Optimizing new therapeutic discoveries from ethnomedical and ethnobotanical data.
Memory Elvin-Lewis
Washington University
Department of Biology
St. Louis MO 63130
INTRODUCTION
Only a few years ago, old concepts hampered the acceptance of the use of herbal
remedies as having any potential therapeutic value. There were a variety of reasons why they
were poorly understood and disregarded, and overall were viewed as having little potential value,
considered unreliable, old fashioned, and if formulated as mixtures of plants, totally
incomprehensible as to worth. Furthermore pharmaceutical companies looking for potent and
unique compounds often applied high-throughput mechanistic methods to screen both random
and ethnobotanical collections with total disregard for the valuable ethnomedical data
accompanying certain specimens. Without matching to presumed bioreactivity their rate of
discovery was disappointing and thus these results continued to discredit their significance. Also,
up until recently clinical trials were poorly conducted, and often so biased as not to be
reproducible outside the country of origin. Thus claims of efficacy continued to be anecdotal and
thus circumspect.
In the past decade there has been a radical change in opinion regarding the worth of
utilizing ethnomedical and ethnobotanical data for the discovery of new therapeutic agents. In
part, this has been related to the increasing interest in utilizing these sources as the basis for
alternative and complementary approaches to medicine; a concept that only a few years ago
would have been disregarded as having little value to serving the needs of global medicine. With
rising health care costs, expanding populations with increased life spans on one hand, and the
seriousness of emerging infections that are decimating others, it is appropriate to search for
remedies that could have a greater cosmopolitan application. Currently, with support from both
the World Health Organization, and in the United States, the National Institute of Health and
particularly, the National Center for Complementary and Alternative Medicine (NCCAM), serious
attempts are being made to understand the basis for their mode of actions and their clinical
efficacy.
In definition, an herbal remedy may be traditionally or serendipitously derived, varying in
formulation and preparation, often unreliable as to plant identification, and depending upon its
cultural source, infrequently validated as to efficacy. It may be prescribed by a healer of
experience or of questionable skill, or used in self-medication. Generally most of these remedies
have moderate potency and toxicity, and thus are not fast acting nor overtly dangerous. They
are, however, not inert and adverse reactions, or interactions with other medications can occur
(Elvin-Lewis, 2001). Treatments do not necessarily depend upon one plant. Many involve using
plants in a sequential manner, or in many traditional Asian formulations they carefully mixed for
maximum efficacy of each bioreactive ingredient. Today, many of these ancient remedies are
being clinically evaluated, and modified for optimal efficacy. If bioreactive components are known,
the plant or plants may be formulated or blended into standardized botanicals or
phytopharmaceuticals. In these forms they are likely to contain several bioreactive components,
which can act together to affect an optimal therapeutic response. With anti-infectives, for
example, the risk of evolving resistance to the medication is lowered. Moreover, this form of
combinational therapy, may elicit additive or synergistic effects that are not apparent when the
bioreactive compounds are used independently from one another. Only rarely will any plant yield
a compound low in toxicity, potent and unique enough to be worthy of becoming a
pharmaceutical.
There are many reasons why regional variations in herbal remedies using the same flora
can occur, particularly since cultural differences often dictate how diagnosis and efficacy is
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determined. Much depends upon the origins of the medicinal systems that are being applied, as
well as outside influences that are affecting both formulation and application. For example,
knowledge may be widespread within a population, known to only a few specialized healers
through oral tradition, or applied by trained practitioners using well-documented formulations
outlined in traditional pharmacopeias. Many pharmacopeias are constantly evolving, and those of
current Western origin may incorporate both traditional and novel uses of phytomedicines.
Within this context, one can expect to find deviations in appropriate plant identification, nuances
of formula preparation, dosage, and types of treatment regimens. The formulations are
comprised of individual or mixed formulations of plant material and sometimes other products,
used together or sequentially and are prepared to be used as infusions, decoctions, poultices and
salves, eye, ear and nose drops, enemas, purgatives, suppositories, emetics, snuffs, vapor baths,
inhalants, and injectibles etc.
To determine how a particular remedy is impacting upon the health of its users, this type
of expected variability needs to be understood. By accumulating sufficient data, general patterns
of choice can become apparent that can allow the evolution of appropriate formulations and
treatment regimens. Appropriate use of a particular remedy may have a significant impact on the
patterns of health care that are observed. However in the evolution of any new therapeutic agent,
it is also important to establish its basis for bioreactivity and to conduct appropriate clinical
evaluations based upon conventional (allopathic) criteria. .
When a specific disease can be related to its etiology, its clinical definition is apparent to
both patients and practitioners, and clinical assay parameters are available to establish efficacy,
patterns of change can be followed during treatment. Allopathic parameters can include
modifications in clinical presentation, physiologic, serologic or other defined responses relative to
the disease entity before, during and after treatment. Value is further confirmed by showing how
a remedy affects degrees of incidence, that specific bioreactivities can be identified,
dereplications affirm value, clinical evaluations have merit, and toxic or adverse effects are
minimal. While definitions of resolution may vary among herbal practitioners, a well-defined
response to therapy is an important factor if allopathic confirmation is to be obtained. Fitting
remedies for these types of studies are Hepatitis B (Elvin-Lewis et al 2002, Elvin-Lewis, in
manuscript) and diabetes (Lewis and Elvin-Lewis, 2003). Applying these techniques would be
unsuitable when symptoms are vague and confusing, multiple etiologies are known, the disease
is of minor importance, treatment regimens unclear, and complex diagnostic procedures are
required.
When numerous bioreactive remedies for a disease make identifying the best for a region
challenging then it is important to evoke a consensus of worth throughout a population by eliciting
appropriate clinical data, and proof of efficacy from individuals using the remedies, as well as
practitioners that may be prescribing. This technique referred to as ethnomedical focusing avoids
bias associated with limited interviews and provides a more accurate assessment of value. It is
noteworthy, that uses within a family unit can vary, so depending on only a few informants could
skew the accuracy of the results. In my research this technique has been applied to chewingstick use in Ghana Adu-tutu et al, 1979, Elvin-Lewis et al, 1980b) and tooth blackening (ElvinLewis, 1983; Lewis and Elvin-Lewis, 1984) and use of hepatitis remedies in Amazonia (ElvinLewis et al 2002). It followed that the most popular remedies are generally the most bioreactive.
Moreover, selective criteria are applied, and plant use can vary in the same region depending
upon tribal or community preferences, age, gender, availability and the like.
POLYETHNIC DERIVATION OF PHARMACOPEIAS OF THE CARIBBEAN BASIN.
