Workshop: “Animals bred, but not used in experiments”, October 18-20, 2013, Hotel Duin & Kruidberg, Santpoort, the Netherlands.
Experiments in biomedical science use large numbers of laboratory animals. It is a fact that to provide these animals, regularly more animals are bred than are finally used in the experiments planned. The Ministry of Economic Affairs as the competent body of the Netherlands had asked Prof. Coenraad Hendriksen and Dr. Jan-Bas Prins to organize a workshop to identify the reasons for the breeding of surplus animals and to devise recommendations as to how the number of animals that are bred but not used can be reduced to a minimum.
A number of experts from different fields of laboratory animal science were invited for a two day workshop to the Hotel Duin & Kruidberg in Santpoort, a town close to Amsterdam, to discuss these issues and to develop a paper for the Dutch authorities. Obviously, many of the laboratory animals bred are genetically altered (GA) animals. Moreover, techniques to cryopreserve GA animal lines could be a means to reduce the number of animals that are bred. The invitation was therefore extended to the ISTT to send a representative to take part in this workshop.
Here, I will give a short summary of the topics that have been discussed and of the outcomes. However, I refer you to the final report of the workshop, parts of which have been developed within individual small workgroups and will be put together into a final document by the kind efforts of Coenraad and Jan-Bas. I will inform you immediately upon the publication of this report.
A topic central to the discussion was the identification of reasons for the production of animals that are then not used in experiments. A major reason for this is the production of unwanted sexes and unwanted genotypes. The participants agreed that good planning can considerably reduce the number of surplus animals. At the same time, resources can be saved and either used for additional experiments or for cost reduction. However, breeding schemes with multiple alleles, as well as the organization of a facility, can be complex. A strong need for counseling as well as education of users of laboratory animals was identified, to make them competent to plan accordingly. The centralization of the breeding colonies under the responsibility of the facility management was discussed as a possibility to streamline breeding strategies. On the other hand, for the time being, this does not seem to be feasible for very many facilities. Local Animal Welfare Committees should evaluate local SOPs and develop a catalogue of best practices to help keep surplus animals to a minimum. GA animal lines should be cryopreserved immediately after their creation when there is no need to breed extra animals for this purpose and when animals from test rederivations can be used for experiments or for the breeding colony. Thereby, the lines are protected from disaster and from genetic drift at the same time, live mice can be terminated at any time, and the lines can be easily shipped to collaborators. Lines should be made available to collaborators as early as possibly to avoid generating the same line at different places. In case expertise for cryopreservation is lacking, lines can be donated to repositories like EMMA where they are cryopreserved free of charge. Investigators should always consider sharing lines with the scientific community through such repositories.
A second important topic discussed during the workshop was the use of new technologies for the generation of GA animals as well as for their experimental analysis. New lines should be directly generated on the desired background. In case backcrossing is needed, speed congenic strategies should be used to reduce the number of animals needed during that process. Technologies utilizing the targeting of nucleases to the locus of interest (ZFNs, TALENs, CRISPER/Cas9) promise to eventually allow the generation of GA lines with reduced numbers of animals directly on the desired background. Complex strategies for the generation of customized animals for specific experiments were presented. It was agreed that these should be freely available. However, individual scientists and institutes should evaluate whether it is worth adopting a new and complicated technique. Since the process of setting up complex protocols may well lead to the use of high numbers of animals, investigators should consider collaborating with colleagues who perform similar experiments at large scales.
Ethical considerations let us come to the understanding that there is an intrinsic value of life. We found that it is for this reason that it is morally wrong to kill more animals than absolutely necessary. Biomedical science is tasked with producing answers to pressing questions on the molecular functions of life and disease and finding new cures. It was pointed out that the principles of the 3R’s have to be respected at all times, but a number of animal experiments are indispensable. In this context, it is unavoidable to breed animals that are not used for these experiments, but it is important to ensure that their numbers are kept to a minimum.
Member of ISTT’s Executive Council
October 23, 2013
List of participants and affiliations, excluding those who were unable to send permission for disclosure:
van der Broek, Frank, NVWA, The Netherlands; Aleström, Peter, The Norwegian Zebrafish Platform, Norway; Benavides, Fernando, University of Texas, USA*; Bussell, James, Wellcom Trust Sanger Institute, UK*; Chrobot, Nichola, MRC Harwell, UK; van Es, Johan, Hubrecht University, The Netherlands; Fentener van Vlissingen, Martje, Erasmus MC, The Netherlands; Hendriksen, Coenraad, InTraVacc, The Netherlands; Hohenstein, Peter, Roslin Intitute, UK*; Krimpenfort, Paul, NKI, The Netherlands; Morton, David, UK; Prins, Jan-Bas, LUMC, The Netherlands; Raspa, Marcello, EMMA, Italy*; Tramper, Ronno, Consultant, The Netherlands; van der Valk, Jan, NKCA; Wilbertz, Johannes, Karolinska Institutet, Sweden*; Ohl, Frauke, Utrecht University, The Netherlands; Pool, Chris, KNAW, The Netherlands; Witler, Lars, Max-Planck Institute Mol. Gen., Berlin, Germany*.