http://www.reuters.com/article/2012/03/28/us-science-cancer-idUSBRE82R12P20120328 A former researcher at Amgen Inc has found that many basic studies on cancer -- a high proportion of them from university labs -- are unreliable, with grim consequences for producing new medicines in the future. During a decade as head of global cancer research at Amgen, C. Glenn Begley identified 53 "landmark" publications -- papers in top journals, from reputable labs -- for his team to reproduce. Begley sought to double-check the findings before trying to build on them for drug development. Result: 47 of the 53 could not be replicated. He described his findings in a commentary piece published on Wednesday in the journal Nature. "It was shocking," said Begley, now senior vice president of privately held biotechnology company TetraLogic, which develops cancer drugs. "These are the studies the pharmaceutical industry relies on to identify new targets for drug development. But if you're going to place a $1 million or $2 million or $5 million bet on an observation, you need to be sure it's true. As we tried to reproduce these papers we became convinced you can't take anything at face value." The failure to win "the war on cancer" has been blamed on many factors, from the use of mouse models that are irrelevant to human cancers to risk-averse funding agencies. But recently a new culprit has emerged: too many basic scientific discoveries, done in animals or cells growing in lab dishes and meant to show the way to a new drug, are wrong. Begley's experience echoes a report from scientists at Bayer AG last year. Neither group of researchers alleges fraud, nor would they identify the research they had tried to replicate. But they and others fear the phenomenon is the product of a skewed system of incentives that has academics cutting corners to further their careers. George Robertson of Dalhousie University in Nova Scotia previously worked at Merck on neurodegenerative diseases such as Parkinson's. While at Merck, he also found many academic studies that did not hold up. "It drives people in industry crazy. Why are we seeing a collapse of the pharma and biotech industries? One possibility is that academia is not providing accurate findings," he said. BELIEVE IT OR NOT Over the last two decades, the most promising route to new cancer drugs has been one pioneered by the discoverers of Gleevec, the Novartis drug that targets a form of leukemia, and Herceptin, Genentech's breast-cancer drug. In each case, scientists discovered a genetic change that turned a normal cell into a malignant one. Those findings allowed them to develop a molecule that blocks the cancer-producing process. This approach led to an explosion of claims of other potential "druggable" targets. Amgen tried to replicate the new papers before launching its own drug-discovery projects. Scientists at Bayer did not have much more success. In a 2011 paper titled, "Believe it or not," they analyzed in-house projects that built on "exciting published data" from basic science studies. "Often, key data could not be reproduced," wrote Khusru Asadullah, vice president and head of target discovery at Bayer HealthCare in Berlin, and colleagues. Of 47 cancer projects at Bayer during 2011, less than one-quarter could reproduce previously reported findings, despite the efforts of three or four scientists working full time for up to a year. Bayer dropped the projects. Bayer and Amgen found that the prestige of a journal was no guarantee a paper would be solid. "The scientific community assumes that the claims in a preclinical study can be taken at face value," Begley and Lee Ellis of MD Anderson Cancer Center wrote in Nature. It assumes, too, that "the main message of the paper can be relied on ... Unfortunately, this is not always the case." When the Amgen replication team of about 100 scientists could not confirm reported results, they contacted the authors. Those who cooperated discussed what might account for the inability of Amgen to confirm the results. Some let Amgen borrow antibodies and other materials used in the original study or even repeat experiments under the original authors' direction. Some authors required the Amgen scientists sign a confidentiality agreement barring them from disclosing data at odds with the original findings. "The world will never know" which 47 studies -- many of them highly cited -- are apparently wrong, Begley said. The most common response by the challenged scientists was: "you didn't do it right." Indeed, cancer biology is fiendishly complex, noted Phil Sharp, a cancer biologist and Nobel laureate at the Massachusetts Institute of Technology. Even in the most rigorous studies, the results might be reproducible only in very specific conditions, Sharp explained: "A cancer cell might respond one way in one set of conditions and another way in different conditions. I think a lot of the variability can come from that." THE BEST STORY Other scientists worry that something less innocuous explains the lack of reproducibility. Part way through his project to reproduce promising studies, Begley met for breakfast at a cancer conference with the lead scientist of one of the problematic studies. "We went through the paper line by line, figure by figure," said Begley. "I explained that we re-did their experiment 50 times and never got their result. He said they'd done it six times and got this result once, but put it in the paper because it made the best story. It's very disillusioning." Such selective publication is just one reason the scientific literature is peppered with incorrect results. For one thing, basic science studies are rarely "blinded" the way clinical trials are. That is, researchers know which cell line or mouse got a treatment or had cancer. That can be a problem when data are subject to interpretation, as a researcher who is intellectually invested in a theory is more likely to interpret ambiguous evidence in its favor. The problem goes beyond cancer. On Tuesday, a committee of the National Academy of Sciences heard testimony that the number of scientific papers that had to be retracted increased more than tenfold over the last decade; the number of journal articles published rose only 44 percent. Ferric Fang of the University of Washington, speaking to the panel, said he blamed a hypercompetitive academic environment that fosters poor science and even fraud, as too many researchers compete for diminishing funding. "The surest ticket to getting a grant or job is getting published in a high-profile journal," said Fang. "This is an unhealthy belief that can lead a scientist to engage in sensationalism and sometimes even dishonest behavior." The academic reward system discourages efforts to ensure a finding was not a fluke. Nor is there an incentive to verify someone else's discovery. As recently as the late 1990s, most potential cancer-drug targets were backed by 100 to 200 publications. Now each may have fewer than half a dozen. "If you can write it up and get it published you're not even thinking of reproducibility," said Ken Kaitin, director of the Tufts Center for the Study of Drug Development. "You make an observation and move on. There is no incentive to find out it was wrong." (Note: Amgen researcher C. Glenn Begley is not related to the author of this story, Sharon Begley) (Reporting By Sharon Begley; Editing by Michele Gershberg and Maureen Bavdek)
