Experimental Animal Research - 3 R's

What are Tissue-engineered vascular substitutes used to study?

the role of the adventitia layer of blood vessels in vascular physiology and related mechanisms.

Give example of how a slime moulds can be used in relative replacement?

(Physarum polycephalum, Dictyostelium sp.) has been used in research on epilepsy and bipolar disorder

In what aspects can refinement be applied?

- Animal production - Animal Care - Techniques - Pain management - Welfare assessment - Imaging technology

How can reduction be achieved?

- Choosing the right model and sample size - Data sharing (between experiments) - Tissue sharing (conservation) - Telemetry: collect data remotely

What should we not confuse pharmacokinetics with?

- Do not confuse with pharmacodynamics (what effect substances have on the body)

What are some examples of tissue engineering?

- Human vascular and skin substitutes - Skin substitutes may provide more relevant information - Tissue-engineered human cornea are used to study corneal wound healing

How can relative replacement be done?

- Invertebrates - Early stage embryo - Abattoir material - High fidelity fallacy

How can replacement be done?

- Literature search - Physical & chemical analysis - Computer models - In vitro systems - Human volunteers, epidemiology - Relative replacement - see next slide

What are certain things that can be done in Human volunteers for replacement?

- Microdosing - Imaging techniques - Behavioural, physiological and dietary studies. - Human cells and tissues obtained from normal volunteers or patients can replace the use of animal for in vitro experiments

What is the goal of refinement? How long should refinement last?

- Modification of husbandry or experimental procedures to: minimize pain and distress to enhance the welfare of an animal used in science - From the time it is born until its death

However why should replacement never be dismissed?

- Never dismiss replacement because you ultimately need animals - Evaluate each part and at every stage

When is microdosing used?

- Part of pre-clinical and phase 1 clinical testing - Used to study pharmacokinetics (how substances travel through body)

What is Organ on a chip?

using cells from a human grown in a lab and put in a chip to mimic the reaction that would occur in the body

What is Bioengineered bronchial equivalents (BE)?

- prepared in vitro from bronchial epithelial (HBEC) and fibroblastic cells (HBFC) - from biopsies of asthmatic and non-asthmatic human volunteers.

Give examples of some imaging techniques?

- such as MRI and PET scanning - Functional neuro-imaging

Why would replacement not be possible or as desirable in some studies?

- whole physiological systems - animal behaviour - applied animal agriculture - wildlife populations

When was the 3 R's invented?

1959: W.M.S. Russell and R.L. Burch The Principles of Humane Experimental Technique Concept of 3R introduced

When was the concept of alternatives introduced?

1978: David Smyth Alternatives to Animal Experiments Concept of alternatives

Replacement, is it all or nothing?

Before: idea for medication use animals Now: idea for medication review literature use computer model -> test with cell culture use animals

How can replacement be used for Human volunteers, epidemiology?

Data collection from the regular population instead of a lab population

Give example of how a fruit fly can be used in relative replacement?

Fruit fly (Drosophila): used to study the development of Alzheimer's disease, and other neurodegenerative conditions. Also used for genetic studies (30 day life cycle). 75% of genes that cause disease in humans found in fruit flies

What are some animal care refinements?

Housing and Enrichment

What is a high fidelity fallacy?

In the case of very basic biological functions it is often unnecessary, at least in the first instance, to use a closely related species.

When would Replacement not work?

It may be that animal experiments are considered unavoidable within an overall program of research - one project - one procedure

What are some challenges with replacement?

Limited by complexity of whole organisms

What is micrdosing?

Microdosing: the use of very low drug doses to study distribution and metabolism

Give examples of Bioengineered bronchial equivalents (BE)?

The BE provide in vitro models to study the mechanisms involved in asthma

Give example of how toxicology can be used in relative replacement?

Toxicology: effects such as mutation can be detected using almost any organism, including bacteria and yeast. - Bacterial tests for mutation are used to test almost all types of chemical for mutagenicity

What is Reduction?

any strategy that will result in fewer animals being used

What are some in vitro replacement?

cell cultures

How can replacement be used in literature search?

don't do again what's already been done

How can Skin substitutes provide more relevant information ?

include cell surface molecules that are present in human cells but not animal cells - Better fidelity

What is Replacement?

methods which avoid or replace the use of animals in an area where animals would otherwise have been used

What is Refinement?

modification of husbandry or experimental procedures to minimize pain and distress

How can replacement be used for Physical & chemical analysis?

sample sizes and sources (urine vs blood)

What are Human vascular and skin substitutes used for?

to study the molecular mechanisms of transendothelial migration (e.g. human cancer cells through a human endothelium layer, WBCs during inflammation)