Billions and Decades Wasted on Worthless Mouse Experiments

[Diesel]

Billions and Decades Wasted on Worthless Mouse Experiments

http://www.care2.com/causes/billions-an ... ments.html

Mice are the most common subjects of medical experiments. For decades drugs and treatments have been tested on mice before humans. But it turns out that was a waste of years and of billions of dollars, and that the torture and death of countless animals was pointless.

A Ground-Breaking Study

Researchers published a study on February 11, 2013, in the Proceedings of the National Academy of Sciences of the United States of America showing that mice’s reactions to inflammatory diseases have nothing in common with human reactions. In fact, when the two species’ responses were compared, “the outcomes appeared to be random.”

Some of the differences, reported by CBS News: humans had more than three times as many genes affected as the mice did, and humans showed genetic responses up to six months after injury, while mice experienced changes for a few days at most.

The study looked at “nearly 150 potential treatments for severe inflammation” that have been tested on mice in a wide variety of gruesome ways, like scalding them with hot water or slicing open their bellies “and reliev[ing them] of a major portion of their blood supply.” All of the experimental treatments this study included looked promising in mice, but not a single one of them helped humans.

The study focused on “three major killers,” according to The New York Times: “sepsis, burns and trauma.” The study’s authors say that their findings raise the possibility that other experiments on mice are equally worthless, including diseases involving the immune system like cancer.

It is remarkable that scientists are only now reaching this conclusion — and that they didn’t bother even to ask the question a few billion dollars ago. Slate reports that the differences between mice and humans’ immune systems and inflammatory responses were obvious:

“If you inject a person with a bolus of bacteria, she might get a fever. Her heart rate could go up, and her breathing might start to quicken. Left unchecked, there’s a chance her body would succumb to inflammation, her organs failing as she dies.”

Do the same to a laboratory mouse and it recovers. To kill the mouse, “the relative dose must be increased a million times.”

One would think that would have alerted scientists that they were barking up the wrong tree with their mouse obsession.

Whether or not they knew about the fundamental defect in their work, scientists are digging their heels in now. The authors of this study could barely get it published as their colleagues united against them and their findings, which should upset quite a few apple carts. The response from publications that rejected the paper:

“It has to be wrong. I don’t know why it is wrong, but it has to be wrong.”

Whither Animal Research Now?

The New York Times quotes Dr. Mitchell Fink, “a sepsis expert at the University of California, Los Angeles,” about the study (which he was not involved with): “This is a game changer,” he proclaimed. The Times reported that “medical experts not associated with the study said that the findings should change the course of research worldwide” for some conditions.

Or not. Slate concludes that we are “not yet on the eve of a Great Mouse Reckoning.” It contends that the study’s authors themselves “have no interest in abandoning” mice as “the standard model even in their modest field of inflammation.” No game changing there.

The reason for the inertia is that a line of mice has been bred over 90 years to be nearly identical to each other. That is why that line has “been the subject of a million research papers and will be the subject of a million more. No model organism provides more depth and flexibility. None is as brilliantly efficient.”

So the study’s authors make a modest call for change: “they’d like to ‘raise the bar’ for mouse studies aimed at curing human disease by asking colleagues to show, first of all, that whichever gene or molecule turns up in animals applies to humans, too. This vital step has been ignored for far too long.”

This is astonishing: scientists have been running experiments on mice with the putative intention of applying the conclusions to humans, without even checking to see that humans have the same genes or molecules as those involved in the experiment. It’s as though scientists have abandoned curing humans as the goal of their work. Is their mission now to secure funding so they remain employed? To achieve professional kudos? Science for its own sake?

Wherever their heads are at, animal experimenters need to screw them back on real tight. However “brilliantly efficient” mice may have seemed as vivisection victims, they are not at all efficient at helping cure humans with inflammatory diseases. Researchers: it is time to let go and move on.

Diesel

[Tulipano]

Het artikel over de TLR2 receptor in muizen (viewtopic.php?f=8&t=8082)
deed me ook denken aan bovenstaand artikel van Diesel waarvan hieronder waarschijnlijk de originele bron:

http://www.nytimes.com/2013/02/12/scien ... ed=1&_r=1&

MICE FALL SHORT AS TEST SUBJECTS FOR SOME OF HUMANS' DEADLY ILLS
By Gina Kolata

For decades, mice have been the species of choice in the study of human diseases. But now, researchers report 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’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.

“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 Proceedings of the National Academy of Sciences, helps explain why every one of nearly 150 drugs tested at a huge expense in patients with sepsis has failed. The drug tests all were based on studies in mice. And mice, it turns out, can have something that looks like sepsis in humans, but is very different from the condition in humans.

Medical experts not associated with the study said that the findings should change the course of research worldwide for a deadly and frustrating condition. Sepsis, a potentially deadly reaction that occurs as the body tries to fight an infection, afflicts 750.000 patients a year in the United States, kills one-fourth to one-half of them, and costs the nation $17 billion a year. It is the leading cause of death in intensive-care units.

“This is a game changer,” said Dr. Mitchell Fink, a sepsis expert at the University of California, Los Angeles, of the new study.

“It’s amazing,” said Dr. Richard Wenzel, a former chairman at the department of internal medicine at Virginia Commonwealth University and a former editor of the New England Journal of Medicine. “They are absolutely right on.”

