S*****a
发帖数: 63 | 1 In cancer science, many "discoveries" don't hold up
(Reuters) - 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." | C*******I
发帖数: 151 | 2 的确，很多的文章都是垃圾。当年，一个被好几个不同实验室互相验证的假结果，浪费
了我不少宝贵的tenure clock 时间...现在想起来还想骂人。真想用自己的结果发个证
伪文章，后来想想算了,没时间精力去干这种得罪人又没funding的事...... | e*******d
发帖数: 23 | 3 这种造假或者边缘造假行为，迟早会毁了生物。
future.
Begley
a
【在 S*****a 的大作中提到】
: In cancer science, many "discoveries" don't hold up
: (Reuters) - 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.
| b*****n
发帖数: 1841 | 4 做癌症研究的形成利益团体，不能自我纠错，就只能靠外头公司的人来彻底曝光黑幕。
future.
Begley
a
【在 S*****a 的大作中提到】
: In cancer science, many "discoveries" don't hold up
: (Reuters) - 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.
| b******s
发帖数: 1089 | 5 有人的地方就有江湖。而江湖最险恶之地就是利益最大之处。所以很多重要的发现（长
远来看被证实，而不是一时概念炒作）根本不是在最hot的领域。你让那些牛霸王们来
分植物领域一杯羹，他们还不屑呢。
【在 b*****n 的大作中提到】
: 做癌症研究的形成利益团体，不能自我纠错，就只能靠外头公司的人来彻底曝光黑幕。
:
: future.
: Begley
: a
| m*********r
发帖数: 2456 | 6 NCI 养了不少懒虫～
很多所谓的基础研究，已经变相成为养家糊口的工具和自欺欺人的借口 | S****y
发帖数: 751 | | O*C
发帖数: 649 | 8 这个讲的不完全对。有不少假的，但是Amgen重复不出来不等于原来的发现不是真的。
现在实验越来越精细，越来越复杂。远远不是HCl+NaOH那么肯定反应的了。你可能按照
人家的protocol的99.9%重复了，但是可能那0.1%就把你screw up了。
future.
Begley
a
【在 S*****a 的大作中提到】
: In cancer science, many "discoveries" don't hold up
: (Reuters) - 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.
| k****o
发帖数: 589 | 9
我觉得应该设立少数刊物，搞全匿名制，专发质疑文章。到时候就有好戏看了
重复不出来的文章真害人，体会很深。关键很多时候PI不信你
【在 C*******I 的大作中提到】
: 的确，很多的文章都是垃圾。当年，一个被好几个不同实验室互相验证的假结果，浪费
: 了我不少宝贵的tenure clock 时间...现在想起来还想骂人。真想用自己的结果发个证
: 伪文章，后来想想算了,没时间精力去干这种得罪人又没funding的事......
| P*******e
发帖数: 96 | 10
那这个刊物得依附在很有品牌的刊物下面,这样申grant的时候问主编讨封信证明你今年
在这上面发了若干文章总引用多少才有公信力.
【在 k****o 的大作中提到】
:
: 我觉得应该设立少数刊物，搞全匿名制，专发质疑文章。到时候就有好戏看了
: 重复不出来的文章真害人，体会很深。关键很多时候PI不信你
| | | C*******I
发帖数: 151 | 11 匿名恐怕也行不通。这样会给道德败坏的家伙可乘之机，比如，搞个假质疑文章打击竞
争对手...
【在 k****o 的大作中提到】
:
: 我觉得应该设立少数刊物，搞全匿名制，专发质疑文章。到时候就有好戏看了
: 重复不出来的文章真害人，体会很深。关键很多时候PI不信你
| S*M
发帖数: 10832 | 12 重复不出来也不代表是弄虚作假
有些实验可能就是比较finicky
future.
Begley
a
【在 S*****a 的大作中提到】
: In cancer science, many "discoveries" don't hold up
: (Reuters) - 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.
| b*****n
发帖数: 1841 | 13 你当这些公司做实验的都是饭桶？
【在 S*M 的大作中提到】
: 重复不出来也不代表是弄虚作假
: 有些实验可能就是比较finicky
:
: future.
: Begley
: a
| g*******3
发帖数: 2520 | 14 如果试验结果都这么的脆弱，那这结果不管从理论指导上还是face value上都没有任何
意义。 所以，不能拿试验完全没有follow protocol当理由。
【在 O*C 的大作中提到】
: 这个讲的不完全对。有不少假的，但是Amgen重复不出来不等于原来的发现不是真的。
: 现在实验越来越精细，越来越复杂。远远不是HCl+NaOH那么肯定反应的了。你可能按照
: 人家的protocol的99.9%重复了，但是可能那0.1%就把你screw up了。
:
: future.
: Begley
: a
| A*****R
发帖数: 4 | 15 同意各位所说，这些假数据，烂文章确实把生物学带向深渊，平心而论，要是我做评委
，也会cut funding的。
future.
