An article in Nature on April 15th, 2015 creates an interesting dilemma for the concept of the 3Rs, but first let’s explain the 3Rs.

The guiding principles in animal research today are called the 3Rs:

  • Reduce the number of animals used to a minimum
  • Refine the way experiments are carried out, to minimize any possible animal suffering
  • Replace animal experiments with non-animal techniques wherever possible.


The number of animals can sometimes be reduced if it is established at the outset of the experiment what is needed to obtain   statistically significant data. . If too few animals are used, then the results of the experiment are not reliable and the experiment needs to be repeated, causing more animals to be used. In some cases, the number of animals can be reduced by using genetically identical animals.


The principal of refinement refers to the use of methods that alleviate or minimize potential pain, suffering or distress, and enhance animal welfare.  Types of refinement can include using non-invasive techniques; adjusting anesthetic and analgesic regimes for pain relief; reducing stress in animals by properly training them to participate in routine procedures, such as a blood draws, or providing suitable, species-specific enrichment for the animal, such as a chew toy, or puzzle.


Much of the focus of the 3Rs has been on replacement. There have been some notable successes, but overall, progress has been slow.

The government group, the Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM), that spearheads the efforts to develop non-animal alternatives in the United States has made some progress, including approved alternative test methods for many types of product safety testing, including the four most commonly conducted safety tests: acute oral toxicity, dermal irritation/corrosion, ocular irritation/corrosion, and allergic contact dermatitis.

The first test method evaluated and recommended by ICCVAM was a mechanism-based assay for allergic contact dermatitis testing that uses fewer animals and eliminates pain and distress compared to the traditional assay. The comprehensive ICCVAM evaluation served a key role in achieving rapid international acceptance and widespread use of this alternative method.

Since that time, ICCVAM has contributed to the national and/or international regulatory acceptance of 27 alternative safety-testing methods, including 17 that do not use live animals.

Now, back to that Nature article.  The article noted that major funders of medical research in the UK now are questioning the reduction of the numbers of animals used in studies.  They wonder if sample sizes are becoming too small to be statistically valid. The consortium has issued a report that states:

All proposals using animals should explain not only the need to use animals and the ethical implications of the planned experiments, but also clearly describe how the planned experimental design is appropriate to give robust results. In explaining the latter, applicants are expected to detail how the number of animals to be used was decided, plans to minimise experimental bias, and provide information on statistical aspects of the study including statistical power and appropriate statistical analysis.

Indeed, a follow-up article in The Guardian noted that unless animal studies are well-designed and use enough animals, then the study is useless, in effect, wasting animal lives. Interestingly, some animal groups misinterpreted the report as a call to end animal use.

What will all of this mean? Well, it’s too soon to tell, but it could have implications for the current interpretation and application of the 3Rs. It could very well mean that the principals of the 3Rs could include, in some cases, using MORE animals in research.





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