Some thoughts on the future of ethnopharmacology

Abstract

A discussion is offered of the future potential role of ethnopharmacology in global health care.

Introduction

“The presence of this tiny sheet of paper proves the presence of the whole cosmos”. (Thich Nhat Hanh, Being Peace)

“…the ability of ecosystems to sustain future generations can no longer be taken for granted”. (Millennium Ecosystem Assessment, United Nations, April, 2005)

“All nature is at the disposal of humankind. We are to work with it. For without it, we cannot survive”. (Saint Hildegarde of Bingen, 12th Century, quoted in Matthew Fox, Original Blessing)

“If you are on the fifth step and you think you are too high, you will never make it to the sixth step”. (Ajahn Chah, A Still Forest Pool)

“With a stout heart, a mouse can lift an elephant”. (Tibetan proverb, quoted in Feldman, A World Treasury)

Perhaps there is nothing more to be said. Perhaps if we can see the deeper reality in those quotations and aphorisms, and can evolve as visionary global citizens and scientists, all will be well. Perhaps. But to understand the “how”, it's all in the details, as Mies van der Rohe indicated (1959).

When you think about the future of ethnopharmacology, the first thing you have to do is to step out of the box. Working in the existing box is not proving to be optimal for us as a group of scientists. Did you know that? Do you feel that? There are some quite fundamental aspects of what we do that have to change, for us and for the community we serve. Let us try to explain, and by the end of the article we hope that you too will feel the need to step out side of that proverbial box. In my view, we must be on a mission, perhaps to try to save health care based on natural resources, no less. As Lao Tzu said, “Each journey starts with a single step” (Lao Tzu, 1990). Let our first step be the topic of oil and how it relates to the future of ethnopharmacology.

“G.M. (General Motors) is…reallocating engineering resources to rush the next generation of large sport utility vehicles…into production by the end of the year. G.M. is also…abandoning some planned small and midsize sporty cars” (Hakim, 2005).

They are doing WHAT?! Oil recently hit record highs of over US$ 60 per barrel (Bloomberg.com, 2005). Estimates are that it will go even higher later this year, and may reach US$ 135 per barrel within 3 years (Sherer, 2005). It is estimated that based on the known, reasonably accessible oil reserves, global production of oil will peak sometime late in 2007 (Campbell, 2002; Anonymous Peak Oil, 2005a). According to the United Nations and other sources (Anonymous, 2005b), and based on current estimates of known reserves, production capacity, and usage, the global oil supply may last another 60–70 years, albeit at steadily escalating costs. No less than 96% of our transportation needs are based on oil (Anonymous, 2005b). Nature gave us this gift of oil only once. What we have now, no-one else on this planet will ever have again. Ever. And yes, it is all there in that piece of paper. All of the myriad connections. Everything. We are living an illusion of no limits.

Since 1987 (Cordell, 1987, Cordell, 1990, Cordell, 1993, Cordell, 1995a, Cordell, 2000, Cordell, 2002a, Cordell, 2002b, Cordell, 2002c, Cordell, 2003, Cordell, 2004), one of us has been writing about the future of pharmacognosy and its’ “fit” in the world. Whether the topic of discussion is related to the evolution of pharmacognosy (defined as “The study of biologically active natural products”) or ethnopharmacology is moot. The real topic is what health care, particularly the use of medicinal agents for the prevention of disease and for treatment, will look like in 20, 30, and 40 years from now, By this time the global population is estimated to be at least 9.2 billion (United States Census Bureau, 2005a), 44% more than today (United States Census Bureau, 2005b).

So let's pause here for a moment. What do YOU envisage health care using medicinal agents to look like in the next 20, or 30, or 40 years? On a global basis, what will those medicinal agents be? Currently, 75% of prescription drugs sold in the United States are synthetic, and many of the remaining 25% are semisynthetic derivatives of natural products (Farnsworth and Morris, 1976). Is that the global model we should be striving for? Remember, it may take 10, 15, 20 years, or even (as in the case of camptothecin) 30 years, to transition a compound from the bench to the market. In your vision, what will be the origin of those medicinal agents? Who will be producing them, and where? How will they be regulated? Will those agents be different in the developed compared with the developing world? From where will enough raw material originate for the production of synthetic and semisynthetic drugs for a population of 8 or 9 billion people, and at prices that are affordable?