Begley
a
【在 S*****a 的大作中提到】
: In cancer science, many "discoveries" don't hold up
: (Reuters) - 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.
| b*******n
发帖数: 8420 | 16 去大公司做实验的基本上也都是有两把刷子的，至少得发个PNAS或者JCI级别的文章。
而且这帮人也相对更unbiased，如果这帮人重复几遍用了各种试剂和条件都做不出来，
我觉得学术界里的人能真正重复出来的可能性更小。
【在 b*****n 的大作中提到】
: 你当这些公司做实验的都是饭桶？
| l**********1
发帖数: 5204 | 17 Sure
please go to
HTTPS//www.rocq.inria.fr/bang/research.html
>
Research topics of the BANG project, briefly reviewed:
partial differential equations, ordinary differential equations,
methods of statistical physics, numerical algorithms and applications to:
Cell division cycle modelling for healthy and cancer cells
Aggregation-fragmentation models for prion and Alzheimer's diseases (ANR TOPPAZ)
Cell chemotaxis and cell aggregation (in French)
Molecular cancer pharmacotherapy and its optimisation
Individual-based models of tissue and tumour growth
Free surface flows (Saint-Venant, Navier-Stokes)
See also a short general presentation of the project team:
and one their paper:
Clairambault, J.
Modelling physiological and pharmacological control on cell proliferation to
optimise cancer treatments. Mathematical Modelling of Natural Phenomena, 4(
3):12-67, 2009
HTTPS//www.rocq.inria.fr/bang/JC/JC4MMNP2009.pdf
【在 b*******n 的大作中提到】
: 去大公司做实验的基本上也都是有两把刷子的，至少得发个PNAS或者JCI级别的文章。
: 而且这帮人也相对更unbiased，如果这帮人重复几遍用了各种试剂和条件都做不出来，
: 我觉得学术界里的人能真正重复出来的可能性更小。
| l**********1
发帖数: 5204 | 18 NIH R01 Tumor Stem Fundings 的关键是 双方的PIs 实验方面的 和计算统计方面的
是互认对方是idiot,respectively Lol ^~^
TOPPAZ)
【在 l**********1 的大作中提到】
: Sure
: please go to
: HTTPS//www.rocq.inria.fr/bang/research.html
: >
: Research topics of the BANG project, briefly reviewed:
: partial differential equations, ordinary differential equations,
: methods of statistical physics, numerical algorithms and applications to:
: Cell division cycle modelling for healthy and cancer cells
: Aggregation-fragmentation models for prion and Alzheimer's diseases (ANR TOPPAZ)
: Cell chemotaxis and cell aggregation (in French)
| g*********5
发帖数: 2533 | 19 I feel very uncomfortable about your post....
TOPPAZ)
【在 l**********1 的大作中提到】
: Sure
: please go to
: HTTPS//www.rocq.inria.fr/bang/research.html
: >
: Research topics of the BANG project, briefly reviewed:
: partial differential equations, ordinary differential equations,
: methods of statistical physics, numerical algorithms and applications to:
: Cell division cycle modelling for healthy and cancer cells
: Aggregation-fragmentation models for prion and Alzheimer's diseases (ANR TOPPAZ)
: Cell chemotaxis and cell aggregation (in French)
| d*******8
发帖数: 93 | 20
A solid observation has to be reproducible, other wise it is solid. And if
you decide to be a cheater, why choose to be bio-researcher? you won't get
much money out of it. Be a car or drug dealer. The meaning of it all for bio
-research is one day knowledge from your work can be used to treat a
diseases. If you are there providing false information, it will not help but
harm.
【在 S*M 的大作中提到】
: 重复不出来也不代表是弄虚作假
: 有些实验可能就是比较finicky
:
: future.
: Begley
: a
| l**********1
发帖数: 5204 | 21 Bingo
Begley CG, Ellis LM.
Drug development: Raise standards for preclinical cancer research.(2012)
Nature 483:531-533. doi: 10.1038/483531a.
//www.ncbi.nlm.nih.gov/pubmed/22460880
BUILDING A STRONGER SYSTEM
it is important to remember that
patients are at the centre of all these efforts.
If we in the field forget this, it is easy to
lose our sense of focus, transparency and
urgency. Cancer researchers are funded
by community taxes and by the hard work
and philanthropic donations of advocates.
More importantly, patients rely on us to
embrace innovation, make advances and
deliver new therapies that will improve their
lives. Although hundreds of thousands of
research papers are published annually, too
few clinical successes have been produced
given the public investment of significant
financial resources. We need a system that
will facilitate a transparent discovery process
that frequently and consistently leads to
significant patient benefit.
bio
but
【在 d*******8 的大作中提到】
:
: A solid observation has to be reproducible, other wise it is solid. And if
: you decide to be a cheater, why choose to be bio-researcher? you won't get
: much money out of it. Be a car or drug dealer. The meaning of it all for bio
: -research is one day knowledge from your work can be used to treat a
: diseases. If you are there providing false information, it will not help but
: harm.
| B*******u
发帖数: 3789 | 22 刚参加了一个stem cell的会，跟别人聊了一下说，IPS的过程本来就是随机的，所以很
多结果重复不出来也正常。 |
|
