Drug Testing In Mice May Be a Waste of Time, Researchers Warn 148
An anonymous reader writes "A group of researchers including Dr. H. Shaw Warren of Mass. General Hospital and Stanford genomics researcher Ronald W. Davis have published a paper challenging the effectiveness of the 'mouse model' as a basis for medical research, based on a decade-long study involving 39 doctors and scientists across the country. In clinical studies of sepsis (a severe inflammatory disorder caused by the immune system's abnormal response to a pathogen), trauma, and burns, the researchers found that certain drugs triggered completely different genetic responses in mice compared with humans. The Warren-Davis paper was rejected by both Science and Nature before its acceptance by the Proceedings of the National Academy of Science, perhaps suggesting the degree to which the 'mouse model' has become entrenched within the medical research community. Ninety five percent of the laboratory animals used in research are mice or rats. Mice in particular are ideal subjects for research: they are cheap to obtain and house, easy to handle, and share at least 80 percent of their genes with humans (by some reckoning, closer to 99 percent). Over the past twenty five years, powerful methods of genetically engineering mice by 'knocking out' individual genes have become widely adopted, so that use of mice for drug testing prior to human clinical trials has become standard procedure."
Of course it is (Score:5, Funny)
A mouse can't even roll a joint, much less handle a lighter. Nor do they make syringes that small.
Why was anyone suspecting their mice of using drugs in the first place?
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A mouse can't even roll a joint, much less handle a lighter.
This is why mice use vaporizers.
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No Mod points left or this would have one from me.
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Why was anyone suspecting their mice of using drugs in the first place?
It's because of that mouse that admitted it all in an interview with Oprah.
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A mouse can't even roll a joint, much less handle a lighter. Nor do they make syringes that small.
Why was anyone suspecting their mice of using drugs in the first place?
I work for a background screening and drug testing company. Now ^^^ that's ^^^ funny, right there!
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Re:Mice welfare (Score:5, Insightful)
Sorry but like Florida just showed you spend more money on that drug testing program than you save on kicking them out of the system. Plus it is unfair to the mouselets, they did not choose their parents.
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I mean, maybe thats YOUR takeaway. You say it like its such a bad thing...when the program was a resounding success.
The positive takeaway is this.... if you are governor, you can make gobs of money by funneling state contracts to your own company? Why even bother looking at outcomes when they are clearly not the major decision indfluencer.
As long as his pockets got lined....and they did.... why does something as niggling as cost effectiveness matter? It wasn't a money saving measure, that would have defeate
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You are not taking into account my anti-drug stone that I bought right before they started this thing.
People who do those sorts of drugs are not more responsible when they are deprived of them and never will take better care of their kids. They will just drink or use hard drugs that do not stay in the system very long. More over people doing addictive drugs do not stop for a drug test, if they could they would not be drug addicts in the first place.
Rejection (Score:5, Insightful)
>> The Warren-Davis paper was rejected by both Science and Nature before its acceptance by the Proceedings of the National Academy of Science, perhaps suggesting the degree to which the 'mouse model' has become entrenched within the medical research community.
Or maybe it was rejected because it isn't a good paper? Just a thought.
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Re:Rejection (Score:5, Informative)
Science's and Nature's rejection rates are very high, there are just this many articles they can publish every week, 15 to 20 for Nature. Almost every paper gets rejected on the first draft, good ones are encouraged to resubmit after revisions. It can take a few years to get your paper into one of these journals, that's what makes the papers of highest quality -- not to be confused with "certainly true", even high quality research can turn out to be wrong.
The leftovers get resubmitted to lower-ranked journals; that's what you usually do if you want to submit something, you aim for a high ranked journal and hope to get in, if not you revise and resubmit or submit to another journal.
Re:Rejection or Science Nature (Score:4, Insightful)
Exactly. I've worked with some labs that got original biological and biochemical papers published in both Science and Nature, and it's very hard to get in those. Even with new biochemistry or new biology.
Try publishing a paper on methodology of statistical inference. That's not easy at all.
