Office for the
Responsible Conduct of Research
Use of live, vertebrate
animal subjects in research
B. Helen Jost, PhD
IACUC Director
IACUC Co-Chair
Historical use of research animals

Research animals have been used as human
surrogates for well over a century
 Without regulation
 Often without concern for animal welfare

During that time, there were a number of
animal cruelty laws in several states across
the country
 However, there were no laws that specifically
addressed the procurement and use of animals in
research
Genesis of animal research regulation

Several affiliated research groups formulated
and used standards of care for rodents
 Standardized conditions were important to
experimental reproducibility
 Animal welfare was also considered (3 R’s)

Dognapping of “strays” to sell to research labs
was a reality
 In 1965, a story in Time about Pepper the
Dalmatian sparked a strong desire across the
country to halt this practice
The Animal Welfare Act

The Animal Welfare Act (AWA) was
enacted in 1966
 Only included dogs and cats
The AWA covers animals used in commerce,
exhibition, teaching, testing, and research
 The AWA excludes:

 Cold-blooded animals (reptiles, fish, frogs)
 Animals used for agriculture (cattle, pigs, sheep, goats,
horses, llamas)
 Mice, rats and birds purposely bred for use in research
■
90% animal research uses lab mice and rats
AWA oversight
Unannounced inspections by a USDA
Veterinary Medical Officer (VMO)
 The VMO is charged with identifying
non-compliance with the AWA and its regulations

 Visits facilities, inspects animals, reviews records

Non-compliant items (NCIs) are published on-line
and may incur fines
 Identification and correction prior to inspection is
not cited as an NCI
Public Health Service Assurance

Institutions receiving PHS funds for animal
research must assure that research will be
conducted as described in the PHS Policy on
the Humane Care and Use of Laboratory
Animals
 Must follow all applicable laws
 Must follow the Guide to the Care and Use of
Laboratory Animals

The Assurance is renewed every 5 years, with
reports submitted annually
 Without this Assurance there is no NIH/NCI funding
for research involving animals
OLAW oversight
The Office of Lab Animal Welfare
monitors compliance with the PHS Policy
 OLAW uses a mechanism of self-policing and
self-reporting

 The institution identifies non-compliance and reports to
OLAW with corrective actions

There are no unannounced inspections
 However, audits can occur, usually for cause

Serious and uncorrected violations can result in
the loss of PHS funding
 To individuals
 To the institution as a whole
AAALAC accreditation
 Association
for the Assessment and
Accreditation of Laboratory Animal Care
 AAALAC is a voluntary organization that makes
recommendations based on results of site visits
 Standards are continually updated to reflect
current knowledge in laboratory animal science
 OLAW
accepts AAALAC accreditation
in lieu of additional OLAW oversight
Regulatory authority at UA

The University of Arizona is:
 Registered with the USDA as a research institution
 PHS assured
 AAALAC accredited

The Institutional Official (IO) has ultimate
responsibility for the animal care and use
program
 Vice President for Research

The Institutional Animal Care and Use
Committee (IACUC) administers the animal
care and use program
The IACUC

IACUC membership must include:
 Scientists
 Veterinarians
 Non-scientists
 Non-affiliated “community” members

Due to the diversity of the Committee, the
rationale for the use of animals must be
written in easy to understand language
 The “lay” description

Unlike humans, animals can’t consent
 The IACUC acts as their voice
IACUC responsibilities

Oversees the Animal Care and Use Program
 Make recommendations to the IO for improvements

Inspects animal housing and research labs
 Semi-annual inspections

Ensures protocol participants have training
 To understand the laws and ethics of animal research
 To conduct specific animal activities
 To understand occupational health issues

Reviews and approves animal research and
teaching
 Protocols and amendments
IACUC review of animal studies
 IACUC
review and approval is required for
all activities involving warm and cold
blooded vertebrate animals, including:
 Research
 Teaching
 Agriculture or field studies
 Use of UA-funded animals at other institutions
 Approval
must be obtained before the
work begins
Description of animal activities
A brief description of the aim/purpose
 A narrative description of all animal activities, in
the order they will occur
 Identification of the scientific endpoints

 The point at which the experimental aims are met

Identification of humane endpoints
 The point at which animals must be removed from the
study, even if the experimental aims are not met

