1. Marine Toxins: From Harm to Charm Daniel G. Baden, Ph.D. Director, Center for Marine Science University of North Carolina Wilmington Cone Shell Toxins In Pain Management Diarrheic Shellfish Poisons for Intestinal Water Balance Inhaled Red Tide Brevetoxins In the Treatment of Cystic Fibrosis Marine toxins disturb: Nerve conduction Memory and learning Pulmonary function Immune function Metabolism Marine Poisons As Molecular Tools Shellfish, Toxins, And Resistance How can such Can such exquisite toxicity be controlled for useful purposes?

2. Renewable (Cultured) Resources For Ample Starting Materials: Brevetoxin Example Identify environmental episode Isolate clonal cultures Purify bioactive material(s) from culture Establish criteria for purity Characterize mechanism of action Determine standard and probe sizes Package bioactive material Continually revise standards and probes Develop distribution system Bioactive becomes tool for research Availability promotes research and development Bioactive becomes precursor to drugs Baden et al:

3. Renewable (Synthetic) Resources For Pain Management: Cone Shell Toxin Example Venomous cone shells Toxin purification Peptide sequencing Synthetic Peptide Toxin Production For Drug Development Beginning Clinical Studies in Treatment Of Chronic Pain Research Showed Nerve Signal Disruption Olivera et al:

4. A Formal Mechanism to Couple Ocean Studies to Human Health: A Paralytic Shellfish Toxin Story Alexandriumtamarense Toxic Shellfish X Humans possess binding domains Shellfish have modified channels Changes involve one AA change Trainer et al:

5. synthetic PbTx-3-  -naphthoate Natural Brevetoxin Site-Directed Chemical Modification and Activity Measurement: (Turn Harm Into Charm) Brevetoxins cause severe respiratory distress Effects caused at picogram concentrations Airway restriction increases over 250% Natural Brevenal Both chemicals counteract all toxin actions treat symptoms of Cystic Fibrosis treat mucociliary disorders administered by nebulizer Three patents are pending for seafood poisoning therapies for treatment of mucociliary disease general chemical structures of drugs Bourdelais et al:

6. Renewable sources of material (environmental exploitation is in the past) Need a formal mechanism to couple ocean studies to human studies (synergy) Targeted technology to discover new drugs and antidotes (assays) Mechanisms for standards and “leads” to be distributed (supply is not free) Site-directed chemical modification and testing (turn harm into charm) Recommendations http://www.niehs.nih.gov/oc/news/ocean.htm http://www.nsf.gov/news/news_summ.jsp?cntn_id=100371&org=OCE&from=news http://www.ogp.noaa.gov/mpe/ohi/centers.htm