Responsible Conduct of Research Involving Animals

James HicksAssociate Vice Chancellor for Research

University of California, Irvine

OutlineAnimal use definition and examples

History of animal welfare regulations

Ethical and humane use of animals

Requirements before working with animals

Definition of Animal Use

“Any live, vertebrate animal used or intended for use in research, research training, experimentation, or biological testing or for related purposes”

Why Use Animals in Medicine, Biology and Biomedical Research?

Animals as spare partsAnimals as factoriesAnimals as models for human diseaseAnimals as test subjectsAnimals to study basic physiological principles and integration of systems

Evolutionary and comparative physiologyNovel solutions to complex problems

Bioinformatics, comparative genomics, proteomics, metabolomicsSystems biology

Animals for the study of animals and the environmentConservation biologyEcological interactions and community structureVeterinary medicine

Animals to study basic principles in biologyEvolutionary biology

Experimental evolutionPopulation geneticsPopulation genomicsAnimal behavior

Animals for the study of diseaseVirology and viral evolution

Benefits of Animal Research

PenicillinMice

Blood TransfusionsDogs

Tuberculosis MedicineGuinea pigs

Meningitis VaccineMice

Kidney TransplantsDogs and Pigs

Breast Cancer TreatmentsMice, Rats and Dogs

Asthma InhalersGuinea Pigs and Rabbits

Polio VaccineMice

Insulin for DiabeticsDogs

Deep Brain Stimulation for Parkinson's DiseaseMonkeys

Benefits Continued…Vaccine for Smallpox

Vaccine for Anthrax

Rabies Vaccine

Typhoid Vaccine

Cholera Vaccine

Treatment for Beriberi

Treatment for Rickets

Corneal Transplants

Local Anaesthetics

Discovery of Vitamin C

Canine Distemper Vaccine

Coronary Bypass Operation

German Measles Vaccine

MMR Vaccine

Antidepressants and Antipsychotic

CT Scanning for Improved Diagnosis

Chemotherapy for Leukaemia

Medicines to Treat Ulcers

Inhaled Asthma Medication

Combined Therapy for HIV infection

Medicines for Type 2 Diabetes

Cervical Caner Antibodies

Bird Flu Vaccine

Malaria Vaccine

Modern Anaesthetics

Tetanus Vaccine

Diphtheria Vaccine

Anticoagulants

Streptomycin

Kidney Dialysis

Whooping cough Vaccine

Heart Lung Machine

Hip replacements

Cardiac Pacemakers

High Blood Pressure Medicines

Replacements of Heart Valves

Chlorpromazine Psychiatric Medicine

MRI Scanning for improved Diagnosis

Prenatal Corticosteroids for Premature Babies

Treatment for River Blindness

Life Support for premature Babies

Medicines to control Transplant Rejection

Hepatitis B Vaccine

Leprosy Treatment

Oral and Inhaled Insulin for Type 1 Diabetes

Angiogenesis Inhibitors for Cancer and Blindness

Gene Therapy for Muscular Dystrophy

Alzheimer’s Vaccine

US Yearly Benefits of Animal Research

450,000 Prescriptions for anabolic (growth) hormones1

520,000 Heart bypass operations2

1,500,000 Prescribed for Erythropoietin (for Anaemia)3

34,000,000 Anticoagulants dispensed4

95,000,000 Prescriptions for asthma5

150,000,000 Prescriptions for antibiotics6

1. Source: IMS Health, IMS National Prescription Audit TM, 2/20082. Source: IMS Health, ClinicalPlus3. Source: IMS Health, IMS National Sales Perspectives TM, 2/20084. Source: IMS Health, IMS National Prescription Audit TM, 2/20085. Source: IMS Health, IMS National Prescription Audit TM, 2/20086. US Center for Disease Control and Prevention

Veterinary advancesVaccines developed to protect pets, farm animals, working animals and animals in the wild

The Numbers…

Numbers in Perspective

Pain - The Percentages

“Some Pain, No Anesthesia”

This is only the case when anaesthesia (or other pain relief) would have affected results e.g., when testing another pain relief drug

Examples of Animal Use at UCI

development of new therapies for humans and animalspre-clinical drug/device trialsclasses to teach surgical and other medical techniquesbehavioral studiestissue harvest for in-vitro studiescomparative and evolutionary studies

Animal RightsAnimals and man share equal rights-- “personhood” for animalsAll sentient beings deserve equal moral considerationAnimal-based research is never justified, nor is pet ownership, food or fiber production, etc.“A rat is a pig is a dog is a boy. They’re all animals.” Ingrid Newkirk, PETA

Animal Rights vs. Animal Welfare

Animal WelfareAnimals and man are not equal, animals do not have the same rights as peopleStewardship: Man has an obligation to protect the welfare of animals (ie: provide food and shelter, limit pain and suffering, treat when injured, etc.)Foundation of contemporary animal welfare regulations and guidelines

Animal Rights vs. Animal Welfare

Humane Standards Milestones

1966

1966

1966

Life Magazine--1966

Raid of a Baltimore, MD animal dealer by Humane Society of the United States (HSUS) 29 charges of animal cruelty brought against Lester BrownCongress put forth eight bills to outlaw inhumane treatment of animals

