I. Introduction
a. Why laboratory animal sciences?
Undercover action of GAIA
- Organization that is against animal experimentation
Made a video on practices that where going on at the VUB (Jette)
o Raised a lot of questions because some things were not okay, but certain things
were depicted as cruel while they were taken out of context: this is why this course
is important (need to know what is allowed and what isn’t)
▪ Ethics: is this ethical?
• Everything needs to be approved by an ethics committee: describe
the experiment into detail
• Veterinaries and animal welfare buddies are in place to watch over
the researchers to check that what is done is what was described
• The researchers also have a big responsibility to do what was
asked for
▪ Legislation: what is allowed?
• Techniques that are used, what is allowed …
• E.g. pups cannot be killed by carbon dioxide (resistant to hypoxia)
so in the legislation decapitation is one of the preferred methods
because it is the only good method to get them killed very quickly
o Freezing: until a couple of years ago it was one of the
standard methods to euthanize pups: physiologically for
the animal this is better than using CO2
▪ Research: do we have to continue using animals?
• We try to move away as much as possible away from animals
• A lot of research is done on alternatives, but for some research
whole body systems are needed (e.g. immunology, cancer …)
• Legislation: if you want to put drugs on the market, you have to
have done animal testing
Multidisciplinary field
- Studies welfare and care of research animals
How do you recognize sick animals, how do you care for them, what are their basic needs
- Reliability and reproducibility of animal research
If you use animals, you want it to be reliable and reproducible (big problem at this moment)
- How to handle animals in a responsible and respectful manner
If you’re good at handling animals, it lowers their stress significantly
- A lot of things have to be taken into consideration
Husbandry: basic care (cleaning cages, food and water) but also cleaning the rooms, taking
hygiene measures …
Nutrition: food can also alter the physiology of the animal, it cannot change from one week
to another for the experiment
Experiments, anesthesia and analgesia (pain medication): see LAS2
Environment: has a big impact on the wellbeing of the animals: standardized
Genetics and microbiology: you don’t want the animals to get sick: monitoring for specific
pathogens + a lot of the animals are GMOs
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, II. History of LAS
a. The ancient Greeks
Use of lab animals in parallel with discoveries in medicine
- Basics of western medicine: Greek philosophers
Descriptive research based on vivisections
o Vivisections: cut open an animal before it was dead
- Corpus Hippocraticum (400 BC)
Vivisections for descriptive research: how do certain things work in animals
- Galen/Galenus (130-210)
Physiological experiment in animals
o Animal as a model for human (still done today, but back then there was no scientific
basis for it besides that they look like humans)
o Use of healthy animals: did not know how most of it worked
b. Romans and middle ages
After the Greeks not much progress in medicine and sciences
- Not because they didn’t want to, but a sign of the times
Middle ages
- Catholicism reigns and no big scientific progress is made
They had their standpoints and science was often not in the open (probably a lot of
information was lost) since it was not encouraged
- But in the Arabic world: a lot of progress in medicine that later came back to the western world
Muhammed Ibn Zakariya al-Razi (654-925): discovery of measles and smallpox
Al-Zharawi (936-1013): father of surgery
o Did studies on humans
Ibn Al-Nafis (1213-1288): discovery of the pulmonary system before Harvey described it
c. Renaissance
Renaissance (15th century)
- Revival of the sciences: went to the Greek ideas
- Vesalius: de humani fabrica corporis
Considered as the first book on human anatomy
- Moving from observations to an empirical approach
Testing how things work, react, …
17th century: more physiological research
- Anatomy is connected to the function
There is a reason why a kidney is built how it is
- William Harvey
Discovery of the blood circulation (actually already found by Al-Nafis)
- Francis Bacon
Poses the inductive method: you test things and on the basis of this, you can predict
something else
- René Descartes
Important philosopher for that time
Only the human has a soul and can thus suffer, however mechanistically human and animal
are alike, so animals can be used to study human
- Marcello Malpighi
Analogy principle: lower species (e.g. mouse) can be used to research mechanisms in
higher species (e.g. human): data can be extrapolated: part still used today
