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Animal experimentation

Science without guinea pigs

   

Millions of animals are subjected to experiments in European laboratories every year - all for the benefit of mankind. But could science, medicine and industry dispense with such practices? The 3rd World Congress on Alternatives and Animal Use in Life Sciences, held in Bologna at the end of last summer, provided an occasion both to assess the situation, and for wide-ranging debate.

     
   

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European Centre for the Validation of Alternative Methods (ECVAM) - Institute for Health and Consumer Protection (JRC-Ispra) - Analysis of culture cells.

Replace. Reduce. Refine. The 'Three Rs' rule was first formulated in The Principles of Humane Experimental Technique(1) by William Russell and Rex Burch. Forty years ago, these two British scientists defined three objectives in the field of experimentation on living creatures. They advocated the use of any scientific method using "insentient material" which could replace methods using "conscious living higher animals"; any means of reducing "the number of animals used to obtain information of a given amount and precision"; and, in regard to refinement, any development leading to a "decrease in the incidence or severity of inhumane procedures applied to animals". The implication of these three principles, and progress made in applying them, were discussed at length during the 3rd World Congress on Alternatives and Animal Use in Life Sciences, held in Bologna (I) under the auspices of ECVAM (European Centre for the Validation of Alternative Methods), from 29 August to 2 September 1999. The event - the occasion for no fewer than 65 conferences, workshops and debates - was attended by some 800 researchers, as well as representatives of legislative authorities and animal-welfare campaigners.

Experiments: a decade of progress
"Many researchers are now working on these Three Rs and more and more countries are incorporating them into their legislation. The situation changed a great deal in this field during the 1980s," pointed out William Russell, who was present at the debates. He cited the creation of the NCA (Netherlands Centre on Animal Use), the Zebet (Centre for the evaluation of alternative methods to animal experiments) in Germany, and the CAAT (Centre for Alternatives to Animal Testing) at the Johns Hopkins University in the USA, by way of example. Having reached a peak in the mid-seventies, it now seems that this type of experimentation is diminishing generally. In France, for example, the number of laboratory animals fell from 7 million in 1980 to 2.6 million in 1997.

A growing number of alternative solutions are being made available to researchers. Organ, cell and tissue cultures are now commonplace while our improved knowledge of genetics is making it possible to study certain human biochemical mechanisms in micro-organisms. Innovative molecular biology techniques are resulting in the application of tests based on the use of isolated enzymes (some of which have replaced the thousands of rabbits and rats used 25 years ago for pregnancy tests). Physics, mathematics and information technology are also making their contribution to the Three Rs, with imaging techniques, modelling, non-invasive methods of investigation, telemetry and biostatistics helping researchers to learn as much as possible from the data available.

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Model of a dog's head subjected to radiation.

Testing: European validation
But animals are not used solely for research purposes. They are also used in regulatory testing for standardised evaluation of the possible dangers of substances released onto the market. In this sector, which makes it possible to guarantee that consumers are both protected and well informed, it is much more complicated to replace animal experimentation and consequently progress has been slower. This is why ECVAM (European Centre for the Validation of Alternative Methods), was set up at the Joint Research Centre in Ispra, in 1991. "Validation aims to show the reliability and pertinence of an established test procedure in relation to a particular objective. Our principal mission is to facilitate and coordinate the validation of new procedures adopted at Union level and for this we work in close cooperation with the authorities, universities and industry in the Member States," explains Michael Balls, the centre's director. With an annual budget of around 6 million euros, ECVAM allocates half this amount to research, two-thirds of which goes to contracts with European university or industrial laboratories.

How many? Which ones? Why?

In 1996, 11 646 130 animals were used for various experimental purposes in the EU. In 1991, the figure was 11.8 million - but that was for just ten countries. Rodents and rabbits account for 81% of the warm-blooded animals used in experiments.

Source: Statistics on the number of animals used for experimental and other scientific purposes in the Member States of the European Union - 1996

To date, ECVAM has validated a phototoxicity test and three others in the field of skin corrosion. The validation of another test for vaccines should be completed within the next three months and other research is under way, in particular on the risks of skin sensibilisation and irritation, haematotoxicity, nephrotoxicity, reproduction toxicity, toxicity of the metabolism, neurotoxicity and metal toxicity. The methods validated are at present being studied by the European and international regulatory bodies - in particular the OECD - whose recommendations are applied to tests carried out in the EU, North America, Japan, Australia and New Zealand.

