Of Mice and Cancer

Maximum Prophet points out a series of articles in Slate about the role of mice and rats in the fight against cancer. The first article discusses the problem of using the same type of animal for many tests; the reactions may be consistent, but they can also be different from the reactions a human has to the same treatment. "The inbred, factory-farmed rodents in use today—raised by the millions in germ-free barrier rooms, overfed and understimulated and in some cases pumped through with antibiotics—may be placing unseen constraints on what we know and learn." The second article focuses on one particular type of mouse, bred specifically for consistency and for its suitability to labwork, which has come to dominate biological testing. The final piece examines what researchers are trying to learn from the naked mole rat, a species that doesn't seem to get cancer on its own, and is resistant to attempts to induce cancer. "Buffenstein and her students tried one of these shortcuts. They placed some mole rats in a gamma chamber and blasted their pale, pink bodies with ionizing rays. The animals were unimpressed."

Comments

ohshi-

[Moheeheeko]

"They placed some mole rats in a gamma chamber and blasted their pale, pink bodies with ionizing rays."

Please dont poke the rats, you might make them angry, and you wont like them when they are angry.

So is there an alternative?

[TWX]

Last time I checked, most people don't want to be lab subjects even when there's not a whole lot of risk, and a lot of modern research means the destruction of the lifeform being tested upon, either by the disease process or by the technicians and scientists studying the progression of the disease or the treatments.

We don't allow for experimentation on prisoners generally, regardless of the possibility of consent, and that really only leaves us with the down-and-out or the insane, and even with the latter, we don't generally allow it if they're diagnosed insane as they no longer can consent either.

Most higher order or larger animals that might make better analogs to humans have gestation periods that are too long, or they're endangered or threatened, or they're more difficult to work with.

I don't see a better solution, though if one is brought to our attention I certainly won't blanket-disapprove without giving it consideration...

Re:So is there an alternative?

[jasno]

People are hard to experiment on, because you can't control all of the variables. People also have different genes. It's hard to tell if an effect was due to the drug, their environment, or their genetic makeup.

Mice, while definitely not people, have fairly homogeneous genetics and you can control what they eat, their exercise, etc.

Re:So is there an alternative?

[macklin01]

This is part of the motivation for developing computational models of cancer. Code up the biological assumptions, calibrate to mouse data, validate to the mouse. If it works, then the biology and calibration protocols are probably fine. Re-calibrate to humans (with changes to geometry, tissue properties, cell parameters, etc.), run the models on clinical data (pathology, imaging, proteomics, etc.), and see how it does.

Now, actually doing this is the subject of tricky ongoing work by many many teams of people (see the work in the NCI Physical Sciences Oncology Network), but it's being driven by just the types of problems stated in this thread.

We've been testing various aspects of this on breast cancer and lymphoma, and the results are encouraging, ranging from explaining "tissue artifacts" in pathology (due to fast timescale biophysics) to predicting correlations between mammography and pathology (due in part to necrotic core biomechanics + oxygen diffusion limitations), to predicting DCIS excision volumes. (See stuff here and a few movies.)

Yeah, we knew that already.

[SecurityGuy]

I worked with mice and rats in oncology research. That this stuff isn't directly translatable to humans is something everyone knows. For someone to comment on that would be like someone saying "Whoa! This room is just FULL of air!" Uh, yeah. And?

They use mice and rats because testing things on people is unethical and testing things on animals a lot more like us (primates, pigs, etc) is either unethical or expensive.

In my experience it wasn't the case that the biological effects were wildly different. A substance that produced a particular effect in rats often would in humans (or other animals) too, but often at a different dose. The problem with mice/rats was their tolerance. You might find a drug that was effective in rats, but its toxic dose in humans is less than or too close to its therapeutic dose.

Re:Yeah, we knew that already.

