THE HUMANE CARE AND USE OF LABORATORY ANIMALS

THE HUMANE CARE AND USE OF LABORATORY ANIMALS Improving the lives of humans and animals through animal research Virtually every major medical advance of the last century has depended upon research with animals. Animals serve as surrogates in the investigation of new ways to treat, cure or prevent disease and disability. Following are facts about the realities of animal research and researchers strong motivations to protect animals from harm. These points deserve consideration when deciding how well science is meeting its obligations to laboratory animals. National Association for Biomedical Research 818 Connecticut Avenue, NW, Suite 900 Washington DC 20006 Tel: 202.857.0540 Fax: 202.659.1902 info@nabr.org www.nabr.org

THE HUMANE CARE AND USE OF LABORATORY ANIMALS Improving the lives of humans and animals through animal research From firsthand experience, those working in biomedical research understand the necessity of studying animals in order to save and benefit all life. At the same time researchers attitudes about animals are no different than most other Americans i. Like the general public, they are also concerned about the humane care and treatment of laboratory animals. Members of the research community want assurance that animals are treated humanely, do not suffer and are kept in conditions that allow them to be as healthy and comfortable as possible. Given these concerns, the scientific community has the obligation to safeguard and improve the welfare of laboratory animals. This responsibility is fully accepted not only because of the essential contributions of animals to research, but also because society expects no less. Following are facts about the realities of animal research and researchers strong motivations to protect animals from harm. These points deserve consideration when deciding how well science is meeting its obligations to laboratory animals. ABOUT RESEARCH ANIMALS Most research animals in U.S. laboratories are rodents. All other larger animal species combined represent a very small fraction likely 2 to 3%. Rats, Mice, and Fish NABR estimated that 23 million rats and mice were needed for U.S. research in 1998 and that rodents accounted for 95% of the animals used. ii Predictions from NABR s 1998 survey said that rodent numbers could easily double in ten years and they may well have done so. Research mice, especially transgenic varieties, are probably the most common research animal in use today. New trends in research Most research animals in the U.S. are rodents. All other larger animals species combined represent a small fraction likely 2 to 3%. animal use also have emerged in the last decade. Because of their small size and short reproductive life cycles, fish have become important animal models. For example, researchers are now relying upon millions of little zebra fish. The use of invertebrate animals, such as fruit flies and similar insects, appears to be increasing as well. 1

Other Animal Species Unfortunately, current estimates are not available for all laboratory animal species, nor for the total overall. Without recent statistics, it is not possible to determine what the percentage breakdown may be by species. The only recent annual estimates come from the U. S. Department of Agriculture (USDA) for those species it regulates under the Animal Welfare Act. iii Research facilities reported using 1,027,450 animals in FY 2007, including dogs, cats, nonhuman primates, guinea pigs, hamsters, rabbits, various farm animals and other warm-blooded species. Even with the addition of farm animals and more research facilities having to report to USDA, the total number of USDA-regulated animals has decreased significantly over time. From a high of 2,134,182 animals in 1992, two years after farm animals used in biomedical research began to be regulated, total usage has dropped approximately 50%. The use of nonhuman primates has increased somewhat and all numbers have fluctuated, but still the general trend for USDA-regulated research animals has been a steady decline. The greatest change has been seen for dogs and cats, where usage of each has decreased by two-thirds, or about 66%. NON-ANIMAL RESEARCH METHODS Non-animal research methods are used whenever possible, but such alternatives do not exist for all worthwhile research. Animal models remain essential for investigations that stand to relieve both human and other animal suffering. Types of Non-Animal Methods Scientists use a variety of methods in research. In some areas, the use of animals is neither necessary nor appropriate. In others, such as developing a fundamental understanding of how complex biological systems function, the use of animals has been and continues to be essential. Data obtained from humans are obviously the most scientifically valid; however, in many cases human experimentation is ethically unacceptable under any circumstances or not advisable without first establishing a level of safety. For this reason, researchers study animals, living systems most closely related to humans, before humans are asked to participate in research. The largest federal expenditure for US research involves human subjects, with a much smaller amount spent on the animal and non-animal work that precedes it. Non-animal research methods are used whenever possible, but such alternative do not exist for all worthwhile research Scientists have developed valuable nonanimal research methods, such as physiochemical techniques, computer and mathematical models, microbiological systems, and cell and tissue cultures. These methods are useful for some research, and in other cases they complement work in animal systems. One of the widest uses of 2

