Three dimensional structure determination of protein, DNA and RNA by X-ray andlor NMR is very important for drug discovery. For example, Merck Research Laboratories which is the R & D unit of Merck (parent company of Banyu) is putting a lot of effort into structural biology. For example, the back cover of Merck's recent annual report, a photograph is shown of three-dimensional structure of the complex of angiotensin II receptor with enalapril (Blood pressure lowering drug developed by Merck). Annual sales of Merck in 1995 was 16,681 million dollars. Research and Development expense was 1,331 million dollars. It is more than 10 times as that of Banyu. With this large organization, it becomes possible to put substantial amount of money and manpower on basic research such as structural biology, which eventually leads to innovative drug development and is also recognized as outstanding accomplishment in basic science. For new drug discovery, not only structural biology, but other new techniques such as combinatorial synthetic chemistry and high-throughput screening are going to be essential tools. For most Japanese pharmaceutical companies with much smaller size, it is a critical issue how to pursue such an operation effectively. Under such circumstance, I am very grateful to TARA Sakabe Project that Banyu Tsukuba Research Institute can participate in the project by providing a relatively small amount of capital.

For efficient structural determination of macromolecules, acquisition of expensive facility such as a synchrotron is essential. However, perhaps more important factor is to assign excellent researchers to the projects. These days, it is evident that biochemists or molecular biologists themselves rather than X-ray crystallographers should to be involved in X-ray crystallography, starting from isolation of a gene, its expression, purification of the protein, crystallization and finally X-ray analysis. In order to make such an assignment possible, supervision and education of these amateur scientists by prominent crystallographers are essential. From this point of view, we owe very much to Professor Sakabe and his colleagues in Sakabe Project Team. I sincerely hope that the joint program between the university and the industries, established by TARA helps stimulate innovative drug discovery by Japanese pharmaceutical companies.