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Drug Testing In Mice May Be a Waste of Time, Researchers Warn

Soulskill posted about a year and a half ago | from the research-sponsored-by-mice dept.

Medicine 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."

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Of course it is (5, Funny)

h4rr4r (612664) | about a year and a half ago | (#42873661)

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?

Mice welfare (-1)

Anonymous Coward | about a year and a half ago | (#42873789)

Sure, but if they're going to go on mice welfare, shouldn't we at least make sure they're not a junkie first?

Re:Mice welfare (4, Insightful)

h4rr4r (612664) | about a year and a half ago | (#42873829)

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.

Re:Mice welfare (1)

TheCarp (96830) | about a year and a half ago | (#42874849)

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 defeated the purpose.

Yeah! (0)

Anonymous Coward | about a year and a half ago | (#42873865)

And the mice DO talk among themselves and know ALL the tricks to beat these tests! And ya know, if the mice are doing their jobs well, what difference does it make what drugs they're taking! Really.

Running on that wheel day in, day out, and day in and day out is stressful! And the hipocracy of society! Why no one says anyting about the mice who drink alcohol to deal with the stresses of mice!

Fuck'n a, man!

What mice do in the privacy of their own cage is none of anyone's business!

Re:Of course it is (0)

Anonymous Coward | about a year and a half ago | (#42874007)

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?

Best internet snark of the day. I just had to acknowledge, thank you.

Re:Of course it is (1)

WillAffleckUW (858324) | about a year and a half ago | (#42874487)

A mouse can't even roll a joint, much less handle a lighter.

This is why mice use vaporizers.

Re:Of course it is (1)

BRGeek (2734365) | about a year and a half ago | (#42874555)

No Mod points left or this would have one from me.

Re:Of course it is (0)

Anonymous Coward | about a year and a half ago | (#42874651)

they actually have done tests on mice with regular drugs. fun shit to watch.

Re:Of course it is (1)

rwyoder (759998) | about a year and a half ago | (#42874661)

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.

Re:Of course it is (-1, Offtopic)

ruyagatu (2839505) | about a year and a half ago | (#42874779)

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Re:Of course it is (-1, Offtopic)

Pope (17780) | about a year and a half ago | (#42874891)

Nice spam there, jackass.

Re:Of course it is (2)

FlopEJoe (784551) | about a year and a half ago | (#42874781)

Plus the tests were culturally biased against inner city mice.

Re:Of course it is (1)

poofmeisterp (650750) | about a year and a half ago | (#42874881)

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!

Re:Of course it is (1)

SpaceLifeForm (228190) | about a year and a half ago | (#42875223)

Because they were hanging out in the dead ends in the maze.

Rejection (5, Insightful)

Anonymous Coward | about a year and a half ago | (#42873671)

>> 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.

Re:Rejection (1)

K. S. Kyosuke (729550) | about a year and a half ago | (#42873793)

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.

Re:Rejection (5, Informative)

Silas is back (765580) | about a year and a half ago | (#42873995)

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 (4, Insightful)

WillAffleckUW (858324) | about a year and a half ago | (#42874507)

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 (4, Interesting)

repapetilto (1219852) | about a year and a half ago | (#42875075)

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.

Re:Rejection or Science Nature (1)

WillAffleckUW (858324) | about a year and a half ago | (#42875141)

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.

Re:Rejection (-1)

Anonymous Coward | about a year and a half ago | (#42875125)

"... 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..."

Except in Climate Science, where the consensus is NEVER wrong, and anyone who believes that it could be is a denier...

Re:Rejection (1)

fuzzyfuzzyfungus (1223518) | about a year and a half ago | (#42874061)

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 work down the list to less selective journals(or other selective journals where their luck is better).

Re:Rejection (1)

Anonymous Coward | about a year and a half ago | (#42873801)

Or more likely it was rejected because it was not a true Scotsman.

Re:Rejection (3, Funny)

moderatorrater (1095745) | about a year and a half ago | (#42874477)

No real scientist would do that.

