Comment

Kokoza et al.10 provide an example of

how to take advantage of the molecular
genetics of both D. melanogaster and Ae.
aegypti. These investigators have an ongoing research program examining
bloodmeal-induced gene expression in
adult female mosquitoes. They have
characterized the gene encoding vitellogenin (Vg), the major secreted protein
produced in the fat body and transported to the developing oocytes. The
temporal and spatial expression pattern
of Vg makes its promoter a viable candidate to direct the expression of an antiparasite effector gene in the mosquito
hemolymph. Because transformation
rates of D. melanogaster can be as high
as 3050%, proper function of the mosquito Vg promoter was first analyzed in Pelement transformed fruit flies (V. Kokoza
and A. Raikhel, pers. commun.). These
experiments identified a 2.1 kb functional fragment of the Vg promoter.
Subsequently, Ae. aegypti were transformed with a Hermes element5 carrying
a hybrid gene consisting of the Vg promoter cloned so as to permit the tissuespecific, inducible expression of the gene
encoding defensin A (Def A). Significant
levels of the defensin peptide were
maintained for 22 days after initial gene
expression. Insect defensins will kill
P. gallinaceum11,12 and, in experiments that
are in progress, it is anticipated that the
transgenic mosquitoes expressing Def A
should be resistant to the development

of this parasite. Mosquito gene promoter function has been assayed before
in D. melanogaster13, but the Vg work
was the first systematic use of the information obtained from heterologous
transformation experiments to produce
transgenic mosquitoes with relevant
gene expression characteristics.
While much attention has focused
on population replacement strategies,
other genetics-based approaches are
also being investigated. Genetic sexing
methods to produce only males for sterile insect release would greatly facilitate
population reduction measures. The
molecular dissection of the mosquito olfactory system might lead to better
repellants or vectors with genetically
modified host preferences. All of these
studies could benefit from technology
transfer from Drosophila and the
exploitation of molecular genetic tools
developed in both fruit flies and mosquitoes. We can expect to see more of
this type of work in the future.
References
1 Wright, J.W. and Pal, W. (1967) Genetics of
Insect Vectors of Diseases, Elsevier
2 James, A.A. et al. (1999) Controlling malaria
transmission with genetically-engineered,
Plasmodium-resistant mosquitoes: milestones
in a model system. Parassitologia 41, 461 471
3 Coates, C.J. et al. (1998) Mariner
transposition and transformation of the
yellow fever mosquito, Aedes aegypti. Proc.
Natl. Acad. Sci. U. S. A. 95, 37433747
4 Coates, C.J. et al. (1999) Promoter-directed

6
7

8
9
10

11

12

13

expression of recombinant fire-fly luciferase

in the salivary glands of Hermes-transformed
Aedes aegypti. Gene 226, 317325
Jasinskiene, N. et al. (1998) Stable
transformation of the yellow fever mosquito,
Aedes aegypti, using the Hermes element
from the housefly. Proc. Natl. Acad. Sci. U. S. A.
95, 37483751
Catteruccia, F. et al. (2000) Stable germline
transformation of the malaria mosquito
Anopheles stephensi. Nature 405, 959962
Catteruccia, F. et al. (2000) Toward
Anopheles transformation: Minos element
activity in anopheline cells, and embryos. Proc.
Natl. Acad. Sci. U. S. A. 97, 21572162
Schneider, D. and Shahabuddin, M. (2000)
Malaria parasite development in a Drosophila
model. Science 288, 23762379
Adams, M.D. et al. (2000) The genome
sequence of Drosophila melanogaster. Science
287, 21852195
Kokoza, V. et al. (2000) Utilization of
transgenic technology for modeling blood
meal-activated systemic immunity in the
mosquito vector, Aedes aegypti. Proc. Natl.
Acad. Sci. U. S. A. 97, 91449149
Shahabuddin, M. et al. (1998) Plasmodium
gallinaceum: differential killing of some
mosquito stages of the parasite by insect
defensin. Exp. Parasitol. 89, 103112
Lowenberger, C.A. et al. (1999) Mosquito
Plasmodium interactions in response to
immune activation of the vector. Exp.
Parasitol. 91, 5969
Skavdis, G. et al. (1996) Conserved function of
Anopheles gambiae midgut-specific promoters
in the fruitfly. EMBO J. 15, 344350

Anthony A. James is at the Department of

Molecular Biology and Biochemistry, 3205 Bio
Sci II, University of California, Irvine, CA 926973900, USA. Tel: +1 949 824 5930, Fax: +1
949 824 2814, e-mail: [email protected]

