Systems biology brings hope of speeding up drug development

Nov 19 2008

Almost every day brings news of an apparent breakthrough against cancer, infectious diseases, or metabolic conditions like diabetes, but these rarely translate into effective therapies or drugs, and even if they do clinical development usually takes well over a decade.

One reason is that medical research is conducted in highly fragmented groups focusing on specific pathways or components leading to drugs that turn out not to work properly or to have dangerous side effects after cycles of animal and then clinical testing in humans. This process is expensive and wasteful, resulting from the fact that at present researchers lack tools to assess in advance how candidate drugs work across the human's whole biological system. The discipline of systems biology represents an attempt to unite the medical research community behind a common approach to understanding and modelling the complex interactions of the human, leading to more effective and faster drug development.

Europe is now at the forefront of this growing movement that brings together a number of disciplines including mathematics, physics, statistics, bioinformatics, genetics and all the "omics" technologies dealing with genes, proteins, and biological pathways. Earlier this year leading specialists in systems biology met at an important conference organised jointly by the European Science Foundation and the University of Barcelona, providing a snapshot of current progress and a roadmap for future research.

The conference provided a platform to direct and accelerate other ongoing programmes in which the emerging tools of systems biology are being applied to specific areas of medicine, notably the SBMS (Systems Biology to combat Metabolic Syndrome) initiative. Metabolic syndrome is the term for various conditions that can lead to diseases such as type 2 diabetes where cells of the body develop resistance against insulin, impairing the regulation of blood glucose levels. The aim of SBMS is to understand the molecular and cellular systems that underlie risk factors associated with various diseases resulting from metabolic syndrome, by studying them at a systems wide level rather than focusing on individual specific components even when these appear to play a central role.

Yet the challenge of system biology as a whole is to integrate different components of the body at widely different scales of time and size, without being swamped by immense quantities of data, or computational models that are impossibly complex to handle, according to Roel van Driel, systems biology specialist at the University of Amsterdam, who was co-convenor of the ESF conference as well as head of the SBMS initiative. A big problem in medical research lies in duplication of effort and in particular creation of large sets of data that are difficult to share between projects, according to van Driel, who said that biology as a whole needed to become a big science, based on a stronger more analytical framework, more like physics. "The problem is not shortage of funding in medical research, but fragmentation into too many small projects," said van Driel. "We need a large-scale programme."

In fact biology has already had one large-scale programme involving focused collaboration between many projects across the world, the Human Genome Project of the 1990s. This led to a basic map of the genetic code common to all humans, although not of all the variations, or alleles, that give rise to individual differences. In fact the genome project yielded only limited information about the underlying genes and what they do, let alone how they are regulated and interact in different organs and metabolic pathways. That is the much greater challenge of systems biology, requiring the whole organism to be broken down into manageable systems that can be linked together to make predictions such as the effect of a particular candidate drug. These systems were discussed at the ESF conference, which also highlighted progress in the important related field of synthetic biology, involving engineering of organisms such as bacteria to create novel "systems" capable of manufacturing effective drugs.

http://www.esf.org/