Position paper: What is contemporary systems biology?

Systems Biology may be defined as the Science that deciphers how properties that are functional biologically, arise in the interactions between components of living organisms. Because the simplest systems that are alive are unicellular organisms, the Systems Biology between (macro)molecule and living cell studies the gap between (‘dead’) molecules and Life. Genomics essentially enables the comprehensive analysis of complete living systems, in terms of the identity and concentration of all their components. Without Systems Biology, genomics will not lead to the understanding of the living cell, hence of Life.

Systems Biology underwent an exponential growth in the area between molecule and living cell, due to the genomics revolution. In this program, we shall focus on the Systems Biology on this newer terrain, i.e. between molecule and living cell.

Because new functional properties only arise in non-linear interactions, and because ultimate biological function is in the context of at least a living cell, (i) quantitative experimentation under physiological conditions, (ii) mathematical modelling, and (iii) genome-wide analyses are highly important tools for Systems Biology. They are not the defining properties however, i.e. Systems Biology is not the same as computational biology, or genomics.

Systems Biology is a true science in that it aims to discover general (though perhaps not universal) principles that govern living systems. The Analytical branch of Systems Biology may start with pattern analysis of large datasets, but then aims to find empirical laws. The Synthetic branch may formulate an hypothesis on how a new property might arise when two biological components interact, and then test this experimentally. Integrative Systems Biology, which integrates the two branches, finds and proves new mechanisms that are responsible for the functional behavior of biological systems.

It is the Philosophy (and not so much the definition) of this Systems Biology that we should like the Symposium to address.

Challenging claims often associated with systems biology:

1. The essence of life can be found somewhere between molecule and autonomously living, unicellular cell. The defining difference between a living organism and any non-living object is that an organism is a system of material components that are organised in such a way that the system can autonomously and continuously fabricate itself, i.e., it can live longer than the lifetimes of all its individual components.

2. Biology is in need of a discipline that goes beyond the properties of individual biomolecules, but takes seriously their organisation into a functional living whole. So, rather than a molecular biological theory of the cell (which keeps the matter, but throws away the organisation), we need a systems theory of the cell (which throws away the matter, but keeps the organisation).

3. There is much more to the philosophy of biology than the current fixation on the evolutionary point of view. The other great theory in biology, namely cell theory, seems to have been forgotten. Systems biology is a direct descendant of cell theory.

4. Life is calculable and can therefore be captured in a computer model. Within 10 years a silicon cell will have been constructed that accurately describes the living cell and therefore can be rightfully considered a replica of the cell.

5. One does not need evolution to distinguish between the living and the dead; one can understand life without evolution, but not evolution without life. Biology is about being and becoming of organisms: being is the subject of systems biology, becoming is that of evolution.

6. There is no explicit genetic program encoded in DNA that directly controls the living process. If there is such a program, it would be found distributed throughout the cell in the functional properties of all molecular agents such as enzymes.