Tips for Searching for Alternatives to Animal Research and Testing

AWIC Tips for Searching for Alternatives to Animal Research and Testing

(Edited version of this document published in March 1994 issue of Lab Animal)

Cynthia P. Smith, M.S.
Technical Information Specialist
Animal Welfare Information Center

The following guidelines were developed to assist researchers, information specialists, and Institutional Animal Care and Use Committee (IACUC) members, when conducting literature searches to determine if alternatives to the use of animals exist and whether a protocol unnecessary duplicates previous research. When searching for alternatives, the staff at the Animal Welfare Information Center (AWIC) refer to the tenets of the 3 R's introduced by W.M.S. Russell and R.L Burch(1959) in their book The Principles of Humane Experimental Technique1. The 3 R's represent reduction in the number of animals used, refinement of techniques and procedures that reduce pain and distress, and replacement of animal with non-animal techniques.

The first step in conducting a search for alternatives, involves communication between the investigator and the information specialist. The specialist cannot effectively search for alternatives without a basic understanding of the type of research the investigator is proposing. The most efficient means of communicating is a direct dialogue between the investigator and the information specialist. A third party should not be used to convey information.

Investigators can assist information specialists by being prepared to give precise and specific information about their research or testing procedures. The following may serve as a guideline for the type of information the investigator may be asked to provide:

1. What is your general area of study (e.g., cardiology, neurology, toxicology, etc.)?
   
2. What species are you currently working with (e.g., rats, dogs, swine, etc.)?
3. Briefly describe your experimental protocol.
   
4. What specific systems or parts of the anatomy are involved (e.g., central nervous system, brain stem, parabrachial nucleus)?
   
5. Please give correct spellings of these structures and any acronyms (e.g., CNS, PBN). European spellings are important as well.
   
6. If you are studying the effects of a particular hormone, enzyme, or chemical agent, please give the complete spelling of the compound as well as its trade name and acronym (e.g., bovine somatotropin, BST).
   
7. Do you know of any prominent authors in your area of research? Have you published any previous literature that relates to your current study?
   
8. What makes your study unique from previous studies (e.g., testing a new technique, investigating a new compound, further understanding of a biochemical pathway)?
   
9. Are you aware of any possible alternatives to your research, such as experiments conducted on alternative species, cell culture, or in vitro studies?
   
10. Have you had any other searches conducted for you? If so, what databases were used (e.g., MEDLINE, AGRICOLA, BIOSIS)?
    1. What keywords were used (e.g., kidney, parathyroid hormone)?
       
    2. What years were searched (e.g., 1985-present)?

As with any type of searching, success in retrieving relevant citations will depend directly on the quality of the information provided.

Search Strategy
Once the initial exchange of information has taken place, the information specialist can begin to formulate a search strategy. Search strategies for alternatives may be divided into two phases, reduction and refinement, and replacement.

Phase I (Reduction and Refinement)
Phase I consists of a generalized database search used to retrieve citations pertinent to the investigator's field of study. Citations retrieved during this phase, should provide information on current research, alert the investigator to whether or not they are performing duplicative studies, and possibly provide information to refine experimental techniques.

During Phase I, the information specialist may find it helpful to develop search strategies using databases available on Compact Disc Read Only Memory (CD-ROM). AGRICOLA, MEDLINE, TOXLINE, and LIFE SCIENCES, are examples of several useful databases available on CD-ROM. Searching on CD-ROM allows the information specialist the freedom to experiment with keywords, explore indexes and thesauruses, and read abstracts without the pressure of being charged for online time. If the investigator has published previous literature this is a good time to read abstracts of his or hers previous work and become familiar with terminology used to describe the study and to note what terms were used to index the abstract. Searching on CD-ROM should provide the information specialist with a general idea of how much literature exists on a specific topic. If few relevant citations are found, the information specialist may need to broaden the search strategy or use the expanded capabilities of online database searching to develop the search. If hundreds of citations are retrieved using only a few years worth of bibliographic data, then it is necessary to further consult with the investigator on ways to narrow the search.

Phase II (Replacement)
Upon completion of Phase I, the information specialist should have a basic understanding of the research area including: 1) the literature published in the particular field, 2) the techniques used, and 3) the commonly used species. The information specialist is now ready to search for possible replacement alternatives.

The following questions may be used to assist in the search for replacement alternatives:

• Are there in vitro techniques that may reduce or replace the number of animals used (e.g., chorioallantoic membrane assay, use of primary cultured hepatocytes)?
• Are there any alternative animal models (e.g., invertebrates, fish, protozoa, etc.)?
• Have any computer simulations or statistical models been developed that relate to the study?
• When searching for alternatives, information specialists should search multiple databases. A multidisciplinary approach to searching may yield surprising results particularly for individuals who are not accustomed to searching the literature outside their general area of study, (e.g., Medicine). AWIC provides a factsheet entitled Databases for Biomedical, Veterinary and Animal Science Resources2 that describes a number of useful databases.

