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Notes lectures on Laboratory Animal Sciences BMS
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Notes from all lectures during the Laboratory Animal Sciences course of the master Biomedical Sciences - research track at the LUMC.
[Meer zien]Voorbeeld 3 van de 23 pagina's
Voorbeeld 3 van de 23 pagina's
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Introduction Animal Experimentation in the NetherlandsAnimals that are killed prior handlings are not reported to the EU as animal experiments
procedures. Only animals older than 5 days are reported.
Most animals are used for basic research (30%, fundamental/exploratory research),
translational and applied research (30%); regulatory use and routine production (30%, tox
and safety testing), and education and training (2%)
From a sociological view, the context (pet, wild animal, laboratory animal) and species of the
animal matters
Discussion: intrinsic value versus instrumental value; to what extent do we respect the
integrity of the animals
TPI = ‘transitie proefdiervrije innovatie’ in the Netherlands
Descartes: instrumentalism = beasts don’t feel pain, just automatic
reflexes
Immanuel Kant: anthropocentrism = the philosophical viewpoint arguing
that human beings are the central or most significant entities in the world;
only humans have intrinsic value: “Animals are there merely as a means
to an end. That end is man.”
Jeremy Bentham: when you don’t know, at least give the benefit of the
doubt to the animal: “The question is not, can they reason logically? Nor
can they talk? But can they suffer?”
Peter Singer: against speciesism (= discrimination based on specific
species) so only amount of suffering/enjoyment is relevant; marginal
cases-argument = humans with lowered capacities and/or consciousness
and/or who don’t have an image of the future, the marginal cases, have
direct moral status. Hence, animals must have a similar status (if we don’t’
perform tests on babies or Alzheimer/coma patients, why do this to
animals?)
Animal models
When choosing models, validity and reliability of research outcomes are considered
3 R’s: replacement, reduction, and refinement
Replacement: only use animal models when there’s no other option; now it’s also essential
that the research is relevant based on the latest science and technology
Reduction: minimizing the number of animals used consistent with scientific aims;
experiments are appropriately designed and analyzed in a robust and reproducible way
which adds to our knowledge base
Refinement: minimizing the pain, suffering, distress, and lasting harm that animals might
experience; understand the impact on the animal welfare
Relevance – pushing the boundaries of science and technology – what is considered as
scientific important (e.g., lifestyle diseases)
Choice for an animal: current alternatives don’t come close to the complexity of the human
body; one can do things with animals that one cannot do with humans (questionable)
Choice of model can be based on:
- Model that is available rather than the best model for the question (poor
reproducibility and translation); availability is a limiting factor
, o Lack of ‘in-house’ resources
- Use the same model since it’s done before
- Non-animal technologies are currently unable to study multi-morbidity as effectively
as animal models
Safety reasons for withdrawal of marketed drugs are liver toxicity, cardiovascular toxicity,
and CNS effects – all hard to verify in a model
NAMs = new approach methodologies / non animal methods
Predictive validity = predictive value of experimental results, depends on research question
Face/phenomenological validity = apparent resemblance of the model and the
phenomenon being modelled – quantifiable models are needed
Construct validity = extent to which the underlying biological mechanics in the animal model
resemble those of the phenomenon in the target species; the degree to which a test
measures what it claims to be measuring
External validity = generalizability of the results; indicator whether results can be
extrapolated to other species (incl. humans) and other conditions (out of the lab)
Internal validity = whether whatever you find is reliable; if there’re confounding factors
HARKing = changing the hypothesis so it fits your results
Registration of preclinical research is done to prevent testing on humans while is already
done; why isn’t that done for animal science?
ARRIVE 2.0 guidelines are used before publishing
Putting animals in cages should also be randomized (since some are harder to catch) to avoid
mitigating bias.
Light can be a confounding factor (circadian rhythm), collecting blood takes time so may
affect your results
Similarity between humans and animals raises the ethical concerns
The mouse genome is highly similar to that of humans. However, the expression of the genes
is very different. Those differences are clustered along certain pathways, such as in genes
regulating the immune system
PDX model: use xenografts of human tumors and put them in mice. Problem: mouse-specific
tumor evolution affects the results
Legislation, ethical review, and project license
Wod = wet op de dieproeven
The European laws are the most important. The Dutch laws have to fit those, and we cannot
be stricter. Ministers can change the laws
Codes of Practice (CoP), guidelines and recommendations are important, but less strict
A law should have significant increase in animal welfare, a level playing field for industry and
academia, and an active promotion and implementation of the principle of the 3 Rs
According to the law, we cannot use animals because they have intrinsic value. But there are
exceptions: having a license
When do you need a project license:
- Use of Live, non-human vertebrate animals, larval, fetal (2/3 rd of gestation) and
octopus. Based on whether the animals may perceive pain
, - Experiments may only be used for scientific or educational purposes
- Discomfort to the animal is stated as more than the introduction of a needle in an
animal. More than 50% of discomfort is mild (= injection). Around 35% is
moderate/severe discomfort such as surgery. This includes the full experiment
(cumulative discomfort), so frequency is relevant. Examples in annex page 19
In the Netherlands it’s a procedure when an animal is killed for an organ, in the rest of
Europe it’s not, it’s a mild discomfort. When you do tests under anesthesia and kill it (non-
recovery), it’s not a procedure, which is weird.
Ethical evaluation is required (harm-benefit analysis) is done for a project license. The
analysis by the DEC and CCD includes: are the objective and goals are profound,
discomfort/suffering, is the scientific approach achievable, implementation of the 3 Rs, look
at motivations for deviations of standards.
The ethical committee should include persons who know stuff about laboratory veterinarian,
scientific area’s including 3 Rs, ethics, housing and care for laboratory animals, experimental
design, laboratory animals and their protection, persons in charge of overseeing welfare
The committees should be independent and impartial of the project proposal
AWB = animal welfare body (is part of the facility; discuss project license, evaluation of
protocols, monitoring of animal welfare and execution, advice the execution, do we want
this in our facility, 3Rs, advised by designated veterinarian)
CCD = central authority for scientific procedures on animals (committee granting licenses,
execute policies, publish (easy to read) non-technical summaries, answers questions of the
public, accredits DECs, issues guidelines, deals with appeals)
DEC = animal experimental committee (ethics committee)
NCad = national committee for the protection of animals (ensuring sharing of best practice,
advise ministers, animal-welfare bodies how they do their work)
NVWA = inspection and law enforcement (may retain documents and collect samples, right
to enter premises)
Figure of connection of all organizations in PowerPoint page 26
Licenses you need: establishment license is to perform animal experiments in your facility;
License to breed and supply experimental animals; project license
You need licensed personnel including a person carrying out procedures on animals
(research technicians), person designing procedures and projects (researcher), person of
taking care of animals (animal caretakers), person killing animals (animal caretakers)
Licensed doesn’t mean competent, therefore there’s the principle of lifelong learning (LLL) /
continuing professional development (CPD) achieved by training and examination
Everything is documented in the welfare log
Behavior, recognition of pain and humane endpoints
Welfare: avoidance of abuse, respectful, appropriate standards, healthy, comfortable, no
unnecessary discomfort and pain.
Brambell’s five freedoms: rights of animals under human control:
- Freedom from thirst and hunger
- Freedom from discomfort,
- Freedom from pain, injury, and disease
- Freedom to express normal behavior
- Freedom from fear and distress
Welfare can be stated as the possibility to homeostasis over time
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