
Lab Mice Are Being Kept Too Cold, Apparently - mhb
http://pipeline.corante.com/archives/2013/12/18/lab_mice_are_being_kept_too_cold_apparently.php
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peterwwillis
A friend of mine at hopkins (several, actually) do lab experiments with mice.
Recently one experiment a co-worker was doing was continually failing even
though it had been proven to work in other cases. Several of the mice tested
would behave fine, but one or two were in terrible health and became highly
antagonistic. They couldn't figure out why the experiment was failing.

My friend took a look at their setup. During the day there was a machine that
was turned on next to the unhealthy mice. It vibrated and emanated a faint
noise. He told them to turn off the machine. In a week, the mice were back to
normal.

Nobody had thought about it, but mice are much more sensitive to sound and
vibration than humans and it was stressing them out so much they were going
crazy. There's probably lots of other things that can be overlooked (like
temperature), but it's hard for us to notice because we aren't mice.

~~~
herbig
"it was stressing them out so much they were going crazy"

An interesting theory, but one that they can't really say was the issue
without a controlled experiment.

~~~
stephenhuey
Construction Noise Decreases Reproductive Efficiency in Mice:
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2715925/](http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2715925/)

Noise in a Laboratory Animal Facility from the Human and Mouse Perspectives:
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2949429/](http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2949429/)

~~~
herbig
Right. The point being, if we're talking scientifically here, you can't just
say that the machine was the issue and be done with it.

What kind of machine was it? Was the machine emitting radiation? Was it
emitting light? What time of day was is turned off? What color was it? Could
the mice see if from their cage, or was it out of view?

~~~
peterwwillis
The science i've seen done in university labs does not follow the kind of
rigor you're talking about. Much of the time, you simply need to get "pretty
close" to best practices.

The biggest indicator that the machine was the _likely_ culprit (without
considering any of the factors you mention) was that the experiment had been
proven in the past to work, with a control group for comparison. Add to that
the other mice that were doing fine that were away from the machine, and that
the mice close to the machine got better when it was turned off. It's not
"scientific" per se, but it makes more sense than any other reason that anyone
could come up with for this scenario.

To deal with this in future projects, a researcher could take an approach that
treats everything as a set of systems, and examining every part of each system
for potential problems. But I doubt anyone's getting paid well enough to do
all that for every experiment. But it is reasonable that if you're doing an
experiment that depends on a bunch of other experimental results, you do your
due diligence and vet all the information and results.

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RyanMcGreal
I'm reminded of the study that found rats will choose heroin over food, over
and over again, until they die; and the follow-up study that compared rats
kept in isolation (matching the original study) with rats allowed to live more
naturally in communities and found that rats living in communities try the
heroin but then go back to eating food.

~~~
mathgladiator
For the curious, I think this is the study:

[http://en.wikipedia.org/wiki/Rat_Park](http://en.wikipedia.org/wiki/Rat_Park)

~~~
RyanMcGreal
Thank you. That's the study.

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mapt
The hazard here is not inside a fully parallel blinded trial with controls in
the same environment, but in comparison and replication of studies, as well as
sequential studies where the lab temperature changed. If quite minor, to human
senses, changes in temperature significantly affect tumor formation, then up
until now that's been a huge noise source in cross-study comparison, and
temperature should be at least recorded precisely over time for all future tox
studies.

~~~
tehwalrus
not necessarily so - the article mentions that the cold inhibits two specific
immune cell types; discovered drugs may only be effective in combating tumors
arising from these specific deficits, which aren't relevant in real scenarios,
i.e. a systematic error from cold in all studies.

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brianbreslin
When I was in middle school my science fair project involved the temperature
controls for experiments on electric fish. I ended up getting a byline in
science mag for the project, as it had thrown into question a lot of existing
studies that hadn't controlled for temperature.

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comicjk
Richard Feynman wrote about a very similar problem, that rat-maze experiments
rarely controlled for the rats' ability to hear differences in the floor. He
used it as an example of "Cargo Cult Science"
([http://neurotheory.columbia.edu/~ken/cargo_cult.html](http://neurotheory.columbia.edu/~ken/cargo_cult.html))
- if you aren't rigorous with your assumptions, you are not doing science, and
the truth is not going to come.

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loceng
Did anyone else assume that temperature would be something they'd realize they
need to control for? I would even suggest they should have a control group
with a fluctuating temperature, as humans go through temperature fluctuations
- and perhaps even seasonally alter temperatures.

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saalweachter
They _did_ control for temperature. They mandated mice be kept between 20C and
26C, which is between 68F and 78F. Mice live in houses, that's the temperature
of houses.

31C is 88F. It's not _absurdly_ hot, but it's hot enough that it's
surprisingly hot to me.

