Derek Lowe's commentary on drug discovery and the pharma industry. An editorially independent blog from the publishers of Science Translational Medicine . All content is Derek’s own, and he does not in any way speak for his employer.

Let’s file this one under “We’ve seen this before, and I’ll bet we’ll see it again”. Anyone who’s worked for some years in cell culture (or with people who have) should appreciate the dangers of cell line contamination. You can get mycoplasma, you can get other cell lines entirely (particularly others that are more vigorous and hardy than the ones you’re trying to grow), and you can get viral thingies that cause you so much trouble that your entire company gets bought by someone else.

Here’s a new paper in PLoS ONE that tries to get a handle on the problem. The real kicker is that some of these cell lines became contaminated along the way, so that earlier papers and later ones in the field are actually referring to different cells. And others became contaminated (or mis-identified) so early that basically all of the literature on them is mistaken. Warnings have taken place about this stuff again and again, and the current literature is surely cleaner than the older papers. But how bad is it in the published record?

By correlating the literature with a list of known contaminated cell lines (many of them invaded by HeLa cells), the authors estimate a lower bound of over 32,000 papers that have worked on the wrong cells, compared to what they report. In turn, these papers are cited by at least 500,000 more articles, and that total excludes self-citations. And as the authors note, they were quite conservative with their name strings in the searches, so although there are also still a few false positives in those numbers, they are surely tiny compared to the false negatives – the mistaken papers that haven’t been flagged yet. A representative example: