Presentation on theme: "Responsible Conduct of Research Involving Animals"— Presentation transcript:
1 Responsible Conduct of Research Involving Animals James HicksAssociate Vice Chancellor for ResearchUniversity of California, Irvine
2 Outline Animal use definition and examples History of animal welfare regulationsEthical and humane use of animalsRequirements before working with animals
3 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”
4 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 systemsEvolutionary and comparative physiologyNovel solutions to complex problemsBioinformatics, comparative genomics, proteomics, metabolomicsSystems biologyAnimals for the study of animals and the environmentConservation biologyEcological interactions and community structureVeterinary medicineAnimals to study basic principles in biologyEvolutionary biologyExperimental evolutionPopulation geneticsPopulation genomicsAnimal behaviorAnimals for the study of diseaseVirology and viral evolution
5 Benefits of Animal Research PenicillinMiceBlood TransfusionsDogsTuberculosis MedicineGuinea pigsMeningitis VaccineKidney TransplantsDogs and PigsBreast Cancer TreatmentsMice, Rats and DogsAsthma InhalersGuinea Pigs and RabbitsPolio VaccineMiceInsulin for DiabeticsDogsDeep Brain Stimulation for Parkinson's DiseaseMonkeys
6 Benefits Continued… Modern Anaesthetics Tetanus Vaccine Vaccine for SmallpoxVaccine for AnthraxRabies VaccineTyphoid VaccineCholera VaccineTreatment for BeriberiTreatment for RicketsCorneal TransplantsLocal AnaestheticsDiscovery of Vitamin CCanine Distemper VaccineCoronary Bypass OperationGerman Measles VaccineMMR VaccineAntidepressants and AntipsychoticCT Scanning for Improved DiagnosisChemotherapy for LeukaemiaMedicines to Treat UlcersInhaled Asthma MedicationCombined Therapy for HIV infectionMedicines for Type 2 DiabetesCervical Caner AntibodiesBird Flu VaccineMalaria VaccineModern AnaestheticsTetanus VaccineDiphtheria VaccineAnticoagulantsStreptomycinKidney DialysisWhooping cough VaccineHeart Lung MachineHip replacementsCardiac PacemakersHigh Blood Pressure MedicinesReplacements of Heart ValvesChlorpromazine Psychiatric MedicineMRI Scanning for improved DiagnosisPrenatal Corticosteroids for Premature BabiesTreatment for River BlindnessLife Support for premature BabiesMedicines to control Transplant RejectionHepatitis B VaccineLeprosy TreatmentOral and Inhaled Insulin for Type 1 DiabetesAngiogenesis Inhibitors for Cancer and BlindnessGene Therapy for Muscular DystrophyAlzheimer’s Vaccine
7 US Yearly Benefits of Animal Research 450,000 Prescriptions for anabolic (growth) hormones1520,000 Heart bypass operations21,500,000 Prescribed for Erythropoietin (for Anaemia)334,000,000 Anticoagulants dispensed495,000,000 Prescriptions for asthma5150,000,000 Prescriptions for antibiotics61. 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
8 Veterinary advancesVaccines developed to protect pets, farm animals, working animals and animals in the wild
11 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
12 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
13 Animal Rights vs. Animal Welfare Animals 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, PETAPeople’s attitudes fall somewhere along a continuum – at the far end on one side is Animal Rights
14 Animal Rights vs. Animal Welfare Animals 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
15 Humane Standards Milestones Public perception requires the research community to strive for excellence in humane care and use of animals.This is perfect segway into the NASA ethical principles and the resurgence of the 3Rs concept
16 In 1966, LIFE magazine published an article titled, “Your Dog is in Cruel Danger.” The article was about pets being stolen for use in research1966
17 1966Concentration camp for dogs --article depicted under nourished, unhappy dogs and poor living conditions in a Baltimore, MD animal dealer facility
18 1966Public outrage and worry about their animals. Public trust in research was at an all time low.