~~~
mikeash
Control _for_ temperature doesn't mean "control the temperature". It means to
set up the experiments such that you can detect the effect of temperature.
Basically, how did they decided that 20-26C was the right range? If it wasn't
by testing differences between mice at colder and warmer temperatures, then
they weren't controlling for temperature.

~~~
jonlucc
Mice in a particular experiment tend to be housed in the same room or same
rack, with enough circulation in the room to hopefully assure a homogeneous
temperature in the room. Therefore, the control animals were likely right next
to treatment animals. In this way, one could reasonably say that variations
between the groups is not due to the way they were housed. Many other things
that are controlled in housing include their feed, bedding, access to water,
number of animals in a cage, etc.

~~~
mikeash
Thank you both, I wasn't thinking clearly. I was thinking of the sort of
"control for" that involves accounting for differences between groups, but
totally spaced on the part where you can just "control for" something by
ensuring it's the same.

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qwerty_asdf
Does PNAS realize that their acronym is ridiculous and hilarious? Was that
done on purpose?

~~~
Florin_Andrei
It took me a while to realize why you said that.

I think you've been over-sensitized by spending too much time in certain
regions of the Internet. When the only tool in your possession is a hammer,
everything looks like a nail. When most of your informational input is of a
certain nature, everything else tends to relate to it.

~~~
colanderman
No. There is only one way to pronounce "PNAS" (other than spelling it), and it
sounds exactly like "penis". Not "cock", "dong", "member", "wang", or any
other arguably childish euphemism. It sounds exactly like the proper English
noun for male genitalia.

And this has nothing to do with you me or the parent thinking it sounds like
"penis". EVERYBODY WE TALK TO will think we're saying "penis". Believe me, I
get this enough with Coq (the theorem prover) and "cock"'s merely slang.

~~~
moocowduckquack
I'd pronounce PNAS with a hard a, like in ass, not like the end of penis,
which has the i in kiss, so personally I don't find it that much of a
homophone. Though I hate to think what that sentence has just done to you,
given your sensitivity in such matters.

~~~
colanderman
_Though I hate to think what that sentence has just done to you, given your
sensitivity in such matters._

Beside being unnecessarily snide, you missed my point, like, _entirely_.

 _I_ don't give a rat's ass that it sounds like penis. But I couldn't say it
in public without eliciting childish sniggers from whomever I'm trying to talk
to.

~~~
moocowduckquack
Well, they have been managing fine since 1915, apparently without it hindering
things all that much.

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VLM
Thermoneutral means zilch energy consumption at basal metabolic rate when
motionless in a windless environment. Its a narrow temp range. For bare humans
its about 80F which seems warm because we're usually not motionless and
usually wear clothes.

You can make a joke out of the whole thing in that they're trying to turn the
mice into couch potatoes who don't burn a single excess calorie to better
match the human couch potatoes.

Its not totally ridiculous to think a drug could be developed that would have
different effects on human couch potatoes vs the now somewhat unusual athletic
humans. We already have identified compounds like that, take all the roids you
want, no exercise means no gains. Off the top of my head there's some
medications that screw up human thermoregulation, like prevent or reduce
sweating, so exercise for someone on those meds equals heatstroke (well, not
guaranteed, but close)

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ry0ohki
Am I reading this wrong, or has something else been accidentally discovered:
Being cold/stressed out causes tumors?

~~~
knowtheory
I'd be super uncomfortable with anybody asserting that conclusion.

What the quote in the original article says is that they have data that in a
preliminary fashion supports the hypothesis that being cold (and trying to
keep warm) suppresses a mouse's ability to fight off tumor growth.