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, d. 18th century and later
Animal experiments contributed a lot to the development of medicine (and science)
- 1859: Charles Darwin – On the Origin of species
Resemblance, physically and mentally
- 1865: Claude Bernard – Introduction à l’étude de la medicine experimentale
- 1821-1902: Virchow
Test new medication on animals
- Ehrlich and Pasteur
Vaccine development, is now moved away from (but for certain vaccines might still be
applicable)
- 1884: Postulates of Koch
Proof of pathogenicity by inoculating animals resulting in disease
19th century
- First widespread opposition to animal experiments
Anti-vivisectionist movement (England, 1875)
o Victoria street society
1867: Cruelty to Animals Act
o Law for the protection of animals used in research
o In this period England was the only one that had a very specific legislation on the
use of animals for experiments
Modern times
- After WWII: exponential growth in different research domains
Animals are seen as a means to obtain knowledge
o Use of dogs and cats moves to mice and rats: smaller, cheaper, easier to handle,
more of them in the same amount of space, short gestation and life cycle
- 1953: Watson and Crick (with Wilkins and Franklin): technology boom
Transgenesis: genetics are easily changed in mice
- Growing interest into the ‘capacities’ of animals: still being studied today
Behaviorism: Pavlov and Skinner
o Animals are stimulus-reaction machines
Ethology: Tinbergen and Lorenz
o Focus on species-specific patterns in their natural habitat
▪ What is important to have in this habitat? (e.g. nesting material for mice is
essential)
o E.g. why do ducks follow their mother (imprinting)
- Late 20th century: idea of animals within society changes: animals are now seen as companions
1929 + 1979: Law for animal protection (Belgium)
o Law for animals in general like pigs, cows … on farms
1975: Animal liberation movement (Peter Singer)
1983: Animal rights movement (Tom Regan)
o Make a harm-benefit analysis based on different philosophies than the Animal
liberation movement
1986: European convention and directive
o Promotion of alternative methods (no animals)
o Use the lowest species possible
▪ Nowadays: discussion about what defines a lower species: is a mouse
worth more than a fish?
Russell and Burch (1959) – The principles of humane experimental technique
o Replacement: using alternative techniques
o Reduction: minimum amount of animals needed
o Refinement: how do you reduce stress on the animals?
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, Laboratory animal sciences becomes a separate discipline within biomedical research
- Standardization and quality management
Animals
Housing conditions
- Well being of animals: animal welfare
- Organization of knowledge into one field
e. Use of laboratory animals
Why are animals used
- Discovery
Animals are used in the early stages of research to investigate how organisms and diseases
behave, develop and function
- Development
New medicines and vaccines are tested in animals to ensure they are safe and effective for
use in humans
- Alternatives
Cell cultures or organoids
Computer simulations: can process a lot of data, use historical data to give computational
ideas about the outcome of certain things
Benefits
- Further fundamental knowledge in biology and physiology
- Drug development (including regulatory testing)
Both a benefit and a disadvantage: softenon was tested on pregnant mice, but in humans
the drug could enter the placenta
o Because of this drugs need to be tested on at least 2 different species
- Treatment and diagnosis of diseases
- New surgical techniques
- Benefits for animals
Developing medication for e.g. a horse (in the vet industry)
Disadvantages
- Extrapolation of data
Still a big problem
Inbred versus outbred strains
o Testing in inbred might mean that you will not see a reaction you will see in reality
since they are so homozygous
Wrong animal model
o E.g. certain diseases are studied in mice, but is naturally present in dogs: the dog
would be a better choice
- Controlled environment
Always between 21-24°C, 12 hours light, 12 hours dark, humidity between 45-65%
o Otherwise experiments in different seasons might have different outcomes
In reality, we experience a lot of different environmental factors
- Repeatability of experiments
Sometimes specific animal models will work in one facility, but not in another
Not often that acceptable
The 3R principle
- The use of animals is only acceptable when
There are no non-animal alternatives
o Have to show that you looked into alternatives, but that there are none
Cost-benefit analysis: importance of the research question
Welfare and care of the animals, as well as reliability of results
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