Every clinician can relate to the frustration of when a blood or urine sample sent for culture turned out to be contaminated. Indeed, contamination has the potential to jeopardise patient treatment. Likewise, the scientific community is facing a massive contamination issue that has quietly infected research since the 1960s1.

Contaminated cells cast doubt on findings of more than 30,000 scientific papers

Even as warnings of contamination persisted, studies using flawed cell lines boomed. Photo credit: Tom Deerinck/NIH/PLoS ONE/ArsTechnica UK
Even as warnings of contamination persisted, studies using flawed cell lines boomed. Photo credit: Tom Deerinck/NIH/PLoS ONE/ArsTechnica UK

A recent study from Radboud University in the Netherlands picked old wounds in the scientific community regarding the integrity of cell lines. Cell lines are previously established cells of human or animal origin, for example, from human lung or monkey kidney. Cell lines have greatly simplified research, and are essential in vaccine production, drug testing, as well as in studies on cellular protein metabolism and genetic function2.

The scientific community have been privy to decades of warnings that the cell lines used in their research may have been impure or wrongly identified. For example, prostate cells may in fact have been cervical cells. Implications of this flaw reach far and wide. Treatment that was developed based on these research findings may be null and void.

Scientists Serge Horbach and Willem Halffman brought fresh attention to an old problem. The Dutch duo dug deeper into this 60-year old issue, and sought to quantify its magnitude. What they found was astounding – uncovering at least 33,000 papers were published based on these ‘bad cells’. And these were only open access papers. These flawed articles are estimated to be referenced by another half a million additional papers – about 10% of the scientific literature of relevant subject areas1.

“We’re not saying those 33,000 articles are wrong,” remarked Halffman. “But, among those 33,000 there are definitely some with wrong conclusions3.”

“The problem is not going to go away”

This threat of contamination shakes the very foundations of cellular research. How did this happen?

Labs end up with misidentified or contaminated cells in a myriad of ways. It is common practice for some facilities to get different cell lines from other labs, instead of purchasing them from an authorised manufacturer. A miniscule speck of what shouldn’t be in those cells is enough to contaminate the entire batch. Furthermore, cell lines often spend years in the corner of freezers. Unless meticulous recordkeeping is practiced, mistakes are bound to happen. Although there are ways of confirming a cell’s identity, these tests are not run consistently enough4.

A timeline of HeLa cells. Photo credit: Justine Chia; Henrietta lacks: lacks family; polio: David Goodsell; cloning: NIH; HPV: Ed Uthman; DNA helix: NHGRI; HELA cells: NIH/Berkeley Science Review
A timeline of HeLa cells. Photo credit: Justine Chia; Henrietta lacks: lacks family; polio: David Goodsell; cloning: NIH; HPV: Ed Uthman; DNA helix: NHGRI; HELA cells: NIH/Berkeley Science Review

The infamous HeLa cells play a large role in this contamination fiasco. Obtained in the 1950s by less-than-ethical means from an African American woman named Henrietta Lacks, HeLa cells shot to stardom by being the first ‘immortal human cell line’. Henrietta Lacks was a woman suffering from cervical cancer. Samples of her cancer cells were found to be heavily mutated and could continue multiplying indefinitely. Amazed by the resilience of HeLa cells, it wasn’t long before the entire scientific community were using them for experiments – while her family remained in the dark, only to be informed more than two decades later4.

Later on, however, HeLa cells were found to be extremely aggressive. Scientist Dr Stanley Gartler, also a geneticist, was the first to raise the alarm in the 1960s after he discovered that all 18 of his different cell lines had been ‘infected’ and transformed into HeLa-like cells. Despite this revelation, many scientists had already become so entranced by the opportunities offered by HeLa cells and refused to accept its implications4.

Indeed, a recent study in the 21st century found that of all the scientists who worked in labs with HeLa cells, only 50% ran tests to check if their other samples were contaminated4. Two supposedly unique cell lines, Hep-2 and INT 407 were in fact found to be HeLa derivatives5. Some estimate that more than 90% of contaminated cell lines in China contain HeLa cells2.

Researchers need to break free from the shackles of complacency

To the scientific community’s credit, various efforts such as the International Cell Line Authentication Committee as well as an official registry that keeps records of known cell line contamination were established. However, are these methods enough?

"We should just add a little label, nothing too drastic, we don't want to damage anybody's reputation or claim any kind of major mistake, but all we're saying is those papers should get an expression of concern," said Halffman.

Research integrity is an area with very little room for compromise. The responsibility of upholding the sanctity of research falls on the shoulders of each and every scientist. Hopefully, the efforts of a few can drive the many to take more stringent steps to ensure that a half-a-century old problem does not come back to haunt us. MIMS

Read more:
107 papers by Chinese researchers retracted by Springer Nature
Cancer research body criticized for methods of evaluation
Medical technology advances: 3 modern breakthrough innovations shaping the future of medicine

Sources:
1. https://arstechnica.co.uk/science/2017/10/50-year-old-research-issue-still-biting-biologists/
2. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3341241/
3. http://www.cbc.ca/news/health/second-opinion-171021-1.4365023
4. http://berkeleysciencereview.com/article/good-bad-hela/
5. https://www.statnews.com/2016/07/21/studies-wrong-cells/