Biological research is now on the brink of a major paradigm shift that will have massive and unknown consequences for healthcare research and treatments. This new biology is known as systems biology or integrative biology. As the name suggests, it is integrative in approach and an immediate benefit will be a revolution in personalised medicine.
Biology is becoming an information science and systems biology is set to create a flood of new and unexpected information about biological systems. This emerging field will have many practical and unexpected applications that we cannot even imagine. The massive amount of information analysed will enable personalised medicine to flourish, resulting in more specific treatments for patients based on their individual biology.
The future in personalised medicine is mainly based on two factors. First, systems biology enables the recognition of patterns of interactions, especially those associated with particular diseases. Second, sequencing the human genome is now relatively cheap (currently thousands of dollars rather than billions). This gives the potential to sequence an individualâs genetic code, characterise the disease state and target treatments to suit his or her body and disease. This will translate to more cost effective treatment and better response rates to drugs, while lowering unnecessary exposure to the risk of side effects.
What is systems biology?
Systems or integrative biology is a post-genomic technology. In other words, it builds on the advances made in molecular biology over the past 30 years, the so-called genomic era.
Molecular biology is arguably the culmination of the reductionist view of biology, where organisms are broken down into increasingly small components. As the name suggests, it involves studying living things at the molecular level.
The reductionist approach to biology has resulted in massive databases storing information about molecules such as DNA, proteins and carbohydrates. A need to relate this wealth of information to the biology of cells or tissues has spawned a new field called functional genomics. Here, the genome is systematically manipulated gene-by-gene and the effects on biological processes are assessed. With new high throughput robotic approaches, all the 30,000 genes in the human genome can now be screened.
In contrast to âold schoolâ biology, integrative biology is not reductive but seeks to integrate information to look for patterns. Integrative biologists use advanced information science skills to curate the accumulated data and look for patterns that describe biology and life. At a minimum, they will look for patterns of interactions that are associated with diseases.
Professor Liam OâConnor has been at the cutting edge of integrative biology in the pharmaceutical industry in the US. He is now Head of the Division of Personalised Medicine and Systems Biology at The Walter and Eliza Hall Institute of Medical Research and Professor of Systems Biology and Bioinformatics at La Trobe University. OâConnor has come back to Australia to advance integrative biology in Australian research.
Professor OâConnor believes that integrative or systems biology is not a fad that will go away. âAll biology is going to be systems biology in 4 or 5 years,â he said. âAs the technology becomes available, scientists are going to use it. We all have an itch to find out whatâs going on.â
How does integrative biology revolutionise personalised medicine?
Integrative biology will give an ability to predict which patient would respond well to a particular drug or which of the drugs available would better treat a patientâs condition. This is the essence of personalised medicine.
âIntegrative biology does not just look through gene-by-gene. You look at all the genes,â OâConnor said. âYou ask what the pattern tells us and if it is predictive.â
As well as the ability to predict, it is the power to discover the unexpected that is also exciting. This will lead to novel treatments that would not have been discovered using conventional means.
OâConnor was involved in a project that is an example of both the ability to predict treatment outcomes and the ability to discover new interactions that might result in novel treatments. His team looked at the expression of 30,000 genes in the transplants of patients to see if the patterns of expression would be predictive of transplant rejection. What they found was unexpected. As well as the usual genes involved in transplant rejection (such as those coding for inflammatory and immune proteins) they found a more subtle association between transplant rejection and genes involved in tissue remodelling. Given this new information about tissue remodelling, the team then looked at existing compounds that had been used in the past for wound healing. These compounds then became new potential drug candidates for transplantation.
âWhen you understand more about whatâs going on with the biology, the potential therapeutic windows and ways of treating it open up,â OâConnor said.
Systems biology in Australia
Because of the high costs, Australia did not fully participate in the genomic era. However, as costs have come down markedly, there is an opportunity for participation in this post-genomic era if scientists are empowered to collaborate and compete globally. Australian scientists already have some momentum in this area.
The Australian Government has provided some funding from the National Collaborative Research Infrastructure Strategy and there is access to facilities such as Metabolomics Australia and national proteomics centres. In addition, individual institutions have developed platform technologies, such as the Victorian Centre for Functional Genomics at the Peter MacCallum Cancer Centre. Groups around Australia are using the systems biology approach to look at a range of health and agricultural systems. However, tackling the issues we have around systems biology requires fast action if this country is to keep up with advances in other countries.
In a workshop supported by the Australian Government, Dr Ewan Birney of the European Bioinformatics Institute presented a discussion paper raising a number of issues for integrative biology in Australia, including the talent shortage. He suggested an investment of A$60 million dollars per year for 5 years was needed and would yield a large return for Australia.
Systems or integrative biology will rapidly sweep through biological and healthcare research in the next few years. Given sufficient immediate support, Australia can benefit from the opportunities for cutting edge research, improved healthcare and export and productivity advantages.
Dr. Julie Milland
Director, Scribblers Inc