Just when you think you know everything there is to know about a model you run tests on, out comes some whippersnapper to upset the scientific apple cart. It makes you wonder how this could have gone on for so long, but as the article says, the researchers became “ingrained” to a certain way of doing research, which I think is also a problem with climate science. – Anthony
Tests in Mice Misled Researchers on 3 Diseases, Study Says
By GINA KOLATA, NYT
For decades, mice have been the species of choice in the study of human diseases. But now, researchers report stunning evidence that the mouse model has been totally misleading for at least three major killers — sepsis, burns and trauma. As a result, years and billions of dollars have been wasted following false leads, they say.
The study does not mean that mice are useless models for all human diseases. But, its authors said, it does raise troubling questions about diseases like the ones in the study that involve the immune system, including cancer and heart disease.
“Our article raises at least the possibility that a parallel situation may be present,” said Dr. H. Shaw Warren, a sepsis researcher at Massachusetts General Hospital and a lead author of the new study.
The paper, published Monday in the Proceedings of the National Academy of Sciences, helps explain why every one of nearly 150 drugs tested at huge expense in patients with sepsis has failed. The drug tests all were based on studies in mice. And mice, it turns out, have a disease that looks like sepsis in humans, but is very different from the human disease.
…
“They were so used to doing mouse studies that they thought that was how you validate things,” he said. “They are so ingrained in trying to cure mice that they forget we are trying to cure humans.”
“That started us thinking,” he continued. “Is it the same in the mouse or not?”
The group decided to look, expecting to find some similarities. But when the data were analyzed, there were none at all.
“We were kind of blown away,” Dr. Davis said.
Full story here
h/t to Indur Goklany
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Why we are lucky to have penicillin.
In 1940 the UK was at war with Germany and its allies. Only essentials were being imported, and guinea pigs were deemed non-essential. Nor were they bred for research purposes, so Florey and Chain were forced to test penicillin in mice – with great success. Had they had access to guinea pigs, they would have all died – penicillin is highly toxic to these rodents – and trials would have ceased. In an ironic way we have to thank Herr Hitler for the life-saving antibiotic that made its way to the front lines his madness created.
This has been known for one hell of a lot longer than that, you know.
This has been known since the 1960s, when thalidomide caused terrible birth defects after being found to be a drug with no side effects whatever in animals.
The assumption is that the proteins in mice, rats, rabbits or even primates respond identically to those in humans.
In many cases it is true, but in some it is not.
In this day and age, you would think that they purify the protein from both humans and mice and confirm that binding profiles, affinities etc etc are similar.
Perhaps they don’t?
This is all in a days work for drug testing. Nearly all drug tests fail. So a model that was thought to be equivalent, turns out not to be. So find another model, move on. Geoff Sherringham is right, cancer toxicology (including radiation carcinogenesis) is another science that has been corrupted and politicised by environmentalism, so that in its current state it is not fit for purpose. Environmental activism itself is TOXIC to normal, honest science.
Billions of dollars spent to make very effective drugs for the health of mice seems to be some what misplaced in the greater scheme of things. With that sort of money some better method could surely be developed. Good Grief
‘Burns’.
I’d hate to see how they tested that one.
So characteristically insightfulof you, Tony, to see this link! Nice sounding conclusion that the problem with climate “science” is that it has become “ingrained” to a certain way of doing research.
Help me (and maybe others in our little community) to find the next dot to join. The use of mice correlates to the practice of using climate computer models by so-called climate scientists?
Researchers are starting to use Climate Scientists in place of rats, they find that they don’t get quite so attached to them
In response to Michael Palmer
Biogerontologists are already aware of the problems inherent in mouse models of ageing (at least all my colleagues are). This is why there have been attempts to generate other animal models that more resemble humans (sheep and dog come to mind). One of the key problems with mouse models is that their cells appear to be immortal in culture (under the right conditions), whereas human cells have a limited lifespan.
It’s a bit too early to ridicule the use of mice as hosts for human disease (or common mammalian diseases, to be precise). The mice are not going anywhere from the lab research; their reputation will not suffer from this debacle, not in the least. They are way too good. And like a few of us have observed upthread, there are no tenable parallels between mouse research and climate modelling, except that both can be screwed up by stupid humans.
In this particular case — I don’t know the exact details, but I am making an educated guess — the whole idea of a drug against sepsis was a misguided one. It probably started a long time ago, before we knew better, and continued to crawl to the end despite more effective alternatives popping up in the meantime, and if this had to be the end of it, so be it.
Sepsis, as nearly always as we can tell, is a gut-derived condition (and that has been aptly demonstrated in mice). It had long been linked to trauma and wounds, but because wounds were an obvious suspect, the research into its real causes was not given a high priority. The cases of sepsis in the absence of open wounds were dismissed as freak irregularities. But as we progressed away from the more violent modes of existence (global wars, unprotected workspaces, poor traffic safety), more and more cases of sepsis could no longer be blamed on septic wounds. All that remained was trauma of some sort, or more generally, an intense shock of pretty much any nature. That is, if you only looked at patients already presenting sepsis on arrival. But there was also a steady stream of sepsis cases arising within hours or days after a surgical intervention of some sort. Sepsis became the #1 cause of post-op mortality. Again, the presence of wounds muddied the picture, and so did the use of antibiotics.