19 Life Magazine--1966Raid 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
20 Pet Protection Act 1966: 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 hamstersPublic outcry led to first federal law governing animal welfareSpecifically addressed animals most often considered pets – cats and dogs.
21 Pet Protection Act (cont’d) Established humane standards for treatment of animalsSet licensing requirements for animal dealersRequired annual USDA inspections of dealers and research institutionsPPA = Groundbreaking law – for research, breeders, many other uses of animals (breeders were unregulated, leading to problems with pet health)Set the stage for other laws and regulations that followed, many as amendments of the original act
22 1985 Animal Welfare Act Amendment Establishment of an Institutional Animal Care and Use Committee (IACUC)Requirements for veterinary consult and oversightRequirements for canine exercise and non-human primate psychological enrichmentRequirements for consideration of alternatives to animal use and painful procedures and avoidance of unnecessary duplication of already-conducted studiesSeveral amendments through the years – name changed to Animal Welfare Act to reflect its broadening focusMost important amendment for research institutions – provisions were added that directly applied to the use of animals by research institutions...UCLA early 80’s – no IACUC
23 Humane Standards Milestones Public perception requires the research community to strive for excellence in humane care and use of animals.This is perfect segway into the NASA ethical principles and the resurgence of the 3Rs concept
24 USDA RegulationsSet requirements for committee (IACUC) composition and functionProvide performance standards for:veterinary careanimal husbandryanimal transportationCovers all warm-blooded animalsexcludes rats, mice and birdsSpecific to research institutions –Much overlap with Public Health Service policyRats, mice of the genus Mus, and all birds: USDA does not currently cover themWhy: lack of manpower, high costs, etc. Not a high political priority (HSUS notwithstanding) Most rodents are considered (a) snake food or (b) VERMIN. Ongoing talk about expanding the AWA to cover these species, particularly pet-trade birds (like parrots)
25 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 policyAlso in 1985, Congress enacted Health Research Extension Act: Public Health Service in the animal-regulating businessPublic Health Service Policy on Humane Care and Use of Laboratory Animals (hold up booklet).PHS policy: Only research, testing and teaching activities funded by PHS money (taxpayer funds)Cover all vertebrate animals: rats, mice, birds, and anything else with a spine, like goldfish, snakes, and frogs.All PHS funded institutions must have an Assurance of Compliance with PHS Policy – a negotiated agreementHANDOUT #3 (FIRST ORANGE) – UCI’s OLAW Assurance, detailed description of our animal program.
26 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 methodsMain difference between the USDA regulations and PHS Policy:USDA’s focus is broader as far as use of the animals is concerned, but oversight is limited to warm blooded animalsPHS policy narrows the focus to animals used in research, testing and teaching, and broadens the species covered to include all live vertebrate animals. Key elements are essentially the same
27 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, 1959Two documents that provide the guiding principles for ethical treatment of animals in research.Unlike the regulations, these principles aren’t mandated by law, but rather they are the guidelines voluntarily followed by all ethical animal care and use programs.
28 NASA Principles - “Sundowner Report” Respect for LifeAll living creatures deserve respectSocietal BenefitSome valuable return in exchange for the sacrifice of the animal’s lifeNon-maleficience“Do no harm”Pain, distress and discomfort to the animals must be minimizedNASA Principles is based on three basic ethical principles.All life is precious and deserving of respectSocietal benefit – we talked about that as being basic to the whole issue of research in animals – some return for the animal’s sacrificeDo no harm, or rather as little harm as possible.
