BIOMEDICAL IMPORTANCE OF MARINE ORGANISMS Edited by Daphne G. Fautin Published by California Academy of Sciences San Francisco 1988 Memoirs of the California Academy of Sciences Number 13 Biomedical Importance of Marine Organisms Biomedical Importance of Marine Organisms Edited By Daphne G. Fautin Published by California Academy of Sciences EEE3EE1 San Francisco 1988 Memoirs of the California Academy of Sciences Number 13 Cover Illustration: This jelly fish — a member of the order Semaeostomeae — was rendered by Ernst Heinrich Haeckel (1834-1919), and published in his 1904 book Kunstformen dcr Natur (Art Forms in Nature). Haeckel was a specialist in "lower" organisms, many of which, like this jellyfish, exhibit lovely symmetry. However, he was a general zoologist, having founded the Phyletisches Museum in Jena, and originated the "tree of life" diagram, perhaps his most famous zoological rendering. Thus, for several reasons, this is an appropriate symbol for the symposium Biomedical Importance of Marine Organisms. © 1988 by the California Academy of Sciences, Golden Gate Park, San Francisco, CA 941 18 ISBN 0-940228-20-3 Library of Congress Catalog Card Number: 88-70980 Contents Introduction — Daphne Gail Fautin vii The Systematists' Perspective— Judith E. Winston 1 Maximizing the Potential of Marine Organism Collections for Both Pharmacological and Systematic Studies- Shirley A. Pomponi 7 Screening to Detect Biological Activity— Kenneth L. Rinehart 13 Marine Chemical Ecology and Natural Products Research — Valerie J. Paul 23 Feeding Deterrents in Molluscs— D. John Faulkner 29 Ethno-Natural Historical Leads— Paul J. Scheuer 37 Uniqueness of the Marine Chemical Environment: Categories of Marine Natural Products from Invertebrates— Chris M. Ireland, Deborah M. Roll, Tadeusz F. Molinski, Tawnya C. McK.ee, T. Mark Zabriskie, and J. Christopher Swersey 41 Characterization of Factors that are Intimately Involved in the Life of Marine Organisms— Koji NakanishL 59 Peptide Chain Toxins of Marine Animals— William R. Kern 69 The Phylogenetic and Biomedical Significance of Extended Neuropeptide Families— Michael J. Greenberg and David A. Price 85 Marine Organisms as Models for the Study of Neuropharmacology— Toshio Narahashi 97 Use of Selective Toxins to Examine Acetylcholine Receptor Structure— Palmer Taylor, Paul Culver, Stewart Abramson, Linda Wasserman, Toni Kline, and William Femcal 109 Olfactory Receptors of Crustaceans with Similarities to Internal Receptors for Neuroactive Substances- William E. S. Carr, Richard A. Gleeson, and Henry G. Trapido-Rosenthal 1 15 Importance of Marine Natural Products in the Study of Inflammation and Calcium Channels— Larry A. Wheeler, George Sachs, Danon Goodrum, Larry Amdahl, Nancy Horowitz, and Gerald W. De Vries 125 Manoalide: An Antiinflammatory and Analgesic Marine Natural Product— Alejandro M. S. Mayer and Robert S. Jacobs 133 New Pharmaceuticals from Cultured Blue-Green Algae— Richard E. Moore, Gregory M. L. Patterson, and Wayne W. Carmichael _ 143 National Cancer Institute's Role in the Discovery of New Antineoplastic Agents — Matthew Suffness and Janice E, Thompson _ 151 Concluding Remarks — William Fenical 159 INTRODUCTION pharmacology. From my perspective, that begins and ends with organismal biology, while chemistry, pharmacology/physiology, The multifaceted field known as marine pharmacology has and pharmaceutical science are sandwiched between. First, or- recently experienced a rapid expansion in pure and applied re- ganisms are collected and identified. In the case of extracts for sults, which has led to a resurgence of funding. Whole families probes or therapeutic use, successive phases of screening and of chemical compounds rare or unknown in the terrestrial realm purification come next, with chemical characterization and, pos- are being characterized. Model systems involving marine or- sibly, synthesis and drug trials following. Where organs or or- ganisms have been developed that aid in understanding many ganisms are of interest as models or test systems, isolations, physiological processes. Compounds of marine origin are finding preparations, and techniques must be developed. For complete- increasing use as highly specific probes for investigation of cel- ness, the focus should eventually return to marine organisms lular function and structure. The first drugs developed from and to the function of the molecule or structure in the plant or marine organisms are now in clinical trials, and the National animal from which it was derived. Cancer Institute has launched a new program for collecting and Practitioners of marine pharmacology who deal in organs or screening the sources of possible therapeutic agents. organisms seem frequently and explicitly to recognize that