Re:Rejection or Science Nature (Score:5, Interesting)
Its very hard to publish there, but the quality of publications is not that high, possibly even lower than elsewhere if you measure by false positive rate. There is a mass failure to understand the importance of the assumptions underlying statistical inference (as you mentioned), as well as the importance of completely reporting your methods and data so that it is possible for others to intelligently draw their own inferences and replicate your work. In short, those journals have a culture that encourages "sexy" and "conclusive" results at the expense of the fundamental basis for successful science that we learn in gradeschool.
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That, plus you need to have some sexy pictures. Not sure why, but it helps increase acceptance.
OK, you might not think a picture of beta sheets is sexy, but they do.
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Aren't there some quotas for printed pages? If there are many good candidates, what do they do with the leftovers? Those don't necessarily have to be bad papers.
My understanding is that researchers shop them around, and that the large number of available journals, some more prestigious than others, and some more narrowly focused than others, is supposed to handle that(there has been some concern, especially regarding papers with negative results, that it may not do so optimally in some respects). If a paper is rejected from the very high prestige, relatively broad journals, it can work down the list toward journals more narrowly focused on its exact topic, and/or w
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Or more likely it was rejected because it was not a true Scotsman.
Re:Rejection (Score:4, Funny)
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Also I must add that the summary takes liberty with the point of "challenging the effectiveness of the mouse model as basis for medical research." Clearly mice share some physiology and developmental characteristics with humans
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But PNAS is dodgy... Was it really peer-reviewed or was it invited?
It is true however that Science and Nature will publish on the grounds of sexyness above all consideration, sometimes at the expense of being actually correct. Also, there is a tendency to discount papers showing a mechanism in humans which is already known in mouse, despite the fact that there was no garantee of commonality and the fact that experiments using human cells are much harder.
I guess there is some underlying truth to the fact tha
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PNAS isn't 'dodgy', but it has a different twist. If you are a member of the NAS (not easy to do) you have a bit of influence - certainly not all that much - to get people to review the paper. It serves as a bit of an old boys club, but it also serves as an additional foil to the insular tendencies of Nature and Science. To be fair, there is so much published that it's hard to pick the winners all of the time. It's not even necessary. Good research tends to get out, maybe not as fast as some would like
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Oh, no, if you are a member you can get paper passed pretty much without review. But I agree that godd research tends to get out, and I certainly have no particular sympathy for the hype-oriented selection process of Nature and Science.
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> I guess there is some underlying truth to the fact that no-one wants too much questionning of the
> usage of mouse models. The alternatives are much farther away from humans, or emotionally
> difficult to work with (cat models are great I hear, but unsurprisingly no one wants to do to cats what
> is commonly done to mice...)
I personally know people who have done this sort of work with dogs. I have also worked in (not as a lab tech or scientist, but in the lab and around the people who were) labs
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>> The Warren-Davis paper was rejected by both Science and Nature before its acceptance by the Proceedings of the National Academy of Science, perhaps suggesting the degree to which the 'mouse model' has become entrenched within the medical research community.
Or maybe it was rejected because it isn't a good paper? Just a thought.
I would say it is a very good paper, but Science and Nature have somewhat higher benchmark for accepting papers: the paper has to be truly innovative and to open new directions for research. The PNAS paper that the post links to is very well research and convincingly shows how bad the mouse models for sepsis are in representing the human disease. Well, we know that animal models have quirks and some are really bad, and some are really good. So this is one more addition to the first list, which is very impo
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The benchmark is not "higher". It could be said to be higher if the papers needed to meet proper scientific criteria as well as being truly innovative. The benchmark is different. The perceived "innovation" aspect is used at the expense of other qualities of good scientific reports (ie using statistics properly and reporting all your methods and data).
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The paper was torpedoed by Big Mice.
They stand to lose billions I bet if they stop testing on mice.
Cheating? (Score:2)
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Are they using synthetic urine to pass their tests now, too?
Have to. Their pH is insane!
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Are they using synthetic urine to pass their tests now, too?