  "Animal testing alternatives" is a phrase used to index citations regarding alternatives in the AGRICOLA, MEDLINE, TOXLINE, and CANCERLIT databases. However it is not used to index alternative studies in other databases such as EMBASE, BIOSIS PREVIEWS, LIFE SCIENCES, and CAB Abstracts. Although useful, this phrase should never be the only strategy used to retrieve information on alternatives. Depending on the study, other terms such as tissue culture, cell culture, in vitro, simulation, model, refinement, reduction, or alternative may be used. For a listing of terms that may be helpful when conducting alternative searches information specialists may refer to Animal Welfare Information Center Scope Notes3 available from AWIC at no charge.

It is important to keep in mind that although electronic databases are powerful resource tools, most databases do not index journals before the mid-sixties and relevant information from early studies will not be retrieved. In addition, information on alternatives is available in newsletters, books, and proceedings, which not all databases index.

Sample Search for Alternatives
The following is an actual search that was requested by an IACUC member and a description of the steps that the AWIC information specialist performed. The IACUC member requested a search for alternatives to the use of zona free hamster oocytes to test human sperm penetration, motility, and viability.

After initial information was exchanged about the protocol, a list of keywords were developed. The specialist then conducted a brief initial search on MEDLINE and AGRICOLA on CD-ROM to become familiar with abstracts in which human sperm penetration, motility, and viability were tested. The specialist was aware that extensive tests have been developed to assess semen characteristics in domestic farm species and therefore contacted a farm animal reproductive physiologist for further information. The physiologist confirmed that alternative methods exist to test bovine and human sperm penetration such as a variety of cervical mucus tests. Based on this information the specialist developed the following search strategy.

Databases Selected
Thirty five different biological and medical databases were selected and searched simultaneously including BIOSIS PREVIEWS, AGRICOLA, CAB ABSTRACTS, CRIS, PASCAL, MEDLINE, EMBASE, PHARMACEUTICAL HEALTH CARE INDUSTRY NEWS, LIFE SCIENCES, SCISEARCH and others.

Search Strategy

Set	Items*	Description
1	214550	SPERM OR SPERMATID? OR SPERMATOZOA? OR SEMEN
2	1104759	MOTILITY OR VIABILITY OR MORPHOLOGY OR MOTILE OR VIABLE
3	45369	S1 AND S2
4	42329	S3 NOT HAMSTER
5	1384	S4 AND (MUCUS OR MUCOUS)
6	1049	S5 AND HUMAN
7	364	S6 AND PY=1988:1993
8	191	RD S7 (UNIQUE ITEMS)
9	154	S8 AND (EVALUAT? OR ANALYSIS OR TEST? OR VITRO)
10	94	S9 AND PY=1990:1993
11	2	S4 AND (COMPUTER(2N)IMAGING)

* ITEMS = number of citations retrieved that contain search terms

Sample Titles Retrieved Hyaluronic acid as a medium for human sperm migration tests. Keywords: cervical mucus, spermatozoa, penetration.

Human sperm-cervical mucus interaction using bovine cervical mucus and hen's egg white in the evaluation of male infertility. Keywords: penetration, sperm motility, physiological model, in-vitro test.

The use of hen's egg white as a substitute for human cervical mucus in assessing human infertility. Keywords: penetration, semen analysis, sperm capacity, sperm motility.

Comparison of measurements of human sperm motility characteristics by the automated CELLSOFT system and time exposure photomicrography. KEYWORDS: automated analysis, sperm motility.

In this case, consultation with an expert and review of the literature supported information available on replacement alternatives. If that had not been the case the search may have focused more on refinement and/or replacement alternatives. The IACUC may have asked, what methods are being used to superovulate and flush oocytes from the hamster, how are the hamsters anesthetized during procedures, and what are the fewest number of animals that can be used?

General Comments
Protocols should be evaluated on a case by case basis. A perfect strategy to retrieve every citation regarding reduction, refinement, and replacement does not exist. Many factors may affect the outcome of a literature search, including the area of research, species involved, procedures used, chemical(s) tested, experimental design, and whether or not articles have been indexed. Additional factors include: 1) the degree of communication between the information specialist and the investigator, 2) the knowledge and educational background of the information specialist, and 3) time and money constraints.

References

1. Russell, W. and R. Burch (1959) The Principles of Humane Experimental Technique Methuen and Company, London. 2. Bielenberg, K. and D. Berry. (December 1990) Databases for Biomedical, Veterinary and Animal Science Resources AWIC Fact Sheet. 3. Swanson, J. (March 1991) Animal Welfare Information Center Scope Notes. AWIC Series #6. 8 p.

Additional Resources
Clingerman, K., C. Dowling, and J. Swanson. (June 1990) Searching AGRICOLA for Animal Welfare STS-03. June 1990. 20 p.

Kreger, M. and T. Allen. (October 1993) Electronic Information for Animal Care and Use. Lab Animal 22(10):52-53.

Snow, B. (July 1990) Online Searching for Alternatives to Animal Testing Online p. 94-97.

Note. Mention or use of a trademark does not constitute endorsement by the United States Department of Agriculture.

Return to:
Top of Document
Animal Welfare Information Center
National Agricultural Library

The Animal Welfare Information Center, awic@nal.usda.gov
http://www.nal.usda.gov/awic/alternatives/tips.htm

Last updated October 2, 2001