Reduction of surplus animals

Today, animal models continue to make an important contribution in drug development as well as in research into the fundamentals of various human diseases. The major advances in medicine are largely due to such models, with mice, in particular genetically modified strains, being the most commonly used.¹

Breeding often produces a large number of so-called surplus animals that cannot be used in research. If one recalls Mr. Mendel's theory of heredity, it will occur to one that when two individuals are crossed, offspring are produced with different genotypes and are by no means all genetically identical. In science, however, the aim is to achieve reproducibility of experiments, which can only be guaranteed if one uses animals that are as identical as possible and have one and the same genetic background, the same age and even the same sex.²

EU Directive 2010/63/EU requires member states to keep statistics on the number of all animals used (not only those used in animal experiments, but also those used in breeding). Statistics of these data are published by the European Commission every five years. In the latest published report from 2017, it can be seen that 12.6 million surplus animals were killed in the EU. The publication of the next figures, which had to be submitted by member states in 2022, is expected in 2024.³

In addition to the precise documentation of such data from experiments with and on animals, however, the implementation of the 3Rs (Replacement, Reduction, Refinement) in the experiment is also required by law. If no suitable replacement method can be found, then at least the reduction of the used test animals must be aimed at. Thus, it is in the spirit of the law to plan the breeding in such a way that none or as few surplus animals as possible are produced. Unfortunately, in view of the wide variety of molecular genetic methods used to create an animal line, there is no uniform method that can be used to optimize breeding. Rather, an individually adapted concept must be looked for. For example, the Jackson Laboratory offers support in the form of a worksheet. The Institute of Laboratory Animal Science of the University of Zurich (UZH) provides a BreedingCalculator, a special software to calculate the required breedings.⁴

Apart from establishing a suitable breeding strategy, there are other ways of reducing the number of surplus animals or at least using them for other purposes. In principle, cryopreservation of sperm and embryos is a means to achieve this goal. It not only leads to a reduction of experimental animals by interrupting continuous breeding, but also saves costs incurred in keeping, prevents transport and reduces the risk of changes in the genome of an animal line in the form of spontaneous mutations and genetic drifts. The only criticism, however, is that animals are needed for kyro conservation itself and subsequently for revitalization of the conserved line.⁵

Furthermore, surplus animals can often be used as control animals in experiments instead of wild types. If this is not possible, they could be used for training purposes if they are not unaffected. Training courses and other courses often require mice, which would therefore not have to be bred specifically. Another possibility is the use as feed animals, but for this purpose legal requirements according to Article 23 of Regulation EC 1069/2009 have to be met. According to existing law, only wild types or, at most, animals with spontaneous mutations may be given to zoos or similar institutions. For genetically modified laboratory animals, a special permit is required according to Regulation EC 1829/2003, which usually prevents this undertaking. However, it would be in the interest of animal welfare to adapt the law and thus allow the feeding of these animals at least in a killed state. Discussions are already underway in Germany in this regard. ^6,7

Some platforms for the exchange of animals or their organs offer another possibility for meaningful use. In some cases, however, there are contractual restrictions that require licenses for transfer to third parties. For genetically unmodified laboratory animals, there are also adoption programs that allow placement with private individuals.⁵

Considering the options that exist to significantly reduce the number of surplus animals or at least to find useful applications, it should not be a problem to act in the sense of reduction. It must be the goal of the international scientific community to strive for the 3Rs in research in order to meet the ethical and legal requirements of animal experimentation.

Sources:
1) Bundesministerium für Bildung, Wissenschaft und Forschung, https://www.bmbwf.gv.at/Themen/Forschung/Forschung-in-%C3%96sterreich/Services/TierV/TVStat.html (accessed on 19.04.2023)
2) Wewetzer H, Wagenknecht T, Bert B, Schönfelder G. The fate of surplus laboratory animals: Minimizing the production of surplus animals has the greatest potential to reduce the number of laboratory animals: Minimizing the production of surplus animals has greatest potential to reduce the number of laboratory animals. EMBO Rep. 2023 Mar 6;24(3):e56551. doi: 10.15252/embr.202256551. Epub 2023 Jan 30. PMID: 36715165; PMCID: PMC9986809; Buch T, Davidson J, Hose K, Jerchow B, Nagel-Riedasch S, Schenkel J. Reduktion der Zahl nicht verwendbarer Tiere in Versuchstierzuchten, GV SOLAS (März 2022). https://www.gv-solas.de/wp-content/uploads/2022/04/Reduktion-von-Zuchtueberschuessen_03-2022.pdf (accessed on 19.04.2023)
3) RL 2010/63/EU Report from the commission to the European parliament and the council, https://eur-lex.europa.eu/legal-content/EN/TXT/HTML/?uri=CELEX:52020DC0015&from=EN (accessed on 31.08.2023); Wewetzer H, Wagenknecht T, Bert B, Schönfelder G. The fate of surplus laboratory animals: Minimizing the production of surplus animals has the greatest potential to reduce the number of laboratory animals: Minimizing the production of surplus animals has greatest potential to reduce the number of laboratory animals. EMBO Rep. 2023 Mar 6;24(3):e56551. doi: 10.15252/embr.202256551. Epub 2023 Jan 30. PMID: 36715165; PMCID: PMC9986809.
4) RL 2010/63/EU; Buch T, Davidson J, Hose K, Jerchow B, Nagel-Riedasch S, Schenkel J. Reduktion der Zahl nicht verwendbarer Tiere in Versuchstierzuchten, GV SOLAS (März 2022). https://www.gv-solas.de/wp-content/uploads/2022/04/Reduktion-von-Zuchtueberschuessen_03-2022.pdf (accessed on 19.04.2023); The Jackson Laboratory, https://www.jax.org/jax-mice-and-services/customer-support/technical-support/breeding-and-husbandry-support/colony-planning; UZH, https://www.ltk.uzh.ch/en/Breeding.html (accessed on 19.04.2023)
5) Buch T, Davidson J, Hose K, Jerchow B, Nagel-Riedasch S, Schenkel J. Reduktion der Zahl nicht verwendbarer Tiere in Versuchstierzuchten, GV SOLAS (März 2022). https://www.gv-solas.de/wp-content/uploads/2022/04/Reduktion-von-Zuchtueberschuessen_03-2022.pdf (accessed on 19.04.2023)
6) Verordnung (EG) 1069/2009 des Europäischen Parlaments und des Rates; Verordnung (EG) 1829/2003 des Europäischen Parlaments und des Rates; Buch T, Davidson J, Hose K, Jerchow B, Nagel-Riedasch S, Schenkel J. Reduktion der Zahl nicht verwendbarer Tiere in Versuchstierzuchten, GV SOLAS (März 2022). https://www.gv-solas.de/wp-content/uploads/2022/04/Reduktion-von-Zuchtueberschuessen_03-2022.pdf (accessed on 19.04.2023)
7) Offener Brief GV-SOLAS zum Thema GVO Verfütterung https://www.gv-solas.de/wp-content/uploads/2023/01/Brief-GVO-Verfuetterung-GV-SOLAS-2022.pdf (accessed on 31.08.2023)

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