 

Ethics and necessity
As co-organiser of the "Bologna Congress", Michael Balls is pleased to have provided the opportunity for dialogue between scientists and members of animal rights associations, even if at times they took up opposing positions in the invariably lively debates. But then the scientists themselves were far from being all of the same opinion. "The atmosphere was constructive," stresses the ECVAM director. "These two worlds came together to speak and listen to each other. The researchers are now more ready to answer questions about their work than was previously the case." A relative consensus led the delegates to add guidelines on animal experimentation to the 1964 Helsinki declaration which lays down the principles of the use of humans by science, placing the emphasis on the "Three Rs".

These "Three Rs" do not, however, mean the end of such practices. "It is accepted today that an experiment on an animal is only authorised if the expected benefit outweighs the suffering inflicted upon it," stresses Bert van Zutphen, an expert in genetics and animal models, and professor at the Faculty of Veterinary Medicine at Utrecht University (NL). "There remains the question of who evaluates the cost/benefit ratio, and how. In several European countries, such as Sweden, the Netherlands, the United Kingdom, Germany and France, this type of experimentation has to be approved by an ethics committee."

Species and genes
A majority of scientists take the view that the study of many diseases and the search for effective treatments will always require the use of animals. The liveliest debates therefore often revolve around the choice of species. "The phylogenetic proximity of man and non-human primates makes the latter the ideal model for the development of drugs and vaccines against diseases such as Aids, malaria or yellow fever," believes Jann Hau of the Department of Comparative Medicine at Uppsala University (S), while for Michael Balls, "The greater the proximity between non-human primates and man, the stronger the ethical and humanitarian reasons for not using them." Martha Armstrong, of the Humane Society of the United States, notes a growing reluctance among laboratory personnel to working with certain "domestic" animals such as cats and dogs.

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The number of animals used in the laboratory has been falling over the last 30 years. In France, from 7 million to 2.6 million between 1980 and 1997. But rodents and rabbits still account for 81% of the warm-blooded animals used as guinea pigs.

Finally, for a number of years now, gene transfer techniques have been raising new questions on the use of animals. "The methods and objectives can vary greatly and prudence is required," explains Michael Balls. "It could be possible, for example, to imagine a transgenic ewe whose milk contains a protein of interest. The milk would be collected, the protein extracted, and the ewe would not be affected. A totally different approach involves producing animals possessing the desired genetic message to develop a human disease, such as cancer. Such an approach could lead to progress in research into the disease. But this does not alter the fact that we must consider the welfare of animals on a case-by-case basis. My personal hope is that in the future we will not have to use them at all. This implies persuading an increasing number of scientists that such an approach is well founded and that we must pursue our work so that this desire can become a reality."

(1) London, Methuen, 1959


Contact

Michael Balls
michael.balls@jrc.it

EU-backed alternatives

Upstream of the validations coordinated by ECVAM, the European Union also supports various research projects aimed at developing alternative methods to animal experimentation. Some 15 projects - focusing in particular on the development of tests based on cell or tissue cultures - were carried out under the Fourth Framework Programme. New methods are currently being encouraged under the Quality of Life and Management of Living Resources programme. Also, the dissemination of in vitro techniques is being encouraged by the IVTIP (In Vitro Testing Industrial Platform), a group of Europe's leading pharmaceutical and cosmetics companies.
At the Bologna congress, Epiflow - developed by Professor Pfaller's team at the Institute of Physiology, Innsbruck University, and supported by the EU - won a prize of 2,000 dollars, an award made by the RIVM (Netherlands National Institute for Public Health and the Environment) and the ICAAT (Institute of the Centre for Alternatives to Animal Testing) to encourage the development of alternative methods. Selected from the 200 projects presented, the Epiflow project developed a new cell culture system using a continuously changing environment and a constant gas supply. The process developed makes it possible to maintain primary cultures of differentiated cells during much longer periods than conventional systems, thereby permitting tests of chronic toxicity. The device also makes it possible to produce co-cultures of two different types of cell.

European directives

European Directive 86/609/EEC on the protection of animals used for experimental and other scientific purposes stipulates that the Commission and Member States must encourage research aimed at developing and testing other techniques able to provide the same level of information as that obtained by experiments carried out on animals, but which use fewer animals or less painful procedures. Although Member States must provide the Commission with certain statistical information on the use of animals for experimental and scientific purposes, it was not until 1997 that the national authorities responsible for implementing the directive reached agreement on a body of harmonised statistical data. Present figures (1996) therefore continue to reflect approaches for which it is difficult to obtain genuinely comparable information.
There is also an earlier directive (76/768/EEC) on harmonising Member States' legislation on cosmetic products. This stipulates, through recent amendments, that Member States must ban the marketing of cosmetic products containing ingredients or combinations of ingredients tested on animals since 1 January 1998. Its application - postponed until June 2000 - remains subject to the development of methods able to adequately replace animal experimentation and scientifically validated as providing the consumer with an equivalent level of protection.

     
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