Identification of pain and distress
 Clinical signs
 How will pain/distress be alleviated?
 Why can’t pain/distress be alleviated?
Modifications to approved activities
 Any
changes in your research with animals
must be approved before the work starts
 Additional animals or species
 Addition of new strains or breeding
 New or modified procedures or time points
 Additional of surgery
 Additional drugs/compounds
 Changes in dosages/administration route
 Changes in euthanasia methods
The ethical balance
Scientific
value
Ethical
cost
 To humans
 Pain
 To animals
 Distress
 To science
 Morbidity
 To society
 Mortality
The 3 R’s (Russell and Birch, 1959)
3 R’s are one tool that the IACUC uses
to balance the scales
 The
 Can we replace the use of animals with
non-
animal models or lower species?
 Can we reduce the number of animals used and
still achieve statistically significant data?
 Can we refine the procedures to minimize or
eliminate pain and distress?
Do animals need to be used?

Does the benefit outweigh the harm to the animal?
 The data can be translated into future human or animal
clinical studies
■
Development of drugs or therapies
 When there are clear benefits to society and the
advancement of knowledge
■

Species ecology and conservation
Can a non-animal model be used?
 In vitro assays, tissue culture
 Computer models, simulations
 Manikins, especially for training
Does the species need to be used?

Hierarchy of species
 Non-human primates
 Farm animals (cattle, pigs, sheep)
 Rabbits, ferrets
USDA
regulated
 Companion animals (dogs, cats)
 Guinea pigs, hamsters, gerbils
 Lab rats
 Lab mice
 Fish, frogs
 Invertebrates

Ag and field studies do not follow this paradigm
 Not animal models
Are the fewest animals used?

The number of animals requested must be
justified

The number of animals per experimental
group should be consistent with generation
of scientifically sound data
 Justification
can include use of:
 A statistical method to ensure a p value
 Previously documented experience (PI or
literature)
The most important R – refine?
Review current scientific literature to identify
modified techniques that reduce pain or distress
 Use appropriate sedation, analgesia and/or
anesthesia for painful or distressful procedures
 Limit the number of procedures experienced by
any individual animal
 Ensure adequate post-procedural care



Know the signs of pain and distress
Identify appropriate scientific and humane
endpoints

Remove animals from the study based on humane
endpoints to minimize pain and suffering
The ethics of animal research

Animal research is affected by the same ethical
issues as other kinds of research
 Data fabrication or falsification; researcher bias;
conflict of interest; intellectual property issues;
misuse of funds

However, there is also protocol non-compliance,
that is performing animal activities that have not
been reviewed and approved by the IACUC
 Non-compliance may be reportable to the USDA or
OLAW

It is critical that everyone know what is approved
 Submit amendments to modify animal activities before
starting the work
The ethics of animal research

As scientists, we should be aware of the impact
that animal research has on our accumulated
knowledge
 Much of what we know about the biological sciences
had its start with animal research
 Most human studies being conducted today rely directly
or indirectly on data from animal studies

However, animal research should only be
undertaken
 After careful consideration of the scientific value
obtained as compared to the ethical cost of using
animals
 With the utmost concern for animal welfare
IACUC Contacts
Sean Limesand, PhD, IACUC Chair
Phone: 626-8903
Email: limesand@email.arizona.edu
 David Besselsen, DVM, PhD, Attending Veterinarian
Phone: 626-1066 or 621-1564
Email: besselsd@email.arizona.edu
 Helen Jost, PhD, IACUC Director and IACUC co-Chair
Phone: 626-5304
Email: jost@email.arizona.edu

Or email: ORCR-iacuc@email.arizona.edu
Resources

USDA Animal Welfare Act
 http://www.aphis.usda.gov/wps/portal/aphis/ourfocus/an
imalwelfare?1dmy&urile=wcm%3apath%3a%2Faphis_
content_library%2Fsa_our_focus%2Fsa_animal_welfar
e%2Fsa_awa%2Fct_awa_program_information

PHS Policy
 http://grants.nih.gov/grants/olaw/references/phspol.htm

The Guide
 http://grants.nih.gov/grants/olaw/Guide-for-the-Care-
and-Use-of-Laboratory-Animals.pdf

IACUC home page
 http://orcr.arizona.edu/iacuc