CONTENTS LABORATORY ANIMAL SCIENCE
LESSON 1 History and Ethics
LESSON 2 Legislation
LESSON 3 Legislation Part 2 – ethics committee, AWB, national committee
LESSON 4 Surgical Techniques
LESSON 5 Project design: experimental set-up, sample size
LESSON 6 Task specific module - principles of surgery: Pre-operative managment and care
LESSON 7 Task specific module - principles of anesthesia and humane killing
LESSON 8 Project design: alternatives, severity assessment, humane endpoint
LESSON 9 Task specific module - principles of anethesia and humane killing - Pain management
Genetically altered animals: impact on care, health, managment (record keeping) - Genetic
LESSON 10 modification
LESSON 11 Genotyping
LESSON 12 RODENTS - what are models - intro assignment RODENT
LESSON 13 FISH - Basic and appropriate biology - zebrafish research
LESSON 14 FISH - vervolg
LESSON 15 RODENTS - basic and appropriate biology part 1 anatomy, nutrition, reproduction
LESSON 16 RODENTS - basic and appropriate biology (skills) - handing and restraint - genotype
LESSON 17 RODENTS - Behavioral Evaluation
LESSON 18 RODENTS - Behavioral Evaluation Part 2
LESSON 19 RODENTS - minimally invasive procedures incl anesthesia
LESSON 20 RODENTS - minimally invasive procedures (welfare assessment and pain score sheets)
LESSON 21 RODENTS - Animal Husbandry
LESSON 22 RODENTS - discussion on pain assessment and welfare in rodents
LESSON 23 RODENTS - Diseases
LESSON 24 RODENTS - advanced care (health monitoring)
E-LESSONS
E21-1 Pre-anesthetic preparations
E21-2 Choosing an anesthetic
E21-3 Anesthetic Monitoring and Intraoperative Care
E21-4 Anesthetic Breathing Systems, Airway Management and Neuromuscular Blocking Agents
E21-5 Anesthetic Management and Preventing Problems
E-6 Humane Killing/Euthanasia
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,LESSON 1: HISTORY AND ETHICS
History
Both the terms ‘Laboratory Animal’ and ‘Animal Experiment’ have evolved over time.
" the current definition can be found in the lesson about legislation
Prehistorical times
In prehistorical times, e.g. the Ancient Greeks, people studied anatomy and physiology of animals.
- there was a taboo on studying of human bodies: so it was on dogs, cattle, …
- a natural order was already established, with humans having a distance from animals
- people were comfortable with performing research on animals
o dissection of living animals (=vivisection) was executed " no anaesthesia
o in ancient times, science was important to develop
Middle Ages
In the Middle Ages, gaining knowledge for science came to a standstill.
" people were more focused on staying alive then on further developing science
" there was no real reason to do science, certainly in Europe, because of Christianity
o if you became sick " this was a curse, or a punishment of God
o if you cured from the disease, this was because of faith
o a lot of phenomena were explained by religion, not by science
" natural order: there was a certain God – angels – people – animals – trees
o animals were there to serve mankind
o to come closer to God, people forsake their animal instincts
Early Modern Times (± 1500 – 1750)
In the Early Modern Times, things got way better.
- Industrial Revolution: great social changes in society because of advancements in industry
- Reformation of the Catholic Church: a bit of disconnection between people and the church
o predominance of Christianity weakened
In general, people were able to do more than just managing how to survive: they could think
- e.g. Vesalius: a Flemish anatomist that laid the foundation of comparative anatomy
o he dissected corpses of people that were convicted
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, - e.g. Descartes (1596-1650): “Je pense donc je suis” " the Age of Enlightment
o if you’re able to use reason, that makes you a creature with intrinsic value
o animals were seen as ‘Automata’ because they can’t talk to us and use reason
- there was a revival of animal experimentation
o no-one had a problem with this: still a lot of distance between animals-people
o e.g. you would get a conviction if you have beaten up a horse
§ NOT because you made the horse suffer
§ but because the horse is a possession of someone else!
