[from THE FUTURIST, January-February 2003]
Drugs from Bugs: The Promise of
Pharmaceutical Entomology
By Stephen Trowell
Most research with insects involves getting rid of them or fighting
the diseases they spread. Now, a team of researchers in Australia is focusing on enlisting
insects--or chemicals derived from them--in fighting diseases.
There are about 16 times as many insect species as there are plant
species, yet plant chemistry has been studied 7,000 times more intensively than insect
chemistry on a research-per-species basis. No one has seriously gone after insects for
medicines before now.
Insects have large arsenals of biologically active compounds, such as
molecules that kill cancer cells, proteins that prevent blood from clotting, enzymes that
degrade pesticides, proteins that glow in the dark, and antimicrobial peptides and toxins.
 To tap this potentially enormous chemical resource, a new
Australian company was established in July 2002 as a spin-off of the Entomology Division
of CSIRO, Australia's Commonwealth Scientific and Industrial Research Organization. The
company, Entocosm Pty. Ltd., will develop a unique library already comprising more than
1,000 insects and extracts from them, collected in the Eastern Australian States and
Territories. Entocosm will collaborate with other institutions and companies in screening
the samples for potential pharmaceuticals. The goal is to make insect-derived
pharmaceuticals as well-known and commercially successful as are plant-derived
pharmaceuticals.
Seeking Medically Useful Insects
We have cast our net broadly. Our collection team assembled over a thousand species of
insects and other terrestrial invertebrates from Eastern Australia for this purpose.
Eighty percent of the species are insects, and the other 20% comprise spiders, scorpions
and mites, nematode, oligochaete and annelid worms, millipedes and centipedes, slugs,
snails, freshwater bivalves and crustaceans. Among the insects, we have a broad
representation of 17 out of the 32 insect orders generally recognized by taxonomists (some
of the minor, less-well-known orders are not represented in Australia). Our collection
includes, of course, beetles, butterflies, moths, ants, wasps, bees, crickets,
grasshoppers, stick and leaf insects, flies, dragonflies, cockroaches, termites, earwigs,
and sucking bugs including aphids, cicadas, and other bugs.
The way we are approaching this is to screen broadly across the
available genetic diversity without any preconceptions about where the best sources of
activity might be. This means we hope to pick up both biological activity one might have
predicted (anticoagulants from blood-sucking insects, for example), as well as the
unpredictable, such as analgesics from beetle pheromones or immune-modulators from the eye
pigments of flies. As we go, we are finding that some taxonomic groups are giving us a
larger proportion of antibacterial hits than others.
While our research on specific insects is proprietary, the group I am
most prepared to talk about is termites: We have found a number of new variants of the
trinervitane scaffold and shown that they have selective antimicrobial activity; we have
even found that previously discovered trinervitanes also have antimicrobial activity that
had been unknown.
 For example, we have lodged a patent claiming some
new antibacterial compounds isolated from a species of termite with the scientific Nasutitermes
triodiae. It is also known as the cathedral termite, because it builds mounds more
than seven meters high in the arid regions of Australia. The picture shows a few workers
and some soldiers; the soldiers have a nozzle in the middle of the head through which they
squirt a cocktail of defensive chemicals, including, we believe, the molecules with
antibiotic properties. Analysis shows that only the soldiers have the ability to make the
antimicrobial compounds.
If you look at the broader scientific literature you will see that some
beetles produce cytotoxic compounds that have been used in traditional Chinese medicine to
treat cancer or tested in Western laboratories for cancer-fighting properties. Most
insects have a range of antimicrobial peptides (insect-immune peptides), and we are seeing
a number of non-peptide antibiotics. To my amazement, I have read that the blood of a
beetle was used in South Africa as an arrow poison, and of course leeches produce the most
potent anticoagulants known.
The Next Steps in Development
So far we have no drugs in the clinic. We are at a much earlier stage than that, and
truthfully just at the stage of taking the research out of a purely academic into a
commercial environment. We do have our existing library, we do have many selective
antimicrobial activities, and we do have some molecules that have been purified, which we
know are new to science and which in some cases we have lodged patents for.
As drug-resistant pathogens increasingly threaten human health, the
demand for new agents to treat them is becoming more urgent. Our team hopes insects--and
our increasing knowledge about them--will help win that battle.
About the Author
Stephen Trowell is the Chief Scientific Officer for Entocosm
Pty. Ltd. and Principal Research Scientist, CSIRO Entomology, GPO Box 1700, Canberra, ACT
2601, Australia. Telephone 61-2-6246-4126; fax 61-2-6246-4173; e-mail
Stephen.Trowell@csiro.au.
|
Prospecting
in Nature's Pharmacy
There are about 4 to 6 million species of insects on earth compared
with 250,000 plant species; yet far more research has been done on the medically useful
properties of plants than those of insects.
Ethnobotany, the study of native peoples' use of plants for
medicines and other applications, has already yielded a wealth of treatments. For example,
the rosy periwinkle (Catharanthus roseus) is the source of alkaloids used to treat
childhood leukemia and Hodgkin's disease. Pharmaceutical companies such as Pfizer have
turned their attention to "nature's medicine cabinet," forming partnerships with
botanical research institutions.
In his most recent books Medicine Quest (Viking, 2000) and The Killers Within (Little, Brown and Co., 2002), ethnobotanist Mark Plotkin describes the
search for cures in the study of reptiles, amphibians, fungi, and assorted sea creatures,
and even in the study of ape behavior.
Insects have played a part in healing for centuries; maggots, for
instance, can clean wounds, and honey from bees has been used on burns. But most modern
research on insects has focused on either getting rid of them or curing the diseases they
spread. Now, entomologists are increasingly looking at the good side of insects. The
Transvaal Museum in South Africa, for instance, is developing a project to identify
medically important insects.
One reason ethnoentomology has not caught up to ethnobotany is the
lack of accurate documentation of native uses of insects. According to biologists Robert
Dunn and Monica Sanchez of the University of Connecticut, interview subjects are seldom
even asked if they used insects as treatments. "When uses of insects were reported,
the insect species were typically described as 'the black ant' or the 'red ant' and not
collected," Dunn and Sanchez said at the 2002 conference of the Society of
Ethnobiology. "Recent research and a re-analysis of historical literature suggests
that insects, particularly social insects, were and continue to be commonly used as
medicine."
Two converging trends may accelerate research in medical entomology:
The first is the emergence of more drug-resistant strains of bacteria, which creates an
urgent need for new medicines. One promising development is the recent report of an
antimicrobial peptide derived from European fire bugs by scientists at the University of
Pennsylvania's Wistar Institute. The researchers believe the peptide pyrrhocoricin
not only kills bacteria directly but can also be adapted to use as a drug-delivery system.
The second trend that makes new research more urgent is the
disappearance of species-rich ecosystems such as rain forests and coral reefs. As Mark
Plotkin points out, rain forests contain more than half the world's species, most of which
are as yet unknown to scientists. As forests disappear, so does humanity's hope for future
medicines.
Sources: "The Healing Forest" by Mark J. Plotkin, THE
FUTURIST (January-February 1990).
Transvaal Museum Ethno-Ecology Project, Web site www.nfi.org.za/Ethnobiology/ethno.htm.
"Keeping the Queen Healthy: The Use of Social Insects as Medicine," presented by
Robert R. Dunn and Monica C. Sanchez, 2002 Conference of the Society of Ethnobiology
(March 6-9, 2002, University of Connecticut).
The Wistar Institute, Web site www.wistar.upenn.edu. |
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