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Over 30,000 Published Studies Could Be Wrong Due To Contaminated Cells (sciencealert.com)
An anonymous reader quotes a report from Science Alert: Researchers warn that large parts of biomedical science could be invalid due to a cascading history of flawed data in a systemic failure going back decades. A new investigation reveals more than 30,000 published scientific studies could be compromised by their use of misidentified cell lines, owing to so-called immortal cells contaminating other research cultures in the lab. The problem is as serious as it is simple: researchers studying lung cancer publish a new paper, only it turns out the tissue they were actually using in the lab were liver cells. Or what they thought were human cells were mice cells, or vice versa, or something else entirely. If you think that sounds bad, you're right, as it means the findings of each piece of affected research may be flawed, and could even be completely unreliable.
Horback and fellow researcher Willem Halffman wanted to know how extensive the phenomenon of misidentified cell lines really was, so they searched for evidence of what they call "contaminated" scientific literature. Using the research database Web of Science, they looked for scientific articles based on any of the known misidentified cell lines as listed by the International Cell Line Authentication Committee's (ICLAC) Register of Misidentified Cell Lines.There are currently 451 cell lines on this list, and they're not what you think they are -- having been contaminated by other kinds of cells at some point in scientific history. Worse still, they've been unwittingly used in published laboratory research going as far back as the 1950s.
Horback and fellow researcher Willem Halffman wanted to know how extensive the phenomenon of misidentified cell lines really was, so they searched for evidence of what they call "contaminated" scientific literature. Using the research database Web of Science, they looked for scientific articles based on any of the known misidentified cell lines as listed by the International Cell Line Authentication Committee's (ICLAC) Register of Misidentified Cell Lines.There are currently 451 cell lines on this list, and they're not what you think they are -- having been contaminated by other kinds of cells at some point in scientific history. Worse still, they've been unwittingly used in published laboratory research going as far back as the 1950s.
This is what happens when you don't let scientist harvest live humans for research... sheesh; and they thought *I* was mad.
"Be particularly skeptical when presented with evidence confirming what you already believe." -
*) Effective only if you are a mouse with a liver cancer.
What percentage of published studies are affected? Sure, 30,000 seems like a ton, and if there is critical work in there it is certainly bad, but if this is 30,000 out of 300 million or some arbitrarily large number of studies, it isn't as catastrophic as the headline suggests.
Is this why they report that coffee is bad for you one week and good for you the next?
This is Henrietta's revenge. That is what scientists get for stealing her cells in the first place!
Academic labs aren't really known for following strict protocol, so I imagine quite a bit of cross contamination occurs. That'd be among the reasons to limit how many times you passage the cells before going back to the LN2 tank for more. Still, it isn't like human cells live very long on a stainless steel BSC surface so it wouldn't take too much effort to drop the contamination rate.
Improved medical databases? Blockchain!
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It is easier to test now than it used to be. You wouldn't be able to tell them apart visually with a microscope, for example. It has been a known issue for a while now, the scope is still being sussed out.
On step #4, they may be using the same suppliers. How many suppliers are there for experimental cell lines?
Is this [HL-60] the one that contaminated everything? /i?
I am not a biiochemist, but... That seems to be a human leukemia line.
Are you maybe thinking of HeLa - the very hardy immortalized cervical cancer cell line that was the first to be successfully grown in bulk?
I hear there was a model for the progression of cancer that had to be scrapped, because it was really the result of HeLa cells, escaped into laboratory environments, eventually contaminating virtually any cancer cell culture experiment and replacing the intended cells.
Bantam Dominique roosters crow a four-note song. Once you've heard it as "Happy BIRTHday" you can't NOT hear it that way
This has been known for a while, but perhaps not broadly known, and not by "the general public". The link to the ICLAC in TFS is evidence of that.
The actual paper will answer your questions, but briefly: people make mistakes in maintaining cell lines, and contamination is easier than you think, particularly in primary cell lines.
I didn't see the authors mention if reproducibility sorts this out, if someone can't reproduce the results in another cell line or in an animal model, the original results are considered context dependent.
This is classic.
The bane of modern utopia.
Efficiency and fragility are directly correlated.
This goes for any system and society.
If there is one thing that has a large chance of being modern societies demise, it is this.
Scary, if you think about it.
Just imagine: One replenishing bioculture that goes back some decades turns out to be labled wrong and all of a sudden countless biological studies are beyond worthless.
Long story short: Do not over-optimize. And question the status-quo once in a while. Especially with systems that seem to run flawlessly indefinitely.
We suffer more in our imagination than in reality. - Seneca
4. Other scientist recreate the process that proved or disproves the theory
4.5. Other scientists buy cells from the same misidentified cell line to use in their "repeatability" study. ...
6. Rinse and repeat.
Bantam Dominique roosters crow a four-note song. Once you've heard it as "Happy BIRTHday" you can't NOT hear it that way
It is a problem that has been known for a long time. Initially we lacked tests to validate the origin of the cell lines. Now we have an established panel of markers that can be used to cheaply and reliably confirm the identity of cell lines. The National Institute of Health, which is the major funding source for biomedical research in the US, requires all funding applications to have a plan for authenticating biological materials including cell lines.
Most of the literature using misidentified cell lines is probably old, although there are still people doing research who are either oblivious to the issue or just don't care. I think the conclusion that all these studies are invalid is an overstatement. Many if not most of these works are likely investigating fundamental biological processes that would be the same regardless of the cell line. The studies that are questionable would be the ones relying on the cell line fatefully preserving the characteristics of the original cell, like studies trying to develop therapies for various diseases or investigating processes carried out by specialized cell types.
There are many other problems that are associated with cell lines that I would think are more serious than the mis-authentication. For starters cells change when they are placed in the dish and loose many of the important characteristics of the originating cell. This means people need to be really careful when deciding if a particular experiment can be done on a cell line. Then there are examples of low level microbial contamination that goes unnoticed by the people growing the cells, but can clearly be detected in gene expression data if you look for it (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4239086/ if you look at figure 2 of the paper you can see that some labs are consistently sloppy). There is also a host of technical issues that can impact the conclusions of cell line studies ranging from the quality and source of reagents, to the experience of the staff and the techniques used to maintain the cells. These tend to vary a lot across labs and rarely documented in the publications.
... if all studies were replicated at least twice by other teams in other institutions (and preferably funded by different sponsors).
I am sure that there are many other solipsists out there.
This is exactly the sort of thing that would have been caught during the rigorous, diligent, inherently skeptical peer review process.
erm... while you seem to be taking a dig at peer review, and I'll happily bend your ear for ages over the flaws of it, this isn't really one of them.
Peer review even at its best is basically a test of "seems legit" before publishing to avoid obvious sloppy mistakes, bad stats, unwarranted conclusions. If someone says "we did X, tested hyothesis Y, got results Z and rejected the null hypothesis (p 0.5)", peer review will check if the reaults are plausible givne the experiements, if the boldness of the claims are consistent with the level of evidence and so on and so forth.
Peer review is an indication that something is not obviously bogus. What hapens afer peer review (replication etc) is what eventually catches the stuff that (a) anyone cares about and (b) is subtly bogus. Something isn't generally considered a hard fact until it's been replicated. Scientists generally know this...
SJW n. One who posts facts.