Opinions
Many first-rate researchers develop and use non-animal research techniques that have potential to replace animal experiments. Here, some of them describe briefly why they prefer non-animal models and, where the researchers have held grants from the Dr Hadwen Trust, how that funding was important to their work.
“Currently basal cell carcinoma can only be modelled using animals. Therefore, by developing the proposed three-dimensional model we intend to generate a viable alternative to animals. Also because our model will include genetically modified human cells we hope to demonstrate the flexibility of our model as a system to investigate basic biology underlying the development of skin cancer. Because incidence of basal cell cancer is increasing dramatically we believe that the demand for such models will increase exponentially and currently the only viable option is to use mice. Ultimately we would hope that this model system would also drive further development of three-dimensional models of other skin cancers.”
Prof Michael Philpott, Professor of Cutaneous Biology, Queen Mary’s School of Medicine and Dentistry, University of London
“To answer key questions concerning the pathobiology of airway smooth muscle from patients with asthma, our research relies on access to precious biopsy samples from the airways of these patients. Funding from the Dr Hadwen Trust has been tremendously helpful for the recruitment and screening of suitable patient volunteers for these studies and has allowed our work to progress without the need for additional animal studies.”
Dr Stuart J Hirst, Reader in Respiratory Cell Pharmacology, King’s College London School of Medicine
“The prime money that the Dr Hadwen Trust provided helped the Simcyp project a lot at an early stage. Simcyp, as a Stand Alone University of Sheffield Company, is now doing well and our latest attempts have concentrated on the prediction of the oral absorption, research that traditionally uses beagle dogs or rats but for which there are many problems in predictivity as reported in the recent literature. We are finding that in vitro human cultures and in silico approaches together with appropriate integration and modeling tools are as good as, if not better than traditional animal predictions.”
Dr Amin Rostami-Hodjegan, Reader in Clinical Pharmacokinetics & Drug Metabolism, Academic Unit of Clinical Pharmacology, University of Sheffield
“Nobody likes doing animal experiments – I would say that most researchers find doing animal work intrinsically stressful. Having done my fair share, I am delighted to have been given the opportunity by the Dr Hadwen Trust to work on models that may replace some animal studies and improve the value of existing animal models of lung injury. The approach of the Trust is good for scientists and good for science.”
Dr Mark Griffiths, Consultant in Intensive Care Medicine, Honorary Senior Lecturer, Imperial College London
“Scientifically, there is increasing evidence of cases where animal models can be inaccurate and lead to poor science. The recent clinical trial episode at Northwick Park may be an example where animal testing had failed to identify a problem in humans. Conversely, methods for measuring the effects of disease and treatment in humans are improving. One examples is quantitative MRI, where subtle effects of disease, and the effect of treatment, can often be measured, A second example is PET microdosing, where very small sub-therapeutic doses of a drug can be labelled and then followed in the body to find whether they reach their target or not.
The Dr Hadwen Trust supports a variety of high-quality research projects which raise awareness of these issues. The availability of funds provides an incentive for researchers to invest in new methods.”
Prof Paul S Tofts, Chair in Imaging Physics, Brighton & Sussex Medical School
“Having spent over three decades carrying out research into brain tumours, it is clear to me that laboratory animal models have many major, fundamental differences from their counterpart human disease. Although not yet perfected, three-dimensional in vitro models, which exclusively use human cells and serum, offer a huge potential in the study of the biology of this disease as well as painting an increasingly clear picture of the situation within the brain of affected patients. The Dr Hadwen Trust’s timely support of such novel work has already resulted in the acquisition of considerable knowledge, as well as had a major impact on the usage of laboratory animals in cancer research.”
Prof Geoffrey Pilkington, Professor of Cellular & Molecular Neuro-oncology, School of Pharmacy & Biomedical Sciences, University of Portsmouth
“Current methods for determining the potency and toxicity of pertussis vaccines are outdated and require improvement. The intracerebral challenge test is effective for determining the potency of whole-cell vaccines but is objectionable on animal welfare and technical grounds. Current toxicity assays based on weight gain and histamine sensitization of mice are imprecise and need replacement. More precise non-animal methods based on determination of enzyme activity in tandem with receptor-binding assays are under evaluation. Genome sequence data and the use of gene microarrays to screen responses triggered by vaccine components may also provide leads to improved methods for assessing both toxicity and immunogenicity.”
Dr Dorothy Xing, Principal Scientist, Bacteriology Division, National Institute for Biological Standards and Control, Potters Bar, Herts.
“The successful development of an in vitro model of human liver would have the most far-reaching consequences for reducing the use of animals in research. In Nottingham, human material is directly replacing the use of rat liver in tissue engineering models of liver. The development of a robust, primary hepatocyte culture system which supports viral replication and virion production will enable replacement of small mammals and primates in many areas of hepatitis virus research. More generally, such systems offer powerful models for interrogation of the pathogenesis of a wide range of diseases of the human liver and are of considerable interest for pharmacological studies and drug hepatotoxicity testing by pharmaceutical companies, where the industry gold standard for toxicity testing is in rats.
The Dr Hadwen Trust has been constructively engaged at all stages in the development of this project. The Trust has combined an unswerving commitment to reducing the use of animals in research with a real understanding of the challenges which researchers need to overcome to realise this crucial aim. Overall the Trust has been an outstanding partner in the drive to achieve high quality animal free research.”
Dr Brian Thomson, Senior Lecturer, Centre for Biomedical Sciences, University of Nottingham
“The Dr Hadwen Trust continues to support high quality research across the UK aimed at developing and promoting alternatives to animal experiments. By adopting a rigorous peer review process in selecting projects for funding and by continuing to support those research groups which deliver research outputs, the Trust is effectively building Centres of Research excellence for replacement of animals in research.”
Prof Helen Griffiths, Professor of Biomedical Sciences, University of Aston, Birmingham
“In general, there is an over reliance on the use of transgenic animals for determining the functional impact of individual genes in human biology. For researchers concerned with understanding human labour, there are inherent problems with this approach as mice do not represent a good model for human pregnancy and labour. It is imperative that we develop a validated non-animal replacement technique for silencing gene and protein expression in human uterine tissue as a more scientifically appropriate alternative to using transgenic animals.”
Dr Rachel M Tribe, Senior Lecturer and Divisional Postgraduate Coordinator, Maternal and Fetal Research Unit, King’s College London
“There is intense interest in determining how mesenchymal stem cells may be used in future cell-based therapies, including gene therapy and tissue engineering, and as in vitro models for fundamental research and drug discovery. Targeted gene disruption, usually in mice, is frequently used to determine the potential function of particular a gene(s) or the genetic basis of human disease. The generation of knockout animals is technically demanding, time consuming and has low efficiency. Significantly, it is unclear how accurately the data obtained from knockout models translates to human physiology. This work will for the first time identify the potential for using mesenchymal stem cells to generate ‘knockout tissues’. If successful, this work will have far-reaching implications for cost and efficiency of biological research, our understanding of gene function and will contribute significantly to the reduction and replacement of mouse knockout experiments.”
Dr Paul Genever, Department of Biology, University of York