Amazon rainforest: biodiversity and biopiracy

The Amazon rainforest is home to a flora with an enormous and vastly unexplored pharmacological potential. Klaus Morales and Tulio Vinicius investigate why biopiracy is becoming a threat to Brazilian biodiversity

It seems strange, when we have many advanced chemical compounds, to look for therapeutic resources in rainforests. But modern medicine relies on natural products, which make up more than half of all drugs in industrialised countries.¹ There's still a lot to be explored in the 7 800 000 km- Amazon region, which is home to as many as 80 000 plant species. Brazilian flora comprise more than 20% of the known species worldwide, and the Portuguese described their use in the management of disease as early as 1500.²

Phytopharmaceuticals and phytotherapeutics

Basic concepts
Plant pharmacology has a specific terminology of its own. Phytopharmaceuticals is the name given to the active principles extracted from plants used by the drug industry in a technologically processed way, such as digoxin, escopolamine, or morphine. Phytotherapeutics include a range of plant based pharmaceutical agents which vary widely in quality and are made from modified plants that have therapeutic properties but were not previously purified. According to the World Health Organization, these products have been through some sort of pharmacological or toxicological modification. Thousands of plants are currently used for therapeutic purposes, but few have been transformed into phytotherapeutics, such as the spasmolytic and anti-inflammatory activity of Matricana chamomilla, and the laxative formulations from Cassia certa, Ginkgo biloba, Allium sativum (garlic), and Calendula officinalis (calendula).¹

An increasingly popular option
Around the world, people are increasingly mixing elements of local and biomedical tradition. In developing countries, medicinal plants are used extensively by local care givers, mainly because of their low cost and the difficulties in seeing a doctor. In Brazil, 60% of all processed drugs are consumed by 23°/o of the population, and 841/o of all drugs are imported. Local pharmaceutical companies are not able to compete with the advertising power of foreign companies. In addition, government taxes are usually attractive to companies from overseas. The low income of the population and the high costs of drugs also contribute to this awful picture .^{2 3} There is a shortage of studies of new therapeutic agents-fewer than 21% of Amazon higher plant species have been tested for pharmacological activity.⁴ One way of reducing drug imports, or even making drugs available at a lower cost, would be cultivating locally species that are known to have therapeutic compounds.

Lack of evidence
There have been few scientific studies on the efficacy and safety of phytotherapeutics. In Brazil, the requirement of preclinical and clinical tests for registration was established in 1995, and the manufacturers of products already on the market had 10 years to assess and confirm their efficacy.² These trials were supposed to be carried out with local universities, but few institutions got involved. Since government inspection agencies are unable to assess whether manufacturers are complying with the legislation, examples of products taken off the market are unheard of.² The European Union accepts such products on the basis of well documented minimal quality criteria established by the WHO:' There is also the mistaken view that phytopharmaceuticals are harmless to the body because they come from nature. These agents have biologically active components which have the same pharmacodynamic principles as any other agent.

How new drugs are discovered
Methods of identification
Species with the largest therapeutic potential can be identified by different methods. One way is to look for information on the traditional use of the plants. "That is the way we proceed here at our laboratory," explains Dr GraCa Brandao from the pharmacognosy laboratory of the Faculty of Pharmacy of the Federal University of Minas Gerais, Brazil. "We study plants used in Brazilian traditional medicine to treat malaria, diabetes, and hypertension."

Another method is to study various species of the same botanical genus or family of already known phytotherapeutics. After the screening stage, the material is collected, identified, dehydrated, and its chemical components extracted. It is then possible to purify those components and to identify the compounds which are pharmacologically active. The pharmacological effects may be identified by tests performed in-vitro or in-vivo.

Clinical studies
After its pharmacological activity has been established, the product is evaluated in clinical trials. Hundreds of plants undergo some type of invitro study. Roughly one third are evaluated in-vivo, but few plants go through clinical assessment, according to Professor Brandao. One of the difficulties in doing research with natural products is the high cost.

Box 1 shows the strategies used in in-vitro screening. These methods are preferred by the screening programmes of drug companies.¹

Ethnopharmacology
Although plants can be collected randomly or included in a chemotaxonomic classification-one incorporating botanical genus and species sharing common characteristics, thus possibly grouping plants with similar therapeutic potential-regional folklore may reveal useful clues and guide appropriate studies.

