Cell culture forensics
- Laboratory of Genomic Diversity, National Cancer Institute, Frederick, MD 21702
Genomics, proteomics, vaccinology, transgenics, stem cell—advances in all these areas critically stack on the shoulders of tissue culture, our ability to cultivate an organism's living cells in plastic dishes. Nutritional trial and error for decades of painstaking cell gardening laid the groundwork for the several thousand human primary cell explants and immortal tumor lines available to modern biotechnology. Now, the 50-year-old problem of cell line misidentification from cell contamination, mislabeling, or, in some cases, conscious deceit, has a brand-new tool for cell and individual validation, a composite short tandem repeat (STR, also called genomic microsatellite) genotype signature (1). The new advances, the latest in cell identification technologies, represent the most advanced and powerful forensic approach to dispense with the embarrassing, expensive, and maddening cell contamination that occurs in biomedical laboratories.
The extent of inadvertent cell line contamination is enormous. During the 1970s and 1980s, as many as one in three cell lines deposited in cell culture repositories were imposters, one cell line overtaking or masquerading as another. The most notorious culprit was a cervical carcinoma line, HeLa, established by George Gey at the Johns Hopkins Medical School in 1951 from a 31-year-old mother of four, Henrietta Lacks (2) (Fig. 1). HeLa cells were unlike other primary cervical cancer explants in that they grew horrifically in culture, perhaps too aggressively. In the years that followed, nearly every basic cancer research laboratory grew HeLa cells and attempted to repeat primary tumor cell explantation from other people's cancer cells. But too frequently, as vividly documented in Michael Gold's popular book, A Conspiracy of Cells (3), the new tumor cells mysteriously became replaced with ubiquitous HeLa cells. Stanley Gartler, subject editor of the report in this issue of PNAS (1), first unveiled the hoary deception at a cell culture …
