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Medicine Science

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

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  • by h4rr4r ( 612664 ) on Tuesday February 12, 2013 @02:28PM (#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?

  • Rejection (Score:5, Insightful)

    by Anonymous Coward on Tuesday February 12, 2013 @02:29PM (#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.

    • by K. S. Kyosuke ( 729550 ) on Tuesday February 12, 2013 @02:38PM (#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 (Score:5, Informative)

        by Silas is back ( 765580 ) on Tuesday February 12, 2013 @02:52PM (#42873995) Homepage Journal

        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.

        • by WillAffleckUW ( 858324 ) on Tuesday February 12, 2013 @03:35PM (#42874507) Homepage Journal

          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.

          • by repapetilto ( 1219852 ) on Tuesday February 12, 2013 @04:37PM (#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.

      • by fuzzyfuzzyfungus ( 1223518 ) on Tuesday February 12, 2013 @02:57PM (#42874061) Journal

        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).

    • by Anonymous Coward on Tuesday February 12, 2013 @02:39PM (#42873801)

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

    • by Stem_Cell_Brad ( 1847248 ) on Tuesday February 12, 2013 @02:48PM (#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.

      • by SomeKDEUser ( 1243392 ) on Tuesday February 12, 2013 @03:47PM (#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...)

        • by ColdWetDog ( 752185 ) on Tuesday February 12, 2013 @05:08PM (#42875349) Homepage

          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.

        • by TheCarp ( 96830 ) <sjc AT carpanet DOT net> on Tuesday February 12, 2013 @06:02PM (#42875825) Homepage

          > 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 doing mouse experiments. There are a few considerations:

          1. It may be people being squeamish. The people who did doc necropsies displayed a decidedly twisted sense of humor, far beyond anything the people who worked on mice did (using old facial skin as a hand puppet was one I particularly remember hearing about; or sending the groomer in to a dog that was just euthenized... which went a bit too far, i hear she broke down crying). Perhaps this was one of those cultural things between a local private lab (the dogs) and a large non-profit lab that employed researchers from all over the world? I don't know.

          2. A cat eats about 2-3 mice worth of food a day. Not mouse food, adult mice. An average cat can weigh upwards of 15 lbs, compared to a few oz for a mouse. This means, larger facility, more food, and more work. You can put 20 mice in individual carriers on a small cart and cart them around easily.

          3. Sticking with size, everything is larger. Procedures often involve surgery. A bigger animal means bigger incisions, more work....more space required. I have seen researchers doing surgical procedures on mice, right on the same lab bench that they work at. A cat would require a larger prep area. In fact... I have seen 4 researchers with binocular microscopes, each processing mice, all standing around a lab bench no bigger than a mid sized kitchen island.

          None of this, of course, has any bearing on animal models or any of that, its almost 100% logistics. I wouldn't be shocked if running tests in cats rather than mice would, at base, cost a lot more than mice, before you even factor in that facilities are mostly already setup for mice... so adding cats means changing facilities, new protocols, and possibly a new variable too all studies.... now we have to see if mice or cats react differently when they can smell eachother in the lab.
          (I imagine the mice would find that stressful)

    • by JoeMac ( 102847 ) on Tuesday February 12, 2013 @03:42PM (#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.
    • by pesho ( 843750 ) on Tuesday February 12, 2013 @04:10PM (#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.

      • by repapetilto ( 1219852 ) on Tuesday February 12, 2013 @05:33PM (#42875581)

        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).

    • by sycodon ( 149926 ) on Tuesday February 12, 2013 @06:05PM (#42875847)

      The paper was torpedoed by Big Mice.

      They stand to lose billions I bet if they stop testing on mice.

  • by Heed00 ( 1473203 ) on Tuesday February 12, 2013 @02:29PM (#42873681)
    Are they using synthetic urine to pass their tests now, too?
  • How many (Score:5, Insightful)

    by canadiannomad ( 1745008 ) on Tuesday February 12, 2013 @02:39PM (#42873799) Homepage

    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]

    • by dragon-file ( 2241656 ) on Tuesday February 12, 2013 @02:41PM (#42873837)
      Was about to post the same thing... damn you.
    • by the biologist ( 1659443 ) on Tuesday February 12, 2013 @03:02PM (#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.
    • by interkin3tic ( 1469267 ) on Tuesday February 12, 2013 @03:03PM (#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.
    • by poofmeisterp ( 650750 ) on Tuesday February 12, 2013 @04:24PM (#42874979) Journal

      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.

    • by blivit42 ( 980582 ) on Tuesday February 12, 2013 @06:43PM (#42876167)
      I can somewhat answer the inverse of this question, though: "How many drugs do we reject in clinical trials because some researcher used the wrong animal model to test?"

