Interior of an incubator showing cells growing in culture flasks, petri dishes, and microtiter plates.

Cell lines are standard tools in biomedical research, and yet when it comes to their genetic identity, they are remarkably unstable. That volatility comes with their defining traitimmortality. Over time, cells accumulate mutations that may ultimately change the structure of chromosomes and alter cellular functions.

A number of those genetic changes can be detected with cell line authentication, although despite the authority implied by its name, such testing is not yet performed routinely in many laboratories. In fact, for the better part of the 60 years since its inception, authentication has not featured prominently on scientists to-do lists. It was even actively dismissed for a time, because the manner in which attention had been called to scientists mistakes (in many cases committed unknowingly) was perceived as career-threatening.

By the 1960s, it was clear that authentication would be an effective way to catch obvious mix-ups and contamination between cell lines. But it would have been difficult to predict its usefulness for detecting the many diverse genetic variations that bear so critically on cell line identity over time, since those variations were unknown then. And even now, equipped with relatively advanced technologies and with an understanding that genetic variation can be both powerful in effect and subtle in form, they are still able to escape detection.

The elusiveness of variation is a fascinating aspect of cell biology, and its significance is emphasized particularly by the widespread use of immortalized cell lines in laboratory research and by the fact that genetic variation is now a cornerstone of biomedical science. Curiosity about variation in nature is not a new phenomenon, of course. Observations of plants, notably those recorded by Gregor Mendel and Dutch botanist Hugo De Vries in the 19th century, were critical to the realization that genetic variation is the basis for evolution by natural selection. Knowledge of induced mutation, or mutagenesis, introduced in the 1920s with the work of German geneticist Hermann Joseph Mller, piqued the interest of not only scientists but also writers and the general public, notably in the form of science fiction and comics, which are rife with mutant characters.

Types of chromosomal mutations.

Still today it is difficult not to be amazed by genetic variation and mutagenesis. The depth of variation that exists in the human genome, for instance, is astonishing. In 2006 scientists reported that copy number variations, which include relatively large deletions, duplications, and insertions of genetic material that alter the structure of DNA, affect from 6 to 19 percent of any given chromosome in the human genome. Prior to that study, it had been estimated that just 0.1 percent of the human genome was affected by genetic variation, much of which had been attributed to single nucleotide polymorphisms, which alter individual building blocks of DNA (changing an A to a T, for example).

The sheer diversity of variation in humans is illustrated further by cancer. Scientists have identified nearly 225,000 unique variants for this disease alone. Presumably many of those represent acquired mutations, or changes that have occurred as a result of time or exposure to cellular stressors, such as certain chemicals.

Which brings us back to cell lines.

The longer cells are kept in culture, and the more stressors they are exposed to, the more mutations they acquire. Eventually, they gain the mutations they need to make them immortal, giving rise to a cell line. A cell line, then, is an established lineage of continuously dividing cells, one in which the cells have effectively surpassed the Hayflick limit, or the finite number of cell divisions that normally would bring about replicative senescence (a state in which cells are metabolically active but not capable of division).

Excerpt from:
Authenticating Cells Out of Curiosity, Not Fear

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