Interesting articles. Some years back, I listened to a radio program about the placebo effect in double blind studies. The researcher claimed that many studies assumed there was no such effect because many medicines would not have passed. So the effect would swamp the statistics and therefore ruin the results. I am not sure he was right and I can't find the paper anymore, but if was true but that would be an astounding admission! My dad decades ago used to show me aisles of cold remedies and other magic cures that were proven not effective by studies but still allowed to sell. We learned as kids never to bring our health concerns to him since he scared the living daylights out of us with stuff like "well, you could have beri-beri etc.". All his kids were very healthy. Scared straight you might say. The recent scandals over oxycontin is a modern day example of drug company behavior. IMO, the objective of some drug companies is not to cure the patient but to force you to take an expensive pill for the rest of your life to boost their bottom line. Many also factor in lawsuit cost into the payback time of the medicine. It must frustrate those trying to make a living that way that so little can be known with certainty. People listening to the media or their doctor, can hear cheap and effective ways of keeping many illnesses at bay - vaccines, reduce stress, certain vitamins, exercise, weight reduction and the like. Still most people want someone in authority to give them a pill rather than do any of those things. In some ways, mankind has never left the jungles.
The jungle can actually be exquisite. I've been a lot happier since I realized what a fraud nearly everything in this world really is, with science leading the way in that most of the time. I've become a lot more catlike in my outlook perhaps, more suited for the surrounding jungleness, just looking for what I need, and avoiding what I do not need and not worrying about the rest of the mess...
Eight, it it would take only a moment of reflection to recognize that what you think you have "realized" is not true. Once science and Madison Avenue become intermingled the lines between what is science and what is hype get blurred, but it is a mistake to conclude science is a fraud. If it were, you'd still be living under 19th century conditions. If you could look back in time, you would find that the number of science publications per principal investigator ( http://en.wikipedia.org/wiki/Principal_investigator ) has increased greatly since the 1950's, and the fraction of unreliable papers, while still small, has increased too. There are many reasons including changes in the nature of University science funding, the advent of word processors and the personal computer, the less careful peer review process brought about by the onslaught of papers, and especially the nature of science knowledge itself -- not linear but exponential. Despite all this, any data collected so far on the incidence of unreliable papers coming from Western Europe, Great Britain, Scandinavia or North America --and there hasn't been much in the way of these studies so far-- have indicated that the number of unreliable papers in still very small compared to the millions published. Some fields seem to have a slightly higher chance for error than others, especially those involving complex biology, which by its nature is a very experimentally difficult field. In truth, it is impossible to know with much accuracy what fraction of papers published is reliable simply because the majority of papers published don't get much attention. Scientists use how many times a paper gets cited in other papers as a measure of a papers importance. It is only in the more important papers where less obvious errors are likely to be discovered. It is therefore safe to say that the number of unreliable papers is almost certain to be higher than realized, nevertheless judging by the reliability of those papers that do get lots of attention it must still be quite small in relation to the total number of papers published. Curiously, a notable exception to the reliability of scientific papers would be those coming from the Soviet Union. These papers, in some fields, were notoriously unreliable. The most famous instances being the "polywater" fiasco-- http://en.wikipedia.org/wiki/Polywater and the Lysenko fiasco -- http://books.google.com/books/about/The_Lysenko_effect.html?id=TP4PAQAAMAAJ -- but there were many other instances of even well-known soviet scientists attaching their names to clearly erroneous papers. I don't know the reason.I only know from personal experience that the results reported in papers coming from the old Soviet Union, if it wasn't immediately obvious that there must be something wrong with them, were quite often impossible to reproduce.
============== Excellant points,MK Trender, especially true in eco, economic, global warming -scam. WE ARE assuming if any trader makes a bullish comments on silver or gold, probably bullish;bearish comments on big banks probaly bearish. Another helpful rule, most gov studies are crooked, especially Chicago related. Most bearish coffee studies by Mormans , are crooked. Egg studies by grain cereal companys are suspect also.LOL, but true.
I could populate the Journal of Negative Results with a slew of broken trading strategies alone. Heck, you could rename it Journal of Clearinghouse's Broken Stuff.
A related problem is discussed this weekend on Quirks and Quarks. You can search "october 6: prize fight" and click on the cbc podcast button to listen to it. It is a short discussion of a book about the fights between Nobel prize winners. Perhaps this also hints at why some of the misconduct (fraud) occurs.