Scientific research involving animals is a vital tool for understanding and treating diseases; scientists can recreate aspects of human diseases and investigate how the complicated array of body systems respond. Nevertheless, it is an ethical question that divides opinion and many scientists are now working on the ‘3Rs’ of animal research: to reduce animal numbers, replace them wherever possible and refine techniques to prevent animal suffering. There is a whole field of science dedicated to this approach; finding alternative models in lower order species, building predictive AI models of cellular processes, sharing tissues from the same animal across disciplines, and informing pre-clinical studies in a “bedside to bench” approach. At The University of Manchester, scientists have developed new models to investigate brain haemorrhages that would replace the use of mammals in early studies.Haemorrhagic stroke is a leading cause of death and disability worldwide but scientists still do not fully understand when or why it happens, or how to treat patients afterwards. These questions can only be answered in the lab and due to the complex interactions between blood, brain tissues and immune cells this has mostly been performed in mice, rats and other mammals. Mammalian models are excellent systems to study brain haemorrhages, as they have brains and interacting circulatory systems that look quite similar to a human. However, it is difficult to generate a reliable brain haemorrhage in a rodent without surgery, which is very technically demanding and time consuming and therefore impossible to scale-up to screen hundreds of drugs to identify a potential therapy. If scientists are to find a potential therapy for those patients who have suffered from a stroke, such an approach needs to be possible.New alternative models used at The University of Manchester include a larval stage zebrafish and a human cell system, using a seaweed polymer to hold blood in culture. Both approaches offer alternatives to mammals, and will add to the toolkit scientists can use for pre-clinical study of brain haemorrhages. Each model has different advantages. Up until 5 days old, larval zebrafish are not a protected species under UK legislation because they are not capable of independent feeding, and so are a replacement for protected species like mice and rats. A larval zebrafish is very small so we can study many individual animals at one time meaning that we can get results that are m...