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Science

Over 30,000 Published Studies Could Be Wrong Due To Contaminated Cells (sciencealert.com) 106

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.

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Over 30,000 Published Studies Could Be Wrong Due To Contaminated Cells

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  • by TheReaperD ( 937405 ) on Wednesday October 18, 2017 @05:10AM (#55388605)

    This is what happens when you don't let scientist harvest live humans for research... sheesh; and they thought *I* was mad.

    • by Z00L00K ( 682162 )

      I'm more curious about how many cases that have been contaminated with the HeLa [wikipedia.org] strain which is one of the most known immortal strains out there. Fun fact is that the scientists have grown about 20 tons of that strain so far - that's a huge woman.

      • by msauve ( 701917 )
        If you were actually curious, you would have simply checked the linked-to register. Instead, you jumped in to show everyone you've read that book about Henrietta Lacks.
        • All this big ruckus for a simple editing error? From my orientation, Technical Writers,(TW), now have something to do. Update Humanity's knowledge, and tell others about this new discovery. TW's don't want to? It's this, or they can go home and wait for their next gig.
    • by Anonymous Coward

      Would not make a difference. They switched human lung and human liver cell as well as many other human cells.

  • Whew (Score:2, Insightful)

    by Kazymyr ( 190114 )

    The HL-60 line isn't listed there. That's what I used in my research back in the day.

    • Is this the one that contaminated everything? Would be smart to just plan your research on that line, althoughyour colleagues might not like to have it around
      • 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 repla

  • by qbast ( 1265706 ) on Wednesday October 18, 2017 @05:33AM (#55388647)
    *) Effective only if you are a mouse with a liver cancer.
  • by Anonymous Coward

    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.

    • by Anonymous Coward on Wednesday October 18, 2017 @06:23AM (#55388773)

      0,8% - the paper is open access if you want the details.
      http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0186281

      • 0,8% - the paper is open access if you want the details. http://journals.plos.org/ploso... [plos.org]

        What percentage of the population is affected by that seemingly small impact?

        How many billions (or trillions) in costs are associated with that seemingly small impact?

        Risk mitigation relies on asking the right questions. Unfortunately, TFA starts to answer my questions. Oncology is the field most contaminated by a large margin. I'd say it's pretty damn important to understand just how fucked our studies are related to one of mankinds most pervasive killers. Cancer affects a hell of a lot more than 0.8% o

        • It is important to note that immortalized cell lines are essentially cancer cells in culture. So while using the wrong line due to contamination hurts the direct usefulness of research, it doesn't render that research useless, because the data is still about whether or not the compound of interest killed cancer cells... just different ones than you thought. This sort of thing could be the reason that so many treatments that seem promising in academia fail to pan out when they move to industry with more fu
          • by jedidiah ( 1196 )

            You kind hit at the problem in your own answer. I don't give a f*ck if MY wonder drug cures some other cancer. I want it to cure MY particular cancer. If the basic lab research was botched then there will be some very disappointed (and desperate) cancer patients when it comes time for the human trials.

            ALL of that is going to cost a big pile of money and make everything more expensive. The successes will have to subsidize the failures (as they always do).

            You will end up having to pay a lot more, or your insu

            • Oh it'd go through a bunch of stuff after academia before it got put it you, unless it'd be on an experimental protocol where "oops, he died" isn't so bad an outcome. These sorts of mistakes are impacting basic research, not third party safety and efficacy testing or manufacturing. FDA GLP/GMP inspections are no joke, people make livings just being consultants for telling companies how not to get their asses handed to them. New cancer treatments don't come directly out of some pottering professor's lab w
              • FDA GLP/GMP inspections are no joke...

                When validating basic research turns into a joke creating 30,000+ contaminated documents, other vetting processes tend to become rather irrelevant.

                ...New cancer treatments don't come directly out of some pottering professor's lab where the hung over grad students throw something together in the centrifuge after sacrificing a few mice.

                After finding 30,000+ mistakes, they might as well have.

                • Basic research is the scientific equivalent of brainstorming, or throwing shit at the wall and seeing what sticks. This sort of contamination problem means you have a higher failure rate at the next step of development, not that vetting and validation is irrelevant. It is worth solving because we're missing out on potential solutions and spending more grant money than we should for the data we're getting out of it, but your views appear to lack perspective.
            • You will end up having to pay a lot more, or your insurance company will, or your government health care entity will just say "fuck it" and leave you to die because the meds are too expensive.

              Looking for the answer in the Medical Industrial Complex fueled by relentless greed?

              D) All the above

            • Don't worry too much. The failure results will be obfuscated by a paywall and/or HIPAA protection so you don't have to trouble yourself with them. The pharma company gets paid for your chemo round whether it works or not.
          • It is important to note that immortalized cell lines are essentially cancer cells in culture. So while using the wrong line due to contamination hurts the direct usefulness of research, it doesn't render that research useless, because the data is still about whether or not the compound of interest killed cancer cells... just different ones than you thought. This sort of thing could be the reason that so many treatments that seem promising in academia fail to pan out when they move to industry with more funding for quality control.

            I completely agree with your point. Even though the cells in researches were contaminated, it doesn't render those researches completely useless as long as they can identified what cells they were using in their research. If they could identify the cells they used in their research, then they just need to update the conclusion of their research.

            However, the nature of science researches is to cite/refer to previous research results. That said, some (if not most) contaminated cell researches could become less

          • Before it was used clinically there would have been in vivo trials, no? I doubt anybody died from this.