Why Veterinarians Should Care More

About Parasitology
A.M. Zajac, N.C. Sangster and T.G. Geary
The field of veterinary parasitology has
far-reaching implications for human and
animal health1. Parasites remain a major
factor limiting animal production and
well being, and parasite control is undeniably a primary task of all veterinarians.
Why, then, are so many veterinary parasitologists left with the disquieting
sense that the veterinary educational
system has marginalized parasitology?
Investment in veterinary parasitology by
governments and veterinary colleges appears to be, at best, stagnant, and, more
likely, declining2,3. The number of faculty
slots reserved for parasitologists seems
to be decreasing and we have seen cuts
in the number of hours devoted to the
subject in veterinary and undergraduate
curricula2. However, parasites represent
504

a major source of income for veterinarians. In the USA, the control of fleas and
heartworms alone provides a market of
hundreds of millions of dollars annually*.
Globally, antiparasite drugs accounted
for 45% of veterinary pharmaceutical
sales in 1998*.
We now have remarkably safe and
effective treatments for nearly all important animal parasitoses, including heartworms, gastrointestinal (GI) worms and
ectoparasites. New veterinary antiparasitic drugs have profoundly influenced
human medicine as well, especially ivermectin, mebendazole and albendazole.
Much has been learned about parasite
* Veterinary Pharmaceuticals (1998) Wood
Mackenzie Report, November, Edinburgh, UK

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pathology and transmission, and about

previously little-known parasites. We
have witnessed marked reductions in
the incidence of many parasite infections
in animals. The contributions of veterinary parasitologists to animal health
should be celebrated and expanded.
Why is this not the case?
We have identified three interrelated
factors that might contribute to the apparently low status of veterinary parasitology.
(1) Shortage of headline achievements
in basic research. Investment in research
on veterinary infectious diseases reflects
the investment made in human infectious disease research. Viral and bacterial diseases plague humans in wealthy
countries, and have rightly generated
Parasitology Today, vol. 16, no. 12, 2000

Comment
abundant government and industrial
support. This resource develops tools
and expertise that naturally spin off
into research on related veterinary
pathogens. In contrast, parasitic diseases
are of little immediate concern to
wealthy countries, resulting in a correspondingly minor investment from industry and governments. Few parasitologists are trained in the developed
world, because there is little demand for
their services. Little opportunity for spin
off from human research exists, and veterinary parasitologists must therefore
compete for the rather small amount of
government and industrial support available for work on animal diseases. These
funds are further limited by fluctuations
in livestock industries. Veterinarians and
other animal health specialists see few
dramatic changes in diagnostic tests and
methods of control, and are likely to
conclude that the field of parasitology
cannot be very important.
This situation has unfortunately
widened a schism between industrial
and academic research. With little government support for research on veterinary parasites, a role for the animal
health industry in this regard becomes
more crucial. However, the animal
health industry is less lucrative than the
human pharmaceutical business and,
therefore, is less willing to provide funding for basic research on animal parasites. Furthermore, intense emphasis on
profits has reduced the ability of many
companies to be research benefactors.
Consequently, what could be a healthy
partnership is withering. Although antiparasite drugs account for 45% of veterinary medicines used today*, a paucity
of science supports their use. There is an
increasing level of antiparasite drug resistance throughout the world4, a phenomenon we are ill equipped to address
scientifically. We understand little about
the molecular bases of antiparasite drug
resistance, and so have difficulty detecting resistance genes. We lack data on
how resistance develops and spreads in
various host populations. Industry is increasingly unable or unwilling to support
research into these questions in academic
laboratories.
Instead, animal health companies
seem likely to continue funding only field
trials or other applied clinical studies in
academia. Parasitologists who depend
on these trials to survive as researchers
might find themselves limited in the ability to investigate more fundamental aspects of parasite biology, epidemiology
and control. To obtain non-industrial
funding, academics must advance nonchemical strategies for parasite control,
Parasitology Today, vol. 16, no. 12, 2000