Re:Rejection (2)

Stem_Cell_Brad (1847248) | about a year and a half ago | (#42873921)

Being rejected by Science and Nature doesn't say much about the paper, other than the editors didn't want it in their magazine. Many possible reasons exist for this. These journals are very picky on the timeliness of the topic of research. Maybe they didn't think it was sexy enough.

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. The article does not support a questioning of all mouse research, but it makes a strong case against using it to study sepsis.

Re:Rejection (1)

SomeKDEUser (1243392) | about a year and a half ago | (#42874649)

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 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...)

Re:Rejection (1)

ColdWetDog (752185) | about a year and a half ago | (#42875349)

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 but it gets out.

This isn't a race.

Re:Rejection (1)

JoeMac (102847) | about a year and a half ago | (#42874585)

I agree. There are many alternative scenarios for rejection that the submitter did not mention, although we must admit the possibility that it was rejected for the suggested reason (community reticence and its significant funding implications). It's hardly a perfect process. PNAS isn't exactly slumming it, though.

Re:Rejection (1)

pesho (843750) | about a year and a half ago | (#42874855)

>> 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 important if you are trying to develop a drug for sepsis, but not really ground braking. Their main conclusion is that we need to do genome wide profiling to compare the responses of the animal models to the responses in humans to make sure they match. I can point you to a half a dozen papers that have come to the same conclusion. My guess is that if they have used the data to develop or suggest a new animal model that can do a better job, the paper would have been enthusiastically accepted in the Science and Nature journals. This is probably what they would do next.

Cheating? (1)

Heed00 (1473203) | about a year and a half ago | (#42873681)

Are they using synthetic urine to pass their tests now, too?

Re:Cheating? (1)

poofmeisterp (650750) | about a year and a half ago | (#42874895)

Are they using synthetic urine to pass their tests now, too?

Have to. Their pH is insane!

Peer review (0, Interesting)

Anonymous Coward | about a year and a half ago | (#42873709)

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.

Re:Peer review (4, Insightful)

fuzzyfuzzyfungus (1223518) | about a year and a half ago | (#42873935)

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...

Re:Peer review (1, Troll)

poofmeisterp (650750) | about a year and a half ago | (#42874915)

PNAS isn't exactly some chickenshit vanity press...

No, it's a bodily organ which urine is disposed through. Also used for sexual purposes.

Re:Peer review (2)

Stem_Cell_Brad (1847248) | about a year and a half ago | (#42873973)

Almost everything gets rejected by Nature and Science. The article notes Science only accepts about 7% of the papers it receives.

Re:Peer review (1)

poofmeisterp (650750) | about a year and a half ago | (#42874935)

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. :)

Re:Peer review (1)

Firethorn (177587) | about a year and a half ago | (#42874025)

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.

Re:Peer review (1)

SomeKDEUser (1243392) | about a year and a half ago | (#42874675)

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.

Broken Link (0)

Anonymous Coward | about a year and a half ago | (#42873719)

Please fix the link for "99 percent". Thanks.

Re:Broken Link (0)

Anonymous Coward | about a year and a half ago | (#42873915)

Sorry, my bad. This is not the same article I saw before I posted, but it's probably just as good:

http://www.genomenewsnetwork.org/articles/12_02/mouse.shtml

Note that the "percentage of common genes" is subject to interpretation.

Nazis (0)

Anonymous Coward | about a year and a half ago | (#42873763)

We need a couple to advance science again it seems... :/

How many (5, Insightful)

canadiannomad (1745008) | about a year and a half ago | (#42873799)

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]

Re:How many (1)

dragon-file (2241656) | about a year and a half ago | (#42873837)

Was about to post the same thing... damn you.

Re:How many (1)

the biologist (1659443) | about a year and a half ago | (#42874127)

Folks have been working to produce inbred lines of pigmy marmoset for use as an improved model for drug testing. It has a 2-3 year life cycle, making it much more useful than typical primate (rhesus monkey, chimpanzee, etc) studies for early stage work like mice are used for. Unfortunately, there's still a lot of work before people will be using them instead of mice.

Re:How many (1)

interkin3tic (1469267) | about a year and a half ago | (#42874167)

Undoubtedly an extremely small fraction of the number of cases in which the opposite happens: drug shows promise in cell culture or mouse trials, has no effect in humans or is toxic.

