Research with animals and animal models

1. Research with animals
and animal models
S. Parasuraman, M.Pharm., Ph.D.,
Snr. Associate Professor & Unit Head,
Unit of Pharmacology,
Faculty of Pharmacy, AIMST University,
Bedong 08100, Malaysia.

2. Why Animals are Used in Research?*
• Animals are biologically very similar to humans. In fact,
mice share more than 98% DNA with us!
• Animals are susceptible to many of the same health
problems as humans – cancer, diabetes, heart disease,
etc.
• With a shorter life cycle than humans, animal models
can be studied throughout their whole life span and
across several generations, a critical element in
understanding how a disease processes and how it
interacts with a whole, living biological system.
*https://med.stanford.edu/animalresearch/why-animal-research.html?tab=proxy [Last assessed on 20/12/2023]

3. Why Animals are Used in Research?
• Animals have unique and important roles in biomedical
and behavioral research.
• Animals used in basic research can help researchers to
understand important biological and physiological
processes. This understanding may inform how can
better prevent, diagnose, treat, and cure diseases.
• For more than 2000 years, humans have used animal
models (e.g., dogs, chicks, pigs, rats, monkeys) to
understand our own biology, behavior, and health.*
*Phillips NLH, Roth TL. Animal Models and Their Contribution to Our Understanding of the Relationship Between
Environments, Epigenetic Modifications, and Behavior. Genes (Basel). 2019 Jan 15;10(1):47.

4. About Animal Testing*
• The term “animal testing” refers to procedures
performed on living animals for purposes of research
into basic biology and diseases, assessing the
effectiveness of new medicinal products, and testing
the human health and/or environmental safety of
consumer and industry products such as cosmetics,
household cleaners, food additives, pharmaceuticals
and industrial/agro-chemicals.
*https://www.hsi.org/news-resources/about/

5. Types of animals are used in research*,#
• Mice
• Fish
• Rats
• Rabbits
• Guinea pigs
• Hamsters
• Birds
• Cats
• Dogs
• Non-human primates
(monkeys, and in some
countries, chimpanzees)
* https://www.hsi.org/news-resources/about/
# https://www.rspca.org.uk/home

6. Annual number of animals used in research and
testing in selected countries worldwide as of 2020*
* https://www.statista.com/statistics/639954/animals-used-in-research-experiments-worldwide/
Numbers in 2020 – By c
•United States 20 million
•China 16 million
•Japan 11 million
•European Union 9.4 million
•Australia 6.7 million
•Canada 4.3 million
•New Zealand 0.24 million

7. *1Phillips NLH, Roth TL. Animal Models and Their Contribution to Our Understanding of the Relationship Between
Environments, Epigenetic Modifications, and Behavior. Genes (Basel). 2019 Jan 15;10(1):47.
Relationship between animal models and human
studies*
• Both provide important insight into biology and behavior, guide the direction of one
another’s research
• Non-human animal models utilize genetic, epigenetic, and pharmacological
manipulations to help elucidate mechanisms

8. Animal models
Definition (By National Human Genome Research Institute [NIH])*
• An animal model is a non-human species used in biomedical
research because it can mimic aspects of a biological process or
disease found in humans. Animal models (e.g., mice, rats,
zebrafish and others) are sufficiently like humans in their
anatomy, physiology or response to a pathogen that researchers
can extrapolate the results of animal model studies to better
understand human physiology and disease. By using animal
models, researchers can perform experiments that would be
impractical or ethically prohibited with humans.
*https://www.genome.gov/genetics-glossary/Animal-Model

9. categories of animal models*
• There are four main categories of animal models:
1. Induced or experimental models (attempt to reproduce
conditions found in the original species)
2. Spontaneous or natural models (recognized as being similar
to some condition in the original species)
3. Negative or nonreactive models (normal counterparts of a
disease model)
4. Orphan models (diseases for which there is no human
analog)
*Davidson MK, Lindsey JR, Davis JK. Requirements and selection of an animal model. Isr J Med Sci. 1987 Jun;23(6):551-5.

10. Requirements and selection of an animal models*
• Animal models for research should be based on the
following considerations:
1. appropriateness as an analog
2. transferability of information
3. genetic uniformity of organisms, where applicable
4. background knowledge of biological properties
5. cost and availability
6. generalizability of the results
7. ease of and adaptability to experimental manipulation
8. ecological consequences
9. ethical implications.
*Davidson MK, Lindsey JR, Davis JK. Requirements and selection of an animal model. Isr J Med Sci. 1987 Jun;23(6):551-5.