mol- At this watershed, I invited 22 speakers, each selected to ecules and structures represent strategies for dealing with the represent a segment of concern along a broad spectrum of the problems of survival common to all living beings, and that they discipline, to present retrospective and prospective views of usually reflect evolutionary relationships. For example, both those facets, providing an historical context to current trajec- vertebrates and molluscs evolved sophisticated nervous sys- tories. The purpose of the Third Biennial Symposium of the tems, with image-forming eyes and nerves capable of rapid im- California Academy of Sciences, held 30 April-2 May 1987, in pulse transmission. Comparative physiological and anatomical San Francisco, was to gather together speakers not only from research revealed these similarities to be analogous rather than different fields within marine pharmacology, but from govern- homologous— the animals accomplish similar ends from totally ment, industry, and academe as well. My explicit intention was distinct beginnings: nervous transmission is accelerated by my- to cross-cut conventional boundaries that often prevent people elin sheaths around vertebrate nerves, and by increased diam- with similar interests from learning about one another's work; eter in molluscan nerves. Neurophysiologists took advantage of this was a forum for the exchange of ideas among colleagues molluscan nerve size, as described by Toshio Narahashi in this who have few formal opportunities to meet. The symposium volume, to unravel the mechanism of impulse transmission, was not the place to communicate late-breaking discoveries, nor which, despite the differences in structure, turned out to be the for minute technical details in conventional research format same in vertebrates and molluscs. Therefore, much of what was where peers and competitors are addressed in a language few learned from squid giant axons was directly applicable to ver- others might understand — there are plenty of those already. tebrate nervous systems. Rather, I sought overviews of topics, with emphasis on implicit Even when direct application is impossible, understanding or explicit connections between fields and among speakers. alternative evolutionary pathways through comparative study The focus of the meeting is reflected in its title, and that of of structure and function almost invariably casts light on the this resultant volume, "Biomedical Importance of Marine Or- system of interest. One of the most intriguing— and ignored— ganisms." As a marine biologist, my primary interest in marine issues to me, an evolutionary biologist, is whether physiologi- pharmacology is the organisms that are the source of extracts, cally active compounds act similarly in the organisms producing or that provide models, or that are used as evaluation systems. them and in experimental systems. Biochemists, pharmacolo- For other scientists, the organisms may be of secondary or even gists, and the like can sometimes lose sight of the obvious- tertiary concern, but sight of them should never be lost, I believe. compounds they study were not put in marine invertebrates to It is the plants and animals— as objects and subjects of research, cure mouse Ehrlich ascites tumor or to puzzle chemists. I appeal or the sources of parts and molecules— that all participants in for structural and functional studies on extracts from marine the symposium, whether systematists, biochemists, pharma- organisms to be brought full circle, to address explicitly ques- cologists, or physicians, have in common. tions of evolutionary relationships. The body of information This perspective also explains why holding such a meeting is already extant can probably shed important light on issues of appropriate to a natural history museum. Among the conditions analogy and homology. This symposium can only hint at the imposed by NCI on contractors in its new program are those value of two-way information exchange between all possible dealing with documenting the provenance of the organisms in combinations of people working in this multifarious field, and question, obtaining accurate identifications of them, and de- the gains to be made from keeping marine organisms squarely position of documentary samples in appropriate archival facil- in the foreground. ities. Many curators at natural history museums, including the Following the time line, the two lead-off papers, by Judy California Academy of Sciences, are frequently called upon to Winston and Shirley Pomponi, address issues of collection and identify specimens for physiologists, chemists, and pharmacol- identification of organisms— current techniques and suggestions ogists. Thus, the first step in the process of "doing" marine for