Question

One of the difficulties in geolocational profiling plant-derived drugs is obtaining reliable standards. Elaborate on this statement.

Subject: (Forensic Chemistry)

Answer 1

Since very often plants are collected directly from their natural habitat, the correct identification and nomenclature are essential. For an unambiguous identification, a combination of methods might be necessary, such as genetic and chemical analysis in addition to morphological and anatomical characterization. Moreover, collection of the plant material and accurate documentation, botanical identification, as well as preparation of the herbarium vouchers are tasks that cannot be automated and need specialists who become increasingly rare.

Important challenges related with the use of plants as a source for identification of bioactive compounds are related with the accessibility of the starting material. Limited availability of such plants is a major problem and becomes even more problematic when a bioactive plant-derived natural product is identified to have a very promising bioactivity and becomes a pharmaceutical lead. Recollections of wild species may turn difficult, since plant habitats can rapidly disappear under anthropic pressure. Moreover, the habitat of plants, particularly of protected species, needs to be respected when collecting from the wild, and season-dependent chemical composition of plant material may limit the time window for recollection. Therefore, researchers conclude that natural products occurring in many different species are more favorable for medicinal use, and that supply constraints are a major obstacle to the successful research, development and commercialization of natural products.

In many cases, when a plant becomes commercialized as a herbal medicine or when one of its constituents starts getting used as a pharmaceutical drug, its populations become threatened due to extensive wildcrafting and unsustainable harvesting techniques. The classical example for this compound supply problem was the so-called “taxol supply crisis”. When the compound turned out to possess remarkable clinical efficacy in ovarian cancer, suddenly the demand for taxol increased tremendously. However, at that time, the compound was only accessible from the bark of the western yew. This was on one hand problematic because the whole production process including tedious bark collection and drying, extraction, and purification was very time-consuming. Therefore, development of guidelines on good agricultural and collection practices for medicinal plants in order to promote sustainable plant collection techniques and to reduce the ecological problems produced by wildcrafting of medicinal plants has been done.

Apart from that, ecological and legal considerations also have an important influence on accessibility of plants as a source of drug discovery, especially laws dealing with plant access and sharing of benefits, as well as patentability issues with local governments in the countries of origin. The United Nation's Convention on Biological Diversity aims at conserving the biodiversity, sustainably using its genetic resources and sharing the benefits from their use in a fair and equitable manner. Although the CBD provided a framework for countries to regulate and define bioprospecting, the treaty left many open questions, particularly in the issue of access and benefit sharing and it could not always rebut the skepticism toward bioprospecting in many developing countries due to previous exploitation of their biodiversity; some countries issued very stringent protective regulations, and some were very slow in establishing the necessary legal framework, leading to confusion where to go for permissions and who had authority to grant them. On the other hand, the expectations of biodiversity-rich countries on the potential monetary benefits to achieve from drugs developed from their genetic resources were highly exaggerated.

These issues frequently hampered the access to samples from biodiversity-rich countries in the last two decades and thereby discouraged pharmaceutical companies from natural product-based drug discovery.

Besides the accessibility of the plant material, also its quality is of great importance. Available plant material often varies on quality and composition and this can hamper the assessment of its therapeutic claims. The chemical composition is not only dependent on species identity and harvest time, but also on soil composition, altitude, actual climate, processing, and storage conditions.

Due to the challenges described above, the interest in natural product-based drug discovery has been gradually declining. Even in the last decade, many big and medium-sized pharmaceutical companies, which were still active in the area in the 1990s, terminated their natural product programs, leaving natural product research to a major extent to academic universities and start-up companies.