THE MADAGASCAR INTERNATIONAL COOPERATIVE BIODIVERSITY GROUP: BACKGROUND AND HISTORY

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THE MADAGASCAR INTERNATIONAL COOPERATIVE
BIODIVERSITY GROUP BACKGROUND AND
HISTORY
David Kingston Department of
Chemistry Virginia Polytechnic Institute
State University Web www .kingston.chem.vt.edu
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Natural Products as Drugs and Drug Leads

• WHO estimates that 80 of the worlds population
  use traditional medicine.
• Between 1983 and 1994 41 of new approved drugs
  had natural products as their source.
• David J. Newman, et al. Nat. Prod. Rep., 2000,
  17, 215-234
• Gordon M. Cragg, et al. J. Nat. Prod., 1997, 60,
  52-60

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• Natural Product Drugs
• Modified Natural Product Drugs
• Synthetic Drugs Based on Natural Product Models
• Synthetic Drugs

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MORE REASONS FOR FAITH IN NATURAL PRODUCTS
61 of all the new drugs introduced Worldwide
during 1981-2002 can be traced to or were
inspired by Natural Products. Newman, Cragg,
Snader 2003 J Nat Prod 661022
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SOME IMPORTANT ANTICANCER NATURAL PRODUCTS

• TAXOL, from Taxus brevifolia

• Treatment for ovarian and breast cancer
• Also used in stents to prevent restenosis
• Major drug, with sales of over one billion
  dollars/year

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WHY NATURAL PRODUCTS?

• NATURAL PRODUCTS CAN FORM THE BASIS OF NEW
  COMPOUND LIBRARIES
• R. Breinbauer et al, Angew. Chem. Int. Ed. 2002,
  41, 2878
• EXAMPLE THE HALICHONDRINS
• M. J. Yu 224th ACS National Meeting, Boston, MA,
  August 21, 2001, Abstract MEDI 238.

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DRUG DISCOVERY THROUGH NATURAL PRODUCTS

• COLLECT LARGE NUMBERS OF PLANT,
  MARINE, OR MICROBIAL SPECIES
• PREPARE EXTRACTS AND TEST IN RELEVANT BIOASSAY
  SYSTEMS
• RECOLLECT OR REFERMENT ACTIVE SPECIES AND ISOLATE
  ACTIVE COMPOUNDS BY A BIOASSAY-DIRECTED
  FRACTIONATION
• DETERMINE STRUCTURES OF BIOACTIVE COMPOUNDS
• CARRY OUT ADDITIONAL BIOLOGICAL TESTING

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THE PROBLEM OF BIODIVERSITY LOSS

• DRUG DISCOVERY REQUIRES RANDOM SCREENING OF
  THOUSANDS OF SPECIES YOU HAVE TO KISS A LOT OF
  FROGS TO FIND A PRINCE
• TROPICAL RAINFORESTS COVER ONLY 8 OF THE EARTHS
  SURFACE BUT HOLD 50 OF ITS PLANTS
• TROPICAL FORESTS ARE DISAPPEARING FAST DOWN FROM
  16 OF EARTHS LAND SURFACE IN 1950 TO LESS THAN
  8 TODAY
• TROPICAL REEFS ARE ALSO UNDER THREAT
• LOSS OF RAINFOREST MEANS THE POTENTIAL LOSS OF
  CURES FOR CANCER, AIDS, ETC.

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Brazil Vegetation 1960
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Brazil Brazil Vegetation 1988
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THE MADAGASCAR ICBG APPROACH TO BIODIVERSITY
CONSERVATION

• CARRY OUT BIOPROSPECTING WITH FULL INFORMED
  CONSENT OF ALL PARTIES
• PARTNER WITH PHARMACEUTICAL AND AGROCHEMICAL
  COMPANIES
• SINCE BIODIVERSITY LOSS IS CLOSELY ASSOCIATED
  WITH POVERTY, COMBINE BIOPROSPECTING WITH
  ECONOMIC DEVELOPMENT ACTIVITIES
• COMMIT TO RETURN ANY ROYALTY PAYMENTS IN PART TO
  THE HOST COUNTRY IN COMPENSATION FOR USE OF ITS
  BIODIVERSITY

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HOW AND WHERE TO DO THIS?

