Scientists and the 3Rs: attitudes to animal use in biomedical research and the effect of mandatory training in laboratory animal science

The 3Rs principle of replacement, reduction, and refinement has increasingly been endorsed by legislators and regulatory bodies as the best approach to tackle the ethical dilemma presented by animal experimentation in which the potential benefits for humans stand against the costs borne by the animals. Even when animal use is tightly regulated and supervised, the individual researcher’s responsibility is still decisive in the implementation of the 3Rs. Training in laboratory animal science (LAS) aims to raise researchers’ awareness and increase their knowledge, but its effect on scientists’ attitudes and practice has not so far been systematically assessed. Participants (n=206) in eight LAS courses (following the Federation of European Laboratory Animal Science Associations category C recommendations) in Portugal were surveyed in a self-administered questionnaire during the course. Questions were related mainly to the 3Rs and their application, attitudes to animal use and the ethical review of animal experiments. One year later, all the respondents were asked to answer a similar questionnaire (57% response rate) with added self-evaluation questions on the impact of training. Our results suggest that the course is effective in promoting awareness and increasing knowledge of the 3Rs, particularly with regard to refinement. However, participation in the course did not change perceptions on the current and future needs for animal use in research

Federation of European Laboratory Animal Science Associations recommendations of best practices for the health management of ruminants and pigs used for scientific and educational purposes

Most ruminants and pigs used for scientific and educational aims are bred not for these purposes but in a farm environment. Given the wide range of diseases that these species might have, ensuring that the animals’ health status is appropriate can be complex and challenging. The Federation of European Laboratory Animal Science Associations has previously published recommendations for the health monitoring of experimental colonies of pigs (1998) and, respectively, calves, sheep and goats (2000). Unfortunately, the uptake of those recommendations was poor and insufficiently reported in scientific publications. These new recommendations for best practice focus on the main species of ruminants (cattle, sheep and goats) and pigs. They provide general and specific information helpful for designing a health management programme for the suppliers and for the user establishments, as well as guidance on animal procurement. Critical thinking based on the fields of use of the animals is promoted, aiming to help in taking informed decisions rather than establishing an exhaustive exclusion list for pathogens. Implementing the best health and welfare management practices should be done under the guidance of a competent attending veterinarian, with expertise and sufficient authority to take the appropriate action, doubled by excellent communication skills. It is strongly recommended that the user establishment’s veterinarian works in close collaboration with the supplier’s veterinarian. // Die meisten Wiederkäuer und Schweine, die zu wissenschaftlichen und Ausbildungszwecken dienen, werden nicht eigens dafür, sondern in einem landwirtschaftlichen Umfeld gezüchtet. Angesichts des breiten Spektrums potenzieller Krankheiten bei diesen Tierarten kann die Gewährleistung eines adäquaten Gesundheitszustands der Tiere durchaus komplex und schwierig sein. FELASA hat bereits früher Empfehlungen für die Gesundheitsüberwachung von Versuchskolonien von Schweinen (1998) bzw. Kälbern, Schafen und Ziegen (2000) veröffentlicht. Leider stießen diese Empfehlungen auf mangelndes Echo und wissenschaftliche Publikationen berichteten diesbezüglich nur unzureichend. Die vorliegenden neuen Empfehlungen für beste Praxis konzentrieren sich auf die wichtigsten Arten von Wiederkäuern (Rinder, Schafe und Ziegen) sowie auf Schweine. Sie enthalten allgemeine und spezifische Informationen, die für die Gestaltung eines Gesundheitsmanagementprogramms für die Lieferanten und für die Verwendereinrichtungen nützlich sind, ebenso wie Hinweise zur Tierbeschaffung. Kritisches Denken auf der Grundlage der Anwendungsbereiche der Tiere, das darauf abzielt, fundierte Entscheidungen zu treffen, anstatt eine erschöpfende Ausschlussliste für Krankheitserreger zu erstellen, wird unterstützt. Die Umsetzung der besten Gesundheits- und Tierschutzmanagementpraktiken sollte unter der Anleitung eines kompetenten behandelnden Tierarztes erfolgen, der über Fachwissen und genügend Autorität sowie über ausgezeichnete Kommunikationsfähigkeiten verfügen, um die entsprechenden Maßnahmen zu ergreifen und zu vermitteln. Eine enge Zusammenarbeit zwischen dem Tierarzt der Verwendereinrichtung und dem Tierarzt des Lieferanten wird dringend empfohlen

