Module I: The Business of Biodiversity

Plants have formed the basis for traditional medicinal systems for thousands of years, with the first records dating from about 2600 BC in Mesopotamia. They used oils from cedar and cypress, licorice, myrrh, and poppy juice, among other things--substances that are still in use today for the treatment of a variety of illnesses and infections. Ancient Egyptian, Chinese, and Indian documents show that medicine in these societies included numerous plant-based remedies and preventives. The Greeks and Arabs both contributed substantially to the assimilation, codification, and development of plant-based medicines. Today approximately 80 percent of the world’s population relies on traditional plant-based medicines for primary health care.

The remaining 20 percent of the world’s population also depends on plant products for health care. About 25 percent of prescription drugs dispensed in the United States contain plant extracts or active ingredients derived from plants. Out of a total of 520 new drugs approved for commercial use between 1983 and 1994, 30 were new natural products and 127 were chemically modified natural products. Some prominent plant-based medicines include:

• Quinine, the anti-malarial drug, from the bark of Cinchona species;
• Morphine, the analgesic, from the opium poppy;
• Digoxin, for heart disorders, from Digitalis purpurea;
• Reserpine, the antihypertensive agent, from Rauwolfia serpentina, traditionally used for snakebites and other ailments;
• Ephedrine, an anti-asthma agent, from Ephredra sinica; and
• Tubocurarine, the muscle relaxant, from Chondrodendron and Curarea species, used in the Amazon as the basis for the arrow poison curare.

Microorganisms have also been extremely important in drug applications, ushering in the "golden age of antibiotics":

• Anti-bacterial agents from Penicillium species;
• Immunosuppressants, such as the cyclosporins and rapamycin, from Streptomyces species;
• Cholesterol lowering agents, such as mevastatin and lovastatin, from Penicillium species;
• Anthelmintics and antiparasitic drugs, such as the ivermectins, from Streptomyces species; and
• A potential new antidiabetic agent from a Pseudomassaria fungal species found in the Congolese rainforest.

The world’s oceans and marine organisms also represent a vast resource for new therapeutic agents, including:

• The pseudopterosins, with significant analgesic and anti-inflammatory properties, from the Caribbean gorgonian Pseudopterogorgia elisabethae;
• Manoalide, an anti-inflammatory agent, from the sponge Luffarriella variabilis; and
• Ziconotide and other new pain killers derived from peptides from cone snail venom.

Several key anti-cancer agents have been produced from natural sources; more than 60 percent of cancer drugs on the market are based at least in part on natural products:

• Vinblastine and vincristine were isolated from the Madagascar periwinkle, Catharanthus rosesus;
• Etoposide and teniposide are semi-synthetic derivatives of the natural product epipodophyllotoxin;
• Taxol was initially isolated from the bark of Taxus brevifolia in the northwestern United States; and
• Several clinically active agents have been derived from camptothecin, isolated from the Chinese ornamental tree Camptotheca acuminata.

Natural products should continue to be an important part of drug development well into the future. The sequencing of the human genome opens new territory in terms of our ability to identify the proteins expressed by genes associated with the onset of diseases. These proteins can be used as molecular targets for testing thousands of compounds, including natural products, in high throughput assays. Sequencing of the genomes of pathogens and parasites will also yield important clues about how best to control them.

Despite the great successes already achieved in natural products chemistry and drug development, we have barely begun to tap the potential of our molecular diversity. Only an estimated 5 to 15 percent of the 250,000 species of higher terrestrial plants in existence have been chemically and pharmacologically investigated in systematic fashion. The percentage of insects, marine organisms, and microbes investigated is far lower still. In the case of microbes, it is estimated that 95 to 99 percent of existing species are currently not even known, never mind analyzed. There is currently great interest in exploring extreme habitats for useful enzymes from microbes, including acidophiles (from acidic sulfurous hot springs), alkalophiles (from alkaline lakes), halophiles (from salt lakes), thermophiles (from deep sea vents), and psychrophiles (from extremely cold waters).

Synthetic methods can complement natural products in the search for new drugs. For example, combinatorial biosynthesis creates the potential to generate novel molecules that enhance known bioactivity from natural products, and possibly to generate entirely new bioactivity through manipulation of biosynthetic pathways. Total synthesis of natural products, focusing on the synthesis and modification of drugs from natural sources that are difficult to isolate in sufficient quantities, can sometimes isolate and improve the essential active features of a natural product.

Acknowledging the importance of biological diversity for drug discovery and other uses, the Convention on Biological Diversity (CBD) affirms the rights of genetically rich source countries over their biological resources. As a result, organizations from the industrialized world involved in drug discovery and development now face increasing pressure to adopt policies of equitable collaboration and compensation. This issue is addressed in more detail below and in Module II.