Why Are Animals Used in Research?

1. Why Are Animals Used in Research? • Organs and body systems are similar to humans • Genetic makeup and immune system are similar to humans • Susceptible to same diseases

2. Why Are Animals Used in Research? • Physiological responses to environmental change and to disease are similar to humans • We can control their environment and thus minimize variables • Creation of models of disease

3. Translational Research • Past two decades focused on cellular and molecular biology • Now there is a need to bring that research into body systems • US Senate has mandated additional funding for such research

4. Health Benefits from Biomedical Research • Increased average US life-span and decreased infant mortality rate • Disease protection through immunization: polio, diptheria, mumps, rubella, hepatitis • Diabetes treatment and insulin safety

5. Health Benefits from Biomedical Research • Surgical and minimally invasive procedures: coronary bypass, cardiac catheterization, organ transplantation, joint replacement, cataract surgery • Chronic disease treatment: epilepsy, asthma, renal dialysis

6. Diseases Currently Depending on Biomedical Research • Congenital cardiac defects • Spinal injury • Multiple sclerosis • Schizophrenia • Cancer • Sickle cell anemia • AIDS • Parkinson’s disease

7. Advances in Animal Health • Vaccines for rabies, distemper, parvo-virus infection, hepatitis, anthrax, tetanus, feline leukemia • Treatment of cardiac disease, cancers, traumatic injury, • Neonatal intensive care in foals

9. How Mice and Rats are Used in Research • These are 90% of all animals used in research • Transgenic animals--a foreign gene added • Study of Parkinson’s disease, cancer, cystic fibrosis, heart disease, muscular dystrophy • Genetic knockout animals--specific gene turned off

10. How Mice and Rats are Used in Research • Specific immunodeficiency annimals • Alzheimer’s disease--transgeneic causing over-expression of amyloid protein and vaccination with protein • Cancer--sensitivity to environmental carcinogens and development of resistant genetic strains • Heart attack--regeneration of heart muscle cells

11. How Nonhuman Primates are Used in Research • Development of AIDS vaccine using Simian Immunodeficiency Virus • Vaccine development for hepatitis B and C • Malaria vaccine development--NHP’s are susceptible to the same parasite strain • Periodontal disease--NHP’s naturally develop the same disease

12. How Dogs are Used in Research • Development of surgical procedures for heart valve and artery replacement • Development of organ transplant procedures and management • Cause and treatment of diabetes • Cause and treatment of Narcolepsy • Cause and treatment of retinal degeneration and blindness

13. How Cats are Used in Research • Study of nerve transmission in the brain • Understanding organization of neurons in the brain • Understanding normal and abnormal function of the visual system

14. Oversight of Animal Use in Research • Animal Welfare Act • Public Health Service: NIH Guidelines for federally funded research • FDA: medical devices & drug development and approval • EPA: health effects and environmental effects testing

15. Life Magazine--Feb. 4, 1966

16. The Animal Welfare Act • Passed in 1966 and amended in 1970, 1976, 1985, 1990, 2002 • “Top-down”--passed by Congress in response to publicity over dog theft • Includes input from animal protection and anti-vivisection groups

17. The Animal Welfare Act • 1985 amendment authorizes institutions to form an IACUC, provide and exercise program for dogs, and provide for psychological wellbeing of primates • Covers all warm-blooded animals, but birds, mice and rats are excluded by act of the USDA

18. Enforcement of the Animal Welfare Act • Enforcement through the USDA, specifically APHIS through veterinary inspections • Unannounced site visits by USDA veterinarians and reporting of any non-compliance

19. AWA Summary • Federal law in response to allegations of pet theft--what the public demands • Input from animal protection groups • Enforced by the USDA through inspection of research facilities, animal exhibitions • Protects all warm-blooded animals EXCEPT rats, mice and birds • Mandates the formation of the IACUC

20. Public Health Service: The NIH Guidelines • “Bottom-up” self-regulatory professional standards for lab animal care developed by veterinarians an animal care personnel • No input from animal protectionist groups • The Animal Care Panel wrote the Guide for the Care and Use of Laboratory Animals in 1963

21. The NIH Guidelines • NIH Policy guidelines encoded as law as the Health Research Extension Act in 1985 • With this act, Congress made compliance with the Public Health Service Policy on Humane Care of Laboratory Animals mandatory for any institution receiving federal funds

22. Enforcement of the NIH Guidelines • Through voluntary accreditation by Assoc. for the Assessment and Accreditation of Laboratory Animal Care (AAALAC) founded in 1963 • Inspection every 3 years by lab animal veterinarians • NIH recognizes voluntary AAALAC accreditation as evidence of compliance

23. Enforcement of the NIH Guidelines • All vertebrate animals covered, but only institutions receiving PHS funding are required to comply • An institution may voluntarily make a commitment to comply with PHS policy on care and use of animals in research even if it does not receive federal funds

24. The IACUC--Convergence of the AWA and NIH Guidelines • Committee existence and makeup are mandated by the AWA and the PHS/NIH Office of Laboratory Animal Welfare • IACUC activities are evaluated during both the USDA inspection and the AAALAC inspection • IACUC members include peer scientists, a veterinarian, and a community member

25. Responsibilities of the IACUC • Evaluate the institutional program and facilities every 6 months • Assure compliance with the Guide • Formal report noting deficiencies and time for correction • Evaluate all facilities: housing and procedure space

26. Responsibilities of the IACUC • Approval of all new applications for animal research activity • Re-review of all research protocols every 3 years • Investigate all allegations of mistreatment or non-compliance • investigation, reporting, and correction; suspension of activity if warranted

27. Animal Welfare Considerations • Institutional Animal Care & Use Committee • required by USDA, NIH, AAALAC • Committee composition specified • Semi-annual review of entire program and correction of deficiencies required • Protocol and grant pre-approval required • Dissenting votes recorded

28. The Animal Experimentation Protocol • Section B: narrative description of proposed research--must be understandable by community member • USDA pain category applicable to research and number of animals in each • Description of surgical procedures, anesthesia and post-operative analgesia

29. The Animal Experimentation Protocol • Justification of species and numbers of animals proposed • Federal assurances regarding non-duplication and search for alternatives to painful procedures

30. USDA Pain Categories • Category C: No pain or distress greater than minor or momentary • injections, blood sampling • Category D: Potentially painful or distressing expts. for which analgesic, anesthetic or tranquilizing drugs are used • Category E: As above, but for which use of such drugs would adversely affect results or interpretation

31. Report of Use by USDA Category in 2000 • Category C: 63% of all animals • Category D: 29% • Category E: 7%

32. The Principles of Humane Experimental Technique 1959 WMS Russel and RL Burch

33. Guidelines for Animal Research--The 3 R’s • Replacement • Reduction • Refinement • These principles guide IACUC review of research proposals

34. Replacement • Adopting the: • Use of less (or non) sentient organisms • Use of in vitro techniques • The use of non-biological alternatives • Human Studies

35. Reduction • Reducing the number of vertebrate animals in experiments • Not repeating unnecessary experiments • Using appropriate statistical tools

36. Refinement • Modification of procedures which must involve sentient animals to minimize animal suffering • Use of anesthetics and analgesics to minimize animal suffering • Improved animal husbandry and handling, reducing stress • Development of alternative methods of drug and product development where the severity of the endpoints is reduced

37. References • http://www.aphis.usda.gov/ac/ publications.html • http://www.fbresearch.org • http://altweb.jhsph.edu/publications/ humane_exp/het-toc.htm • Carbone L. What Animals Want. Expertise and advocacy in laboratory animal welfare policy. Oxford U. Press, 2004