
Lab mice have a chill, and that may be messing up study results (2016) - apsec112
https://www.statnews.com/2016/04/19/lab-mice-temperature/
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jmcgough
I worked in a Neuroscience lab as an undergrad research assistant for several
years. My first year in particular involved a lot of cell counting and rat
care.

There was a large room for housing rats for all of the labs in the building -
mostly Sprague Dawley, which are very well studied at this point and chosen
because they're easy to care for. The room was nowhere near 20 - 26C. It felt
like walking into a fridge.

I think there are more problems than just the temperature that rats are kept
at.

There are requirements for minimum standards of housing for animals - every
university that does animal experimentation is required to have a LAR (lab
animal resources) officer who verifies compliance. But researchers have to be
frugal with money (even grad students are expected to live on a 20-30k
research stipend), so they really do the bare minimum. Cages are as small as
they can be, and rats are housed in pairs so that they can socialize, but
their cages are almost barren. They're required to have some form of
environmental enrichment, which means a little wooden rod in every cage that
they can play with and chew.

It's frustrating to think that there are probably many studies that have been
impacted by not studying "normal" rats. We're studying specific research
breeds of stressed rats who're trapped in little boxes for their whole lives.
It'd be like if you studied humans who've been trapped in their apartments for
the last 4 months and assumed normal psychology and physiology.

~~~
wsc981
Yeah, Bret Weinstein mentioned something similar regarding lab mice in a Joe
Rogan podcast:
[https://www.youtube.com/watch?v=ve4q-1D_Ajo](https://www.youtube.com/watch?v=ve4q-1D_Ajo)

~~~
dwd
The podcast he did with his brother Eric (The Portal #19) gives a very good
history of the work he did as a grad student in finding that the telomeres of
the lab mice supplied to US labs were elongated due the selective breeding
process of producing as many mice as possible.

The implications are quite alarming for existing testing and they talk about
how he was basically ignored and the mice quietly fixed.

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ramraj07
We have first hand experienced this - we couldnt induce disease in the same
mice when our lab moved universities and we all knew the temperature was one
of the biggest culprits.

But there are others too - gut microbiome and other microbiomes/viromes change
from facility to facility and this is a huge deal for pretty much every topic
except hardcore neuroscience. Probably. Who knew the bugs inside us are a big
deal for everything that happens in us!

All of this notwithstanding the growing knowledge that no, you can't just give
mice cancer/MS/autism and check if a drug works there, expecting the same
result in humans. I'll chalk the majority of problems in our drug pipelines to
this fallacy.

~~~
Wowfunhappy
> All of this notwithstanding the growing knowledge that no, you can't just
> give mice cancer/MS/autism and check if a drug works there, expecting the
> same result in humans.

...to state the obvious, scientists aren't giving drugs to mice and then
shipping them off to pharmacies. They're testing the drugs in mice first to
see if it's worth testing in humans. Then, the _human_ trials are used to
determine efficacy.

It's not a perfect system to be sure, but what is the alternative? Bypass
animal testing and go straight to human trials? I'd have a lot of obvious
ethical issues with that.

~~~
danieltillett
Test on pets. Seriously our pets get all the same diseases we do (as always
there are some exceptions). Millions of pets every year get cancer (just one
example) and we make almost no use of this resource.

The other approach is to start testing in humans at a very, very low dose.
While this would work it would require a change in the regulatory environment.

~~~
GordonS
A lot of testing maims, disabled and/or kills rats.

Are you going to be happy with a researcher coming to your home and breaking
your dog's back? Or injecting it with toxins to induce neuropathy?

~~~
danieltillett
Don’t be silly. I am talking about treating pets for the diseases they have,
not having people torture my pet.

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jldugger
> “It is not easy for an investigator to go and say, ‘I want the room
> warmer,’” O’Hara said. “They can, but it will probably take multiple
> efforts, multiple times, and more often than not they will give up.”