29 Principles of Humane Experimental Technique The 3 RsReplacementUse of live animals as the research model should be replaced if possibleRefinementProcedures should be refined to minimize pain, distress and discomfortReductionNumber of animals should be reduced to the minimum necessary to achieve scientific significance without increasing pain and distressThe other guiding principle for animal use is a book written in 1959 (quite a while before the first federal law came into being) - introduced the concept of “the three Rs”Replacement – use of computer models, commercially available or existing tissue or cell lines, in vitro or work with non-vertebrates (worms, fruit flies, etc.)Refinement – examples include use of anesthesia, post surgical pain relievers, techniques performed by experienced personnel (example, blood draw by inexperienced technician)Reduction – justify every animal’s life, make the best use each oneBalance: minimizing numbers without unduly increasing the pain and distress (such as multiple survival surgery) or sacrificing scientific rigor (not enough animals to prove the point)
30 Refinement Better living conditions for animals Minimising pain wherever possibleBetter training for animal technicians
32 ReductionRe-evaluating minimum numbers of animals for statistical significanceMethods allowing multiple procedures on single animalsBetter designed experiments to reduce numbers
33 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 officerIACUC reviews all research, testing and teaching projects on campus or elsewhere if supported by UCI-managed funds.Fed regs dictate who must be on the committee – incl. non scientist and representative from community (unaffiliated)Not all faculty members serving on the IACUC currently use animals – clinicians who work with human patients bring a valuable perspective to the committee, since they know what’s painful, what the disease process looks like, etc.
34 The IACUC’s RoleReview and approve activities involving animals at UCI (protocol review)Review the animal program and inspect all facilities every 6 monthsReview concerns involving animal useInvestigate issues of non-complianceReport to regulatory agenciesProgram review – semi-annual tune up of the program, try to troubleshoot what’s ahead.Facility inspection – physical walkthrough of all facilities, including laboratory areas if live animals are used there.Review concerns (whistleblower complaints) /investigate non-compliance – committee (chair) has the authority to suspend activities if necessaryNow I’ll hand the clicker back to Dr. Mulder and he’ll talk about ULAR’s role in UCI’s animal program.
35 Why Do We Review Protocols? The protocol is…The written documentation of all procedures to be performed on live animalsThe means by which adherence to the federal animal welfare regulations is assessedThe document that confirms the ethical treatment of animals used in the researchTo understand the process, let’s look at what the protocol is…
36 What Activities Require Review? Definition:“Any live, vertebrate animal used or intended for use in research, research training, experimentation, or biological testing or for related purposes.”-PHS PolicyThis is a definition from the Public Health Service policy. An animal care and use committee approval is required for all research involving…(read the definition). The words in red are the key terms
37 IACUC Protocol Review Rationale for the use of animals Justification of the species and number of animalsConduct of experimentsUnnecessary duplication of experimentsAppropriate sedation, analgesia, anesthesiaAdequate training of personnelDOCUMENTATIONWhy animals are necessaryHow procedures will be conducted – in detailUnnecessary duplication – that’s specifically listed in the regulations (USDA policy 12). Researchers must keep abreast of what’s being done in their field, and avoid repeating experiments unnecessarily.Analgesics, anesthesia and adequate training = all refinements
38 The Ethical Bottom Line The use of animals is a privilege, not a rightSociety grants permission to use animals with the expectation that health benefits may be derivedthe benefits to society outweigh the adverse effects imposed on individual animals (discovery and new knowledge)
39 Animal Welfare Regulations, Policies & Guidelines USDA 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 StandardsThese regulations establish the committee review procedures and information that needs to be contained in the protocol.They also set the requirement that all individuals working with animals be trained to handle the animals and perform the experiments.
40 Requirements before Working with Animals Be sure the IACUC approves you to work with animalsThe Lead Researcher must submit a modification request to add students to their protocolsComplete the animal tutorialComplete a Qualifications of PersonnelComplete a Work Health History form for EH&S’ Occupational Health Program
41 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
42 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 useNot sure if you taken the animal tutorial?Check the tutorial verification database
43 Lead Researcher Responsibilities Obtain all required approvals prior to commencing the research; follow IACUC approved proceduresEnsure 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
44 Responsibilities (continued) Acquire or procure all animals thorough ULARObtain annual renewals and 3-year renewal in order to continue working with animalswhen protocols expire, all animal work must stopfaculty & staff can access IACUC protocol information via the webPromptly report adverse events or problems to a ULAR Vet and the IACUC
45 Despite medical advancements associated with animal use and ethical arguments for animal experimentation prior to human experimentation there are those who believe animal have rights, the same as human beings.