11. Commonly Used Animal Models - The Mouse*
*Hickman DL, Johnson J, Vemulapalli TH, Crisler JR, Shepherd R. Commonly Used Animal Models. Principles of Animal
Research for Graduate and Undergraduate Students. 2017:117–75.
Model Generation Uses Examples
Inbred strains
20 or more consecutive
generations of sister × brother or
parent × offspring matings
Studies that require
genetically identical
animals
BALB/c, C3H, C57BL/6,
CBA, DBA/2,
C57BL/10, AKR, A,
129, SJL
Outbred stocks
Deliberate mating of unrelated
animals
Studies that require
outbred vigor
Swiss Webster, CD-1,
ICR
Spontaneous
mutant
Strains that have been bred to
conserve phenotypical
characteristics that were due to
spontaneous genetic mutations
Studies of disease
processes associated
with the spontaneous
mutation
Athymic nude,
nonobese diabetic
(NOD)
Genetically
engineered
mice/“Knock-
in”/“Knock-out”
Mice where genes have been
turned on or off
Studies that are seeking
to identify the effects
of specific genes
Transgenic
Mice where a gene from an
unrelated species has been
inserted into the genome
Studies that require a
mouse model of human
disease and toxicology
Mouse fanciers around the turn of the 20th century are the source of the majority
of the laboratory mice that are in use today.

12. Commonly Used Animal Models - The Rat*
• Rattus norvegicus constitutes one of the most
commonly used laboratory species, second only to the
laboratory mouse.
• Rats have been used as animal models in numerous
areas of research from space exploration to answering
more basic scientific questions regarding nutrition,
genetics, immunology, neurology, infectious disease,
metabolic disease, and behavior. Also, the rats are
largely used in drug discovery, efficacy, and toxicity
studies.
*Hickman DL, Johnson J, Vemulapalli TH, Crisler JR, Shepherd R. Commonly Used Animal Models. Principles of Animal
Research for Graduate and Undergraduate Students. 2017:117–75.

13. Commonly Used Animal Models - The Rabbit*
• The New Zealand White rabbit is the most frequent
breed of used in research. The California and Dutch-
belted rabbit breeds are also occasionally used.
Researchers have developed genetically inbred rabbit
strains for particular research applications.
• Rabbits have been used as a model of human pregnancy and
for the production of polyclonal antibodies for use in
immunology research.
• Rabbits are routinely used in atherosclerosis, osteoporosis,
ocular, and immunology research
*Hickman DL, Johnson J, Vemulapalli TH, Crisler JR, Shepherd R. Commonly Used Animal Models. Principles of Animal
Research for Graduate and Undergraduate Students. 2017:117–75.

14. Commonly Used Animal Models - The Zebrafish*
• Publications on the use of zebrafish in research are
cited as early as the 1930s.
• Developmental biology was the initial focus of zebrafish
research use.
• In recent years, use of the zebrafish in research related
to biochemistry and molecular biology, cell biology,
neurological sciences, and genetics
• Interestingly, approximately 70% of zebrafish genes
have at least one orthologous human gene.
*Hickman DL, Johnson J, Vemulapalli TH, Crisler JR, Shepherd R. Commonly Used Animal Models. Principles of Animal
Research for Graduate and Undergraduate Students. 2017:117–75.

15. Commonly Used Animal Models - Amphibians and
Reptiles*
• Frogs are important for studying embryonic
development, metamorphosis, regeneration,
physiology, and climate change.
• Reptiles are used in studies because of their more
simple cardiovascular systems as well as for evaluating
mechanisms of immune responses, hormonal controls,
and unique reproduction methods such as
parthenogenesis.
*Hickman DL, Johnson J, Vemulapalli TH, Crisler JR, Shepherd R. Commonly Used Animal Models. Principles of Animal
Research for Graduate and Undergraduate Students. 2017:117–75.