including vaccination and biological approaches. Advancing alternative strategies demands that the limitations of
existing measures be emphasized, so researchers must find fault with drugs (eg.
resistance and residues) to justify support for finding other ways to control
parasites. This hardly encourages collaboration with an industry that is heavily
reliant on drugs. Advocating such approaches has won considerable support
for applied immunology in veterinary
parasitology for over 20 years.
Unfortunately, this effort has yet to
make a significant contribution to parasite control in veterinary practice, even
though the difficulties of obtaining commercial success were known at the outset5. Rather than being able to count on
a consistent source of funding for basic
research into the immunology of veterinary parasite infections, we have relied
too frequently on quicker, applied research on the vaccine potential of
cloned antigens.
We must boost the output of very
high-quality research on parasites, especially those of veterinary importance.
We need headline-grabbing exposure
to reverse the perception that our
field is incapable of producing excellent
research.
(2) Decline in importance of parasitology in the veterinary curriculum.
Reduced emphasis on parasitology in
veterinary curricula will produce veterinarians who are less able to appreciate
the complexity of parasitic organisms
and their control. This situation guarantees a continuing decline in status for
the field and decreased recruitment of
veterinary graduates into parasitology,
at a time when their broad training is
particularly relevant to the development
of integrated parasite control programs
and the identification and control of
emerging zoonotic diseases.
This situation can only be reversed if
we persuade veterinary educators of the
importance of veterinary parasitology,
from a scientific as well as an economic
perspective.
(3) Perceived irrelevance to clinical
practice. The extreme success of products in the antiparasite market might
have contributed to the decreased emphasis on parasitology among veterinarians. For many veterinarians, the management of common, economically
important parasites requires no further
thought than reaching for the newest
broad-spectrum drug. This attitude does
little to encourage interest in parasitology. As a result, veterinary clinicians,
who predominate in teaching during the
final years of the veterinary curriculum,

are unlikely to stress anything other than

chemotherapeutic control of parasites.
In the USA, the trend of advertising
pharmaceuticals for flea and heartworm
problems to the public, and over the
counter sales of most ruminant and
equine parasiticides, reinforce the decline in the active role of the veterinarian in parasite control.
It is up to us to show them that parasite control beyond dispensing drugs is
not only clinically important, but can be
financially rewarding.
Call to Action
The fallacy of complacency about
veterinary parasitology is exposed by
the fact that no parasite of veterinary importance has been eradicated; control
programs cannot be phased out, but
must be maintained at considerable cost
to the consumer. This situation testifies
to the bedrock importance of parasitology to the veterinary profession. The
discrepancy between attention devoted
to parasitology in veterinary curricula
and the contribution of parasite control
to veterinary practice should be troubling to veterinarians, veterinary educators and state and federal bureaucrats.
Surely, the interests of consumers are
not being served if the providers of animal health services are less schooled in
that area than in many others that are of
less economic significance. We dispense
billions of dollars of drugs to customers
without really knowing how they work.
What is worse, we are doing little to
rectify the situation. The double
whammy of little class time and little
support for research almost guarantees
that such advances will not be made in
the near future, and so veterinary customers will go on paying a lot of money
for parasite control programs that are
built on rather flimsy scientific platforms.
We agree with Thompson1 that many
opportunities exist for new and exciting
research in veterinary parasitology. Our
concern is where support for these will
be found. It is up to us to reverse the decline in the status of and support for veterinary parasitology. Veterinary parasitologists must emerge from the
classroom and laboratory and become
activists in promoting our discipline and
bringing it the recognition it merits.
We suggest that associations of veterinary parasitologists, both nationally and
internationally, undertake the following.
(1) Document the economic importance,
both real and potential, of parasitology to
practicing veterinarians. We have not been
aggressive enough in identifying and promoting activities associated with parasite
505

Comment
control that are economically rewarding
for the veterinarians in practice. The
surest way to increase the status of veterinary parasitology is to demonstrate
that it is economically undervalued. A
good beginning is to quantify efficiently
the economic contribution of parasitology
to various types of veterinary practice, and
then to document the potential for
growth in this area. Key questions to be
answered initially include: (a) What percentage of income can be traced to parasite control in various types of veterinary
practice? (b) What percentage of consumer veterinary medical expenditure is
devoted to parasite control?
(2) Reinvigorate the teaching of veterinary parasitology to make it clear that it is
not obsolete. In addition to important clinical aspects of parasitism, we must strive
to convey the crucial unanswered questions that remain and the exciting work
that must still be done. For example, the
role of veterinarians in identifying and
controlling emerging zoonotic diseases
should be emphasized. How to develop
revenue-generating practice programs
for veterinarians in parasite control
should be an integral part of parasitology
courses. Student interest in and demand
for parasitological instruction will grow
with a change in content and tactics.
Reinvigorated teaching strategies should
also stimulate recruitment into the field.
(3) Devote more attention to developing innovative programs that contribute to
parasite control and add economic value
for consumers and practitioners of veterinary medicine. There are no easy ways to
stimulate innovation, but a renewed
focus on the practitioner as a key cus-

