26 



government laboratories and industry. Indeed, these are duties of each laboratory. NCI has 

 followed the policy of seeking partners in private industry to commercialize its discoveries an 

 inventions. The purpose of our Cooperative Research and Development Agreement 

 (CRADA) with pharmaceutical companies is to conduct collaborative research on the 

 development of drugs and to generate data necessary to obtain FDA approval of the 

 compound. CRADAs are awarded following full and open competition, including publication 

 in the Federal Register, and a thorough scientific review by government scientists of the 

 proposals submitted. Prior to the award of a CRADA, a company must show it is the most 

 qualified to undertake a potentially complicated and expensive effort to produce the agent and 

 to cooperate with NCI in performing necessary clinical trials. In exchange, NCI agrees to 

 provide the company with exclusive access to its clinical and preclinical data for use in 

 obtaining approval for the commercial marketing of the product. The same competitive 

 procedures are followed in licensing NCI-owned patents. 



RECENT NCI DISCOVERIES 



A total of 54,000 extracts, derived from all natural product sources, have been submitted for 

 anti-HIV screening since about 1986. To date, over 35,000 plant samples have been 

 collected by the NCI contractors, and over 25,000 have been extracted to yield more than 

 50,000 plant extracts. Over 25,000 of these plant extracts have been tested in the anti-HIV 

 screen, and about 2,700 have exhibited some in vitro activity; of these, close to 2,400 are 

 aqueous extracts, and in the majority of cases the activity has been attributed to the presence 

 of ubiquitous types of chemicals, such as polysaccharides and tannins. Such compounds are 

 not a current NCI focus for drug development and typically are eliminated early in the 

 discovery process. Therefore, the number of extracts undergoing active investigation is much 

 smaller. 



A number of novel in vitro active anti-HIV agents have been isolated and selected for 

 preclinical development. The dimeric alkaloid, michellamine B, has been isolated from the 

 leaves of a tropical vine collected in the rainforest regions of southwestern Cameroon. 

 Michellamine B shows in vitro activity against both the HIV-1 and HIV-2, and is in advanced 

 preclinical development. Preliminary surveys of the occurrence and abundance of the 

 species, as well as cultivation experiments, have been carried out by Missouri Botanical 

 Garden through its contract with the NCI. Surveys thus far indicate that its range and 

 abundance are very limited, but fallen leaves collected from the forest floor have been shown 

 to contain reasonable quantities of michellamine B; the collection of these leaves has obviated 

 the large-scale harvest of fresh leaves, and avoided possible endangerment of the wild 

 species. Fallen leaf collections wiU provide sufficient michellamine B to complete preclinical 

 studies, but the NCI is proceeding with feasibility studies of the cultivation of the plant 

 through contract mechanisms. The collections and cultivation experiments are being 

 performed with the full participation of Cameroon authorities and scientists, as well as 

 through close collaboration with the Worid Wide Fund for Nature, which is coordinating 

 conservation projects in the Korup region of Cameroon. Thus far, no other related species 

 have shown significant anti-HIV activity. 



