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Why traditional knowledge is important in
drug discovery
We only speak of traditional knowledge at all because there is knowledge in the world that we assume to be radically
different from our knowledge. This article argues that the relationship between drug discovery and traditional knowledge
isreal, yet more complex than most industry insiders and critics suppose.
Recent decades have seen some intense debates
concerning the alleged wholesale misappropria
tion of traditional knowledge by the pharma
ceutical industry. Many within the industry
counter that scientific and technological advances
make traditional knowledge irrelevant in drug
discovery, and bioprospecting a waste of time and
money: it may have been important in the past,
but that does not make it important today or
tomorrow. This article shows, through a number
of historical and present-day examples, that tradi
tional knowledge is a potentially valuable source
of leads for drug discovery and that overlooking
it is not in the interests of industry or the public.
To some people, the pharmaceutical indus
try almost literally preys on indigenous peoples,
patenting their knowledge and making billions
of dollars without sharing a cent with them.
Many people in the industry, while not denying
the past importance of traditional knowledge,
profess to have no interest whatsoever in it as a
source of leads for new pharmaceutical applica
tions and entities, and consider it to be worthless
for their line of business.
To some people, the pharmaceutical industry
almost literally preys on indigenous peoples,
patenting their knowledge and making billions
of dollars without sharing a cent with them.
Both views, that traditional knowledge sub
stantially subsidizes the pharmaceutical industry,
and that traditional knowledge has no relevance
for present and future drug discovery, are incor
rect. The traditional knowledge champions tend
to rely too much on their analysis of a small
number of high profile cases. As for the detractors
to whom this article gives most attention given
the journals readership it is suggested that the
error arises from adhering to a conveniently sim
ple but inaccurate assumption that pharmaceuti
cal research and development invariably follows
10.4155/FMC.10.210 2010 Future Science Ltd
a purely linear, unidirectional pathway starting
with a single discovery, followed 1015 years
later, if at all, by a product. In the paradoxical real
world, progress in pharmaceutical research goes
backwards as well as forwards and along wind
ing complicated pathways often with no obvious
beginning or end. Alternatively, one might sug
gest the complexity of research progress has more
in common with trees having many spreading
branches than with thoroughfares. This is tacitly
acknowledged by industry when, perfectly legiti Graham Dutfield
mately, it invests in the discovery of second uses of School of Law, University of Leeds,
known drugs and in incremental improvements, Leeds, LS2 9JT, UK
Tel.: +44 113 343 1606
and by legislators and judges when they allow E-mail: g.m.dutfield@leeds.ac.uk
these to be patentable. Arguably, then, industry
is hardly unaware of the reality, whether or not
the traditional knowledge-related implications are
ever contemplated. The error is also partly a result
of the misleading assumption that rapid scientific
and technological advances are inevitably making
natural-product research unfeasible.
What is traditional knowledge anyway?
We only speak of traditional knowledge at all
because there is knowledge in the world that
we assume to be radically different from our
knowledge. The latter we prefer to label as mod
ern or scientific knowledge. Holding to a tradi
tionalmodern epistemological dualism as if all
knowledge is either all of one or all of the other is
in fact simplistic, misleading and unhelpful. For
convenience, let us just take traditional knowl
edge to mean the knowledge that predominates
in past and present societies living close to the
land whose livelihoods are relatively unaffected
by industrialization and the mechanical and
chemical outputs of modern industry.
There are two conventional wisdoms about
traditional knowledge regarding its value for
the pharmaceutical industry. Put plainly, one
wisdom is that the pharmaceutical industry has
always needed traditional knowledge relating to
bioactive substances such as medicinal prepara
tions and toxins of plant, animal and mineral
Future Med. Chem. (2010) 2(9), 14051409 ISSN 1756-8919 1405
News & Analysis | Opinion
origin, and continues to do so. The other is that
the pharmaceutical industry does not need tradi
tional knowledge. According to the first wisdom,
traditional knowledge is so important that not
to use it would have substantial negative impacts
on the industry as reflected in decreasing rates
of drug discovery and development and lower
profits from sales [1] .
one might suggest the complexity of
research progress has more in common with
trees having many spreading branches than
with thoroughfares.