tomer for what veterinary parasitologists do is a worthy initiative. Starting

with students is a good way to begin.
(4) Improve the prospects for better and
more consistent funding by agreeing, at a national level, on research priorities in veterinary
parasitology. The adoption of commonly
accepted experimental goals, running the
gamut from basic to applied, could help
end the divisive competition for a small
pool of funds. The goals must be integrated, balanced between the field and
the bench, and thoroughly justified. Basing
a research strategy firmly on the foundation of the economic importance of
parasites in the veterinary sector is a way
to attract endorsement of the agenda,
which must be adapted for each country6.
We should be reinvigorated by the
biotechnological revolution. The recent
completion of the Caenorhabditis elegans genome sequencing project7 offers
an unprecedented opportunity to gain
insight into the biology of parasitic
nematodes. Similar opportunities are already well established among apicomplexan protozoa8. Now is the time to
develop tools to extend genetic techniques to parasitic species. Industrial and
academic veterinary parasitologists
should unite to refocus the field on the
application of new technologies to basic
problems of parasite biology6. Much
groundwork in basic parasite biology will
first be necessary. Such research will
eventually generate unpredictable advances in parasite control, and will help
dispel the common myth that parasitology research is old-fashioned and unsophisticated, out of place in a modern
academic department.

Acknowledgements
The material presented here is derived, in
part, from an address at the WAAVP conference in Copenhagen, 1519 August 1999.
An expanded version of some of it has been
published6.
References
1 Thompson, R.C.A. (1999) Veterinary
parasitology: looking to the next millennium.
Parasitol. Today 15, 320325
2 Andrews, R.H. (1999) ASP annual scientific
meeting 1998: will parasites outlive
parasitologists? Int. J. Parasitol. 29, 803808
3 Mitchell, G. and Nossal, G. (1999) Funding
options for research: facing the market as
well as government. Int. J. Parasitol. 29,
819831
4 Sangster, N.C. (1999) Anthelmintic
resistance: past, present and future. Int. J.
Parasitol. 29, 115124
5 Williams, J.F. (1986) Prospects for prophylaxis
of parasitism, in Parasitology: Quo Vadit
(Howell, M.J., ed.), pp 711720, Australian
Academy of Science
6 Geary, T.G. et al. (1999) Frontiers in
anthelmintic pharmacology. Vet. Parasitol. 84,
275295
7 Caenorhabditis elegans Sequencing
Consortium (1998) Genome sequence of
the nematode C. elegans: a platform for
investigating biology. Science 282, 20122018
8 Ajioka, J.W., ed. (1997) Analysis of
Apicomplexan Parasites, in Methods: A
Companion to Methods in Enzymology (Vol.
13) (No. 2), Academic Press

Anne M. Zajac is at the Virginia-Maryland

Regional College of Veterinary Medicine,
Blacksburg, VA 24061-0442, USA. Nick C.
Sangster is at the Department of Veterinary
Anatomy and Pathology, University of Sydney,
NSW 2006, Australia. Timothy G. Geary is at
Pharmacia and Upjohn, Animal Health
Discovery Research, 7923-25-111, 7000
Portage Road, Kalamazoo, MI 49001-0199,
USA. Tel: +1 540 231 7017, Fax: +1 540
231 7367, e-mail: [email protected]

In Search of the Red Queen

M.E.J. Woolhouse and J.P. Webster
The Red Queen hypothesis is about coevolution, reciprocal adaptive genetic
changes within populations of interacting
species1. The hypothesis (at least, in one
of its guises) states that one possible outcome of co-evolution is endless selection
for adaptation and counter-adaptation. It
takes its name from Lewis Carrolls book
Through the Looking Glass in which the
Red Queen explains to Alice that here,
you see, it takes all the running you can
do, to keep in the same place. The Red
Queen hypothesis has been widely invoked to explain fundamental biological
observations such as the existence of
sex, the evolution of virulence and the
506

maintenance of genetic polymorphisms.

The hypothesis applies potentially to all
kinds of species interactions, such as
preypredator or plant herbivore, but
here we shall focus on hostparasite
interactions and polymorphisms in host
susceptibility and parasite infectivity.
Host susceptibility and parasite infectivity are often found to be genetically
variable2,3. But if polymorphisms in these
traits are to be explained in terms of the
Red Queen hypothesis, then they must
be genetically correlated, which is much
harder to demonstrate. The most direct
evidence for such correlations comes
from studies of plant pathogens: in

0169-4758/00/$ see front matter 2000 Elsevier Science Ltd. All rights reserved. PII: S0169-4758(00)01820-2

several plantpathogen systems, host

susceptibility and parasite infectivity are
both determined at single loci, and only
certain combinations of host alleles and
parasite alleles are compatible4. This kind
of gene-for-gene interaction is the simplest arrangement that would allow the
Red Queen to operate. Unfortunately,
the genetics of animal hostparasite
interactions are not usually so transparent
or so well understood and evidence for
co-evolution in these systems tends to
be much more indirect.
The most widely cited evidence for
co-evolution in animal hostparasite
systems concerns local adaptation, which
Parasitology Today, vol. 16, no. 12, 2000