Free-electron lasers (FELs), which produce extremely intense, ultrashort X-ray pulses, have previously been used to determine structures of microscale protein crystals. But so far, all of the crystal structures solved this way have required the addition of data from already known and related structures. Now, researchers have used only FEL data to solve a known structure, lysozyme, at 2.1-Å resolution (Nature 2013, DOI: 10.1038/nature12773). Ilme Schlichting and Thomas R. M. Barends of the Max Planck Institute for Medical Research, in Heidelberg, Germany, and coworkers there and at SLAC National Accelerator Laboratory acquired diffraction images from a gadolinium derivative of lysozyme. They used the heavy atoms to align the images. The researchers collected more than 2.4 million images to obtain 60,000 images with usable data. The method is ready to move on to unknown protein structures, Barends says. “I would trust it just as much as any crystal structure determined using another X-ray source.” The method is particularly suited to proteins that are difficult to crystallize or are extremely sensitive to radiation damage.