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Thousands of studies could be flawed due to contaminated cells

4:00pm Thursday 19th October 2017 content supplied byNHS Choices


How did they estimate the size of the problem?

The researchers searched the scientific databases for reports of misidentified cell lines.
In particular they were interested in cell lines where none of the original "correct" cell line (the "original stock") is known to exist. When this is the case, there is no way to cross-check the identification of a cell line against the original stock. This means that most or all of the cells in the stock may be different to the original stock, or misidentified.

Misidentified cell lines are reported to the International Cell Line Authentication Committee's (ICLAC) database, which lists 451 cell lines with no original stock.

The researchers then searched the following databases for articles reporting research studies using these misidentified cell lines:

  • the Cellosaurus database
  • the German Collection of Microorganisms and Cell Cultures database (DSMZ)
  • the American Type Culture Collection database (ATCC)
  • the European Collection of Authenticated Cell Cultures database (ECACC)
  • the Web of Science, a scientific literature database

They also identified any secondary published research articles that had mentioned in their references any of the studies using the misidentified cell lines.

As well as reporting on the amount of articles they found, the researchers also presented three case studies tracking publications about a single misidentified cell line to show how information based on these cell lines can spread.
Because this study has relied on researchers identifying and reporting misidentified cell lines not all cases where the problem has occurred will be captured.


What did they find?

The researchers identified 32,755 research articles that were "contaminated" by studying misidentified cell lines. Over half of these papers were published since the year 2000, and 58 articles were published as recently as February 2017. This suggests that the problem is not fading away.

Looking at how far the potentially incorrect information from these "contaminated" articles had spread, the researchers found:

  • overall, more than half a million research papers were estimated to mention one of the "contaminated" articles
  • almost all (about 92%) of the "contaminated" articles had been mentioned by at least one other research paper
  • 46 of the articles had been mentioned in over a thousand other research papers
  • 2,600 of the articles had been mentioned in over a hundred (but under a thousand) other research papers

To give an example of how misidentification can affect subsequent research there is a cell line called ALVA-31. This cell line was established in 1993 from a human prostate cancer, but in 2001 it was identified that the "stock" in use was identical to a different human prostate cancer cell line called PC-3.

Fifty six published articles referring to the ALVA-31 cell line were found. Of these, 22 were published after the discovery that the ALVA-31 cell line had been misidentified. Of those 22 articles, only two mentioned the potential misidentification of ALVA-31. Some of these papers were published in 2016 - 15 years after the misidentification was reported.

The 56 articles on ALVA-31 had been mentioned in 2,615 other research papers.


What is the impact of this contamination?

The first concerns about contaminated literature were raised over half a century ago. Given some of the contaminated literature found in this study was published this year, clearly this issue remains a pressing one for researchers.

Although some articles mentioning the "contaminated" research may be doing so to point out the misidentification, the sheer mass of research potentially built on false grounds is still alarming.

The contaminated literature may have important impacts. The findings of these studies may lead researchers to draw incorrect conclusions, and perform additional studies based on these. As a result, these studies could waste both valuable research time and money.

On the other hand, the researchers recognise that not all of the papers they identified found serious errors. In some cases, the exact origin or characteristics of a cell line may not actually affect the results of an experiment that much.


What steps can be taken to remedy this problem?

This is a known problem and ICLAC has published guidelines aimed at minimising misidentification issues.

Good researchers are likely to already carry out checks to make sure their cell lines are what they think they are. They also take steps to make sure they don't contaminate their cells. This study shows why it is important for researchers to consistently take these steps.

The authors of the current research make a number of suggestions for additional improvements to the current situation, including that:

  • papers reporting on the discovery of misidentified cell lines need to be clearly labelled so that other researchers can easily find them
  • to make sure they don't "spread" misleading research in their own publications
  • those aiming to clean up the contamination problem should write about the contamination, using social media campaigns and general media coverage to highlight the issue and inspire greater research scrutiny
  • in cases where uses of misidentified cell lines produce a false conclusion papers should be officially withdrawn

The findings should not cause unnecessary concern about existing drug treatments. Not all of these "contaminated" studies would have assessed potential new drugs. If they did, any that showed promise would then have had to undergo rigorous testing in animals, and then humans, before they could be used in routine practice.


'More than 30,000 scientific studies could be wrong due to widespread cell contamination dating back 60 years' reports the Mail Online...

Links to Headlines

More than 30,000 scientific studies could be WRONG due to widespread cell contamination dating back 60 years, new report warns. Mail Online, October 17 2017

Links to Science

Horbach SPJM, Halffman W. The ghosts of HeLa: How cell line misidentification contaminates the scientific literature. PLOS One. Published online October 12 2017

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