Sharing Innovative Experiences (Vol.7)

Bioprospecting of Medicinal and Food Plants: Pakistan

Atta-ur-Rahman and M. Iqbal Choudhary
H.E.J. Research Institute of Chemistry
University of Karachi, Karachi
Pakistan

Summary
Bioprospecting of plants entails the search for economically valuable biochemical resources from the floral wealth of a country. Such initiatives hold the promise of new medicines and biodegradable pesticides that can be a source of income for developing countries, thus providing incentives to conserve biodiversity. About 150 drugs derived from 100 species of medicinal plants currently are on the market. According to recent estimates, 25 percent of all prescribed medicines in the developed world contain ingredients derived from plants and roughly 80 percent of the world's population living in the developing world relies on herbal remedies for their primary health care needs.

The flora of Pakistan is very rich due to the nation's diverse climatic, and soil conditions and multiple ecological regions. The country has about 6,000 species of wild plants of which about 400 to 600 are considered to be medicinally important. According to a survey by Pakistan Forest Institute, 75 crude herbal drugs are extensively exported and more than 200 are locally traded in Pakistan. Indigenous people, who have no training in sustainable harvesting, post-harvesting care and storing of medicinal plants, collect 85 percent of these crude herbs from the wild. Such activity is causing a rapid depletion of medicinal plant resources. In addition, indigenous knowledge used to identity, evaluate and apply medicinal plants I dying out and no systematic documentation of the ethnobotanic information exists.

Realizing that bioprospecting can make a valuable contribution to sustainable development, the H.E.J. Research Institute of Chemistry at the University of Karachi initiated a program about 10 years ago whose thrust was to generate new opportunities to improve national capacities and add value to medicinal plant resources. The program focused on research and development work in the area of chemistry, taxonomy, agronomy and traditional medicine. Although the effort is still in progress, it has already resulted in the development of skills and infrastructure, transfer of technology and increased awareness by concerned participants.

The projects carried out under this program can be broadly classified into two categories. First single plant species were selected on the basis of their folk use and screened for their biological activities (medicinal or agricultural) and chemical constituents. This approach led to the isolation of a large number of bioactive chemical constituents, many of which are in different stages of biological and pharmacological studies. The second set of projects involves the rationalization of composite plant-based remedies and manufacturing of herbal-based medicines that are already in use. These projects include standardization of medicines, toxicological studies and bioassay screenings. This category of projects is far more relevant to the socio-economic conditions of the rural populations of Pakistan.

Background and Justification
The total area of Pakistan is nearly 10 million hectares, of which 88 percent is classified as arid and semi-arid and only 12 percent is humid and sub-humid. The area covered by forests is about 5 percent. Most of the medicinal plants are found in the temperate climates and sub-tropical forests of northern Pakistan.

According to a survey, crude medicinal plants materials worth more than Rs. 150 million (US$2.3 million) per year are used in Pakistan. Most of these plants are obtained from the wild. Pakistan exports large quantities of crude plants at very cheap prices in the international market (worth US$6 million). In the entire business chain, gatherers receive the least money and are forced to collect more and more plant material to survive. In general, Pakistan receives a paltry return from its natural floral wealth. It is an experience shared by most other resource-rich developing countries.

Bioprospecng provides an incentive for the conservation of biodiversity by adding value to natural resources and generating revenues for the conservation efforts. Pakistan, as a developing country, has limited capacities to supply value-added products to the world market that meet the standards of quality control and the strict regulatory requirements of international buyers. As a result, the country has become a major exporter of bulk cheap crude materials leading to the rapid depletion of medicinal plant resources. It is therefore important that research and development efforts focus on the value-addition and sustainable utilization of medicinal plant resources. The project's prime objectives are to bring the medicinal plant sector on a firm scientific footing, develop skills and capacities, raise awareness, add value to the resource and contribute both to the socio-economic well-being of communities and the conservation of the resource base.

