Thursday, June 21, 2012

Hamster Roshambo

With my guts being uncooperative of late, I've been reading up on various studies. Oh, who are we kidding, that's something I do for fun anyway. I'm following @DearSarah on twitter because she's a good aggregator of technical and feminist references. One led me down a habitrail of issues in using rodents for medical testing.

Mild Warning: If animal testing is anathema to you, you may not want to proceed on general principle. But I won't be talking about truly icky stuff, rather one point is about how to improve conditions.

The reasons for testing medical treatments on non-humans are compelling: fast turnaround, many samples, controllable conditions, and fair warning, ala the mine canary, of imminent harm. We can all agree that conditions for test animals should be humane above a certain threshold. We can agree that the number of tests should be minimized, especially if there are alternate assessments - aka testing is not done frivolously. Assuming that to be true, I don't have a problem with most of it even though I have a particular fondness for hamsters. /Disclaimer

I have given animal testing some thought. I don't like that they're generally in barren cages, because bored rodents are not healthy rodents, and a lot of medical testing assumes the controls are healthy. So why don't they all have wheels, at a minimum? Ever since I read the hamster blog about the guy who hooked up a rotation meter to his hamster's wheel and recorded wheel spins per day over the life of the hamster, I've wondered why they don't do that with all lab rodents who run in wheels. It would also be a way to check on whether or not your fountain-of-youth medicine really is extending their quality of life - will the hamsters on your supplement run longer as adults than the controls? Will your hamster have off days? Will there be earlier spikes or longer depressions in activity? And you get this just from them being in their cages.

This article, I think from Discover, was talking about problems with mouse models of disease and how things can improve. What I hadn't known/realized/retained was that medical research used to be dominated by rats. They're pretty intelligent and can entertain themselves pushing levers and running mazes. But all the research these days seems to be on mice, so what gives?

The "knockout mice" revolution happened. Scientists figured out a way to drop genes out of mice then breed them true. They're excellent to find out what a particular gene does/doesn't do and whether or not your drug will fix it. Rats resisted the knockout technique until very recently. So for the last 10 or so years, mice dominated the research. But it's emerging that all the tests that had been so painstakingly developed for testing rats... might not be so great for testing mice who don't much like pushing levers or bright lights in white mazes. Reasons for not changing techniques, I assume,include: some people - even scientists - assume rats and mice are much the same being long tailed rodents. Established testing has support in the way of developed instructions and supplies. Uniformity of testing methods makes findings replicable, and interpretation less sketchy. However, if you're testing for, say, stress, your mouse is already above baseline doing these non-preferred things, so you might not realize as much of a distinction between control and experiment as you should. And your tests kinda show that mice are dumb, but maybe they're just balky, or you're not playing to their strengths.

Enter some scientists who've thought about these things. It's actually pretty fascinating. One lady from the breeding facility can talk all day about interpreting their emotions from their interaction with their bedding - Supplied a compressed cotton pad, happy, healthy mice will shred it and make a nest. Some of their knockouts didn't get that memo and sleep on it like a tatami mat, or hide under it in some fashion. And they haven't even gotten to the testing yet! Yet another in-the-cage passive test.

One researcher gave some thought to what mice prefer to do that is different than rats. They're not big on visuals, but they like smelling things. So he buried treats in sand that had been mixed with various spices. Turns out that mice can learn that treats are in cardamom but not cinnamon, or cinnamon but not pepper (for instance). So cdm>cnn>pp right? So cdm>pp, right? Wrong... Like rock-paper-scissors, this tricky scientist made pepper beat cardamom. And mice can learn this! (I do wonder how well they'd do with rock-paper-scissors-lizard-spock...) It's tricky enough that the test can be used to see if they get confused or not, without unduly stressing them out. I'm just really entertained by the fact that somewhere out there, knockout mice are playing roshambo. For science.


S said...

Two comments based on what I've seen in animal testing:

First, one of the newer ways to get more data points from one animal (thus needing fewer animals overall) as well as to have the animal experience fewer separate needle sticks, is to have the animal hooked up to a line that allows for multiple sampling. The animal can roam about its cage while tethered to the line, but I don't think it could run on a wheel without getting tangled.

Second, regarding the boredom and measurement-of-stress aspect, most of the mouse studies I've seen data for were of the "dose it for seven days, then euthanize it and puree its liver to look for metabolites" as opposed to long-term dosing and behavioral observation.

So yes, if someone is studying fountain-of-youth stuff, then wheels in rodent cages would be a very good thing. For short-term testing of antibiotics or cancer drugs, it's probably not as key, especially if it means not being able to use the continuous sampling approach.

CrankyOtter said...

I've been buying large microscope slides for work (2"x3" instead of 1"x3") and it's a little freaky because adjacent to these slides in the catalog is the reason they need the wider ones - brain slices.

So you can buy what is essentially an egg slicer for various different animal brains, and the wider 2" slides for your rat brain slices. I thought about ordering one but they're $650 or so, which is too much for me to spend on what amounts to an off color joke.