Enhancing animal welfare in biomedical research through behaviour management and training of large laboratory animals and non-human primates

Radomir Ratajac1*, Björg Pauling2

1Scientific Veterinary Institute Novi Sad, Rumenacki put 20, Novi Sad, Serbia
2German Primate Center – Leibniz Institute for Primate Research, Kellnerweg 4, 37077 Göttingen, Germany; email: bpauling@dpz.eu
*Correspondence and present address: Radomir Ratajac, Scientific Veterinary Institute Novi Sad, Rumenacki put 20, Novi Sad, Serbia; email: ratajac@niv.ns.ac.rs

From 17 to 19 March 2019, the third PRIMTRAIN Annual Conference took place at the University of Novi Sad in Serbia, hosted by Dr. Radomir Ratajac from the Scientific Veterinary Institute Novi Sad. PRIMTRAIN (CA15131; https://www.primtrain.eu) is funded by the COST Association (https://www.cost.eu), bringing together animal trainers and staff involved in animal training and behaviour management of large laboratory animals (LLA), including non-human primates (NHPs). The aim of the meeting was to exchange knowledge between the representatives from 14 European countries and share state-of-the-art practices in order to work with animals that are best prepared for the tasks or procedures they are supposed to perform or undergo. Nearly half of the participants were women and 43% came from inclusiveness target countries.

At the meeting opening the attendants were addressed by conference hosts: Rector of the University of Novi Sad Professor Dejan Jakšić and Chief Research Officer of the Scientific Veterinary Institute Novi Sad Dr Tamaš Petrović. In their presentation, Jakšić and Petrović introduced the host institutions (University of Novi Sad: https://www.uns.ac.rs/index.php/en/; Scientific Veterinary Institute Novi Sad: https://niv.ns.ac.rs/en/) and briefly informed participants about the organizational structure, educational programs and research projects currently underway, as well as future prospects.

Presentations were clustered in three sessions on (1) behaviour management and training of LLA; (2) animal welfare of LLA in biomedical research; and (3) one workshop, "3Rs in research with LLA". The twelve speakers presented various laboratory animals and their handling and training, as well as the challenges faced by authorities dealing with the regulation of animal experimentation, to the 50 participants of the meeting.

In the first session, which was chaired by Marijana Vučinić from the University of Belgrade, Mirjam Roth, a veterinarian, offered consultancy in the areas of behaviour and animal training. She addressed the question of when to start with the actual training with dogs, minipigs and cats after first contact and recommended animal-paced progression of the training based on a trusting human–animal relationship.

Initial training was also the subject of Evelin Kiefer's talk. She explained how new NHPs at her facility are acclimated to new places and personnel using positive reinforcement training (PRT) and rarely negative reinforcement training (NRT) and how animals are chair trained. Evelin came from the University of Pécs, Hungary.

Balasz Knakker, also from the University of Pécs, has trained NHPs for the paired associates learning (PAL) task and described training strategies accompanied by characteristic learning patterns and behaviours.

Environmental enrichment, clicker training and pre-conditioning techniques of beagle dogs were explained by Anton Pikhovych from Bayer AG. He also presented behaviour assessment as a tool for improved animal welfare in the experimental facility.

Chantal Kapteijn from Utrecht University talked about the reduction of stress and fearful behaviour of dogs in the veterinary clinic and how early-life socialisation and PRT focussed on veterinary procedures may prevent traumatic experiences.

For the workshop Eddie Clutton from the Wellcome Trust Critical Care Laboratory for Large Animals described the importance of anaesthesia, analgesia and the 3Rs principles for large animals in translational research. He emphasised that improved study design and more precise analytical methods can reduce the number of, but not obviate, the need for animals in experiments in which in vitro or in silico alternatives are unavailable. Here, refinement is needed which involves methods and techniques that minimise (ideally eliminate) the pain, suffering, distress or lasting harm that may be experienced by research animals and so improve their welfare. This refinement has six main components: (1) environmental acclimatization and enrichment; (2) training animals to cooperate with procedures; (3) minimally invasive surgery; (4) anaesthesia; (5) pain management (recognition, quantification, treatment); (6) establishing humane end-points, and euthanasia.

He put up a case for prospective pain studies in these species but declared the reduction and refinement principles would be better served by improved reporting, describing animal experiments and providing precise details of all procedures, including how anaesthesia and analgesia are used. Amongst ARRIVE-subscribing journals (and others) a more determined editorial enforcement of the guidelines would increase the information available on pain management in pigs and sheep undergoing translational research.

Augusto Vitale from University La Sapienza, Rome, Italy, recapitulated the origin and development of the 3Rs principle starting from the original idea by Charles Hume, and the following work developed by William Russell and Rex Burch. He discussed modern concepts such as "partial replacement" and "intra-reduction" and illustrated the effect that the application of the 3Rs principle can have on both the quality of life of the animals involved and the quality of the data recorded. The take-home message of his talk was that the application of the 3Rs principle to experimental work with animal models is not only an ethical issue, but scientific as well, contributing to a modern and more scientifically and ethically sound use of animals in scientific research.

Jan Langermans from the Biomedical Primate Research Centre, Rijswijk, and the University of Utrecht, the Netherlands, chaired the session on "animal welfare of large laboratory animals in biomedical research" and was the first speaker talking about animal welfare in large animals. He advocated good knowledge of genetics, microbiome and behaviour when keeping NHPs.

Hands-on information on the work with Göttingen minipigs was shared by Lars Friis Mikkelsen from Ellegaard, Dalmose, Denmark. After demonstrating the advantages of minipigs in translational research, he explained that even young males can be group-housed and how, if group-housing is not possible, minipigs can be kept happy, e.g. with environmental enrichment.

Caroline Bergmann from Oxford University, UK, introduced to the audience domestic ferrets (Mustela putorius furo) as a model in various fields of biomedical research, such as research on human influenza, reproductive research, cognitive neuroscience and others. The presentation covered their unique physiological and behavioural requirements such as nutrition, mating and rearing and provided guidance on establishing a comprehensive ferret healthcare program.

Welfare assessment of farm animals used in research was the topic of Vlatko Ilieski's presentation. This assessment should include staff and be performed by qualified persons and by applying appropriate welfare indicators. For each project welfare depends on the particular facilities and working practices, the nature of the research, and the species and number of animals involved. Welfare assessment requires a multidisciplinary approach including physiology, neurobiology and behaviour. Vlatko came from the University of Skopje, North Macedonia.

Marijana Vučinić described the process of ethical evaluation and approval in Serbia. She emphasised that scientists as well as institutional ethical committee members need to be familiar with all legal, scientific and ethical principles of experimentation, testing and education on animals. Only laypersons in committees, often members of NGOs who oppose animal experimentation, need to be familiar with ethical principles only.

Professionalization with regards to both ethical and scientific principles at all stages of the ethical evaluation of projects on animals can form the basis for a critical discussion of the ethical concept of animal experimentation and harm–benefit analysis. This should also help on the way to harmonisation with EU legislation.

The conference also hosted work group meetings and the PRIMTRAIN Management Committee meeting.