Session 4 - Communities of practice Natural Products Drug Discovery The ICBG Program: A view from afar* Special thanks to Joshua Rosenthal of the NIH Fogarty Center for his helpful discussions and figures on the ICBG program

Program goals and accomplishments Objectives International Cooperative Biodiversity Groups Biodiversity exploration Scientific and economic development Biodiversity conservation Modeled on CBD ABS and Merck/InBIO agreement PIC, IP, and benefit sharing Transitional period New awards Philipines, Indonesia continuing Panama, Madagascar “ending” Uzbekastan/Kurdistan, Papua New Guinea, VietNam Laos Fiji, Costa Rica (only two will survive) Down to six in the end 800k/yr Implementation Competitive research grants (NIH/NSF/USDA) Five years, $300 – 600k/year direct costs Groups required academic institution and/or NFP, partner country, industrial partner The grand challenge Managing expectations Technology vs. sociology

State of the field Commercial Competing technologies and strategies Combinatorial chemistry HTP and UHTP screening Therapeutic targets/privileged stuctures Economic pressures Decline in new chemical entities Biodiversity as a commodity Transitional period New awards Philipines, Indonesia continuing Panama, Madagascar “ending” Uzbekastan/Kurdistan, Papua New Guinea, VietNam Laos Fiji, Costa Rica (only two will survive) Down to six in the end 800k/yr Political Uncertainty of access Uncertainty of provenance Uncertainty of benefit

Microbial Structure Screening cultures Fermentation Solvent extraction Primary assays Synthetic compounds Biocatalysis Strain improvement Chemical isolation Dereplication Secondary assays Bioprospecting Safety Assessment Clinical Trials Patent Scale-up Medicinal chemistry Pharmacology New product Toxicology Plants Animals

Reality check # 1 N=natural product ND = natural derivatives s’ = synthetic S = pure syntehtic downward trend, natural product molecular structure tends to have All sources – total number of drugs David J. Newman, NCI/NIH, 2005 Unpublished

Reality check # 2 Baltz, R., Microbe 2007 2:125-131

Outcomes Drug discovery Other benefits 14 years $50 M (US govt) 12 groups 7 companies 21 countries 12,000 species 1500 bioactive compounds 0 drugs >12,000+ spp collected >1300 bioactive compounds isolated >4000 people trained (350 long term) Institutional capacity built in 16 countries Informed bioprospecting policies in at least 6 countries Initiated/ strengthened biodiversity reserves in 7 countries Tested models of intellectual property rights and benefit-sharing/Established 14 Trust Funds >500 publications

Market size Approx. $100B From A. Kuo and G.M.Garrity 2002 Exploiting Microbial Diversity, In Biodiversity of Microbial Life, J.T. Staley and A-L Reysenbach, ed, John Wiley

Why me? 1996 - present Professor, Microbiology & Molecular Genetics Cofounder - Genomic Standards Consortium, Editor-in-Chief of SIGS (current), Bergey’s Manual (1996-2006) Chair, International Committee on Systematics of Prokaryotes Cofounder, NamesforLife, LLC 1981 - 1996 Merck and Co., Microbial Resources Group Bioprospecting and culture acquisition agreements, culture collection Natural products dereplication Co-inventor on 22 natural product patents