The fundamental property that distinguishes the living from the non-living is the ability to fabricate itself, i.e., to autonomously synthesise all of its molecular machinery from nutrients obtained from its environment. This is possible because organisms are, in Robert Rosen’s words, closed to efficient causation, or, in Maturana and Varela’s, autopoietic. This property, which holds for both the organism and its individual cells, is also the most basic expression of biological anticipation in that organisms and their cells take antecedent action, continuously fabricating themselves in anticipation of a future non-functional and deleterious internal state.

Rosen’s formalisation of the four Aristotelean causes (material, efficient, formal, final) allowed him to construct a graph-theoretical depiction of a functional component of any system that shows how efficient and formal cause act on material cause (input) to give final cause (output). The functional organisation of any system can be visualised as a graph that shows how the components of a system are connected. For the living cell to be closed to efficient causation its fabrication processes must be arranged in a so-called hierarchical cycle; to form a hierarchical cycle all the efficient causes if the system must be internal edges in the graph. The quintessential example is Rosen’s metabolism-repair system, abbreviated as (M,R)-system. However, the mappings in Rosen's diagram of an (M,R)-system, especially the so-called replication map, have been notoriously problematic to realise in terms of real biochemical processes. From a category-theoretical point of view the replication map is a perfectly valid way of closing the system to efficient cause, but neither Rosen nor anybody else has been able to find a biological realisation of it.

I approach the problem of realising the hierarchical cycle in the cell from a biochemical point of view by identifying the classes of efficient biochemical causes in the cell and showing how they are organised in a hierarchical cycle. Broadly speaking, the three classes of efficient causes are the catalysts that drive covalent metabolic chemistry and produce (as yet non-functional) polypeptides and polynucleotides, the intracellular milieu that drives the supramolecular processes of chaperone-assisted folding and self-assembly of polypeptides and nucleic acids into functional molecular machinery (catalysts and transporters), and the membrane transporters that maintain the intracellular milieu, in particular its electrolyte composition. The key to my analysis is the realisation the matrix in which the functional components of a system are embedded (what I call the intracellular milieu) is itself a functional component of the system, an efficient cause. I use Rosen’s graph-theoretical formalism to construct an alternative diagram that shows how these three classes of efficient cause are related to form a hierarchical cycle. What is particularly interesting is that my analysis shows how Von Neumann’s universal constructor organisation is embedded in the diagram, albeit in a new guise, and how it merges with Rosen’s metabolism and repair components. It also makes explicit Howard Pattee’s symbol-matter system in the cell and Marcello Barbieri’s genotype-ribotype-phenotype ontology.