Blog 1: An unexpected risk?
Cell lines are regularly used in experiments that aim to increase the understanding of the causes of cancer and their treatments. Problems occur though when these cell lines are misidentified or contaminated. There have been several high-profile stories since the 1960s (Horbach and Halffman, 2017) of instances where cell lines have been misidentified or contaminated, leading to significant problems:
The Chang Liver cell line
In December 1962, Dr R. Shihman Chang, a pioneer in cell culture, deposited a “Chang Liver” cell line at the American Type Culture Collection (ATCC). This cell line was useful for research that needed an immortalised “normal liver” in vitro model. As cell culture techniques were still being devised and implemented, the “Chang Liver” cell line was a rare commodity. In 1967, Stanley Gartler, a University of Washington researcher, discovered that the Chang Liver cell lines had identical characteristics to HeLa cells, an extremely aggressive cancer cell line, known for previous cell line contaminations. In the early 1970s cultures of the Chang Liver cells were submitted for analysis and in 2001 the Chang Liver cell line was found to definitely match the HeLa cell line. (ICLAC)
In June 2007, Kenneth Ain, a renowned creator of over 18 immortal cancer cell lines, attended the annual Endocrine Society meeting in Toronto. During this conference he was informed that several of his cell lines did not originate from thyroid cancer. As these cell lines, were used worldwide to study cellular changes in thyroid carcinoma and to screen treatment drugs, Kenneth Ain was appalled. After investigating his cancer cell lines, Kenneth Ain discovered that 17 of the 18 cell lines were imposters. (Discover Magazine)
Why does it matter?
Using a control within your experiments is crucial to ensure you limit the number of variables that could potentially affect your experiment and to ensure the validity of your results. Without this validation, it can be difficult for the scientific community to accept the results of your experiment or the quality of the reagents you have created. Using misidentified or contaminated cell lines, not only effects the results of your experiment, but also effects the reagent inventor’s experiments and any other experiments that have used the same cell lines.
The ramifications of the contamination and misidentification of the Chang Liver cell lines and the KAT lines are still being felt today:
The Chang Liver cell line
The Chang Liver cell line is still available for purchase from ATCC, but it has now been updated so that the title reads HeLa [Chang Liver]. However between 2000 and 2016, 352 articles were published that still referred to the Chang Liver cell line as a liver model (ICLAC ).
After it was confirmed that the 17 cell lines were imposters, Kenneth Ain stopped distributing the cell lines. He also informed the researchers and institutes who had purchased these cell lines about the cell contamination. Only two responded. (Discover Magazine)
Taking back control
Although progress has been slow, with many scientists hostile and resistant idea that cell cultures have been misidentified or contaminated, since 2004 there has been a concerted effort to establish a standardized method of human cell line authentication and to identify all cell lines that have been contaminated or misidentified.
Many scientific journals now require some level of cell line authentication before research articles can be published. The list of these journals can be found on the Cell Line Authentication website.
The International Cell Line Authentication Committee (ICLAC) was set up in 2012 to increase the visibility of cell line and to promote awareness and authentication testing as effective ways of combating this problem. As well as promoting a list of misidentified cell lines, ICLAC advises researchers to purchase cell lines from a validated source and to perform regular authentication testing.
To this end, at Ximbio, we work closely with our cell line repositories – American Type Culture Collection (ATCC) and European Collection of (ECACC) to ensure any cell lines that we deposit are thoroughly investigated, therefore reducing the risk of cell line contamination or misidentification.
Both ATCC and ECACC use a variety of procedures to ensure the cell lines stored with them are routinely authenticated. These tests include Short Tandem Repeat (STR) profiling, Cellular morphology, karyotyping, Cytochrome C Oxidase | (COI) Assay testing and DNA barcoding.
For more information on ATCC and ECACCs validation processes, visit their websites: