Welcome to the inaugural issue of the UC ALERT, a publication of the UC Center for Animal Alternatives (UCCAA) at the University of California, Davis. This center was established within the University of California system in November 1991 following a three-year planning process. The role of this new center is to facilitate information access and exchange concerning alternatives to the use of animals in research, teaching and testing. The Center's charge is to complement similar efforts along these lines occurring elsewhere throughout the United States and the world.

This newsletter is directed to several audiences who share interests and involvement in the use of animals in research, teaching, and testing. Within the campus communities, faculty in the biological sciences, animal care staff, librarians, and persons working in news and public relations have interests in alternatives to the use of animals; off-campus, people working in libraries and public schools will find this information useful. UC ALERT reflects this broad readership and includes articles of general interest, as well as those directed to one specific audience.

The Center for Animal Alternatives builds on the concept of alternatives establishment in 1959 by W. . . Russell and R. . Burch, simply expressed as "(I) replacement, reduction and refinement ...the 3Rs.(/I)" Russell and Burch drew attention to the importance of avoiding disruptions to the comfort and well-being of animals while still finding methods to yield the information or results being sought in the research, teaching, or testing context. Because much attention is already directed to replacement and reduction methods in the uses of animals, the CAA is focusing specifically on refinement--factors affecting the well-being of animals. This is especially appropriate given the access to the resources of the UC Davis campus, including the largest number of faculty engaged in the study of animal behavior of any UC campus. Studies of animal ehavior make it possible to more accurately evaluate what constitutes well-being from the animal's perspective, rather than simply from a human's viewpoint.
 

The importance of alternatives for use in teaching.

Education and teaching are at the heart of higher education's reason for being. The university's mission is to achieve excellence in teaching, sometimes involving the use of animals. Teaching comprises one of the most repetitious uses of animals. New students appear each time a particular course is taught, and the animals involved in instruction are required each time the course is offered. When an appropriate alternative becomes available, it can be used not only for instruction in that particular course, but could conceivably be accessible each subsequent time the course is taught, replacing the use of animals many times over.
 

How do teaching alternatives come about? Not surprisingly, faculty who teach are thinking about other ways to aid students in learning about biological organisms. Very little funding is available to design new alternatives for teaching; yet many faculty, in developing their own teaching materials, have created and are creating new methods for teaching that employ alternatives to the use of animals.
 

The UC Center for Animal Alternatives is well-situated to catalyze the attention and information exchange necessary to the development of teaching methods that aid learning by employing alternatives to the use of animals. At the School of Veterinary Medicine, many of our faculty have found new and creative ways to teach students anatomy and physiology. At times, they have invested "from their own pockets" to create new resources. And, of course, many faculty at other institutions are engaged in creating alternatives. Increasingly, these are highlighted in special issues of professional journals and in sessions of conferences.
 

We still have far to go in acknowledging the value of these creative accomplishments that benefit faculty and students everywhere. More appreciation and incentives are needed for faculty who develop teaching alternatives.
 

Contexts for animal use.

Animals are used to provide information concerning biological organisms and processes, including anatomy, physiology, and behavior. In research, the effort is to gain new information about biological organisms. In teaching, the objective is to help the student gain knowledge and "ands-on" skills concerning biological organisms. In testing, the objective is to gain information regarding the efficacy and safety of new pharmaceutical, cosmetic, or household products.
 

There are many relatively non-controversial uses of animals in research and teaching. When there is no intrusion or discomfort for the animal, it can be assumed that there is no reason to seek an alternative. For example, field or laboratory observations of animals could be conducted with minimal intervention. Once an animal has died, using and re-using its preserved parts for research or teaching may constitute a desirable alternative. Using photography or realistic, synthesized models or analogs of animals are other methods for creating teaching devices. A list of examples of alternatives currently in use at the School of Veterinary Medicine is provided in the article "Alternatives to the Live Animal Model" by Ann Birkhaus in this issue.

Animal Alternatives in the University of California System.

Concerning animals, some UC campuses emphasize the humanities and others are strong in the sciences. A few highlights within the UC system are discussed here, since each campus is paving new ground to improve animal care.
 

