Animal welfare and good science: where are we going?
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1 Animal welfare and good science: where are we going? Vera Baumans DVM PhD DipECLAM Dept of Animals in Science and Society, Div Laboratory Animal Science Utrecht University, Utrecht, The Netherlands
2 Attitude towards animals? Vera Baumans UU 2
3 Descartes Dualism mind/body - nonhuman animals are machines, devoid of mind and consciousness, and hence lacking sentience. Thus: no consciousness and no pain (insensate machine) Vera Baumans UU 3
4 18th century: 1789: Jeremy Bentham The question is not, can they reason? nor, can they talk? but, can they suffer?
5 Russell and Burch The Principles of Humane Experimental Technique, 1959 Replacement Reduction Refinement Vera Baumans UU 5
6 Welfare of Laboratory Animals - Role of Refinement? Hypothetical ideal level of welfare : The state of being in animals when their nutritional, environmental, health, behavioural and mental needs are met. Hawkins P et al. A guide to defining and implementing protocols for the welfare assessment of laboratory animals. Laboratory Animals 45, 1-13, 2011
7 Animal Welfare : many definitions! The animals freedom to adapt to environmental conditions up to a level that it perceives as positive Ohl F & van der Staay FJ ( 2012) Vet J 192, Vera Baumans UU 7
8 Why important? Animal welfare Scientific results Legal obligation Judgement ethical admissibility Vera Baumans KI/UU 8
9 Intended and unintended effects of procedures on experimental results Experimental procedure intended effect Experimental results nonspecific nonintended effects effects Disturbance of homeostatic balance compensatory mechanisms Changes endocrinology immunology blood circulation food intake clinical disease etc. Vera Baumans UU 9
10 Non- intended effects Environmental factors Pain, discomfort, distress...
11 Environmental factors affecting the laboratory animal cage size structure/enrichment cage cage mates contra-specifics odours noise light RH T man food/water air/ventilation bedding NH 3, CO 2 pathogens Vera Baumans KI/UU 11
12 What about housing? Vera Baumans KI/UU 12
13 From here Vera Baumans UU 13
14 To here Vera Baumans UU 14
15 And to environmental refinement Vera Baumans UU 15
16 Environmental Refinement/enrichment A method to enhance animal well-being by providing animals with sensory and motor stimulation, through structures and resources that facilitate the expression of species-typical behaviors and promote psychological well-being through physical exercise, manipulative activities and cognitive challenges according to speciesspecific characteristics. Guide for the Care and Use of Laboratory Animals, NRC 2011, Baumans 2000 Vera Baumans UU 16
17 Super enrichment as a tool: changing brain and behaviour Vera Baumans UU 17
18 Refinement: meeting needs of animals Vera Baumans UU 18
19 Council Directive 2010/63/EU All animals should be allowed adequate space to express a wide behavioural repertoire. Animals should be socially housed wherever possible and provided with an adequately complex environment to enable them to carry out a range of normal behaviours. Vera Baumans UU 19
20 How do we know what is adequately complex? Vera Baumans UU 20
21 Preference tests Ask animals what they prefer Strength of preference Combine with behavioural observation Vera Baumans UU 21
22 Preference test Vera Baumans UU 22
23 How to refine the animal s environment? Socially social partners humans Physically sensory ( auditory, visual, olfactory, tactile) nutritionally ( supply, type of food) Psychologically (controllability, predictability) structure and complexity in the cage (e.g. nesting material, nest- boxes, platforms, tubes, partitions) Vera Baumans UU 23
24 Social, physical, psychological stimuli Vera Baumans UU 24
25 Social, physical, psychological stimuli Vera Baumans UU 25
26 Social, physical, psychological stimuli: impact on animal welfare! Vera Baumans UU 26
27 Housing environment influences the need for pain relief during post-operative recovery in mice. Pham et al ( 2010). Physiology & Behavior 99,
28 Impact of invasive experimental procedures on animal well-being dependent on: Social / individual housing Cage refinement/enrichment Anaesthetics/analgesics Post-invasive recovery appetite, body temperature, food intake, body weight, wound healing Vera Baumans KI/UU 28
29 Self-administration 2x250 ml bottles drinking water, 1 plain water, 1 Ipren (Ibuprofen) susp. 20mg/ml Dose: 40mg/kg body weight Pilot with 2 bottles plain water preference for right bottle Half of the groups Ipren water in right bottle, other half in left bottle Vera Baumans KI/UU 29
30 Material & Methods 72 female C57BL/6 mice, g 2 cohorts 36 enriched condition (E), 36 non enriched (NE) Mac II ( 370 cm 2 ), 3 mice per cage Surgery: laparotomy and caecal manipulation under isoflurane anaesthesia vs anaesthesia only Post-operative: group vs individual housing Duration of study: 2 weeks Vera Baumans KI/UU 30
31 Results Body weight: lower in operated groups Regain of bodyweight lower in individually, nonenriched housed mice Water intake pre- operatively: no differences Ipren self-administration: after operation Ipren intake Individually housed: Ipren intake Non-enriched operated groups: Ipren intake Nest building: no differences Wound healing: no differences Vera Baumans KI/UU 31