Pet Protection Act1966: Congress enacted the Pet Protection Act

Precursor to today’s Animal Welfare ActProtected against theft of pets by research dealersGave authority to USDA to enforce and administer the ActProvided protection to dogs, cats, rabbits, monkeys, guinea pigs and hamsters

Pet Protection Act (cont’d)

Established humane standards for treatment of animalsSet licensing requirements for animal dealersRequired annual USDA inspections of dealers and research institutions

1985 Animal Welfare Act Amendment

Establishment of an Institutional Animal Care and Use Committee (IACUC)

Requirements for veterinary consult and oversight

Requirements for canine exercise and non-human primate psychological enrichment

Requirements for consideration of alternatives to animal use and painful procedures and avoidance of unnecessary duplication of already-conducted studies

Humane Standards Milestones

USDA RegulationsSet requirements for committee (IACUC) composition and functionProvide performance standards for:

veterinary careanimal husbandryanimal transportation

Covers all warm-blooded animalsexcludes rats, mice and birds

NIH Office of Laboratory Animal Welfare

Health Research Extension Act is the legislative mandate for Public Health Service (PHS) policyCovers all vertebrate animalsNIH funded institutions must adhere to the PHS PolicyOffice of Laboratory Animal Welfare is responsible for assuring compliance with PHS policy

Key Elements of the Federal Regulations

Justify why animals are necessaryMinimize pain and distressPersonnel must be qualified to perform their dutiesProvide appropriate husbandry and careUse of appropriate euthanasia methods

Ethical Guidance1996 NASA Principles for Ethical Care & Use of Animals: “Sundowner Report”

Principles of Humane Experimental Technique by W. M. Russell and R. L. Burch, 1959

NASA Principles - “Sundowner Report”

Respect for LifeAll living creatures deserve respect

Societal BenefitSome valuable return in exchange for the sacrifice of the animal’s life

Non-maleficience“Do no harm”Pain, distress and discomfort to the animals must be minimized

Principles of Humane Experimental Technique

The 3 Rs

ReplacementUse of live animals as the research model should be replaced if possible

RefinementProcedures should be refined to minimize pain, distress and discomfort

ReductionNumber of animals should be reduced to the minimum necessary to achieve scientific significance without increasing pain and distress

Refinement• Better living conditions for animals

• Minimising pain wherever possible

•Better training for animal technicians

ReplacementIn Vitro Testing

Computer Modelling

MRI Scanning

Micro dosing

Reduction• Re-evaluating minimum numbers of animals for statistical significance

• Methods allowing multiple procedures on single animals

• Better designed experiments to reduce numbers

Institutional Animal Care and Use Committee

Campus committee charged with oversight of UCI’s animal programMember Composition:

Faculty with animal expertiseAttending VeterinarianNon-scientific memberUnaffiliated memberBiosafety officer

The IACUC’s RoleReview and approve activities involving animals at UCI (protocol review)Review the animal program and inspect all facilities every 6 months Review concerns involving animal useInvestigate issues of non-complianceReport to regulatory agencies

Why Do We Review Protocols?

The protocol is…The written documentation of all procedures to be performed on live animals

The means by which adherence to the federal animal welfare regulations is assessed

The document that confirms the ethical treatment of animals used in the research

What Activities Require Review?

“Any live, vertebrate animal used or intended for use in research, research training, experimentation, or biological testing or for related purposes.”

-PHS Policy

Definition:

IACUC Protocol Review

Rationale for the use of animalsJustification of the species and number of animalsConduct of experiments Unnecessary duplication of experimentsAppropriate sedation, analgesia, anesthesia Adequate training of personnel

The Ethical Bottom Line

The use of animals is a privilege, not a right

Society grants permission to use animals with the expectation that health benefits may be derived

the benefits to society outweigh the adverse effects imposed on individual animals (discovery and new knowledge)

Animal Welfare Regulations, Policies &

GuidelinesUSDA AWRs-- Title 9 CFR, Chapter 1USDA Animal Care PoliciesOLAW PHS Policy (1986)

The Guide (NRC--8th Ed.)2000 Report of AVMA Panel on EuthanasiaAAALAC, Intl. Accreditation Standards

Requirements before Working with

AnimalsBe sure the IACUC approves you to work with animals

The Lead Researcher must submit a modification request to add students to their protocols

Complete the animal tutorialComplete a Qualifications of PersonnelComplete a Work Health History form for EH&S’ Occupational Health Program

Requirements (cont’d)

Read the approved protocolEnsure the procedures you will perform are approved by the IACUCNew procedures?

LR should file a modification request and wait for IACUC approval

RGS On-Line TutorialFulfills a federal investigator

education requirementIs required for all personnel working with animalsRequires log-in with a UCINetID and passwordCovers core concepts of animal use Not sure if you taken the animal tutorial?

Check the tutorial verification database

Lead Researcher Responsibilities

Obtain all required approvals prior to commencing the research; follow IACUC approved procedures

Ensure all personnel are trained to handle animals and perform proceduresMake no changes to the approved protocol without first having submitted those changes for review and approval by the IACUC

Responsibilities (continued)

Acquire or procure all animals thorough ULARObtain annual renewals and 3-year renewal in order to continue working with animals

when protocols expire, all animal work must stopfaculty & staff can access IACUC protocol information via the web

Promptly report adverse events or problems to a ULAR Vet and the IACUC