In this study, four main issues of bioprospecting were analyzed: (1) how to add value to the medicinal plant resources, (2) how to develop institutional capacities, (3) how to build skills in bioprospecting, and (4) how to develop indigenous technology. These issues, if resolved, could dramatically transform Pakistan's involvement in the world economy from a raw material provider to a final product producer. Such a development would not only make full use of Pakistan's rich natural resources, but have a positive impact on the nation's economy.

Description
The bioprospecting practices of the institute focused on six main areas: (1) identifying bioactive constituents, (2) producing plant-based pesticides, (3) studying the efficacy and safety of plant-based composite medicines, (4) producing garlic-based edible oil, (5) cultivating Cathareanthus roseus and vinblastine, and (6) developing programmes to increase the value of raw plant materials.

Pakistan enjoys a rich tradition in the use of medicinal plants for the treatment of ailments. The ethnobotanic information, folk literature and herbal pharmacopia document a large number of plants used in medicine. One of the best criteria for the selection of plants for bioprospecting is based on ethnobotanic and traditional use.

Drawing on the ethnobotanic information, the institute selected certain plants phytochemical and biological studies. This approach led to the discovery of a large number of bioactive constituents. Notable among them was the discovery of a new class of anti-epileptic terpenes, delphadiones A and B from a medicinal plant Delphinium denudatum. This plant is used as to treat epilepsy in the folk culture. Compounds isolated from this plant are among the most potent antiepileptic natural products known and pre-clinical work on them is in progress.

The production of plant-based pesticides provide another focus for the institute. Today, adverse health effects and pest-resistance are two of the most serious problems associated with the use of synthetic pesticides. Thus, there is growing interest in the discovery of natural pesticides that are affordable, biodegradable and host-specific. Pakistan has a rich tradition in the use of plant materials as pesticides. Based on the folk use, researchers at the institute selected several abundantly available plants and screened them for pesticidal properties. From this effort, two plant-based pesticide formulations were developed. Initial field trials on cotton and horticulture crops have shown extremely promising results. Both formulations were found to be active against white fly, an insect considered one of the most destructive agriculture pests in Pakistan. Patents on both formulations have been filed.

The institute has published several studies on the efficacy and safety of plant-based composite medicines. In collaboration with the Hamdard Laboratories, Pakistan's largest herbal medicine manufacturer, researchers initiated a project to rationalize some of the herbal-medicines manufactured and marketed by Hamdard. This project was funded by US Agency for International Development (USAID) under the Institutional Excellence Program (IEP). The major thrust of the project was to study the effects of six herbal formulations as an anti-diabetic drug. These herbal medicines had been extensively used in Pakistan. Detailed chemical, pharmacological and toxicological work on the vegetative constituents of these plant-based medicines was conducted to test its toxicity and safety levels. As a result several unsafe (mildly toxic) constituents were identified and reported to the manufacturer. Hamdard has modified its anti-diabetic formulations based on our recommendations.

The production of garlic-based edible oil has been another focus of the institute. Garlic (Allium satirvm) is a common herb used extensively all over the world. Both the folk use and scientific literature confirm its efficacy against several health disorders. Ajoene, a constituent of garlic, is reported to have clinically proven cholesterol-lowering effect in human patients. Researchers have developed a process for isolating and chemically enriching the ajoene. This additive, when blended with the edible oil, can reduce blood-cholesterol levels substantially with moderate use. Wazir Ali Industries, one of the largest manufacturers of edible oils in Pakistan, has leased this product from the institute for large-scale manufacturing. It will be on the market nationally and internationally in a short time.

Catharanthus roseus is one of the most important medicinal plants in the world. The plant contains two binary indole alkaloids, vinblastine and vincristine that are drugs of choice for pediatric leukemia and Hodgkin disease. Because of its importance, the institute has cultivated Catharanthus roseus and produced vinblastine at its plant section for bioprocessing. Although chemical syntheses of these alkaloids are well established (Atta-ur-Rahman reported the first total synthesis of vinblastine in 1976), these medicines are still produced from natural sources due to very high synthetic cost and poor yields. A large-scale isolation process was developed that gives 30-fold higher yields (up to 60 grams per ton of leaves) of vinblastine than the previous process. Currently, Catharanthus roseus is cultivated on 8 to 10 acres and the materials is processed in the pilot-plant section of the institute. If all goes according to plan, bioprocessing will eventually be initiated on a large scale.

