Can Computer Models and Cell Cultures Replace Animal Research?
• Non-animal models are very important, but have limitations. They cannot duplicate the complicated interactions in a whole system.
• Final testing depends on studies in living, whole animals or people.
This is actually required by federal law.
Are the animals used in research &
education protected?
• Many federal and local laws ensure animals used in research & education are being treated
humanely.
• These include:
– Animal Welfare Act – Public Health Service
– IACUCs (committees that must approve research protocols)
– AAALAC (agency that accredits animal care facilities)
Animal Welfare Act
• The Animal Welfare Act is a Federal law that has been passed to protect warm-blooded animals (dogs, cats,
primates, guinea pigs, hamsters, and farm animals) used in research,
• bred for commercial sale,
• exhibited to the public,
• commercially transported.
The law requires standards of animal care to be established and enforced.
Animal Welfare Act
• Includes rules for mandatory surprise inspections of animal research facilities.
• These federal laws & regulations are in place to ensure that all research animals receive:
– Good veterinary care – Appropriate housing – Proper Feeding
– Humane handling
– Sound sanitation and ventilation
Lab animal care inspection
If research animals are not being cared for
properly, then the researchers that are
responsible are breaking the law!
Institutional Animal Care and Use Committees (IACUCs)/
Ethical committee
• Required at all research institutions.
• Committees consist of veterinarians, scientists, members of the public.
• Without IACUC approval, no research using animals may proceed.
• Among IACUC considerations
• To control potential pain and distress in animals
• Assess the potential value of any scientific outcome from the proposed studies.
• All animal protocols must be reviewed and approved by an outside monitoring committee.
Why do scientists care about animals?
• Can’t get good results from unhealthy or mis-treated animals. It is in the best interest of researchers to treat them well.
• Most animal research facilities have a dedicated staff whose provides daily care to the animals.
• Research animals must be cared for 7 days a week, 365 days a year regardless of weather or holidays.
“Good science and good animal care go hand-in-hand.”
The goal is to get reliable data and make sure animals are
healthy and well cared for.
The 3Rs
Replacement – Reduction –
Refinement –
The 3Rs are to improve animal welfare and scientific accuracy.
The Three R’s of using animals in research
• The Three R’s are principles of good science that scientists must adhere to when conducting
animal-based research.
First R- Replacement
Using non-animal alternative wherever they exist.
Animals used only when it
can be done no other way. This is synthetic skin.
It can be used in some research situations.
http://www.popsci.com/scitech/article/2009-07/scientists-design- technique-artificial-skin-mass-production
Alternatives
Scientists use many ways to try to replace animals by using cell cultures, computer modelling etc.
Researchers must, by law, use these techniques if they would be as effective as using animals.
Alternatives
Researchers also try to use the “lowest” type of
animal– perhaps a fish instead of a sheep or a fruit fly instead of a mouse.
or
• Second R- Reduction
– Using as few animals as possible to attain statistically significant results.
– Finding ways to cut down on the number of animals used for any specific piece of research.
• Third R- Refinement
– Finding ways of making animals’ lives better in labs, this can include toys for animals or other resources.
– Improving animal welfare in laboratories by
enhanced lab technician training, better enrichment inside the cages for animals, redesign of an
experiment, etc.
ETHICAL ISSUES
There are different regulations regarding research on different animals.
Species :
Fruit Flies Mice
Fish Cows Birds Dogs
Monkeys
Points to consider:
Cage sizes
Cage enrichment (toys etc.) Housing animals together Playtime
Veterinary checks
What research can be done
Animal Welfare and Animal Rights
• Animal welfare is not the same as animal rights.
– Animal welfare is fully supported by the scientific community.
– We should treat animals with compassion & provide for their humane treatment.
• Some groups argue that animals have the same rights as humans and should not be used even to preserve
human life, educate physicians or veterinarians, or cure human disease.
