CyberSightings

In the Spotlight

In this issue, we focus on the Virtual Physiological Human (VPH), an international research initiative that started in 2005 at the crossroads between information technology and biomedical sciences. The roots of the VPH initiative are in reflection that started some 20 years ago about how we investigate biological systems. Traditionally, biomedicine revolves around methodological reductionism, defined as “an approach to understanding the nature of complex things by reducing them to the interactions of their parts, or to simpler or more fundamental things” (http://en.wikipedia.org/wiki/reductionism/). The problem with this approach is that too frequently methodological reductionism becomes causal reductionism, “which implies that the causes acting on the whole are simply the sum of the effects of the individual causalities of the parts” (ibid). If we can understand how the parts work, the understanding on how the whole works will follow. This excessive attention to the so-called upward causation (genes cause the cell behaviour, which causes the tissues behavior, which causes the organs behavior, which define the behavior of our whole body) has long since shaded the strong evidence that, in most living organisms, upward causation coexist with mechanisms of downward causation. This term, introduced by Donald T. Campbell in the context of systems theory, can be summarised by the following statement: “the whole is to some degree constrained by the parts (upward causation), but at the same time the parts are to some degree constrained by the whole (downward causation).” The idea that a number of key research questions in biomedicine can be answered only by using an integrative approach, where the interactions between complex processes observable at radically different space–time scales has inspired some very original thinking under a number of names, including physiome, systems biology, multiscale bioengineering, and so on. Today this perspective is indicated with the generic name of integrative biomedical research. However, the work done in the first days was mostly focused on what should be done, not on how it could be done.

In 2005, a small group of European researchers started to reflect on how integrative research could be made practically possible. In 2006, the EuroPhysiome group launched the STEP support action, which produced in 2007 the European Research Roadmap to Integrative Research (www.europhysiome.org/roadmap/). This document defines the VPH as “a methodological and technological framework that once established will enable the investigation of the human body as a single complex system.” The fundamental idea behind the VPH is that knowledge can be captured into predictive models. This not only makes it possible to store, share, and reuse knowledge, but also to allow us to compose fragments of reductionist knowledge of various subsystems into an integrative model, a model of models, where each sub-model represents a relevant part of the process at a specific space–time scale (component model), or a relation between separate sub-models (relation model). Thus the goal of the VPH initiative is to develop a framework of methods, technologies, and standards, which make it possible to capture all reductionist knowledge on the human physiology and pathology into predictive models and to combine them to compose growingly complex integrative models.

Today the VPH initiative has received more than €200m of funding through national and European grant agencies. In addition, similar programs in the United States and Japan are pursuing fairly similar objectives. It is estimated that more than 2,000 researchers and technologists are involved with VPH research one way or another. With more than 20 projects funded only at the European level and a Network of Excellence that coordinates the common activities, the VPH is now moving to the next level with the recent establishment of the VPH Institute, a nonprofit virtual organisation that will provide a permanent identity to the initiative in the years to come.

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