The 6th World Congress on Alternatives and Animal Use in the Life Sciences, to be held in Tokyo in August 2007, will provide an international showcase for ideas, case-studies, technologies and practices that will both enhance biomedical research and make better provision for animal welfare. If you wonder why you or your colleagues should attend or participate, then read on. General Principles Although for some people animal welfare may be considered to be the primary reason to devise and implement improved research methods, the benefits to science and, through the resulting scientific progress, the benefits to society are the main reasons for the scientific community to celebrate and publicise its successes and continue to make progress in these areas. It is generally accepted good animal welfare and good science are inseparable; that one of the hallmarks of good science is that scientifically valid, reproducible experiments seek to identify and eliminate unwanted variables; and that the primary effects directly attributable to the controlled experimental variables can be confused with secondary and tertiary changes if other variables or animal welfare issues are unrecognized or uncorrected. I am clear in my own mind that what are often considered to be 'alternative methods' are in reality 'advanced methods': "alternative" suggests only the animal welfare issues are being addressed - "advanced" emphasises the scientific progress they represent and make possible. Four key concepts have shaped my thinking in this area. …
This review paper will discuss some of the opportunities for three Rs approaches in the production and quality control of immunobiologicals. Major products in terms of animal use are the polyclonal antibodies(Pab), monoclonal antibodies (Mab) and vaccines. These categories of products are also characterized by the high percentage of experimental procedures that involve substantial pain and suffering to the animals. Nowadays a wide range of approaches and test methods are available that are able to substantially refine, reduce and replace animal use. These include for instance the use of humane endpoints, replacement of challenge procedures in vaccine potency testing by serological approaches or the replacement of ascites production in Mab production by in vitro techniques. Although total replacement of animals for production and quality control of immunobiologicals will not be possible within the near future, it is concluded that substantial three R's progress can be made quite easily without the need for exorbitant human and financial resources.
The use of human tissue in drug discovery and development is now well accepted, however, its use for experimental purposes is still restricted not only by practical, but also by ethical and legal constraints. The UK government, through its Human Tissue Act 2004, is leading the way in establishing clear ethical and legal guidelines that will both facilitate and regulate the process. It has also set up a Human Tissue Authority, whose task is to establish codes of practice to regulate all aspects of the Act. The Act emphasises donor anonymisation, freely given informed consent, independent ethical review and the licensing of tissue banks. The UK's approach could serve as a model for this important, but still contentious, area of activity worldwide. With the expansion of the availability of human tissue for research, it will undoubtedly eventually become a mandatory part of the regulatory filing for new drugs. This may well first be seen in the testing of cross reactivity of new therapeutic antibodies, for which the FDA has already identified a set of tissues against which they are to be tested. It is timely therefore that the development of frozen tissue microarrays looks to make this a simple and routine operation.
Although cells live in three-dimensional environments which consist of neighboring cells and cells' own extra-cellular matrices (ECMs), so far Cell Biology restricted itself to only two dimensions of Petri dishes. However, micromechanical strains on cell surfaces significantly differ on Petri dishes from that in ECMs. It is now possible to culture most cells in three-dimensional environments using a chemically defined synthetic matrix peptide, PuraMatrixTM, and this will change the face of basic research and in study areas where animal models have been traditionally used. An example of hepatocyte culture is described.
Using 3-dimensional cultured human skin and epidermal models, an alternative to skin irritation testing have been developed. In the ECVAM (European Centre for the Validation of Alternative Methods) validation protocol, hazardous chemicals have been identified using these models. We considered it likely that these models would also be useful for examining the dose-response of the toxicity of a chemical. Therefore, we used the epidermal model (LabcyteTM, Japan Tissue Engineering Co. Ltd.) to evaluate the dose-response of cytotoxicity and compared the findings with those for irritancy by human patch testing of 4 chemicals: sodium lauryl sulfate, benzethonium chloride, nonanoic acid and propylene glycol. The cytotoxicity of the chemicals was found to be stronger than the irritancy shown by human patch data. Difference ratios ranging from 1.4 to 52.7 were found between irritancy and EC50(concentration causing a 50% reduction in the MTT assay compared to the untreated control value) in LabCyteTM for 4 chemicals and solvents. We consider that these models are useful for evaluating the dose-response of skin irritancy, and could be used to establish a database for risk assessment of chemicals.
Animal experiments are an integral part of the pharmacology teaching at medical schools in India. Various medical schools in India, and rest of the world, have either introduced alternatives to these experiments or are debating the issue. There have been very few studies that have tried to define the relevance of these experiments and report the attitude of the medical students towards them. This survey aims to assess the attitude of undergraduate medical students towards animal experiments and alternatives to these experiments, in the process trying to explore the issues pertaining to their relevance. A questionnaire based survey was conducted amongst second professional medical students at Government Medical College, Amritsar, India. Questions explored various aspects of animal experiments in pharmacology teaching and provided a platform for expressing views on alternatives to animal experiments. Majority of the students understood the importance of animal experiments in pharmacology but did not favour the use of animals in medical education. There was a strong opinion against the sacrifice of animals for these experiments. There was a strong wave in favour of reducing the number of animals involved in experiments apart from the various other alternatives suggested.