• 1992 NATIONAL INSTITUTES OF HEALTH INVITED
  SCIENTISTS TO COMPETE FOR FUNDS TO DO DRUG
  DISCOVERY AND BIODIVERSITY CONSERVATION
• 1993-1998 VIRGINIA TECH PROPOSAL FUNDED TO DO
  WORK IN SURINAME
• 1998-2003 RENEWAL PROPOSAL FUNDED TO DO WORK IN
  SURINAME AND MADAGASCAR
• 2003-2008 THIRD ROUND OF FUNDING AWARDED FOR WORK
  IN MADAGASCAR

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MADAGASCAR GROUP STRUCTURE

• VIRGINIA POLYTECHNIC INSTITUTE STATE UNIVERSITY
• CENTRAL OPERATIONS OFFICE
• MISSOURI BOTANICAL GARDEN
• BOTANICAL COLLECTIONS, BIODIVERSITY SURVEY
• CONSERVATION INTERNATIONAL
• ECONOMIC DEVELOPMENT, BIODIVERSITY CONSERVATION
• CENTRE NATIONAL DAPPLICATION ET DES RECHERCHES
  PHARMACEUTIQUES
• PLANT EXTRACTS, ANTIMALARIAL FRACTIONATION
• CENTRE NATIONAL DE RECHERCHES SUR
  LENVIRONNEMENT
• MARINE COLLECTION, MICROBIAL ISOLATIONS
• EISAI RESEARCH INSTITUTE
• BIOASSAY, DRUG DISCOVERY AND DEVELOPMENT
• DOW AGROSCIENCES
• AGROCHEMICAL DISCOVERY AND DEVELOPMENT
• VIRGINIA POLYTECHNIC INSTITUTE STATE UNIVERSITY
• BIOASSAY AND ANTICANCER DRUG DISCOVERY

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GOALS OF THE MADAGASCAR ICBG PROGRAM

• TO INTEGRATE THE PROCESS OF DRUG AND
  AGROCHEMICAL DISCOVERY FROM NATURAL PRODUCTS WITH
  CONSERVATION OF BIODIVERSITY AND SUSTAINABLE
  ECONOMIC DEVELOPMENT, WHILE PROVIDING FINANCIAL
  BENEFITS TO MADAGASCAR AND ITS PEOPLE

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WHY MADAGASCAR?

• Madagascar is a prime
• source of biodiversity.
• Madagascar is one of
• the highest priority
• Biodiversity Hotspots
• Home to 25 of the plant
• species in the African region
• Approximately 80 of species
• are endemic
• Great ecosystem diversity
• Work is urgent, since much of the country has
  been deforested

MADAGASCAR
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SCIENTIFIC DEVELOPMENT IN MADAGASCAR

• Laboratories at CNARP have been equipped to
  prepare plant extracts
• Laboratories at CNARP have been equipped and
  personnel trained to carry out antimalarial
  bioassays
• Facilities at CNRO (Nosy be) are being equipped
  to carry out marine collections
• Personnel at CNRE will be trained in microbial
  isolations
• Data handling infrastructure has been expanded

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ECONOMIC DEVELOPMENT IN MADAGASCAR

• SMALL-SCALE ECONOMIC DEVELOPMENT PROJECTS IN THE
  VILLAGES AROUND ZAHAMENA PARK, SITE OF 1998-2003
  COLLECTIONS
• BEE KEEPING
• ECOTOURISM INITIATIVE
• IMPROVED CROPS

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ECONOMIC DEVELOPMENT IN MADAGASCAR

• SMALL-SCALE ECONOMIC DEVELOPMENT PROJECTS IN THE
  VILLAGES AROUND ZAHAMENA PARK, SITE OF 1998-2003
  COLLECTIONS
• BEE KEEPING
• ECOTOURISM INITIATIVE
• IMPROVED CROPS
• INFRASTRUCTURE IMPROVEMENTS USING UPFRONT
  COMPENSATION FUNDS IN THE SAME VILLAGES
• AGRICULTURAL WAREHOUSE
• RENOVATION OF A PRIMARY SCHOOL
• CONSTRUCTION OF A FOOTBRIDGE