Countries of the Caribbean Basin with their evolving polyethnic herbal medicines have
the potential of contributing significantly to this effort primarily because so many types of
traditional medicines have employed this region’s unique flora. Empirical evaluations are not just
of post Colombian origin but have been ongoing for over 500 years. While contributions of the
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original inhabitants of the Caribbean island nations are unknown, it is clear that both indigenous
plant sources and those imported from elsewhere are being widely utilized for medicinal
purposes. This knowledge has not been necessarily exclusive to one group or another, and with
the admixture of cultural approaches to healing has resulted in the development of
pharmacopeias that deserve appropriate assessment as sources of new therapeutic agents
whether they be eventually used as botanicals, phytopharmaceuticals or pharmaceuticals. To
appreciate present-day medicinal practices within the Caribbean Basin it is important to recognize
the contribution of these various medicinal systems (Elvin-Lewis, 2001). While several decades
old, Morton’s Atlas of Medicinal Plants of Middle America is sufficiently comprehensive to provide
the basis for understanding the therapeutic uses of this regional flora (Morton 1981).
Nowadays, national policies related to the collection and utilization of primary data within
Caribbean countries may differ fundamentally from several decades ago when collection of
information was obtained without fiduciary constraints. Within this context all laws and policies
regarding bioprospecting activities to which the host country is a signature must be understood
and applied to prevent the project being labeled as “biopiracy”. This is particularly true when
indigenous pharmacopeias are being explored. In this respect, it is important to engage oversight
from national authorities and to employ a comprehensive scientific team and legal entities
representing all parties, so that parameters of access are appropriately defined, collection of data
and specimens are optimally achieved, and equitable benefit sharing is officially evolved and
appropriately understood. When evolution of commercial products is the goal, appropriate
entities must be identified to make this possible, and renewable resource strategies well thoughtout.
EUROPEAN TRADITIONAL MEDICINE
European traditional medicine has its origins in ancient Egypt, Assyrian, Greek, Arabian
and Roman cultures. Many plant choices were the product of the concept of the Doctrine of
Signatures. The plant’s appearance (e.g., shape, color) often determined its use in specific
therapies. During the 19th century, formal types of herbalism in the form of both homeopathy and
naturopathy evolved that are still practiced today. In addition, many herbalists undergo specified
apprenticeships and belong to professional societies. Although regulatory standards for herbal
drugs vary from country to country the policies regarding their formulation and use continue to
develop. The current pharmacopeias often appear in the form of monographs outlining
parameters of formulation, use, efficacy and toxicity of each individual herb. The uses of
phytopharmaceuticals standardized to bioreactivity levels are becoming increasingly popular, and
in Germany, appear in monographs that carefully outline parameters of use and safety. There,
physicians may prescribe certain types. Currently new formulations may contain plants obtained
from any where in the world. Self-medication is common (Elvin-Lewis, 2001).
ASIAN TRADITIONAL MEDICAL SYSTEMS.
Asian medical systems are based on a long tradition of use of pharmacopeias that
appear in ancient texts. Practitioners are formally schooled, and generally adhere very closely to
well-defined methods of diagnosis, formulation of drugs containing plants, sometimes, animal
parts and minerals, and treatment regimens. In India, for example, practitioners of Aryuveda
(Hindu), Unani (Arabic) and Siddha may work in the same medical centers with conventional
allopathic physicians. Also in India, the regional “tribal” pharmacopeias are now being recognized
as a valuable new resource of healing plants, and are being actively investigated for their value.
Sometimes these medicinal plants are used as substitutes in traditional formulations. It is unclear
if this “tribal” knowledge resides primarily with traditional healers or is generally known to a
particular group. However when appropriately identified, policies are in place for appropriate
benefit sharing should a commercially viable discovery be made.
The medical systems of East Asia e.g., China (Wu-Hsing) and Japan (Kampo) are
philosophically linked through commonalities in diagnosis, formulation and treatments. In some
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instances, only slight variations in the concentration of components may exist as seen for
hepatitis remedies used in China (Xiao Chai Hu Tang) and Japan (Sho-Saiko-To), respectively.
Bioreactivities associated with plants used in these formulations denote complementary modes of
action and several are considered hepatoprotective, anti-inflammatory, immunostimulating,
antiviral, antiemetic and antipyretic.
Many of these Asian formulations represent complex mixtures of plants designed to
optimize the value of the remedy, however accompanying packaging inserts may not describe all
ingredients or potential adverse effects. Unfortunately, undesirable reactions to traditional Asian
formulations exist. Because of the lack of regulatory policies, advertent or inadvertent
substitutions of ingredients can occur. Since the practitioner often formulates according to the
patient’s needs, remedies bearing the same name may vary in content. This may be
problematical if adverse reactions result. Disconcerting also is the inclusion of unapproved
ingredients including potent pharmaceuticals, toxic and allergenic substances, and a number of
heavy metals in concentrations of over 30 ppm.
Generally, when compared to pharmaceutically derived drugs, the incidence of lifethreatening situations is significantly lower with most of these therapeutic remedies. However,
until the time that appropriate regulatory practices are properly instituted so that drug content and
treatments are standardized, the meaning of well-designed clinical evaluations will remain
circumspect. Unlike a few years ago when claims of efficacy could not be substantiated, suitable
studies are beginning to be published that indicate that attempts are being made to overcome
these difficulties. Moreover, the increased interaction of scientists studying these complementary
Asian medicinal systems should be valuable in authenticating their cosmopolitan value (ElvinLewis, 2001).
AFRICAN MEDICINAL SYSTEMS.
North African Saharan traditional medical practices are generally derived from the Arabic
system of medicine with European nuances. In sub Sahara Africa, these pharmacopeias are
usually tribally based, with some regional overlap of plant use seen. Knowledge is often
exclusive to one healer that is the custodian of traditional family secrets. Plants may be used
alone or as mixtures. Much data, generated primarily during the European colonial period, has
already been published (Dalziel, 1937; Watt and Breyer-Brandwijk, 1962) as well as being
currently updated (Burkill 1985, 1994, 1995, 1997, 2000; Neuwinger, 1996). It is unknown how
much information still remains proprietorial.
Regional and national societies of healers do exist, and in many countries they are
collaborating with state authorities or international organizations like the World Health
Organization (WHO) to formulate needed botanicals or phytopharmaceuticals. Fetish priests do
not practice herbal medicine, but may use psychotropic plants. Some function much like village
psychiatrists; others are knowledgeable of the occult such as seen in the voodoo practices of
some Caribbean societies.
INDIGENOUS MEDICAL SYSTEMS.
Where indigenous cultures are intact, indigenous medical practices are still known. This
information is being rapidly lost or modified as contacts with other people continue. Depending
upon the level of literacy, this form of traditional knowledge may be transmitted from one
generation to another as a form of oral history. Healers trained in this customary fashion are
known worldwide. Plants used as therapeutics may be selected generically, specifically or among
the inexperienced, can be incorrect. Today this knowledge can still reside exclusively with
traditional healers, be generally known by a tribe or within a region, or published in some form as
secondary data. Much of the data concerning North Amerindian uses is in this latter form
(Moerman, 1999). The “sacredness” associated with many of these plants and the need for
repetitive chanting or prayers, often eliciting ancestral support, may be associated with the
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therapeutic process. This an aspect not well understood outside of North Amerindian
communities.
