Madagascar periwinkle (Catharanthus roseus) Salix - willow. Biodiversity: Use it or lose it. Biodiversity: Use it or lose it

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1 Applying basic ecological science to make a difference Human Impact on Earth s Ecosystems ~50% of land surface and accessible fresh water used by humans C increase is leading to climate change H H H H H /3 of extant species may be extinct by 100. /3 of marine fisheries at limits of exploitation or worse >0% of birds driven extinct in last 000 years Invasive species cost money and are damaging natural systems 50% of world s mangroves transformed or destroyed Chemicals released into the environment without testing Human activity doubled the global N input into terrestrial habitats Biodiversity: Use it or lose it Biodiversity: Use it or lose it Plant life history and growth rates influence optimal defense levels Pioneer (gap) species (grow fast and require high light) Shade-tolerant species (grow slowly and can persist in low light) Shade-tolerant species invest more in defense than gap species (because it is hard to replace leaves in the low light of the understory (1% full sunlight) Salix - willow Madagascar periwinkle (Catharanthus roseus) Vincristine and vinblastine provide effective treatments against leukemia and other cancers 1

2 Bioprospecting: Search nature for chemicals or genes with pharmaceutical or agricultural applications Two benefits: helping human health global health (conservation) How do pharmaceutical companies develop new medicines? 1. Rational drug design (designer drugs). Combinatorial chemistry (shotgun) 3. Bioprospecting (chemicals from nature) novel molecules novel modes of action! For >0 yrs, including today, 0-50% of new pharmaceutical drugs come from natural products combinatorial compounds n = 13,506 natural compounds n = 3,87 Natural compounds are more complex They have: 5 times more chiral centers 3X more N atoms X more atoms M Fehler & J Schmidt. 003 J Chem Inf Comput 3: Property distributions: differences between drugs, natural products, and molecules from combinatorial chemistry. Tropical forests are a promising source Tropical plants have both higher concentrations and more toxic chemical defenses Strategies for plant collections Use of ecological insight to design more effective collection strategies for drug discovery Young leaves are preferred by herbivores because they are tender and high in protein

3 H H H H H N H H Young leaves are not defenseless Greater chemical defenses than mature leaves % dry weight of the leaf % Leaf DW Nitrogen-containing defensive compound of Inga umbellifera leaves early 10% mid 50% late 80% mature --young, expanding-- Mature Leaf Age Young leaves are excellent chemists Collection strategies: ecological insight NH H NH H Conventional bioprospecting: collections of mature leaves (defended by toughness and tannins, traits with no pharmaceutical use) H H H H 7''' 6''' H H 7''' 6''' H ''' H ''' H 7'''' 3 H H H H Novel compounds (new to science) are often unique to young leaves ur approach: Young leaves invest more in chemical defenses than mature leaves! better source of pharmaceuticals Comparison of % of samples with activity against cancer (National Cancer Institute and the Panama ICBG) % active samples NCI Mature Young - Leaves from Panama - Bioprospecting: using ecological insight to guide collections Two benefits: helping human health global health (conservation) 3

4 Criticisms of bioprospecting as a conservation tool " Royalties are the only rewards in most benefit-sharing agreements " The chances of receiving royalties are <1 in 100,000s " >7 years for royalty payments Little chance of host country receiving any benefits A solution: conduct the drug discovery research in source countries " $3 billion spent annually worldwide by pharmaceutical companies (Agnew 000) " additional funds provided by first-world governments and NG s " much research conducted at universities or small biotech companies " at least 1/3 of funds are expended on research that could be done in developing countries (ten Kate and Laird 1999) Biodiversity-rich nations could tap these existing funds to support drug discovery research in their own countries Goals of the Panama Bioprospecting Project (funded ) Summary of bioprospecting steps Effective drug discovery Economic development Human Clinical trials Animal trials Biodiversity conservation accomplished in Panama or in progress Collections Plants, fungi and marine organisms Established Bioassays in Panama " Major disease targets: Cancer (lung, breast, CNS) HIV " Tropical disease targets: Malaria Trypanosomiasis (Chagas disease) Leishmaniasis Dengue " Agricultural pests: White-fly and aphids

5 Natural Products Chemistry in Panama Recent patents Isolation, purification, identification of the bioactive compounds " Anti-malarial compound has similar or better inhibition with lower general toxicity than current drugs and is a completely new structural class for anti-malarial therapy. " Anti-leishmanial compound from an endophytic fungus has activity similar to the drug amphotericin B. " Anti-cancer compound from a blue-green alga, with very high anticancer activity, low toxicity to normal cells, and a new mechanism of action (coibamide). Have we been able do do first-class research? " Technical and infrastructure development in Panama - established bioassays labs - equipped chemistry labs - purchased equipment (air conditioners, HPLC, NMR, etc.). " Technical and infrastructure development in Panama " Research and educational opportunities for Panamanians 10 principal investigators 70+ paid assistants BS and MS degrees in Panama 16 MS and 8 PhD degrees abroad La Prensa, April 0, 000 " Technical and infrastructure development in Panama " Research and educational opportunities for Panamanians " Conservation impact Created more jobs than logging Protected Coiba as a World Heritage Site Engaged the powerful urban community Changed government development goals 5