The July episode of 3-Minute 3Rs from the North American 3Rs Collaborative (www.na3rsc.org), the NC3Rs (www.nc3rs.org.uk), and Lab Animal (www.nature.com/laban)
[NC3Rs] Colorectal cancer is particularly hard to treat, and only 11% of patients whose tumours have metastasised survive five years after diagnosis. Mouse models that incorporate patient tissue are widely used in drug discovery, but they’re both expensive and time consuming, and often don’t fully represent human disease.
A team at the Mount Sinai Hospital in New York, led by Erdem Bangi, developed a screening platform using Drosophila to test potential therapies for a patient whose cancer had proved resistant to treatment. The team identified nine genes that were driving the progression of the disease, so they modified orthologs of these genes in the flies. They were able to use the flies to screen a raft of drug combinations, discovering that the most effective treatment combined trametinib, a chemotherapy drug, and zoledronate, usually used to treat bone diseases. When the patient was treated with this novel combination, their tumours shrank, then remained stable for a total of 11 months. This platform could reduce the number of mice used to find effective cancer treatments, not to mention getting them to patients quicker and cheaper. Personalised medicine is often said to be the next big thing in healthcare, but this new approach might just live up to the buzz.
[NA3RsC] Too much standardization of experimental design may be unintentionally contributing to the reproducibility crisis in animal-based research. Today, rigorously standardized behavioral studies may be so well controlled that statistically significant findings may actually be irrelevant and not reproducible across laboratories. Bodden and colleagues at the University of Münster, in Germany, explore whether systematically varying study conditions can improve reproducibility. They specifically investigated the impact of the time of day the testing occurred on the outcomes of five different behavioral tasks across several replicates. They found that behavioral task results differed significantly depending on the time of day animals were tested, morning, noon, or afternoon. Follow-up simulations using the data generated suggest that systematically introducing two testing times, both morning and afternoon, into the same experimental design can significantly improve reproducibility of results within the same lab and, more importantly, is predicted to lead to better reproducibility across laboratories. This study describes a novel, easy to implement methodological approach to refining study design that has the potential to improve reproducibility of animal-based research.
[LA] Researchers will want to know that their animals are in good health. But how can you tell if your zebrafish are in pain or stressed out from a procedure? Recent studies say that such fish tend to be less active and linger near the bottoms of their tanks. Perhaps easy enough to gauge by eye if your numbers are small, but some facilities maintain hundreds of tanks at a time. To help make those assessments more feasible for large-scale operations, and to reduce the risk of human bias, researchers from Lynne Sneddon’s lab at the University of Liverpool developed the automated Fish Behaviour Index, or FBI. The FBI is based on swimming activity and swimming distance, recorded by cameras. The researchers developed the FBI with female AB strain zebrafish after different invasive procedures, such fin clipping and PIT tagging, and to evaluate the effects of different analgesics. Against human assessment, the FBI correlated well. You can read more and find links to the software in the journal Scientific Reports.