Shaminism, like Fetish practices of Sub Saharan African communities, or voodoo
practices within the Caribbean Basin, may require the practitioner or patient to take psychotropic
plants. Shamans, sometimes called Brujos (witches) can combine forms of psychiatric healing
with occult practices and also may use repetitive chants in their routines. Contrary to current
beliefs, their healing usually does not involve the use of other types of phytotherapy.
In some societies, such as Samoa or among certain North Amerindian communities’
specific individuals are known as healers or are called “medicine men or medicine women”. In
Latin America, community herbal practitioners are often referred to as “curandaros”. Among the
Quichua-speaking people of the Andes, often of mixed heritage, medicinal plants are available in
market places and in specialty stores run by knowledgeable phytotherapists. However, in many
parts of Amazonia, the use of herbal remedies is generally known rather than being exclusive to a
particular community healer. Plants with uses often have very specific epithets, those not
considered valuable are less likely to be identified in that manner. Nowadays, post Colombian
introductions e.g., ginger (Zingiber officinalis) and turmeric (Curcuma longa) can be found as a
part of many ‘traditional’ pharmacopeias including those of South America.
In Amazonia, already prized for providing the world with quinine and curare our studies
and others, continue to indicate that pharmacopeias of this region are a rich potential source of
new pharmaceuticals and phytomedicines. Within these communities, my collaborator, Dr. Walter
Lewis and I have observed that there can be a wide variation in how plant remedies are
formulated and applied. Men tend to be more conversant of plants needed by both genders e.g.,
healing wounds, or for other ethnobotanical purposes e.g., building homes, canoes etc. Women
are particularly well informed of medicinal plants needed for themselves or their children. As
aculturization continues, much of this unique knowledge is rapidly disappearing. These remedies
may contain one plant or several combined together or used sequentially. Polyherbal treatments
usually combine a number of plants with complementary bioreactivities. Generally, claims of
efficacy are primarily anecdotal and studies to affirm their clinical value are only beginning (Lewis
and Elvin-Lewis, 1994; Elvin-Lewis and Lewis, 1996; Lewis et al 1999; Elvin-Lewis et al 2002).
A compilation of secondary data from studies on South American medicinal plants is
currently underway utilizing both published and herbarium sources. This several volume work,
designed for reference, includes information from NAPRALERT and other sources and will
provide additional studies related to phytochemistry and any relevant preclinical and clinical data
that has been published (Lewis et al, in manuscript).
NEOWESTERN HERBALISM.
NeoWestern herbalism, as exemplified in the United States and Canada, is a composite
mixture of a wide variety of plants selected from disparate sources. This system arose during the
“age of Aquarius” and was a part of the “return to nature” ethic, known a quarter of a century ago.
It has become mainstream and is constantly evolving. Some formulations are traditionally derived
with known parameters of use, whereas other plants are incorporated without understanding their
efficacies or parameters of safety. Ethnomedical claims may be substantiated or otherwise, but
this linkage is nonetheless a useful ploy for commercial promotion. In the latter instance, these
types of fabrications are not always easy to detect primarily because there is a presumption that
such claims could not be otherwise than authentic.
The quality and quantity of claimed ingredients cannot always be substantiated any more
than can claims of worth. Each day, newly conjured herbal products are promoted. Most of these
formulations are readily available to the general public and in the U.S., categorized as
nutriceuticals, are categorized as food supplements under the guise of the Dietary Supplement
Health and Education Act (DSHEA). Packaging claims, without specifically implying medical
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uses, are often vague and suggestive of worth. This ploy is necessary to comply with the Federal
Trade Commission (FTC) regulations on how advertising claims for nutritional supplements can
be stated. Since herbal medications are not classified as medications they are not under the
Federal Drug Administration (FDA) scrutiny. However, the FDA is mandated to intercede when
adverse reactions threaten human health e.g., recent removal by the FTC (March, July 2003) of
Ephedra-containing products in slimming and cold remedies is one current example. Overall the
evolution of practical regulatory policies to ensure the availability of only safe and useful products
has yet to be conceived.
At this time, the US herb trade is self-regulating. Their recent review of the disparity in
bioreactive components contained in available ginseng products is but one example of how such
studies are conducted (Hall et al 2001). The impact of this study on improving the quality of
commercially available formulations is unknown.
The Federal Trade Commission Canadian regulatory policies are handled through the
Office of Natural Health. Many popular remedies are undergoing appropriate clinical evaluations
through the National Center for Complementary and Alternative Medicine (NCCAM), NIH and
Office of Natural Health (Canada). In Canada, the recent legalization of the use of marihuana,
and its compounds for medical (not recreational) purposes is a noteworthy example of how
changes in perception of the value of a plant, can take place. In the United Kingdom, clinical
Phase 3 evaluations to establish the medicinal value of a number of its cannabinoids are on
going.
Attempts are being made to encourage the adoption of regulatory systems similar to
those seen in Germany. Within this context Naturopathic and Homeopathic physicians only
utilize well-defined formulations. Most other herbal practitioners, unlike Europe, are often selftaught, with only a fragmentary understanding of what they are promoting. The majority of
formulations are acquired over-the-counter and are taken by those believing that the indistinct
package inserts have value.
However, American Eclectic remedies evolved in the 18th and early 19th century, perhaps
derived from North American indigenous medicines, have contributed to the popularity and worth
of some North American plants. Alcoholic tinctures of Saw Palmetto (Serenoa repens) berries
for the treatment of various prostatic conditions was cited in the United States Pharmacopeia as
early as 1906. It was considered a “remedy for prostatic irritation and relaxation of tissue (rather)
than for a hypertrophied prostate”. Phytotherapists in Europe also valued its use for prostatic
hyperplasia and by the 1990’s a proprietary lipophilic (fat soluble portion) called Permixon was
developed. Numerous controlled clinical studies have confirmed saw palmetto’s value and safety
in the treatment of benign prostatic hyperplasia (Lewis and Elvin-Lewis, 2003). Echinacea (E.
angustifolia, E. pallida, E. purpurea) is by far the most popularly used herb in current Western
phytotherapy of both North America and Europe. Known to Eclectic physicians in the late 1800s,
and to European phytotherapists since the early 1900s, its clinical value as an immune stimulant
in the treatment of colds has yet to be firmly established. While anecdotally acclaimed, the
variable etiology of colds, and self-treatment trials employed make definitive conclusions
regarding it value difficult to achieve (Lewis and Elvin-Lewis, 2003).
