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Each year, around three million animals suffer and die in research laboratories worldwide. According to figures from the German Animal Welfare Federation, a total of 2,825,066 vertebrates and cephalopods (octopuses and squid) were ‘used’ for scientific purposes in 2018. Of those, 686,352 animals were killed without actually being subjected to experiments. At the invitation of the University of Bern (Switzerland), international scientists have now drawn up new recommendations for animal experiments and sent out “a call for a paradigm shift to improve the reproducibility of test results and simultaneously reduce the number of animals used in experiments.”

In general, animal experiments are carried out under strictly standardized laboratory conditions. These are aimed at improving the reproducibility of test results, except that this is rarely the outcome. On the contrary, reproducibility is surprisingly poor. However, by deliberately including biological variation in the design of the experiments, the results should become more reliable in the future, if researchers from different disciplines are to have their way.

“The ability to reproduce scientific findings through an independent replication study is the acid test by which scientists distinguish facts from mere anecdotes,” says Bernhard Völkl. He organized the workshop together with Hanno Würbel, Professor of Animal Welfare at the University of Bern. Würbel explains that “poor reproducibility produces economic costs and scientific uncertainty – and also raises ethical concerns if it hampers medical progress and animals are used for inconclusive studies.”

More biological variation needed

The scientists state that strict standardization in terms of animals and environmental conditions is the norm in animal experiments. For example, when researching the effect of new drugs. By eliminating as many influential factors as possible, except for the experiment conditions and treatment, the “precision of the test results should increase and at the same time the use of animals should be reduced.” Nonetheless, such a degree of standardization implies that the experimental results can only be applied to a very limited extent.

“Many animal experiments are conducted under such a narrow range of conditions that there is a significant risk of obtaining results that are unlikely to be reproducible,” Würbel goes on to explain. That’s why the researchers recommend ‘heterogenization.’ This type of planned biological variation in the experimental design of animal experiments is intended to expand the scope of the results and thereby improve reproducibility.

Fewer animals for more findings

“With this design, we can balance the need to compare interventions under similar conditions with the ability to introduce heterogeneity, which allows us to determine whether effects are robust over a range of conditions,” says Naomi Altman, a recently retired professor at Penn State University (Philadelphia, USA). There are many different options available to accommodate this biological variation, for example using several breeding lines or age groups of the animals, or different environmental conditions. In addition, experiments could also be carried out in several sub-experiments or in various laboratories.

“There is no single best solution for every experiment,” says Völkl. “Therefore, we recommend the heterogenization of animals and environmental conditions in general terms. Researchers should justify their choices with respect to the range of animals and conditions to which their findings should generalize.” The researchers underline in their study, (published in the journal Nature Reviews Neuroscience) that even if more animals were used for individual experiments, this would still reduce the overall use of animals. “We propose a paradigm shift to increase the benefit of the research and reduce the number of animals used in research,” Würbel adds: “Instead of minimizing the number of animals per experiment, we should maximize the amount of knowledge we gain per animal and experiment.”

The workshop was supported by the Swiss National Science Foundation (SNSF) and the Department of Animal Welfare at the University of Bern.