The Three Rs concept was welcomed in Austria, Germany and Switzerland, after the EEC had accepted Directive 86/609/EEC on the protection of animals used for experimental and other scientific purposes. However, it was implemented quite differently in each of the three countries. In 1985, Switzerland took the lead, because of generous funding by the Doerenkamp-Zbinden Foundation, by focusing on replacing the LD50 test, and in 2002, by establishing five chairs on alternatives in Germany, India, Switzerland, The Netherlands and the USA. In 1989, Germany established ZEBET at the Federal Health Institute (BGA) in Berlin, as the first national centre for alternatives, which significantly contributed to the international acceptance of the first in vitro OECD Test Guideline for local toxicity testing, for phototoxicity. Since 1992, the Austrian government has supported annual international Three Rs congresses in Linz, which are now organised by EUSAAT, the European Society for Alternatives to Animal Testing.

In contrast to animal testing required by law to guarantee minimum safety standards for the licensing of drugs and chemicals, there are no regulations in basic research forcing scientists to perform animal tests. By (usually) free choice, questions are posed and hypotheses are examined which, in many cases, can only be answered by means of animal tests. Just as easily, different questions could be asked or different hypotheses could be examined which do not require animal tests. The only criterion for the choice of a topic is its relevance which cannot necessarily be judged in the short-term. Thus, it is up to the individual scientist to judge what is worth studying and therefore worth animal consumption. The educated mind will consider ethical aspects of this choice. However, on the other hand, this decision is largely influenced by questions of efficacy or (in a negative sense) by the obstacles posed to an animal consuming approach. Here, peer review and general attitude will strongly influence the methodology chosen. Availability and awareness of adequate in vitro techniques represent the prerequisites for the use of alternative methods. The least one can do in basic research is to avoid tests which cause severe suffering to animals, as is required in Switzerland and other European countries by binding ethical principles and guidelines. The increasing standard of approval and control procedures has improved the situation over the years. There are many examples of successful alternative methods in basic research. But, the application of such methods is in most cases limited to the laboratories in which they were developed, calling for technology transfer. Exceptions are procedures that are used worldwide, like the production of monoclonal antibodies, which instead of using the ascites mouse can also be performed in vitro with some good will. In these cases, commercialisation of the techniques has aided their spread within the scientific community. Sadly, many methods, even if published in the scientific literature, are little standardised and reproducible. The suggestion is put forward that publicly accessible databases should make available more detailed descriptions of methodologies. Due to limitations in space, many scientific journals cannot publish detailed methodological descriptions. However, nowadays a supplementary central deposit of methods could easily be linked to the respective article. In numerous cases though, there is simply a lack of will to change procedures to methods without animal tests or to pose questions differently in order to avoid the use of animals or to reduce their number or, at least, to reduce stress. In other cases, researchers are simply not aware of the limitations of the animal experiment as such. A thorough review of the validity of critical animal experiments should be carried out and made available publicly. For example, many animal experiments are dramatically "under-powered", i.e. carried out with groups that are too small to allow conclusions to be drawn from the outcome. This stands in marked contrast to in vitro experiments where replicate experiments usually represent no major problem. Since in vitro models are generally more prone to artefacts due to the numerous variables, e.g. of cell culture, the key requirement for their application is their validation and quality control. Guided by the experience from validation studies for alternative methods in toxicology, concepts of a Good Cell Culture Practice (GCCP) are currently being developed which aim to define minimum quality standards for in vitro techniques. This initiative aiming to increase quality must be complemented by a concept to systematically assess the relevance of the tests in order to finally achieve an evidence-based biomedical research. A change in this direction is only possible if those public funds, which were previously assigned predominantly to alternatives to the animal tests required by law, are now channelled increasingly into developing those for basic research. A financial incentive is necessary to change procedures in basic research to animal free procedures. Ethical considerations alone will bring little movement or change. It is unacceptable that, while numbers of animal tests decrease in development and notification of drugs and chemicals, they are increasing in basic research. Due to the central role of publishing scientific results, the key options for control are the respective rules of journals for the acceptance of articles. By demanding certain standards in the instructions for authors, e.g. of quality (GCCP), relevance and in case of animal experiments proof that no alternative is available, pressure could be dramatically increased. It is suggested to hold a consensus conference of journals in the life sciences on this topic.

In education, it is important that students are not put in a position in which they are forced to participate in animal experiments or to use dead animals, killed especially for such purposes. Continued use of animal experiments to demonstrate known facts or teach skills which can be taught using non-animal methods evidences only a lack of sensitivity towards students who still maintain respect for life. In countries where animal testing in education is reduced to close to zero, there is no evidence that the students who are being trained are less capable or qualified. There are sufficient alternatives available at relatively low-cost and with proven educational efficacy to allow the vast majority of students who study biomedical science courses to qualify without using animal experiments. However, in many universities across Europe, there is still a resistance to adoption of such methods amongst faculty. The global situation is probably worse with animals still being used in high school teaching in some countries such as the USA.

There are positive examples of transgenic animals where transgenic technology has allowed the use of less animals to answer a specific research question. On the other hand, it requires large numbers of animals to produce transgenic strains. And there remains the question, when these animals show clinical signs of disease, if they suffer more or less than their "pretransgenic" counterparts. To what extent transgenic animals further the cause of the 3Rs must be evaluated on an individual basis.

From 1980 until 1991, 98 research projects covering a total amount of 86.1 million German Marks were sponsored by the German Ministry for Education, Science, Research, and Technology in a research grant programme for the promotion of alternatives to animal experiments. The German Ministry for Education, Science, Research, and Technology appointed the German foundation SET (Foundation for the Promotion of Research on Replacement and Supplementary Methods for the Reduction of Animal Experiments) to carry out an essay on the efficiency of this grant programme. This essay was done with the help of a questionnaire that was to be filled out by the project managers on a voluntary basis. 23 of the 98 projects had not been completed by the time of the survey. Not all of the questionnaires returned were suitable for the purposes of the study. Therefore only projects covering 73.7 million German marks of the total grant amount were evaluated. According to their research subjects, the research projects were classified by the following categories: Reduction of distress or of the number of laboratory animals used in an experiment (5.9%); reduction of the number of animals by performing an animal free method before the animal test (38.8%); replacement of animal test by an animal free method (24.7%); basic research (20%); promotion of its acceptance by optimisation of an animal free method (8.2%); and validation of an animal free method (2.4%). It is remarkable that not even half of those projects that were performed with the goal of reducing the number of laboratory animals mentioned any success concerning this goal. There were large differences between industrial research projects and non-industrial research projects (universities, state-owned and private research institutes): The main goals of industrial projects were "reduction of distress or of the number of laboratory animals used in an experiment" and "reduction of the number of animals by performing an animal free method before the animal test"; whereas the main goals of university projects were "replacement of an animal test by an animal free method" or topics covering basic research. In 17 projects (grand amount 13.1 million German Marks) of the latter category a reduction of the number of laboratory animals was not to be foreseen; 13 of these projects were pursued at universities. Due to a change in the policy of the grant programme, no project of this category was sponsored after 1989. The reason for the very small number of projects on the validation of alternative methods might be that almost no more validation studies are performed on a national level; instead they are coordinated internationally.