HOW IS THE ORIGIN OF A REMEDY DERIVED?
A number of factors should be considered when trying to derive the origin of a remedy.
When comparative data are available it is possible to determine if it is ethnically specific or
derived, and if similar formulations are widespread or limited. A wide variety of botanical sources
can be utilized to ascertain the origins of the plants it might contain, and provide information
regarding their distributions regionally and/or globally. These data are useful when the nature of a
polyherbal suggests a mixed origin. Sometimes clues may be obtained from the criteria of
diagnosis, treatment and cure used by the herbal practitioner or user.
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IS THE REMEDY ETHNICALLY SPECIFIC?
Chewing sponge use for dental hygiene and to treat gingivitis is known both to specific
tribes in Ghana and among those of African origin in the Caribbean (Elvin-Lewis, 1980). The
choices of plants are an example of how an ethnically derived custom of West Africa was
established in the Caribbean when suitable substitutes, with similar properties, where identified.
In this regard, both Old world (Acacia pennata, Hibiscus spp, Lasianthera africana) and new
world taxa (Gouania lupiloides and G. polygama) possess foamy saponins and styptic and
astringent tannins. Their components can elicit antimicrobial and healing activities (Elvin-Lewis,
1980; Kennelly et al 1992).
Similarly, historical records suggest that the favored chewing-sticks of African slaves in
North Carolina during the Colonial period were twigs of the dogwood (Cornus florida) (Barton
1817).
Other taxa were preferred by nearby colonists and indigenous populations and so until
recently, their criteria for selecting this species remained a mystery. I was able to elicit the
information from a Ghanian ethnobotanist who affirmed that its flavor and texture was much like
the popular Garcinia species still used in West Africa.
DO THEY BRING FAVORED PLANTS WITH THEM?
Sometimes plants are brought along with the émigrés, as was the use of the lime tree
(Citrus aurantiifolia), for teeth cleaning and for other medicinal purposes e.g. gonorrhea.
Originally brought by Arabic traders from South East Asia, the tree was introduced into Europe in
the 13th century and was introduced into the Neotropics during the colonial period. In the West
Indies, like in Africa and South Asia, its value by African slaves and “Indians” (possibly of East
Indian origin) for teeth cleaning was known.
IS THE USE OF THE REMEDY WIDESPREAD?
Maclura tinctoria enjoys pantropic (from Madagascar, the Caribbean Basin to Amazonia)
use for tooth extraction, and in many countries of West Central South America (Kaufmann and
Elvin-Lewis, 1995), Croton lechleri is popular for wound healing. Widespread or global use of
certain taxa often makes it difficult to determine how similar uses evolved. For example,
worldwide Phyllanthus spp. can be found in hepatitis remedies, as can Catharanthus roseus in
treatments for diabetes (Lewis and Elvin-Lewis, 2003).
WHAT IS THE ORIGIN OF THE PLANT?
It is logical for widespread use to occur when plants are globally available. For example
the ubiquity of Phyllanthus spp, and the horticultural uses of Catharanthus roseus provide the
appropriate rationale for their extensive medicinal uses. Current plant introductions to the
Caribbean like the Indian neem tree (Azadirachta indica) known to have come from West Africa to
Haiti are a recent example. There, as in West Africa the plant is recognized for use to treat
malaria (Lewis and Elvin-Lewis 1982). However, Gouania species, used for teeth cleaning, are
regionally circumscribed to the Caribbean basin, including Central America (Elvin-Lewis, 1980;
Morton, 1981).
IS THE REMEDY USED ALONE, OR AS A MIXTURE?
Certain remedies, can be used alone, e.g., the sap of the Amazonian tree, Croton lechleri
for wound healing. Others, such as Phyllanthus spp must be used as a fresh herb and combined
with either Eclipta alba or Silybum marianum to affect an optimal healing response for hepatitis in
India and Europe, respectively (Elvin-Lewis, in manuscript). As exemplified in other hepatitis
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remedies certain Amazonian mestizo treatment regimens combine local taxa with post Colombian
introductions such as turmeric (Curcuma longa) (Elvin-Lewis, 2002). This later species also
appears in hepatitis remedies of Egypt and India.
DO TREATMENT CRITERIA GIVE A CLUE?
Diagnostic criteria for treatment may be linked to a specific, well-defined disease, such as
malaria, a vague malady, such as the “frightened disease” of Latin America, or those that are
psychiatric/cosmically based e.g., spiritual visitations. Cultural differences may also dictate how
diagnosis and treatment is followed. Asian medicinal systems are noteworthy examples of how
certain diagnostic criteria, e.g., pulse diagnosis, differs from conventional allopathic medicine.
WHAT TYPES OF NEW THERAPEUTICS ARE WARRANTED?
In determining how to identify studies related to the development of new therapeutic
agents, local, regional or global needs clearly have the highest priority. Often anecdotal
information is valuable, as is knowledge of the potential, or known worth, of some regional taxa.
Studies are also more likely to be successful in areas were regional pharmacopoeias are
still used, when data from practitioners and patients are readily available, when surveys of value
can encompass a representative part of the population, when a need for a definable disease is
identified, and when meaningful assays can be employed to determine bioreactivities and
efficacy.
HOW DO YOU SELECT FROM ALL THESE CHOICES?
In further determining remedies to study, it is obvious that much more information can be
obtained about parameters of value if they are still being used. In this way estimates from
practitioners and/or patient populations can provide clues regarding parameters of efficacy and
safety. If the disease is known to conventional medicine appropriate clinical evaluations and
diagnostic laboratory tests can also be utilized to follow therapeutic effects during treatments, and
comparative data generated to determine which of those remedies available, is the best
candidate. This information may be very useful when development of a botanical or
phytopharmaceutical is being considered. Efficacy is further validated when a plant remedy has
widespread acceptance, when the same plant or its allies are used worldwide, and when toxicity
is not a factor.
Added value may also be derived if appropriate dereplication reveals similar
ethnomedical uses, potential mechanisms of action, and types of bioreactive compounds in allied
species, genera or families of plants. Reference to appropriate databases can also make known
the relationship of diseases to each other and thus further identify additional potential afflictions
that might respond similarly.
IDENTIFYING THE NATURE OF THE FORMULATION.
In conducting surveys of plant use, it is important to understand how regional or local
names translate into either a generic or specific entity (Elvin-Lewis 1982). Collecting voucher
specimens to verify the taxonomic identity of taxa are critical.
Reliance on a few informants, who depend on oral tradition for information, may not
provide an accurate understanding of the nuances of collection, preparation, or use of plant parts
and other non-plant components that are included. Since family members have been observed to
vary in ways they may prepare or take a remedy, the evolution of a standard formulation can only
be made once a widespread assessment of formulator diversity is made within a community or
region (Elvin-Lewis et al 2002).