Animal care and the IACUC.

The offices of campus veterinarians oversee animal care on each campus. Protocols for animals to be used in research or teaching are submitted by scientists or faculty and evaluated by each campus's animal care and use committee. Committees range from ten to twenty members and include a cross-section of faculty, a representative from the veterinary staff, and an outside member.
 

The veterinarians and their staffs on the various UC campuses are responsible for diverse numbers and species of animals, as well as the physical arrangement of the animal housing. The centralization of animal care supervision to permit the veterinary staff more convenient daily access for monitoring animals is the focus of current changes. The veterinary staff is involved in the initial stages of any new procedure, closely monitoring new techniques or treatments. From time to time, UC veterinarians meet with California veterinarians through their state organization, California Laboratory Animal Medical Specialists (CLAMS), to discuss new developments in the field of animal care.
 

Each campus has developed programs for regular training of all personnel involved in handling animals. At UC Davis, the training program of the Office of the Campus Veterinarian is formalized in a series of courses and lectures that are announced regularly in Animal Research News. A laboratory technician course involving lecture, discussion, and demonstration covers the fundamental principles of laboratory animal science. Laboratory animal skills classes are also offered regularly. To apprize scientists, research technicians, animal technicians and other personnel involved with animal care concerning the relevant laws and regulations, a brief seminar is offered at the beginning of each quarter and is required of all students who work in laboratory animal facilities.
 

Finally, the UC San Francisco animal adoption program initiated in 1982 has been particularly rewarding to the animal care staff. Investigators who wish to adopt out animals at the end of a study request that the animal be medically and temperamentally tested. When appropriate, these animals are made available for adoption. Jan Wyrick, DVM, can provide more detailed information about this program at UCSF.
 

Library and Information Services.

Since the National Institutes of Health now requires that protocols for funded projects involving animals include verification that a literature search was made for alternatives to the use of animals, the science libraries are becoming more directly involved in animal studies.
 

Efficient methods for information retrieval are more important than ever in this age of rapid information technology. Librarians are the invaluable link to locating key information. Through their knowledge of specific databases, they can provide a rational road map for finding the needed information. Scientists in partnership with librarians can determine whether other disciplines may be developing methods that can be used in place of animals.

It became clear at the May 1992 UC-Animal Welfare Information Center (AWIC) Workshops that librarians do know where to look. While MELVYL® is extremely useful, it may not be a good source for some subjects. The presentation by AWIC's Jean Larson and Janice Swansonstressed the importance of having a librarian on each campus's animal care and use committee. Protocols now often require that the scientist search the literature to assess whether alternatives are available, and some protocols require specifying the database and search terms used. A librarian could readily evaluate whether the most appropriate searches had been conducted. How will these library searches be paid for? Ultimately, funding for bibliographic searching must be included in grant budgets and budget requests.
 

A variety of other resources are available. AWIC regularly prepares and updates complimentary bibliographies on a wide range of general interest topics, and offers limited, individualized searching. Fee-based searches and document delivery can be ordered through most UC libraries. If scientists need information on abstracts but lack hands-on access to an extensive library, they can order the papers. Combining veterinary, medical and biological emphases, the UC Davis Health Sciences Libraries have the most extensive UC collection dealing with animals. They offer fee-based Document Delivery Service to UCD faculty and staff, and a similar service is available for health care professionals who lack an institutional library. IDEAS (Information Dissemination, Exchange and Access Service) at the UC Riverside library offers a fee-based document delivery service to the public.
 

News Service.

On each campus, the news service office regularly deals with animal issues and develops stories involving animals. This has often led to a closer dialog with members of the community and increased public awareness of the scientific process. In News and Communication at UC Santa Barbara, director Margie Weeks and science and technologyh writer David Salisbury play active roles in regular interaction with their community. The public is invited to lectures featuring state-of-the-art science and medicine.
 

Public Relations.

The public relations activities of any college or university provide a key mechanism for educating the public concerning scientific activities occurring on the campus. (It has been suggested in a Science editorial that each faculty member spend an hour per week in this activity.) Virtually every UC campus has developed an outreach program in which members of the campus community interact with the public or local schools on a regular basis. In some cases, this role is carried by a single faculty member who regularly receives and fulfills speaking invitations from local schools and community groups. A few campuses have designated staff time for public relations and have organized major programs for reaching the public. Whatever the scale of activity, these programs are essential to educating our communities about what we do on our campuses, and for establishing and maintaining dialog with our communities. Some excellent examples follow.
 

Morris Barenfus, the campus veterinarian at UC Santa Cruz, regularly speaks within the community and participates in the local science fair. At UC Diego, Ms Marky Pitts serves as animal subjects coordinator and public relations representative, and is active in national and state organizations that address the use of animals in research. She has established a speaker's bureau consisting of 52 UCSD staff and faculty who respond to speaking invitations. She enticed them by alluding to their essential role in informing the public campus activities. To prepare them for speaking invitations, she offers a two-session media training. She has also sent letters to clubs in the San Diego area informing them that UCSD speakers are available.
 

Julie McNeal, animal issues coordinator for UC Davis, manages issues related to the humane use of animals in research and teaching on campus. She recently completed a position as a management fellow and one of her accomplishments has been establishing an adopt-a-scientist program with school classrooms.
 

Bob Phalen, a UC Irvine faculty member, teaches in the biosciences and is concerned with biomedical ethics. He regularly responses to community invitations to speak. Staff at the Beckman Laser Institute, which is affiliated with UC Irvine, have developed printed and graphic teaching materials to inform the interested lay public concerning their activities. Additionally, their Veterinary Outreach Program provides training in the medical use of lasers and furnishes equipment, staff expertise and a small animal laser facility to veterinarians.
 

The Science and Health Education Partnership (SEP) is a particularly ambitious joint project of UC San Francisco and the San Francisco Unified School District. Supported by governmental agencies, foundations and various charitable organizations, SEP fosters contact between scientists and students and sponsors contests for lesson plans developed by students for science teaching. Summer training sessions for teachers are taught by a master teacher and a UCSF scientist team. Another large endeavor offered at UCSF is the "Brown Bag Lectures" program offered weekly to the public.

The Executive Committee on the UC Center for Animal Alternatives held its initial meeting at UC Davis in December 1992. The Committee consists of one appointee from each of the nine University of California campuses, as well as a delegate from each of the three UC laboratories. The busy one-day meeting combined an overview of the activities of the preceding year and an action plan for the coming year.
 

Highlighting some activities on the Davis campus, Julie McNeal described the "Adopt-a-Scientist Program" through which a scientist establishes a year-long relationship with a local elementary school class. A new development on campus is the curriculum for teaching surgical techniques to veterinary students. George Cardinet, associate dean of academic programs, School of Veterinary Medicine, provided an overview of the new curriculum that mainstreams alternatives rather than offering them separately. Much of the surgery instruction now occurs during the increased time students spend assisting at the Veterinary Medical Teaching Hospital and while performing spay-neuter surgeries on animals that will subsequently be made available for adoption from animal shelters. John Pascoe, assistant professor of surgery, offered a faculty perspective and Laura Weatherford commented from a veterinary student's point of view. Maril Stratton, director of public communications, spoke of the value of developing a more pro-active stance to inform the public about animal use at the university.

Ray Eden, associate dean of the UCLA School of medicine, led a discussion on goals for the Center for Animal Alternatives. Morris Barenfus, UC Santa Cruz campus veterinarian, pointed out that the center is not simply "a nice thing to do that was requested by the California Legislature"; it also relates to a Federal mandate. A sub-committee consisting of Michael Heymann, professor, UC San Francisco, Morris Barenfus, Don Low, associate dean of public programs for the School of Veterinary Medicine, Harry Greene, associate professor, UC Berkeley, and Ray Eden, was formed to explore funding sources for the center. Lynette Hart and Kelly Nimtz, assistant dean of development, will serve as ex officio members. Harry Greene then led a general discussion concerning the role of the Executive Committee during which it was decided to meet again in the Spring.

