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Drug Testing In Mice May Be a Waste of Time, Researchers Warn
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."
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?
>> 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.
Are they using synthetic urine to pass their tests now, too?
Thought thinks itself.
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.
Please fix the link for "99 percent". Thanks.
We need a couple to advance science again it seems... :/
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
Hmm, the humour and sarcasm seem to have been be lost on you.
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.”
Some people die at 25 and aren't buried until 75. -Benjamin Franklin
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.
Medical research or research to justify social policy is meaningless. The outcome is determined before the experiments begin.
Saturday Morning Breakfast Cereal #2881
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!
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'?
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.
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.
The correlation between ignorance of statistics and using "correlation is not causation" as an argument is close to 1.
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)
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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.
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?)
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.
Mice are cheap, ubiquitous, readily available, and have very low genetic variation between samples (unless variation is purposefully induced.)
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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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.
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.
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The one thing we learned is that medical research causes cancer in mice.
Don't fight for your country, if your country does not fight for you.
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.
"I opened my eyes, and everything went dark again"
...These little guys can get up to some crazy stuff, http://www.youtube.com/watch?v=WP60WCrQl4U No wonder they are poor models for drug use. Think of the children. Wait, what? Awesome dude.
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.
Don't complain about syntax, grammar, or spelling. There is no.hell like input on android.
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.
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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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.
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?
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.
No trees were killed to send this message, but a great number of electrons were terribly inconvenienced.
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.
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.
How can we ever trust the legitimacy of the Mouse Olympics results if we don't tests the medalists for doping?
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.
"The agriculture ministry is not in charge of Gundam" - Japanese ministry official.
Do the testing on little monkeys.
http://4.bp.blogspot.com/-nw4xUBJp5as/T_X7saOqmDI/AAAAAAAAKnA/Ev-PfLmgEm0/s1600/chimplips.jpeg
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.
Give a hand, not a hand-out.
I was using the cover of drugtesting on mice to make genetically modified mouse-minions to take over the world. Now my cover will stop being believable!
http://www.safermedicines.org
92% of drugs which pass animal tests FAIL human tests (AKA 'clinical trials').
You didn't take into account the people who would have used drugs, but didn't because they wanted to remain eligible for benefits. That represents a significant benefit for society, as those people become more responsible and take better care of their kids.
(Disclaimer: I am thinking of addictive and harmful drugs. Testing for marijuana is indeed a waste, but the problem is not with the testing program, it's with the fact that marijuana is illegal to begin with.)
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.
For a majority of people, what you say is correct. It is entirely possible that for some people the financial reward does make a difference. Unfortunately neither of us has data on the subject.