No, but they have a hard time maintaining a realistic temperature that doesn't trigger alarms. Borrowed is good as long as its not from a hamster.
How many (Score:5, Insightful)
I often wonder how many drugs we reject long before human trials because some researcher used the wrong animal to test.
Also an obligatory SMBC comic [smbc-comics.com]
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I often wonder how many drugs we reject long before human trials because some researcher used the wrong animal to test.
Also an obligatory SMBC comic [smbc-comics.com]
No kidding.
Trial Drug 1035832B:
Side effects in mice: Congenital defects, swelling of the urethra, kidney failure, liver failure, seizures, heightened blood pressure with occasional heart attacks, loss of vision and motor function, death.
Side effects in Humans: Occasional diarrhea.
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My memory is a little fuzzy on the exact number from when I worked in the industry, but something like 70% of all drugs that pass Phase 1 trials fail in Phase 2 trials. Phase 1 trials are small and test for safety problems, and Phase 2 trials expand to a larger cohort to test for efficacy -- does the drug work. The pharmaceutical industr
Comment removed (Score:5, Interesting)
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rats and mice are around so my cat has something to eat that is not raw chicken
Drug testing on mice (Score:1)
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Is so-called 'objective reality' also a social construct?
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Only to those people who find objective reality gets in the way of the reality they prefer.
If you can convince the rubes that objective reality is just an opinion, you can say anything.
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Only to those people who find objective reality gets in the way of the reality they prefer.
If you can convince the rubes that objective reality is just an opinion, you can have any job in education you wish.
Tidied that up just a hair. :)
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Is so-called 'objective reality' also a social construct?
The parent comment is why teachers want you to "show your work", objective reality is where teachers lose consciousness with a bottle of booze in front of the television, or, you know, just give you a C- for the hell of it because they TOTALLY understood your non-linear thought. ;)
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Medical research or research to justify social policy is meaningless. The outcome is determined before the experiments begin.
You just mixed together medical research, which is why lots of things don't kill you anymore, with a fake category.
TFS... (Score:3)
So, any word on how we managed to get from 'researchers identify class of conditions for which mice are an unexpectedly lousy model' to 'drug testing in mice may be a waste of time'?
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So, any word on how we managed to get from 'researchers identify class of conditions for which mice are an unexpectedly lousy model' to 'drug testing in mice may be a waste of time'?
I blame the cat and dog lobbies. They never liked mice.
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Well, one of the linked articles says:
It may well be a case of either the subm
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The study certainly does suggest that mice(and some mouse findings) are much more troublesome than previously suspected. On the plus side, the methods that they used to establish that there was a real problem with mice(the examination of gene expression under the various conditions) seem like they might also be broadly applicable for examining the problem of what is and isn't a good model organism for a given problem...
Obviously, in an ideal world further research would confirm that you are on the right tra
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So, any word on how we managed to get from 'researchers identify class of conditions for which mice are an unexpectedly lousy model' to 'drug testing in mice may be a waste of time'?
Honestly, that sounds like another way of saying "we don't know what to effing do now. We have no test Humans!"
You know, capital punishment should include the obligatory 'island of murder/rape/pedophile criminals', but instead of serving time ad nauseam, you get to be randomly picked for drug trials.
Better than the alternatives (Score:2)
Anyone volunteering, you've clearly got some problems and would be unsuitable to study anyway. And forcing people to participate in the research and letting them
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Anyone paying any attention to biomedical research knows that if some amazing cure is demonstrated in mice, it will likely never be heard of again since it didn't pan out.
OTOH, if it's not demonstrated in mice, it's even more likely never to be heard of again. ;)
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it's also important to realize that drug testing in mice IS necessary.
See that is the part I don't understand... Why must it be mice? And how many drugs have a negligible effect in mice, but would work well in humans, or have a toxic effect in mice, but only minor side effects in humans? These days the drug would be overlooked or rejected. Humans are not mice... How often are we overlooking good drugs because of bad animal models?