Potentially deadly immune responses occur when a person’s immune system overreacts to what it perceives as danger signals, including toxic molecules from bacteria, viruses, fungi, or proteins released from cells damaged by trauma or burns, said Dr. Clifford S. Deutschman, who directs sepsis research at the University of Pennsylvania and was not part of the study.

The ramped-up immune system releases it own proteins in such overwhelming amounts that capillaries begin to leak. The leak becomes excessive, and serum seeps out of the tiny blood vessels. Blood pressure falls and vital organs do not get enough blood. Despite efforts, doctors and nurses in an intensive-care unit or an emergency room may be unable to keep up with the leaks, stop the infection or halt the tissue damage. Viral organs eventually fail.

The new study, which took 10 years and involved 39 researchers from across the country, began by studying white blood cells from hundreds of patients with severe burns, trauma of sepsis to see what genes were being used by white blood cells when responding to these danger signals.

The researchers found some interesting patterns and accumulated a large, rigorously collected data set that should help move the field forward, said Ronald W. Davis, a genomics expert at Stanford University and a lead author of the new paper. Some patterns seemed to predict who would survive and who would end up in intensive care, clinging to life and, often, dying.

The group had tried to publish its findings in several papers. One objection, Dr. Davis said, what that the researchers had not shown the same gene response had happened in mice.

“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.

The drugs failures became clear. For example, often in mice, a gene would be used, while in humans, the comparable gene would be suppressed. A drug that worked in mice by disabling that gene could make the response even more deadly in humans.

Even more surprising, Dr. Warren said, was that different conditions in mice – burns, trauma, sepsis – did not fit the same pattern. Each condition used different groups of genes. In humans, though, similar genes were used in all three conditions. That means, Dr. Warren said, that if researchers can find a drug that works for one of those conditions in people, it might work for all three.

The study’s investigators tried for more than a year to publish their paper, which showed that there was no relationship between the genetic responses of mice and those of humans. They submitted it to the publications Science and Nature, hoping to reach a wide audience. It was rejected from both.

Science and Nature said it was their policy not to comment on the fate of a rejected paper, or whether it had even been submitted to them. But, Ginger Pinholster of Science said, the journal accepts only about 7 percent of the nearly 13,000 papers submitted each year, so it is not uncommon for a paper to make the rounds.

Still, Dr. Davis said, reviewers did not point out scientific errors. Instead, he said, “the most common response was, ‘It has to be wrong. I don’t know why it is wrong, but is has to be wrong.’ ”

The investigators turned to Proceedings of the National Academy of Sciences. As a member of the academy, Dr. Davis could suggest reviewers for his paper, and he proposed researchers who he thought would give the work a fair hearing. “If they don’t like it, I want to know why”. He said. They recommended publication, and the editorial board of the journal, which independently assesses papers, agreed.

Some researchers, reading the paper now, say they are as astonished as the researchers were when they saw the data.

“When I read the paper, I was stunned by just how bad the mouse data are,” Dr. Fink said. “It’s really amazing – no correlation at all. These data are so persuasive and so robust that I think funding agencies are going to take note.” Until now, he said, “to get funding, you had to propose experiments using the mouse model.”

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.”

Researchers said that if they could figure out why mice were so resistant, they might be able to use that discovery to find something to make people resistant.

“This is a very important paper,” said Dr. Richard Hotchkiss, a sepsis researcher at Washington University who was not involved in the study. “It argues strongly – go to the patients. Get their cells. Get their tissues whenever you can. Get cells from airways.”

“To understand sepsis, you have to go to the patients,” he said.

Correction: February 11, 2013
An earlier version of this article misstated the position of Dr. Richard Wenzel. He is a former chairman of the department of internal medicine at Virginia Commonwealth University. He is not currently the chairman.

Best verontrustend als we bedenken dat ook bij de ontwikkeling van het nieuwe Lymevaccin opnieuw de muis als proefdier wordt gebruikt.

[Foetsie]

Hpypocrisie ten top.
Wel goed voor onze poezen en honden, maar als het om een iets kleiner dier gaat, gelden er plotseling andere regels?
Maar ja, je hoeft nieteens per sé klein te zijn om mishandeld te worden, kijk maar naar de kalvermesterijen en de varkensmesterijen, zijn jullie daar al ooit eens binnen geweest?
Nu is meestal eventjes 1 close look niet lang genoeg eigenlijk,
Want:

Mijn ouders woonden schuin tegenover zo'n mesterij.
Zag regelmatig dode kalfjes buiten liggen als ik er langs fietste naar school, soms lagen ze er wel meer dan 3 dagen voordat ze naar het slachthuis gingen.
Je zag die mooie grote ogen met die lange wimpers: kalfjes zien er van de buitenkant heel mooi uit.

Soms hadden ze(omdat ze gespleten hoeven hebben) kapot gescheurde poten, van onderen naar boven.
Dan kon je zien hoe ze aan hun einde waren gekomen, want dan hadden ze vast gezeten met 1 v.d. hoeven in het ijzeren rooster waar ze in hun veel te kleine hok in vastgezeten hadden, waardoor ze uiteindelijk stierven.

De eigenaren van deze mesterijen woonden ergens anders en hadden van de gemeente een vergunning voor een stukje grond om een mesterij te bouwen, zonder woonhuis.