Given the audience for this article, and in the
interests of being constructively provocative, we
will focus critically on the second wisdom. At its
most extreme, the view here is that traditional
medicines are crude and unsophisticated prepara
tions delivered on the basis of incorrect theories
and practices that mostly do not work or else rely
on a placebo effect. Consequently, observing
traditional use of plant extracts, animal extracts
or minerals is of little use in drug research and
development either in providing helpful clues, raw
materials or intermediates, or as finished articles.
This article argues that the relationship between
drug discovery and traditional knowledge is real,
yet more complex than most industry insiders and
critics suppose. This complexity does not make it
easy for the antibiopiracy critics to score political
points against the industry for making vast profits
from the free use of traditional knowledge (though
it does justify calls for greater respect for traditional
knowledge holders and fair benefit sharing) [2] .
However, it also means industry needs to be more
aware of the major role traditional knowledge has
played in drug discovery and its potential for con
tributing to commercial success. Such awareness is,
I argue, in the best interests of an industry whose
productivity rates in terms of getting new chemical
entities to market has diminished in recent years;
but is also a matter of justice.
The rest of this article attempts to justify this
in-between view on the basis of the empirical
evidence. It seeks to demonstrate, without exag
geration, traditional knowledges continuing
commercial importance as a source of biological
information worth investigating. It also empha
sizes the continued relevance of traditional knowl
edge at a time when the industry is broadening its
range of drug-discovery strategies in the face of a
persisting failure to increase the rate of developing
new molecular entities (NMEs), which includes
taking an intensified interest in naturalproducts.
1406 Future Med. Chem. (2010) 2(9)
Why traditional knowledge
stillmatters
There are three reasons why traditional knowl
edge matters more than people may think. First,
because the learning trails that have led from
traditional knowledge to some highly profitable
drugs and classes of drugs can be so long and
winding that they become hard to retrace with
lengthy sections disappearing from most peoples
sights. Rediscovering these trails may show past
traditional knowledge connections to some of
todays best-selling drugs. Second, because the
pharmaceutical industry, for all its investment
and acquired expertise in new biological tech
nologies and synthetic chemistry, is surprisingly
dependent on the re-engineering (or renewing,
as I call it) of past discoveries, some of which
will definitely have traditional knowledge ori
gins. The third reason is that natural-product
research continues, despite the promise of new
chemical, biotechnological and screening tech
nologies, to be absolutely essential for the indus
try. Where the natural products have plant or
animal origin, traditional knowledge has a good
chance of being relevant. Admittedly the first
reason may seem rather academic, but this is not
the case when we consider that learning trails are
potentiallyendless.
Losing track of the learning trails
The first reason requires us to reject the repeti
tive clich that drug research and development is
a linear one-way process in which one molecule
in 10,000 will enter the market 1015years after
its discovery; the discovery of the successful mol
ecule marking the start of the trail and the end
being the placement of the approved drug on
the market.
In reality, the learning trails from the ini
tial find (or set of initial finds) to a product or
class of pharmaceutical products is usually long
and complex with the likelihood that the trails
will fade away in the course of time. Enormous
lengths of time may elapse between finding or
rediscovering some early clue, such as a reported
use of a plant for a particular purpose by an indig
enous group, and the marketing of a pharma
ceutical product whose therapeutic use may in
fact be quite different. Trails have no obvious
end, since one product leads to another. Trails
may branch off in some very fruitful directions,
possibly before any product has been developed,
and also merge with others. Of course every
accession in a natural-product extract library has
a past and an origin. But there is no particular
reason why a pharmaceutical scientist should
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be aware of the history and geography of any
given extracts usage unless such information is
reported in the recent scientificliterature.
Arguably, the patent system encourages this
neglect of history and geography. As technology
historian George Basalla once put it, a patent
bestows societal recognition on an inventor and
distorts the extent of the debt owed to the past
by encouraging the concealment of the network
of ties that lead from earlier, related artifacts [3] .