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Defining the value of a polyherbal need not be insurmountable. It simply takes more time
to record information regarding each component, as well as conducting suitable dereplication first
before doing a comprehensive bioreactive or chemical study on each component. In many cases
only one or two components may warrant further study. Determining core ingredients is essential
to rationale evaluations since some polyherbals may vary in composition, or the types of plants
represented. One of the best early examples of such deductive reasoning was the 18 th century
discovery by William Withering (1785) of the bioreactive ingredient, Digitalis purpurea leaves,
from English polyherbals used to treat dropsy. This lead to the isolation of digitalis glycosides and
digoxin used manage heart failure in patients with atrial fibrillation (Lewis and Elvin-Lewis, 2003).
UNDERSTANDING OF THE BIOREACTIVITIES OF A FORMULATION.
Polyherbal therapies use components together as a mixture or sequentially. This
difference dictates how bioreactivity screening can be logically conducted. Functional screens,
particularly in distinctively evolved in vivo models can have value in determining the efficacy of
these formulations, particularly if their content is well circumscribed.
Depending upon the expense and accuracy of functional screens, mechanistic screens
may be employed if these are expressly related to a critical aspect of the disease, and have been
identified as a worthy pharmaceutical target. Mechanistic screening, while well suited to high
throughput methods has its limitations particularly when one plant may contain several
components with complementary activities. Bioreactivity dereplication, often reported in the
medical rather than the chemical literature is fundamental to these types of analyses. Needed
also are data elicited through taxonomic dereplication, a technique valuable in amplifying the
potential use of a formulation. Isolation of active components may not reveal a pharmaceutical
candidate meeting the stringent requirements of high potency, unique structure and low toxicity.
However, the revelation of bioreactive compounds useful in one context or the other can provide
the basis for understanding the remedy, and possibly ways in which it can be evolved for more
general use.
ASSAYS TO DETECT BIOREACTIVITY.
Functional screens were once the only type of screening tool available. In the context of
ethnomedical studies, the human being is the first, not the last animal to establish parameters of
use. Applying these observations to studying effects in suitable animal models is particularly
valuable if the function of the remedy is considered to be identical or similar. Within this context it
is important to appreciate that the pharmacokinetic processes of humans and certain test animals
such as rodents can differ. Suitable animal models may continue to be applied, particularly when
other methods are not available. However it is noteworthy that the loss of the ready availability of
primate species, such as the Rhesus monkey, commonly used for these endeavors, suggests
that other approaches may have to be considered in the future. Functional screens may
precisely follow the human ailment e.g., infectious disease, or induce a condition that mimics the
affliction e.g., chemical injury to the liver or pancreas needed to understand hepatoprotective or
hypoglycemic agents, respectively.
More and more, functional screens using animal cells, including “gene chip analyses” are
replacing them since they are more suited for high throughput methods. This is also true for
toxicology testing. Overall functional screens can still provide valuable data, albeit somewhat
limited in nature due to the complexity of the physiology of the animal, isolated cells, or
microorganisms involved.
Mechanistic screens are by far the most popular method for evaluating large chemical
and extract libraries. Such random screening has wide acceptance within the pharmaceutical
industry, but have yielded only a few viable candidates. While bioreactivity may be identified,
without knowledge of pharmacokinetic activities, the majority does not even reach early stages of
early development as a drug. Toxicity of even pharmaceuticals developed through this method,
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has always continued to be a problematical feature. Overall the industry has not considered
accompanying ethnomedical data when surveying these types of specimens. Therefore the
potential of the plant is rarely met by using this type of method.
THE TYPE OF SPECIMEN CLEARLY DICTATES THE BIOREACTIVITY THAT CAN BE
FOUND.
When plant-extract libraries are composed of plant collections made on a random basis,
and often representing a particular flora, the “hit rate” is usually very low (<5%). When medicinal
plants are evaluated, without matching them to the specific assay, hit rates are proportionally
higher (15-25%), primarily because medicinal plants are likely to possess bioreactive
components. When secondary data, without confirmed value is used, these targeted specimens
may elicit a significantly higher ratio (40-50%), and when primary data is used, and assays
closely matched more than 75% can show some form of bioreactivity. However when clinical
data statistically confirms the value of a remedy, as seen with “focused” data 90%, or more of the
plants tested are likely to be significantly bioreactive. These types of data have been elicited in
the laboratory of Dr. Walter Lewis and myself, and those of our collaborators studying Hepatitis B
virus (including its cross reactivity to HIV) and malaria; other investigators have evoked additional
evidence of a similar nature.
USING DATA TO IDENTIFY THERAPEUTIC LEADS.
PRIMARY DATA:
Obtaining primary data elicited from healers and populations still applying a specific
pharmacopeia is by far the best source of identifying new sources of therapeutics. This is
particularly useful when “targeted” to a specific disease that is clearly recognized by conventional
and traditional diagnostic methods, where appropriate bioassays can elicit the therapeutic
rationale for use, and where field studies are applicable to establish its value. From our
experience we have found that optimal results are likely to be achieved when this type of primary
data is appropriately elicited since one is more able to associate value that translates into
associated bioreactivities and proven efficacies. Linking these “targeted” medicinal uses to
appropriate functional and mechanistic assays (Lewis et al, 1999) frequently provides high “hit
rates”. Also, by applying ethnomedical-focusing techniques (Elvin-Lewis et al, 2002), preferred
choices, which are identified, can translate into recognizable clinical benefits. Like elsewhere, the
reliability of secondary data is variable.
Eliciting such data requires complex negotiations with local and national agencies that
oversee access to their natural resources and the populations of people that use them. Regional
medicinal plant use inventories may be necessary to establish the parameters of ownership both
in a temporal and regional sense so that benefit sharing can be appropriately allocated. In order
to protect this knowledge, care must be taken to obtain prior informed consent. Importantly,
academic investigators and their students must understand that this “know how” has value of its
own and thus should not be squandered at the expense of those providing the information. This
impacts upon the ability of investigators to prematurely publish or present data (including their
inclusion in grant proposals), until such times all intellectual property issues have been
appropriately accommodated. Before utility is proven and protected, complying with fiduciary
obligations to withhold this information during the early assessment phase is essential. This
aspect is challenging since it can impair the ability of investigators to generate funds from many
agencies that require full disclosure of names of plants and/or their compounds.
In this context, and particularly when assessment of the availability of particular taxa
suggests it is rare or uncommon, the investigators are further obligated to protect its precise
whereabouts, by not citing this information, including geopositioning data, on herbarium sheets or
publications, until resource management issues have been addressed. Compliance to national,
regional and international laws is mandated not only to accommodate these issues but also to
10
ensure that protection of the host countries’ genetic resources be appropriately managed. Usually
national oversight agencies will insist their policies regarding these issues be closely followed.