Update on Animal Use Alternatives at UC Davis

Since February 1990, the California Horse Racing Board has required a post-mortem program to evaluate the cause of death in race horses. This has permitted an opportunity to learn retrospectively about stress fractures and callus responses in equine bones. Analyses of over 150 necropsies have provided information on the pathogenesis of fatigue fractures in intricate detail. Through analyses of racing records, it will also be possible to assess whether stress fractures have any relationship to the training and management regime used with the horses. No animal undergoes any discomfort for the purposes of this work. Much of the knowledge gained could not otherwise be acquired.

Theses anatomical materials, in addition to providing new research data, are used in teaching veterinary students and for many presentations each year to specialized audiences of campus visitors. This only one aspect of a host of projects that involved students, faculty, and veterinary residents in teaching and research. This work is conducted by veterinarian Sue Stover and her large team of collaborators.
 

Cell Cultures Detect Phototoxins.

In the area of alternatives to animals in testing, an in vitro toxicity test has been developed by Richard Lasarow, R. Rivkah Isseroff and Edward Gomez of the Department of Dermatology at the UCD School of Medicine. The procedure involves using neonatal human foreskins collected from hospitals to grow cell cultures in which irritants and toxic substances are tested. The cell cultures are also used to detect phototoxins by exposing them to ultraviolet light. The authors believe that this may be useful for determining the phototoxic potential of new drugs or suspected phototoxins. Their work has been published by the Society for Investigative Dermatology, Inc., and is being supported by the International Foundation for Ethical Research (IFER).
 

Computerized Radiographic Anatomy as a Teaching Aid.

Veterinarians William Hornof and Phil Koblik and technician John Doval from the radiology department at the veterinary school have developed Canine Radiographic Anatomy, a computerized, interactive textbook for the study of veterinary anatomy. Although this particular program is an instructional aid rather than an alternative to the use of live animals, the authors are planning to develop a technical program for teaching students set technique for radiography. This would allow students more time to experiment with different settings before getting hands-on practice with live animals.
 

Alternatives to the Live Animal Model

Many people are unaware of the ongoing commitment of the School of Veterinary Medicine to the humane use of animals. Following is a list, which is continually evolving, of teaching and research methods used by faculty in the school that lessen or eliminate the use of the live animal model. It should be pointed out, however, that the last alternative in many cases is a study involving the live animal. More than likely this will always hold true in one way or another as physiological systems are so complex and their interactions so important, they must be studied in their entirety.
 

Since the profession of veterinary medicine is charged with maintaining the well being of all animal species, save humans, research performed under the aegis of the School of Veterinary Medicine, be it pure, applied, or clinical, eventually benefits animals and, in turn, humans.
 

It should also be noted that in some cases a live animal model was used to create the alternative, but this, in itself, demonstrates a commitment to the principles of replacement, reduction, and refinement.
 

Traditional or ongoing alternatives:

Wall charts

Plastic skeletal and organ models

Anatomical illustrations

Movies

Slides

Materials drawn from clinical cases that are presented in classroom lectures or discussed in rounds.

The body of scientific and veterinary medical literature

Clinical research

Epidemiological studies

Continuing education courses and conferences

Professional societies and meetings

In vitro studies (tissue culture, organ culture, cell culture)

Genetic research which takes advantage of the delineation of the laboratory mouse genome or uses simpler organisms such as the bacteria Escherichia coli

Statistical modeling

Internships, externships, and residencies

Knot boards, foam boards and cloth (used for teaching surgical techniques)

Plastic bone for orthopedic surgery

Mechanical models to demonstrate physiological actions that are too small or complicated to actually see (for example, Michael Bruss uses a model to demonstrate glomerular functions in the kidney)

In the fourth or clinical year of veterinary education, all animals are client-owned and all studies are clinical oriented
 

More recent (post-1953) alternatives include:*

Biotechnology and genetic engineering

Northern & Southern blots

DNA probes

Transfer of genetic materials & gene therapy

Recombinant DNA techniques

DNA structure & protein synthesis

Modern diagnostics, including ELISA and serological tests

Virology and modern microbiology

Computer modeling

Computer technology

Interactive and latent image teaching programs

Data bases such as ZEBET and INVITTOX

Computer simulation

Videotapes

Interactive video disks
 

* The year 1953 was chosen arbitrarily as it is the year Watson and Crick described the structure of the DNA molecule, making possible the development of molecular biology. Additionally most computer technology used today came into being after this date.
 

