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image European Research News Centre > Medecine and Health > In vitro versus in vivo
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image image image Date published: 11/07/2001
  image In vitro versus in vivo
RTD info 30
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  The search for alternative methods to experiments on animals is stimulating reliable, more effective and less costly techniques for the development of new therapeutic molecules. Under the combined effect of a strict legislative framework and adequate financial support, Europe is providing the impetus in the field which is producing encouraging results.
   
     
   

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).

(1) Another directive, proposed as early as 1976, concerns the particular case of animal experimentation in the cosmetics industry; it is still pending with its seventh amendment currently being discussed at the Council and European Parliament.

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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