That is very different from saying cold/stress causes tumors.

~~~
DougWebb
"causes" is the troubling word there. From what I've read, in most people and
animals tumors are growing all of the time due to cell replication defects,
but normally the immune system gets rid of them. Cancer, as a disease, isn't
"your body is making tumors", it's "your immune system isn't keeping up with
your tumors".

From that point of view, anything which makes your immune system less
effective "causes" cancer by making it harder for your immune system to kill
tumor cells faster than they occur. Being cold all of the time, or being
subjected to any type of chronic stress, certainly seems like it could do
that.

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aroch
I'll have to double check, but I believe we keep our mouse room at ~25ºC (+/\-
5%). 31C for housing seems very high and probably well outside mean
temperatures for native habitat

~~~
bryne
Apparently not.

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contextual
Even putting aside the moral and ethic issues, how can animal testing be
allowed to continue when the studies are rife with bias and error? Officials
at America's National Institutes of Health (NIH) state over three quarters of
all published biomedical findings are irreproducible due to fraud and
incompetence.

Moreso, the number of retractions has grown over tenfold in the past decade -
but it's only 0.2% of the 1.4 million papers published in academic journals.
The studies that were retracted were only done so when fundamental flaws were
exposed by others. Many more false studies go on unnoticed and continue to be
referenced.

Worse of all, 90 percent of drugs that were "successfully" tested on animals
then failed in human trials.

EDIT: It should be a criminal offence for researchers to subject animals to
harm and death and produce fraudulent papers.

Sources:
[http://www.economist.com/news/briefing/21588057-scientists-t...](http://www.economist.com/news/briefing/21588057-scientists-
think-science-self-correcting-alarming-degree-it-not-trouble)

[http://www.popsci.com/article/science/how-get-rid-animal-
tes...](http://www.popsci.com/article/science/how-get-rid-animal-testing)

~~~
icegreentea
What makes you think that they aren't trying to get it right? The animal to
human failure rate isn't really related to scientist's insight, skill, or
knowledge, but to the fact that biology is really fucking complicated. A
researcher can pour their life and soul into their work, watch it work its way
through all the layers of testing, showing consistent and sencial results, and
then watch it blow up when it reaches a human, cause surprise! Third and
higher order effects can't be predicted!

Also, your line of logic seems like a non-sequitur. The poor overall quality
of papers (irreproducability for example) has nothing to do with animal
testing. If you put aside moral and ethical issues of animal testing, the
question isn't 'how can animal testing continue given how crappy their results
are' its 'how can testing continue given how crappy their results are'.

~~~
contextual
_What makes you think that they aren 't trying to get it right?_

There's countless examples of fraud, complacency and bias in scientific
research, but I'll just quote the wise (albeit fictional) Jedi Master Yoda:
"Do, or do not. There is no try." Especially when the fate of sentient life
hangs in the balance.

~~~
icegreentea
Still doesn't make sense. There are countless examples of shit gone wrong, but
until you can prove that it is systemic and/or that the responsibility of the
fraud, complacency, etc lie in the majority (or hell, say significant
minority) of researchers and scientist, it's really not fair to paint them all
with the same brush.

Certainly there are countless examples of fraud, complacency and bias in all
human endeavors, but that hardly indites all of humanity to "not trying to get
it right".

Furthermore, "do or do not" is childish when applied out of its proper
context. The intention of "do or do not" is to remind you that in terms of
your effect on the world, the effort you put into an unsuccessful act doesn't
get you any closer to the actual act. What "do or do not" does not make -any-
sense in is in situations with many factors out of your control (especially
factors you don't even know about!), and especially when trying to judge
someone or a group of people.

I'm not sure exactly what point you're trying to make, but I think its that
"when the fate of sentient beings hang in the balance, how hard you tried to
do it right doesn't matter in my judgement of your ability to conduct your
work". Which is completely nonsense. Go tell that you a paramedic, or a doctor
right after they had someone die on them.

~~~
contextual
Submitting and publishing dodgy, fraudulent or sloppy studies isn't trying, it
undermines all of science. And when animals are subjected to pain and death
for fame or career advancement, it's morally corrupt, even criminal.

