To understand the rationale behind the VPH/Physiome Project, it helps to contrast it with the Human Genome Project. The latter built understanding of the DNA underpinning human life through reductionism. That is, breaking the body down into its tiniest parts: the three billion chemical base pairs that make up human DNA. The VPH/Physiome Project is doing the opposite. It’s putting “Humpty Dumpty” back together again in a concerted effort to explain how each and every component in the body works as part of the integrated whole.
The physiome challenge
The nursery rhyme analogy belies the vast scope and complexity of the physiome challenge. ‘Physi’ means ‘life’ and ‘ome’ means ‘as a whole’. Major diseases like cancer and neurological and cardiovascular diseases are complex in nature, involving everything from genes to environment, lifestyle and aging. Integrating knowledge of all these different components into robust, reliable computer models will yield enormous medical advances in the shape of new therapies and diagnostic tools. Already, mathematical modelling is being used to make better diagnoses and to design advanced medical devices. Within five years, in silico models (computer simulations) will be used for trialling pharmaceutical drugs as well.
Piecing together the complete virtual physiological human
Dozens of research institutions around the world are contributing to the building of the online computational modelling framework for integrating every level in human biology – one that links genes, proteins, cells and organs to the whole body. Ultimately, the goal of the VPH/Physiome Project is to piece together the complete virtual physiological human: a personalised, 3-D model of an individual’s unique physiological make-up. Clinicians will use virtual individuals for applications such as trialling drugs, personalising medicine (including designing implants to suit a particular person’s body) and performing virtual ‘surgery’ to gauge the outcome of a proposed operation.
Software, model repositories and collaboration
The Auckland Bioengineering Institute, as a key player in the VPH/Physiome Project, has led the development of mark-up languages for encoding anatomical and physiological models that have become the mandated standards for European Commission and National Institutes of Health- funded research; set up standardised model repositories that researchers use worldwide; and developed many of the online tools for authoring, visualising, executing and analysing the models that the Auckland Bioengineering Imstitute and other research institutions build.
The last 50 years of molecular biology has provided an extraordinary detailed ‘parts list’ for life, but comparatively little in the way of understanding how these parts integrate into the whole body. It’s here that bringing mathematics, physics, computing and engineering to bear on biology can produce new understandings. In particular, engineering brings a systematic approach to managing knowledge at multiple scales and a history of using mathematical modelling to explain physical behaviours.
Modelling the heart
The VPH/Physiome Project dates back to informal beginnings in the early 1980s when Professor Peter Hunter and Professor Bruce Smaill (now the Director and Deputy Director of the Auckland Bioengineering Imstitute respectively) started modelling the heart. The Physiome Project wasn’t officially launched until 1997 when the International Union of Physiological Sciences (IUPS) set up a committee headed by Professor Hunter to govern the development of models for all 12 organ systems in the body. Today, Professor Hunter co-chairs the Physiome and Bioengineering commission with Professor Aleksander Popel of Johns Hopkins University.
Towards personalised healthcare
The work of the IUPS Physiome Project has been boosted by the European Commission-funded Virtual Physiological Human Initiative. The VPH Initiative’s main goals are to develop patient- specific computer models for personalised healthcare and simulate disease-related processes. The initiative comprises more than 20 projects, including for example euHeart, the development of personalised heart models for diagnosing and treating heart disease; and HAMAM, highly accurate breast cancer diagnosis technology that combines novel imaging methods with modelling.