Should a fundamental discovery be made that advances human health, the effort is nonetheless
worthwhile.
SECONDARY DATA:
Secondary data identifies possible leads from information in the public domain and may
be derived from a variety of sources including herbals, floras, pharmacopoeias, herbarium sheets,
theses, dissertations, books, published pamphlets, poster presentations, verbal presentations etc.
Their use does not impose the same proprietary obligations to persons or populations, however
national laws will apply to plant collection and export.
PRELIMINARY BIOREACTIVITY:
Preliminary bioreactivity screening is used to identify functional or mechanistic activities.
Dereplication identifies uses, taxa, chemical, and bioreactivity links. Empirical selection of
medicinal plants in traditional medicine has a variety of origins. Most are related to the
identification of worth in treatment over eons of trial and error, this is called the empirical
approach. It often follows that those most valued will have proven worth. This is especially
evident when the technique of “Ethnomedical Focusing” is applied to identify the most valuable
bioreactive candidates used for a specific purpose in a pharmacopeia. This requires that clinical
verification as to efficacy and safety be conducted at the population level and that sufficient data
is acquired so that statistical relevance is achieved. These data also may provide the underlying
reasons for why rationale choices are being made, and can translate into perceived values of
efficacy, user friendliness, safety, and availability (Elvin-Lewis et al 1980b, Elvin-Lewis et al
2002).
DOCTRINE OF SIGNATURES:
What continues to be inexplicable are the many therapeutic discoveries associated with
plants chosen according to the ancient doctrine of the “Doctrine of Signatures”. This criterion
denotes that the plant part’s appearance (shape or color) mimics the appearance or a symptom
of a disease, and in the cosmic sense, is considered to provide a clue to its value in therapy.
Pharmacopeias are replete with worthy examples. For logic to prevail, since so many efficacious
plants are known, the final winnowing process obviously applied other empirical criteria as well.
Of note, is the global selection of many yellow fruit, seeds, rhizomes, flowers or whole
plant infusions found in many efficacious hepatitis remedies (Elvin-Lewis, in manuscript).
Another example was the Penobscot Amerindian use of the mayapple (Podophyllum spp) to treat
venereal warts (Condyloma acuminata). The serrated and multi-lobed leaf shape of this plant is
remniscent of this condition. This remedy was adopted by 19th century midwestern physicans
and the resin is still valued. It contains podophyllotoxins that have been rendered less toxic
through semi-synthesis to form teniposide and etoposide that are topisomerase inhibitors useful
in the treatment of lymphomas, leukemias, and brain and bladder cancer (Lewis and Elvin-Lewis,
2003).
PHYLOGENETIC AMPLIFICATION:
An understanding of phylogenetic relationships among plants, microorganisms, or
etiologic agents of disease can amplify drug discovery in a number of ways. It is appreciated that
related plant or microbial taxa are likely to share similar biosynthetic pathways that affect the
commonality of their ability to elicit certain types of associated bioreactive metabolites which can
result in the production of a wide range of similar or associated compounds. Similarly, related
etiologic agents, by virtue of physiological similarities are likely to exhibit cross sensitivity to
certain inhibiting agents.
11
Allied compounds can differ in potency, toxicity, and in the range of their bioreactivity and
thus options exist to select the appropriate renewable resource for any desired compound or
compounds. Depending upon their type, examples may be found intraspecifically,
intragenerically, and at the family level. Also with flowering plants, certain related orders are
known to share similar bioreactivities, suggesting a commonality of certain compounds. These
are often found in the same phylogenetic group (10 in all) made up of subclasses and/or
monophyletic clades. However, this is not always the case, and if the compound is ubiquitous,
similar pathways may also be detected in totally disparate taxa. In addition, endophytic and
epiphytic fungi may produce the same compounds as the plants they are associated with, thus
providing additional sources for exploitation (Lewis and Elvin-Lewis, 2003).
Endophytic And Epiphytic Fungi.
The recent discovery that temperate and tropical genera in the same fungal family are
used for the same purposes in disparate parts of the world is noteworthy. Ergot as a parturition
aid was derived from European herbal practices of using rye (Secale cereale ) grains, infected
with the fungus, Claviceps purpurea (Lewis and Elvin-Lewis, 2003) and is widely used in
conventional medicine today. In examining the use of parturition plants of the Achual Jivaro and
neighboring populations in Amazonia, we found that the choice of a sclerotia infected sedge, piri
piri (Cyperus prolixus) was widespread. The sclerotia were found to contain the tropical fungus
Balansia cyperi which like Claviceps is a member of the Clavicepitaceae, and also produces ergot
alkaloids (Lewis and Elvin-Lewis, 1990).
Also, studies have indicated that paclitaxel, used as an antiestrogen in the treatment of
breast cancer, and its derivatives are not as generically restricted to Taxus spp., as was first
presumed. In this respect, Corylus (hazelnuts) species also produce paclitaxel, albeit in much
lower quantities, and its derivatives can also be found in Ilex marcrophylla (holly). Other
producers include fungi such as endophytes of Taxus (e.g, Taxomyces, Pestalotioposis,
Sporomia, Trichthecium), those of Corylus (hazelnut) speciosus (Rubiaceae), the ubiquitous
fungus, Aspergillus niger and the epiphyte, Seimatoantlerium tepuiense, which resides on the
tropical Guyanian Rubiaceae, Maguireothamnus speciousus. These discoveries have led to the
production of paclitaxel as a fermentative biproduct (Lewis and Elvin-Lewis 2003).
Antiinfective agents.
In seeking to discover the potential value of antiinfective agents, utilizing knowledge of
phylogenetic relationships of infectious taxa, and their potential of cross-sensitivity, is useful in
amplifying the worth of particular bioreactive compounds. This is particularly relevant when
infections with related organisms may manifest themselves differently and when there is a need
to identify antiinfectives for emerging or understudied diseases.
Care also must be taken to understand the relevance of all ethnobotanical data
accompanying a medicinal plant specimen, since clues to cross reactivity may be missed. For
example, one would never guess that a malaria remedy also used to treat diarrhea made much
sense unless it was recognized that the potential of inhibiting Plasmodia as well as related
intestinal coccidia (Cryptosporidium, Cyclospora, Isopora) was possible. Our current work on
targeted anti-malarial medicinal plants is proving there is relevance to testing for cross-sensitivity
to these parasites, and Toxoplasma gondii. Since Pnemocystis jerovici (now reclassified as a
fungus) is also sensitive to compounds used to treat these protozoa, it is interesting that crosssensitivity has also been found to this organism.
Since traditional remedies are clearly lacking for emerging infections, such as AIDS, it is
important to understand how cross sensitivity can be used to identify herbal remedies that might
be applied. In this regard, the evaluation of hepatitis remedies used to treat Hepatitis B virus
12
(HBV) infections has been particularly fruitful. This is because there is an ancestral relationship
between these two viruses, in that they both use reverse transcriptases in their replication cycle.