Re:How many (1)

poofmeisterp (650750) | about a year and a half ago | (#42874979)

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.

Bacteria as a major clue (4, Interesting)

schneidafunk (795759) | about a year and a half ago | (#42873813)

I found this in the article particularly interesting:

Yet there was always one major clue that mice might not really mimic humans in this regard: it is very hard to kill a mouse with a bacterial infection. Mice need a million times more bacteria in their blood than what would kill a person.

“Mice can eat garbage and food that is lying around and is rotten,” Dr. Davis said. “Humans can’t do that. We are too sensitive.”

Re:Bacteria as a major clue (0)

Anonymous Coward | about a year and a half ago | (#42874125)

Do wonder if that applies to alcohol poisoning as well...

Re:Bacteria as a major clue (0)

Anonymous Coward | about a year and a half ago | (#42875145)

Never mind that. When dealing with pests at my old place I learned that mice don't need water. They can get all their moisture from food. That seems like a very alien physiology to me.

BTW, this makes mice harder to eliminate than rats. Rats need to drink. If you can control water, you can control rats. They need to drink. This is why you have fewer rats in California; but they are still here because people irrigate their stupid lawns.

Re:Bacteria as a major clue (0)

Anonymous Coward | about a year and a half ago | (#42875427)

Fewer rats in California, eh? Tell that to a neighbor who leave out food bowls and water dishes to feed every stray animal in sight! The rat and flying rat (aka pigeons) population in the neighborhood has exploded. Plus, the stagnant bowls of water does wonders for mosquitoes.

Drug testing on mice (1)

SBlaire (2839471) | about a year and a half ago | (#42873835)

Medical research or research to justify social policy is meaningless. The outcome is determined before the experiments begin.

Re:Drug testing on mice (1)

fuzzyfuzzyfungus (1223518) | about a year and a half ago | (#42874113)

Is so-called 'objective reality' also a social construct?

Re:Drug testing on mice (1)

gstoddart (321705) | about a year and a half ago | (#42874267)

Is so-called 'objective reality' also a social construct?

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.

Re:Drug testing on mice (1)

poofmeisterp (650750) | about a year and a half ago | (#42875067)

Is so-called 'objective reality' also a social construct?

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. :)

Re:Drug testing on mice (1)

poofmeisterp (650750) | about a year and a half ago | (#42875053)

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. ;)

Re:Drug testing on mice (1)

WillAffleckUW (858324) | about a year and a half ago | (#42874145)

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.

Obligatory (0)

Anonymous Coward | about a year and a half ago | (#42873861)

TFS... (2)

fuzzyfuzzyfungus (1223518) | about a year and a half ago | (#42873989)

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'?

Re:TFS... (1)

Stem_Cell_Brad (1847248) | about a year and a half ago | (#42874117)

I am somewhat confused by that leap of logic, too. I am afraid people will use this interesting work to support the idea that mice are not a good model to study anything human-related. TFS is pointed this direction anyway...

Re:TFS... (1)

WillAffleckUW (858324) | about a year and a half ago | (#42874119)

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.

Re:TFS... (0)

Anonymous Coward | about a year and a half ago | (#42874131)

Hyperbole = eyeballs = ad revenue

Re:TFS... (1)

gstoddart (321705) | about a year and a half ago | (#42874459)

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'?

Well, one of the linked articles says:

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.

It may well be a case of either the submitter or an intermediate press agency adding the words "waste of time". The author didn't reach such a bold conclusion.

Re:TFS... (1)

fuzzyfuzzyfungus (1223518) | about a year and a half ago | (#42875041)

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 track and everything is just wonderful; but by our non-ideal world standards, a paper that hints at how animal models may be more accurately chosen or excluded for given lines of research seems like it could be quite handy.

Re:TFS... (1)

poofmeisterp (650750) | about a year and a half ago | (#42875113)

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 (1)

interkin3tic (1469267) | about a year and a half ago | (#42874015)

Any volunteers to have doctors intentionally give you blood poisoning, then take experimental drugs to cure it? Keep in mind that a quarter of those TREATED for sepsis will die, and naturally you wouldn't be able to take other treatments or that would cloud the results. So you'll die of sepsis, unless the drugs they're testing kills you first.

