All life forms on Earth use the same genetic alphabet of the bases A, T, C, and G—nitrogen-containing compounds that constitute the building blocks of DNA and spell out the instructions for making proteins. Now, scientists have developed the first bacterium to use extra letters, or unnatural bases, to build proteins. The new research builds on the team’s previous efforts to expand the natural genetic code. In 2014, the scientists engineered Escherichia coli bacteria (pictured) to incorporate an additional pair of bases—X and Y—into their DNA. The bacteria could store the unnatural bases and pass them onto daughter cells. But to be useful, these bases need to be transcribed into RNA molecules and then translated into proteins. So in the new study the researchers slipped the “alien” pair of bases into bacterial genes that also contained traditional bases. The microbes successfully “read” DNA containing the unnatural bases and transcribed it into RNA molecules. What’s more, the bacteria could use these RNA molecules to produce a variant of green fluorescent protein that contains unnatural amino acids, the team reports today in Nature. The traditional four DNA bases code for 20 amino acids, but the addition of X and Y could produce up to 152 amino acids, which might become building blocks for new drugs and novel materials, the scientists say.