Logistics and Politics in Plant Drug Discovery - ACS Publications

Chapter 8

Logistics and Politics in Plant Drug Discovery The Other End of the Spectrum

Downloaded by EAST CAROLINA UNIV on January 3, 2018 | http://pubs.acs.org Publication Date: May 5, 1993 | doi: 10.1021/bk-1993-0534.ch008

Djaja Doel Soejarto Program for Collaborative Research in the Pharmaceutical Sciences, College of Pharmacy, University of Illinois at Chicago, Chicago, EL 60612 and Department of Botany, Field Museum of Natural History, Chicago, IL 60605

Plant-drug discovery comprises a spectrum of activities, with the collection and identification of the plant materials to be tested on one end and the isolation and evaluation of biologically active compound(s) on the other. During the period of 1986-1991, a plant-collecting program was undertaken in the tropical rain forests of Southeast Asia as part of the National Cancer Institute's (NCI's) anticancer and anti-AIDS screening program. After five years of operation, the first cycle of the plant collection program was successfully completed, with the collection of more than 10,000 samples, comprising more than 2,500 angiosperm species, distributed in more than 200 families. In vitro anti-HIV test results provided by the NCI to date clearly demonstrate that logistics and politics have played an important role in this plant-drug discovery program.

Plant drug discovery and development comprise a spectrum of activities which start with field explorations to collect and identify the plant material to be investigated, followed by the extraction of the plant material, the testing of the extracts, the isolation of the active chemical constitutent(s), and the in-depth study of the purified compounds in preclinical and clinical evaluations. Whether it is an endeavor to discover drugs from plants of the temperate or tropical

0097-6156/93/0534-0096506.00/0 © 1993 American Chemical Society

Kinghorn and Balandrin; Human Medicinal Agents from Plants ACS Symposium Series; American Chemical Society: Washington, DC, 1993.


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forests, the field exploratory role is fundamental, since without the collected plant material, the remaining chain of events cannot be activated. The logistical aspects of plant procurement in drug discovery has been discussed at length by Perdue (2), based on experiences from the U.S. National Cancer Institute's (NCI's) plant anticancer-screening program, during the period of 1960-1976. At that time, plant exploration and collection efforts were directed to a broad geographic area worldwide, though the major focus was on the temperate and subtropical regions of the world (2). In 1986, following a four-year hiatus (see chapter by Cragg et al. in this volume) the NCI's anticancer-terrestrial plant screening program was re-established (3, 4). This time, however, the plant exploration and collection efforts were targeted to the tropical rain forests of the world, which had received only token attention in the previous program. Whether the goal is to collect plants from temperate or tropical rain forest regions, the basic logistical problems to be faced are the same. However, in tropical rain forest areas, the logistical challenges are compounded and include, among others, the high biodiversity of these forests, the inadequacy or lack of road communications in most forested areas, the various red tape issues and different cultures and language barriers that must be overcome in order to enter these forests, and the unique climatic conditions that present a challenge to the collection and drying of plant materials throughout major portion of the year. It is the purpose of this chapter to examine some aspects of the plantcollection phase of the NCI's tropical rain forest plant drug discovery program, based on on experiences obtained in the Southeast Asian region during the past few years. Plant Collecting Contracts Since 1986, when the NCI re-established its terrestrial plant-screening program, the Program for Collaborative Research in the Pharmaceutical Sciences of the College of Pharmacy, University of Illinois at Chicago, has been under contract to explore the tropical rain forests of Southeast Asia to collect plants, originally to be screened against cancer cell lines, but later also against HIV, the causative agent of AIDS. The actual laboratory testing is performed at the NCI's Frederick Cancer Research and Development Cfenter, Frederick, Maryland. Two other institutions have also been under contract, the New York Botanical Garden, for tropical American plants, and the Missouri Botanical Garden, for tropical African and Madagascaan plants. The goal of each of these contracts has been to collect a minimum of 1,500 different, vouchered and identified plant samples of high biological diversity per year (primarily flowering plants), each of 1/2-1 kg dry weight in quantity, as well as to recollect specific samples of interest that showed promiising activity in preliminary bioassay(s) in a somewhat larger quantity (10 kg dry weight). The University of Illinois at Chicago has carried out this mission with the support and collaboration of a number of U.S. botanical institutions. Among these are the Field Museum of


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Natural History (Chicago), the Arnold Arboretum of Harvard University (Cambridge, Massachusetts) and the Botany Department of the Bishop Museum (Honolulu, Hawaii), as well as collaborating host institutions in Southeast Asian countries, in particular the Forest Herbarium of the Royal Forest Department (Bangkok, Thailand), the Department of Botany of the University of Malaya (Kuala Lumpur, Malaysia), the Heng-chun Tropical Botanical Garden (Kenting, Taiwan), the Philippine National Herbarium (Manila, Philippines), the Bogor Herbarium of the Biology Research Center (Bogor, Indonesia) and the Forest Research Institute (Lae, Papua New Guinea). General Strategy To undertake a plant procurement program of this magnitude, a number of factors must be considered. These include: (i) selection criteria, (ii) permits to conduct field research in and to export plant materials from the country of collection, and (iii) cooperation with a host institution(s) during the collecting operation. The complete logistical aspects of the NCI-sponsored Southeast Asia plant collection program, in its broader context, is summarized in Figure 1. Selection Criteria. An important consideration in any plant collecting operation in a drug discovery program is the selection of plant species to be collected for study. If the selection process is based on literature analysis, normally, a list of plants to be procured is used as a guide in the collection process. This approach is known as a selective-collecting program. If plants to be collected are selected randomly, without any specific criteria, this approach is called a random-collecting program. However, a truly random approach in which one blindly collects everything encountered, without giving consideration even to the possibility of duplication, is not practical. The approach used in most drug discovery programs falls between these two basic approaches. In the NCIsponsored plant collection program, the ethnotaxonomic approach has been utilized. Plants to be collected are selected, first, with the primary goal of achieving the highest biodiversity of the samples as possible and, second, based on information of their medicinal uses. In order to achieve a high taxonomic diversity, a pre-collection documentation is necessary. This involves a literature survey and documentation on the floristic diversity of the area(s) targeted for collection, followed by a survey of the medicinal uses of plants from such area(s), as well as on-site field interviews with the populace or indigenous tribal groups on the uses of the plants for medicinal purposes. In the NCI plantscreening program, collection efforts have focussed primarily on the flowering plants, with field operations in a given region carried out in different months of the year. Permits to Conduct Field Research in and to Export Plant Materials from the Country of Collection. All tropical rain forests of the world are located within


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Flora of SE Asia TAXONLIST Medicinal Flora ETHNOLIST

J

Endemic Taxa ENDEMICLIST

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Botanical Profiles of Selected Species

l Visa, Collecting/Export Permits in Country of Collection


Establish Headquarters in Host Institution Facility Field Ethnomedical Information

Field Personnel 4-

i Scouting/Search for Plants COLLECTION (Avoid CITES-Listed Plants)

i

. Transportation

Voucher Herbarium Specimens

Screening-Sized Samples (Use Nylon Mesh Bags) Temporary FieldLabeling

Special Collection (70% ETOH/Isopropanol)

i Air-Drying (

Logistics and Politics in Plant Drug Discovery - ACS Publications

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