      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 industry loses around 70% of all its drug candidates due to them plain not working. Often times, this is due to it working in mice/rats, but not working in humans. This isn't entirely surprising, since rodents are a good bit different than humans. Also, many animal models simply mimic human disease, rather than actually being related to how the human disease works. For example, many animal models are done over a short period of time, say 30 days or less between the initial insult (do something nasty to the rodent to induce disease-like symptoms). For inflammatory diseases, real human disease may take years from the initial problem (whatever it may be) to develop into full blown disease. When you're comparing an animal model on the time scale of a few weeks to human disease over several years, and the insult is something very very different from what it could possibly ever be in a human, it should come as no surprise that the model is often biologically very different from what is going on the human. This isn't necessarily due to rodents being too different from humans, but could easily be due to the model simply being the wrong model to mimic human disease.

      Long story short, many animal models just don't do a good job at representing human disease. This is not news to anyone who has worked with them or been in the pharmaceutical industry. However, not everything is gloom and doom here. There are, actually, many animal models that *DO* do a good job of modeling human disease. The trick is to know which ones are good and which ones aren't for various diseases, drugs, pathways, etc. before you start spending the big money on clinical trials....
  • by schneidafunk ( 795759 ) on Tuesday February 12, 2013 @02:40PM (#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.”
  • by SBlaire ( 2839471 ) on Tuesday February 12, 2013 @02:41PM (#42873835)
    Medical research or research to justify social policy is meaningless. The outcome is determined before the experiments begin.
  • by fuzzyfuzzyfungus ( 1223518 ) on Tuesday February 12, 2013 @02:51PM (#42873989) Journal

    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'?

    • by Stem_Cell_Brad ( 1847248 ) on Tuesday February 12, 2013 @03:01PM (#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...
    • by WillAffleckUW ( 858324 ) on Tuesday February 12, 2013 @03:01PM (#42874119) Homepage Journal

      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.

    • by gstoddart ( 321705 ) on Tuesday February 12, 2013 @03:30PM (#42874459) Homepage

      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.

      • by fuzzyfuzzyfungus ( 1223518 ) on Tuesday February 12, 2013 @04:32PM (#42875041) Journal

        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.

    • by poofmeisterp ( 650750 ) on Tuesday February 12, 2013 @04:40PM (#42875113) Journal

      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.

  • by interkin3tic ( 1469267 ) on Tuesday February 12, 2013 @02:53PM (#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.
    • by Daniel Dvorkin ( 106857 ) on Tuesday February 12, 2013 @03:01PM (#42874121) Homepage Journal

      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. ;)

    • by canadiannomad ( 1745008 ) on Tuesday February 12, 2013 @03:46PM (#42874643) Homepage

      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.

    • by poofmeisterp ( 650750 ) on Tuesday February 12, 2013 @04:44PM (#42875159) Journal

      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.

  • by Daniel Dvorkin ( 106857 ) on Tuesday February 12, 2013 @02:55PM (#42874045) Homepage Journal

    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.

    • by jfengel ( 409917 ) on Tuesday February 12, 2013 @05:44PM (#42875683) Homepage Journal

      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 Science News, where the writers have degrees in science fields instead of (or in addition to) journalism. Seeing something in the NYT may cause me to keep an eye out for that article, but I'm never surprised when it fails to make a more serious scientific medium.

    • by luckymutt ( 996573 ) on Wednesday February 13, 2013 @01:36AM (#42879943)

      it should have no place in serious discourse from a reputable organization like the NYT.

      BWAHAHAHAHAHAHAHAHA!!!!!!!!!!!!!!!!!

  • by WillAffleckUW ( 858324 ) on Tuesday February 12, 2013 @03:00PM (#42874107) Homepage Journal

    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)

    • by sirwired ( 27582 ) on Tuesday February 12, 2013 @03:11PM (#42874253)

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

    • 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. ;)

  • by sirwired ( 27582 ) on Tuesday February 12, 2013 @03:09PM (#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.

  • by mutube ( 981006 ) on Tuesday February 12, 2013 @03:20PM (#42874351) Homepage

    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.

    • by repapetilto ( 1219852 ) on Tuesday February 12, 2013 @05:05PM (#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.

  • by kiehlster ( 844523 ) on Tuesday February 12, 2013 @03:24PM (#42874387) Homepage
    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.
  • by account_deleted ( 4530225 ) on Tuesday February 12, 2013 @03:50PM (#42874671)
    Comment removed based on user account deletion
  • by aussie.virologist ( 1429001 ) on Tuesday February 12, 2013 @04:30PM (#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.
  • by Jmc23 ( 2353706 ) on Tuesday February 12, 2013 @04:32PM (#42875031) Journal
    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.