I get the point, we need to protect humans first, and not be doing stupid/dangerous tests on humans just for the sake of science. I think, for m
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See that is the part I don't understand... Why must it be mice?.
Because mice have short life spans, are cheap, are easy to squish between plates to test, and people don't go wonky on you researching on mice.
That's "why".
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Researchers already knew that mice models were far from perfect. Anyone paying any attention to biomedical research knows that if some amazing cure is demonstrated in mice, it will likely never be heard of again since it didn't pan out. It's important to realize if one hadn't already that mice weren't perfect models for humans, but it's also important to realize that drug testing in mice IS necessary.
This isn't directed at you, but I don't understand the logic, and never will, where you can use an animal with a DNA model that is different from the animal that will be using the drug. Sure, it can show some serious negative effects or positive ones, but the DNA difference can also give you a laboratory set where one animal has 130 side effects (including death or worse), and the other has zero or one.
Chemistry is a little more complicated with animals than it is with test tubes.
From the comments on TFA: (Score:5, Informative)
As a 13 year veteran of academic science, and a 3 year veteran of a pharmaceutical company, I can personally attest that scientists disagreeing on matters of great significance, difficulty publishing publishing what one believes to be important work, exasperation at peer review, and unending questions about the ability to translate findings in mice to humans are everyday concerns. I know of no scientist who has not faced criticism from their peers, despite how well respected they may be. I know of no scientist who has not had their papers rejected only to complain that the reviewers just didn't "get it." And contrary to what this article may assert, questions about how well mouse models recapitulate human disease are frequent topics of conversation. To read this article one would think that the scientific enterprise had never considered the notion that mice and humans are not equivalent. What a complete misdirection from reality.
This article takes the tone of a courageous and noble researcher struggling valiantly against an entrenched evil empire intent on stifling dissent. While this may be a good approach for a movie, it should have no place in serious discourse from a reputable organization like the NYT. A pragmatic discussion of the research and implications are in order, not the quasi-sensationalist man vs empire approach taken here.
It's really important to remember this, because people just eat the "courageous and noble researcher struggling valiantly against an entrenched evil empire intent on stifling dissent" narrative up, and it's hardly ever the way things actually work. Most important discoveries in science, positive or negative, have been building for years in the field--with many, many people on both (or all, as the case may be) sides of the debate--before they ever reach the public eye.
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Sadly, the New York Times isn't all that much better at science reporting than other general newspapers. It's better than tabloid journals, of course, but they're still scanning science with an eye to making Big Exciting News rather than the incremental work that makes up the vast majority of science. Which makes them prone to blowing things out of proportion on the slow science news days (i.e. most days).
Honestly, when it comes to science stories, I wait until I see it in a dedicated science source such as
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it should have no place in serious discourse from a reputable organization like the NYT.
BWAHAHAHAHAHAHAHAHA!!!!!!!!!!!!!!!!!
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Without this narrative, there wouldn't be hundreds of slashdotters reading this.
[sigh] You're probably right.
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Without this narrative, there wouldn't be hundreds of slashdotters reading this. This is a great non-story... I think everyone knows that there isn't a high correlation of what works in mice / works in humans and vice versa, but it's the best we have. It's not like you can just give people random drugs and see if it kills them.
You *CAN*, scientifically. You just can't morally. Death penalty should be expanded upon a hair, IMHO. Not to 'go Hitler' or anything, but hey.
I agree but there are reasons why we use mice (Score:3, Interesting)
1. Mice have no lobby.
2. Mice have shorter lifespans.
3. You freak out every time we use chimps or human analogues in the simian world.
4. Mice are easier to squish between plates to measure changes, especially when we use flourescent tags on the meds or target we're looking at, so we don't have to cut them up to find out what's going on.
(yes, my point 4 is really what happens - we used to cut them up before we figured out how to make them glow with jellyfish gene tags - and once you cut open the brain, it's game over)
5. Cheap, 6. Uniform, 7. Everywhere (Score:2)
Mice are cheap, ubiquitous, readily available, and have very low genetic variation between samples (unless variation is purposefully induced.)
