This document provides background information on common laboratory animals used in drug development. It discusses how rodents like rats, mice, and guinea pigs are widely used due to their low cost, ease of handling, and physiological similarities to humans. Rats and mice are used in toxicity, cancer, and genetic studies. Guinea pigs were important in developing vaccines and studying respiratory diseases. Rabbits, dogs, cats, and monkeys are also used as they resemble humans in size or have similar organ systems. Other animals discussed include frogs, zebrafish, chickens, and pigeons which provide models for specific research areas. While animal testing has advanced medical knowledge, it unfortunately requires animals to be killed or kept in captivity.
2. BACKGROUND
• The first major reference to animal testing occurred in the late nineteenth century
when Louis Pasteur administered anthrax to sheep and showed the importance of
vaccines with his germ theory.
• Charles Darwin's evolutionary theory in the mid 1850s also served to suggest that
animals could serve as effective models to facilitate biological understanding in
humans.
• Other cases of animal testing include psychological experiments such as the one by
Ivan Pavlov in the late nineteenth century. He conducted experiments on dogs to
demonstrate how dogs could be conditioned with regards to memory and repetitive
tasks.
• An enormous breakthrough came in 1922 when animal testing allowed for insulin
to be isolated from dogs. In the 1930s, modern anaesthetics and antibiotics were
developed from the use of animal testing. In addition, anticoagulants and kidney
dialysis, both life-saving treatments, were introduced following animal testing.
• The 1950s saw animal testing aiding in the development of vaccines. The other
developments include many potent cancer drugs as well as drugs for HIV that were
developed in the latter quarter of the twentieth century
3. Why are animals used in clinical
research?
• The basic cell processes are the same in
all animals, and they perform similar
vital functions such as breathing,
digestion, movement, sight, hearing and
reproduction
• Simple animals can be used to study
complex biological systems such as the
nervous or immune systems, which
follow the same basic organisation and
function in all animals.
To advance
scientific
understanding
4. • Studying disease mechanisms in animal models
leads directly to the development of new
technologies and medicines that benefit both
humans and animals.
• While contributing to our understanding of
diseases, animal models enable researchers to
explore potential therapies in ways which would
be impossible in humans.
• Animals which are altered to create models of
disease are known as induced models.
• These animal models help researchers understand
what happens in the body following this type of
damage, and have been used in the development of
new therapies.
• Recent advances in genetic technology have
allowed the development of transgenic animals,
which have new genes inserted into their DNA,
allowing them to develop human diseases which
do not naturally affect them.
As
models
to study
disease
5. • Once researchers learn more about a particular disease,
animals are used to develop and test these potential
therapies as part of the applied research process.
• Data from animal studies is essential before new
therapeutic techniques and surgical procedures can be
tested on human patients.
• For example, medicines for Parkinson's disease have
been developed using animal models with induced
Parkinson's-like symptoms.
• Diagnostic tools such as scanners, and implants such as
pacemakers are safe and effective only because they
were developed and tested in animals.
• Many surgical techniques, such as open heart surgery
and heart transplants, rely on methods and equipment
that were developed using animals.
To
develop
and test
potential
forms of
treatment
6. • New medicines require testing because researchers
must measure both the beneficial and the harmful
effects of a compound on an organism.
• The animal tests provide data on efficacy and
safety of a new compound. They not only identify
potential safety concerns, but also determine the
doses which will be given to volunteers and
patients during the first human trials.
• Testing on animals also serves to protect
consumers, workers and the environment from the
harmful effects of chemicals.
To protect
and ensure
the safety of
people,
animals and
the
environment
11. RAT(Rattus norvegicus)
Rats have been useful for research in the following fields-
• Study of analgesics and anticonvulsants.
• Study of oestrus cycle, mating behaviour and lactation.
• Gastric acid secretion
• Hepatotoxicity studies
• Study on mast cells
• Bioassay of various hormones, such as insulin, oxytocin, vasopressin .