nonanimal tests presently is in initial screening of substances for potentially toxic and harmful effects. With increasingly sophisticated computer technology and laboratory instrumentation, more preliminary studies have become possible without using whole animals. Additional innovation is highly desirable, especially if faster, less costly research results can be obtained. Limitations of Non-Animal Models Still, our knowledge of higher organisms is far from complete. With evolving knowledge, one day science may be able to dispense with those research methods that now require animals. However, that possibility is far from being implementable with our current knowledge. Today, the replacement of whole animals with nonanimal models for advanced biomedical research is simply not possible. HUMANE LABORATORY ANIMAL CARE Researchers take action to prevent laboratory animals from experiencing pain, except in rare cases when it is unavoidable because of research objectives. The Need for Quality Animal Care No responsible person wants an animal to be subjected to avoidable pain or distress. Animal-loving people everywhere share this conviction. For research personnel, the ethical treatment of animals is a professional as well as a personal imperative. Good animal care is good science. If a laboratory animal is adversely affected by pain or distress, the research data collected from that animal may not be reliable. Animals that are treated well, on the other hand, provide the normal biological or behavioral responses that researchers need to examine. In protecting their laboratory animals, researchers are also protecting the source of their scientific data and the successful results that their work intends. The Animal Welfare Enforcement Report Good animal care is good science. According to the 2007 USDA Animal Welfare Enforcement Report, most research (92%) was not painful to the animals involved. iv In the majority of cases (54%), animals were not exposed to or involved in any painful procedures. In approximately 38% of cases, anesthesia or pain-relieving drugs were given because the animals may experience some pain or distress. In less than 8% of research projects, anesthetics or analgesics (pain-relieving drugs) were not used because they would have interfered with the end results. In these rare cases in which research may require that pain not be relieved, prior institutional approval and full justification is necessary. 3

THE RESEARCH COMMUNITY AND ANIMAL WELFARE Protecting and improving the well-being of laboratory animals is a longstanding endeavor within the research community. Professional principles have long been in existence to guide animal care and minimize any animal pain or distress. Commitment to Ethical Treatment Scientists commitment to ethical treatment for animals is not new. Individual researchers concerned about the treatment of laboratory animals were the first to set voluntary care standards at the turn of the century, long before federal laws and regulations were instituted. In 1909, the first voluntary procedures regarding animal care were adopted and enforced in medical school Individual researchers were the first to set voluntary care standards at the turn of the century laboratories. Later, to care more effectively for research animals, veterinarians created a board-certified specialty in laboratory animal medicine. The American College of Laboratory Animal Medicine (ACLAM) v was established in 1957 to administer the certification program. Academic and professional organizations comprising researchers, veterinarians and others were pioneers in the creation of laboratory animal welfare standards. The Association for the Assessment and Accreditation of Laboratory Animal Care International (AAALAC) vi and the American Association for Laboratory Animal Science (AALAS) vii are two of the most prominent organizations. Professional Animal Care Organizations During the 1940s, a group of professionals involved in animal research became concerned about varying standards of animal care. In 1950, this group founded AALAS, which today has more than 12,000 individual and institutional members ranging from veterinarians to laboratory technicians to university administrators. AALAS is dedicated to developing and maintaining the highest standards of animal care. The Association serves as a forum for presenting and exchanging scientific information on all phases of laboratory animal welfare through its many educational activities and certification programs. Leading veterinarians and researchers organized AAALAC in 1965 to promote high standards of animal care, use and well-being and enhance life sciences research and education through the accreditation process. AAALAC conducts voluntary peer review evaluation of laboratory animal care facilities and programs, which involves site visits, evaluation of site visit reports and recommendations concerning proposed accreditation status. Approximately 700 of the largest and most prestigious research institutions in the U.S. have earned currently earned AAALAC accreditation, a distinction considered the gold standard among animal care programs. 4

