SINCE they were discovered, X-rays have been used to study biology. They can photograph things light cannot reach and probe the atomic structures of protein molecules. As the AAAS learned in a session on the latest X-ray technology, though, they are being pushed further every day. Now they are being used to take three-dimensional pictures of individual cells, to map the distribution of trace elements inside cells and to work out hitherto intractable molecular structures. The pictures of cells are made - as Carolyn Larabell of the Lawrence Berkeley National Laboratory, in California, described - using a technique called soft X-ray tomography. Unlike electron microscopy, this does not require a cell to be chemically fixed, stained or embedded in plastic in order to be photographed. It is flash-frozen just before it has its picture taken, so is much closer to its living state. The X-rays used detect nitrogen and carbon atoms, so they can see proteins and DNA (which have a lot of these atoms) without being confused by water. And by taking pictures from many directions, soft X-ray tomography can build up a three-dimensional image of the cell. Dr Larabell and her collaborators have used the technique to study molecules called peptoids that are being tested as drugs against Candida albicans, a disease-causing fungus. The peptoids work by disrupting a region of Candida's nucleus, known as the nucleolus, which turns out the components of its protein factories. Using her soft X-rays Dr Larabell was able to see, in a way that is impossible with an electron microscope, the holes that the peptoids punch in the nucleolus. Chris Jacobsen, of Argonne National Laboratory, in Illinois, can observe even more subtle things using X-rays. Tune the beam correctly and power it up a bit, and it becomes sensitive to metal atoms such as iron, copper and zinc, instead of non-metals like carbon and nitrogen. Dr Jacobsen works with a team that have used this trick to map iron atoms inside diatoms - single-celled, oceanic algae that are important absorbers of carbon dioxide from the atmosphere, but whose growth is often restricted by a lack of iron. The team are looking at what the iron actually does, and have found it forms patterns in a diatom's outer shell that resemble the staves of a barrel. Anton Barty, of the Centre for Free-Electron Laser Science in Hamburg, Germany, meanwhile, has helped solve a problem that has long stumped biologists: how to work out the structure of a protein that cannot be crystallised. If you can make a reasonably large crystal out of it, a technique called X-ray crystallography will yield the arrangement of a protein molecule's atoms. If you cannot, though, this method will not work. Smaller crystals need bigger exposures to collect enough data for analysis, and the bigger the exposure, the more damage the X-rays do to the crystal. If a crystal is too small, it is therefore impossible to collect the data before it is destroyed. Dr Barty and his colleagues have overcome this problem using a redundant particle accelerator (the Stanford Linear Collider, SLAC) that has been "repurposed" as a device called a free-electron laser. The SLAC laser produces pulses of X-rays so short (40 millionths of a billionth of a second) that protein molecules do not have time to react before the X-rays have passed through them, yet the pulses are so powerful for this brief period (50 gigawatts - or about 50 times the output of a modern nuclear power station - focused onto one square micron) that a useful picture emerges. This means even tiny crystals can be interrogated, a technique that promises to transform molecular biology, particularly the part that seeks to understand how drugs and proteins interact.