The ghosts of immortal cells: how misidentified cells contaminate scientific literature


Biomedical research relies on the use of established model systems, such as immortal cell lines that replicate indefinitely, which provide the surrogate environment for a targeted study.

It is therefore important to correctly identify the context in which the experiment has been performed, and inculcate appropriate quality-control measures to authenticate the cell line used for research.

And yet, cell line misidentification has been, and continues to be a problem since it was first flagged in the 1950s. Databases such as the ICLAC (International Cell Line Authentication Committee) register reports of cell lines that have been misidentified or mislabeled.

So far, 451 individual cases of contamination have been identified. The problem is further compounded by the fact that some cell lines have overlapping names, leading to complications in tracing potential contamination.

In an effort to understand the scope and scale of the problem, researchers from the Radboud University in The Netherlands, mined data from publications and the ICLAC register, and found that misidentifications are still persistent in literature. The results were published in PLOS ONE.

“We researched what happened to scientific publications about misidentified cell lines from 1955 on,” says Dr. Halffman, co-author of the study and Associate Professor of Philosophy and Science Studies at the Radboud University.

“Many of these still list the wrong cells online and are often cited by other authors. After an extensive literary study, we believe this involves some 33,000 publications. That means there are more than 30,000 scientific articles online that are reporting on the wrong cells,” he adds.

Incidents of misidentification could happen due to cross-contamination, or even mislabeling. For example, a cell line for skin cancer cells may be contaminated by a completely different cell line, such as cervical cancer cells. The contaminating cells eventually erase and substitute the original cell line.

Credit: Radboud University

Surprisingly, problems with misidentification and contamination still occur, despite the availability of authentication methods, and as recently as last year. Cell lines may be authenticated by genetic profiling methods, such as identification of short tandem repeats (STRs) markers, to establish that the cell line belongs to the correct family.

However, the attitude towards cell line misidentification as a problem appears to be contentious, and could depend on a number of factors such as the area of research and the experimental context in which the cell line is used. In some cases, the results of the experiment may be unaffected by the cell line. In other papers however, the results could be rendered meaningless, leading to data that can’t be reproduced.

The most important factor is the problem with scientific retraction, and the questions that may be raised regarding the scientific integrity of the reporting groups. However, with the ever-expanding use of biological materials and protocols in multidisciplinary research, it’s becoming increasingly important to maintain consistent practices that ensure reproducible data in scientific literature.

“Most scientists don’t intentionally publish findings on the wrong cells,” explains Horbach, also co-author on the paper.

“It’s an honest mistake. The more concerning problem is that the research data is potentially invalid and impossible to reproduce. What’s even scarier is that we’ve known about these wrongly identified cells for half a century, yet many researchers aren’t aware of this. New articles are published every week about misidentified cells.”

The problems with misidentification clearly requires more awareness or enforcement of quality-control measures to ensure correct reporting and reproducible results in science. A 2010 review in Nature Reviews Cancer highlights the role that funding agencies and journals could play in this process, by introducing additional requirements for authentication before publishing.

The current paper focuses on the problem that already exists, relating to the papers that report on the wrong cell line. Though the research may not all be invalid, the difficulties in tracing the contamination might engender mistrust in publication quality and could impair scientific progress.

“It’s not our intention to damage anyone’s reputation with this publication. It’s about the overarching problem: what are we going to do about the mistakes that have been made? That’s all we want to determine.

One solution would be to put a disclaimer on all 30,000 publications explaining that they report on the wrong cell line.

It would then be up to readers to decide whether it’s a problem or not, because sometimes it really doesn’t matter. Basically, we want to caution people to be careful with the interpretation of results. Then again, labelling problematic papers also takes time and money,” say Halffman and Horbach.

Source: Radboud University

Original PLOS ONE paper: “The ghosts of HeLa: How cell line misidentification contaminates the scientific literature”