Bioprocessing at the institute also involves adding value to the large quantities of plant materials that are exported in crude forms from Pakistan. This includes Glycyrrliza glabra, Hypercum performatus, Commiphora mukul, Carum copticum, Valeriara wallichlii, and Cassia fistula. These plants are collected from wild sources and sold to local traders who, through a chain of middlemen, are able to reach international traders. In this chain of profit makers, the plant gatherers receive virtually virtually nothing. The logical solution to this problem would be to eliminate the middlemen and add value to the herbal material. Such a solution would ultimately benefit local communities in Pakistan while preserving the ecosystem.

Two programmes have been launched to add value to the herbal material. The first program involves the manufacture of homeopathic medicine. Homeopathy is a widely practiced system of medicine in Pakistan. Most of the nation's homeopathy medicines, which are imported from Germany, are unaffordable for common people. Ironically, most of the raw material required for these medicines found in Pakistan and is exported in crude form. What makes these circumstances particularly troublesome is that procedures for the manufacture of homeopathic mother tinctures are fairly simple and straightforward.

The institute is currently establishing small manufacturing units to bring Pakistan to a higher level of economic involvement. With the help of SDC-IC (Swiss Development Cooperation-Inter-Cooperation) and MAPA (Medicinal and Aromatic Plant Project in Asia), it is hoped that financing for the implementation phase of this project can be secured. The project could offer opportunities for the participation of young members of local communities in the manufacturing process whereas the standardization and quality control could be conducted in other institutions such as the H.E.J. Research institute of Chemistry. This practice, if implemented successfully, will provide incentives to the communities to add value to the natural resources they own and to use them in a sustainable fashion. The SDS-IC, in a parallel effort, is implementing a project for the promotion of the cultivation of major medicinal plant species so that the pressure on wild resources can be reduced.

The manufacture of value-added extracts is a key component of the institute's programme. Such crude plant materials as the resin of Commiphora mukul and leaves of Hypericum patulum bring only meager revenues to the country. In collaboration with a local herbal medicine manufacturing company, Medics Laboratory, researchers have initiated a programme in which standardized extracts of medicinal plants are manufactured for the international market. These extracts generate several fold more value in terms of price in the quality-conscious global market. The institute has developed procedures to standardize these extracts on the basis of their active constituents. One example of this work includes the extracts of Commiphora mukul (Guggul), standardized on the basis of E- and Z- guggulaterone; H. perforatrum (St. John Wort), standardized on the basis of hypercin and hyperforin contents; and garlic extract, optimized on the basis of ajoene content.

In the absence of venture capital, it is important to explore the economic feasibility of bioprospecting practices through pilot-plant level production. The institute has established a large pilot-plant section equipped with large-scale extractors, solvent evaporators, and distillation units. This pilot plant can handle 500-800 kg plant materials and is currently used for medicinal plant processing for local manufacturers of herbal remedies.

The majority of these projects have been very successful. Results either have been published in scientific journals or patented nationally for commercialization. Standardized extracts of some medicinal plants have been supplied to an industrial partner, Medics Laboratory in Karachi, for international export. These include extracts of St. John Wart, Commiphora mukul and garlic. The garlic-based edible oil, which lowers cholesterol, will be marketed by Wazir Ali Industries group within the year. The plant-based pesticides developed at the institute are in different stages of commercialization. In collaboration with PARC (Pakistan Agricultural Research Council), large-scale cultivation of the plant has been planned. The provincial government of Sindh, sponsor of the project, is in the process of finding suitable industrial partners for the manufacture of these plant-based natural pesticides on a large-scale.