I won’t bore you with details; in the end, surgeons have found ways to prevent it, rather that treat it (and again, mice played a huge role in their research). Surgical patients no longer die from sepsis. If you are really interested in the details, a good place to start is John Alverdy’s home page at UfC:
http://biomed.uchicago.edu/common/faculty/alverdy.html
There is a system in this madness, namely genocentric vision of species evolution, also known as Neo-Darwinism. All mammals are very much alike in their genetic makeup, and so people who see no difference between mice and men because this alikeness, tend to forget about epigenetics: pattern of gene expression which produce all the difference. That is how we differ from mice: the same genes are used in different regulatory schemes. In some traits this is quite important, while in others it is not. But as long as people will see genes as actors in individual development, not as reference texts to be read and interpretated by emergent individ, such blunders will happen. Recognition of this reality is ideologically impossible because it would retire Darwinsm to dust bin of history, and we can not allow it, can we?
We are looking at a phenomena that concerns all fields of science and it has name that perfectly describes it: indoctrination. Couple this with the vested interests on a personal level in form of years of academic work invested in a specific academic school of thinking and topple it with the modern politically defined research financing programs and the problems ahead of us are unavoidable.
We are looking at a phenomenon that concerns all fields of science and it has name that perfectly describes it: indoctrination. Couple this with the vested interests on a personal level in form of years of academic work invested in a specific academic school of thinking and topple it with the modern politically defined research financing programs and the problems ahead of us are unavoidable.
I am sure climate research is the same. All models have CO2 as a cause of heating, GHG theory, and are used as proof that CO2 causes warming. Pure sophistry.
The GHG theory was thought up to make up for a lack of enough solar heat to get the average 15C. There is more than enough solar heat. We are able to measure 1000W/m2 of insolation in the solar zenith position but the GHG theory assumes about 240W/m2 which is not true as actual measurement shows. It is the low 240W/m2 used to calculate the -18C giving 33C to find. !000W/m2, the actual figure, gives a temperature equivalent of 88C. More than enough, the surplus heat warms the below surface soil and the atmosphere which convects the heat eventually to space.
That mice and men are not the same was known. It is also known that:
– you cant transport conclusions from the US to Europe etc. without checking
– you cant transport conclusions from caucasians to africans and vice-versa without checking
– models are not reality
– people forget everything that is not convenient to their aims, such has producing papers.
– mice are cheap, considering
– Science, Nature, Scientific American and New Scientist are primarily not scientific, but about science
We use lots of animals as human models, nematodes, mice, rats, dogs and primates. However, we ARE aware that a mouse is not a human. This article is yet another ‘we recognized that mice aren’t human’ feature, based on a university press release.
We know.
Honest we know that mice are not people. However, they are cheap, we can generate gene knock-outs and knock-ins, and most importantly we can do things to a mouse that we can’t do to a human.
As to the billions spent on Sepsis/trauma and burns; I wish.
This is a review of NIH spending by disease
http://report.nih.gov/categorical_spending.aspx
Almost all trauma funding is on brain and spine injuries, not hemorrhagic shock
Septicemia gets 98 million a year, only about 1/3 will involve animal models. Burns do not meet the $500,000 threshold.
So bottom line. We know mice aren’t human. We use them as a mammalian model. For somethings they are fantastic, for other things less so. You don’t need to tattoo ‘Mice aren’t people’ to our foreheads, as it is etched on our souls*.
*Even the ones we sold to get that R01 three years ago.
Biogerontologist says:
“Biogerontologists are already aware of the problems inherent in mouse models of ageing (at least all my colleagues are).”
Good. But there has been and still is quite a bit of research on mice.
“One of the key problems with mouse models is that their cells appear to be immortal in culture (under the right conditions), whereas human cells have a limited lifespan.”
Cell lifespan is not the key problem of aging.
Mice aren’t miniature humans? Who would have guessed?
/snark
RE: “Jason says:
February 11, 2013 at 7:04 pm
On the positive side, now there are many promising drugs available to treat mouse sepsis.”
So funny!
Whenever I see this sort of reserch I smell a rat.
One possibility now is that we have a closetful of previously rejected chemicals which might actually work on some human ailments. The challenge is to devise a non-mouse screening test panel to determine where some of these my be developed to their potential.
Sadly typical of medical research. It, too, is a hotbed of vested interest, big money, tenure decisions that hang on positive, not negative, results, confirmation bias, data dredging, and political interest (at the same time many of the practitioners are basically good people who genuinely want to do good for the world, paradoxically) — just like Climate Science.
We might see this change the day we see people getting tenure and promotions for null results, which (as Feynman pointed out) are often MORE useful in the search for positive results. They are WAY more useful than bogus positive results, statistically marginal positive results, data dredged results, cherrypicked results, results based on an incorrect inferential model, simulated results, theoretical results, and results that make somebody piles of money (as long as you don’t look at them too closely and notice that they are really null, failing the test of independent verification).
Papers like the one above with its NULL result are good examples of what should lead the way. It is almost as satisfying to shoot down a widespread but incorrect belief as it is to find something positive, and in the long run, our brains work by BOTH building neural connections AND brutally pruning back the ones that don’t work. Without the pruning, you get a teenage adolescent (literally — proliferation has happened but not the pruning) — and as those of us who have raised or been them well know, teenagers have a sort of brilliant and self-destructive madness until that pruning takes place.
So does science.
rgb
In re “biogerontology” and human cell life, Henrietta Lacks’ cancerous cell line HeLa and its vast mutations have long survived her death in 1951. Quibbles are for the biogerontologists.
Are there abiotic-gerontologists too?
There’s some terrible replies to that article (at the NYT). They’re very defensive and ignoring the main criticism which is against the peer review handling. A lot of anxious mouse choppers defending the “rodent model”.
Re Doug Hoffman
Thanks for the correction – I meant primary cells not cancer cells.
Re Michael Palmer and cell lifespan
This is still under debate in the ageing field. The causes of human ageing are not understood at this time.
DocMartyn is that really all you gleaned from the article? They made a discovery and couldn’t get published even though the journals couldn’t tell them where they were wrong. It wasn’t all about mice not being people, far from it.