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Why, when it is now possible,
do we not stop using animals? Researchers are not against the idea.
Leaving aside the ethical issues, animal experimentation is far
from a panacea in scientific terms. An animal's reactions to a particular
drug or toxic substance do not always perfectly mimic reactions
in man. Furthermore, in some fields - in particular the study of
the effects of new drugs which require the use of a very large number
of animals as models - the search for alternatives is yielding new
solutions which are more useful and efficient than traditional tests.
Progress in neurology
Neurological research is a field where the demand
for alternative methods is particularly high. Scientists in this
field are seeking to evaluate the action and thus the potential
risks of toxicity of a growing number of new molecules of possible
therapeutic value.
An avenue being explored under one European project concerns potassium
(K+) ion channels. These tiny generators of electrical
signals, present everywhere in nerve cells, are a prime pharmacological
target. According to Hella Lichtenberg (Bonn University), the coordinator
of this research, a number of disorders - which are found in many
body organs and tissues with no apparent correlation - may be linked
to changes in the genes that code for proteins in these channels.
But due to their extreme diversity, the genes are much more difficult
to study than other possible targets, such as receptors.
Using yeast as a model, the project conducted
research on a heterologous expression of proteins in these
well-known channels. Long used by man, and the first eukaryote to
have been sequenced, this small fungus has many genes which resemble
those found in the human genome. 'As soon as a gene involved in
a human pathology has been identified, its function can be deduced
from, or at least perceived by, the known function of a similar
genome sequence in yeast,' explains Hella Lichtenberg. Six European
teams have contributed to this project: five universities and one
Swedish company, Astra Arcus AB. The experimental system developed
has made it possible to demonstrate the validity of an approach
which is able to replace animal experimentation for an initial identification
of interesting active molecules and screening tests for their toxicity.
It was also in the field of research on the neurotoxicity
of drug molecules that seven European partners worked on a new multi-electrode
device for in vitro electro-physiological measurements. Previously,
this type of test involved studying the propagation of electrical
signals in sections of animal brain, thereby establishing a 'map'
of the brain's responses to each molecule. This required the death
of many 'guinea pigs'. 'With our technique, we are able to study
a dozen drugs using just one animal,' points out project coordinator
Massimo Grattarola. 'The brain sample in fact acts as a biological
sensor whose response to the various molecules to be tested is analysed,'
explains Yves Du Pont of the French instrumentation company Bio-Logic
Instruments, which contributed its skills in the field of electro-physiological
data recording.
Stimulating the liver and kidneys
In a completely different area, a project
involving five university teams and three industrial partners has
developed a system enabling the in vitro study of the action on
the liver and kidneys of cytokines. These are recombinant proteins
produced by the body which influence cell growth and immune reactions.
Advances in molecular biology and genomics are today making it possible
to use biotechnology to produce cytokines with a view to possible
applications in the treatment of cancer or immune disorders. But
there remains the fundamental problem that, for genetic reasons,
cytokines are 'dependent species'. Not only must they be of human
origin to be applied to man, but they cannot be tested on animals
as the results would be of no relevance. Direct tests on man are
also clearly impossible for ethical reasons.
'Our project allowed us to develop the Epiflow
bio-reactor, now commercially available, which enables stable cultures
of various human liver and kidney cells to be produced, these two
organs being extremely sensitive to the effects of cytokines,' explains
project coordinator Walter Pfaller of Innsbruck University. 'This
in vitro system makes it possible to simulate and model the basic
functions of the liver and kidney, and to test the cellular reactions
to the different kinds of cytokines, by examining their treatment
and/or toxic effects.'
Even if this project represents a particular
case of an alternative to animal experimentation - and one where
the latter was not an option in any event - it does show that the
possibilities for in vitro analysis open up particularly
interesting possibilities for the pre-clinical study of the increasingly
sophisticated new medicines now being developed by molecular biology.
Contact
Hella Lichtenberg
Bonn University (DE)
h.lichtenberg@uni-bonn.de
Massimo Grattarola
Genoa University (IT)
gratta@dibe.unige.it
www.bio.dibe.unige.it/
Walter Pfaller
Innsbruck University (AT)
walter.pfaller@uibk.ac.at
To find out more:
Ethical criteria for the evaluation of European
research projects
ftp://ftp.cordis.europa.eu/pub/life/docs/ethical_review.pdf
Scientific Information Service on advanced
alternative methods to animal experiments in biomedical sciences
http://ecvam-sis.jrc.it/index.html
Fund for the Replacement of Animals in
Medical Experiments
http://www.frame.org.uk/index.htm
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Research and
legislation
'Replacing, reducing, refining.' Europe
has set itself the clear objective of applying the ethical
code of the 'three Rs' which guides the practices of a very
large part of the scientific community in the field of animal
experimentation. This desire is reflected both in the legislation
- the directive adopted in 1986 (86/609/EEC) aimed at harmonising
the provisions of Member States for the protection of animals
(1) - and in consultation between the various Commission services
concerned by the problem. The ball is in fact just as much
in the court of the research programmes as of the Environment
Directorate-General (initiator of the 1986 directive), the
Health and Consumer Protection Directorate-General - where
a scientific committee is specifically responsible for the
applicability of alternative methods for evaluating the safety
of ingredients used in cosmetics - and the industrial policy
units.
In terms of research, the ethical framework
drawn up by the 'Quality of Life' programme to assess projects
supported by the EU requires researchers to explicitly mention
the use of animal experimentation and to justify it. Also,
25 million euros were allocated to support alternative research
methods (as described above) under the Fourth Framework Programme,
an amount already exceeded by projects under the current Fifth
Framework Programme. Finally, in 1991 the Commission set up
the European Centre for the Validation of Alternative Methods,
managed at the Joint Research Centre (Ispra, IT).
Contact
Béatrice Lucaroni
Research DG
beatrice.lucaroni@ec.europa.eu
Michael Balls
ECVAM-IHCP-JRC
ecvam.sis@jrc.it
http://cordis.europa.eu/life/src/ptc_sel.htm#ethical
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