What the Information Requirements of the Animal Welfare Act Mean to the Principal Investigator (PI) and the Information Provider (PI)

In 1959, Russell and Birch presented three headings for humane techniques of research involving animals-- Reduction, Replacement, and Refinement, now commonly known as "the 3Rs."

In relation to federally supported research which involves animals, the Animal Welfare Act (9 CFR Part 3, Animal Welfare; Standards) states that the "IACUC review of activities involving animals... shall determine that the proposed activities or significant changes in ongoing activities meet the following requirements: (i) Procedures involving animals will avoid or minimize discomfort, stress, and pain to the animals; (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 of the methods, e.g., the Animal Welfare Information Center, used to determine that alternatives were not available..." ⁽¹⁾

The United States Department of Agriculture's regulatory definition of alternatives is: The IACUC must determine whether the primary investigator has considered alternatives to procedures that cause more than momentary or slight pain or distress to animals. Hence, the regulations only specify alternatives to painful procedures.

In developing search strategies,⁽²⁾ in addition to the ordinary questions that the information provider (IP) should ask and the principal investigator (PI) should think about (what is your general area of study; have you had other studies conducted for you; in what databases?), there should be an in-depth reference interview between the two. The PI, who knows the research protocol backwards and forwards, needs to describe to the IP the protocol itself, the systems or anatomy involved, the animal model/s used, spellings or structures, compounds, including acronyms, trade names and variations, and names of other authors in the same area of research, and possible alternatives.

The literature search of book and journal articles should be undertaken in two phases: Phase one should cover reduction and refinement, with the goal of obtaining citations which pertain to the investigator's topic. In it, explore the following, as pertinent to the individual research protocol:

Is the research duplicative or replicative?

Can alternative techniques or methods be used?

If pain or invasive techniques are an integral part of the protocol, can they be made less stressful, less painful, or less invasive?

Can care or husbandry produce a less-stressed animal?

Are responsible, humane techniques used in the husbandry?

Are the observations of the animal care technicians discussed with the PI?

Are they accounted for in the results?

Can the study size be reduced?

Are the statistical methods for the study size-appropriate?

Is there literature on experimental research design that may assist in more effective utilization of the animals?

Can pre-existing animals be used?

Can the animals be re-used?

If the animals to be used are euthanized, are appropriate methods and agents used?
 

Phase two of the search deals with replacement questions such as the following?

Can non-animal models be used?

What alternatives are available?

Can the species be changed to a related species or a lower level (e.g., invertebrates, fish, protozoa, etc.)?

Is there an in vitro model? In terms of cell cultures, organ cultures, or tissue cultures?

Have any computer models or simulations been developed that relate? Other "high tech" research tools?
 

The information provider should treat an information request for a research project involving animals or for an animal care committee expeditiously, with the same priority as one involving human patients.

2. Credit should go to Cynthia P. Smith, AWIC tips for searching for alternatives to animal research and testing, Animal Welfare Information Center Newsletter, 2(1) Jan-Mar 1991:3,5

Have You Seen...

Bernhardt, Dept of Biology, Williams College, Williamstown MA 01267; Other authors are former or current students in the Department. Recommends adoption of the reuse of sciatic nerves. Recommends that instructors and researchers choose X. laevis raised specifically for education and research in preference to collected specimens, especially of Rana pipiens or Rana catesbiana.

$29.95 each (hdbd); $3.00/order p&h; CA residents add applicable sales tax; orders to National Academy Press, 2101 Constitution Ave, NW, PO Box 285, Washington DC 20055; cite code DISTRE, ISBN 0-309-04275-5.