• Rats are better at removing toxins from their bodies than humans, so it may be
possible to refine the use of rats in toxicology studies.
• Rat brain tissue is extensively employed in radio-receptor ligand studies.
12. WISTAR RATS
These were developed at the Wistar
Institute in 1906 and is notably the first rat
developed to serve as a model organism.
The Wistar rat is currently one of the most
popular rats used for laboratory research.
It is characterized by its wide head, long ears,
and having a tail length that is always less than
the body length.
SPRAGUE DAWLEY RATS
These rats typically have increased tail to body
length ratio as compared to Wistar rats.
13. Long-Evans rat
They are utilized as a multipurpose
model organism, frequently in
behavioral and obesity research
ZUCKER RATS –
They are genetically modified rats used
to study obesity and hypertension.
14. BIOBREEDING RATS –
They are used as models to study
autoimmune type 1 diabetes
HAIRLESS RATS –
They are use to study compromised
immune systems and genetic kidney
diseases.
15. DIFFERENCE BETWEEN RATS AND MICE
• The rat is much larger in size and has greater body wieght as
compared to the mouse.
• The mouse has a pointed face when compared to the rat.
• The rat has a thick and heavy tail. On the other hand, a mouse
has a very thin tail
• The rat has a higher pair of chromosomes, ie 22 pairs. On the
contrary, the mouse has only a 20 pairs.
• The rats have a longer gestation period compared with the
mice.
16. MICE(Mus musculus)
• They are most widely used in clinical
research as they are small, inexpensive and
easy to handle .
• Mice are used in a vast range of experiments,
many of which are classified as fundamental
research, investigating the physiology of
mammals.
• They have similar reproductive and nervous
systems to humans, and suffer from same
diseases such as cancer, diabetes and even
anxiety
• Their short life span and fast reproductive
rate, makes it possible to investigate
biological processes at all stages of the life
cycle.
• Swiss albino mice are the most commonly
used species.
17. EXPERIMENTAL USES
• Toxicological studies
• Teratogenicity studies
• Bioassay of insulin, screening of analgesic and
anticonvulsant drugs
• Screening of chemotherapeutic agents
• Studies related to genetics and cancer research
• Drug action on CNS
18. GUINEA PIG(Cavia porcellus)
• Guinea pigs have biological
similarities to humans, which
make them useful in many fields
of research.
• Vitamin C was discovered
through research on guinea pigs.
• Their serum contains enzyme
Aspariginase which shows anti-
leukaemic action.
They were also crucial to the
development of :
• Vaccines for diphtheria, TB,etc
• Evaluation of local anaesthetics
19. • Antibiotics,
• Histamine and antihistamines
• Anticoagulants
• Bronchodilators
• Bioassay of Digitalis.
Guinea pig tissue
• Guinea pig blood components and isolated organ preparations such as lung
and intestines are extensively used in research to develop new medicines.
• Terminal portion of ileum used for screening spasmodic and anti spasmodic
agents.
• They were important in the discovery and early development of beta
blockers to treat high blood pressure and drugs to treat stomach ulcers.
• Numerous developments have used their intestine for example the anti-
nausea drugs used by cancer patients and the identification of naturally
occurring pain killing substances known as enkephalins.
20. • Allergies and respiratory diseases
• The extreme allergic reaction, anaphylactic shock has been studied
extensively in guinea pigs.
• Their airway is sensitive to allergens, so it has been widely used
in asthma studies. The inhaled medications that are the mainstays
of asthma treatment were developed using guinea pigs as were
orally-active drugs for asthma such as montelukast.
• They are also used in the testing of vaccines against anthrax and
new medicines to treat drug-resistant tuberculosis.
• Also used to test for allergic skin reactions due to their skin
sensitivity.
21. • Nutritional research
Along with Vitamin C , guinea pigs also need high levels of
folic acid, thiamine, arginine and potassium, which make them
useful in nutrition studies.
