Inspired by the glow of the firefly, scientists have created bioluminescent cells that are visible deep within an animal’s body—and that could one day be used in medical imaging. A firefly’s glow relies on the reaction between an enzyme called luciferase and a compound called luciferin, which scientists had previously adapted to produce a near-infrared light, capable of passing through animal tissue. However, the natural firefly enzyme didn’t pair very well with this new compound, so the researchers wanted to improve it. They created versions of the enzyme with random mutations and inserted these into bacteria, which they sprayed with the synthetic luciferin compound to produce a glow. They then took the enzymes from the brightest glowing bacteria and repeated the whole process. After 21 generations, the scientists ended up with a new enzyme optimized to work with the synthetic compound. When they injected cells expressing this new enzyme into a mouse’s blood supply, along with the synthetic compound, the resulting light passed through the mouse’s tissues and could be captured outside the body with an infrared camera. Even a single cell lodged in a mouse’s lung produced a detectable glow, the researchers report today in Science. The team also inserted the enzyme’s genes directly into neurons of a marmoset monkey, and were able to view the bioluminescent glow from the brain area more than a year later. In the future, this kind of imaging technology could allow doctors to track transplanted cells or monitor the growth of tumors—all without the need for invasive surgery.