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Chemistry International
Vol. 23, No. 2
March 2001

 

Medicinal Chemistry in the Development of Societies, Biodiversity, and Natural Products

by Prof. Antonio Monge-Vega et al.

Introduction

Links
Situation in South and Central America and Sub-Saharan Africa
Preservation and utilization of natural biodiversity
>> The Manila Declaration
>> The Melaka Accord
Contracts for natural products collaborations

The Phuket declaration

Originating Project
Related Project

Modern times have seen globalization of all human endeavors accompanied by a seamless, sans frontières, diffusion of culture, ideas, and science across traditional boundaries of territories, cultures, and societies. However, all societies are not at the same level of development, and a significant challenge still lies ahead in respecting and harnessing our differences to ensure peace, justice, and liberty for all.

For example, within the context of he life sciences, a man-made medicinal agent should receive special, international attention. Any compound that can help restore lost health or prevent a disease should be made available to all countries, regardless of the continental location or the degree of societal development. The only limits that should exist are those that are organizational, linked to preparation, distribution, etc.

Currently, there are countries that are the discoverers of medicinal agents, and there are countries that are simply consumers. Likewise, there are countries whose legislation pertaining to intellectual property rights is quite sophisticated, while there are others who do not have this type of legislation at all. Some countries are in search of development with an overabundance of natural resources and biodiversity, while others have the potential for scientific and technological exploitation, but lack such resources. In this wide panorama, the field of chemistry can play an important role, because medicinal agents are chemical products that, in many cases, are often modified–if not entirely prepared– by chemical reactions. Likewise, biodiversity is attributable to chemical constituents of plants with an array of complex structures, many of which have not yet succumbed to total, practical syntheses by man. To lose biodiversity is to lose information of great potential value.

Members of the IUPAC Medicinal Chemistry Section
Standing (left to right): Dr. E. Kyburz (Switzerland); Prof. C.R. Ganellin (England); Prof. C.G. Wermuth (France);
Dr. B.K. Trivedi (U.S.A.)
Seated (left to right): Dr. T.J. Perun (U.S.A.); Dr. N. Koga (Japan); Prof. A. Monge (Spain)

This article intends to refine and further promote ideas proposed during earlier projects of the IUPAC Medicinal Chemistry Section (VII.M) [1-3]. Specifically, the authors seek to enhance the transfer of science and technology associated with drug discovery and development between developed and developing societies in the most mutually beneficial scenarios possible.

Inverting the Model

Regardless of administrative or political considerations, companies and centers having high levels of development need to be brought together with those that lack it by means of joint projects within the broad field of chemistry and, especially, within the distinct area of biologically active compounds. Various modes of interaction can be proposed; the most often used is one wherein samples of materials from developing countries with biodiversity are extracted and transported for study in developed societies. We make a case for an inversion of this traditional model, namely, that of offering technology to the countries with biodiversity so that they themselves may carry out the necessary developmental work. Chemical research conducted in the country where samples originate would enhance that country’s scientific development. Competitive capacity, research methodology, and infrastructure could be the focus of negotiation and agreement. Contributions to chemical research on bioactive molecules that biodiversity-rich, developing countries then may be able to return can be ascertained on the basis of:

Strengths:

  • Biological material, both of animal and vegetable origin, with demonstrated or potential activity
  • Traditional knowledge concerning biological activities, linked to plants or animals

Weaknesses:

  • Infrastructure deficiencies that cause difficulties for conducting scientific research

Salient features of such programs should provide for conservation of biodiversity, equitable intellectual property rights/duties, and development of scientific resources/facilities/infrastructure.

Medicinal Chemistry and Biodiversity

Realizing that biodiversity can be lost by man-made cataclysms such as the construction of large public works or by natural catastrophes such as fires, volcanoes etc., medicinal chemistry can function as a great ally by emphasizing the ecobalance between life and its surroundings, plants and microfauna, and other relationships.

Medicinal chemistry also recognizes the symbiotic interaction between native communities and cultures as a foundation and wellspring for potential discoveries. These interrelationships must be nurtured, and their key elements preserved. Researchers studying natural medicinal agents subscribe to this rationale.

