We know that mutations in DNA occur in all of our cells as they divide over the course of our lives. Some of these mutations cause cancers though most do not. But we don’t really know exactly what distinguishes the former from the latter—what makes some mutations drivers of tumorigenesis while others are tolerated as part of healthy tissue?

Sometimes the difference is the particular gene that is mutated; sometimes it is the tissue or cell type in which the mutation occurs, or the time of life, or the presence of other mutations in the same cell. Part of the reason we can’t tease out these disparate effects is because we don’t have that much information about the accrual of mutations in normal, healthy cells over the course of life. A new analysis in last week’s Science looks at precisely that issue, but it only muddies the picture further.

Surveying the mutant landscape

The researchers examined cells lining the esophagus of nine deceased organ donors ranging in age from 20 to 75. Four of them had been smokers, but none of them had any chronic diseases or were on prescription meds. These cells have a high rate of proliferation, as they are constantly being sloughed off and replaced.