Our commitment to the 3Rs at the University of Southampton

Cutaneous squamous cell carcinoma (cSCC) is a type of skin cancer and is one of the most common cancers worldwide. When it spreads from the skin to other parts of the body (metastasises) treatment options are limited. An immune treatment (called anti-PD1 therapy) causes the body’s immune cells to attack the tumour. It is used in cSCC, but fewer than 1 in 7 people fully respond to it. Researchers at the university think that combining immunotherapies may increase their effectiveness, but they need better ways to understand how these treatments might interact. It is common to test such treatments in mouse models of cancers, but it is increasingly clear that the responses seen in mice do not always mirror those seen in humans. Researchers have therefore developed a tissue slice culture system in cSCC. This allows them to take very thin slices of fresh patient cSCC samples and keep them alive for up to 5 days. Using this, they can measure how different treatments affect the immune response in cSCC to predict which treatments might prove effective in patients in the future. A significant advantage of this system is that it uses human samples. Not only does this provide a way of testing treatments without using animals, but it is likely to predict the treatment responses of patients better, as has been shown with similar systems in other cancers.

Southampton researchers have developed a new 3-dimensional cell culture system to study how human breast cancer develops in patients who are overweight. Although cancer research has heavily relied on mouse models, there are limits to their applicability to human disease. In this new approach, researchers can investigate how different types of cells grow and interact with each other. This provides an appropriate model of the disease in humans.

Representing the changes to airway structure and inflammation that occur during chronic lung disease, such as asthma, can be a challenge for new drug development and testing, which may require a large number of animals (such as mice). Researchers at the University of Southampton have newly established in their laboratory the method of generating approximately 50 thin lung tissue slices from a single mouse lung, also called Precision Cut Lung Slices (PCLS). This method significantly reduces by up to 50-fold the number of mice needed for studying multiple novel drugs at different concentrations and time points, and their effect on complex changes in the airways of these lung slices. This technique can be applied to other animal tissues such as the liver and brain, and importantly to human tissue samples, which may further reduce the need for animals in drug testing.

In an innovative project aimed at transforming approaches to drug discovery, Southampton researchers have used specialist analytical methods to gain more information from cell cultures that are used to replace animals. Using magnetic resonance spectroscopy (MRS and imaging (MRI) to analyse tissue slices, or clusters of cells (organoids), has enabled these alternatives to be used for a wider range of tests, further reducing animal use. This allows an individual organ to be utilised for hundreds of assays including tests of metabolic activity and other complex cellular functions.  The innovation can also be used with human tissue biopsies, which may further reduce the reliance on animal tissue while providing data that are directly relevant for humans.

Osteosarcoma is the most common bone cancer in children and adolescents, but survival rates haven’t improved greatly over the last few decades. New treatments for these cancer patients are needed but their development is hampered by the complexity of the disease and the environment in which it grows. In this research project, researchers aimed to generate a new 3-dimensional bone model of osteosarcoma. They wanted to use this to study the disease, while also testing new drugs and strategies to impove patient outcomes. To do this, they put osteosarcoma cells, specialised bone marrow cells and macrophages (important immune cells) in a bone cylinder. This is then grown on a chick embryo blood vessel membrane (blood vessels are integral to tumour development). They added an osteosarcoma drug, that may target macrophages, to this model to try and understand how this drug works and potentially how to make it work better. This project refined the use of animals in research by not using established mouse models, instead, they placed their model onto the rapidly expanding blood vessel membrane (also known as the CAM), which grows around the developing chick inside of the shell. Importantly, placing their bone cancer model structure onto the CAM ('piggybacking' the chick's growth and support networks) causes minimal impact to the chick embryo, which continues to develop normally, but is humanley killed prior to hatching at the end of the study.

Southampton researchers have been investigating ways to optimise fish tagging and population estimate methods in environmental studies. Typically, fish are captured and marked using physical tags, causing discomfort, and potentially making it more difficult to swim. In this study, researchers explored the use of a less invasive approach to identifying individual fish. Using unique identifiable features such as spots or scales, together with remote underwater video capture from submersible cameras, the group was able to reliably identify individual fish and predict population size without physical capture. This could improve animal welfare whilst ensuring accurate and reproducible data collection.

An additional “R” referred to as "Repopulation," was introduced in one of the sessions. This was raised from the work conducted by Ms. Fiona Woods in her investigation of "Exploring the 3Rs of Animal Welfare in the Solent Oyster Restoration ."

A philosophical-orientated presentation was given by Dr Heather Browning, which revolved around the significance of animal sentience, this particularly caught the audience’s attention. The talk explored the intricacies of sentience, how sentience is studied, and its role in the application of the 3Rs.

The event also featured workshops hosted by Dr Chris Barkus from the NC3Rs , Mr John Meredith from UAR, Dr Penny Hawkins from the RSPCA Animals in Science Department , as well as Dr Leo Westbury, a medical statistician from the MRC Lifecourse Epidemiology Centre (UoS). These workshops provided invaluable insight and guidance on the implementation of the 3Rs principles, sharing best practices and engaging openly about animals used in research.

Among the notable highlights of the event was Miss Rhianna Blyth's presentation, "Development of a 3D In Vitro Breast Cancer Organotypic Model of Obesity-Associated Inflammation." This presentation was awarded the 3Rs impact award by the members of the University of Southampton Animal Welfare and Ethical Review Body (AWERB), who were notably impressed by the substantial body of work that had been accomplished, especially by such an early career researcher.

Quotes from some of our attendees:

“The talks were really informative, and I would definitely attend any other future events organised”.

“It was an excellent forum to know what 3Rs activities are going on at the University of Southampton”.

“A good range of talks covering all aspects of what the animals used in research at the University of Southampton are for and what is being done to improve on the way in which they are used”