Interview: Professor Tom Kirkwood
Tom Kirkwood is Professor of Medicine and Co-Director of the Institute for Ageing and Health at the University of Newcastle. He has published more than 240 scientific papers and won several prizes for his research. His books include The End of Age based on his BBC Reith Lectures in 2001.
1. What is your field of work? Are there particular areas that are directed towards the replacement of animal-based methods?
I work on understanding the biological basis of the ageing process – what it is that makes us age and why we become more vulnerable to frailty, disability and disease. The aim of this research is to improve the quality of the later years of life, something of increasing importance as more of us are living longer. Ageing is found in a diverse range of species.
2. What aspects of animal experimentation motivated you to explore the use of alternative methods? Do you find that this motivation is shared by others in the research community?
Although there are some questions that at present can only be studied in animals, there are scientific and ethical reasons to question how much reliance should be placed on non-human animals. In the particular context of ageing, there are two big issues to be addressed.
Firstly, how similar are the underlying mechanisms of ageing in us and other animals? Secondly, it is clear that non-genetic factors such as nutrition, lifestyle and social environment have big effects on human ageing. In terms of the most basic mechanisms – such as free radical damage of DNA – there is considerable similarity across species. But the individuality of human ageing can really only be studied in humans.
3. What area of your research was funded by the Dr Hadwen Trust?
The Dr Hadwen Trust funded a PhD student, Fotios Drenos, to develop theoretical models of the genetic and non-genetic factors affecting human longevity. Genes account for about 25 per cent of the individual differences in human longevity, leaving 75 per cent to be explained by non-genetic factors. One part of Fotios’s work has looked at how advances in hygiene, vaccination and antibiotics over the last century have altered the selection pressure imposed by infectious disease and what impact this has had on genes regulating the body’s innate immune defences. This is important because there is evidence for a trade-off between the capacity to survive infections and the ease of conception (the implanting fetus being ‘foreign’ to the mother’s immune system).
The second major part of the work has explored the interactions between genes affecting human longevity and an individual’s diet, lifestyle and socio-economic status.
4. What are the particular strengths and weaknesses of mathematical and computational modelling in medical research?
When studying a process as complex as ageing, mathematical and computational modelling is essential. Models cannot entirely replace experiments, but equally experiments are becoming increasingly narrow in their focus and require models to link the data together. Models permit examination of interactions between different mechanisms in a way that might require a prohibitively large experimental study.
The proper use of models can streamline research programmes and facilitate the design of better experiments. In the long run, modelling is likely to have a big impact on how we plan investigations and use the results of research, resulting in much increased efficiency.
5. How was the Trust’s grant especially important to your research?
Without the Trust’s grant this particular piece of research might not have been done. It provided the means to support a very bright young zoologist who was keen to move into theoretical modelling of the ageing process. For me it was the opportunity to look in detail at some important questions that I probably would not have found time for, without the grant. Although there is a growing recognition of the value of theoretical research of this kind, it is still quite hard to win funding through the conventional routes.
6. In your view, what are the major barriers to the replacement of animal experiments within your research field?
In ageing research quite a lot of the animal-based experimental work uses relatively simple animals such as nematode worms and insects (as well as rodents). These animals have the advantage of being short-lived, so lifespan can be measured quickly, and being cheap to rear. Their genetics are also very well characterised. However, they do have important limitations, especially their lack of the more complex cell and organ systems of mammals.
There is also research undertaken using human cell cultures but these do not readily permit study of cellular interactions within the whole organism. Realistically, it may be some time before computer modelling studies or cell culture techniques advance to the point where they can reliably address all the questions currently being studied using animals. However, there is significant scope for reduction in animal use through better research design.
7. The government has recently announced a new national centre for replacing, refining and reducing animal experiments. How should it push forward the development of non-animal approaches to medical questions?
The centre can potentially provide an environment where new effective techniques can be developed. In order to make the greatest impact, it should also seek to show how animal usage can be reduced by linking research more effectively throughout integration with approaches that include computer-based mathematical modelling. To effect major change, the centre will need to develop ways of working that can be taken and adopted across the whole area of biomedical research.
Selected publications
Drenos F & Kirkwood TB (2005). A model for the disposable soma theory in humans. Mech Ageing Dev 126:99-103.
Proctor CJ & Kirkwood TB (2003). Modelling cellular senescence as a result of telomere state. Aging Cell 2:151-157.
Kirkwood TB & Proctor CJ (2003). Somatic mutations and ageing in silico. Mech Ageing Dev 124:85-92.