Biology Reference
In-Depth Information
3
Methodology is Philosophy
Robert G. Shulman
SUMMARY
Systems biology aims to explain functions of the whole organism in terms
of component molecules, cells, or structures. Given the varied disciplines that
participate in this goal, e.g., genomics, proteomics, and cognitive neuroscience,
it is timely to consider if their common strategies can be identified and addressed
most generally at their philosophical level. The scope of this topic proposes that
scientists should respond to the novel questions raised by systems biology with
new experimental and theoretical methods. Any methodology both determines
and reflects a philosophy so that necessarily methodology is philosophy.
More specifically I propose that systems biology can be studied by a method-
ology that my laboratory has been developing for more than 30 years, which
will be exemplified by one set of experiments. We have conducted magnetic
resonance spectroscopic (MRS) measurements of fluxes and metabolites non-
invasively in humans, animals, perfused organs, and microorganisms. These
experiments measure the parameters that metabolic control analysis (MCA)
needs to relate higher level functions to the physical properties of the constituent
molecules. The philosophical basis of this study will be presented and contrasted
with alternatives.
The studies to be discussed started with
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CMRS measurements of the flux
from labeled glucose into muscle glycogen in humans and were subsequently
supplemented by
in vivo
concentrations of key metabolites. An MCA analysis
of these results showed that the flux was under supply control by plasma glu-
cose concentration and glucose transporters, mediated by insulin. The allosteric,
phosphorylated enzyme Glycogen Synthase in the pathway was shown not to