• They also carry most of their plasma cholesterol in low density
lipoprotein, so they are also useful in the study of cholesterol
and lipoprotein metabolism.
22. • Infectious Diseases
• The German scientist Robert Koch used guinea pigs to discover
that TB was caused by the bacterium Mycobacterium tuberculosis.
• In 1919 research showed that inoculation of guinea pigs with a small
amount of blood from Yellow Fever patients produced a mild
reaction in the animals. The same animals were later resistant to
infection with Leptospira icteroides
• The animals which had received no previous inoculation, or which
had been inoculated with blood from malaria patients, died.
• Safety testing
• The long gestation period of 59–72 days and mature central nervous
system at birth means that guinea pigs are important in safety testing,
particularly to prevent birth defects .
23. GERBIL(Meriones unguiculatus)
• Also known as sand rats or jirds.
Their size lies between that of rats
and mice.
• Used as research animal in stroke,
epilepsy and heart diseases.
• Useful in study of parasitic and
bacterial infections.
• Used in auditory studies because
hearing curve is similar to that of
humans.
24. HAMSTER(Mesocricetus Auratus)
• Third commonly used laboratory
animal.
• Two species are commonly used-
Golden or syrian hamster
Chinese hamster
25. • Hamsters are used extensively in onco virus, Influenza virus and
Respiratory Syncitical Virus (RSV) studies and vaccine production.
• Their cheek pouches do not have lymphatic drainage and hence they are
ideal sites for tissue transplants.
• Syrian Hamster is most commonly used for biomedical research because of
ease of availability.
• European Hamster is more suitable model for highly concentrated and
prolonged smoke inhalation studies.
• Chinese Hamster is suitable for cytogenesis research.
27. RABBIT(Oryctolagus cuniculus)
• Historically, Louis Pasteur used
rabbits to develop the rabies
vaccine.
• Studies in rabbits are key to
many aspects of medical research,
including cancer, glaucoma, eye
and ear infections, skin
conditions, diabetes and
emphysema.
• The rabbit has been important in
the study of cardiovascular
diseases , particularly
hypertension and atherosclerosis.
• Enzyme atropine esterase is
present in rabbit liver and plasma
so it can tolerate large doses of
belladona (atropine)
28. RABBITS HAVE BEEN USED FOR RESEARCH IN FOLLOWING FIELDS -
• Pyrogen testing
• Bioassay of anti-diabetic drugs
• Screening of agents affecting capillary permeability
• Drugs used in glaucoma
• Studies related to antifertility agents
• It has simple cardiac tissue free of connective tissue and hence is the animal of
choice for cardiac studies.
• The rabbit has provided an excellent model system to simulate the response of
human tissue to the radiation produced by surgical lasers.
• Laser advancements made possible by research on rabbits include eye surgery and
the dissolving of plaque build-up on the walls of arteries.
• TESTING OF COSMETICS USING DRAIZE TEST –
• Rabbits - particularly albino rabbits - are commonly used in testing for cosmetics
and other chemicals, where they are used to perform the Draize test. This test
involves the substance being placed on the rabbit's eyes or skin, which are then
observed for redness, irritation or any other damage.
29. MONKEY(Macaca mulatta)
• Used as primate model
to study drug
metabolism .
• Suitable for undertaking
psycho-pharmacological
studies.
• Uterus resembles that of
humans, showing
regular menstrual
cycles.
• Best for studying drugs
acting on CNS, CVS,
GIT and fertility.
30. CAT(Felis catus)
Since 1898, cats have contributed to the
study of emotion, cardiac disease, spinal
cord injury, cataract surgery, glaucoma,
lupus, diabetes, spina bifida and more.
• Cats are mainly used as models to study
sensory systems and neuroscience.
• Cats have a distinct nictitating membrane
used for studying ganglionic drugs.
