The ghosts of HeLa: How cell line misidentification contaminates the scientific literature

Abstract

While problems with cell line misidentification have been known for decades, an unknown number of published papers remains in circulation reporting on the wrong cells without warning or correction. Here we attempt to make a conservative estimate of this 'contaminated' literature. We found 32,755 articles reporting on research with misidentified cells, in turn cited by an estimated half a million other papers. The contamination of the literature is not decreasing over time and is anything but restricted to countries in the periphery of global science. The decades-old and often contentious attempts to stop misidentification of cell lines have proven to be insufficient. The contamination of the literature calls for a fair and reasonable notification system, warning users and readers to interpret these papers with appropriate care.

Fig 1. The creation, distribution and literature of a cell line: A cultured sample of cells (blue cells) may produce an immortal cell line (red cells), sometimes announced in ‘an establishing paper’ (in white).

Cells may then be distributed to other researchers and reported in research papers, the ‘primary literature’. If misidentification of cells is reported in ‘a notifying paper’ (in red, bottom left), this may raise questions about the entire cell line (question marks) and the papers based on it, since misidentification commonly occurs at the source. Notifying papers should be reported to ICLAC, which will decide whether cell lines should be added to the ICLAC misidentified cell line register. Meanwhile, the contaminated primary literature is cited (dotted lines) by ‘secondary literature’, spreading the contamination further.

Fig 2. The distribution of the contaminated primary literature over the years.

The graph includes references to the first report on intraspecies cell line misidentification [10], a major list of misidentified cell lines based on HeLa contaminations [44] and the introduction of Short Tandem Repeat (STR) as technique for cell line authentication [45].

Fig 3. The percentage of contaminated primary articles as a fraction of the total number of articles on cells per country.

The figure includes the 25 countries with the largest absolute number of articles in the contaminated primary literature.

Fig 4. The distribution of contaminated primary literature over the research areas as defined by Web of Science.

Only the 25 most affected research areas are included.