Module II Flashcards

1
Q
  1. Explain and discuss different ethical views on use of animals for experimental research
A

Most people working with laboratory animals – either as researchers or technical staff – will accept the use of animals for experimental purposes. The public perception, however, can overall be split into three views on animal use. Either people approve (human interest are more important than the interest of animals, no matter the cost to the animals), they disapprove (all sentient animals have rights that must not be denied) or they approve, but within certain limits (harms and benefits must be balanced and animal suffering is not to be ignored).

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2
Q
  1. Describe how the public perception of Animal experimentation overall relate to the ethical theories of Utilitarianism, Contractarianism, and Animal Rights View
A

Animal rights (disapprovers): a sentient being must never be used as a tool; as a mean to obtain a goal. If a morally valid criteria cannot be found, it must be concluded that all sentient animals – including humans - have an absolute right to be treated with respect.

Contractarianism (approvers): as long as society allows for it, it is not a problem to use animals for experimental purposes. Morality based agreement which is established between rational persons (moral agents) capable of negotiating such an agreement. Animals and for example newborn infants do not have ethical rights unless a rational person negotiates rights for these individuals.

Utilitarianism (approvers with reservations): the suffering in the experiment must be compensated by the resulting benefits, so that the overall consequences of the experiment has more welfare than before. It is logical and more acceptable to sacrifice one or more individuals if this action will save a greater number of individuals.
○ All suffering must be diminished to the highest possible extent.

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3
Q
  1. Describe how 3Rs and a Culture of Care combined can promote animal welfare and support staff job satisfaction
A

Replacement: methods which avoid or replace the use of animals.
1) substitution of a conscious, living sentient being with insentient material (plants, microorganism)
2) absolute replacement - use a technique not involving the us of animals (computer modeling)
3) relative replacement - use of establishment of animal cell lines as en animal has been used to provide cells for the cell line.

Reduction: methods which minimise the number of animals used per experiment.
Improve experimental design and statistical analysis; improve techniques and methods to reduce the number of animals needed to obtain the data needed; establishing biobanks to share animal tissues; reduce variation in animal models.

Refinement: methods which minimise suffering and improve animal welfare.
1) Applies to the entire lifetime experience of the animal, so Refinement must be implemented both in breeding facilities, during transport, in all housing facilities, as well as during procedures and interventions.
2) Using non-invasive techniques, improving methods, using appropriate analgesia, optimise methods for pain recognition, environmental enrichment, cognitive enrichment, training animals to cooperate with certain procedures.

A Culture of Care complements the 3Rs by fostering an environment where animal welfare is prioritized and staff are empowered to provide the best possible care. E.g. by providing comprehensive training to staff on animal handling, husbandry, and the principles of the 3Rs ensures that they are equipped with the knowledge and skills necessary to promote animal welfare effectively.

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4
Q
  1. Discuss the use of live animals for training and teaching purposes in Laboratory Animal Science in courses such as the one, you are taking right now
A

Animals have an intrinsic value which must be respected. There are also ethical concerns of the general public regarding the use of animals in procedures. Therefore, animals should always be treated as sentient creatures and their use in procedures should be restricted to areas which may ultimately benefit human or animal health, or the environment.
Training and teaching purposes have the end goal of training scientists to undertake research hence the use of animals for these purposes will ultimately benefit research.

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5
Q
  1. Explain how the pharmaceutical industry and academia can inform the public on animal experimentation and discuss the benefits of such openness and transparency
A

It is vital that the scientific community and the laboratory animal facilities make their ethical principles for handling and use of animals accessible for the public to facilitate communication and trust. In Denmark, there are seminars that address various aspects on experimental animal use, and these seminars are open to the public. On the Novo Nordisk website, there are videos on their animal housing facilities. Such communication and transparency is important to maintain the trust and acceptance from the public and it should always be given a high priority.