Numerous professional societies, such as the American Physiological Society, the American Psychological Association, the Association for Research in Vision and Ophthalmology, and the Society for Neuroscience have codes and policies governing animal research. Voluntary health organizations, such as the American Cancer Society, the American Heart Association and Juvenile Diabetes Research Foundation, have adopted official policies outlining acceptable standards for the care and use of laboratory animals. Research funded by these organizations must meet these criteria. STANDARDS FOR ANIMAL CARE All of these activities and standards are predicated upon four basic principles: ensure all research animals receive good care and humane treatment in accordance with applicable laws; use animal models only when nonanimal methods are inadequate or inappropriate; use as few animals as possible and minimize the potential for pain and distress in those that must be used design experiments so that all animal studies yield scientifically reliable results. Research Oversight Federal laws and regulations exist to ensure humane care and treatment of laboratory animals. Penalties for non-compliance are severe. The National Institutes of Health and Animal Care The National Institutes of Health (NIH) published the first federal laboratory animal guidelines in 1963, now entitled the Guide for the Care and Use of Laboratory Animals. In 1985, the U.S. Congress created a statutory mandate (42U.S.C.289d) for the Guide and the Public Health Service Policy for the Humane Care and Use of Laboratory Animals. The USDA developed the first federal regulations under the Animal Welfare Act (AWA), originally passed in 1966 (7U.S.C.2131 and 9C.F.R. Ch.1, Parts 1, 2 and 3). For detailed information, please refer to NABR Issue: Federal Regulation of Biomedical Research Involving Animals. Many people, however, are unaware of the extensive system of laws, guidelines, regulations and principles that ensure the welfare of laboratory animals in the U.S. Requirements, which are periodically updated, address veterinary care (surgery, analgesics, anesthesia, and euthanasia methods) and housing conditions (food, water, sanitation, space, temperature, humidity, and Many people, however, are unaware of the extensive system of laws, guidelines, regulations, and principles that ensure the welfare of laboratory animals in the US. 5

lighting), many special considerations (exercise for dogs and the psychological well-being of nonhuman primates among others) and overall institutional responsibilities (review of animal research projects in advance, program oversight and reporting.) Research facilities and those who work in them are well aware of the legal requirements that must be followed when laboratory animals are used. Failure to comply with federal rules can result in the loss of funding and/or the loss of the privilege to work with animals. Monetary fines from USDA are possible for violations. However, the severest penalty that can ensue from inappropriate treatment of animals is condemnation by professional peers and the public. Negative publicity can ruin careers and destroy the good reputation that institutions must have to attract research staff, students, financial and other support from its community. For this reason it is not unusual for academic and industry laboratories to make animal welfare compliance a condition of employment. It can be grounds for immediate dismissal if an employee does not adhere to animal care standards and report fellow workers for non-compliance. Permission to Use Animals Researchers must request in advance and receive permission to use animal models. As required by the AWA, Public Health Service Policy and the Guide as well as voluntary AAALAC accreditation standards, a researcher must submit a detailed plan for utilizing any vertebrate animal to a review committee at the institution. The Institutional Animal Care and Use Committee (IACUC) is required by law and must have no less than three members; one must be a veterinarian and one must not be affiliated with the institution in any way. The legally required animal care and use plan contains the following: Rationale for involving animals and the species and number to be used; Complete description of the proposed use of the animals; Description of procedures designed to assure that discomfort and pain to animals will be limited to that which is unavoidable for the conduct of scientifically valuable research, including the provision for the use of analgesic, anesthetic and tranquilizing drugs where indicated and appropriate to minimize discomfort and pain; and Description of any euthanasia method. The Institutional Animal Care and Use Committee Researchers must request in advance and receive permission to use animal models. The researcher also must provide the IACUC with written assurance that the plan does not unnecessarily duplicate previous research. Finally, the researcher must consider alternatives 6

