The concept of alternatives to the use of animals in research is not only espoused by animal welfare groups but required by federal law. The US Government Principles for the Care and Use of Animals Used in Testing, Research and Education state in part that “…Methods such as mathematical models, computer simulation, and in vitro biological systems should be considered.” Public Health Service Policy endorses this principle and the Guide for the Care and Use of Laboratory Animals states that the ‘availability or appropriateness of the use of less-invasive procedures, other species, isolated organ preparation, cell or tissue culture, or computer simulation’ must be considered in the preparation and review of animal care and use protocols. The Animal Welfare Act states in section 2.31 “…(ii) The principal investigator has considered alternatives to procedures that may cause more than momentary or slight pain or distress to the animals, and has provided a written narrative description of the methods and sources, e. g., the Animal Welfare Information Center, used to determine that alternatives were not available…”. USDA Animal Care Policies 11 and 12 further refine this by defining what constitutes a painful procedure and what should be included in a narrative describing an alternatives search.

What are Alternatives?
The use of animals remains necessary except where valid scientific methods are available. The concept of alternatives was originally put forth in The Principles of Humane Experimental Technique by Russell and Burch (1959). In this book, the authors proposed three categories now commonly referred to as the “3 R’s”. These principles are:

Reduction – To minimize the number of animals used in a research protocol; to reduce the number of animals used to obtain information with statistically relevant results.

Refinement – Use of techniques that reduce the incidence or severity of pain and/or distress* in those animals that are used.

Replacement – Substitution of a lower species that may be less sensitive to pain and distress for a higher species or substitution of non-animal methods or material for animals.

There are a number of useful web sites that can help instruct faculty, staff and students in the art of performing an alternatives search. Some are listed below.

Search Terms and Strategies for Information on the Three Rs - FRAME - The most descriptive, one stop web site for alternatives searching, it discusses from start to finish why and how to perform a search for alternatives.

Tips for Searching for Alternatives to Animal Research and Testing – Animal Welfare Information Center, hosted by the USDA

Searching for Alternatives to Painful Procedures Used on Research Animals - NIH Library

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Possible search terms for the 3Rs (these are not all inclusive)

General guidelines for first step - combine proposed animal testing procedure(s) with:

Alternative(s) +/- animal testing
assay
method
model(s) or animal model(s)
replace
replacement
surrogate system
system
technique

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Refinement - 'animal' combined with one or more of the following terms:

Reduction in the number of animals - with or without 'animal' or 'species'

Replacement of animals with non-animal alternatives

Computers +/-

Physicochemical Systems

In Vitro Systems - appropriate combinations of the following:

Non-mammalian organisms

Databases

The Interagency Coordinating Committee on the Validation of Animal Models (ICCVAM) - The site provides information on models that have been validated, those under development, and how the process of validation works.

MEDLINE – National Library of Medicine's premier database covering biomedical literature, related life sciences and research. Coverage: 1966-present.

NORINA - database on alternatives to animals in education

TOXNET - A cluster of databases on toxicology, hazardous chemicals, and related areas.

Web of Science - A collection of multidisciplinary citation databases, including Science Citation Index; the information includes the article's cited reference list and allows cited reference searching. Coverage: 1975-present

Zoological Record - A subset database of BIOSIS. Zoological and animal science literature covering all research from biochemistry to veterinary medicine; references are from international serial publications, books, meetings, reviews and other non serial literature. Coverage: 1978-present