Interview: Professor Louise Jones
Louise Jones is Professor of Breast Pathology at Queen Mary’s School of Medicine and Dentistry, St Bartholomew’s Hospital, London. She received a three-year research grant from the Dr Hadwen Trust. Here she talks about non-animal models in breast cancer research.
1. What research did the Dr Hadwen Trust fund and why was the grant important?
The Dr Hadwen Trust funded our project to develop physiologically relevant in vitro culture models of normal breast tissue and the pre-invasive ductal carcinoma in-situ (DCIS). DCIS is a growing clinical problem with the advent of screening and now accounts for up to 40% of clinical cases. Yet there is still much that is not understood about DCIS and there are no targeted therapies. This grant was important as it allowed us to focus on the development of non-animal models that could be used to study the biology of DCIS and how it may be treated.
2. How is your work directed to replacing animal experiments?
To date, experimental models of DCIS focus on the use of animal systems – either xenograft models, where tumours are implanted into animals, or tumour models, where genetic modifications promote the progression of breast cancer. These models are powerful because they provide the ability to analyse disease progression in a complex environment, and they allow direct manipulation of different components of the tumour environment.
The Dr Hadwen Trust grant has allowed us to develop viable alternatives to these animal models, which recapitulate the complex tumour microenvironment and allow direct manipulation.
3. What are the strengths and weaknesses of non-animal research?
The major strength of non-animal research is its direct relevance to human disease. The main weakness to date has been the lack of three-dimensional complexity of the models employed, which is what this project has aimed to address.
4. What are the barriers to replacement of animal experiments in your own research field?
In my field, the delay in developing robust in vitro methods to replace animal studies involves the widely held perception in the research world that animal studies represent the ‘gold standard’.
5. What motivates you to explore the use of non-animal methods?
A belief that human disease is best modelled using human cells.
6. Animal experiments conducted in universities and hospitals are rising relentlessly. Does the research community have a sufficient understanding of, and interest in, replacing animal experiments?
There is growing interest in developing complex in vitro models of disease, particularly in the clinical setting. However, it is important that the value of such models is emphasised in the academic forum. It is only by demonstrating the power of alternative models that the scientific world will be persuaded that there are viable replacements.
7. How can the profile of replacement research be raised among researchers? Does training play a part?
Good quality research presented at high-calibre meetings will be the most persuasive approach. Workshops for young researchers and incentives to develop creative alternatives (grants, prizes etc.) are also valuable. I believe we also need to question the relevance of animal models to human disease. Replacement of animal models will only occur if researchers are convinced of the value of alternatives – that is why projects such as this supported by the Dr Hadwen Trust are of such importance.
8. Among researchers, what most strongly drives interest in replacing animal experiments: ethics, better scientific methods or models, cost, innovation?
The priority of most research groups is to prove the value and relevance of their research. If it can be demonstrated that non-animal models are accurate and physiologically relevant, then they are more likely to be adopted. My experience over recent years suggests there is growing interest and excitement about the development of complex in vitro models and this needs to be harnessed.
9. Do you think informed public opinion should play a part in the research methods used by scientists?
Much research is funded by the public so it is important that the public is comfortable with the approaches used – but this must be informed public opinion. The vast majority of animal research is carried out in an ethical manner and with the best intentions: the challenge is to provide researchers with equally powerful non-animal models to work with, and we should focus on this.
10. What are the next steps in the use of cell culture research to understand breast cancer and replace animal experiments?
We are continuing to build the complexity of our models and are also using them now to test out small molecule inhibitors – these experiments have previously been done in animal models by our collaborators, so this will offer an excellent opportunity to directly validate the culture models against accepted animal models.
Selected publications
Jones JL (2006). Overdiagnosis and overtreatment of breast cancer: progression of ductal carcinoma in situ: the pathological perspective. Breast Cancer Res 8:204.
Holliday DL, Shaw JA, Walker RA & Jones JL (2004). Stromal contribution to breast cancer invasion, intrinsic genetic differences relate to invasion promoting ability. J Path 204(S1):2A.
Jones JL, Shaw JA, Pringle JH & Walker RA (2003). Primary breast myoepithelial cells exert an invasion-suppressor effect on breast cancer cells via paracrine down-regulation of MMP expression in fibroblasts and tumour cells. J Path 201:562-572.