Their analysis, evaluation, and effective utilization of available resources can greatly assist in maintaining the elements of biodiversity while promoting scientific advances. Alternatively, in developing countries whose economies are based on the exploitation of agricultural and livestock resources principally geared to the production of cash crops and immediate products, there is great pressure on their natural space. Consequently, there is also great pressure toward the potential elimination of their natural flora. Thus, the relationships between biodiversity, opportunity, and the structuring of various alliances become especially important relative to the immediate financial needs of a developing country. In this light, however, biodiversity and medicinal chemistry must find a way to collaborate and optimize opportunities based on new alliances and technology transfer that is not based upon pure economics. Enormous benefits can accrue in the fields of education, scientific research, and innovation when an approach other than immediate financial gain is taken. Some examples can be illustrative. The "uña de gato," Uncaria tomentosa, DC, is a liana which has long been used by native communities of South America. However, the people from the countries where the plant grows became wary of exporting extracts for medicinal chemistry research because they thought they might not receive commensurate benefits. Ultimately, the plant became offered on the Internet in any quantity anywhere in the world by a few financially opportunistic companies.

The result is that the opportunity for incorporating technology and technological development for the countries that originally possessed the plant has been lost. Alternatively, the domestication of plants, such as the Catharanthus roseus G. Don of great interest in the production of anticancer alkaloids like vincristine, represents a form of conserving biodiversity, of training in agricultural techniques of economic interest, and of creating a local chemical industry.

Medicinal Chemistry and Ownership of Natural Resources

Recognizing the sovereign rights that each country has over its resources [4], the aim of this report is to prompt compromises between developed countries and developing countries in the area of ownership. New circumstances [5] have emerged that suggest reform of the traditional system of patents essential for commercialization and diffusion of science. Currently, when a native community produces a unique cloth, it can be copied by the whole world because it is not legally protected. Alternatively, when an entity in a developed country copies and registers modifications based on the designs of a native community, absolutely no one, not even the original artists, can legally copy them [6]. It could be argued that the native community has the sole responsibility to register its work in order to obtain legal protection.

However, such countries are typically unable to do this because of a lack of knowledge regarding these types of procedures or owing to a scarcity of the means to achieve such ends. The same situation can happen with a galenic preparation of a plant that has biological activity when initially used by a traditional culture.

Establishing ownership may not be simple. It is imperative to begin by defining the discoverer [7]. In the discovery of medicinal agents by traditional ways of medicinal chemistry, ownership can correspond to an individual researcher or to an entire research team. For plants with therapeutic applications originating from native communities, the question is much more complicated. Here we are speaking more of a "chain" of inventors. This process can result in problems when it comes to the selection of the beneficiaries and the distribution of the benefits obtained. A matter of equal importance is the fact that certain cultures hold nature to be sacred and look askance at any attempts at its legal protection as a prelude to commercialization.

Whether the traditional use of a plant for a given pathology constitutes public property and prior art is a vexing question. The protection of knowledge, within the context of plants with biological activity, cannot be easily accomplished via patents, and it becomes necessary to search for further avenues. From the standpoint of equity, answers may be found during the transfer of knowledge. Consider that the number of plants that are currently used in their original form in therapeutics is quite limited. In practice, it is the process of biodirected fractionation of plant extracts that eventually permits us to find compounds that then typically also undergo further structural modification ultimately to provide preferred molecules that are more active and less toxic. Consequently, in this type of scenario a patent covering the initial plant material may not be adequate. The solution to this scenario of "plant development" can lead to an impasse precisely for the countries in search of development, thereby possibly losing by default the possibilities for the use of their biodiversity.

Economic compensation for historical knowledge should not be lost during the overall development process because the living materials may have needed protection and conservation, sometimes throughout centuries, in order ultimately to afford the current validation of their use. This effort might be compensated for through a contract, establishing royalties that could be obtained when commercialization takes place. In line with our previous discussion, the contract might also specify in advance of commercialization and as part of a collaborative development venture, the training of persons and the acquisition of equipment and technologies as well as the more typical payment for samples. For example, compensation could be provided to the persons that provide the plant, make the extracts, and carry out biological assays, in such a way that each one can maintain his or her own interest and ultimate stake in commercialization. The country obtains benefits directly through taxation corresponding to the activities, and more importantly, through the scientific and technological upgrading of its society. The possibility of regional subsidiary or local companies playing a more important role in the transference of research and technology in such collaborative scenarios should also be seriously considered.

In countries with emerging economies, biodiversity and related activities constitute "green gold." For this reason, at times, the governments assume quick, financially driven policies that can sometimes be contrary to ecorelationships. Thus, both parties must be prepared to adopt longer-range planning considerations into their decision-making processes. Equity and equal opportunity must be given to protect the discoveries made by any society. This principle of equity can ameliorate any misunderstanding arising out of the actions of medicinal chemists in developed countries in their relationship with their counterparts in developing countries.