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A lot of the cheap part is they are small. If there was a variant of human that didn't have intelligence and was small and had a short life span we'd probably use that, if we're looking at medical drug experiments.
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Your branching off into a discussion that's teeming with ethical concerns. In fact we have the ability right now to make "human" mice, or in other words mice with human organs and genes. These mice don't exist (in wide use) right now because of the ethical concerns.
You might find it silly, but there are people that don't even want mice with human organs because of the ethical and moral (read religious) concerns of creating such an organism.
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1. Mice have no lobby.
Oh, God. Don't let animal activists read this or even mice won't be valid test subjects anymore.
Wait.... Keep talking. ;)
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Don't let Big Squeek hear you saying they've got no lobby!
Well, there are providers of mice, and I presume they have some kind of lobby organization, but when I used to work on cancer research, I don't remember it affected purchasing much. However, I refer more to the non-scientist non-corporate lobbying. Animal and human medical research varies greatly depending on which country, state, or county one is in.
Face it, most people aren't pro-mouse, and identify more with dogs, cats, monkeys, and pigs - all of which are eaten by humans at various places around the wor
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Plus let's not forget this: World's Scientists Admit They Just Don't Like Mice. [theonion.com]
"As a man of science, I deal with facts, and the fact is that mice are gross," said Dr. Douglas White, chair of the Oxford biogenetics department and lifelong mouse-hater. "They're squirmy, scurrying little vermin, and they make my skin crawl. I speak for all of my assembled colleagues when I say that the horrible little things deserve the worst we can dish out."
The headline is misleading (Score:5, Informative)
The Researchers did not warn that "Drug Testing in Mice May Be a Waste of Time"; they suggested that Drug testing for drugs for sepsis, trauma, and burns may be a waste of time. The discovery was that the process that induces death in humans for those problems (capillary leakage leading to uncontrollable blood pressure loss) works differently in mice vs. humans, and therefore, for those specific conditions, the mouse model is of limited usefulness. The discovery was NOT: "Drug tests in mice are pointless."
It has been known for some time that the mouse model is not universally applicable; it's finding those times when it's not that is tricky. We still use mice because they are much cheaper than the alternatives... using the alternatives when not necessary would drive up research costs.
In many cases, it IS useful (Score:2)
In many cases the mouse model IS quite useful.
To paraphrase the famous by Churchill saying about government: "It has been said that the mouse model is worst way to perform easy, cheap, repeatable medical tests. Except for all others that have been tried."
The researchers that use mice in experiments are not blithering idiots. They have indeed gotten the memo that mice are not people. But they also have research to perform, a limited budget to perform it with, and no viable alternative.
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It depends just how bad a model it is. I don't believe there is evidence to support it for most rodent research, but it is possible that it would be better if those researchers simply had their brainpower and funding put to use in a different field rather than trying to force the issue with mouse biomedical research.
The chosen approach appears to be just do a bunch of mouse research and see how it turns out after decades of this without verifying whether the model is useful or not to begin with. Notably, th
Come on, please. (Score:3)
TFA doesn't say what the headline says it does.
Even if did say that, as someone working in medical research, I can vouch for the fact that the first question to follow any claims of something working in an animal model is "so what about in humans". It's a running joke that we can cure every disease known to man - in mice. But that's what a model is: a controlled, repeatable, system in which to roughly test hypothesis before moving onto the real subject.
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That joke is there because the "cures" are most often based on faulty statistical inference. A closer look at much of the data will reveal the cure did not exist for mice in the first place, the results were just much more likely to occur by chance than conveyed by the literature. The issue of mice not being completely analogous to humans is an issue faced by researchers but it is being used to hide failure to correctly report and interpret the results of studies (systemic incompetence). All the evidence po
Radiate them first (Score:2)
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Techno mouse... (Score:1)
Other problems (Score:2)
The problem with this? I could NOT get the rats to self administer any drugs.
That really doesn't matter when you're slicing brains to map out pathways, however it is telling us something more important. Social animals that socialize don't take drugs.
