by Kirk Beebe

Continuing on the topic of my last post, I wanted to find an analogy that could paint a familiar, vivid picture of how metabolism relates to living systems and genetics and, therefore, why it’s an important research tool. The example a colleague and I came up with was that of a living organism being analogous to a house and the process by which they are constructed.

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The analogy begins at the inception of life where the genome or the architect’s vision set a course for the finished product. Along the way, transcripts and proteins execute on this vision in biology, just as instructions and workers do for building construction. Finally, form and function are defined by construction materials, and metabolites are essentially the bricks and mortar in biology.

In life, the genome maintains all of the necessary information to be used either proactively or reactively (Koonin, 2014). Likewise, for home construction, limitless architectural options exist. What happens in both cases is dependent on the vision and how it plays out in the context of the constraints and demands that occur along the way.

In both living systems and home construction, many external factors dictate the process and end product. At the construction site, environment, weather, influence of geography on available building materials, and the demands of the home-owner are key factors, just as diet, lifestyle, the environment and the microbiome are important influences in living systems. Further, mistakes, misconceptions or unanticipated complications can occur during the process. These mistakes can be mitigated to result in no outward defect or can be strikingly apparent. In biology this is described by the concept of genetic penetrance and epigenetics. Finally, in both life and housing, things age and deteriorate over time due to all kinds of factors.

So, here is where this analogy is important regarding the role of metabolites. Imagine wanting to assess the suitability of a home for occupancy (analogous to assessing the phenotype of a living system in biology). Would you solely rely on the stated architectural vision or plans? Although they may provide important and sometimes accurate insight, they would frequently produce an incomplete understanding of the finished product. Observing the activity of workers (proteins in biology) would also only produce a simulation of the finished product.

The most relevant way to assess both a home and a living system is to directly inspect the materials and their organization as they are. In biology, this is where interrogating metabolism comes in - in particular, by its comprehensive assessment with metabolomics. Since metabolites reflect the real-time form and function of a living system (i.e. the bricks and mortar), metabolomics effectively serves as the building inspector for biological systems. Metabolomics is integral to understanding the concerted activity and natural history of the complex network of genes, epigenetics, transcripts and proteins, since the activity of this network converges at metabolism.

This analogy - and the need to directly inspect - becomes even more important when one considers that in both biology and residential structures, renovation, maintenance, and remodeling never ceases. So, a real-time snapshot is required to faithfully assess a system.

Extensive literature citations and scientific rationale also make the same points (Cooper et al., 2013Dewey et al., 2014Monte et al., 2014Shin et al., 2014). But, it’s my hope that this simple building analogy is useful in connecting you or one of your colleagues to the essence of the value of utilizing biology’s building inspector - metabolomics. In practical terms, the direct inspection that metabolomics provides gives researchers and clinicians knowledge of the phenotype to get ahead of and understand diseases to establish new strategies for improving health.

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