The HeLa problem: What a retraction says about whether cancer researchers can trust their cell lines
Retraction Watch readers who’ve read Rebecca Skloot’s bestseller The Immortal Life of Henrietta Lacks may remember that decades ago, scientists began realizing that Lacks’s cells, now known as the HeLa cell line and used in labs around the world, were so good at proliferating that they had taken over many other cell lines researchers use to study human disease.
Such readers would have been nodding their heads at a front-page Wall Street Journal on Saturday. As Amy Dockser Marcus (no relation to Adam) reports:
Cancer experts seeking to solve the problem have found that a fifth to a third or more of cancer cell lines tested were mistakenly identified—with researchers unwittingly studying the wrong cancers, slowing progress toward new treatments and wasting precious time and money.
In hundreds of documented cases that undermine a broad swath of research, cancer samples that were supposed to be one type of tumor have turned out to be another, through either careless laboratory handling, mislabeling or other mistakes.
It’s not just HeLa cells that have been found as contaminants; a melanoma cell line is thought to have been mixed up with a breast cancer line, for example. As has become a common refrain on Retraction Watch, however, when scientists tried to sound alarm bells, they went unheard:
But researchers who yelled loudest were mostly ignored by colleagues fearful such a mistake in their own labs would discredit years of work.
Leaders in the field say one of the biggest obstacles to finding a cancer cure may not be the many defenses nature affords malignancies, but the reluctance of scientists to address the problem.
The WSJ study leads with an anecdote about a retraction in Oral Oncology. The retraction notice in question is quite detailed, which we appreciate, but what’s particularly puzzling is the reason for the retraction:
The cell line ACC3 which was used in the study reported in the above named paper was reportedly found cross contaminated with HeLa in several laboratories world-wide (Phuchareon et al., PLoS One 2009;4:e6040). This point was raised during the peer-review process of the manuscript. The authors obtained the cells directly from one of the original sources (Dr. Saku, Niigata University School of Dentistry, Japan) and observed a TP53 mutation in the ACC3 cells, which led them to believe that the cell line was distinct from HeLa because the latter is known to carry wild type p53.
Following acceptance of the paper for publication, the authors were unable to confirm the TP53 mutation during a repeated sequence analysis. A short tandem repeat (STR) analysis, which is recommended for cell line verification, was then performed. The results found that the ACC3 cells used in the study correspond to the ACC cell lines cross contaminated with HeLa as reported by Phuchareon et al. The authors communicated this new information to the Editors of Oral Oncology.
The scope of Oral Oncology covers only head and neck cancers. As the findings of this paper no longer refer to a cell line that is implicated in these tumours, the paper has been retracted from the journal, since it would not have been acceptable for publication during peer-review based on the information now available.
The major conclusions of the manuscript regarding the influence of SIVmac239-Nef on tumor cell proliferation and migration in CXCR4 expressing tumor cells, as well as on angiogenesis, are not affected.
In other words, the real reason the paper is being retracted isn’t because the results were no longer valid, but that they were no longer valid for a head or neck cancer.
In a January 2011 article describing how estrogen metabolites influence the release of inflammatory molecules from human amnion-derived cells, Italian researchers took advantage of a cell line called WISH, which they describe as “constituting a model for in vitro studies of amnion functions.”
There was just one problem: WISH cells have been known for more than 40 years to be highly proliferative HeLa cervical cancer cells. The authors did acknowledge this fact in their conclusions, albeit obliquely and only briefly: “… considering WISH cells as a suitable model for human amnion cells, our results suggest that active estrogen metabolites may finely modulate the onset of human labor. Yet, looking on recent reports, by which WISH cells should be more meaningfully be likened to neoplastic cells, our results could support estrogen metabolite relevance in neoplastic competence via inflammation pathway activation.”
That “caveat,” Perkel notes, “makes the study’s scientific relevance open for debate.” We particularly like this quote from Perkel’s piece, which we’d recommend reading in its entirety:
“What really frustrates me is that Stan Gartler showed that a whole series of lines were cross-contaminated with HeLa cells, and yet those bloody cells are still being used now in their false guise,” exclaims John Masters, professor of experimental pathology at University College London. “For nearly 50 years, people have been using falsely identified cells totally unnecessarily because they haven’t checked.”
The Wall Street Journal story — which we’d also recommend reading in its entirety — also quotes Masters, and highlights another issue. We’ve actually been aware of the Oral Oncology retraction since January, and have been meaning to write about it, but it got lost in our steady deluge of great tips from helpful readers. That’s just another reminder of just how many good retraction stories there are nowadays. (And that we’re two guys with day jobs, of course.)