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 die has its own problems.

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.

Re:Better than the alternatives (2)

Daniel Dvorkin (106857) | about a year and a half ago | (#42874121)

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. ;)

Re:Better than the alternatives (1)

canadiannomad (1745008) | about a year and a half ago | (#42874643)

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 me, this just makes more of a point that suggests we should go in the direction of testing first with human tissues and actual model organs then test in full system creatures like marmosets.
So far, this ted.com talk [ted.com] is the direction I think would benefit us most as a species. Not that I think we are there yet, it definitely looks like the way to go.

Re:Better than the alternatives (1)

WillAffleckUW (858324) | about a year and a half ago | (#42875105)

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".

Re:Better than the alternatives (1)

interkin3tic (1469267) | about a year and a half ago | (#42875209)

Tissue culture is more expensive than mice in many cases. I'm not sure circulatory systems are well modeled in tissue culture yet anyway. So few agencies would be willing to fund it, they'd say "why don't you just do it in mice." At least, before this study.

Re:Better than the alternatives (1)

poofmeisterp (650750) | about a year and a half ago | (#42875159)

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: (4, Informative)

Daniel Dvorkin (106857) | about a year and a half ago | (#42874045)

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.

Re:From the comments on TFA: (0)

Anonymous Coward | about a year and a half ago | (#42874247)

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.

 

Re:From the comments on TFA: (1)

Daniel Dvorkin (106857) | about a year and a half ago | (#42874429)

Without this narrative, there wouldn't be hundreds of slashdotters reading this.

[sigh] You're probably right.

Re:From the comments on TFA: (1)

poofmeisterp (650750) | about a year and a half ago | (#42875175)

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 (3, Interesting)

WillAffleckUW (858324) | about a year and a half ago | (#42874107)

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 (1)

sirwired (27582) | about a year and a half ago | (#42874253)

Mice are cheap, ubiquitous, readily available, and have very low genetic variation between samples (unless variation is purposefully induced.)

Re:5. Cheap, 6. Uniform, 7. Everywhere (1)

WillAffleckUW (858324) | about a year and a half ago | (#42874537)

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.

Re:I agree but there are reasons why we use mice (0)

Anonymous Coward | about a year and a half ago | (#42874281)

Don't let Big Squeek hear you saying they've got no lobby!

Re:I agree but there are reasons why we use mice (1)

WillAffleckUW (858324) | about a year and a half ago | (#42874469)

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 world. The lifespan has a lot more to do with why mice are chosen.

Unless you really want us to test medical dosage levels and new drugs on humans before we test them on animals? Be a lot more dead people that way, of course. One problem is dosage levels are frequently based on volunteers who are veterans, and until recently this was a mostly male category, so data for women and children was not always available, leading to questionable dosage level decisions based on study populations that were too small.

Testing is how we find that a drug that clears out plaque in brain cells might be too effective for some patients, causing their brain cells to leak. Are you sure you want to start with humans first? Then, after testing, you look for drug interactions, dosage levels, and adjust.

That's how research works. And it takes DECADES to complete in humans.

Re:I agree but there are reasons why we use mice (0)

Anonymous Coward | about a year and a half ago | (#42874313)

Update of an old joke.

In response to the Proceedings of NAS paper, some research institutions have decided to use lawyers instead of mice for medical testing. The reasons:

1) While lab mice have sometimes been in short supply, there has never been a shortage of lawyers.
2) There is no danger that the researchers will form emotional bonds with the lawyers.
3) There are some things that mice won't do.

Re:I agree but there are reasons why we use mice (1)

Ol Biscuitbarrel (1859702) | about a year and a half ago | (#42874907)

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."

Re:I agree but there are reasons why we use mice (1)

poofmeisterp (650750) | about a year and a half ago | (#42875191)

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. ;)

Allright then (0)

Anonymous Coward | about a year and a half ago | (#42874123)

Lets use aborted fetuses for drug testing. Harvest the cells, make them immortal by inducing cancer and back again, differentiate to the tissues under test. All this, in the future.