Additional inhibitors such as the protease inhibitor prostratin have also been isolated from
Homolanthus nutalii a Samoan remedy for hepatitis. This was an important discovery for other
reasons, since it had been presumed for 20 years that this ubiquitous phorbol ester, readily
synthesized, was carcinogenic like others in this class. It not only strongly inhibits the killing of
host cells by HIV, but also up regulates viral expression from latent proviruses. Used in
combinational therapies it would have the ability of aiding in the elimination of persistent
infections. It has been proposed that any benefits derived from its commercialization will be
shared with the Samoans (Lewis and Elvin-Lewis 2003).
Applying the concept of cross-sensitivity further our studies and others are showing that
medicinal plants derived from tropical sources, such as Peru and tropical Asia, are yielding a
disproportionate number of leads inhibiting Mycobacterium tuberculosis, with some having the
capacity to inhibit cell wall synthesis, an appropriate target for pharmaceutical development. The
rationale for this discovery is based upon the assumption that tropical medicinal plants are likely
to contain a wide range of secondary metabolites needed to protect the plant from soil pathogens,
including those in the related Streptomyces (Lewis et al 2000, Ma et al 2001).
CHEMICAL DEREPLICATION:
Once a phytochemical has been isolated through broad screening or biodirected isolation
methods, retrospective chemical dereplication, including patent searches, may reveal that this
compound, or others similar to it have already been studied, and that its range of bioreactivity,
use, toxicity and/or parameters of medical worth have been previously substantiated. In certain
instances this compound may have been identified in the same, or in related or unrelated plants.
New sources of the phytochemical or others related to of equal or greater worth may be found.
ETHNOMEDICAL DEREPLICATION:
Ethnomedical uses may provide a way to understand the full medical potential of the
plant and perhaps the compound in question. Retrospective dereplication and phylogenetic
amplification have proven that arbitrary discoveries, such as paclitaxel (taxol), may not be what
they appear to be. Initially taxol’s discovery, about 30 years ago, from Taxus brevifolia, the
Western Yew, was heralded as a stellar example of the success of the random screening efforts
at NCI. More important to scientists of that era was taxol’s unique structure and antimitotic
activity that was found to stabilize microtubules and prevent depolymerization. Then these
investigators chose to ignore as meaningful the ethnomedical link of the Indian and Himalayan
cancer remedy, T. baccata, cited in the Bower manuscript, written between 1893-1912 and cited
in an NCI publication in 1967 (Hartwell 1967). They were also unaware that the Western
Tsimshian Amerindians used T. brevifolia for treating cancer, since this information did not
become available until the 1990’s (Moerman, 1999).
However as clinical development proceeded and taxol’s clinical worthiness as an antiestrogen treatment for breast cancer was proven it became evident that the slow growing and
uncommon, T. brevifolia would be extirpated. New sources were needed and phylogenetic
amplification techniques were employed. The Asian T. baccata (European Yew), a common
horticultural variety, was substituted and currently other species are also used, including T.
wallachiana (Himalyan yew) and the cultivated variety Taxus X media “Hicsksii”. Semisynthesis
of precursor molecules of these taxa further enhanced availability. These triterpenoid precursor
baccatins provide both taxol (paclitaxel) and docetaxel (Lewis and Elvin-Lewis, 2003).
TARGETED RESEARCH.
13
Information related to the traditional uses of medicinal plants can translate into the
discovery of valuable pharmaceuticals used for similar purposes. Since so many medicinal plants
contain compounds of moderate bioreactivity and toxicity, discovering a pharmaceutical
candidate is a rare event. Stellar examples do exist where unique and potent compounds have
been discovered and commercialized (Lewis and Elvin-Lewis, 2003). As need for the compounds
have increased, resource management issues related to wild crafting have been overcome
through the development of plantations, the identification of lead compounds from other plant
sources, as well as the total synthesis of these compounds and the evolution of more potent
derivatives.
Malaria.
Of particular relevance is the story of an antimalarial derived from a South American
indigenous pharmacopeia. In 1630, local natives living in the cordillera of Peru provided the bark
of Cinchona officinalis and other related species to Spanish missionaries. This malaria remedy
was introduced into Europe and was so successful it rapidly replaced others used globally. To
satisfy the need of raw material, plantations were developed throughout tropical areas.
Eventually isolation of its primary bioreactive alkaloids quinine and quinidine led to the
development of several pharmaceuticals. These and related synthetic quinoline compounds, still
remain the mainstay of malaria therapy.
Until an increasing resistance to these molecules arose in the late 20 th century, little effort
was made to look for alternatives. To overcome this serious problem, investigations, for
appropriate substitutes were initiated. Ongoing studies are being conducted in Central
(Guatemala, Puerto Rico), South America (Argentina, Brazil, Bolivia, Peru), in Africa (South
Africa, Mali, Sierra Leone, Mozambique) and SE Asia (Malaysia and Thailand). Again, targeted
medicinal plants are proving to be useful sources of new antimalarials. For example, the
traditional Chinese herb, Artemisia annua has yielded the terpene, artemisinin, and its
derivatives, artesunate and aremether, which are active against multi-drug resistant strains of
Plasmodium falciparum (Lewis and Elvin-Lewis, 2003).
Helicobacter, Gastritis, Stomach Ulcers And Cancer
Worldwide Helicobacter pylori is considered the primary cause of gastritis, stomach and
duodenal ulcers and related cancers. Current studies are identifying plants used in
ethnomedicine to treat these afflictions. Various mechanisms related to their healing capacities
are being used to assay their usefulness and include their capacity to be antiinfective,
antiinflammatory, healing, gastro-protective, antiulcerogenic, analgesic and antisecretory.
Within the context of regional studies, antiinfective activity has been associated with a
number of Brazilian and Yucatec Mayan taxa. The compounds cabreuvin and N benzolmescaline
have been isolated (Ohsaki et al 1999). Also, other anti-ulcer activities have been identified from
Brazilian and Caribbean plants; among these are the phenolics associated with the mangrove
(Rhizophora mangle) (Fig 21) (Sanchez et al 1998, Armenteros and Caridad 1998, Melchor et al
2001).
ANTICANCER DISCOVERIES CAN VARY.
Serindipitous Observations.
Sometimes a serendipitous observation related to ancillary bioreactivities of a medicinal
plant can lead to a fundamental, but different use. Such were the events leading to the discovery
of powerful anti-cancer agents. In the 1960s Nobel and Beer were studying the antidiabetic
effects of Catharanathus roseus; a plant used for this purpose in the West Indies and elsewhere.
