
each layer, we can reconstruct how differ-
ent environmental parameters have
changed over time.” Martínez-Pillado and
her colleagues are now analyzing the sta-
lagmites to trace ancient variations in rain-
fall and vegetation above Goi koe txe Cave.
This technique can also be applied to other
caves with speleothems rich in organic mat-
ter, the researchers say. — Katherine KorneiSpain’s Goikoetxe Cave© 2020 Scientific American