Re:Allright then (0)

Anonymous Coward | about a year and a half ago | (#42875245)

Lets use aborted fetuses for drug testing. Harvest the cells, make them immortal by inducing cancer and back again, differentiate to the tissues under test. All this, in the future.

It will take many, many years before people can use deductive, logical reasoning to that degree. We have a long way to go before we can solve problems quickly and easily with little TRUE negative effects (only emotional). Keep dreaming. Hopefully the thing you die from in time couldn't have been prevented by the use of aborted fetuses for testing.

Alternatives? (0)

Anonymous Coward | about a year and a half ago | (#42874213)

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?)

Re:Alternatives? (1)

WillAffleckUW (858324) | about a year and a half ago | (#42874563)

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.

Re:Alternatives? (1)

poofmeisterp (650750) | about a year and a half ago | (#42875253)

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.

The headline is misleading (4, Informative)

sirwired (27582) | about a year and a half ago | (#42874231)

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.

Come on, please. (2)

mutube (981006) | about a year and a half ago | (#42874351)

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.

Re:Come on, please. (0)

Anonymous Coward | about a year and a half ago | (#42875173)

The positive findings in mice go on for later testing, so I'm not too worried about them. It's the negative findings, which cause researchers to lose interest/funding that scare me. Given, we can't and shouldn't test everything in primates or humans, but I'm sure there are lifesaving drugs we've rejected because they happen to not work well enough in mice.

Re:Come on, please. (0)

Anonymous Coward | about a year and a half ago | (#42875429)

You underestimate how bad the filter for false positives is currently functioning.

Re:Come on, please. (2)

repapetilto (1219852) | about a year and a half ago | (#42875333)

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 points towards false positive rates of 70% or higher throughout biomedical literature.

Radiate them first (1)

kiehlster (844523) | about a year and a half ago | (#42874387)

Everyone knows you need to expose the mice to radioactive waste before their genes come anywhere close to resembling human genetics. After that, then you can think about doing trauma and burn research on them. However, last I heard, that research department was raided by some ninjas. No one knows quite what happened.

One thing we learned (1)

houghi (78078) | about a year and a half ago | (#42874671)

The one thing we learned is that medical research causes cancer in mice.

Techno mouse... (1)

aussie.virologist (1429001) | about a year and a half ago | (#42875017)

...These little guys can get up to some crazy stuff, http://www.youtube.com/watch?v=WP60WCrQl4U [youtube.com] No wonder they are poor models for drug use. Think of the children. Wait, what? Awesome dude.

Other problems (1)

Jmc23 (2353706) | about a year and a half ago | (#42875031)

I remember when doing addiction research I treated my rats so well and allowed them time for social interaction, just because that's the way I am and I couldn't stand the way other researchers treated their animals.

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.

Re:Other problems (1)

SecurityGuy (217807) | about a year and a half ago | (#42875371)

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.

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.

cheap and easy (1)

stenvar (2789879) | about a year and a half ago | (#42875233)

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 (1)

kwyjibo87 (2792329) | about a year and a half ago | (#42875307)

Mice aren't humans, human experimentation is still morally objectionable and illegal, and medical testing on primates / apes is much more expensive and considerably less ethical in most people's minds. It's important to note where mouse research fails to properly recapitulate human biology, but sensationalist journalism acting as though the animal rights crowd is finally vindicated in proving, through a few heroes in the scientific community, that animal testing is cruelty without merit is harmful to the field, both in terms of basic biological research and discovering new medical treatments. Mice are still the only mammalian model organism where gene knockouts and knock-ins are reliably possible (some new DNA modifying technology involving proteins called zinc fingers are changing this) and this study is only demonstrating that some aspects of mouse research cannot be translated into human medicine. And for those questioning how many drugs failed in mouse models that may work in human subjects, are you going to be the group / company testing drugs on humans that are toxic or otherwise not working in mice? Would you rather kill an equivalent number of chimpanzees as we do mice to get a more accurate model of human biology, ignoring the added cost of housing and longer time of maturity?
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