Partnerships
The bioprospecting practices documented in this case study have been conducted in partnership with public and private sectors. Pakistan's Ministry of Science and Technology and Agricultural Research Council of the government of Sindh have sponsored the project on plant-based pesticides. The project on the manufacture of homeopathic drugs from local medicinal plants have been funded by the University Grants Commission of Pakistan and MAPPA. A number of private companies such as Medics Laboratory, Hamdard (Waqf.) and Highnoon Laboratories, have sponsored and participated in other programs mentioned in this case study.

In addition, partnerships with other countries and international organizations have been established. Indeed during these bioprospecting practices, active collaborations and partnerships have been forged with a large number of individuals and institutions abroad. Collaborative projects have been conducted on the chemistry and pharmacology of medicinal plants in several countries, including Turkey, Sri Lanka, Ethiopia, Mongolia, Jordan, Bangladesh, and Iran. All of these partnerships have involved exchanges with universities.

This case study has great relevance to other developing countries. Most developing countries have rich natural resources. Countries in Asia, Africa, Central and South America and the Caribbean are rich floral wealth. Except for a few countries, the majority of these nations have received little income from their medicinal plant resources.

The bioprospecting practices mentioned in this case study could spur substantial increases in the value of genetic resources. By instituting effective bioprospecting methods, the value of natural resources could be substantially enhanced, a prospect that, in turn, could increase revenues for conservation efforts.

Lessons Learned
This case study brings to light several important issues for developing countries. Countries such as Pakistan need to find a way to sustainably utilize their medicinal plant resources. Such efforts would result in the participation of communities as potential benefactors of resources and as real owners of the resource base.

The impetus for this case study came from a growing realization that the plant resources of Pakistan are depleting rapidly due to overexploitation and unsustainable practices. This disturbing circumstance is mainly due to the low value of Pakistan's unprocessed raw materials. With an expanding base of scientific and technological capabilities to effectively carry out bioprospecting practices and growing public demand for plant-based products, the institute has helped increase the economic potential of our biological resources.

The institute has brought together a diverse range of human and material resources to accomplish its goals. As a prime research institute of Pakistan, the trust and confidence of donors and other partners was already in place. Similarly, organizational support, such as necessary flexibility in defining research strategies and goals, non-technical staff assistance and the backing of senior management helped us initiate and successfully carry out these efforts.

Among the more universal experiences learned from this study is that bioprospecting is an interdisciplinary field. To reach goals in an efficient manner requires the expertise and technical support of a team of scientists with diverse training. This team should include botanists, chemists, and pharmacologists. We also learned that without the support of private sector, the economic potential of any bioprospecting practice cannot be fully explored or realized.

Problems Faced
As in most development projects, the lack of resources for bioprospecting reslated to R&D work impeded the institute's efforts. During the course of many projects, it became evident that there was lack of reliable inventory of medicinal plants of Pakistan. Currently, there is no national herbal pharmacopoeia, herbarium of economic plants and ethnobotanic data in Pakistan. It is difficult to find suitable commercial partners because industries based on indigenous R&D do not exist in Pakistan. These is also no clear policy on profit sharing, intellectual property rights and other potential relevant legislation. Nongovernmental organizations, moreover, are not fully prepared to handle issues related to bioprospecting and benefit sharing.

Education is an important prerequisite for developing research and legislation in this area. The two main investigators, Atta-ur-Rahman and M. Iqbal Choudhary, have delivered dozens of lectures on bioprospecting and related issues. He investigators have also written extensively on this topic both in scientific journals and national newspapers. The institute organizes a series of symposia on the chemistry of natural products in which an average or 350 researchers, industrial representatives, students and government officials participate from different countries of the world. This is a biannual event organized since 1984.

Impact
Bioprospecting can lead to substantial increases in value of natural resources. With a balanced approach and careful planning, these revenues can be used for conservation and reforestation of medicinal plants and can contribute towards sustainable development in the South. A substantial part of the revenues generated by bioprospecting should be channeled to communities and invested in conservation efforts. In addition, periodic assessments of the resource base should be conducted and a socio-economic survey of community participation should be administered to assess the overall impact of the bioprospecting practices.

