9th EMBL/EMBO Joint Conference 2008
Adriano Henney, AstraZeneca, UK
Dr Henney obtained a PhD in Medicine and has 23 years research experience in cardiovascular disease in laboratories in London, Cambridge and Oxford. His interests have focused predominantly on atherosclerosis, with studies ranging from pathology, through molecular and cellular biology to molecular genetics.
In 1997, he was recruited by Zeneca Pharmaceuticals from a Senior Fellowship position leading his own molecular genetics group in Oxford, to lead the exploration of new therapeutic approaches in atherosclerosis, specifically focusing on his interests in vascular biology. Following the merger with Astra, Dr Henney moved within AstraZeneca to a position of Global Programme Manager responsible for prototyping strategic improvements to the companys approaches to pharmaceutical target identification, and the reduction of attrition in early development. This involved directing activities both across research sites and across functional project teams in the US, Sweden and the UK.
The work undertaken in this programme resulted in the creation in July 2003 of an entirely new multidisciplinary department that focused on pathway mapping, modelling and simulation. With personnel based in the UK and US, and global project interactions across all therapy areas, the work of this department has supported projects across research and development. Under his leadership, the department has recently evolved further into a fully functional systems biology capability. Together with strong relationships established with key academic centres, the department has been prototyping the application of mechanistic, disease modelling approaches to the discovery of innovative new medicines.
Challenges and opportunities for systems biology and drug discovery: a perspective
Over the last ten years the cost of developing new drugs has escalated hugely, matched by a significant decline in the number of new medicines reaching the market. Further, compared with the 1960s, the time taken to develop a new drug has doubled to approximately 12 years. Industry statistics show an increased productivity in the discovery phase, but this has not been matched by success in development, with a number of well-publicised failures recently of drugs in the later stages of the development pipeline. This suggests that whilst the output of projects from discovery into development has increased, the quality of the output has not. Pharmaceutical R&D generally has been an empirically data-driven, qualitatively oriented activity. Whilst the targets being studied may be placed within a network, it is not necessarily clear which of the many targets is the one worth pursuing therapeutically because of the complexity of the biological system itself, compounded by variability between individuals.
Typically, each drug and target combination tends to be considered in isolation and removed from their physiological context. The key weakness of reductionism is that it cannot predict how the wider system will behave in a quantitative way: the dynamic context (pathway, cell, patient or population of patients) is missing. Systems Biology is seen increasingly as an approach that can help tackle these challenges, and in the last two years many column inches have been written in the technical and industry press on this subject. A number of initiatives, reports and symposia have also covered the topic, and we are beginning to witness an increasing and unwelcome tendency to hype what Systems Biology might be able to offer. This is likely to damage how Systems Biology is perceived by the wider community, through a combination of misunderstanding, misinterpretation and, potentially, misrepresentation of the discipline, which many regard as the natural successor to the Human Genome Project.
As a result, policy makers, pharma executives, venture capitalists and many other stakeholders are unclear whether it can have any impact on human health, or as some sceptics believe, it is likely to fall significantly short of expectations and deliver nothing but disappointment.