Adrian Smith, Norecopa, Norway National Consensus Platform for the Replacement, Reduction and Refinementof Animal Experiments [email protected]http://norecopa.no/Brno A practical approach to 3Rs policy Animal Models for Human Diseases: Best Practices for in vivo research Brno, 6-7 June 2016
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Adrian Smith, Norecopa, Norway
National Consensus Platform for the Replacement, Reduction and Refinement of Animal Experiments
• RefinementMethodstoimprove experimental procedures,andother factors such ashousing andcare,toreduce suffering andimprovewelfare throughout the animals’lives
’Thegreatest scientific achievements havealways been the mosthumane’– awin-win situation foranimals andscientists
www.frame.org.uk/tag/russell-and-burch
Content
A few words on practical ethics and animal welfareThe 3Rs in practiceQuality assurance in animal studies
Planning (including literature searches)Conducting experimentsReporting animal experiments
Guidelines and other 3R resourcesCultures of Care and Challenge
Practical ethics behind the 3Rs
The paradox of “inverse veterinary medicine”SpeciesismWhat is the animal really experiencing?Weaknesses in animals as research models
Two sets of “guidelines” emerge, that address very different questions:
• Wow that was cool, how do you do it?• Hmm, should we really be doing this?
The first group are more technical specifications than guidelines in the 3R sense…
The second set tend to be running fast in an attempt to catch up with the first set.
Reporting
Literaturesearch
Planning
ResearchIdentify and ensure the quality of (at least) the critical points in the
experiment:critical for animal welfare and scientific value
What is an alternative?
A method without the use of animals that gives the same answers as an animal experiment.
Are these alternatives?
• Cell cultures• Use of bacteria to test carcinogenicity• Chemical analysis of biologically active compounds
N.B. Animal experiments are usually needed to develop and validate alternatives.
Replacement alternatives
3D modelsAudiovisual aidsComputer simulationsMannekins, simulators, robotsQSAR (Quantitative Analysis of Structure/Activity Relationships)Cell and tissue cultures, organoids, organ perfusion
High Throughput Screening (HTS), organs-on-a-chipBiochemical & immunological methods (RIA, ELISA) Hybrid DNA technique, GMMTrials on “lower” organismsAcute experiments (terminal anaesthesia)Trials on dead animalsTrials on humans (microdosing and medical imaging)Synthesis of new evidence from experiments that have already been
performed
Next generation Multi-Organ-Chip
- Norecopa -
Marx et al., Altern Lab Anim. 2012 Oct;40(5):235-57
The potential for 3R alternatives cannot be evaluated until the objective of the study is known.
This applies to all use of animals in research, testing, education and training
e.g. Possible objectives in education & training:
• Teaching and practising:- laboratory skills- general animal handling skills- preparation-specific animal skills
• imparting good ethical thinking• new knowledge and reinforcing existing• data handling skills• experimental design skills• communication skills (oral, written)• groupwork• staff-student interaction
Rats from IKEA
AJ Smith & K Smith, 2004
Guidelines for humane education: Alternatives to the use of animals in
teaching and trainingProceedings of the 4th World Congress on Alternatives and Animal
Use in the Life Sciences, New Orleans, August 2002.
• Age, sex, weight• Stress, subclinical disease• Room temperature, animal cage• Environmental “enrichment”• Temporal differences between treatments• Climatic factors• Position of cage in the room• Experimenter• Animal Technician (weekend workers)• and many more
y 21.6% age (discrepancy between production and demand)
y 13.5% surplus breeding (not longer suitable for experimental purposes)
Quality assurance at all levels of the animal facility.For example:
• SOPs describing good techniques, carried out by competent operators• Checklist (“contract”) between researcher and the facility• The AAALAC Program Description template* as an overall performance
checklist• Institutional policies on animal care and use• Animal environment, housing and management• Veterinary care• Physical plant
• A Master Plan as a weekly checklist for the whole facility during the year
Smith AJ & Hawkins P (submitted) The Three S’s of Carol Newton
A Culture of Care
All about
• Attitude• Not just lip-service, but actually implemented• Commitment to continual improvement• Constant challenge of the way things are done• Everyone involved and having responsibility• Education in 3R alternatives from the day staff join• Finding the time to discuss the present situation and
possible 3R solutions• Transparency – involve all stakeholders
ResearchCorrect literature searches are a vital part of
the work to advance the 3Rs
Are scientists good at looking for alternatives?
• Bibliographic databases are often not used adequately (poor overlapping)• Too few scientists are aware of the specialist databases on alternatives• Scientists rarely use ”3R” words when they write titles/abstracts/keywordsfor their papers• This is a major problem because we have no single ”Journal ofAlternatives”
• Standing Committee on Business Affairs, Norwegian Parliament• Ministries of Agriculture and Fisheries• Novo Nordisk• Nordic Society Against Painful Experiments• Scottish Accreditation Board• Dag S. Stiansen Foundation• Laboratory Animals Ltd.• Norwegian Research Council