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Introduction Chemical ecology: Can it survive without natural products chemistry? Thomas Eisner* Department of Neurobiology and Behavior, Cornell University, Ithaca, NY 14853 New disciplines arise by convergence of interests. Chemical ecology is the product of a partnership between biologists and natural products chemists united by a shared vision and empowered by complementary skills. The vision stems from the realization that all organisms emit chemical signals and that all, in their respective ways, respond to the chemical emissions of others. Nature, in accord with this construct, is a dynamic assemblage of vast complexity, driven by interactions that are, for the most part, mediated by molecules. The natural products chemist brings to the partnership the ability to decipher these chemical signals. Not surprisingly, the collaboration between the chemical ecologist and the natural products chemist is a close one (see Fig. 1~. Chemical ecology came into its own in the midst of the molecular biological revolution, in the 1950s, at the same time that vastly improved techniques and instruments came on line by which chemicals could be isolated and characterized. Natural products chemistry traditionally had been applied in its orien- tation. Its primary goal was the discovery of molecules of use, substances of medical, industrial, and agricultural interest, and it was highly successful in such endeavors. Its expansion into the domain of chemical ecology represented a shift in goals, to problems of fundamental rather than applied significance, but the challenge was immense and the potential significance of the findings enormous. At stake was the understanding of the chemical basis of biotic interaction. Think of how profoundly chemical ecology has been affected by what relatively little we have learned so far about the signaling agents of nature. Think of how this knowledge has affected the way we view the biotic world. And think also of how profoundly this knowledge has affected our view of the physical world. The air, the oceans, and the inland waters can no longer be viewed as simple matrices. All, in accord with the grander view, are seen as carriers, as the vehicles by which the communicative messages of life are conveyed. Chemical ecology was to derive further advantage by what can be termed its "molecularization," that is, its ever-widening linkage with various molecular subdisciplines of the biological sciences. The signal molecules that convey information from one organism to another are biosynthesized under genetic control, deciphered at specific receptor sites, transduced into neuronal, neuroendocrine, or phytoendocrine signals, and, eventually, after triggering intermediate cascading effects, translated into behavioral or morphogenetic responses. Each step in this se- quence of events lends itself to interpretation in molecular terms. Not surprisingly, chemical ecology is poised to broaden its inquiries in accord with opportunities offered by advances in molecular biology. It is clear from all these developments that chemical ecology has major exploratory potential and that the path ahead for the discipline is rich in opportunity. Yet there is a disturbing development that needs attention, lest it prevent that path from being taken. Ironic as it may seem, natural products chemistry is currently slated for deemphasis. This turn of events is partic- www.pnas.org/cgi/doi/ 10.1 073/pnas.2436167 100 ~ Industry Medicine BASIC Agnculture KNOWLEDGE Fig. 1. Chemical ecology and natural products chemistry are linked in a productive partnership aimed at clarifying the chemical basis of ecological and behavioral interactions in nature. To curtail natural products chemistry now is to put on hold the acquisition of this fundamental Icnowledge. ularly disconcerting because it comes at a time when, technically, the discipline is ideally positioned to meet its goals. Thanks to vast improvements in techniques and instrumentation, com- pounds can now be isolated and characterized on the basis of minute amounts of material. One can now literally reach into the air or the waters to capture, selectively, and in the desired amounts, the messenger molecules of one's choice. Where gram or kilogram quantities of starting material were once needed, microgram or nanogram quantities now suffice. Given the promise and the significance of the discoveries at stake, does it make sense that one should now put constraints on natural products chemistry? Some recent events are worth pondering. At the very time when one is finally in possession of the proper analytical tools, chemistry departments and funding agencies, not to mention industrial concerns, are backing away from support of natural products chemistry. The very universities that in years past provided a home for the birth of chemical ecology are now relinquishing leadership in the area. Chemistry departments, caught up in the campuswide struggle for control of the genomic, postgenomic, and other molecular programs, are seeking glory in name change. "Department of Chemistry and Chemical Biology" is what more than one university chemistry department now calls itself, even after taking the paradoxical step of This paper serves as an introc~uction to the following papers, which result from the Arthur M. Sackier Colloquium of the National Acaclemy of Sciences, "Chemical Communication in a Post-Genomic WoricI," held January 17-19, 2003, at the Arnold anc' Mabel Beckman Center of the National Academies of Science and Engineering in Irvine, CA. *E-maii: te14@corneiEedu. 2003 by The National Academy of Sciences of the USA PNAS 1 November 25, 2003 1 vol. 100 1 suppl. 2 1 14517-14518

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eliminating natural products chemistry from the curriculum. And industries themselves are increasingly inclined to curtail their analytical and synthetic natural products programs. Chemical ecologists, and for that matter biologists generally, will do well to stand in opposition to this trend. The biological research effort will wither on many fronts unless the capability to characterize natural products is maintained. If chemistry departments are unwilling to house the necessary instrumenta- tion, or recruit faculty in the area, then these requirements will need to be met by the biological establishment itself. There is precedent for the incorporation into biology of a discipline that could just as well formally have been linked to chemistry. Biochemistry, at the time of its emergence, did not gain accep- 14518 1 www.pnas.org/cgi/doi/1 0.1073/pnas.24361671 00 lance in chemistry but in biology, and the affiliation, quite obviously, has been a successful one. I would suggest that the same could be done for chemical ecology. If this discipline is to live up to its promise, it will need to find a home that is sympathetic both to its biological and to its chemical needs. Chemical ecology is now embarking on the most ambitious and inventive phase of its existence. To stand by and allow natural products chemistry to vanish, or even to be weakened, is to deny chemical ecology its future. My research in chemical ecology is supported by National Institutes of Health Grant AI 02908. Eisner