As I have argued elsewhere, one could go further
than Basalla and suggest that a patent tends to
legally sever the ties leading to related artifacts
developed not just in the past but also at the
same time, whether in the same place or in a far
away location. Arguably, this view holds even if
such ties are acknowledged in the specification,
since a reference to the work of others does not
amount to a sharing of rights or an admission
that they are co-inventors [4] . Obviously, it is
never likely to be the case that the originators
and holders of traditional knowledge inspiring
the discovery of a pharmaceutical compound in
one of their medicinal plants would themselves
have known how to isolate or describe it chemi
cally. Even so, the logic of treating a descrip
tion of the traditional knowledge as part of the
public domain and owned by nobody, and the
isolation and chemical description, no matter
how creatively and expensively achieved, as a
patentable invention subject to private owner
ship, is unlikely to appear just or reasonable to
the indigenous traditional knowledge-holding
group. This is especially so if group members
actually assisted the researchers. In this con
text, it is worth noting that while the names of
plants containing a pharmaceutical chemical
are usually mentioned in patents, traditional
knowledge leads are frequently not.
Let us consider the example of curare, a name
originally applied to certain plant-based prepara
tions from South America. It is admittedly rather
easy to retrace the link from curare the surgical
muscle relaxant, to curare the Amazonian arrow
poison despite the long period of time between
the observation by Europeans that some Amazon
Indians used certain plant extracts to asphyxi
ate their prey and the use of curare in surgery,
which began in 1942. However, to suggest that
the learning trail ended in 1942 is false for two
reasons. First, curare inspired the discovery and
development of better surgical muscle relaxants.
Second, and more important, scientific investi
gation of curare from the 1930s was incredibly
fruitful. Using curare as a research tool proved
the essential role of chemicals in channeling
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messages within the brain and from the brain to
the rest of the body, thereby radically enhancing
our understanding of physiology and brain func
tion. This led directly to the subsequent develop
ment of numerous spin-off drugs including the
b-blockers, antidepressants such as Prozac and
treatments for Parkinsons disease, asthma and
diarrhea [5] . Needless to say perhaps, the trail
from curare the arrow poison to Prozac is hardly
an obvious one, which of course is testament to
the considerable amount of scientific research
conducted over a long period that began with no
more than an observation made by a few curious
European explorers. Who knows where else this
particular trail will lead in the future?
Arguably, the patent system encourages this
neglect of history and geography.
Similarly, the willow bark extracts used to
treat fevers and inflammation in ancient Greece
and Rome became aspirin, the synthetically pro
duced mass-consumption pharmaceutical prod
uct at the end of the 19th century. Willow tree
barks antipyretic properties were rediscovered in
the 18th century by English clergyman Edward
Stone, whose search was inspired, at least indi
rectly, by the Peruvian Indians use of cinchona
tree bark extract (quinine) to treat fevers like
malaria, and by the European doctrine of sig
natures, often attributed to Paracelsus but that
has much earlier roots, which led him to search
for such a product in the known source of fevers,
marshy ground. Aspirin, as a treatment for mild
fevers and headaches, is far from being the end
of the story. It was the first of a class of drug
(i.e.,NSAIDs). It would be going too far to sug
gest that aspirin inspired the development of all
NSAIDs that followed. Ibuprofen, for example,
was discovered in an effort to find alternatives
to cortisone, the first hormonal anti-inflamma
tory drug, which has some very unpleasant side
effects. Nonetheless, it was research on aspirin
that demonstrated the mode of action of this
whole class of drugs and underlines the long-
term importance of aspirin as a product, the first
of a class of product and as a research tool for
future discovery.