• Cats have been used to study neurological
problems, such as epilepsy, deafness, and
vision problems .
Studies on Aging -
• The relatively long life span of cats makes
it possible to observe the slower and more
subtle effects of aging.
31. DOG(Canis familiaris)
• Most preferred large experimental
animal due to small alimentary tract
and ease of training.
• Used for studying various anti-
arrythmic, cardiovascular drugs.
• Mongrel and Beagles are the most
preferred due to manageable size,
moderate hair coat and docile nature
.
• Good model for Diabetes Mellitus,
Ulcerative Colitis, Open heart
surgery and organ transplantation.
33. FROG(Rana tigrina)
The study of frog muscles in the
1920's led to the discovery of
neurotransmitter acetylcholine .
Frog eggs are large and resilient
hence, used to train cell biologists in
genetic manipulation.
Studying embryonic development
The African clawed frog, Xenopus
laevis, is often used in early studies
of development. They have been
useful for studying early events, such
as the formation of the neural plate.
35. • When genetics is an important part of the study , Xenopus
tropicalis is the preferred species as they have a shorter breeding
cycle, and have diploid cells.
A new type of antibiotic
• Another peculiarity of frogs is their ability to survive in bacteria-
filled water without wounds becoming infected.
• Studying this property of Xenopus laevis, Michael Zasloff,
discovered a new class of antibiotic compounds in their skin called
magainins . They may provide a future solution to the problem of
antibiotic-resistant bacteria.
• Recently, the first transparent frog was developed a Horoshima
University in Japan , making it a great model for studying the
aspects of human physiology .
• Transparent frogs will make it easier and cheaper to observe the
development and progress of cancer, the growth and aging of
internal organs, and the effects of chemicals on organs.
36. ZEBRA FISH(Danio reiro)
• It is an excellent model for
studying development in
vertebrates.
• The embryos develop externally to
the mother and are transparent,
hence can be easily viewed and
manipulated.
• The organization of the embryo is
simple, and they develop quickly
• They are suitable for genetic
models of human diseases. Genes
responsible for human diseases
have equivalents in the zebra fish.
37. CREATING TRANSGENIC
MODELS
• Zebra fish mutants are currently used to model many human diseases,
including Alzheimer’s disease, congenital heart disease, polycystic kidney
disease , cancers and development of the nervous system.
• Its aim is to use the zebra fish to produce new disease models, find new
drug targets and learn more about the gene-regulation pathways involved
in human development and disease.
• Using genetic techniques, a team of researchers stimulated the
development of a type of leukaemia - T cell acute lymphoblastic
leukaemia - in the fish.
• Creating zebra fish which develop leukaemia will enable researchers to
test the effect of various anti-cancer agents.
38. CHICKEN (Gallus gallus)
Chicken are used when birds are
needed for a physiological study.
They are easy to keep, and have
been bred domestically for many
years.
Since chickens are vertebrates,
their developmental process is
quite similar to that of humans.
Chick embryos are being used to
model atrial septal defect
condition, because like humans,
they have a four-chambered
heart.
40. PIGEON (Columbia livia)
• Pigeons are good screening
models for anti-emetic drugs.
• They also find application in
bioassay of prolactin.
• Used for screening of intravenous
anaesthetics.
• Used for standardisation of
cardiac glycosides.
42. Animals are killed or kept in captivity:
In animal testing, countless animals are experimented on and then killed after their
use. Others are injured and will still live the remainder of their lives in captivity.
• Some substances tested, may never be used for anything useful:
The unfortunate aspect is that many of these animals received tests for substances
that will never actually see approval or public consumption and use. It is this aspect
of animal testing that many view as a major negative against the practice, as it seems
that the animal died in vain because no direct benefit to humans occurred.
• It is very expensive:
Animal testing generally costs an enormous amount of money, as the animals must
be fed, housed, cared for and treated with drugs or a similar experimental substance.
