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BACKGROLHSfD 



Throughout the ages humans have looked to nature as a source of medicines for the treatment 

 of a wide variety of diseases. Plants have formed the basis for sophisticated systems of 

 traditional medicine, which have been in existence for thousands of years throughout the 

 globe. Microorganisms and marine organisms have, however, played lesser roles in such 

 traditional systems. 



Natural products also play an essential role in the health care systems of developed countries, 

 in providing new types of biologically active substances that either cannot be made chemically 

 or would not have been conceived by chemists. Well-known examples of plant-derived 

 medicinal agents include the antimalarial drug quinine, the analgesics codeine and morphine, 

 the tranquilizer reserpine, and the cardiac glycoside, digitalis. The role of microbial 

 fermentations has been predominant in the development of antibiotics, with over 8,500 

 substances isolated from microbial sources, and close to 100,000 prepared by chemical 

 modification of the native material. Well-known classes of antibiotics are the penicillins, 

 cephalosporins, and tetracyclines, while other microbial products include immunosuppressive, 

 antiparasitic, and antifungal agents. Until the development of SCUBA (Self-Contained 

 Underwater Breathing Apparatus), the exploration of the marine environment was virtually 

 impossible, with the result that few marine natural products of medicinal value have been 

 developed to date. That, however, is changing rapidly, and more thorough investigation of 

 this area is yielding an increasing number of novel active substances. 



NCI's NATURAL PRODUCTS PROGRAM: 

 1955-1980 



Plants have a long history of use in the treatment of cancer, though many of the early claims 

 for the efficacy of such treatments might be viewed with some skepticism since cancer, as a 

 specific disease entity, is likely to be pooriy defined in terms of folklore and traditional 

 medicine. The NCI, however, recognized the potential value of plants and other natural 

 materials as sources of new anticancer agents when it established its Cancer Chemotherapy 

 National Service Center (CCNSC) in 1955. The aim of CCNSC was to coordinate a national 

 program for the procurement and screening of materials for chemotherapeutic activity, and to 

 develop and evaluate any active agents as potential drugs for the treatment of cancer. All 

 materials, including synthetic compounds, purified natural products, and extracts, were 

 screened against a range of animal tumor systems, principally experimental mouse leukemias. 

 Bioassay-guided fractionation of active extracts led to the isolation and characterization of a 

 large number of active agents belonging to a wide variety of chemical classes. 



Extensive involvement of the pharmaceutical industry, either through contracts or voluntary 

 submissions, provided over 180,000 microbial extracts from soil during this period, which 

 yielded a number of active anticancer agents. Commercially available drugs from microbial 

 origins that evolved through NCI efforts, as well as those developed by industry, include 

 doxorubicin (adriamycin), mitomycin C, bleomycin, streptozotocin, L-asparaginase, and 