In a lot of unis I've been in, the buildings are kinda centrally managed.
Steam pipes serving multiple buildings that are often not even enabled during
the summer. And in one case, the central management system for that stuff was
running on a DOS PC from a vendor who went bankrupt and had no forseeable
replacement. Fortunately I'm not around to experience what happens when that
box finally can't be repaired.

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jmaygarden
This doesn’t even get into how they’ve been bread to favor early survival
versus longevity. Lab mice have abnormally long telomeres.

~~~
bz33t
According to Bret Weinstein who figured out the connection between telomere
length and breeding, they seem to have quietly changed the breeding protocols
to bring the telomere length back down to be in line with wild type mice. He
talks about it in a long interview that gets really interesting about a hour
in: [https://youtu.be/JLb5hZLw44s?t=4083](https://youtu.be/JLb5hZLw44s?t=4083)

~~~
kobieyc
The real question is why is this not the headline news

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kleer001
The hand waving answer is The DISC or the distributed idea suppression
complex.

~~~
dwd
I think that is Eric's facetious term for what Universities are (a play on the
military/industrial complex) but the main problem he points to is the
inventivisation through market forces to not release non-monitisable research
and that the best researchers don't teach because they are more value to the
University generating grant money and basically being salespeople.

The not publishing research was interesting in that holding research in-house,
making predictions, getting grants to research those predictions and then
using the original unpublished discovery as the basis for the whole lot makes
a lot more money.

~~~
kleer001
As I understand it the DISC was a bit more diffuse and while it had tendrils
in Universities, it didn't stop there. But yes, that was the main thrust of
the DISC in the discussions.

Yes, the perverse incentives of the market play havoc with the spirit of the
process of science. Which seems to be the source of the brain drain, in as
much as talent leaves the university for the market instead of staying and
teaching more talent.

~~~
dwd
It was interesting to listen to Bret in a podcast talking about whether it was
a conspiracy of silence and in describing it as an emergent phenomena rather
than being planned he was very much reading from Assange's manifesto on how
they form and operate and the need for open government.

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Wowfunhappy
> a variety of factors, including researchers’ and technicians’ comfort at
> those temperatures, have prevented anyone from changing the thermostat.

As long as the temperature is kept _consistently_ cooler for both the
experimental and control groups (and whatever other groups), it shouldn't
matter, right? Seems to me the problem is the variation and the fact that it's
not controlled.

~~~
ralusek
Just because it's consistent doesn't mean it's not impacting the outcomes in
an important way.

~~~
Wowfunhappy
But a warmer temperature could also be impacting outcomes, right? It seems to
me that the temperature just needs to be both controlled and documented.

~~~
nwienert
It would at least need to be tested at both, you can’t guarantee the cooler
temp isn’t doing anything.

~~~
frabert
I think the point is, whatever the impact of cool or warm temperatures are, as
long as it is the same in all the experiments it should not matter.

~~~
jmcgough
I have read hundreds of research papers, and I don't think I've ever seen one
that described the temperature that the rat housing is kept at. It's
definitely not something that's controlled for right now.

~~~
Wowfunhappy
Oh, totally understood, that clearly ought to change!

My only point was, the article was framing this as an issue of scientist
comfort, ie human researchers don't want to work in hot labs. I don't see why
they should have to, at least in most cases.

~~~
jmcgough
We study rats because they're an inexpensive and ethical replacement for
humans, with the assumption that some of the research will carry over to other
mammals. It's harder for that work to translate over if we keep them in
abnormal environments that affect their behavior or physiology.

~~~
methodin
Is it even possible not to "keep them in abnormal environments that affect
their behavior or physiology"? Putting a rate in a cage alone is an abnormal
environment for a rat.

~~~
nwienert
The point is to reduce confounders as much as possible.

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godelski
I've seen this come up several times and this article is 4 years old. Does
anyone know if anything has changed since then?