The sustainable nature of the activities describe above should generate revenues for additional growth and expansion. Most importantly, these practices are directly relevant to the well-being of the local people making such efforts not only sustainable but economically desirable. The economic potential of bioprospecting can also play a pivotal role in bringing necessary investments from the private sector. This will only help ensure that the practice is sustainable.

Future Plans
Plans to improve and expand the project are underway. The institute intends to continue bioprospecting work with a major emphasis on developing linkages with other institutions around the globe to learn from their experiences. The institute also wants to ensure that local communities that own the plant resources and possess ethnobotanic knowledge are the ultimate beneficiaries of the bioprospecting practices.

The results of many of the bioprospecting practices mentioned above are patented locally. These include the technology for the extraction of essential oils of spices, aromatic and medicinal plants and chemical synthesis and new high yielding extraction process for the isolation of vinblastine. Other projects have yielded scientifically and economically significant results that deserve protection under patent and intellectual property rights.

Plans for collaboration and sharing of results with other organizations/countries have proven successful. Future emphasis will be on strengthening linkages with other institutions nationally and internationally. A workshop on "Technology for New Product Development from Medicinal Plants," which was organized January 20-26, 2000, marked an important step towards achieving this objective. Asia Pacific Center for Technology Transfer (APCTT), United Nations Educations Scientific and Cultural Organization (UNESCO), Islamic Development Bank (Jeddah), Asian Network of Research on Antidiabetic Plants (ANRAP, Dhaka), Medocoma; and Aromatic Plants Project in Asia (MAPPA), SDC-IC, Inter-Islamic Network on Tropical Medicine, International Union for Conservation of Nature (IUCN), Aga Khan Rural Support Program (AKRSP), and World Wide Fund for Nature (WWF) were among the most active participants in the conference.

Future Partherships
In the future, the institute intends to forge partnerships with many stakeholders and major players, including governmental organizations, R&D institutions, nongovernmental organizations and private sector firms. The institute views the Pakistani government as a facilitator and an enabler in the process. Government, at the provincial and local level, is expected to encourage conservation and sustainable utilization of resources through community participation once such projects prove successful. This can be done by providing soft loans, consultations and technical assistance to the local people to encourage ex-site cultivation of medicinal plants and value addition at community levels.

The private sector is an important player in the process. The institute intends to involve private industrial partners in the production of herbal-based products, the large-scale cultivation of plants and the search for new markets both nationally and internationally. Several industrial partners have been contacted for potential collaboration in the production of plant-based pesticides, essential oils and other herbal-based products.

Nongovernmental organizations are playing an important role in the conservation of bioresources of Pakistan. Many have developed innovative approaches, including income-generation programmes for communities, horticulture development projects, and shared management of forest resources. In the future, the institute intends to collaborate with nongovernmental organizations, including SDC (Swiss Development Coopertion), AKRSP (Aga Khan Rural Support Programme), WWF (Worldwide for Nature) and IUCN (International Union for Conservation of Nature) in mobilizing communities for cultivation of medicinal plants and sustainable utilization of vegetative resources. Production of homeopathic mother tinctures, manufacture of vegetative resources. Production of homeopathic mother tinctures, manufacture of essential oils, and development of medicinal plant organic farming are major areas in which the help of nongovernmental organizations will be required. The institute understands that all major stakeholders are aware of the economic potential of bioprospecting and the importance of the sustainable utilization of natural resources. With this in mind, it hopes to develop fruitful partnerships as a primary means of achieving its objectives.

Implementing Institution
H.E.J. Research Institute of Chemistry
International Centre for Chemical Science
University of Karachi
Karachi 75270
Pakistan

Phone: +92 21 9243224, 9243235
Fax: +92 21 9243190, 9243191
Email: hej@digicom.net.pk. zainraa@digicom.net.pk
Website: www.hej.edu.pk