Small crystals, fast dynamics and noisy data are indeed beautiful

Abstract

Free electron lasers represent a rare example of disruptive innovation in technology (Bower & Christensen, 1995). Such an innovation requires us to identify the ways in which the new technology differs significantly from the old and to decide how best to deploy that technology. Most importantly, we must consider what hitherto inaccessible scientific problems can now be successfully attacked, and reconsider what older problems can be better attacked. Free electron lasers had been developed at much longer wavelengths in the electromagnetic spectrum and used effectively for some time. It was however not a foregone conclusion that the self-amplified spontaneous emission process that underpins lasing would continue to hold for a hard X-ray FEL (XFEL), and that the roughly 100 m long undulator necessary for saturation of this lasing process could be constructed with the required precision. Even if lasing were achieved, it was not at all clear -particularly to reviewers ten years ago of grant applications to NIH in XFELbased structural biology -that the prodigious peak brilliance of hard X-ray pulses could be harnessed to conduct any useful scattering or spectroscopic experiments before all atoms became fully ionized and the sample was destroyed.We know how that all turned out: the world's first hard X-ray laser, the Linac Coherent Light Source at the Stanford Linear Accelerator Center, speedily achieved lasing and was a roaring success. More to the point for X-ray experimentalists, a brief time window in the femtosecond range turned out to exist -as predicted by a few far-sighted scientistsduring which scattering or spectroscopy data could be collected before the sample was indeed destroyed in the ultimate destructive experiment: 'diffraction before destruction ' (Chapman et al., 2011). As one of the pioneers of XFEL science in structural biology and its associated technologies, John Spence now presents a magisterial review (Spence, 2017) that illustrates his command of a large swath of the recent literature and of course, of the experiments that underlie it. The field is expanding so rapidly that this may turn out to be the last review that realistically covers the entire field. That expansion also illustrates that the field is quite immature and to many of us, wildly exciting. Developments are being vigorously pursued in such areas as the source itself (e.g. seeding; control of the bandpass of the X-ray spectrum or of the X-ray pulse structure), the X-ray optics (e.g. split-anddelay schemes to manipulate the X-ray pulse structure delivered to the sample; chirping of the pulse in time or space), the design of experiments (e.g. fixed target or jet-based modes of sample delivery; sample manipulation in dynamic experiments by rapid mixing, an intense pump pulse by a visible or IR laser, a temperature jump or an electric field jump; the combination of X-ray scattering and spectroscopic experiments), the detector and perhaps above all, in modes of analysis of the data. All are dealt with in the review, some at length, oth...