International collaboration in drug discovery and development: the NCI experience

Over the millennia, natural products, mainly of plant origin, have been use d for the treatment of diseases, and an impressive number of modern drugs h ave been isolated from natural sources based on their use in traditional me dicine. The past century, however, has seen an increasing role played by mi cro-organisms in the production of antibiotics and other drugs for the trea tment of diseases, ranging from bacterial infections to cardiovascular prob lems and cancer. The role of nature will continue to grow with the explorat ion of tropical rainforests and marine environments, as well as the huge un tapped resource of micro-organisms which have, as yet, defied culture. With less than 1% of the microbial world currently known, the extraction of nuc leic acids from environmental samples from soil and marine habitats, from s ymbiotic and endophytic microbes associated with terrestrial and marine mac ro-organisms, as well as from extreme habitats, such as hot springs and dee p sea vents, will permit access to a vast reservoir of genetic and metaboli c diversity. These resources will provide a host of novel chemical scaffold s which can be further developed by combinatorial chemical and biosynthetic approaches to yield chemotherapeutic and other bioactive agents which have been optimized on the basis of their biological activities.