Lab Mice Are Being Kept Too Cold, Apparently

http://pipeline.corante.com/archives/2013/12/18/lab_mice_are_being_kept_too_cold_apparently.php

by mhb • 13 years ago

83 77 13 years ago

pipeline.corante.com

loceng3• 13 years ago

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.

mhb• 13 years ago

Then there's also humidity, altitude and who knows what else.

GotAnyMegadeth2• 13 years ago

Gravity

gosub• 13 years ago

ventilation, illumination type and intensity, human presence.

saalweachter5• 13 years ago

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.

mikeash2• 13 years ago

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.

collyw• 13 years ago

Surely mice live outside as well. I mean, I assume there were mice around before humans evolved enough to build houses, and heat them.

loceng3• 13 years ago

Perhaps I just don't know the correct terminology, though you can have multiple control groups, no? That is what I was meaning, I realize I wasn't very clear.

Florin_Andrei2• 13 years ago

Mice are small. Their surface / volume ratio is MUCH higher. They lose heat a lot faster than we do.

mapt2• 13 years ago

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• 13 years ago

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.

aroch• 13 years ago

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• 13 years ago

Apparently not.

brianbreslin• 13 years ago

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.

contextual4• 13 years ago

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.popsci.com/article/science/how-get-rid-animal-tes...

angersock2• 13 years ago

I really, really, really hate having to make this argument, but:

Would you rather that all the drugs that didn't succeed in animals fail in humans first?

contextual4• 13 years ago

If humans were tested, many of these badly designed and fraudulent experiments would have never been done in the first place.

asciimo• 13 years ago

Putting ethical and philosophical issues front-and-center, absolutely. Why is this a difficult argument to make? It's our disease. It affects our bodies. If we want a cure then we should put our own skin in the game.

craigyk2• 13 years ago

Science is a process and not a state. It doesn't need to be perfect, as long as you take slightly more steps forward than backwards the extent of knowledge progresses.

I think virtually no one likes experimenting on animals and scientists are acutely aware of all sorts of problems with these systems, but what else should humankind do? just twiddle our thumbs until better alternatives come around? The better alternatives also often come out of this type of research.

jonlucc4• 13 years ago

I agree, but I can't wait until organs on a chip are cheaper than rats!

arbitrarilyHigh• 13 years ago

I generally agree with your criticisms, but what alternative do you propose? Of course we should have better vetting of studies before publication, more replication effort, and ideally a process that doesn't incentivize fraud/incompetence. But how to implement such a system? Also, I don't see how these issues are limited to animal studies. Your (entirely valid) criticisms of bias, uncaught error, and irreproducability apply much more broadly, to the vast majority of published modern experimental science, again raising the question of how we can address those issues so that the scientific literature is reliable.

icegreentea2• 13 years ago

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'.

contextual4• 13 years ago

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.

peterwwillis5• 13 years ago

A lot of animal testing is general research, not drug testing. For example, it's fairly impossible to do brain research on anything but a brain. Also, a lot of research is basically infinite trial-and-error until you find something that works; doing this on a scale large enough for humans would kill lots of people, versus lots of mice. It's also faster with mice because they breed quickly and prodigiously, so we don't have to wait 300 years for enough testing to find a result.

Your basic argument is "it's error prone so we shouldn't do it." But that's exactly why we do testing - to work out the errors! The fact that all of these failures are occurring is proof that doing human research would simply take more time, not less.

"Organ on a chip" is also only useful to test for specific response. It does not show how the experiment works when introduced to an entire system of organs.

jonlucc4• 13 years ago

I envision a future when we can grab a handful of organs on a chip, then decide on what kind of experiment we want to run. Want to see if something affects the cells in bone marrow? Bone chip. Want to understand if a drug is cleared exclusively through the kidney? Bone chip + kidney chip vs bone chip + kidney + liver chip. Want to test subcutaneous vs intravenous delivery kinetics? Put together a bunch of chips: bone, kidney, liver, gut, and skin.

VladRussian2• 13 years ago

yep, the same logic of vivisection, concentration camp hypothermia experiments, Tuskegee syphilis experiment, etc... - "it advances science"

Also, a lot of research is basically infinite trial-and-error until you find something that works; doing this on a scale large enough for humans would kill lots of people, versus lots of mice.

Doing research on humans vs. mice would [these days, though not even 40-60 years ago] force to do the research differently, mindfully and efficiently, instead of meat chopping factory it is now.

ry0ohki• 13 years ago

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

craigyk2• 13 years ago

depends. a lot of these mice are specific breeds designed to make it at least feasible to perform experimentation. It's common to use mouse lines that have extremely deficient immune systems. Otherwise there would be almost zero chance of tumor cells transferred from a different species (i.e. human) being able to grow on the mouse for study.

jonlucc4• 13 years ago

This is a very good point. It is important for non-researchers to know that when you want to do a mouse (or rat, dog, or non-human primate) study, you have to decide what particular strain of mouse to buy. There are MANY options from Harlan, Charles River, etc, and each strain has its own genetic composition. Some of the strains are intentionally inbred, or intentionally outbred.

I think this variation might also be more important than some people are giving credit for. It is entirely possible to run a mouse study twice, confirming the results. Then, you can run the same protocol in a different strain and get no results or different results. Then, you have to try to understand which strain might be more applicable in a human population.

knowtheory• 13 years ago

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• 13 years ago

"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.

qwerty_asdf2• 13 years ago

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

Florin_Andrei2• 13 years ago

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.

colanderman3• 13 years ago

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.

RyanMcGreal2• 13 years ago

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• 13 years ago

For the curious, I think this is the study:

http://en.wikipedia.org/wiki/Rat_Park

RyanMcGreal2• 13 years ago

Thank you. That's the study.

peterwwillis5• 13 years ago

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.

herbig2• 13 years ago

"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• 13 years ago

Construction Noise Decreases Reproductive Efficiency in Mice: 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/

comicjk• 13 years ago

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) - if you aren't rigorous with your assumptions, you are not doing science, and the truth is not going to come.

VLM2• 13 years ago

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)

Lab Mice Are Being Kept Too Cold, Apparently

Related Stories