Use of Animals in Research

Use of Animals in Research
Alison Smith, DVM, DACLAM
Animal Care
Surgery and Postoperative Care
Animal Ordering
Collaborative Research
Technical Services
US Laws and Regulations
Animal Welfare Act
Health Research Extension Act –
PHS Guidelines
NRC “Guide for the Care and Use of
Laboratory Animals”
Other Guidelines
Veterans Administration
State and local
“Guide for the Care and Use of Agricultural
Animals in Agricultural Research and
Guidelines by other professional societies
Panel on Euthanasia
Panel on Surgery
Case Study #1
You would like to test several new
compounds for efficacy to produce tumor
regression in a scid mouse model of breast
cancer. Experimental groups include
controls that receive vehicle only, mice that
have received subcutaneous injections of
two different human breast cancer cell lines,
and a metastic model produced by i.v.
injection of cancer cells.
Case Study #1
The drugs to be tested must be
administered via different routes. One
must be given orally, daily for 3 weeks.
The other must be given by i.v. injection
every 3 days for 3 weeks. What technical
details must be considered to ensure that
animals receive the required amount of
study drug?
Case Study #1
Study design
Both drugs fall under the category of chemotherapy,
i.e. potentially toxic, drugs.
Are special precautions necessary?
If so, what are they?
Are there any precautions posed by the cell lines
used to create the tumors?
Case Study #2
A company has developed several new compounds
that may promote bone healing. Their standard
model for this stage of development is to produce
bone defects in the rear limbs of rabbits that are filled
with a matrix impregnated with the various test
compounds. They have approached you about
performing the study here at MUSC because of your
expertise in this area. Although you do not have the
surgical expertise to perform the surgery, you have
arranged to collaborate with a trained orthopedic
surgeon. The experimental time points for harvesting
the implants are 6 weeks and 6 months.
Case Study #2
Study design
The company has decided to fund the project here
at MUSC, but you discover soon afterwards (but
prior to project initiation) that the MD surgeon has
no previous experience performing orthopedic
procedures on rabbits.
– What are your options?
– If a rabbit develops clinical problems prior to
the experimental endpoint(s), what should be
Case study #3
The emphasis in your laboratory is to develop new
biomaterials for human use. The current project
requires that the implant under development is
seeded with cartilage cells that have been expanded
in culture after aseptic harvest from an animal. To
avoid issues involving tissue rejection and the need
to use immunosuppressive therapy, the model will
involve implanting the seeded device into the same
animal from which the cells were harvested. There
will be 6 weeks between operative procedures and
different surgical sites will be used for cell harvest
and device implantation. The device will be
harvested 6 months after implantation.
Case Study #4
Your current animal research is proceeding well despite being
technically challenging and time consuming. You surgically
implant mice with jugular catheters and then train them to selfadminister alcohol by standard lever pressing techniques.
Using standard behavioral techniques of extinction and reinstatement you then use a battery of behavioral tests to test the
ability of various test substances to alter alcohol selfadministration in your experimental mice.
You realize that your work is taking you in a direction that will
require you to examine brain neurotransmitters by analyzing
microdialysates from implanted brain cannulas. This means that
your mice will require two implants at different sites, but the
technique will help elucidate the mechanism of action for the
compounds under study.
What factors will determine
euthanasia method(s) appropriate for
study objectives?
Potential interactions with
DLAR personnel
• Animal care technicians
– will alert you if they notice health problems. They
may also simultaneously alert DLAR veterinary
tech/vet if they believe the problem is potentially
• May result in a recommendation for
euthanasia from DLAR vet if problem is
considered to be a humane issue. Prompt
response from research staff expected for
health-related issues.
Top 5 Questionable Practices
• Incomplete knowledge regarding
requirements for rodent survival surgery,
including use of aseptic technique
• Incomplete knowledge of the animal
protocol. Have you read the protocol? Is
there a copy in the lab for research
personnel to access (recommended ‘best
practice”)? If there are multiple animal
protocols, be sure usage matches the
Top 5 Questionable Practices
• Training
• Knowing when it is OK to modify a
protocol. What changes are
• Viewing DLAR and the veterinary
staff as the animal police.