As a part of their pharmacokinetic studies, they discovered that treated mice also developed
14
reduced white cell counts (leukopenia). Using this as a clue, they initiated studies on leukemic
mice. According to Nobel “6 leaves could cure a mouse of leukemia. This observation lead to
the isolation of vincaleukoblastine sulfate used in the treatment of Hodgkin’s disease,
choriocarcinoma and other neoplasms (Lewis and Elvin-Lewis, 2003).
Choice Of The Appropriate Assay.
Simultaneously, the same plant was also been evaluated for anticancer activity in NCI’s
broad screening program, but activity was not demonstrated on the cancer cell lines used.
However, by utilizing a different group of cell lines, Svoboda and his co-workers at Eli Lily were
able to identify bioreactivity which resulted in the isolation of leurocristin sulfate valued for treating
acute leukemia in children. These results were reported simultaneously with those of Nobel and
Beer (Lewis and Elvin-Lewis, 2003).
Drug Delivery
Occasionally new technology also provides the answer for drug delivery and overcomes
inherent toxicity problems associated with the molecule. Maytenus senagelensis is an East
African remedy for cancer that contains the anti-cancer compound maytansine. This compound
had an interesting bioreactive spectra associated with antileukemic, cytotoxic, antitubuline and
antimitotic properties. Early studies in the 60’s showed that it had potential for use, but clinical
trials were abandoned when toxicity became problematical. Recently new technology has shown
that linking the molecule to an idiotype antibody that specifically targets the tumor cell,
circumvents the toxic reactions seen with the original systemic treatment regimen (Lewis and
Elvin-Lewis, 2003). The fact that this genus (ca 200 species) is widespread in the tropics,
including the neotropics, suggests that there is the potential for the discovery of many new
maytensoids from the rich diversity of this genus.
In a similar way, the selective delivery of prodrugs containing cyanogenic glycosides
(e.g., laetrile) to cancer cells, so that only malignant cells are killed, is being explored (Syrigos et
al, 1998).
GUARANTEEING SUSTAINABILITY
In order to ensure ready availability, in Amazonian communities, some well-known
medicinal taxa are grown in nearby gardens. Each of these plants are usually propagated for a
single specified purpose, and it is not uncommon to see identical species in the same plot, but
each designated for a specific purpose, e.g., to treat diarrhea, or to stop internal bleeding. These
cultivars are not used interchangeably, and are believed to “lose” their healing capacity if the plot
is abandoned (this practice is not altogether illogical considering that variances in the chemotypic
profile of certain medicinal plants such as Ilex guayasa (Lewis et al, 1991) and Croton lechleri
(Milanowski et al, 2002) are known). Other medicinal plants may have to be collected in the wild.
Sometimes this practice may lead to depletion of valued taxa, particularly when plants such as
specific trees are needed for a widespread malady and are not readily cultivatable. Except for a
few garden-grown herbs, resource management strategies to replenish popularly used forest
plants are not undertaken. If possible, the preference is to identify a suitable substitute that is
readily available (Elvin-Lewis et al, 2002). Similar practices have also been observed among
Mesoamerican curandaros.
Therefore, whenever valuable taxa are identified, then ecological evaluations should be
undertaken to determine how additional uses, as botanicals, phytopharmaceuticals or as the
source of a pharmaceutical compound, might impact on its availability. This is essential should
the plant prove to be rare or endangered. The need to determine ways in which these plants can
be cultivated will be necessary. When plantation propagation is not logical then appropriate
strategies must be employed to ensure its reproduction. For example, if it is a canopy plant, such
as ginseng, then growing under lattice or in woods-grown conditions may be necessary.
Considerations regarding drainage, soil conditions, natural pests, and climate etc all need to be
15
considered. In certain instances, organ culture may be the only viable option. These, and other
alternatives should be explored during the period when commercialization is being considered.
In a long-term perspective, practical synthesis of active components may occur, thus
diminishing the need for the plant itself. This event happened in Amazonia in the 1980’s, when
the synthetic derivatives, atracurium and vecuronium replaced the need for natural
menispermaceious curares (Lewis and Elvin-Lewis, 2003). In the wake of these discoveries, an
active cottage industry surrounding the wild crafting of Chondrodendron tomentosum, was
unfortunately left in disarray.
However, there may be certain instances where chemical synthesis is not possible and
creating boutique medicinal plants may be necessary. In these cases, the need to look for
suitable naturally occurring chemotypes that yield the compound in optimal amounts may be
required. Within this context, should polyploid races be known, amplified gene expression may
be the result of the duplication of certain genes. Should gene splicing be applied, the amount of
bioreactive compound/s may be amplified in the original host species, or needed genes
transferred to a plant more suited for cultivation.
Also, semi-synthesis of the original compound or another related to it may be applied
once the metabolic pathways are elucidated and alternative and practical sources of base
material determined. Refining the original molecule through semi-synthetic strategies can lower
toxicity, remove mutagenicity, improve solubility, increase potency, increase the bioreactive
spectra, improve user friendliness and allow for evolution of a mechanistic profile.
In the future, to ensure quality products, many types of technologies will be utilized to
naturally enhance the worth of a wide variety of medicinal plant crops. The success of these
endeavors may also provide a positive alternative to the subsistence farmer that now relies on
growing noxious crops, such as tobacco, for additional revenue. This is because a small-sized
farm is particularly suited to the additional effort that will be required to grow these crops
organically, in order to prevent contamination with noxious herbicides and insecticides in as much
as hand weeding and use of companion plants may be necessary to provide optimal yields under
these constraints. This endeavor will likely translate into a profitable margin for the farmer and,
provide more reliable and safer products when marketed.
CONCLUSION
Overall, there are numerous ways in which new therapeutic discoveries from
ethnomedical and ethnobotanical data can be achieved and verified. There is an increasing
awareness that these resources, if appropriately understood and managed can provide new
therapeutic remedies in the form of botanicals, phytopharmaceuticals or pharmaceuticals. From
our experience we have found that optimal results are likely to be achieved when primary data is
appropriately elicited since one is more able to associate value that translates into associated
bioreactivities and proven efficacies. Linking these “targeted” medicinal uses to appropriate
functional and mechanistic assays (Lewis et al, 1999) frequently provides high “hit rates”. Also,
by applying ethnomedical-focusing techniques (Elvin-Lewis et al, 2002), preferred choices, which
are identified, can translate into recognizable clinical benefits. Like elsewhere, the reliability of
secondary data is variable. Within this context, it is essential that issues related to appropriate
benefit sharing and resource management issues be appropriately and legally addressed.
ACKNOWLEDGEMENT
As long time professional collaborators, it is with appreciation that I acknowledge
the significant contributions of Dr. Walter Lewis, Professor Emeritus of Biology,
Washington University, and Senior Botanist at the Missouri Botanical Garden, St. Louis,
MO to the research and concepts cited in this paper.
16
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