Renewing the old
Industry has in recent years been responding
to the present shortfall in the number of new
chemical entities entering the market by, among
other activities, returning to known substances
to identify undiscovered properties. They are,
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News & Analysis | Opinion
as I put it, seeking to renew the old. Since old
products are more likely to have some kind of
traditional knowledge connection, it follows that
traditional knowledge will most likely continue
at least indirectly to provide a source of leads for
new uses for old drugs for as long as companies
are doing this. This is not widely appreciated,
given the common assumption that modern
technologies such as high-throughput screening,
genomics and combinatorial and synthetic chem
istry are reducing the need for natural-product
research and, hence, for traditionalknowledge.
What is the evidence? It is no secret that the
number of NMEs entering the market has been
disappointing in recent decades despite the ever-
growing research and development expenditures.
As they continue to be hard to identify, scien
tists often go back to earlier substances. There
is nothing inherently wrong with this. Even as
innovative a scientist as Sir James Black knew
that looking forward often meant looking back
first. As he put it: the most fruitful basis for the
discovery of a new drug is to start with an old
drug [6] . Nowadays, though, discovery seems
often to end with the old drugtoo.
Out of 1264 new drug applications submit
ted to the US FDA between 1993 and 2004,
68% were not NMEs [7] . Of the 961 that were
approved, 67% were non-NMEs, meaning that
each was one of the following types of drug: a
new salt, formulation or indication of a previously
approved drug; a new combination of more than
one drug; a duplication of an already marketed
drug or an already marketed drug that had not
previously been approved by the FDA, such as a
very old drug (e.g.,aspirin)[7] .
The key point to be made is that if so many
new drugs are not in fact new molecules, it
becomes more likely that the sources of a sig
nificant proportion of drugs currently on the
market can be traced to indigenous communi
ties, if one takes the trouble to find out. The fact
that aspirin is mentioned in the above-referenced
US government report is somewhat telling in
this regard, given its traditional knowledge con
nections, although one should not overstate the
case since recent drugs that are completely syn
thetic can turn out, upon further examination,
to have therapeutic applications different from
those previously envisaged. Of course, even com
pletely new drugs may have origins in traditional
knowledge, as we will see, but non-NMEs are far
more likely to. Let us now consider some exam
ples of old traditional medicines being turned
into new products or at least being the subject
of new discoveries.
1408 Future Med. Chem. (2010) 2(9)
Again, aspirin is relevant. Since John Vane
worked out its mode of action in 1971, aspirin
has been found to have therapeutic applications
other than relieving pain and fever. Indeed, pat
ents relating to new uses of aspirin are still being
granted. To turn from a plant to a mineral, arsenic
was both a drug and a poison in Ancient Greece
and Rome and it is used currently in Chinese tradi
tional medicine. Although it was never a treatment
for cancer (and in fact has been known for almost
two centuries to be carcinogenic), it is used to treat
trypanosomiasis as it previously was for syphilis,
and Chinese scientists have even investigated its
potential use as a treatment for leukemia [8] .
Perhaps the best renewing cases are those
where traditional knowledge offers a direct lead
to a (supposedly) new product. Artemesinins
antimalarial activity was documented in Fourth
Century China. In the 1960s, the Chinese mili
tary conducted research into medicinal plants,
and in 1972 found a substance known as arteme
sinin in the leaves of the Artemisia annua (worm
wood) plant. Structurally modified artemesinin,
used in combination with other products, is now
the most effective antimalarial available. Despite
this, its mode of action has still not been fully
established. Nonetheless, numerous methods for
converting, extracting and making analogs have
been discovered and patented. Many more are
likely to follow.
loss of traditional knowledge means cutting
off access to a potentially huge and priceless
stock of complex biological substances that
scientists are unlikely to be able to stumble
across elsewhere or invent denovo in
thelaboratory.
Nicosan (or Hemoxin) is another tradi
tional medicine, this time from Nigeria, which
shows effectiveness as a sickle cell anemic treat
ment. Though not yet on the market, except
in Nigeria, it has orphan-drug investigational
status in the USA and Europe. A recent article
describes Nicosan as a mix of plants that came
from native-healer information and can thus
be classified as a true ethnobotanical prepara
tion[9] . This circumstance gives rise of course
to benefit-sharingimplications.
Going back to nature as if we never left
Dependence on nature has not gone away.
