(Bio)crystallography at the turn of the millennium

This review is focused on the present status of X-ray crystallography and i ts impact on chemistry and the life sciences. The discovery of the DNA doub le-helix structure from a fibre X-ray diagram in 1953 marked the last centu ry, whereas the human genome project (to be completed in the year 2003, the 50-th anniversary of Crick's and Watson's discovery) and the proteomics wi ll open the new millennium. The crystal structure determinations of very co mplex biological assemblies such as viruses and ribosomes illustrate the po wer of contemporary X-ray structure analysis. The historical background is given, which touches on some of the important steps from the early days of the discovery of X-rays. The advanced and new methods and technologies of t he modern era, such as third-generation synchrotrons, sensitive area detect ors, up-to date computer technologies with computer graphics, cryo-techniqu es, micro-crystallization methods, and genetic engineering, all contributin g to the development of X-ray crystallography, are evaluated in separate pa ragraphs. Some examples that illustrate the power of the methods are select ed from the contemporary research in the field. Systematics of known crysta l structures of small molecules and macromolecules and their assemblies col lected over the years has developed our perception of the nature of the che mical bond, and the interactions between atoms and molecules, which determi ne the chemical, physical, and biological properties. This fundamental know ledge enables structure and property predictions, useful in many branches o f science and technology. A method, starting with the structure of table sa lt, has developed into a very fine tool for looking into complex living sys tems. Time-resolved crystallography and cryo-electron microscopy are capabl e of recording biological events and they inform us about the dynamics of e nzymes and living cell activities. In combination with bioinformatics, very fast events, recorded experimentally or proposed theoretically, can be int erpreted by the methods of molecular dynamics simulations. The vivid interp lay of ideas coming from different scientific fields and technologies has l ed to capital discoveries, which have opened roads to new disciplines, such as molecular genetics and molecular medicine. These two branches, in parti cular, enriched by findings on DNA and protein structures, can provide effi cient therapies for many diseases, health prevention, and reduce ageing pro blems. Our views on the nature of the chemical bond have been revised and o ur horizons will be extended and clearer in the years to come. Applying an ethical approach in science, humanity will learn how to improve the quality of life all over the world.