The Danish 3R-Center thinks that a broader understanding of the concept of Replacement of experiments on animals is needed

The Board of the Danish 3R-Center

Sixty years have passed since William Russell and Rex Burch introduced the 3Rs in The Principles of Humane Experimental Technique (1959). The principles have been particularly successful, considering that they are currently integrated into animal research legislation in many countries.

Quite a number of scientific reports conclude that the volume of information currently obtained per laboratory animal used is far greater than was the case in 1959, which is one of the fundamental features of Reduction. The housing of laboratory animals has also vastly improved and procedures have become more humane, resulting in Refinement. In addition, a number of routine tests for safety assessments of chemicals and drugs have been superceded by non-animal methods, leading to Replacement. Approval procedures for new chemicals and medicines have also begun to utilise non-animal methods. This is exemplified by the adoption by the OECD (which harmonises testing guidelines) of the Adverse Outcome Pathways concept, specifying guidelines for mechanistic studies without laboratory animals. The Danish 3R-Center expects to see great benefits from sharing of experimental findings to maximize the level of knowledge.

Yet research itself has changed, too, and research results are in far greater demand today than previously. Basic research at universities and the initial develop ment of new candidate drugs are areas that are particularly increasing in scope. These types of research are based far less on routine trials that repeatedly use the same laboratory set-up. Accordingly, there is still a great demand for targeted projects to implement the 3Rs, and for research into non-animal methods to make it possible for the more formative experiments in basic research to be replaced with non-animal methods as well.

Basic research and development is usually founded upon on a scientific question that seeks to be answered, after which an experiment that can answer the question is planned from scratch. Since no one else has probably answered the question previously, there is usually no previous experiment to which a new experiment can be considered to be a direct alternative. Therefore, the use of non-animal methods will largely be dependent upon the researcher, and not least the researcher’s organization, who have multiple options when attempting to answer a research question. This means that a researcher will not only tend to think along the lines of animal research. The entire palette of research methods, including cell cultures, computer simulation and interdisciplinary analyses of research data, should therefore be considered whenever research questions need to be answered in basic research.

The concept of Replacement, as defined by Russell and Burch in 1959, i.e. substituting a single well-defined experiment on animals with a similarly well-defined experiment without animals, cannot at present be considered to be the only indicator if there is an overarching wish to obtain more knowledge using fewer animals in the most basic areas of research. This means that society, institutions and companies conducting the research and, not least, the Danish 3R-Center, need to support in a wider sense an existing infrastructure which addresses research questions using non-animal methods. These methods must be fundamental to the mindset of a research organisation. Accordingly, the Danish 3R-Center aims to widen the extent of its activities to support not only positive trends in the sector which conducts experiments on
animals, but also in the communities which, in an overarching perspective, have the capacity, expertise and infrastructure to answer research questions without experiments on animals. The Center’s vision is that from
now on researchers will include a wide range of options when planning how to answer specific research questions, gradually enlarging their experience base and thus narrowing the area within which animal experiments are deemed to be the best way to answer the question concerned.

Replacement vs non-animal methods

There seems to be some uncertainty about the concept of replacement in laboratory animal milieus. Therefore, it may be relevant to attempt to clarify the issues inherent in replacement and non-animal methods, respectively.


Russell and Burch defined replacement as follows: Replacement means the substitution for conscious, living higher animals of insentient material.

The Danish 3R-Center’s definition: Replacement of conscious higher animals with an ability to perceive external stimuli with insentient material, i.e. without an ability to perceive external stimuli. Replacement entails substituting experiments on live animals, covered by the Animal Research Act, with experiments that do not use whole, live vertebrates.

Thus, replacement involves the actual substitution of an animal research model, which is why replacement is only an option for someone who already conducts experiments on animals. It is only by using an animal-based model that the user of laboratory animals becomes aware of possible alternative methods (replacement) to the animal model or that he/she attempts to develop an alternative method (replacement) to his/her animal-research model.

If the researcher successfully develops such a model, and it is otherwise validated, the method will now be deemed a non-animal method, i.e. it will no longer be considered replacement.

Non-animal method

When a researcher is about to engage in a research task relating to animals, people or the environment, he/she should select the best model available, whether is a non-animal method or an animal model (If an alternative replacement to the animal model exists, this must obviously be chosen).

One or more non-animal methods can supplement one or more animal models, thereby reducing the use of laboratory animals. Each individual method/model provides the answer to smaller parts of the overall research task.


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