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Preface ON THURSDAY AFTERNOON, July 30, 1987, people began to fall ill in Champerico, a small town on the Pacific coast of Guatemala. During the next three days, more than 200 people in this town and neighboring areas were affected; 26 died. All those afflicted had consumed meals prepared from fresh clams. Upon investigation, this was found to be an outbreak of paralytic shellfish poisoning, due to marine toxins accumulated by the clams from phytoplankton growing in the waters along the coast. Why study marine toxins? Episodes like the one above are one reason; they command attention because of the loss of life and health when they occur or because of the costs of preventing and avoiding them. Much research on marine toxins is directed toward moderating their impact by understanding the various syndromes and developing effective strategies to deal with them. However, there are positive reasons for studying marine toxins and their actions. Marine toxins play a significant role in structuring ecological relationships, both as offensive weapons for predators and as defensive weapons by potential prey. The very high potencies of some marine toxins, many of which seem clearly to have evolved to optimize their performance in these roles, are attained through strong, highly selective interactions, frequently with specific sites on excitable membranes. Investigating the mechanisms of toxin action has revealed a great deal about the physiology of affected tissues and systems. For example, the concept of a membrane channel arose from investigations with tetrodotoxin and saxitoxin, marine toxins that block sodium channels. Marine toxins themselves have proven challenging subjects for chemical study—structure elucidation, characterization, and synthesis. This field by its nature draws from several distinct traditional disciplines. One major goal of this book is to present work from these diverse disciplines, embracing the major areas of inquiry and the investigational tools with which information is obtained, in a form accessible to the non-specialist as well as the specialist. Although an exhaustive survey was impractical, great care was taken to include representations from the full range of organisms and compounds—from
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procaryotes to vertebrates, from small molecules to peptides. The scope of the book goes slightly beyond the title, including blue-green algae that occur in fresh or brackish waters. Three themes have been emphasized in assembling this book. The first is a description of the sources of natural toxins, with particular emphasis on the metabolic pathways responsible for their synthesis. The second theme concerns the structures of toxins and, in particular, which features determine both the distribution of toxic materials among the organs of intoxicated species and the stability, disposition, and biotransformation of those toxins. The third theme proceeds on a molecular scale to investigate the interactions between toxins and their primary sites of action, not only to understand these interactions better, but to gain a clearer view of the normal function of the target site. The goal central to these themes is the understanding, on a molecular level, of the toxins, their origins, and the structures with which they interact. It is hoped that this volume will aid in the pursuit of that understanding. As this book goes to press, two events have occurred that bear mention. First, the structure of ciguatoxin has just been published in the Journal of the American Chemical Society (1989, 777, 8929-8931). Despite the determined efforts of many scientists over several years, the structure of this important marine toxin, discussed in Chapters 8, 11, and 13, has resisted elucidation. Its publication marks a notable achievement, attained through the cooperation of investigators with different, complementary skills. Second, there has been another severe outbreak of paralytic shellfish poisoning along the Pacific coast of Central America, with very high levels of shellfish toxicity detected in Guatemala. There have, however, been no deaths and very few illnesses reported there, due to a timely response based on information gained from detailed investigations of the first outbreak. This time they were ready.
Acknowledgments This book has been developed from a conference titled "Natural Toxins from Aquatic and Marine Environments," which was in its final planning stages at the time of the Guatemala outbreak. The conference was held August 27-30, 1987, at the Marine Biological Laboratory in Woods Hole, Massachusetts. Funding for the conference and for the production of this volume were provided by the U.S. Army Medical Research Institute of Infectious Diseases. We wish to thank this organization and particularly Col. David L . Bunner, M.D., for their support and encouragement.
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Finally, and perhaps most significantly, we wish to thank the people at the ACS Books Department for their cooperation and the excellent quality of their work. Particular thanks are due to Robin Giroux, whose professional skill, enduring optimism, and unshakable determination are largely responsible for the successful publication of this volume. SHERWOOD
HALL
U.S. Food and Drug Administration Washington, D C 20204
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GARY
STRICHARTZ
Anesthesia Research Laboratories Brigham and Women's Hospital Harvard Medical School Boston, M A 02115 November 20, 1989
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