In addition , animal testing may occur more than once and over the course of
months, which means that additional costs are incurred. The price of animals
themselves must also be factored into the equation.
43. • Animals and humans are never exactly the same:
There is also an argument that the reaction of a drug in an animal's
body is quite different from the reaction in a human.
The belief that since animals are in an unnatural environment, they
will be under stress. Therefore, they won't react to the drugs in the
same way compared to their potential reaction in a natural
environment. This argument further weakens the validity of animal
experimentation.
45. • While the scientific community generally supports the use of animals to further our
knowledge of health and medicine, they still acknowledge the need for alternatives to
reduce animal suffering. This is accomplished through the use of several different
categories of alternatives, which are often described as the three 'Rs' of biomedical
research. They are:
• Reduction
• Replacement
• Refinement
• Reduction Methods in Animal Testing
Researchers use techniques that allow them to obtain information that is sufficient
but requires fewer animals. Conversely, researchers may be able to employ a method
that allows them to obtain more information from the same number of animals. The
end result is that fewer animals are used and therefore, fewer animals suffering .
• Types of Reduction Methods in Animal Testing
There are currently modified test methods that are essentially traditional models that
have been advanced to provide comparable results with fewer animals. For example,
newer versions of the Draize test can reduce the use of animals and additionally, can
reduce the potential distress as well.
46. • Tissue cultures are also an extremely useful method for reducing the number
of animals used in laboratory experimentation.
• In addition, the use of computer models, databases and similar sources of
information can provide the history of a substance and its use as well as
offering preliminary information on the safety of a formula.
REPLACEMENT METHODS -
Replacement methods in animal testing involve actually replacing the use of
live animals with other methods that are completely non-animal in nature.
• Types of Replacement Methods in Animal Testing
• Whenever it is feasible, a replacement method such as an in vitro method is
performed in place of animal testing. In vitro methods refer to test tube
methods or cell cultures and these can be extremely valuable in replacing
animal models.
47. • Another way to replace animal use is to improve the use of
information.
• This means that by using epidemiological studies and similar
information, it may be possible to avoid animal testing in some
instances. Using previously established information means that
researchers can avoid repeating experiments.
• Also, mathematical and computer models be used
• Another method is the use of plants and microbes instead of
animals.
• Human studies can sometimes completely substitute animal use
in an experiment. In particular, human studies through the use
of human volunteers have replaced animal testing for cosmetics
development.
48. • Importance of Refinement Methods in Animal Testing
Refinement methods in animal testing are important because they aim to alleviate
pain and suffering in animals .The pain experienced by the animal can be caused
by tissue damage ,due to a surgical procedure, an injury or a specific disease.
The animal can also suffer from environmental stress or psychological stress as
well.
• Using Pharmaceuticals
• The use of anaesthetics, analgesics and pain-relievers can be helpful to relieving
pain or distress. Tranquilisers can also calm and relax the animal during an
experiment
• Using Technology
Technologies that are less invasive are also considered refinement techniques.
For instance, ultrasound and Magnetic Resonance Imaging (MRI) can both be
considered as refinement techniques.
49. • Reducing Psychological Distress
A distressed animal will not provide usable laboratory data so it is in the best
interest of the researcher to minimise pain for the animal's sake, while also
minimising pain in the interests of successful experimentation. Providing
animals with larger cages and toys can make a significant difference in the
animal's emotional well-being.
Making a Decision -
• Despite having a look at both sides involved in the controversy of animal
testing, there is still no clear right or wrong that seems to appease everyone.
One thing, however, appears to be unanimous - that at the very least, animal
suffering should be minimized and that animals should be respected during
their care. If animal testing is to continue - and at present it is ongoing -
animals must not be abused.
50. REFERENCES
• Background and History of Animal Testing Author: Ian
Murnaghan B.Sc (hons), M.Sc - Updated: 28 April 2015
• www.aboutanimaltesting.co.uk
• www.animalresearch.info