            • Yes, exactly. Compromised basic research leads to failed follow up experiments and shrugs all around as they move on to the next promising compound. It is a waste of resources and increases the background noise in looking for useful things, but not a danger to the public.
  • Is this why they report that coffee is bad for you one week and good for you the next?
    • by DontBeAMoran ( 4843879 ) on Wednesday October 18, 2017 @07:49AM (#55389117)

      No, that's just the centuries-old fight between coffee-drinking scientists and tea-drinking scientists. There's also a third party of insane scientists who advocate drinking dihydrogen monoxide but they're a minority so you rarely hear from them.

      • They probably died, as anyone who drinks dihydrogen monoxide inevitably does.
        • by Nite_Hawk ( 1304 )

          That's sort of the whole point of the article though. The author discovered evidence that (amonst other things) historical research findings on tea and coffee related fatalities may have used samples with dihydrogen monoxide contamination that previously went unnoticed all the way back to the 1950s. while correlation does not equal causation, there's a strong body of evidence that anyone who ingests large quantities of dihydrogen monoxide eventually dies.

          How much dihydrogen monoxide contamination did the

          • Now don't go and quote me on this, but I've heard that even the temperature of said dihydrogen monoxide can skew the results, by a lot.

  • Henrietta (Score:5, Interesting)

    by 110010001000 ( 697113 ) on Wednesday October 18, 2017 @06:30AM (#55388791) Homepage Journal
    This is Henrietta's revenge. That is what scientists get for stealing her cells in the first place!
  • This is a problem that could be addressed by improved medical databases. Of all the ways in which SV could 'disrupt' medical research and practice, this would be the least controversial.

    • Yes, but what is the reimbursement model for that!?! It doesn't involve microtransactions, nor push notification.

      I suppose it could.... hmmm....

    • Improved medical databases? Blockchain!

    • Here, they looked at "research" results. As soon as you have "medical" results, you're constrained by law, not technology. Disrupting laws sometimes works (Uber), but usually not (Theranos).

    • There are a lot of laboratory information management systems (LIMS) that purport to address issues such as this. But many (most?) research labs don't use them because they are too expensive. Either in terms of licensing proprietary software or managing open source solutions.
  • This is exactly the sort of thing that would have been caught during the rigorous, diligent, inherently skeptical peer review process.

    But seriously, no wonder most studies can't be replicated by others [bbc.com] -- the odds are high that either the cells in the original study, the attempted follow-on, or both were screwed up.

    • 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

      • Peer review even at its best is basically a test of "seems legit" before publishing to avoid obvious sloppy mistakes, bad stats, unwarranted conclusions. . . . Peer review is an indication that something is not obviously bogus.

        I think you're talking about the idealized version of what peer review was originally intended to be. As we're all aware, over the past few decades the mantra "peer reviewed articles in highly regarded journals" has become one of the prominent measuring sticks used to present whatever topic is currently catching grant dollars as "settled" and try to shut down debate. That's pretty much the polar opposite of "not obviously bogus," and that's what I was taking a dig at.

  • Medical research cause cancer in mice.

  • What a relief (Score:2, Offtopic)

    by rastos1 ( 601318 )
    TFA makes me much less worried about the crappy code I write. I mean, reading /. for years taught me to be ashamed about writing sloppy code, and ignoring best practices in SW development and security. It got me in trouble for raising a hell for using obsolete/EOL-ed development tools/languages/OS/, etc etc. But now ? I feel relief. There are people out there that are doing much more important work than me, they fuck it up and it still goes on for decades. I can sleep well. I have nothing to worry about an
  • Makes me happy to know that we use primary cells in the research in my lab rather than cell lines.

    Still, I wonder how many primary cell lines become contaminated with immortalized in labs where both are cultured in the same space?
    • 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.
  • Everything You Know Is Wrong.

  • Can someone who knows more about this process comment how this could possibly be? It smells so much like somebody is feeding us fake information. First off, if this has been a problem since the 1950s, why is it suddenly news that makes it sound like nobody knew of any problems till yesterday? Or is it more like every year we find some bad cells and we need to go back and redo those experiments... and someone decided to add up all problems for the last 100 years and make a write up about it?

    • 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.
    • by drunken_boxer777 ( 985820 ) on Wednesday October 18, 2017 @08:52AM (#55389427)

      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 [plos.org] 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.

    • by pesho ( 843750 ) on Wednesday October 18, 2017 @09:20AM (#55389579)

      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.

    • It's not that hard to believe. In every field, and computer science is one as well, many scientific papers are completely wrong with their analysis, and most of the time, it is pretty hard to detect unless you're an absolute expert in the field. Peer-review is supposed to detect bad papers, but finding experts is not always easy, and sometimes everything you read in the paper seems consistent, so unless you try to reproduce it, you can only say "that looks like good work".

      Now, that's not the end of the wor

  • by Qbertino ( 265505 ) <moiraNO@SPAMmodparlor.com> on Wednesday October 18, 2017 @08:59AM (#55389461)

    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.

  • by Archtech ( 159117 ) on Wednesday October 18, 2017 @09:35AM (#55389681)

    ... if all studies were replicated at least twice by other teams in other institutions (and preferably funded by different sponsors).

    • Every working scientist would love to see this happen. Who's going to pay for it?
      • Every working scientist would love to see this happen.

        Even if it compromises (perhaps significantly) their publication rate / bonuses / career path? I'd love to see a survey or two on that.

        • I think the scientists would like to see the publish or perish schema go away as well...
          • I think the scientists would like to see the publish or perish schema go away as well...

            Helpless victims one and all, I'm sure.

        • Who cares about surveys? Fund some grants to reproduce results. I guarantee there will be takers.
          • Who cares about surveys? Fund some grants to reproduce results. I guarantee there will be takers.

            Not that many. You will never get great publications merely replicating results. Sure it's a grant now, but at the penalty of your future career.

    • and they both order their tissue cultures from the same place? or from different suppliers selling the same wrong one?

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