[HN Gopher] Lab mice have a chill, and that may be messing up st...
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Lab mice have a chill, and that may be messing up study results
(2016)
Author : apsec112
Score : 73 points
Date : 2020-08-06 16:48 UTC (6 hours ago)
(HTM) web link (www.statnews.com)
(TXT) w3m dump (www.statnews.com)
| Wowfunhappy wrote:
| > 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 wrote:
| Just because it's consistent doesn't mean it's not impacting
| the outcomes in an important way.
| rolph wrote:
| it is very common to see publications such as "regulation of
| [gene1] expression by interaction with product of [gene2]"
|
| followed by "temperature dependency of [gene2product]
| regulation of [gene1]"
|
| absolute temperature of culture can confound you into
| negative results so you will never see the genes activity
| until the experiment is replicated with culturally disparate
| subjects. thats just being simple as well, there is normally
| a continuum of influences and its up to experiment to tease
| out the largest contributor[s] to the effect of interest
| Wowfunhappy wrote:
| 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 wrote:
| It would at least need to be tested at both, you can't
| guarantee the cooler temp isn't doing anything.
| frabert wrote:
| 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.
| nitrogen wrote:
| It matters if the effect size is dependent on
| temperature.
| jmcgough wrote:
| 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 wrote:
| 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.
| [deleted]
| jmcgough wrote:
| 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 wrote:
| 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 wrote:
| The point is to reduce confounders as much as possible.
| [deleted]
| mennis16 wrote:
| Not if the temperature has an effect on the intervention
| you are trying to study. Taken to an extreme, you
| obviously cannot house mice in a freezer and expect
| generalizable results.
| [deleted]
| rolph wrote:
| the absolute is also a problem. rats have a hibernative state
| this is a physiological response to temperature. The regulation
| of gene product expression has many factors, temperature being
| a common one at the biochemical level, and the whle organism
| physiological level. Hibernation or torpor is an exploitation
| of thermal dependency of regulation,providing on demand
| alternative physiological state.
| dv_dt wrote:
| It depends on what is being studied and concluded. The Rat Park
| experiments come to mind.
|
| https://en.wikipedia.org/wiki/Rat_Park
| [deleted]
| jldugger wrote:
| > "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.
| jameslk wrote:
| > 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 wrote:
| 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 wrote:
| 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 wrote:
| 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?
| godelski wrote:
| I've seen this come up several times and this article is 4 years
| old. Does anyone know if anything has changed since then?
| strogonoff wrote:
| 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.
| jmcgough wrote:
| 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.
| zenexer wrote:
| > 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.
|
| The description you've provided--especially that line--is
| eerily reminiscent of the "Enrichment Center" from Portal.[0]
| As that game (humorously) demonstrates, it's unreasonable to
| expect that the physiology of an animal wouldn't change under
| those conditions. How much research would've resulted in
| different outcomes had the animals involved been kept under
| different conditions?
|
| [0]: https://en.wikipedia.org/wiki/Portal_(video_game)
| wsc981 wrote:
| Yeah, Bret Weinstein mentioned something similar regarding lab
| mice in a Joe Rogan podcast:
| https://www.youtube.com/watch?v=ve4q-1D_Ajo
| dwd wrote:
| 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.
| [deleted]
| pmiller2 wrote:
| Just to add on to this, a proper cage sized for 2 rats is
| probably going to take up at least a small kitchen table's
| worth of space. When have you ever seen a cage that size in a
| research lab? Besides, groups of 2 are the barest minimum you
| want for keeping rats.
|
| As to the whole "studying stressed out rodents might not give
| representative results" point, I'm reminded of the Rat Park
| experiment [0].
|
| ---
|
| [0]: https://en.wikipedia.org/wiki/Rat_Park
| jt94mf90d wrote:
| Some of us have been boxed up for 4 months, and we have been
| fine.
| bugzz wrote:
| Sure, and some of the rats are probably fine too. But it
| still skews studies...
| pmiller2 wrote:
| And, some of us are starting to reach our limits due to being
| boxed up for 4 months. When you study a population, you want
| to be able to study representative samples of said
| population. Global conditions for humans are not even close
| to representative right now. Given the known effects of
| confinement stress on humans, getting representative
| population samples for most sorts of studies seems difficult,
| at best.
| pvaldes wrote:
| 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 wrote:
| 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 wrote:
| > _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.
| seesawtron wrote:
| That's a good point that this is not a new phenomenon. I am
| aware of some labs that do keep mice at warm temperatures
| already so maybe the scientific community already managed to
| make changes in some places.
| jmaygarden wrote:
| This doesn't even get into how they've been bread to favor early
| survival versus longevity. Lab mice have abnormally long
| telomeres.
| bz33t wrote:
| 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
| kobieyc wrote:
| The real question is why is this not the headline news
| bz33t wrote:
| For headline news, I think we would need studies that show
| that this effect changes results from high ranked studies
| that used mice. But publishing these would be hard in peer
| reviewed journals because the peers who will referee the
| papers will likely be researchers whose own previous
| publications would be questioned by these new results. In
| the same podcast, Bret talks about the failings of peer
| review.
|
| Another problem is that even if the results are published,
| usually it takes a long time for information to diffuse
| into the wider community. I assume this is largely because
| finding a novel ideas is like searching for a needle in the
| haystack of common knowledge that has been spread far and
| wide.
| kleer001 wrote:
| The hand waving answer is The DISC or the distributed idea
| suppression complex.
| dwd wrote:
| 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.
| meremortals wrote:
| +1 Summary: https://podcastnotes.org/portal-with-eric-
| weinstein/bret-eri...
| ramraj07 wrote:
| 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.
| t_serpico wrote:
| Everyone is aware that it's an imperfect model system. We just
| have nothing better to go off of. Granted, it got us to where
| are today so it obviously has had practical utility, but we may
| have exhausted the benefits of simplistic animal models as we
| try tackle more complex diseases (cancer, neurodegenerative
| disorders, etc.).
| Wowfunhappy wrote:
| > 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.
| nwah1 wrote:
| The gut-brain axis is a huge deal. Hardcore neuroscience is
| affected by probiotics.
|
| There is even a class of them called psychobiotics.
| [deleted]
| james_pm wrote:
| Obvious question: If the ambient temperature affects the outcome
| of the treatment for mice, then is that also the case for humans?
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