As any diplomat will attest, nuances in language can dramatically affect the success of communication. But because the idiom of human cells was assumed to be much more literal than that of whole people, a recent discovery surprised even the scientists who made it. Researchers at the National Cancer Institute (NCI) identified a human protein that takes two distinct shapes depending on a subtle difference in its gene that should not make any difference at all. Their finding may explain variations in chemotherapy response among certain cancer patients and raises new questions concerning so-called silent mutations.

Chava Kimchi-Sarfaty and Michael M. Gottesman were examining a gene called MDR1, which is named for its association with multiple-drug resistance in tumor cells. Specifically, they looked at mutations called single-nucleotide polymorphisms (SNPs) in MDR1. Some did not change the amino acid sequence encoded by the gene, so the scientists assumed they could have no effect on the final protein. Still, those synonymous SNPs kept showing up in studies of cancer patients, sometimes seeming to influence drug response. "It drew our attention because there were so many reports, and often really contradicting each other," Kimchi-Sarfaty says, "so we started to explore."