32 Conclusions Mice self-administer analgesics after surgery Housing conditions influence postoperative recovery and the need for pain relief in operated mice Social housing more impact than physical refinement Vera Baumans KI/UU 32
33 Environmental factors affecting the laboratory animal cage size structure/enrichment cage cage mates contra-specifics odours noise light RH T man food/water air/ventilation bedding NH 3, CO 2 pathogens Vera Baumans KI/UU 33
34 To Group or Not to Group? To group or not to group? Good practice for housing male laboratory mice We conclude that it is not possible to give general recommendations for good practice for housing male laboratory mice, as responses to single-and group-housing can be highly context dependent. The welfare implications of housing protocols should be researched and considered in each case. Kappel, S.; Hawkins, P.; Mendl, M.T. (2017), Animals 7,12 Vera Baumans UU 34
35 Past Experience inbreeding procedures age strain gender familiarity Experiment length 35/40
36 Social Isolation in mice and rats Social isolation alters prefrontal cortex function, decreases myelination and c-fos Muchimapura et al Neuroscience 112,3, 2002 Makinodan et al Science 337,2012 Liu et al Nature Neurosc 15,2012 Matsumoto et al Neuroscience Research 73,2012
37 Preference for social contact versus environmental enrichment in male laboratory mice Male mice preferred to sleep in close proximity to their familiar cage mate The need to engage in active social behaviour increased with age. Tissues were used to a large extent for sleeping When individual housing is inevitable due to excessive aggressive behaviour, the presence of nesting material could partly compensate for the deprivation of social contact. PLP Van Loo et al.(2004) Laboratory Animals 38, Vera Baumans UU 37
38 Aggression after cage cleaning: practical solutions? Vera Baumans UU 38
39 Aggression after cage cleaning in male BALB/c mice Van Loo et al, 2000 Vera Baumans KI/UU 39
40 Aggression and group size Van Loo et al, 2001 Vera Baumans KI/UU 40
41 Recommendations Housing in small groups Provision of nesting material Transfer of nest odours when cleaning cages Limit disturbances to minimum PLP van Loo 2001, thesis Utrecht University 41/40
42 Impact of living apart together on postoperative recovery of mice compared with social and individual housing Surgically implantation of a telemetry transmitter Social housing has a positive impact on postoperative recovery LAT housing is not a better option than individual housing. PLP van Loo et al 2007.Laboratory Animals 41, Vera Baumans UU 42
43 Results: Heartrate Heart rate during rest (mean +- SEM) Heart rate (bpm) IND LAT SOC Time post-surgery (days) LAT>IND, LAT>SOC, IND>SOC (P<0.05) 43/24
44 Pain behaviour Stretch ind lat soc Days post-surgery IND and LAT mice show an increase in stretching 6-10 days after operation 44/24
45 Animal welfare and good science: where are we going?
46 Other species as lab animal? Humans when possible Zebrafish Cephalopods (octopus, squid ) Nematodes (C. elegans) e.g. genetic studies, developmental biology, aging Insects Fruitflies (Drosophila) Locusts, Crickets, Grass hoppers Black soldier flies Meal worms Vera Baumans UU 46
47 Fish as experimental animal Increase in use Ecotoxicology Development biologicals Functional genomics Developmental biology Welfare of fish new area Huge diversity Different needs? Ability to experience pain 47
48 Ability to experience pain Poikilothermic vertebrates Nociceptors present Neuropeptides (e.g. Substance P) present Still debate on cognitive abilities 48
49 Other species as lab animal? Humans when possible Zebrafish Cephalopods (octopus, squid ) Nematodes (C.elegans) e.g. genetic studies, developmental biology, aging Insects Fruitflies (Drosophila) Locusts, Crickets, Grass hoppers Black soldier flies Meal worms Protein source Vera Baumans UU 49
50 Fruit fly Drosophila melanogaster Genetics, embryonic development, learning, behaviour, aging Fundamental biological mechanisms and pathways similar Not subject to animal licensing laws. No lengthy applications for personal and project licenses!! (Jennings BH 2011,Materials Today 14,5, ) But what about welfare?? Vera Baumans UU 50
51 Crickets, locusts Sources of protein: Food of the future?! Laboratory animal of the future?? Not covered by EU Directive Most species of cricket seem happy with a regime of 16 hours of daylight to 8 hours of night and need cover (egg cartons, toilet rolls etc) But what about welfare?? Vera Baumans UU 51
52 Russell and Burch The Principles of Humane Experimental Technique, 1959 Replacement Reduction Refinement Responsibility Vera Baumans UU 52
53 Our responsibility as researcher How important is it to use animals for this purpose? Is the use of non-mammalian species a solution? What about their welfare? Can an alternative, non-animal method be used? Can the number of animals be reduced? Can pain/discomfort be reduced? What can be done to improve the living conditions of our animals? Vera Baumans UU 53
54 Best practice Practicality 54/40
55 Food for thought I hope!! Thank you!
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