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6
Q
  1. Present the 3 Rs, the purpose of the 3R and give an example on how the principles of the 3 Rs are not always compatible
A

Replacement is using less sentient or non-living models, if possible. Reduce is using fewer animals. Refinement has a focus on animal welfare. We should never replace or reduce if it means a large reduction in refinement; generally we prioritize refinement.
On the other hand, The Principles of the 3 Rs are not always compatible. Consider for example a study in which the researcher would like to study the effect on treatment X on healing of a bone fracture in dogs. Two scenarios are possible: Either the researcher use 12 dogs (6 treatment and 6 control) who all are subjected to a fracture of the left fibula, a bone in the hind leg of the dog. Or the researcher uses 6 dogs (3 treatment and 3 control) who are now all subjected to a fracture of both left and right fibula, bringing the total number of fractures up to 12 as in the first scenario. Clearly, dogs subjected to two fractures will risk more harm than dogs subjected to only one fracture; so reducing the number of dogs in this hypothetical scenario will compromise Refinement. In other words: Using fewer animals may risk increasing the strain on each individual animal.

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7
Q
  1. Present and discuss different viewpoints on/definitions on the nature of Animal welfare and discuss methods to measure/evaluate animal welfare
A

Animal welfare can be defined in three ways:

1) Health and biological functioning where the animal has a life in good health and with good biological functioning.
a) can be measured via clinical examination (heart rate, body temperature) and physiological parameters (blood, urine, hormone parameters), and appearance of animal products (egg, milk).
b) can be measured by statistical parameters such as mortality rate.
c) can be measured using an ethogram, which is a complete list of species-specific behaviors.

2) Natural living which states that animal welfare is when the animal can express its natural behavior e.g. a pig must be allowed to express his or her nature and perform those behaviors that define a pig such as nest-building in farrowing sows and wallowing for thermoregulation.
a)To measure natural behavior, first need to define what natural behavior is and this can be done by releasing lab animals into the wild and seeing how they act or can also use close wild relatives e.g. wild boar for domesticated pigs.

3) Emotions and preferences where welfare is the presence of positive mental states and absence of negative mental states. This welfare definition also includes the preference theory which states that the more you experience to get what you want, do what you want and avoid what you do not want, the better welfare you have. Seeking to have your preferences fulfilled will bring about positive anticipation as the goal is approached.
a) Positive mental states are joy, caring, playfulness, feeling safe, etc. Can be measured in two ways: measure ultrasonic vocalization in rats (50kHz = human laughter). Judgment or emotional bias assessment will provide a measure for the level of optimism in the animal based on how the animal perceives an unknown stimulus presented during a test.
b) Negative mental states are fear, anxiety, pain and aggression. In mice, fear can be assessed by using an elevated plus maze.
c) Preference of an animal can also be determined:
Choice test: animal is asked to choose between resources.
Operant set-up where an animal has to work to gain access to a resource, the more the animal is prepared to work for the resource, the more preferred the resource is.

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8
Q
  1. Present the Five Freedoms and explain how these apply to laboratory species
A
  1. Freedom from hunger and thirst: by ready access to water and a diet to maintain health and vigor.
  2. Freedom from pain and injury: by prevention or rapid diagnosis and treatment.
  3. Freedom from fear and distress: by ensuring conditions and treatment, which avoid mental suffering.
  4. Freedom from discomfort: by providing an appropriate environment.
  5. Freedom to express normal behavior (normal in majority of the population): by providing sufficient space, proper facilities and appropriate company of the animals’ own kind.
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9
Q
  1. Describe the importance of good animal welfare including its effect on scientific outcomes as well as for ethical reasons
A

Animal welfare is important for scientific reasons relating to the quality of the data obtained by use of live animals and the resulting translatability and reproducibility. Translatability denotes the transfer of basic in-vitro and in vivo research into human applications. Reproducibility denotes that the results can be reproduced if the experiment is repeated.
The housing environment and the procedures that a laboratory animal is subjected to, can have a profound effect on the welfare of the animal. Animal welfare can be affected or challenged in numerous ways in animal experimentation and most likely stress will be the common denominator.
Stress will be defined as the sum of the biological reactions to any adverse stimulus - physical, mental or emotional, external or internal- that tends to disturb the homeostasis of an organism. If this becomes chronic and the animal is not able to cope then it is known as distress. Many procedures and environmental factors may elicit fear, pain or other stressful conditions in the animals. Fear and pain will of course affect animal behavior and stressful conditions will affect for example the immune system, the cardiovascular system and reproduction and the last decades of research has shown that barren cage environments will result in animals with physiological, immunological, neurological and behavioral abnormalities.
To ensure valid data, it is important that animal welfare is not compromised to the extent where the animal is experiencing fear, pain or prolonged stress.