Recent evidence suggests that it is not dimin
ishing by any means. A comprehensive empirical
investigation by Newman and Cragg of the US
future science group

National Cancer Institute demonstrates con
vincingly that, as indicated in previous studies,
natural products play a dominant role in the
discovery of leads for the development of drugs
for the treatment of human diseases [9] .
Finally: a note of caution. One should not
overestimate the value of traditional
knowledgeeither.
Despite this, scientific and technological
advances suggest to many a reduced dependence
on natural products. While this may eventually
prove to be correct, some advances, including
metabolic engineering, appear at least in the
short to medium term to enhance the feasibil
ity of discovering, elucidating, optimizing and
mass-producing therapeutic substances of natu
ral origin [10,11] . This is significant given common
concerns that natural products tend to be com
plicated, heterogeneous, scarce, difficult to work
with and sometimes prohibitively expensive to
synthesize. There may be two kinds of scarcity:
in terms of the supply of the species in which
the chemical resides; and the actual chemical
that the relevant species may produce only in
minuscule quantities. Thus, some recent trends
arguably make natural product research more
appealing. Traditional knowledge is a logical
starting point as a source of initial leads.
Conclusion
This article shows that while the unrealized phar
maceutical value of traditional knowledge can
not readily be ascertained, it is surely significant:
Bibliography
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2 Robinson DF. Challenging Biopiracy: Challenges,
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UK (2010).
3 Basalla G. The Evolution of Technology. Cambridge
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4 Dutfield G. Intellectual Property Rights and the Life
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5 Feldman S. From Poison Arrows to Prozac: How
Deadly Toxins Changed our Lives Forever. Metro
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6 Raju TNK. The Nobel chronicles. Lancet 355, 1022
(2000).
future science group
Opinion | News & Analysis
there is enough evidence to demonstrate that
loss of traditional knowledge means cutting off
access to a potentially huge and priceless stock of
complex biological substances that scientists are
unlikely to be able to stumble across elsewhere or
invent denovo in the laboratory. Consequently,
there is a need for efforts to support the ethno-
ecological systems that conserve this knowl
edge through everyday use and generate further
knowledge. As for benefit sharing, the 1992
Convention on Biological Diversity places legal
obligations on commercial users of traditional
knowledge to share the benefits with the holders
and their communities in a fairmanner.
Finally: a note of caution. One should not
overestimate the value of traditional knowledge
either. It is relevant to present drug discovery, but
it forms just one portion of a very large reserve
of available knowledge, including scientific infor
mation reported in books and journal articles and
inventions disclosed in expired or lapsedpatents.
Acknowledgements
The author gratefully acknowledges helpful comments and
suggestions made by an anonymous reviewer.
Financial & competing interests disclosure
The author has no relevant affiliations or financial involve-
ment with any organization or entity with a financial inter-
est in or financial conflict with the subject matter or materi-
als discussed in the manuscript. This includes employment,
consultancies, honoraria, stock ownership or options, expert
te stimony, grants or patents received or pending,
orroyalties.
No writing assistance was utilized in the production of
this manuscript.
7 United States General Accountability Office. New
Drug Development: Science, Business, Regulatory, and
Intellectual Property Issues Cited as Hampering Drug
Development Efforts. Government Accountability
Office, Washington DC, USA (2006).
8 Shen Z-X etal. Use of arsenic trioxide (As2O3) in the
treatment of acute promyelocytic leukemia (APL):
II. Clinical efficacy and pharmacokinetics in
relapsed patients. Blood 9(1), 33543360 (1997).
9 Newman DJ, Cragg GM. Natural products as
sources of new drugs over the last 25years. J.Nat.
Prod. 70, 461477, 474 (2007).
10 Koehn FE, Carter GT. The evolving role of natural
products in drug discovery. Nat. Rev. Drug Discov.
4,206220 (2005).
11 Khosla C, Keasling JD. Metabolic engineering for
drug discovery and development. Nat. Rev. Drug
Discov. 2, 10191025 (2003).
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