§ if an animal was not in the possession of someone else (like free-living or
wild animals), there were basically no restrictions
Modern Ages (1750 – 1950)
Flanders and Belgium
In Flanders and Belgium in the Modern Ages, there was still no real awareness on animal welfare.
- the Catholic tradition was still very present in society
- science was influenced by predominantly German scientist
o e.g. E. Kant: “all animals exist only as a means and not for their own sake …”
o but he also said that how you handle animals, says something about you as a person
- only the ‘possession’ argument really protected animals (Strafwetboek, 1867)
- so we were still a bit in the Middle Ages concerning Animal Welfare
Important people in animal experimentation
Hogarth (1751): “Four Stages of Cruelty”
" a story about Tom Nero in Four Stages of his life
o Stage 1: as a child Nero was very cruel to animals
o Stage 2: as an adolescent, Nero did cruel things to larger animals
o Stage 3: Nero killed his wife
o Stage 4: Nero was sentenced to death: a lot of people are doing cruel things to him
" if you are cruel to animals in your childhood, you will be cruel to people later in life
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,Jeremy Bentham and Rousseau (18th Century): animals are sentient beings
- “The question is not: ‘Can they reason or talk?’, but ‘Can they suffer?’”
- reasoning is seen as less important than happiness
- utilitarianism: use of animals is accepted as long as the suffering exceeds the benefit for man
o Bentham: has a weighing scale to weight the benefits against the suffering
o important: they were both NOT against animal suffering, but it has to have benefits
Claude Bernard (1813-1878): Foundations of animal experimentation
- he founded that before a test is conducted on people, it had to be done on animals
Louis Pasteur (1822-1895) performed experiments on rabbits for studying rabies
- he defines humane endpoints: endpoints by which lab animals should be euthanized
- so the animal doesn’t have to die from the disease itself!
- this is still practiced today
Other developments in this period
- Cruel Treatment of Cattle Act (1822, UK)
- Cruelty Against Animal Act (1835, UK)
o a reaction against a French surgeon Magendie who did horrible experiments on animals
o there were people who wanted amendments for legislation of cruelty against animals
o this is the first time in history (only in the UK) where animal experimentation is accepted
and put into legislation and where there are also guidelines that define what is permitted
§ only for vertebrates: no guidelines for non-vertebrates
§ rules about anaesthesia, only use 1x, immediate kill after experiment, ...
§ animals can only be used when necessary to advance human health!
§ prosecution was possible!
- Origin of Species (1859) – Charles Darwin
o prior to this book: natural order – large distance between humans and animals because
we had to be as close as possible to God
o Darwin says we are now related, ‘family’, to all this living creatures
o this also gave room to this Cruelty Against Animal Act
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,- National Anti-Vivisection Society (°1875, UK)
o this Society pushed to have these amendments in the legislation
o they questioned the value of animal research
§ e.g. doing a vivisection to study physiology: they said that you can’t take any
conclusions " how an organ functions in a suffering animal is not
respresentative for the actual physiology
- Anaesthesia was first demonstrated in 1846 with the use of diethyl ether.
o discussion shifted from questioning value of animal research to simply preventing harm
o this is largely due to the use of anaesthetics on animals
§ researchers gained ‘carte blanche’: if the animal did not have pain, basically any
experiment on animals was possible (suffering was not an issue anymore)
§ sidenote: most anaesthetics at that time failed to work (e.g. wrong doses)
§ this led to a rise in animal experiments!
- Tremendous increase in the use of rodents
o rodents were seen as test animals: considered as ‘less nice’ (“pest” animals)
" so less difficulties with using them
Current Time: 1950 - ...
Russel and Burch (1959, UK): “The principles of humane experimental technique.”
