CAAT Newsletter: Vol. 13, No. 2, Winter 1996

IACUCs and AWIC: The Search for Alternatives

By Tim Allen and D'Anna Jensen

[Mention of commercial enterprises or brand names in the following article does not constitute endorsement or imply preference by the U.S. Department of Agriculture. The views expressed by the authors do not necessarily represent positions or policies of the U.S. Department of Agriculture or any agency thereof and should not be interpreted as such.]

Do we see some veterinarians still pursuing the methods of the ancients and perpetrating pain on a helpless subject... The result has been, and the feeling still exists, largely among the laity, that we are a hard-hearted profession...

A modern day diatribe by animal activists? Not really. Those words were written by Dr. J.P. Turner in the Proceedings of the American Veterinary Medical Association in 1899. He was lamenting the fact that many of his colleagues were resisting the use of anesthetics to restrain animals during surgery in favor of hobbles and rope tie-downs, "the accustomed way, or the methods we were taught." While things have certainly changed, it is still not uncommon to hear "that's the way we've always done things."

However, with the passage of the Improved Standards for Laboratory Animals Act in 1985, Congress let it be known that it is concerned about the use of animals in painful procedures. Under this law, scientists performing painful experiments on animals must document if there are alternative methods to the painful procedure and report this information to the Institutional Animal Care and Use Committee (IACUC) when they submit their animal use protocol form for approval. It is then the responsibility of the IACUC to determine if the alternative methods should be used.

To assist IACUCs and investigators in complying with this portion of the law, Congress established the Animal Welfare Information Center (AWIC) at the National Agricultural Library. In the next few pages, we will look at the critical role that IACUCs play in the animal use approval process, especially the problems associated with documenting whether or not alternatives exist, and how AWIC can assist members of an IACUC and/or scientists.

The U.S. Department of Agriculture views alternatives with an eye to the 3R's concept so eloquently described by W.M.S. Russell and R.L. Burch in The Principles of Humane Experimental Technique--reduction of animal numbers, refined procedures to minimize or avoid pain, and replacement of animals with non-animal models. According to the Animal Welfare Act (AWA) regulations (9 CFR § 2.31(d)), "the IACUC shall determine that the principal investigator has considered alternatives to procedures that may cause more than slight pain or distress to the animals, and has provided a written narrative of the methods and sources used to determine that alternatives were not available."

The IACUC is also responsible for ensuring that the proposed research does not unnecessarily duplicate other research. Along with several other items, AWIC considers these the information requirements of the act (the other sections being scientific justification for withholding anesthetics or analgesics, or using animals in more than one major operative procedure from which s/he is allowed to recover)

While the regulations seem fairly straightforward, it has been our observation that many people are unsure exactly what an alternative is and are confused as to what information is required to show compliance. There are many opportunities to incorporate alternatives into an experimental procedure; however, many IACUCs and scientists mistakenly assume that only non-animal methods satisfy the definition of an alternative.

Although outside the scope of this paper, some alternatives might include pair-housing of rodents to alleviate the distress of isolation, proper use of analgesics in a post-procedural period, or reducing the volume of a receptor binding assay thereby reducing the amount of animal tissue needed to quantify the reaction and ultimately reducing the number of animals. The point is that IACUCs and investigators need to fully understand that identifying viable alternatives requires more than looking for non-animal models.

Animal welfare regulations require, as a minimum, that an investigator perform a search of the literature in an attempt to identify alternatives to painful procedures. Cynthia Smith, an AWIC staff member, wrote a method paper on searching for alternatives that is an excellent overview of this type of searching. But what is important to realize is that a multidatabase approach is necessary, as an alternative procedure or method may come from outside the specific discipline being studied. For example, if you concentrate on mammalian models for studying Parkinson's disease or diabetes, emerging fish model may be overlooked.

It is also important to conduct the literature search on a case by case basis. AWIC staff often are asked by an IACUC to perform a literature search on a painful procedure outside of the context of an experiment. It is impossible to look for alternatives to something as general as thoracotomies in dogs. Some of the questions that need to be addressed are why is the procedure being performed? What is the expected outcome? Is the procedure terminal? Only with complete information can a search be performed, and the IACUC properly evaluate the literature search. Some IACUCs require attaching a literature search to the protocol with a list of the databases and strategy used to show that a good-faith effort was made to find alternatives.

Many others require only that a box be checked indicating that alternatives are not available or may simply ask for a few key words and the database searched. Still others list AWIC as a source of information on the protocol form leading to many requests for information. Regardless of the system used all are fraught with problems.

When an investigator contacts AWIC for help in completing an alternatives search, we commonly ask them to fax a copy of the protocol to us so that we will have all pertinent experimental information at hand. It is not uncommon to find the statement "AWIC was consulted and no alternatives were found" typed onto the protocol sheet that we are seeing for the first time. Oftentimes it is plain to see that the alternatives search is clearly an afterthought, being performed simply to comply with the law. The most common refrain is, "I'm turning in my protocol tomorrow, and I see that I have to have a literature search, can you fax that to me?"

In our roles as members of Federal IACUCs, we routinely see protocol forms filled out stating that a literature search was performed, but, when we ask the investigator to provide us with a copy of the search, it usually has not been conducted. In other cases, the entire concept of alternatives is simply ignored by both the IACUC and the investigator. Are these examples the norm? Maybe not, but they occur often enough that there clearly is a problem with IACUC oversight of this particular part of the regulations.

