Article - Issue 31, June 2007

Responses to 'Systems Biology' and the MacRobert Awards

Colin Blakemore FMedSci Hon FIBiol FRCP Hon FBAASc FRS, Andrew J Millar, Dr Geoffrey Robinson FREng

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Responses to ‘Systems Biology’

Professor Richard Kitney and Dr Loredana Santoro (Opinion, Ingenia 30) rightly stress the importance and potential of systems biology. This area of science offers not only an exciting challenge to interdisciplinarity, but also a huge opportunity to improve the UK’s health and wealth.

The understanding of the control mechanisms within organisms coming from systems biology will drive the emerging field of systems medicine, which has the potential to transform our ability to foster human health and to treat disease. For example, functional models quantifying the relative contribution of multiple genetic and environmental risk factors in the causation of common human diseases, could be used to underpin personalised and predictive healthcare in the future.

Virtual models of human function could also provide tools to accelerate the development of new drugs, novel combination therapies to treat disease and more efficient approaches to toxicology, possibly reducing the need for the use of animals. Realising the promise of systems medicine will involve integration of the torrent of information about the functional and structural characteristics of human systems at the genetic, cellular and organ level through an iterative cycle of experimentation, computation, analysis and technology. This is a complex, long-term and therefore costly task. However, the potential pay-back is huge. Moreover, the success of the Heart Physiome project (led by Denis Noble of Oxford and his colleagues) and the consequent development of a functional computer model of the human heart provide reassurance about the feasibility of this approach.

We at the Medical Research Council (MRC) have thought about the part that we could play in this area. MRC already has initiatives (with other Research Councils) to promote interdisciplinary collaboration between the engineering and medical sciences, and the development of research capacity in bioinformatics and systems biology. The MRC was also involved in the recent BBSRC/EPSRC call for proposals for Systems Biology Centres. But we hope that our funding allocation in the Comprehensive Spending Review will enable us to take forward a further project that we call “e-Me” – a roadmap towards a virtual model of the entire human body.

Progress towards this vision can be achieved only through interdisciplinary working. Unusual and novel skills will have to be grown through capacity development. E-me aims to build on the present initiatives of systems biology and on the recommendations in the report of the Academy of Medical Sciences and The Royal Academy of Engineering – Biology: a vision for engineering and medicine 2007.

The Human Genome Project (HGP) has given birth to many new approaches to understanding ourselves, including UK Biobank, the International HapMap project and the growing catalogue of case-control studies around the world, aimed at defining complex genetic contributions to disease. It is notable that the scale of these projects – both intellectual and financial – demands international cooperation and the sharing of resources. Systems biology applied to Man, including e-Me, is yet another of the child of the HGP. These offspring will be costly to nurture, but their potential to illuminate human nature and the causes of disease surely makes the investment – and the collaboration – worthwhile.

Colin Blakemore FMedSci Hon FIBiol Hon FRCP Hon FBAASc FRS
Chief Executive of the Medical Research Council and Waynflete Professor of Physiology at the University of Oxford.

Professor Kitney and Dr Santoro are right to highlight the tremendous potential of systems biology and synthetic biology, and the opportunities and the necessity for UK investment.

Coordinated funding for systems biology has just been initiated by the Research Councils, BBSRC and EPSRC, as the report notes. Six Centres for Integrative Systems Biology were funded in 2005 and 2006, in UK universities (Edinburgh, Imperial College, Manchester, Newcastle, Nottingham and Oxford). This investment of over £50 million sees biologists in each location sharing offices, coffee rooms and laboratories with mathematicians, physical and computer scientists. A handful of other universities have similar, home-grown initiatives. In these fertile spots, the new, interdisciplinary approaches to biology are taking root.

Synthetic biology urgently needs a similar investment, with a balance of disciplines that includes more engineering. The new disciplines complement each other in several ways. Synthetic biology is often regarded as applied systems biology. The engineering approach offers a means to manipulate complex biological processes, so that systems understanding can be applied more easily and reliably than by past methods of genetic engineering.

The power of synthetic methods was brought home most strongly to us, when a team of nine of our engineering, biology and informatics undergraduates competed in the International Genetically Engineered Machines competition held at MIT. In 10 weeks they designed, modelled and constructed an arsenic biosensor using the bacterium E. coli as a chassis – and in doing so won the Best Real World Application category. Synthetic biology will be broadly applicable, beyond the bacterial species where it has started, with applications in agriculture and energy as well as in medicine.

Like genetic engineering, synthetic biology will be rightly subject to stringent regulation. The arsenic sensor shows the potential for a positive moral imperative – to do good as well as to avoid harm. Synthetic biology complements systems biology also as a powerful tool for fundamental research. Biological processes have been elaborated by evolution over geological timescales and are now extremely complex. Synthetic circuits can be designed to recapitulate just the key features of a natural system in a far simpler, more tractable form. If the synthetic circuit behaves as predicted, we will gain far more confidence that we have identified the major operating principles of the evolved system.

For the UK to best exploit this potential, capacity building investment is necessary at a point early enough to allow critical momentum to be established. The full value of this momentum may then be realised, rather than trusting to reactive response.

Andrew J Millar
Co-Director, Centre for Systems Biology at Edinburgh

Alistair Elfick
Centre for Biomedical and Biological Engineering, University of Edinburgh

MacRobert Awards

Thank you for your excellent series of articles on last year’s finalists for the MacRobert Award. I am sure that forthcoming articles on this year’s finalists will prove equally interesting to your readers.

I am often asked who was ‘MacRobert’, after whom the UK’s leading award for engineering innovation is named. Lady MacRobert was the widow of Sir Alexander MacRobert, founder of the British India Corporation. She lost her three sons, one in a flying accident and the other two on active service with the RAF in World War II. In their memory she famously donated a number of aircraft to the RAF, the first defiantly named “MacRobert’s Reply”. In 1943 she founded a number of trusts, which were the original benefactors of the MacRobert Award. Amalgamated into a single entity in 2001,The MacRobert Trust continues to provide significant support to causes including science and technology, education, youth, services and sea, disabled and handicapped, and community welfare.

The range, depth and vitality of engineering innovation that we encounter in judging the award is truly amazing, and in stark contrast to the often-heard worries about the state of UK engineering. The explanation for this apparent paradox may lie in the dramatic changes that many of us have seen in both the engineering discipline and the engineering industry over our working lives.

When the Award was established in 1969, the discipline of engineering was largely defined by the scope of the engineering faculties of about thirty universities. Now we have over a hundred universities – many of them without engineering departments, but carrying out work that might well be regarded as engineering. Recent MacRobert finalists trace their origins to research across a wide range of disciplines: from mathematics to medicine to oceanography. In 1969, the engineering industry was pretty much defined by companies listed under the ‘Engineering’ category of the London Stock Exchange. Now it encompasses university spin-offs, venture capital start-ups, privatised public bodies, subsidiaries of global multinationals and a host of other organisations. Many of them are carrying out highly innovative work. The UK engineering industry may not be as visibly obvious as it used to be, but it pervades every aspect of the modern commercial world and is more innovative than ever.

If any of your readers have recently encountered any exciting engineering projects that meet the MacRobert criteria of innovation, commercial success, and benefit to the community, we’d be delighted to hear about them. A brief note to Alex.Pennington@raeng.org.uk is all we need.

Dr Geoffrey Robinson FREng
Chairman, MacRobert Award Committee

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