Human Immune System Research Using Mouse Models Falls Short

[Gemini]

http://www.pnas.org/content/early/2013/02/07/1222878110.abstract

Large-scale genomic study reveals the human and mouse immune system are dissimilar contrary to conventional thinking.

Yesterday's NY Times: "Researchers report evidence the mouse model has been totally misleading for at least three major killers--sepsis, burns and trauma. As a result, years and billions of dollars have been wasted following false leads. The study's findings do not mean that mice are useless models for all human diseases. But its authors said, they do raise troubling questions about diseases like the ones in the study that involve the immune system, including cancer and heart disease."

Mouse models are widely used for drug development & testing and to study disease pathogenesis.

 

[peggy-sue]

And this is just all part and parcel of the normal scientific process.
We learn from it.
And now we have the knowledge that the mouse immune system is not similar enough to the human one to be of use, some other model will need to be found - probably a far more expensive one than mice.
We did not know that before. Now we can try to move on from it.

 

[Gemini]

And this is just all part and parcel of the normal scientific process.
We learn from it.
And now we have the knowledge that the mouse immune system is not similar enough to the human one to be of use, some other model will need to be found - probably a far more expensive one than mice.
We did not know that before. Now we can try to move on from it.

Peggy-Sue,

The good news--science is "self-correcting."
Not so good, "politics" of scientific publishing i.e., Science and Nature rejected this paper before PNAS accepted it.

Lead author Ronald Davis, Stanford University: "Reviewers did not point out scientific errors. Instead he said the most common response was 'It has to be wrong. I don't know why it is wrong, but it has to be wrong.'"

Alternatively a sepsis expert's reaction: "When I read the paper, I was stunned by just how bad the mouse data are. It's just amazing--no correlation at all. These data are so persuasive and so robust that I think funding agencies are going to take note. Until now to get funding, you had to propose experiments using the mouse model."

ME/CFS implications: Open Medicine Institute's Top Ten Research Projects do not mention animal models.

 

[SOC]

This can't be good news for us. If science has to find a new animal model for immune disorders it could be many years before there's a good animal model of ME/CFS and it will almost certainly be more expensive than mice. We'll be stuck waiting for solid treatment research for all that time.

 

[Waverunner]

This is bad news. Most of the scientific breakthroughs regarding health are based on studies with mice. In my eyes we always come back to the root problem, that government prevents a free market and drug development. People and patients should be free to decide, if they take a newly developed compound or not and they should not be forced to wait an average of 15 years. The best way to find out, if a new drug works for humans, is to test it with humans. Phase I trials are mostly conducted with healthy participants. In this case I would require the drug developer and his team to take the drug. After that, the patient should be free to decide.

 

[Gemini]

The best way to find out, if a new drug works for humans, is to test it with humans.

I agree especially now.

Another way to look at it no ME/CFS mouse model albeit we wanted one for many years may be better than having one that produced highly misleading scientific results.

 

[heapsreal]

They can still study live humans and there immune systems as long as they dont need cut us open. There is blood, tissue biopsis, and spinal fluid, probably more??

 

[barbc56]

This can't be good news for us. If science has to find a new animal model for immune disorders it could be many years before there's a good animal model of ME/CFS and it will almost certainly be more expensive than mice. We'll be stuck waiting for solid treatment research for all that time.

Unfortunately, this is probably true but we have to ask ourselves if we want medical knowledge based on incorrect science, now, or wait until science can back treatments.

Many of us can't wait but sometimes we just don't have a choice but to do that.

Barb

 

[Ecoclimber]

There is a more thorough discourse on the MS Blog at Barts and the London School of Medicine and Denistry. I believe Klimas was thinking of developing a mouse model for ME/CFS.

Failure to Translate. Another Nail in the Coffin

http://multiple-sclerosis-research.blogspot.co.uk/2013/02/failure-to-translate-another-nail-in.html

The dose of bactrial toxin used in most published in vivo studies in mice is 1–25 mg/kg, which approximates the dose that causes death in half of the mice. This dose is 1000–10,000 times the dose required to induce severe disease with shock in humans and ∼1,000,000 times the dose used in carefully controlled study environments in which human volunteers are challenged with highly characterized preparations of 2–4 ng/kg bacterial toxin to elicit fever and cytokines, as used in this study. A direct comparison between the species for live bacteria is obviously not possible. However, in most mouse models, it is necessary to administer high doses of live bacteria to induce illness (usually 10billion) and whetherthis difference in sensitivity is the reason that severe infection in mice has little resemblance to sepsis syndrome in humans remains to be established by seems plausible. Guinea pigs are much more sensitive to the effects of bacterial toxin. I wonder if they are more human like?

Eco

 

[MeSci]

Animal 'models' of human conditions are almost invariably misleading. These differences have been my specialist area, and the more papers I have read on the subject the more I am convinced that this practice harms humans as well as the unfortunate animals subjected to so much cruelty.

There is a wide range of methods for studying humans without harming them - cell culture, computer simulation, reproductions of multi-organ systems, using clinical data from human patients (most of this goes to waste), scanning, etc., etc.

A lot of research is rubbish, I'm afraid. I wouldn't pin your hopes on a future wonder drug, and certainly not on any animal model. Very few drugs developed now are safe and effective. The older ones tend to be better, and new uses are constantly being found for them.

But the solution(s) for most of us may be more natural ones. I would like to see immediate clinical trials of diets and supplements that have shown promise in past research, rather than the papers just lying around unused, which is what happens with most such research, presumably because there is no financial incentive for anyone to push for its implementation.