SCIENCE sciencemag.org 19 AUGUST 2016 • VOL 353 ISSUE 6301 741
In the first experiment, Laura McCabe’s lab seemed to hit a home run. The physiologist and her team at Michigan State University (MSU) in East Lan- sing were testing how a certain drug affects bone density, and they found that treated lab mice lost bone com- pared with controls. “I was thinking, ‘Hey, great! Let’s repeat it one more
time to be certain,’” McCabe recalls.
They ordered a seemingly identical batch
of mice—same strain, same vendor—and
kept them under the same conditions: same
type of cage, same bedding, same room.
This time, however, treated mice gained
bone density. “Maybe one was a fluke,”
McCabe thought. They did a third run—and
saw no effect at all. She was baffled.
She knew that signals from the gut can
affect how bone forms and gets reabsorbed,
so her team took fecal samples from control
mice in each of the three experiments and
analyzed their gut microbes. They found
something unexpected: Each group had a
different microbial makeup to begin with.
McCabe has no idea where the mice acquired their distinct gut bacteria—from the
containers that ferried them from the vendor? From a technician’s clothing? But how
the drug affected her subjects clearly depended on what already lived inside them.
It’s easy to see how such effects could
make it difficult to replicate experiments, a
concern that has roiled fields from psycho-
logy to cancer. A few years ago, two pharma-
ceutical companies reported that they
could not replicate the vast majority of aca-
demic findings in preclinical experiments
(Science, 26 June 2015, p. 1411). Pressure to
publish and a bias against negative results
account for some replication problems.
But other failures to replicate likely have
“practical explanations: different animal
strains, different lab environments or subtle
changes in protocol,” as Francis Collins and
Lawrence Tabak, director and principal
deputy director, respectively, of the U.S. Na-
tional Institutes of Health (NIH) in Bethesda,
Maryland, wrote in Nature in 2014. In other
words, sometimes a study doesn’t hold up be-
cause the replicator is unknowingly perform-
ing a slightly different experiment.
Increasingly, experimenters are question-
ing the potential research impact of the
microbiome—a term often used to refer to
commensal gut bacteria, but which also in-
cludes resident viruses, fungi, protozoa, and
single-celled archaea species. Rarely even dis-
cussed a few years ago, this potential source
of variability attracts growing attention at
lab animal care conferences, says MSU’s at-
tending veterinarian, Claire Hankenson. “We
didn’t know to look for it before,” she says.
The zoo of bacteria and viruses each lab animal
harbors may confound experiments
By Kelly Servick
OF MICE AND MICROBES