Mice and Diabetes Research

mouse

Yesterday, Childhood Obesity News looked at the reportage done by Daniel Engber for Slate, on the subject of lab mice. An experiment is designed to compare the effects of an environment, regime, or chemical upon a group of mice, whose reactions are then compared to those of a group of mice that supposedly have not been tampered with. But neuroscientist Mark Mattson and a few other researchers are concerned about the wisdom of conducting studies in this way.

The control animals are presumed to be “normal’ but actually they are far from it. They are a standardized, manufactured product, and in their breeding and raising quite a lot has already been done to them. They laze around all day and eat on demand. They don’t resemble their feral relatives, and their decadent lifestyle would not be tolerated in the natural world. Engber says:

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.

But it gets worse, and here is the angle relevant to childhood obesity and National Diabetes Month. The journalist goes on to say:

Standard lab rats and lab mice are insulin-resistant, hypertensive, and short-lived… Having unlimited access to food makes the animals prone to cancer, type-2 diabetes, and renal failure; it alters their gene expression in substantial ways; and it leads to cognitive decline. And there’s reason to believe that ragged and rundown rodents will respond differently — abnormally, even — to experimental drugs.

Those are the normal lab mice, the supposedly neutral little assembly-line canvasses on which experimental results are painted. But they are not blank slates, Mattson and some of his colleagues allege. They ask how it can be possible to discover therapeutic interventions for illnesses when both the subjects and the control animals are already sick. How can diabetes be studied in a group of animals with impaired internal organs, who are already pre-diabetic?

The journalist also relates the interesting story of how Mattson got onto the track of this problem in the first place. He was seeking a glutamate-blocker for the benefit of stroke victims, which theoretically should have worked on humans. Twenty years later, he proved that his original idea had been right. The reason:

All the original test-animals were chubby. If there’s something about the brain of an obese, sedentary rodent that amplifies the effects of a glutamate-blocker, that would explain why the drugs worked for a population of lab animals but not in the more diverse set of human patients.

An auxiliary problem arises from using a single lab animal across the board to study every disease. Why only mice and rats, out of all the possibilities? There are many reasons, and Engber goes into them, and concludes that in biomedicine, basing everything on a monoculture can be dangerous. To back it up, he calls in another authority, Clif Barry, one of the government’s top tuberculosis researchers. Barry is quoted:

If we look to the mouse to model every aspect of the disease for man, and to model cures, we’re just wasting our time… The vast majority of the money that we spend in clinical trials based on mouse data is completely wasted.

Strong words, and maybe worth looking into.

Your responses and feedback are welcome!

Source: “The Mouse Trap,” Slate, 11/16/11
Image by Dullhunk (Duncan Hull).

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About Dr. Robert A. Pretlow

Dr. Robert A. Pretlow is a pediatrician and childhood obesity specialist. He has been researching and spreading awareness on the childhood obesity epidemic in the US for more than a decade.
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Presentations

Dr. Pretlow’s invited presentation at the American Society of Animal Science 2020 Conference
What’s Causing Obesity in Companion Animals and What Can We Do About It

Dr. Pretlow’s invited presentation at the World Obesity Federation 2019 Conference:
Food/Eating Addiction and the Displacement Mechanism

Dr. Pretlow’s Multi-Center Clinical Trial Kick-off Speech 2018:
Obesity: Tackling the Root Cause

Dr. Pretlow’s 2017 Workshop on
Treatment of Obesity Using the Addiction Model

Dr. Pretlow’s invited presentation for
TEC and UNC 2016

Dr. Pretlow’s invited presentation at the 2015 Obesity Summit in London, UK.

Dr. Pretlow’s invited keynote at the 2014 European Childhood Obesity Group Congress in Salzburg, Austria.

Dr. Pretlow’s presentation at the 2013 European Congress on Obesity in Liverpool, UK.

Dr. Pretlow’s presentation at the 2011 International Conference on Childhood Obesity in Lisbon, Portugal.

Dr. Pretlow’s presentation at the 2010 Uniting Against Childhood Obesity Conference in Houston, TX.

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