16. Commonly Used Animal Models – Birds*
• Birds have been used as research models of human disease
and are important in evaluation of aging, memory,
parasitology, atherosclerosis, reproduction, and infectious
disease.
• Historically, chickens (Gallus domesticus) are the most
common bird species studied in biomedical and agricultural
research and are a classic model in areas such as
immunology, virology, infectious disease, embryology, and
toxicology.
• Chickens are also studied to evaluate reproductive
development and retinal disease.
• Embryonated chicken eggs have been used to commercially
produce vaccines (human influenza).
*Hickman DL, Johnson J, Vemulapalli TH, Crisler JR, Shepherd R. Commonly Used Animal Models. Principles of Animal
Research for Graduate and Undergraduate Students. 2017:117–75.

17. Commonly Used Animal Models - Other Small
Mammals*
• The guinea pig has been used as a model for infectious
diseases such as tuberculosis, Legionnaires disease, sexually
transmitted diseases such as chlamydia and syphilis. Guinea
pigs have also been useful tools in researching cholesterol
metabolism, asthma, fetus and placental development and
aspects of childbirth, as well as Alzheimer's disease.
• Hamster (Golden or Syrian hamster) utilized in studies of
infectious disease, parasitology and dental disease.
Hamsters are still used in many areas of research, including
investigations into metabolic diseases like diabetes mellitus,
cardiovascular disease, reproductive endocrinology, and
oncology.
*Hickman DL, Johnson J, Vemulapalli TH, Crisler JR, Shepherd R. Commonly Used Animal Models. Principles of Animal
Research for Graduate and Undergraduate Students. 2017:117–75.

18. Commonly Used Animal Models - Other Small
Mammals*
• Chinchillas has a large head, large eyes and ears. The
large inner ear anatomy is of specific note as chinchillas
are the traditional model for auditory studies and otitis
media.
• Gerbils (Mongolian gerbils) used as a model for
cerebral ischemia or stroke.
• Armadillo is response to the infectious organism,
Mycobacterium leprae, have made it an ideal model for
studying leprosy.
*Hickman DL, Johnson J, Vemulapalli TH, Crisler JR, Shepherd R. Commonly Used Animal Models. Principles of Animal
Research for Graduate and Undergraduate Students. 2017:117–75.

19. What’s wrong with animal testing?*
• Annually, more than 115 million animals are used
worldwide in experimentation or to supply the
biomedical industry.
• Three major conditions undermine this confidence and
explain why animal experimentation, regardless of the
disease category studied, fails to reliably inform human
health:
• the effects of the laboratory environment and other variables
on study outcomes,
• disparities between animal models of disease and human
diseases, and
• species differences in physiology and genetics.
*Akhtar A. The flaws and human harms of animal experimentation. Camb Q Healthc Ethics. 2015 Oct;24(4):407-19.

20. Alternatives to animal testing*
• Testing cells and tissues in test tubes or cell cultures
• 3D tissue culture
• Computational and mathematical models
• Stem cell research
• Non-invasive diagnostic imaging
• Clinical research - involving people
*https://grants.nih.gov/grants/policy/air/alternatives

21. Facts*
*https://worldanimalfoundation.org/advocate/animal-testing-statistics/
• More Than 70% of the Research Monkeys in the US Were
Imported From China (Wiley)
• Almost 85–95% of the Animals in the USA Are Not Protected by
Any Laws (ALDF)
• In 2020, Mice, Fish, Rats, and Birds Accounted for 91% of
Animals Used in Research Experiments Conducted in Europe
(European Union)
• The US Conducts Almost 53% of Its Scientific Research on
Rabbits, Pigs, and Hamsters (Speaking of Research)
• Back in 2020, 54% of the Scientific Experiments Were Conducted
on Different Animals in UK Universities (UK Gov)
• NIH Has More Than 7,000 Research Monkeys (Science)
• 52% of Adults in the U.S. are Against Animal Experimentation
(PETA)

22. Facts*
*https://worldanimalfoundation.org/advocate/animal-testing-statistics/
• Only About 8% of the Drugs Tested on Animals Have Been
Commercialized. (PETA)
• 95% of the Drugs Which Prove Potency in Animals Have Failed in
Humans. (PETA)
• 100 HIV Vaccines Are Effective in Animals but Have Shown No
Results in Humans. (PETA)
• In the First Phase of Clinical Trials, More Than 93% of the
Chemotherapeutic Drugs Tested on Animals Previously Were
Rejected. (PETA)
• Almost 70% of Nobel Prize Achievers Made Discoveries via
Animal Testing. (Medical Advances)
• Animal Testing Stats Revealed a Reduction Rate in Polio Disease
Occurrence. (WHO)