Explores stresses in the laboratory and the animal behaviors they cause, including discussions of the physiology of pain and distress and the animal's ecological relationship to the laboratory environment. Reviews euthanasia of lab animals--exploring the decision, methods and emotional effects on technicians. Includes listings, by species, of dosages, anesthetics, analgesics, and tranquilizers.

Orders to the Research Animals Dept, RSPCA, Causeway, Horsham, West Sussex RH12 1HG, England. Tel +44 (1403) 264 181; Fax +44 (1403) 241.048.

Also called the RSPCA Stress report. Reviews the literature correlating measurements with known stressors and evaluates the means of assessing stress. Describes factors affecting the stress response. Reviews the effects of stress on behavioral, physiological, and biochemical criteria. Concludes with recommendations for measuring stress and how they may best be made. Extensive bibliographies.

Commentary. Proposes a scoring system to maximize comfort in animal experiments.

Author is deceased.

The dissemination of information about methods in in vitro toxicology is subject to a number of constraints which are identified and discusses, as are the ways in which INVITTOX seeks to address those problems. Scientists' continued interest in INVITTOX suggests that a real gap in information provision is being filled.

Krys Bottrill, FRAME, Russell & Burch House, 96-98 N Sherwood St, Nottingham NG1 4EE, UK; tel +44 (115) 95 84740; fax: +44 (115) 95 03570; invittox@frame-uk.demon.co.uk

To be placed on the mailing list, contact: National Library of Medicine, Specialized Information Services, Office of Hazardous Substances Information, Building 38A, Room 5S-516, 8600 Rockville Pike, Bethesda MD 20984; (301) 496-5022; FAX (301) 480-3537.

Some Money Saving Tips for DIALOG® Searchers

Coordinator of On-Line Searching, Humanities/Social Science Department
Shields Library, University of California, Davis
Davis CA 95616-7252; sjlamprecht@ucdavis.edu

The Animal Welfare Act mandated greater effort to seek alternatives, and it has become critical for scientists to work in close partnership with librarians. Although scientists are already familiar with the literature in their fields, a new key requirement is to conduct a literature search to rule out replication of previous studies that might have been reported in an unrelated field. These can be more complex and costly than conventional searches. Sandra Lamprecht wrote this article to assist researchers who can use these suggestions or take them to a librarian to conduct appropriate searches for alternatives.

Through my years of on-line searching in DIALOG® I have found the following cost-cutting tips that helped me get good results and keep the costs down. They are simple and I hope you find them useful too. I provide them with the thought that the experienced searcher may find something new here and that the new searchers may find some relief from "new searcher panic."

1. After executing a search, print the results on-line by title (format 6) and then temporarily save the search and log off. Let the patron look at the printed titles and select those for which completed citations are desired. Then log in, retrieve the search and order or print only the selected citations. The search cost can be reduced by half with this method, especially in more expensive citation databases (e.g., Social SciSearch, file 7, Arts and Humanities Search, File 439, and various business databases).

2. With broad topics or those with which you are unfamiliar, do a Dial Index search first. It will help you select appropriate databases and formulate the actual search strategy. The posted Dial Index results can also help you determine whether or not you want to conduct the actual search using free text or descriptor/title fields only.

3. When doing a OneSearch (searching two or more databases at the same time), do not forget to use the Reduce Documents command so that duplicates are eliminated (i.e., rd set "n"). Also place the least expensive database, with regard to per citation cost, which will be removed from the last databases listed, will drop out.

4. When going on-line, especially as a beginner, develop both a broader and a narrower search strategy so that if the results do not fit into a "normal" range for the patron's needs, you will have on-line options ready without having to spend on-line time thinking about what to do next, or without having to log off and refine the search strategy.

Don't forget that language and date limitations, as well as limiting free text terms to descriptor, title or identifier fields, are good options for searches that have too many citations to review.

5. When you or the user select citations and there are 20 or more, it is usually less expensive to order prints off-line. I would suggest this option if the user has the time to wait two or three days for the mail. Most do and are pleased with the DIALOG printouts. I usually use the simplex command so that each citation is on a separate page.