to any procedure that may cause more than momentary or slight pain or distress to the animals and provide a written description of the methods and sources used to determine that non-animal alternatives were not available. The IACUC may approve, reject, or ask for additional information about a plan. If the IACUC finds that the plan does not address each area of animal care sufficiently, the plan is not approved, and the researcher cannot begin the project. However, the researcher is given the opportunity to address the IACUC s concerns and may resubmit the plan with appropriate changes. Once a project is under way, subsequent changes must be approved by the IACUC and the committee has the authority to suspend the work for cause. The IACUC must inspect the research institution s animal facilities and review its animal care and use program at least once every six months. REPLICATION OF RESEARCH Duplication of research is sometimes necessary, but there are strong incentives not to do so. New data becomes biomedical knowledge that researchers throughout the world may draw upon Duplication, or more accurately, replication of research may be necessary to validate scientific findings. Such replication provides for rigorous testing of hypotheses and the formulation of conclusions that carry a higher degree of validity. Once sufficiently confirmed, new data becomes biomedical knowledge that researchers throughout the world may draw upon for further investigations. Scientific Peer Review The scientific peer review process and keen competition for federal research funds prevent unnecessary duplication of research as well as support laboratory animal welfare. Reputable scientific and medical journals do not accept research articles for publication that are needlessly redundant or do not comply with established research animal care standards. Funds are not granted for projects that do not stand to make significant contributions to the existing body of biomedical knowledge. The NIH - the largest source of federal funding for biomedical research in the country -- currently is able to support only one-fifth of all competitive grant proposals it receives. viii Scarce NIH funds are not awarded for studies which will not add significantly to biomedical research. ANIMAL CARE STAFF Well-qualified and thoroughly trained staffs care for animals at research laboratories. 7

Each animal research institution has an animal care staff. This staff generally works under the direct supervision of a veterinarian, who is a specialist in the practice of laboratory animal medicine or a related veterinary medical field such as comparative pathology. Like physician specialists who practice human medicine, these veterinarians undergo postgraduate/residency training to qualify for the rigorous certification examinations required for their specialties. Types of Staff Members The animal care staff includes laboratory animal technicians or technologists, occupations that combine traditional animal husbandry skills with an understanding of research methods and requirements. Technicians check on each animal s health daily. They monitor the animal s environment, a responsibility that extends far beyond feeding and watering the animals and keeping them clean, dry and comfortable. Technicians continuously monitor external factors such as noise, light, temperature and humidity, as well as the use of insecticides, detergents and disinfectants. The animal care staff also may include veterinary technicians/technologist who are trained to draw blood, take X-rays, give medications, administer fluid therapy, induce anesthesia, assist at surgery, give postoperative care and humanely, painlessly euthanatize an animal. Today, 140 degree-granting programs for animal technicians/ technologists in 45 states are accredited by the American Veterinary Medical Association. Most are two-year, associate degree programs; sixteen are four-year. As part of its ongoing effort to set high-quality animal care standards, AALAS instituted a national certification program for laboratory animal personnel. AALAS administers qualifying examinations and certifies successful candidates at three levels. Approximately 2,500 examinations are given annually. AALAS certification is highly encouraged for all animal care staff. i Scientists Share Thoughts on Animal Research. News@Nature.com, 13 December, 2006. By subscription. ii More Regulation of Rodents. F.L. Trull and B.A. Rich. 1999. Science 284:1463 iii 2007 Animal Welfare Enforcement Report. U.S. Department of Agriculture, Animal and Plant Health Inspection Service, Animal Care Division. http://www.aphis.usda.gov/publications/animal_welfare/content/printable_version/2007_ac_report.pdf iv 2007 Animal Welfare Enforcement Report. v http://www.aclam.org. 8

vi http://aaalac.org. vii http://www.aalas.org. viii http://sciencecareers.sciencemag.org/career_development/previous_issues/articles/2007_07_27/caredit_a 0700105. 9