evolution of the brain and animal models Flashcards
workshop 1
1
Q
what re the benefits of using animals in research?
A
- For human health:
- Increase in cancer survival rate
- Development of asthma inhalers
- Eradication of smallpox
- For animal health:
- 96% research in UK uses mice, rats, fish and birds
- 0.2% uses dogs, cats and primates
- Consume more fish than the total number of animals used in medical research.
- All veterinary research has relied on the use of animal research.
- Researching disease:
- Animals suffer from similar diseases to humans
- Animals and humans are very similar/ same organ systems
- Modern anaesthetics, tetanus vaccines, penicillin and insulin relied on animal research in their development.
- Scanning techniques developed using non-human participants.
2
Q
what is the Triune brain theory?
A
- Developed in the 1960s by Paul D. Maclean
- Three distinct brains emerged through evolution which co-inhabit the human skull:
- Reptilian brain (old)
- Limbic brain (paleomammalian)
- Neocortex (neomammalian) (new brain)
- individual biological contributors.
3
Q
what is the reptilian brain?
A
- Oldest part
- 300 million years
- Main structures found in a reptiles brain
- Brainstem
- Cerebellum
- “Regulating & Surviving”
- Vital functions
- Basic behaviours (survival)
- Defending territory
- Mating
- Instinctive and automatic
- centred around the vital function of digestion, looking for food, seeking warmth, mating.
- Lizard brain= brainstem, cerebellum and hypothalamus
4
Q
what is the limbic brain?
A
- aka “paleomammalian” brain
- Bird brain been looked at in a lot of detail
- Emerged in the first mammals Limbic system
○ i.e., the feeling centre - Limbic system: revolves around the emotional control
○ Fear, anger, love, attachment and bonding
Main structures: - Hippocampus
- Amygdala
- Hypothalamus
- Helps keep internal state of the body constant:
○ Hunger with satiation
○ Thirst with fluid retention
○ Sweating when hot
○ Shivering when cold - Controls emotions
*Seat of value judgements
5
Q
what is the neocortex?
A
- Emerged in primates but is still important in humans.
- Neocortex= cerebellum
- Emotional and moral (moderator) of the brain
- Cooperation and evolution within our societies.
- aka “neo-mammalian” brain
- Emerged in primates but is most important in humans
- The thinking brain
- Moderator – reining in instinct and emotional responses
- Allows for cooperation
- Responsible for the development of language, imagination and consciousness
- Flexible with almost infinite learning abilities
6
Q
what are the issues with the triune brain theory?
A
- These three brains do not operate independently
- Numerous interconnections through which the regions influence each other
- Therefore… the theory is not widely accepted today
- Independence of the different parts of the brain is a key points- has been criticised.
- Some say they are highly coordinated due to the reciprocal nature and how neurons work between them all.
7
Q
how has our brain evolved?
A
- Brain size has increased
○ Not reflective of cognitive capacity
○ Brain to body mass ratio is key
○ Encephalisation quotient (For a human it is 6) - Proportion of the different areas changed
- Folding of the cerebral cortex increased
8
Q
what are homo naledi’s and why are they significant?
A
- Show highly social behaviours.
○ Did art
○ Bury the dead
○ Scratch symbols in their caves - Lived in south Africa
- Characters of early hominids.
- Shares many primitive and advanced characters
○ Human like hand
○ Human like foot
○ Curved fingers - Entrance is difficult
- Deliberate disposal of the dead
○ Was thought to be unique - Attributed to the prefrontal; cortex- assumed we were the first to have it
○ May not be the case as they were able to complete tasks that we do
9
Q
what is the evolution of hominids?
A
- Australopithecus robustus
- Homo habilis. (Homo Naledi)
- Homo erectus
- Homo sapiens neanderthalensis
- Homo sapiens
10
Q
what are the arguments in favour of animal testing?
A
- Create vaccines
- Saves both humans and animals
- 955 human genes are similar to mouse
- Insulin and diabetes
- 3R’s
11
Q
what are the arguments against animal testing?
A
- Difficult to transfer to humans
- Genetic heterogeneity
- Methodology
- The pain animals experience
- Ethical issues
- 3R’s (Alfred Wallace)
12
Q
what are the key problems with animal testing?
A
- Unpredictable translation of animal models to humans leading to concerns over clinical validity, application, and ethics
- Different evolution of diseases- lacks validity.
- Three areas of concern
1. Study design and data analysis (not scientific or rigours)
2. Heterogeneity of animals and humans (highly bad science)
Translation of preclinical animal trials to human clinical (questioned validity)
13
Q
what are the study design issues of animal testing?
A
- Inconsistent designs
- Lack of randomisation
- Lack of blind studies (experimenters know what they are trying to find)
- Inadequate of absent use of inferential statistics (inaccurate analysis)
Many trials concurrent, or even after, human studies (already been tested)
14
Q
what are the methodological issues of animal testing according to pound et al (2006)?
A
- Disparate species with variety of metabolic pathways and drug metabolites
- Different models for inducing illness or injury with varying similarity to the human condition.
- Variations in drug dosing schedules and regimens
- Variability in the way animals are selected for study methods of randomisation, choice of comparison therapy (none, placebo, vehicle), and reporting of loss to follow up.
- Small experimental groups with inadequate power, simplistic statistical analysis that does not account for potential confounding, and failure to follow intention to treat principles.
- Nuances in laboratory technique that may influence results may be neither recognized nor reported- eg methods for blinding investigators.
- Selection of a variety of outcome measures, which may be disease surrogates or precursors and which are of uncertain relevance to the human clinical condition.
Length of follow up before determination of disease outcome varies and may not correspond to disease latency in humans.
15
Q
how does animal testing show bad science?
A
- Less than 60% of studies reported:
a. a clear rationale or hypotheses,
b. A minimum of 3 animal characteristics (min)
c. number of animals used