Cell Contamination: The Dark Side of Cancer Research
Cell lines are the workhorses of biology. They are routinely stocked and studied to understand all aspects of normal and malignant physiology. All cancer drugs in current use were first tested in a cultured cell model.
However up to 66% of cancer cell lines have been identified as imposters. Today, cell lines known for nearly 50 years are possibly imposters, though they are widely used under wrong identities. There are about 10,000 citations every year on false cell lines and often they are used in several clinical trials. Some instances are:
- HeLa, the most studied cell line is found to be responsible for more than 20 percent of contaminated cell lines. The first widespread HeLa contamination was identified in 1967, when 18 different human cell lines were typed and found that every cell line was actually HeLa.
- “Kentucky Ain Thyroid,” or KAT cell lines were the most relied ones around the globe. However in 2007 it was reported that many of them were not actually thyroid cancer. Systematic thawing and genotyping revealed that 17 of the 18 most frequently shared KAT lines were imposters. It was suspected that the contamination was carried forward from the original lines, received long time back.
The most possible reason of uncontrollable laboratory contamination may be human error. Yet this fact is widely ignored. As exposing contaminated cell lines and cleaning up is a huge task. It takes years and sometimes wipes off a scientist’s career. Sometimes scientists choose to profile their samples by testing the function and morphology rather than DNA profiling, the expensive option. However they are easily fooled as the cells behave differently in different environments (involving applying enzymes, antibiotics and antibiotic-resistant genes) but their genetic material remains the same or vice versa. Even a completely clean lab could be struck by a new contamination at any time.
Contamination is an inevitable part of science. So this problem is widely acknowledged by the National Institutes of Health (NIH), the National Cancer Institute, major journals and innumerable bench scientists.
In 2012, 17 scientists formed the International Cell Line Authentication Committee (ICLAC). They agreed on STR fingerprinting as the global standard for authenticating cell lines. They set up a public database (found at iclac.org) of all known false lines, which numbers more than 400. Recently, the top four cell line repositories, in America, Germany and Japan, have decided to merge their online databases (validated through STR fingerprinting), with each fingerprint converted to a searchable genetic “bar code.” The consortium’s online tool (known as OSTRA, for Online STR Analysis) can be accessed online too.
In April 2013, Nature published more stringent requirements, in which every author had to report the source of a study’s cell lines and whether the lines had been verified recently.
Hopefully these measures would help to get rid of this rigorous problem.
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