Introduction
Macromolecular crystallography has continued to dominate the life sciences. The examples chosen for the Highlights 2000 are illustrative of the power of the technique and the detailed structural-function information that it can yield. The in-house programme of research in this area has also been very active with a detailed study of the effects of radiation damage caused by the use of a third-generation source and an exciting development in the single-wavelength anomalous dispersion (SAD) method. This latter development, whereby sufficient phase information can be obtained from the anomalous scattering of the indigenous sulphur atoms alone, requires high quality intensity data collected to high resolution. However, it obviates the need for manipulating the native protein in terms of selenomethionine substitution or the preparation of other heavy atom derivatives. Clearly, the method needs further exploration.
Future activities in macromolecular crystallography will concentrate on automation. This will involve both instrumental developments such as automatic sample changing (including pattern recognition of micro-crystals and centring them in small X-ray beams), through quality control of data collection, to phase development and structure solution. For the "routine" problems, it is intended to adopt a "send a crystal, obtain a structure" approach. This should not only allow scientists to have more time to think about science, i.e. what does the structural information mean in terms of function, but also to free resources to tackle the genuinely demanding problems. Instrumental developments will centre around beamline ID14-3 and this will obviously mean some disruption to the user service on this beamline. It is hoped that the user community will be sympathetic on the basis that the success of the automation programme will bring medium and long-term benefits to everybody and allow the ESRF to play a leading role in new programmes involving genomic studies.
Despite the dominance of macromolecular crystallography, other techniques including Small-angle X-ray Solution Scattering, X-ray Absorption Spectroscopy and X-ray microscopy continue to play key roles in structural biology and biophysics. It has to be remembered that for many problems in these scientific fields, the production of single crystals is either inappropriate or technically impossible at the present time. Examples of the use of these techniques can be found in other sections of the Highlights.
The medical research facility on beamline ID17 continues to make progress. Jointly conceived and operated by the ESRF and the CHU Grenoble, it supports a wide range of research programmes concerned ultimately with human health issues. Over the past several years, the commissioning of the beamline has seen programmes develop in coronary angiography, bronchography, computed tomography of cerebral blood perfusion, microbeam radiation therapy and user programmes in imaging and radiation therapy. As the final step in the commissioning of this unique facility, the imaging of the coronary arteries of human patients started in January 2000. Since then, 17 patients have been imaged at the facility. With this success, the beamline can now be considered fully operational.