Themes of the symposium

The symposium will have five sessions. Four of these will each be dedicated to one of the themes outlined below; these sessions are open to anyone interested. The fifth session, which is a closed meeting, will involve a general discussion and should lead to a first draft of a conclusion section of the accompanying conference book.

  In cooperation with Reed-Elsevier (http://www.reed-elsevier.com/), the organizers of the symposium plan to publish a book, entitled 'Towards a Philosophy of Systems Biology' in Februari-March 2006. The book, which will not be a symposium proceedings book, will consist of six sections: an introduction, the four themes of the symposium and a conclusion. All invited speakers on the symposium will each write a chapter for the book. The organizers of the symposium will write the introduction and the conclusion. Recently books on Systems Biology itself have been published or will be published. Our book is unique in the sense that it will be the first worldwide that covers the interface between Systems Biology and Philosophy of Science. Every participant of the symposium will be notified by Email when the book will be available for purchase.

We propose the following themes for the four sessions.

Theme 1. Methodology of systems biology
Is systems biology not in need of a methodology that is fundamentally different from existing methodologies? Or do we merely need to supplement the experimental methodologies and theoretical frameworks as they are used in the deductive approaches of molecular biology, physiology, and theoretical physics, and the inductive approach of bioinformatics? Are there questions in systems biology that we at present do not have ways of answering?
   Whereas Theme 4 considers what the philosophy of science has to say about the differences between systems biology and molecular biology, we here need to ask what such differences would imply for the development of systems biology as a successful scientific program? Are the accepted criteria for science largely based on the success of linear superposition and simplicity and should they continue to be so? In other words, will they be as successful in systems biology as they are in the molecular biological sciences? Do we need a new philosophy for the construction of successful theories when we deal with the complex systems that the classical sciences have either shied away or have simplified into systems for which linear superposition holds.

Theme 2. The role of theory, models and simulation in systems biology
Systems biology claims that it will make more use of theories, models and simulations than molecular biology and physiology. It has been argued that this has to do with the present status of biology: many genomes have been sequenced and much is known about the properties of biomolecules and of the networks they form. In this light, systems biology is thought to be the logical step forward from molecular characterization, and towards an understanding of cell function and physiology.. One aspect of systems biology is that experimentation and simulation will be used to analyze how molecular interactions bring about cellular properties through dynamic processes within and between cells (inter- vs. intracellular dynamics).
   An example is dynamic pathway modeling. Can we generalize and integrate mathematical models that represent dynamic interactions in a number of specific pathways to investigate cell functions, including cell growth, differentiation, and proliferation? Is the concept of a “pathway” suitable for a systems approach? Could an appropriately large set of pathway models represent a cell? How do we integrate models of pathways to consider cell function and cell to cell interactions? Which conceptual framework (e.g. stochastic processes, differential equations, formal languages) is most appropriate and can we establish a conceptual framework which integrates those? Would such a mathematical framework lead to the formulation of general biological systems theories? For example, statistical physics can be viewed as a systems theory in physics, which allows for the derivation of many different mathematical models of particular physical systems, e.g. a magnet or a molecule. Likewise, can general biological theories exist? If such a general biological systems theory does not exist what would then be the status of particular mathematical models or theories specific to the different levels in the biological hierarchy from biomolecules to populations of organisms? Or are in such cases the models theories in themselves?

Theme 3. Organisation in biological systems
It is no coincidence that the terms “organism” and “organisation” have the same root. The idea of organisation is key to understanding the phenomenon of life. However, to study and describe organisation one must necessarily decompose the system into interacting components. What makes living systems so complex is that there is no single preferred decomposition; it depends on what aspect of the system one wants to understand. How should we decompose the living cell if we want to understand its functional organisation? Biologists and biochemists have been champions in recognizing functional units (e.g., glycolysis, gene expression, mitochondrion) or hierarchical levels (DNA-mRNA-enzyme or signal transduction cascades), but rarely on a systematic basis. It is not quite obvious to what extent functional units of cells exist, and what these units would look like. Must we use a different decomposition if we want to understand the cell as an autonomous self-fabricating system in the sense of Rosen’s (M,R)-systems or Maturana and Varela’s autopoietic systems, or as a self-reproducing automaton in the sense of Von Neumann? Where does information and the distinction between symbol and matter fit it? How does the ‘analogue’ world of enzymes mesh with the ‘digital’ world of nucleotide and amino acid sequences? Such questions must surely have important consequences for the molecular structure-centered view of contemporary biology.

Theme 4. Philosophical foundations of systems biology
This section is meant to give substance to the widely held view among systems biologists that their discipline is fundamentally different from molecular biology and from physiology. The latter two sciences rarely refer to each other in their explanations – even though molecular biology studies the molecules that give rise to the phenomena studied by physiology -- and can thus be described as predominantly ‘intralevel’ sciences. Systems biology builds a bridge between physiology and biochemistry/molecular biology. The question is, however, if there really is a difference between the ways these intralevel sciences and an interlevel science such as systems biology explain phenomena. One of the distinguishing aspects of systems biology could be that it attempts to understand how the systemic properties studied by physiology are brought about by the interactions among the macromolecules studied by biochemistry, i.e., it attempts to give mechanistic interlevel explanations, whereas physiology and biochemistry are used to give causal intralevel explanations. An examples of an intralevel law in the classical sciences is PV=nRT, because a macroscopic property is related only to other macroscopic properties. An example of a systems biology law is the connectivity theorem of Metabolic Control Analysis (MCA), where system properties such as control coefficients are related to elasticity coefficients, which are properties of the individual parts within the system.
Is there substance to the idea that systems biology lies somewhere in between the study of a system as just a set of independent parts and a study of a system as an irreducible whole? If so, what does `in between’ mean?