Heterochronic faecal transplantation boosts gut germinal centres in aged mice

Ageing is a complex multifactorial process associated with a plethora of disorders, which contribute significantly to morbidity worldwide. One of the organs significantly affected by age is the gut. Age-dependent changes of the gut-associated microbiome have been linked to increased frailty and systemic inflammation. This change in microbial composition with age occurs in parallel with a decline in function of the gut immune system, however it is not clear if there is a causal link between the two. Here we report that the defective germinal centre reaction in Peyer’s patches of aged mice can be rescued by faecal transfers from younger adults into aged mice and by immunisations with cholera toxin, without affecting germinal centre reactions in peripheral lymph nodes. This demonstrates that the poor germinal centre reaction in aged animals is not irreversible, and that it is possible to improve this response in older individuals by providing appropriate stimuli

Macroscopic, microscopic and biochemical characterisation of spontaneous colitis in a transgenic mouse, deficient in the multiple drug resistance 1a gene

1. A novel animal model of spontaneous colonic inflammation, the multiple drug-resistant (mdr1) a(−/−) mouse, was identified by Panwala and colleagues in 1998. The aim of our study was to further characterise this model, specifically by measuring cytokines that have been implicated in inflammatory bowel disease (IBD) (IL-8 and IFN-γ) in the colon/rectum of mdr1a(−/−) mice, and by determining the sensitivity of these, together with the macroscopic, microscopic and disease signs of colitis, to dexamethasone (0.05, 0.3 and 2 mg kg(−1) subcutaneously (s.c.) daily for 7 days). 2. All mdr1a(−/−) mice had microscopic evidence of inflammation in the caecum and colon/rectum, while control mice with the same genetic background did not. Significant increases in colon/rectum and caecal weights and also in cytokine levels (both IFN-γ and IL-8) in homogenised colon/rectum were observed in mdr1a(−/−) mice compared to mdr1a(+/+) mice. 3. Dexamethasone reduced the increases in tissue weights and also microscopic grading of colitis severity, but had no effect on IFN-γ or IL-8. 4. This study supports the similarity of the gastrointestinal inflammation present in mdr1a(−/−) mice to that of human IBD, in particular Crohn's disease. This has been demonstrated at the macroscopic and microscopic levels, and was supported further by elevations in colonic levels of IFN-γ and IL-8 and the disease signs observed. The incidence of colitis was much higher than previously reported, with all mice having microscopic evidence of colitis. The limited variance between animals in the parameters measured suggests that this model is reproducible

Burrowing and nest building behavior as indicators of well-being in mice

The assessment of pain, distress and suffering, as well as evaluation of the efficacy of stress-reduction strategies, is crucial in animal experimentation but can be challenging in laboratory mice. Nest building and burrowing performance, observed in the home cage, have proved to be valuable and easy-to-use tools to assess brain damage or malfunction as well as neurodegenerative diseases. Both behaviors are used as parameters in models of psychiatric disorders or to monitor sickness behavior following infection. Their use has been proposed in more realistic and clinically relevant preclinical models of disease, and reduction of these behaviors seems to be especially useful as an early sign of dysfunction and to monitor disease progression. Finally, both behaviors are reduced by pain and stress. Therefore, in combination with specific disease markers, changes in nest building and burrowing performance may help provide a global picture of a mouse`s state, and thus aid monitoring to ensure well-being in animal experimentation