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
Discover more from Watts Up With That?
Subscribe to get the latest posts sent to your email.
It’s the way it is joanna. The more centers reporting a disease the less the information is worth. It is the dog shit and ice cream problem; what is the amount of ice cream you need to add to dog crap for it to turn into ice cream.
There is a very good reason for double blind trials. looking at sick people doesn’t work.
Right, Doc (backing slowly away). On second thoughts, I feel fine. Just fine …
I have just spoken to a friend who is a Professor in a large teaching hospital. I read him your comments.
He hopes that you are not practising medicine on real patients, and adds that if you have any suggestions for training medical professionals that do not include “looking at sick people”, he would be very interested to hear about them.
He may also have said something like “ye gods and little fishes”.
“Good Calories, Bad Calories” by Gary Taubes documents the same types of problems with dietary “science”. In fact, the studies he cites indicate that obesity epademic that we are experiencing today was caused bad science in the 1960s. He also cites several recent studies performed at Stanford and Harvard that have turned yesterdays dietary “science” on it’s ear.
DocMartyn says:
February 12, 2013 at 5:32 pm
” So don’t shot the pianist’s as they are doing their best.
WE KNOW MICE ARE MODELS; they are bound to be bad in some disease states.
In the case of gerontology and auto-immune diseases mice don’t mimic humans well.”
a) You don’t like being criticized, obviously, so excuse me for the following sentence
b) Why did it take 150 failed drug tests to realize that something is wrong with the sepsis model in mice when YOU KNEW THAT MICE CAN BE BAD MODELS.
Nobody looked at it until now. You were sure the model was right. For decades. You are idiots.
Chris R. says:
February 12, 2013 at 2:52 pm
“So how about suggesting an alternative? DocMartyn and
rgbatduke put forth disclaimers up-thread stating
that the assorted biomedical researchers & doctors know that the murine
model is flawed–but the most practical game in town. Suggest a better alternative,
bearing in mind the cautions I voice above.”
The “most practical game in town” obviously has lead to no progress at all, so the funding is a complete waste. So as long as the ROI is zero, use 90% of the money for something useful. Like battling infectious diseases. Put 10% of the money into a fund that pays for an X prize challenge to be won by the person who comes up with a better model.
Oh, you wanted a suggestion FOR FREE? hmm. Sorry.
DirkH, I think you miss the point of what the 150 failed drug tests mean. Someone has used pub med or scopus to look up the number of treatment models used in mouse sepsis models. Most of it is going to be simple stuff; non-steroidal antiinflammatories, antioxidants nitric oxide synthase inhibitors, drugs to alter blood pressure e.t.c. These will give one lots of information about the system and be applicable to people. There are not tests on 150 newly synthesized drugs, this is off the shelf stuff.
johanna, you are incapable of understanding. A patient arrives at hospital with life threatening condition is treated. In the case of sepsis the treatment is very invasive. The patient is being treated but a team who interact with a patients symptoms. Other than a case report you get no data.
1. Observation
2. Hypothesis
3. Experimental design
4. Test hypothesis
You are suggesting that we just sit at the first one.
Bottom line, people with acute diseases are in the process of dying and the treatment team is busy treating and not in conducting research. They not only can’t get informed consent, but if they knowingly use a treatment that is ‘experimental’ they can be sued. Patients are lousy models for a host of reason, mostly ethical and legal, and physicians fighting for a patients life make lousy researchers. Not only is this true, it is known to be true.
DocMartyn: You are absolutely correct, but your focus is on the cases of people arriving to the ER with acute inflammation and sepsis. There are as many or more cases of sepsis resulting from planned surgery, where patients entering the OR are in good general health except for the problem they hope to resolve surgically. Bowel and thoracic surgery are good examples of procedures that cause major stress for reasons other than studying sepsis. During these procedures, circulation is cut and patients are typically placed on a ventilator. Many survive, but many enough die, and a great majority of those who die succumb to sepsis. It is during cases like these that you can observe and test hypotheses. These are just the typical cases where post-op mortality from sepsis is significant and expected.
But there is no shortage of more diverse cases where death from sepsis is not anticipated. The one I remember was much discussed at the UofC Hospitals during my time there: a girl in her late teens comes in with a toe trauma classed as open wound (although the extent was minimal); because of that, the emergency physician immediately gives her antibiotics (just in case, you know), fixes the injury and sends her home. Within the next couple days (can’t recall the exact delay), she’s back with an acute inflammation of her entire intestinal tract and dies in the hospital almost as soon as she arrives. This might seem like a co-incidence to a casual observer, but once you’ve seen hundreds of cases like that, you begin to think it was either her reaction to trauma or the antibiotic that did her in. Or both.
An experiment (or a whole lot of them) done by accident can deliver as good or even better information than direct testing.
Gene, my mother died of post-operation sepsis nine months ago and I work in a major hospital.
The problem with episodic events is that you need very good general surveillance techniques to record all patients, and then to be able to compare them to the person who get ‘X’.
Never mind different centers, different teams in a single department do things differently and the medics and nurses will report what they think they are doing and not what they are doing. Most people fail to grasp this point. People are liars, all the time, and not deliberately. You can monitor exactly what they do and then ask them what they have done and find huge differences.
Aristotelian philosophy; observation/thought/conclusion kills.
DocMartyn, man, I am so sorry. It is such a sad way of losing your mother. Post-operation sepsis should be preventable, now that its causes are understood, in the first approximation. Maybe it is knew knowledge that hasn’t yet reached everybody concerned. If you are still interested, please have a look at Alverdy’s works on virulence activation, or even better, get in touch with him. He knows it better than anybody.
Another outstanding and informative piece, Anthony. My thanks to you and Indur Goklany. Obviously, too many people have taken the “mouse proxy” for granted, thinking that it works as a protocol for all medical research. Hopefully this study will get scientists to correct some fuzzy thinking on their part.
We all insist that industrial sectors such as the food industry, auto industry, drug industry, etc. should utilize lots of quality control in making and developing their products. Why science has been neglectful in the area of quality control is somewhat hard to understand. Continuous quality control in medical and scientific research is just as important as it is in the food or drug industry.
The first question from the FDA is where are your study results on mice? That is why test are done on mice, even though the tests are meaningless. But there are other tests that can be run, on human tissue, or humans. After all, the human innate immune system is significantly different from all other animals, even primates. It is why monkeys don’t get HIV. There is no conspiracy here, it is just bloody stubbornness.
Solve the problem. Use Lawyers:
They are biologically similar to human beings.
The scientists get attached to the cute little mice. This emotional involvement interferes with the objectivity of the lab work. No one gets attached to lawyers.
Lawyers breed faster and are in much greater supply.
Lawyers are much cheaper to care for and the humanitarian societies won’t jump all over you no matter what you you do with them.
There are some things even a mouse won’t do.
We are seeing too many cases of people in intensive care dying from an immune system that has turned against them.
CBDs (cannabinoids) can be used to modulate the immune system.
http://classicalvalues.com/2013/02/cbd-science-hplc-analysis/
Here is another bit of info on immune system modulation:
The Profile of Immune Modulation by Cannabidiol (CBD) Involves Deregulation of Nuclear Factor of Activated T Cells (NFAT)
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2748879/
Theo Goodwin says:February 12, 2013 at 2:34 pm :
This one is for you:
http://classicalvalues.com/2013/02/immune-system-modulation-cannabis-science/