Improving Quality with the 3Rs

James Vitale

Friday, September 15th, 2017

Designing your animal model studies with the 3Rs in mind — Replace, Reduce, Refine — is not only more humane, but can measurably improve the quality and efficiency of your research projects.

When we think of improving quality in the life sciences, we might immediately jump to poorly calibrated equipment, expired reagents, or utilizing unvalidated processes. It is obvious that these will have a negative effect on research outcomes, but what about the quality of your animal models?

Animal models are just as prone to quality issues as reagents or equipment. Some of those issues may be obvious, such as the presence of pathogenic or opportunistic organisms, but there are several serious issues that all too often go unaddressed in study design.

Could the 3Rs be the key to improving quality and efficiency in animal model research?

The 3Rs

The 3Rs — Replace, Reduce, Refine — can be used effectively to help drive quality improvements. They were proposed in The Principles of Humane Experimental Technique, written by W.M.S. Russell and R.L. Burch in 1959¹.

Russell and Burch sought to limit the suffering of laboratory animals used in experiments. They recognized the value in using animals in life sciences research, but they also recognized that animals are sentient beings; anything we could do to remove distress for these animals would improve both the ethics and effectiveness of our research.

Russell and Burch defined the 3Rs as follows¹:

Replacement means the substitution of conscious, living animals with insentient material where possible.
Reduction means reduction in the numbers of animals used to obtain information of a given amount and precision.
Refinement means any decrease in the incidence or severity of inhumane procedures applied to those animals which still must be used.

The 3Rs Revisited

In 2015, Jerrold Tannenbaum and B. Taylor Bennett wrote an extensive expose' published in the Journal of the American Association of Laboratory Animal Science, Russell and Burch's 3Rs Then and Now: The Need for Clarity in Definition and Purpose². Their article discusses Russell and Burch's original definitions of the 3Rs and suggest that some modern 3R definitions have strayed from their original intent.

While these contemporary definitions may be valid in their own right, they differ in one key respect. Russell and Burch did not seek an absolute end to use of animals in research, but rather to decrease distress in those animals in support of higher-quality results.

Tannenbaum and Bennett highlight Russell and Burch's view on how the 3Rs can improve quality in studies using animals:

"Importantly, however, Russell and Burch also maintain that there is a convergence of high-quality research and the use of the 3Rs to minimize inhumanity [emphasis added]. They proclaim that "it is widely recognized that the humanest possible treatment of experimental animals, far from being an obstacle, is actually a prerequisite for successful animal experiments...the intimate relationship between humanity and efficiency in experimentation will recur constantly as a major theme in the present book". Many discussions in the Principles seek to demonstrate that experiments achieve better scientific results when animals experience no distress or the least possible distress consistent with experimental aims. By "efficiency," Russell and Burch also mean generating maximum scientific or medical results from expenditures of monetary and animal resources, facilities, and personnel. They maintain that such resources are often wasted, or do not achieve the best results, when animals suffer distress unnecessarily²."

Note the connection between the 3Rs, aimed at reducing distress, and attaining high quality results.

3Rs and Quality

By considering the 3Rs when designing animal studies, you can drive quality improvements while eliminating unnecessary suffering. Consider the following while designing your next in vivo study:

Is an animal model required for my study?
What is the best animal model for my study?
What is the minimum number of animals required to attain statistically valid results?
Is there a refined genetically engineered model that would allow a reduction in the number of animals required for my study?
Are there refinements in methodology that would reduce distress in the animals, leading to higher quality results?

Available Resources

There are many resources available to help you with this exercise, starting with your attending veterinarian or IACUC.

These websites can support your efforts to design higher-quality animal model studies:

National Center for the Replacement, Refinement & Reduction of Animals in Research (UK)
Understanding Animal Research
Center for Alternatives to Animal Testing (Johns Hopkins University)
AAALAC international
3Rs Microsite (Canada)
Online version of The Principles of Humane Experimental Technique

Obtain the Taconic Biosciences Infographic:

The Power of Laboratory Mice

Read the Other Related Taconic Insights About the 3Rs:

References:

1. Russell WMS, Burch RL. 1959. (as reprinted 1992). The principles of humane experimental technique. Wheathampstead (UK): Universities Federation for Animal Welfare.

2. Jerrold Tannenbaum and B. Taylor Bennett, Russell and Burch's 3Rs Then and Now: The Need for Clarity in Definition and Purpose. J Am Assoc Lab Anim Sci. 2015 Mar; 54(2): 120-132.

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