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ajb
I'm missing something here. What kind of mice have an environment of 30-32
degrees C in the wild? House mice live at the same temperature as people -
they might be able to be warmer in their nest, but presumably so can lab mice,
without making the room warmer. Are lab mice sourced from some species that is
from a hot country?

Regardless of the temperature the mice prefer, obviously it would be a good
idea to record the temperature the experiment was conducted at.

~~~
munificent
_> House mice live at the same temperature as people_

I would guess that the interiors of walls and attic spaces are a good bit
warmer than the open portion of a room where we live.

~~~
ajb
Walls may be better insulated, but to accumulate a high temperature you need a
source of heat. Where is the source of heat in a wall? For attics you might be
on to something as heat rises. Still, 30 degrees seems a lot to me.

~~~
GordonS
Have you ever been in a house attic on a hot day? It's absolutely stiflingly
hot!

It was perhaps 22C at my home yesterday, and by chance I had to get something
from the loft - I'd be surprised if it wasn't 30C.

~~~
ajb
Okay, I concede that Attics could be 30 degrees, at least some of the time :-)

Mine probably isn't because the insulation is on the 'floor' of the attic, so
it should be approximately the same temperature as the outside air (well, if
it were ventilated properly). This is one of the design choices of an attic.
Still, I do wonder if this provides enough hot spaces for mice to have evolved
to expect a 30 degrees environment. Maybe they do in some places.

~~~
GordonS
> Mine probably isn't because the insulation is on the 'floor' of the attic

Hmm, mine too.

> Still, I do wonder if this provides enough hot spaces for mice to have
> evolved to expect a 30 degrees environment

Yeah, this does seem quite questionable to me too, at least for temperate
countries.

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jameslk
> The National Academy of Sciences recommends housing mice between 20 and 26
> degrees Celsius — about 68 to 79 degrees Fahrenheit. But the natural
> comfortable temperature for mice is warmer — between 30 and 32 degrees
> Celsius (86 to 90 degrees Fahrenheit).

I didn't see an explanation of why this recommendation is below the
"comfortable temperature" of mice. Is there a specific reason this temperature
is recommended?

~~~
_red
I dont have an answer, but could be for same reasons why hospitals keep it on
the cooler side: Less fungal / bacteria growth. Less mites, insects, bugs,
etc.

~~~
pmiller2
The GP comment is asking how 30-32 C was determined to be the most comfortable
temperature for mice, not why we keep them cooler than the mice like.

~~~
FrojoS
That's not how I read it.

Anyway, here is my _guess_ for the two questions:

1) The recommended temperature in the lab is based on other factors than the
mice's prefered temperature. E.g. comfort of the scientists and technicians,
spread of bacteria etc.

2) The temperature prefered by mice was determined by studying them in the
wild or in the lab. E.g., if given the choice between two places of different
temperature, which do they pick?

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strogonoff
Lab lighting can also skew the outcomes. Rats exposed to constant white light,
for example, have elevated baseline corticosterone concentrations in plasma
(Scheving & Pauly, 1966).

There are a few of such variables which it's not clear are taken into account
or not, and probably more are unknown.

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pvaldes
The idea is intriguing but lab mice have also plenty of food and in warm
blooded animals this, and the proximity of other mice, should provide the
extra heat.

The article is from 2016 in any case

~~~
pazimzadeh
I can confirm that lab mice in our mouse house are alway huddled up together.

Our lab studies E. coli, and mice require pre-treatment to permit intestinal
colonization by E. coli. However, about 2 in 5 mice are colonized without
antibiotic pre-treatment. I wonder if these are the the colder and more
stressed out mice (outside the cuddle puddle).

~~~
Florin_Andrei
> _I can confirm that lab mice in our mouse house are alway huddled up
> together._

I'm not an expert on mice but that doesn't sound like a good thing.

~~~
pazimzadeh
Why not? You don't think mice huddle in the wild?

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failuser
Are stressed out mice a better model for humans or a worse one?

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james_pm
Obvious question: If the ambient temperature affects the outcome of the
treatment for mice, then is that also the case for humans?