Summary

  • Medicinal chemistry research on extracts from plants and other living organisms that leads to the discovery of therapeutic agents, can also be an important factor toward maintaining biodiversity.
  • Relationships between societies that possess important biodiversity and developed societies that possess advanced technological processes should be based on the principles of equity. Such relationships should operate by means of collaborative contracts that acknowledge progression of scientific research in such a way that the immediate financial aspects are not considered to be of primary interest but rather only a legitimate, longer-term consequence of such partnering [8,9].
  • Because all of humanity benefits from the discovery of new drugs, all societies should collaborate in the preservation and evaluation of the areas of great diversity from which such structures might emerge.

Such collaboration could be carried out through investments made by pharmaceutical companies to help preserve a particular type of land (e.g., of great biodiversity, of fragile environment, or where promising species prosper) and through the promotion of localized searches done in collaborative settings that can allow for both immediate development of identified active substances and sustained cultivation of undefined biodiversity.

Additional Recommendations

  • Strengthen international relationships on medicinal chemistry research projects, particularly including countries at different levels of development.
  • Utilize university-company relationships within less-developed countries.
  • Strengthen international relationships between scientists and the authorities responsible for research in various countries.

This report was prepared for publication by: A. Monge, M. Chorghade, P. W. Erhardt, C. R. Ganellin, N. Koga, P. Lindberg, T. J. Perun, J. G. Topliss, B. K. Trivedi, and C. G. Wermuth.

Acknowledgments

The following persons have collaborated in this work: F. Alcudia González, I. Aldana, M. Benaim, H. Cerecetto, R. S. Compagnone, P. X. Chiriboga, A. J. Farré, M. Fernández Braña, F. Ferrándiz García, E. Ferro, J. Fischer, M. Gattuso, S. Gattuso, S. Guccione, P. Huenchuñir Gómez, T. Kobayashi, Y. Martín, C. Ochoa de Ocáriz, B. Sener, S. Vega Noverola, and S. Zacchino.

*References

1. P. R. Andrews, R. Borris, E. Dagne, M. Gupta, L. A Mistcher, A. Monge, N. J. de Souza, J. G. Topliss. "Preservation and utilization of natural biodiversity in context of search for economically valuable medicinal biota" (Summary of Technical Report), Chem. Int. 19 (3), 77 (1997).
Full text: Pure Appl. Chem., Vol. 68, No.12, pp. 2325-2332, 1996 and web version <http://www.iupac.org/reports/1996/6812andrews/index.html>
2. P. R. Andrews, R. Borris, E. Dagne, M. P. Gupta, L. A. Mitscher, A. Monge, N. J. De Souza, J. G. Topliss. "General features of contracts for natural products collaborations" (Summary of Technical Report), Chem. Int. 19 (3), 77 (1997).
Full text: Pure Appl. Chem., Vol. 68, No.12, pp. 2333-2337, 1996 <http://www.iupac.org/reports/1996/6812andrews2/index.html>
3. A. Monge, R. Ganellin, J. Ide, N. Koga, L. Mitscher, C. Muller, T. J. Perun, J. G. Topliss, C. G. Wermuth. "Research and training in medicinal chemistry in South and Central American and Sub-Saharan Africa", Chem. Int. 21(3), 65-69 (1999).
<http://www.iupac.org/publications/ci/1999/may/africa.html>
4 . "The Phuket declaration", Chem. Int. 20(5) 139 (1998).
<http://www.iupac.org/publications/ci/1998/september/phuket.pdf>
or <http://www.iupac.org/symposia/proceedings/phuket97/declaration.html>
5 . S. Borman. "African AIDS tragedy: Patent rights versus human rights", Chem. Eng. News 49 (1999).
6 . P. Quéan. ¿De quién fue la idea?, Fuentes (UNESCO), (117), 4-5 (1999).
7 . R. Pidgeon. "Patenting–pitfalls and prizes", Chem. Br. 25-28 (1999).
8 . D. E. Nettleton, Jr. "Bioprospecting, compensation, and biopreservation", DN&P, 250-256 (1995).
9. C. M. Rodríguez. "Legal issues: Contracts, intellectual property rights, and other property rights", in Biodiversity, Biotechnology, and Sustainable Development, pp. 183-190 in Health and Agriculture: Emerging Connections, OPS. Washington, DC (1996).

**Prof. Antonio Monge-Vega (Centro de Investigación en Farmacobiología Aplicada, Universidad de Navarra, 31080, Pamplona, Spain; E-mail: cifa@unav.es), Chairman of the IUPAC Chemistry and Human Health Division Commission on Training and Development (VII.M.2) and Member of the Project Teams on Medicinal Chemistry Curriculum, Guidelines for Natural Product Collaborations, and Training and Research in Medicinal Chemistry in Developing Countries, contributed this article in collaboration with the co-authors listed. This overview represents IUPAC’s efforts to develop an awareness of the state of medicinal chemistry in different geographic areas of the world and a proposal to achieve more effective international cooperation.

 

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