- they and their colleagues did not enjoy performing animal experiments, and wanted
procedures how to deal with animal experimentation as humanely as possible
We assume that experimental biologists are only too happy to treat their animals as humanely as possible.” They further
stated, “The central problem then is that of determining what is and what is not humane, and how humanity can be promoted
without prejudice to scientific and medical aims. We must begin by examining the concept of humanity (or inhumanity) as an
objective assessment of the effects of any procedure on the animal subject.
- founders of the 3R-principle: Replacement – Reduction – Refinement
o Replacement: replace with non-vertebrate model
§ e.g. non-vertebrate (e.g. Drosophila), embryonic form (e.g. zebrafish), in vitro
methods, in silico methods
o Reduction: minimize number of animals used per experiment
§ e.g. sample size calculations
§ e.g. re-use animals " e.g. microsampling of blood: small volumes can
repeatedly be sampled in the same animal
§ e.g. report negative data: so other people don’t need to repeat the same
experiment!
§ important: reducing the number of animals should be balanced against any
additional suffering that might be caused by their repeated use
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, o Refinement: minimize pain, suffering, distress or lasting harm and improve welfare
§ e.g. cage enrichment, use of anaesthetics/analgetics, in vivo imaging, ...
Peter Singer
Peter Singer: Animal Liberation (1970) " caused a change in how we look into animals
- speciesism: type of discrimination where the human species is superior to animal species
o Singer responded to this!
o this does not mean that we should treat all animals with equality, not all species
have the same intrinsic value
Tom Regan
Tom Regan: The Case for Animal Rights (1983)
- he extends the Kantian principle of ‘intrinsic value’ to all species
- all animals have an intrinsic value and we cannot ever use them anymore for any means, as it
is science purposes or food, clothes, ...
Implementation in Belgian law
1986 – European directive
1986 – Belgian Law on animal welfare (± 100 years later than in the UK!)
- mentions laboratory animals, animal experiments, registration, ...
2010 – New European Directive: more focus on refinement
" Europe predicted in 1986 that in 2000, no animal experiments are needed anymore
" they were wrong, and in 2010 this Directive came " large focus on refinement
Data in this graph start at 1995, because before it was not
mandatory to report the number of animals used.
" so starting from 1994, reports had to be made
While making reports, they had a thorough look to the law
and this led to a drop in the use of animals from 1995-1997.
This is because before 1994 people did not really know that
animals should be used if there are no other options,
minimum of animals, ...
2005: ban for the use of animals to test cosmetics
2009: ban for the use of primates
2011: ban for the use of animals for tobacco research
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, There is an increase in the use of animals around 2006,
because of the invention of transgenic animals.
The two graphs below give an idea on which animals are mostly used in animal experiments, and for
which purposes the most animals are used.
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,LESSON 2: LEGISLATION
Legislation at European and National (Belgium) level
In 1986 there was a major breakthrough à EU directive 1986/609/EEG
- European directive in which the use of animals for research purposes was acknowledged
Belgium decided to sign and ratify the EU directive 1986/609/EEG and implement it into the Belgium
law of animal welfare
- This law already existed but was changed various times
- Most important change was thus in 1986
- SO: in 1986 lab animals were mentioned into the law of animal welfare, before 1986 the law
was more focused on farm animals, pets,…
This law led to a Royal Decree (RD) in 1993
- which told the Belgian researchers how they should work with lab animals and on which they
should focus: e.g.: reporting of animal numbers (this is the reason why we only have reports
from animal numbers from 1994 onwards)
- RD of 1993 is now replaced by RD 2013 which implemented the changes because of
2010/63/EU (see below)
The directive 1986/609/EEG was revised and replaced by EU directive 2010/63/EU
- People thought that by the year of 2000 we wouldn’t need lab animals anymore
- But this wasn’t true à led to a revision of the EU directive
- In this revised version (completely replaced by the previous one) the EU government still
focused on trying to reduce the number of animals and to replace the animals by alternatives
but the focus was (much more than before) on refinement (housing, food, light,..)