But here are some confounding factors to consider: (i) population growth will occur mostly in the developing world; populations will actually decline in many European countries and Japan (United States Census Bureau, 2005c); (ii) at the present time it is estimated to cost about US$ 800 million to bring a new single agent drug to market in the US (Di Masi et al., 2003, Adams and Brantner, 2004); (iii) the technology and biotechnology which can be applied to the biological evaluation of plant extracts and compounds is advancing at a breathtaking pace; (iv) there has been vast degradation of the many global ecosystems (United Nations, 2005); and (v) there are new killer diseases emerging (SARS, Marburg virus, avian flu virus, etc.), and drug resistance to the known antimicrobial, antiparasitic, and anticancer agents is on the rise (Anonymous, 2000a). How does this change your vision?

And … for the ethnomedical reports on about 14,300 species of plant in NAPRALERT (about 5.2% of all plant species), 58% of these species have never been examined biologically or chemically (Cordell and Quinn-Beattie, 2005). Yet, of those plant-derived products currently available as prescription products, 74% are used in a manner which parallels their ethnomedical use (Fabricant and Farnsworth, 2001). How about your vision now?

As you know, drug discovery is notoriously inefficient. Depending how you estimate compounds synthesized, only about one in a hundred thousand or more compounds evaluated biologically will make it to the market as a drug (Adams and Brantner, 2004). The major pharmaceutical companies have no, repeat NO, interest in screening higher plant (or marine or fungal) extracts for their biological potential. Programs evaluating plant extracts have been closed for several years. Antibiotic drug discovery screening of cultured broths has almost stopped. There are some small biotech companies doing natural product drug discovery, and their hope is to bring potent, novel compounds to the larger pharmaceutical companies for further development. But there is not a single company in the developed world which is basing its discovery strategy on ethnopharmacology. And NOW what is your vision for health care in 2025 or 2040?

Several years ago, we began an article on alkaloids and drug discovery with the phrase “We need to talk” (Cordell et al., 2001). Now we need to talk some more. We need to talk critically and strategically amongst ourselves in forums and in groups at scientific meetings. We need to be more proactive in formulating a consolidated view of where ethnopharmacology must “fit” in the scheme of global health care. And then we need to talk in a much larger arena. We need to assemble the “choir” and then we need to sing, VERY, VERY loudly, all over the world. We need a new vision for the natural product sciences and ethnopharmacology embracing a strategy based in contemporary and evolving science and technology that is relevant to global future health care needs.

Let us examine some “plausible futures” based on contemporary thinking of those outside of ethnopharmacology. The millennium ecosystem assessment (United Nations, 2005) examined four such future scenarios, all of which require a change from our present deleterious relationship with ecosystems: Global Orchestration, Order from Strength, Adapting Mosaic, and Technogarden. These scenarios differ based on whether global development paths are increasingly globalized or increasingly regionalized, and on two different approaches to ecosystem management, based on whether actions to issues are reactive or proactive. Many factors were considered, including population growth, per capita income, land use change, nutrient loading, and climate change. Under each of the examined scenarios the global temperature is expected to increase by 1.5–2.0 °C by 2050. This climate change will result in significant habitat loss, and predominantly negative economic effects throughout the world. It will also lead to possibly 10–15% extinction of plant species. In one of the scenarios, Order from Strength, which focuses on reactive policies in a regionalized world, health care in the developing countries could become worse “as economic inequality increases and as commerce and scientific exchanges … decrease”. The other three models foster more promising health care scenarios. Two aspects related to ethnopharmacology were examined: biochemicals and genetic resources (p. 182) and infectious disease regulation (p. 187). Several areas, including botanical medicines, cosmetics and natural personal care, and crop protection and biological control were anticipated to increase in intensity. Meanwhile, it was concluded that ecosytem modifications had led to increases in numerous infectious diseases on a global basis, including malaria, meningitis, leishmaniasis, dengue, Japanese encephalitis, African trypanosomiasis, Chagas’ disease, schistosomiasis, filariasis, and diarrheal diseases. These effects have occurred and will continue to occur mostly in the tropical areas of the world.

Let's briefly examine some current issues that face the use of plant materials in health care.