Animal Rights vs. Animal Welfare
Animal Rights
• Goal: To end all exploitation
• Ending:
Eating meat
Hunting
any medical or veterinary research, zoos, circuses, rodeos, horse shows, dog shows, animals performing in TV commercials, shows or movies
Using Guide-dogs for the blind
Using Police dogs
Using Search & rescue dogs
Owning pets
Animal Welfare
• Goal: To prevent suffering and cruelty to animals. To provide care and good homes for pets in need.
animal shelters for abandoned, abused, homeless, or unwanted pets.
Enforcement of anti-cruelty statutes
Monitoring and enforcement of legislation to ensure more
humane standards of care for livestock, laboratory animals, performing animals, and pets
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Alternative tests
•According to ECVAM (European Centre for the Validation of alternative methods)
•21 scientifically verified alternative methods
•For tests of phototoxicity, skin irritability,
embryotoxicity etc. are approved at present
time.
• 2D & 3D cell culture
• Computer modelling
• Molecular modelling
• Neuroimaging
• Equipment such as “organ on a chip”
• In vitro studies
• Volunteer studies
• Population research
• Human tissue studies
• Organ culture
• QSAR – toxicity testing
• ACuteTox – cell based toxicity
APPROVED Alternatives
• Fingerprinting microbes
• BioSIM – computer simulations
• Carcino GENOMICS testing for cancer
• Sens-i-iv for skin allergy tests
• ReProTect – toxicity testing
• TOXDROP miniaturised cell assays
• Predictomics for predicting long term safety
• Microdosing
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In vitro methods
Cell and tissue cultures
- plant, animal, human cells cultured in a laboratory - examples:
- Neutral Red assay – examined substance is added to the culture together with contrast dye which is absorbed by living cells only.
- HeLa cells – an immortal cell line used in oncological research derived from cervical cancer cells taken from
Henrietta Lacks 1951.
- 3T3 NRU phototoxicity test - test substance is added to cell cultures in various concentrations, then UV radiation is applied.
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Computer and mathematic models (in silico methods)
-generalizing models, quality of the prediction depends on the quality of input data
Tests in lower animals of lower ontogenetic stadium -Chicken embryo – replacement of DRAIZE test;
-eggs of African clawed frog (Xenopus laevis) –
-tests of mortality, malformations, growth inhibition
Alternative metods using animals
-toxicity of xenobiotics: reduction of number of animals - EYETEX screen test - protein solution prepared from beans –replacement of DRAIZE test of eye irritability.
Destruction caused by the chemical leads to opacification of the solution.
Microorganisms
-example: Ames’s test - test of mutagenicity, tested
substance is added to agar with Salmonella typhimurium with defective gene for histidine synthesis.
Several new approaches, e.g.,
stem cell-based: embryonic stem cell test;
Diseases-in-a-dish and organs-on-a-chip and lab-on-a-chip technologies
Analytical tools;
ex vivo organ models;
induced pluripotent stem cells;
non-invasive imaging;
patient-derived primary cells;
3D cell culture
Project-related: The project must be scientifically justified
essential character and ethical defensibility demonstrated.
experimental result may not be already available from other Person-related: PI of the research project and his deputy must Facility-related: The personal and structural
preconditions for the performance of the animal experiment must be given.
Experiments on animals with “advanced
nervous systems” may only be performed when experiments on animals without advanced nervous systems are inadequate.
Experimental animals must be specially bred. The use of stray dogs and cats is forbidden and “animal catchers” may not sell animals they have caught to laboratories.
Experiments on animals taken from nature are only allowed if specifically bred ani-
Project using animal model:Approval procedure
They require special permission.
More animals may not be used than necessary
. Pain, suffering and harm may only be inflicted on the animals to an extent that is inevitable. Anaesthesia to reduce pain
have priority.
Major operations may not be performed more than once on vertebrates.
If death is expected, the period of suffering must be kept as low as possible.
Follow-up medical care must be provided by a veterinarian, who can decide after an experiment whether the animal can continue to live without pain and suffering.
Animal testing:
History of models :
Challenges faced in extrapolation:
Recommending reading: Online resources