Comments made to us at meetings or workshops reveal that many scientists and IACUC members view the alternatives search as unnecessary government intrusion into the research process, and not as a resource that might enhance or improve their research. Not surprisingly, a Department of Agriculture report on enforcement of the AWA by the Animal and Plant Health Inspection Service, Regulatory Enforcement and Animal Care (REAC), found that IACUCs do not always meet the standards of the act and that this is attributable to the fact that committee members are not always aware of the act's requirements. Two of the major deficiencies noted are failure to properly address the use of alternatives and failure to provide written assurance that activities are not unnecessarily duplicative.

With these problems fresh in mind, what can or does AWIC do to help animal care committees comply with the law? AWIC was established to provide information pertinent to employee training, to prevent unintended duplication of animal experimentation, to reduce or replace animals used in painful experimentation, or on refined methods to minimize pain to animals when no other model can be found.

To help IACUCs, investigators, and animal research support people understand the alternatives section of the regulations, AWIC staff developed a two-day workshop called "Meeting the Information Requirements of the Animal Welfare Act." The workshop provides an overview of the Animal Welfare Act looking specifically at the information requirements, Federally mandated IACUC functions, criteria for granting IACUC approval for animal research, and the required contents for an institutional training program. A representative from the U.S. Department of Agriculture's REAC staff is also available for a question and answer period.

The workshop also provides an overview of the "alternatives concept," multiple database resources, concepts involved in developing search strategies (but no magic formulas), and, finally, the opportunity to gain hands-on searching experience using the DIALOG database system. The success of the workshop is measured not only by the fact that every class held at the National Agricultural Library is booked months in advance but also by the number of requests we receive to bring the workshop to offsite facilities. Even more importantly, however, are the comments received from people who have taken the training class. The most common sentiment is that the class should be required for all members of IACUCs as it addresses many of the problems common to successful IACUC functioning.

If it is true as Ben Franklin said that an investment in knowledge pays the best interest, then perhaps AWIC's greatest utility to the scientific community is the capability of providing comprehensive literature searches or other information on alternatives, animal husbandry, animal models, philosophical issues, and many other topics related to animal research. When AWIC is requested by an IACUC or an investigator to perform a literature search, the package of information they receive includes the search strategy, the databases searched, and the literature information that documents whether alternatives are available and if the research is duplicative. We may also include a copy of one or two pertinent articles. Many IACUCs, working through institutional libraries, also maintain collections of bibliographies produced by AWIC on topics from anesthesia and analgesia to zoonoses. The AWIC staff also produces a newsletter that covers topics such as environmental enrichment, IACUC communications, alternatives, etc.

How is AWIC able to provide such a breadth of information to such a diverse audience? We owe this ability to a much underutilized resource, the National Agricultural Library (NAL), as well as new technology such as the World Wide Web, and the numerous databases available through services such as DIALOG. The NAL houses one of the largest collections of veterinary literature in the world, and is developing one of the most comprehensive collections of laboratory animal literature.

These materials include NAL's AGRICOLA database, more than 400 videos and slide programs that can be used in institutional training programs, most relevant journals, codes of practice, newsletters, texts, and other published materials such as conference proceedings and abstracts relating to laboratory animals and farm animals used in biomedical research. Because of international exchange agreements, AWIC and NAL also work closely with other agencies providing information or regulatory oversight to animal care committees throughout the world. In this way, we are able to bring a broader perspective to many issues.

In 1996, AWIC is celebrating its 10th anniversary. In its brief existence, AWIC and NAL have worked hard to develop a comprehensive resource to assist IACUCs in carrying out their enormous responsibilities. Animal care committees face many problems in assuring that their institutions are complying with the Animal Welfare Act and the Animal Welfare Information Center is available to help them.

Tim Allen and D'Anna Jensen are information specialists at the U.S. Department of Agriculture, Animal Welfare Information Center, Beltsville, MD USA

For additional information contact the staff at: Animal Welfare Information Center, U.S. Department of Agriculture, Agricultural Research Service, National Agricultural Library, 10301 Baltimore Avenue, Beltsville, MD USA 20705-2351, Tel: (301) 504-6212, Fax: (301) 504-7125, E-mail: awic@nal.usda.gov, WWW: http://www.nal.usda.gov/awic

References

1. Allen, T. (1994). Meeting the Information Requirements of the Animal Welfare Act: A Workshop. Animal Welfare Information Center Newsletter 5(3): 6.
2. Byrnes, C. (1995). Reaching the A-Zone. Science and Animal Care 6(4): 1-2,4.Code of Federal Regulations (1995), Title 9, Part 1, Subchapter A, Animal Welfare.
3. Russell, W.M.S. and R.L. Burch (1959). The Principles of Humane Experimental Technique. Universities Federation for Animal Welfare: Potters Bar, Hertfordshire, England, 238 pp.
4. Smith, C.P. (1994). AWIC Tips for Searching for Alternatives to Animal Research and Testing. Lab Animal March 1994: 46-48.
5. Stokes, W.S. and D.J.B. Jensen (1995). Guidelines for Institutional Animal Care and Use Committees: Consideration of Alternatives. Contemporary Topics 34(3): 51-60.
6. Turner, J.P. (1899). A Plea for the More General Use of Anaesthesia in Veterinary Surgery. Proceedings of the American Veterinary Medical Association Session of 1899, p.103-111.
7. U.S. Department of Agriculture, Office of Inspector General, Audit Report No. 33600-1-Ch, January 1995, 60 pp.