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10
Q
  1. Explain what is meant by “A Culture of Care” and discuss why it is important to promote a Culture of Care
A

Culture of Care: a commitment to improving animal welfare, scientific quality, care of the staff, and transparency for stakeholders.
In the context of laboratory animal research, the term has come to indicate a corporate as well as a personal commitment to improve animal welfare and thereby scientific quality whilst also taking into account the welfare of the people working with the animals. Part of culture of care is to implement 3R to the highest possible degree (to reduce animal use and animal stress, pain and suffering) and also reduce the emotional strain on animal care staff as discomfort and suffering in the animals is reduced to a minimum and the staff knows that all possible measures to reduce the harm to the animals have been taken. Such culture will therefore support job satisfaction.

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11
Q
  1. Give examples on homepages where information on laboratory Animal Science, Laboratory Animal Care and 3R can be found. Discuss why you think it is important to continuously stay updated on how to optimise animal welfare during housing, handling and procedures
A

When working with laboratory animals, you should always continuously educate yourself on the 3Rs, the ways to implement these principles and ways to enhance animal welfare and reduce harm to the animals. New methods are constantly being developed to improve animal welfare.
1. https://en.3rcenter.dk/
2. https://www.nc3rs.org.uk/
3. https://www.ccac.ca/
E.g. the use of tunnel handling mice instead of tail handling.

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12
Q
  1. Discuss the 3Rs and why it is important to continuously improve the level of Refinement in animal experimentation
A

Replacement: methods which avoid or replace the use of animals.
Reduction: methods which minimise the number of animals used per experiment.
Refinement: methods which minimise the suffering and improve animal welfare.

Examples of refinement include ensuring the animals are provided with housing that allows the expression of species-specific behaviors, using appropriate anesthesia and analgesia to minimize pain, and training animals to cooperate with procedures to minimize any distress. Evidence suggests that pain and suffering can alter an animal’s behavior, physiology and immunology. Such changes can lead to variation in experimental results that impairs both the reliability and repeatability of the studies.
As we know, if the results are unreliable then more animals will have to be used to improve the confidence in the results and this would not be good hence increasing refinement is very important for overall compliance of the 3 R’s.

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13
Q
  1. Explain the purpose of a Harm/benefit analysis in animal experimentation and give examples on parameters included in a Harm/benefit analysis
A

The Harm:Benefit analysis is an evaluation of the project that considers both the impact on the individual animal and the benefits of the study. In other words: What problem do the researchers expect to solve?; what are the objectives and hypotheses of the study? and how much suffering, pain and distress will the animal be subjected to?
To do this kind of study you need to define the harms of the planned study and moreover need to define the benefits. And then need to decide on how to compare and balance the harms and benefits.

● Harms should be considered all negative impacts on the animals used in a certain study. These harms can be related to Animal welfare aspects, Animal rights and the quality of research.

● Benefits mainly relate to the expected outcome of the studies in the form of improvements in the field of human health including safety testing and vet med. Also benefits to wildlife, the diversity of life on the planet. Experimental animals may also be used for educational purposes and these are considered beneficial.

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14
Q
  1. Discuss the importance of being able to justify on ethical grounds, the decision to use living animals, including the choice of models, their origins, estimated numbers and life stages. Describe the ethical and welfare factors influencing the choice of an appropriate animal or non-animal model
A

Living animals are more complex than computer simulation, cell cultures, plants, etc. and have more translatability of results to humans. The least sentient model possible that still provides applicable results should be used. Animals that are specifically bred for the purpose of research should be used. This allows us to reduce variation in the animals used, allows for reproducibility of results between labs, characterization of specific animal strains, genetic modification, etc. Use of genetically similar animals will set precedence on the number of animals likely required to reach statistical significance in a study. Use an animal at a life stage appropriate for your study.
Contractarianism, Animal Rights View, Utilitarianism to advocate for animal vs. non-animal models.

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15
Q
  1. Describe and explain the challenges when performing a Harm/Benefit analysis of a study using live animals
A

When balancing the harms and benefits, it is important to realize that the resulting harms in a given study are more or less certain, even if there is compliance with the 3 R’s and everything has been done to reduce the harms. On the other hand, the benefits are not guaranteed as there is no way to ensure that the results of the study will contribute to human health improvements or save lives but it is important that there is high quality research and that good results are rendered probable.
It is important that the competent authority has all relevant information to facilitate the assessment, it is a delicate and difficult decision and there is no definite right or wrong.

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