© 2006 STEP Consortium Seeding the EuroPhysiome: a roadmap to the Virtual Physiological Human Marco Viceconti STEP CONSORTIUM

© 2006 STEP Consortium The problems Genetic research is producing less clinical impact than expected because the increasing knowledge on the genome is somehow disconnected with that of proteome and of the physiome The specialisation of western medicine, based on the subdivision of the body in sub-systems, makes difficult to tackle all diseases with a strong systemic component The society a medicine based on quantitative evidences, where every clinical decision can be explained by clear and logical arguments

© 2006 STEP Consortium An example: osteoporosis OP is becoming a pandemic It has a genetic component but it is also strongly modulated by the hormonal balance, the dietary regime, and the type of daily physical activity The best method to monitor OP (DXA) can predict retrospectively only 65% of the OP spontaneous fractures (tossing a coin would give 50%) Preliminary studies suggest that the use of a predictive models that integrate the organ and the tissue scales with metabolic and lifestyle factors can increase accuracy up to 85-95%

© 2006 STEP Consortium The human Puzzle The human body is like a jigsaw puzzle made of a trillion pieces Currently we are trying to understand the whole picture by looking at a single piece, or at a few closely interconnected pieces We do need a frame, within which we can finally start to place the pieces all together, and the glue that connects them The frame is not the whole picture, but it is the only way we might hope to see it one day

© 2006 STEP Consortium Paradigmatic Shift in Biomedical Research Complement Reductionism With Integrationism

© 2006 STEP Consortium Integration across …. Across sub-systems

© 2006 STEP Consortium Integration across …. Across dimensional scales Organism (7) OrganSystem(6 ) Organ (5) Tissue (4) Cell (3) Molecule (2) Atom (1) Across Temporal scales

© 2006 STEP Consortium Integration across …. Across Disciplines Medicine BioEngineering Biology

© 2006 STEP Consortium It is necessary … Accumulate and share observations –laboratory and clinical observation are accumulated and made accessible by all those who can use them to develop or to validate new hypotheses Interconnect knowledge –knowledge we have is formalised and interconnected to those others are developing on contiguous sub- systems, scales, domains Create a framework –This is possible only if we create a powerful framework of technology and methods We call it the Virtual Physiological Human

© 2006 STEP Consortium Virtual Physiological Human Descriptive –a framework within which observations made in the laboratories, in the hospitals, and in the field all over the world can be collected, catalogued, organised, shared and combined in any possible way

© 2006 STEP Consortium Virtual Physiological Human Integrative –a framework that allows experts to collaboratively analyse this observations and develop systemic hypotheses that involve the knowledge of multiple scientific disciplines

© 2006 STEP Consortium Virtual Physiological Human Predictive –a framework that makes possible to interconnect predictive models defined at different scales, with different methods, and with different levels of detail, into systemic networks that provide concretisation to those systemic hypotheses, and make it possible to verify their validity by comparison with other clinical or laboratory observations

© 2006 STEP Consortium EuroPhysiome: Scope The scope of the EuroPhysiome Initiative is to promote the development of the Virtual Physiological Human, a methodological and technological framework that will enable the investigation of the human body as a single complex system We claim that, given sufficient resources, the European Research System can develop in the next 10 years the Virtual Physiological Human

© 2006 STEP Consortium Seeding the EuroPhysiome: a roadmap to the Virtual Physiological Human STEP is developing this roadmap through a consensus process involving hundreds of experts and the representatives of clinical, industrial and societal stakeholders The Roadmap is a document that describes the research and technological development that Europe should follow to achieve the realisation of the Virtual Physiological Human

© 2006 STEP Consortium Towards the VPH: Phase #1 VPH-related projects in IST/e-health: –AneurIST (neurovascular pathology) –ImmunoGrid (immune system physiology) –LHDL (musculoskeletal system physiology)

© 2006 STEP Consortium Towards the VPH: Phase #2 Building the EuroPhysiome –STEP Action: consensus process to write the VPH research roadmap –Biomed Town: Internet community reserved to the biomedical researchers

© 2006 STEP Consortium Towards the VPH: Phase #3 VPH research in multiple FP7 programs –QoL (DGRes): System Biology: linking genome, proteome and physiome Predictive multiscale models of human pathophysiology Clinical applications of VPH models –IST (DGInfso): VPH Technology development Large scale infrastructures VPH Knowledge management Processing, simulation and visualisation

© 2006 STEP Consortium VPH: Economic Impact Strong impact on Body Industry: all industries developing products that interact with the human body –Pharma Industry –Medical device & technology industry –Automotive industry (vehicle safety and comfort) –Tools and workplace industry (ergonomics and safety) –Aerospace industry (effects of weightlessness on humans, extra-vehicle activity suites) –Defence industry (evaluation of biological damage of conventional weapons, armours and shields) –Sport and Leisure industry (equipment for leisure and for competition) –Entertainment industry (creation of digital characters)

© 2006 STEP Consortium VPH: Health Impact Rare diseases Systemic diseases (cancer, osteoporosis, cardiovascular, obesity, diabetes, etc.) Preventive medicine, nutrition and lifestyle Disabling diseases (whiplash, back pain, repeated injury syndromes, etc) Reduced risk in clinical trials

© 2006 STEP Consortium VPH: Policies Impact Towards a quantitative evidence-based medicine Personalised Healthcare (gender, age, etc.) Easier production of public health epidemiology studies Reduced animal experimentation Fighting the “re-invent the wheel” syndrome in research Increase the public visibility of research investments

© 2006 STEP Consortium Thank You!