Another strategy is to consider how different cultures use the drugs. The scientific exploration of biologically active agents in traditional usage is known as ethnopharmacology. This method has shown better results than searching for new treatments by chance.^{1 6 7}  The ethnopharmacological approach depends on considering cultural diversity as biodiversity, since the approach relies heavily on traditional knowledge within ethnic groups.

ARS/USDA
Cinchona ledgeriana - or quinine, a raw material for gin and tonic. Apparently also cures malaria

Resources of the Amazon forest
Commonly used plants
Many plants sold at markets are known locally as "general tonics," "nerve tonics," or "aphrodisiacs." Researchers hypothesise potential links between these agents and central nervous system effects.' A nerve tonic, Chaunochiton kappleri, showed antidepressive-like effects in a number of psychopharmacological evaluations.' A well known example of a drug extracted from the Brazilian biodiversity is the antihypertensive agent captopril. This medicine was developed from the poison of Bothrops jararaca, a Brazilian snake. Other examples of products extracted not only from Amazon plants but from other Brazilian ecosystems are curare (Chondondendron platyphyllum-muscle relaxing action), pilocarpine (Pilocarpus microphyllus - anti - glaucoma agent), and quinine (Cinchona ledgeriana-antimalarial). All these products are exported from Brazil to a variety of countries, where they are widely used.

Box 2 lists some plants whose pharmacological activity is already known.
 

Plants under study
A variety of medicinal plants are currently being studied in Brazil and other parts of the world. Many already show promising results, such as the Brazilian ginseng (Pfaffia paniculata) as a neoplasic inhibitor"" and cat's claw (Tomentosa uncaria) as an antioxidant and anti-inflammatory agent"' Despite the positive results, the challenge remains, especially in Brazil, to transform these products into drugs. Ayahuasca shows promise for the treatment of alcoholism and substance abuse, serotoninergic deficits, and immune modulation, although studies under controlled protocols such as the Food and Drug Administration are still to be conducted." It is an aqueous preparation made from a variety of plants, based on Banisteriopsis caapi and Psycotria viridis (hallucinogens). Both have a high concentration of alkaloids, such as N,N-dimetiltriptamine and others from the (3-carbolin group, respectively. The action of the drink can therefore be attributed to the presence of these substances and not to the rituals associated with it.

Drug companies
The potential of biodiversity has attracted the attention of drug companies, which aim to seek and extract biological resources. The Amazon basin is still the largest intact tropical forest left in the world, but that seems to be changing. Deforestation is transforming forests which are rich in species into biotically impoverished regrowth forests.

Biopiracy
Many Brazilian plants have been collected without the participation of Brazilian researchers. They were patented outside Brazil and are now used commercially worldwide, including in Brazil. This practice is known as biopiracy, which is the extraction of biological resources from national territory without the knowledge of local authorities. In 1992, Rio dejaneiro hosted ECO-92, the United Nations Conference on Environment and Development, which was set to elaborate strategies for implementing sustainable development. Surprisingly, in that event the Convention of Biological Diversity was signed and established the equal partition of benefits from the commercial exploration of natural products. It was expected to complement existing international arrangements for the conservation of biological diversity and sustainable use of its components. Among other objectives, it also aimed to conserve and promote the sustainable use of biological diversity for the benefit of present and future generations.'"

"Although biopiracy and plant trafficking may be confused as synonyms, these terms have distinct meanings. Plant trafficking is the action of collecting, capturing, or transporting biological material, regardless of its origin. Biopiracy, however, is the identification, isolation, or usage of genetic information for the purpose of bioprospection, said Christiane Duarte, environmental analyst of IBAMA, a governmental institution which deals with environment protection, in a recent issue of the regional scientific magazine Minas Faz Ciencia.¹² "Nowadays, transporting genetic material is quite simple: a leaf is simply put in the pocket, a plant seed is swallowed and transferred to any place in the world," Ms Duarte adds. Biopiracy in itself does not have a direct environmental impact. However, natives living in forests are thus prevented from using their products in a sustainable way.¹³ This happens when products are patented and commercialised for companies from other countries.

Plants might be the source of new, revolutionary drugs, but the rainforests which harbour them are still threatened by uncontrolled and irrational exploration.

Klaus Morales dos Santos fifth year medical student,
Tulio Vinicius de Oliveira Campos fifth year medical student,
Federal University of Minas Gerais, Belo Horizonte/MG, Brazil
klausmorales@medicina.ufmg.br

studentBMJ 2005;13:353-396 October ISSN 0966-6494

We thank Dr Grarca Lins Brandao for her contribution to this article.

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