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

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

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

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

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

Diseases Currently Depending on Biomedical Research

Congenital cardiac defectsSpinal injuryMultiple sclerosisSchizophreniaCancerSickle cell anemiaAIDSParkinson’s disease

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

Recent Trends in Animal UseRecent Trends in Animal Use

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20000

40000

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80000

100000

120000

140000

160000

180000

1997 1998 1999 2000 2001 2002

DogsCatsNHPsFarm

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 dystrophyGenetic knockout animals--specific

gene turned off

How Mice and Rats are Used in Research

Specific immunodeficiency annimalsAlzheimer’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

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

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 diabetesCause and treatment of NarcolepsyCause and treatment of retinal

degeneration and blindness

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

Oversight of Animal Use in Research

Animal Welfare ActPublic Health Service: NIH Guidelines

for federally funded researchFDA: medical devices & drug

development and approvalEPA: health effects and

environmental effects testing

Life Magazine--Feb. 4, 1966

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

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

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

AWA Summary

Federal law in response to allegations of pet theft--what the public demands

Input from animal protection groupsEnforced by the USDA through inspection

of research facilities, animal exhibitionsProtects all warm-blooded animals

EXCEPT rats, mice and birdsMandates the formation of the IACUC

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

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

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

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

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

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 correctionEvaluate all facilities: housing and

procedure space

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

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

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

The Animal Experimentation Protocol

Justification of species and numbers of animals proposed

Federal assurances regarding non-duplication and search for alternatives to painful procedures

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

Report of Use by USDA Category in 2000

Category C: 63% of all animalsCategory D: 29%Category E: 7%

The Principles of Humane Experimental Technique 1959

WMS Russel and RL Burch

Guidelines for Animal Research--The 3 R’s

ReplacementReductionRefinement

These principles guide IACUC review of research proposals

Replacement

Adopting the: Use of less (or non) sentient

organisms Use of in vitro techniques The use of non-biological alternatives Human Studies

Reduction

Reducing the number of vertebrate animals in experiments

Not repeating unnecessary experiments

Using appropriate statistical tools

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

References

http://www.aphis.usda.gov/ac/ publications.html

http://www.fbresearch.orghttp://altweb.jhsph.edu/publications/

humane_exp/het-toc.htmCarbone L. What Animals Want.

Expertise and advocacy in laboratory animal welfare policy. Oxford U. Press, 2004