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Life has spent the past few billion years working with a narrow vocabulary. Now researchers have broken those rules, adding extra letters to biology's limited lexicon.

Chemist Floyd Romesberg of the Scripps Research Institute in La Jolla, California, and his colleagues manipulated Escherichia coli bacterial cells to incorporate two types of foreign chemical bases, or letters, into their DNA. The cells then used that information to insert unnatural amino acids into a fluorescent protein1.

Organisms naturally encode heritable information using just four bases: adenine (A), thymine (T), cytosine (C) and guanine (G). These form pairs that hold together DNA’s double helix, and different three-letter sequences code for each of the 20 amino acids that make up the proteins in living cells. The new work is the first to show that unnatural bases can be used to make proteins within a living cell.

The achievement, Romesberg says, shows that synthetic biology — a field focused on imbuing organisms with new traits — can accomplish its goals by reinventing the most basic facets of life. “There is no biological system so fundamental and more intimately related to what we are than information storage and retrieval,” he says. “What we’ve done is design a new part that functions right alongside the existing parts and can do everything they do.”

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