Enfermedades y su control

“An experiment shall not be performed if another scientifically satisfactory method of obtaining the result sought, not entailing the use of an animal, is reasonably and practicably available.”

Directive 86/609/EEC

The alternatives to animal experiments include better use and dissemination of information; computer-based systems; physico-chemical techniques; microarrays; cell, tissue and organ cultures; human studies; and lower organisms and embryos141_{. In some situations, these may}

reduce the number of animals used for experiments or reduce the stress which animals are subjected to rather than replace the experiments altogether.

• Effective use of information: Good dissemination of results can reduce the numbers of

duplicate experiments which are carried out. The integration of historical information and information gathered from human subjects into risk assessment, and the use of analytical tools such as decision networks or ‘parallellogram approaches’ could both improve the accuracy of predictive systems142 _{and reduce the number of animals used.}

• Computer-based systems: Developments in computer modelling have revolutionised drug

development. For example, protease inhibitors used as part of the AIDS triple therapy were developed through computer modelling, which is one of the techniques being used to develop further AIDS therapies141_.

• Physico-chemical techniques: The first chemical substitution of an animal toxicity test was

announced in March 2000143_{. Corrositex, a chemical mixture on a collagen matrix, serves as}

a synthetic skin. Chemicals are placed on this rather than on a rabbit. Once the chemical penetrates the barrier, it causes a colour change. The time taken results in the corrosivity classification. If a ‘non corrosive’ result is forthcoming, an animal test follows. Many

cosmetics companies now use a proprietary reagent to predict the potential of chemicals to irritate the eyes141_.

• Microarrays: The development of microarrays - plates coated with a variety of genes linked

to marker systems which indicate when they are activated - to determine whether genes are activated are showing potential in drug screening for toxicity144_.

• Cell, tissue and organ cultures: Cell cultures could be used extensively for toxicity testing

(see below)130_{.There are also instances where in vitro systems can be used as disease}

models. It is important that human cell lines and tissues should be used to avoid the problems of extrapolating from one species to another which undermine the usefulness of animal models. The Dr Hadwen Trust is funding research into cell culture research on various diseases including meningitis, liver disease, breast cancer and cataracts146_.Since

1990, the USA National Cancer Institute has screened 60,000 potential cancer drugs on 60 human cell lines145 _{after a twenty-five year animal screening programme failed to yield a}

single human drug128_.

• Human studies: Human studies offer the best information on human disease. These

include a wide variety of methods - clinical studies of patients, autopsy, epidemiological studies, drug testing using healthy volunteers and volunteer patients, and rigorous reporting on initial release. New techniques for scanning and imaging allow non-invasive methods for gaining accurate information.

• Lower organisms and embryo stages: Bacteria, plants, and insects can all be used in

some instances, particularly for toxicity testing. The Ames Test for genotoxicity, which has been validated and accepted for screening, uses Salmonella bacteria. Hydra are currently being used for research into diabetes146_.

Animal disease models are the most difficult application for which to find alternatives. However, reliance on animal models may not be the most effective way to discover human therapies and the concentration on experimental animals may lead to under-funding of clinical research. The situation is very different for safety testing, where alternatives already exist which may have greater predictive value than animal tests:

“…many of these novel, advanced, in vitro approaches result in information which is often more relevant than animal studies for human hazard assessment, due to their use of human-derived proteins, cells and tissues.”

Pfaller et al, 2001130_.

The current animal safety tests are beset with problems and the need for new tests has been recognised. Non-animal alternative tests are already in existence or could be developed. The requirements for testing can be met by in vitro systems with the added advantage that results can be obtained for a much wider range of doses and should be more easily reproducible130_.

The decision to use transgenic animals, once enshrined in regulations, would result in their continued use for a long time – regardless of whether it offers the best method. Test regimes

have persisted for many years despite poor applicability to humans. A good example is the Draize test, in which potential eye irritants are tested in rabbit’s eyes. An interlaboratory study in 1971 demonstrated that test results were extremely variable both day by day and between different laboratories147_{.Another study showed that the correlation between rabbit and human eye}

responses was extremely poor - only 0.5148 _{- so tossing a coin could produce results with as much}

value.It has been stated by personnel from the US Food and Drug Administration that there is no clear relationship between rabbit and human eye responses149_{. Despite all this, the test is still in}

routine use today.