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That's called extrapolating beyond the data. If you go to a bar, you'll find that some social animals take drugs while socializing with great consistency.
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There are studies both with rats and humans that point this out. I'm just mentionning my experience because even having read the studies I didn't quite believe it.
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Social animals that socialize don't take drugs.
Explain hippies.
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Ever meet an ex-hippie? They'll either close way back up again or they'll finally be in/a place where the fear of opening up isn't there anymore. Just/think of how sad it is that saying "i love you" is almost taboo in most societies and cultures.
cheap and easy (Score:2)
Mouse testing is cheap and easy. Even if it doesn't work half the time and differs significantly from human reactions, it's still worth doing because you learn quite a bit from it. The only thing that would be unfortunate is if you reject a safe and effective drug prematurely based on a mouse model, but I'd guess that's pretty rare.
In other news (Score:1)
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Like you said - no reason to test the mouse-toxic drugs on human beings before chimpanzees. I'm guessing you wouldn't have to match the sample size, or kill the same amount of chimpanzees, compared with testing on mice.
I'm confused with the resistance on drug testing in animals. Like Bastiat said, you always have to consider the "unseen." If you aren't drug testing on animals, you are forgoing the knowledge received from said testing. Would you stop killing thousands of mice per day via drug testing if it
Cat got your tongue? (Score:1)
Last time I checked, drug testing on(in?) mice wasn't the only step in passing a drug through the FDA. Actually, I haven't done much checking, but I do believe big pharma has to perform clinical trials on humans before giving the "OK GO" to manufacture & mass distribute drugs for general public
From a pharmacology perspective, it would be a good thing to know that mice react differently from humans. More importantly - how do they differ, and for what reasons? For instance - maybe some drugs have severe s
This is potentially very big (Score:1)
Mouse Olympics (Score:2)
I am beginning to lose hope in mice models (Score:2)
We have cured Alzheimers in transgenic model mice at least thrice to my last count. Not one of these drugs have shown significant benefits in Phase III trials.
Change species. (Score:2)
Do the testing on little monkeys.
http://4.bp.blogspot.com/-nw4xUBJp5as/T_X7saOqmDI/AAAAAAAAKnA/Ev-PfLmgEm0/s1600/chimplips.jpeg [blogspot.com]
9 out of 10 mice agree... (Score:2)
Re:Peer review (Score:5, Insightful)
Being rejected by Science and Nature might also be indicative of being bad science. Not reading the report yet, the options seem to be intellectual dishonesty from some of the most respected sources of science, or the mice findings are fundamentally flawed. On the outset, I think being rejected by big names in science is usually pretty telling.
PNAS isn't exactly some chickenshit vanity press...
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PNAS isn't exactly some chickenshit vanity press...
No, it's a bodily organ which urine is disposed through. Also used for sexual purposes.
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Almost everything gets rejected by Nature and Science. The article notes Science only accepts about 7% of the papers it receives.
Accepts, or 7% it bothers to mention that it accepts? Hey, I'm just being scientific. Har. :)
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Not reading the report yet, the options seem to be intellectual dishonesty from some of the most respected sources of science
Unfortunately, I've seen enough scandals involving 'respected sources' that I don't believe it outside the realm of possibility.
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Was it rejected by the reviewers or the editor? A rejection by the editor might mean that your paper is really trivially shitty, but most likely that it is not sexy enough, or not right in the hype of the moment.
A rejection by the reviewers might mean that they were unconvincing/wrong.
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Even though I would say use patent trolls as the new mice, how do you try out potentially lethal compounds in humans with good conscience (that is humans who are not patent trolls?)
/quote
The concern lies with proper identification of patent trolls. First, we start with lawyers.
Wait, never mind, that's good enough.
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Even though I would say use patent trolls as the new mice, how do you try out potentially lethal compounds in humans with good conscience (that is humans who are not patent trolls?)
How about suicidal ones that want to die and have been reasoned with repeatedly to no avail? Wait, that makes too much sense. Disregard.