Prof Philpott – Skin cancer, Queen Mary, London University
Generic questions for grant-holders
In your field of research, what are the particular areas that would lend themselves the most to alternatives to animal use and why?
We work on aspects of skin cancer and also biology of the hair follicle. Skin cancer research has been dominated by murine models based on transgenic animals and there is a need to translate this research to human systems. In particular early oncogenic events in human skin cells is an area that would lend itself to alternatives to animal use. However, the challenge has always been to demonstrate that changes seen in cell culture do relate to cancer development and as such these cells currently have to be grafted back onto mice. We therefore, need to develop better in vitro model systems.
In hair biology the challenge has always been to model the complex three dimensional nature of a hair follicle in vitro. As a PhD student I developed the 'Philpott' model of in vitro human hair growth. However, it has many limitations including the lack of a true hair cycle in vitro-as most diseases affect the hair cycle further models need to be developed.
How is your work directed to replacing animal experiments in your project?
Our skin cancer research is focussed on using human cells into which we either express oncogenes (in our case Gli1 and Gli2 as we work on the Hedgehog pathway and skin cancer) or knockdown regulatory pathways (in skin cancer PTCH receptor). We then place these cells in three-dimensional, in vitro, skin equivalent models to study their biology and attempt to model skin tumour development in vitro. We also expose Gli expressing cells to known carcinogens and investigate early genetic changes.
Our hair research has always focussed on non animal models culturing human hair follicles and more recently developing co- cultures of different cell types in reconstituted spheroid cultures as models to dissect how epithelial and mesenchymal cells communicate in the hair follicle.
What are the strengths and weaknesses of non-animal techniques in medical research?
Strengths are off course most of us work with human disease and so human cells are better than other animals cell types. The major weakness is that non animal models often have short life-spans in vitro and so it is often difficult to maintain an in vitro model long enough to mimic disease. Also many in vitro models do not mimic the complex cell types in organs and disease and off course it has been very hard to model immune influences.
What are the main hurdles to the development of alternative methods to animal experiments in your field of research?
Funding is the major limitation as model development is not considered fundable by most research bodies and second skin cancer is not a high priority. The main scientific hurdles are demonstrating that in vitro models of skin cancer do relate to the disease. Also if you use and develop animal alternatives it is often a struggle to get this published in major journals who always ask for animal work i.e. grafting
I suggest Dr Hadwen Trust and other like minded bodies begin to approach journal editors and ask them to commit to animal replacement models. They could even include a section where cancer research for example, carried out using alternatives is published. It could be accepted that because the data presented has not been backed up with animal models that it may have some intrinsic weakness but all the same merits publication.
What are the main motivations to explore the use of non-animal methods?
Personally a belief that if we are working on human disease we should be using human tissue
How do the aims and objectives of the Dr Hadwen Trust fit in your research?
Very well as the Dr Hadwen Trust fund three-dimensional model development in my lab when this was rejected by the NC3R because it was 'model development' and not 'hypothesis' driven. I still think this is the case with NC3R's they seem to want to fund basic science with a 3R's slant whereas the Dr Hadwen Trust seems to fund projects that are really aimed at the 3R's. Off course NC3R would disagree.
From your own experience, do you find that the replacement of the use of animals in medical research is becoming more accepted in the Science community?
Generally but often more from the angle that for human disease we should be looking at human tissue and not always to relieve animal suffering. I still think that while most scientists accept we must work to 3R principles most will still use the best or most widely accepted model and often this is still the animal. For a young scientist to decide to develop an animal alternative to a human disease where animal models are widely used or accepted as being the benchmark is career suicide.
In the future, what breakthrough would be necessary in order to promote and facilitate the development of non-animal methods?
Demonstration that human in vitro models are better models of human disease than animal and that such models can be published in top journals.