    • by SecurityGuy ( 217807 ) on Tuesday February 12, 2013 @05:10PM (#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.

      • by Jmc23 ( 2353706 ) on Wednesday February 13, 2013 @12:37AM (#42879441) Journal
        Depends if you're using laymen's terms. A properly socialized individual doesn't require drugs to 'be social'.

        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.

    • by Hatta ( 162192 ) on Tuesday February 12, 2013 @06:52PM (#42876249) Journal

      Social animals that socialize don't take drugs.

      Explain hippies.

      • by Jmc23 ( 2353706 ) on Wednesday February 13, 2013 @12:43AM (#42879505) Journal
        Drugs were needed to open the individual enough to be social. Are they really socializing though, i.e., making meaningful connections. Most hippies almost don't recognize any/differences between the people they interact with. Is that really socializing?

        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.

  • by stenvar ( 2789879 ) on Tuesday February 12, 2013 @04:52PM (#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.

  • by kwyjibo87 ( 2792329 ) on Tuesday February 12, 2013 @05:03PM (#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?
    • by dhomstad ( 1424117 ) on Tuesday February 12, 2013 @05:48PM (#42875721)

      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 meant killing 5 more humans per day? I also think we, as a human race, need to sack up when it comes from testing dangerous, yet potentially game changing, drugs. I'm sure some cancer patients might willingly "sacrifice" themselves by taking said drugs, if they thought it could help preventing others in the future from suffering from their disease.

      On a separate note, if it were up to random chance, the LD50 would be higher in mice than humans for 50% of all drugs. I am not sure if this is the case. For example, if you look at the LD50 of nicotine in animals, it is 50 mg/kg for rats and 3.3 mg/kg in mice (not sure what LD50 for nicotine is in humans - could be greater than 50 mg/kg, less than 3.3 mk/kg, or anywhere in between).

  • by dhomstad ( 1424117 ) on Tuesday February 12, 2013 @05:30PM (#42875559)

    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 side affects in mice, but none in humans. Failing a test with mice wouldn't necessarily mean the drug was worthless for humans.

  • by almechist ( 1366403 ) on Tuesday February 12, 2013 @06:04PM (#42875843)
    This has the potential to be a genuinely big deal if the results hold up. Despite the article’s somewhat misleading title, the paper’s authors are not suggesting that we should just throw away the mouse model. They are saying that in one limited area, the treatment of sepsis (burns and trauma are also mentioned, but the emphasis is on sepsis) the mouse may not be the best organism to use as a model. According to their research, mice respond to sepsis in an entirely different manner than humans, with different genes and genetic pathways being activated. They back up this claim with very solid data, according to the independent researchers contacted by the Times. Moreover, as the article points out, there are good longstanding reasons to suspect the mouse model may be flawed in this area. Using the mouse model, which has become an essentially mandatory step under current drug R&D methodologies, no effective sepsis drug has ever been found that also works in humans. A different genetic response to sepsis would not only explain the drug development failure, but would make logical sense given the mouse’s constant exposure to high levels of bacteria and its garbage-ingesting lifestyle. The fact that it takes a million times as much bacteria to kill a mouse as a human suggests strongly that something fundamentally different is going on with the two species. We don’t of course know the real reasons why the paper was initially rejected by both Science and Nature, but the authors seem to be saying it was primarily a matter of disbelief: the mouse model is so strongly accepted and ingrained that the reviewers simply couldn’t accept that there might be a problem with it, and the fault must therefore lie with the paper. This is not at all an uncommon reaction when a longstanding scientific belief or paradigm is first challenged. The paper‘s authors seem pretty sure of themselves, and the outside experts interviewed in the article seem to be impressed with the general quality of the research. The authors are putting forward a well thought out and logical theory backed with solid data. I don’t believe we can dismiss the results as easily as some here are suggesting. It’s not my field, but this looks and smells like the real deal to me.
  • by WillgasM ( 1646719 ) on Tuesday February 12, 2013 @06:33PM (#42876085) Homepage
    How can we ever trust the legitimacy of the Mouse Olympics results if we don't tests the medalists for doping?
  • by blind biker ( 1066130 ) on Tuesday February 12, 2013 @08:17PM (#42877009) Journal

    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.

  • they shouldn't be used for testing. The 10th mouse is actually the inventor of the Pan Galactic Gargle Blaster, and also has 42 good reasons to recommend mice as the perfect lab experiment creatures.

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