The biochemical factory that fabricates itself:

A systems-biological view of the living cell

Jan-Hendrik Hofmeyr

This article attempts to formalise the following statement (which you will recognize as an amalgamation of the first two in our list of challenging claims of systems biology):

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. Biology is in need of a systems theory of the cell that goes beyond the properties of individual biomolecules, but takes seriously their organisation into a living whole.

The concept of autonomous self-fabrication of systems is of course not new; it has a distinguished history (note that I prefer the term 'fabrication' to 'construction', 'production' or 'poeisis'). Although Maturana and Varela's concept of autopoietic systems is perhaps most prominent in this history, I find that for the purpose of formalisation it less useful than either Rosen's theory of metabolism-repair systems or Von Neumann's theory of self-reproducing automata based on the concept of a universal constructor. In particular Rosen has shown, using category theory, how to describe such organizations in terms of relational models, although, and this is crucial, he was never able to realize his metabolism-repair systems in terms of biochemistry as we know it. I shall show how it is possible to combine these two strands of thought into a relational model that commutes with our current knowledge of cellular processes. This model, which I would call a metabolism-fabrication-assembly system, also makes explicit the role of information, and identifies unassisted self-assembly as the process that ultimately makes the system self-fabricating (or, using Rosen's words: 'closes the system with respect to efficient causation'). What makes this model even more interesting is that it is consistent with Barbieri's ribotype theory, and, through that, with the body of thought known as biosemiotics. I shall also discuss the importance of this model of self-fabricating systems for nanotechnology (where a 'philosophy' also seems to be lacking).