Nutrition and the Meaning of Life

I thought I’d start the blogs by addressing the really big question – what has nutrition got to do with the meaning of life?

I read a really interesting review (1), summarising and synthesizing recent and not-so-recent hypotheses about what life is (this, therefore, is the search for a definition of “life” rather than any greater underlying purpose). For those sceptical about how interesting this can be, I’d emphasise that it’s not my area of work and has never been, but it is a wholly engaging read, free from arcane and heavyweight philosophical terminology and likewise free from heavyweight maths. It is also a highly accessible, wry, entertaining paper and an ideal introduction for the general reader into a surprisingly neglected and under taught area of biology. The review did address the impact that the growth of molecular biology has had on the philosophical search for the meaning of life and took the view that the advent and explosion of molecular biology from the 1950s onwards has rather reduced our search for meaning to ever finer understanding of a series of chemical reactions, rather than reaching for definition. This is a shame because as biologists - scientists of life - we should all be able to have a stab at defining what life is (and what science is, for that matter).

An attractive aspect to the review was the ‘compare and contrast’ summary of competing models for what constitutes life, set against a benchmark of tickboxes of what such a definition should include. Pre-eminent, in the authors’ opinion, was a model called Rosen’s (M,R). The authors are slightly critical of Rosen in his almost perverse drive to create a mathematically and linguistically obscure structure, just as they are enthusiastically conscious of the centrality of Rosen’s (M,R) to help us move towards a definition.

The model, made accessible in a previous publication by the authors looks like this:

The model is to be seen as not representative of any one reaction, but a way of conceptualising and simplifying all biological processes. There are two fundamental processes – material causation and efficient causation, the latter being equivalent to catalysis, the former conversion of a metabolite to a second metabolite. Thus the set of metabolites A that enter the system are converted to metabolites B, a process catalysed by f, also metabolites that are produced materially from set B. In turn the production of set f from B is catalysed by set Φ, metabolic products of f. Finally the formation of Φ from f is catalysed by β. β is not B, but is a property of B. Letelier et al argue that all the requirements for metabolic closure, freedom from external efficient causation, are present in the system, and that life is therefore present.

The key feature, that the authors conclude is common to all the models but best described by Rosen’s, is that of metabolic closure. That is that a living system is metabolically complete insofar that it has all the molecular equipment to sustain and recreate itself, it is free from external efficient causation. Intriguingly, here the notion of metabolite is far removed from the hierarchical definitions used in contemporary biochemistry, ‘omics and systems biology, but refers to all molecules produced by the system: nucleic acids and proteins are therefore also metabolites as well as catalysts (and encoders). Their anti-hierachical nature of the model, and the concept of property as distinct from entity suggest very new ways to address omics. I’ll return to the implications of this in a future blog.

The keen eyed will have noted though that in Letelier’s adaptation of the (M,R) that the closure is functional rather than chemical. Letelier’s modification adds in the twinned concepts of an input and an output from the system, “nutrient” and “waste” respectively. Although not detailed as an aspect of the review this does imply the importance, the centrality, of nutrition in a constrained definition of what constitutes life. This model seeks to create a reduced and universal construct of life (in a similar manner to the way in which physicists seek to reduce the universe to ever simpler universally applicable equations). As such the term nutrient is very loose and would mean a very different thing to, for example, a botanist or geobacteriologist than a member of Nutrition Society, nonetheless the concept of nutrient may be at the very heart of defining life itself. This is surely worthwhile pausing and reflecting on a little.

(Just to avoid us all getting too self-congratulatory I should point out that emitting waste is just as central to the definition.)

I remain uncertain about the argument for a couple of reasons. My doubts initially were around organisms which are highly dependent on their environment, potentially suggestive of a case for external causation. Examples of this might include viable non-culturable bacteria from numerous environments; lichens, where algae are so dependent upon their fungal hosts as to be unable to exist independently. Indeed the link to the Panmere website includes extensions of the model on just such symbioses. However there are more prominent examples closer to home. As humans our reliance on nutrition for growth and for function are not merely general, they are in part highly specific. We are incapable of manufacture of several metabolites – vitamins, some amino acids and lipids. These compounds are in turn requisite for metabolic function. In the case of some reactions, for example where vitamins are cofactors in enzymatic processes, one could argue that they are both essential for efficient causation and are external (must be supplied). In Rosenean terms this could represent evidence of external efficient causation. It is clearly the goal of the model to reduce complexity of living systems to the simple and universal, and in doing so to approach definition of that which is readily intuited but challenging to articulate: the distinction between what is life and what is not. The concept of metabolic closure goes a long way towards this, but many/most/all organisms from all domains of life have very specific nutritional requirements, without which metabolism cannot be sustained. As such the relationship between nutrition and efficient causation becomes highly significant and places nutrition centre stage in further work in this area.

I strongly encourage comment, through the response section on the blog or through the forum:

• Are we metabolically closed or open?
• Is nutrition the meaning of life? 
• Do I actually understand the (M,R) at all?

 Bernard

Acknowledgement, reference and further reading:

I am deeply grateful to Prof Athel Cornish-Bowden for permission to reproduce Figure 3 from the paper reviewed.
(1) Letelier, J-C, Cárdenas, ML and Cornish Bowden, A (2011) From L’Homme Machine to metabolic closure: steps towards understanding life. Journal of Theoretical Biology, 286:100-113

 See also: http://www.panmere.com