[geekoid]

I had to read the article a few times. It doesn't make sense. Then I found it. He didn't see a result he wanted, and blamed the mice. Now he is wrapping himself up in a process of deflecting things he doesn't want as a flaw in the mice.

I mean, reread that article and think about that. He logical fallacy pops up a few times.

Re:Yeah, we knew that already.

[ColdWetDog]

Actually, I thought he'd discovered something rather profound:

"I began to realize that the ‘control’ animals used for research studies throughout the world are couch potatoes," he tells me. It's been shown that mice living under standard laboratory conditions eat more and grow bigger than their country cousins. At the National Institute on Aging, as at every major research center, the animals are grouped in plastic cages the size of large shoeboxes, topped with a wire lid and a food hopper that's never empty of pellets. This form of husbandry, known as ad libitum feeding, is cheap and convenient since animal technicians need only check the hoppers from time to time to make sure they haven’t run dry. Without toys or exercise wheels to distract them, the mice are left with nothing to do but eat and sleep—and then eat some more.

(My emphasis)

The mice he had bred were perfect stand in for Americans . Contrary to the thesis in TFA, these critters are
the perfect research subject.

Of course, the article then conflated the issue completely. But he's got a gold mine here.

Much ado about nothing

[geekoid]

", but they can also be different from the reactions a human has"
yeah, no shit. everyone knows that. Mice is just a testing step. It a great way to look at cell interactions, and responce.

"may be placing unseen constraints on what we know and learn."
no, they aren't. We know the constraints. If you find a way to test without those constraints, by all means let researchers know.

" a species that doesn't seem to get cancer on its own, "
can't wait to learn why, might help us all.

Look, having a mouse that gets a specific type of cancer at 3 months, 99.999% of the time(it's actually higher) is very valuable for research.

TO sume up,

Using mice isn't absolutely perfect for all case, and some species have interesting properties we can learn from.

""The inbred, factory-farmed rodents in use today—raised by the millions in germ-free barrier rooms, overfed and understimulated and in some cases pumped through with antibiotics—"
What a bunch of alarmist propaganda. I mean, if you don't have facts or knowledge on your side,. use alarmists word and FUD.

oh and this bit of crap:

""This is important for scientists," says Mattson, "but they don't think about it at all.""
What? every scientist I have ever talked to that does lab work is aware of this. Is this Matterson guy selling something? Clearly he is qualified, but every time I here a scientist talk about lab work with mice, this very subject comes up, and they always point out that just because it happens in mice doesn't mean we will see any affect on people.

And the graph. OMG look at how much more study on rats there is! ahhh!!

well, they are cheaper AND are a first step. So of course they are used. When there is no effect, no other animal is tests so of course it will show fewer of other type of animal is used later in the process.

OTOH, maybe only the scientist I listen to and talk to mention this, and none other do.

The man has the cred:
http://www.grc.nia.nih.gov/branches/irp/mmattson.htm

But I am confused on his statements on mice as if no one knows about those issues.
I wonder how much the reported misrepresented what he said?

Re:Yes, of course they're constraining what we lea

[MozeeToby]

If you judge by the article she's bucking the system by looking at naked mole rats for an explanation for why they don't get cancer. The irony is that if she succeeds in finding the explanation and isolating it out to a treatment protocol the first thing she'll do is give some mice cancer and see if the treatment works on them (ok, maybe the second if the mechanism can be disabled in the naked mole rat somehow). That isn't bucking the system, it's being at a different stage in your research; she's still forming a hypothesis as to what an effective treatment could be. Once she has that she'll move right over to the sterile, genetically identical, and above all biologically consistent lab mice and rats. Why? Because that is how you perform replicatable animal trials. If someone halfway around the world can't replicate your results your experiment isn't worth much, that's why we have millions of essentially cloned lab mice in the first place.

Common knowledge

[houghi]

Research causes cancer in mice.

Re:Yes, of course they're constraining what we lea

[gestalt_n_pepper]

It *can't* be worse than chemo.