- Again Belgium signed and ratified this directive, meaning that again they have changed the
law on animal welfare in order to be in line with the EU directive
! Below, we find a list of the most important legislations (with regard to laboratory animals) at
European level and at National level
- European level
o EU directive 2010/63/EU
- National level (Belgium)
o Law animal welfare 1986
o Royal Decree 30.11.01 Verbod op sommige dierproeven
o Royal Decree 29.05.13 Protection laboratory animals incl annexes
o Decree 17.02.2017 Protection laboratory animals (changes)
o Decree 22.02.2017 Composition Vlaamse proefdierencomissie
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,National legislation
Law
- Applies to the entire country
- Should be voted in parliament
Royal Decree
- Guideline on the law (but mandatory to follow)
- Still functions within the limits of the law
- Decided via the federal parliament
Decree
- Guideline on the law (but mandatory to follow)
- Decided by the regional parliament
o Belgium has different regions: Flanders, Wallonia and Brussels
o Each region has their own parliament which can make own decrees
o Animal welfare is one of the topics for which the regions are responsible
o E.g.: the law says you should report on the number of animals used
§ Decree in Flanders: you should report on these numbers annually
§ Decree in Wallonia: you should report on these numbers every 6 months
! SO: difference between decree and royal decree
à both are guidelines on how to interpret and carry out the law
à but a decree gives more detailed information in comparison with the law (can be
more easily changed in comparison with the law)
! SO: each of the 3 regions can have their own interpretation about animal welfare
à if you check the most important legislations (see before), we can see that from 2013
there is no royal decree anymore with regard to lab animals: can be explained
because from 2013, animal welfare became a regional topic
In a nutshell
‘The protection of laboratory animals in Belgium/Flanders is basically ensured by the Animal Welfare
Law 1986 concerning the protection and welfare of animals and the Royal Decree of 1993 replaced by
the Royal Decree of 2013 concerning the protection of laboratory animals’
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, Laboratory animals
Animal welfare law 1986
Art 3 - 15. Laboratory animal:
15.1. The living cephalopods used or intended for use in animal experiments, or which are
specifically kept so that their organs or tissues can be used for scientific purposes;
15.2. The living non-human vertebrates used or intended for use in animal experiments, or
which are kept specifically so that their organs or tissues may be used for scientific purposes,
including their self-feeding larval forms, as well as fetal forms of mammals from entry of the
last third of their normal development;
15.3. This definition also applies to animals used in animal experiments that are at an earlier
stage of development than the one in section 15.2. if these animals are required to survive
beyond that stage of development and are in danger of suffering pain, suffering, distress or
lasting harm after reaching that stage as a result of the animal experiments performed;
à What is the definition of a laboratory animal?
- Living cephalopods or living non-human vertebrates
o But not all cephalopods or non-human vertebrates are considered lab animals
o Only considered as lab animals from the moment they are prepared for or used into
an animal experiment
o So when these cephalopods or non-human vertebrates are just bred, then they are
not considered as an lab animal
à Can we consider fetuses and embryos as a lab animal?
- Yes, from the stage of self-feeding or from the last third of the pregnancy they are
considered lab animals
à If the animal on which you experimented in utero is born, is it still considered as a lab animal?
- Yes, if the animal has a chance to suffer from the intervention he got in utero then you still
have to consider it as a lab animal
- No, if the animal has no chance to suffer anymore from the intervention in utero then you
don’t need to consider it as a lab animal
! The definition of a laboratory animal is the same throughout EU
RD2001
‘No animal experiments are allowed on Chimpansee, Bonobo, Orang-Oetan, Gorilla’
BUT: Chimpansee, Bonobo, Orang-Oetan and Gorilla can still be used in for example physchological
experiments (e.g. memory games) as long as they are not suffering
à this should be requested to the ethical committee
à if it does not cause harm then it is not considered an animal experiment
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