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on 'Science and Pseudoscience' in a collection of papers on philosophy of
science. For Popper (Popper, 1998), the value of science depended upon the
formulation of revolutionary hypotheses which could be falsified by experiment.
However, my views are in sympathy with Kuhn's response (Kuhn, 1998) whose
main point was 'a careful look at the scientific enterprise suggests that it is normal
science, where Sir Karl's sort of testing does not occur, rather than extraordinary
science which most nearly distinguishes science from other enterprises'.
The high value placed upon normal science in the study of systems biology
requires that the conditions allowing normal science are satisfied in the particular
system considered. Kuhn's central description of normal science was that the
research could be done within a paradigm of theories, experiments, and beliefs
guiding contemporary science. Diabetes satisfied these conditions, when we
include MRS and MCA, because it was identified by a chemical property -
chronic hyperglycemia. Accordingly it was understood by identifying the errant
steps in glucose metabolism. This rather direct identification was readily made
when the flux and control of the glucose storage pathway were measured by
MRS and analyzed by MCA. However, the identification of hyperglycemia as
the pathological condition had not served to allow the gene(s) responsible for
NIDDM to be identified despite years of intensive study, presumably because
the causal relationships between genes and the disease were not nearly as direct
as they were for the metabolic pathways. In this case, and serving as a guide
for the examples of system biology that we propose can be further studied by
these methods, the chemical or physical nature of the disease must first be in
hand and then the molecular mechanisms can be understood, particularly by the
methods we have discussed. But to start from an a priori assumption about the
nature of the systemic function, which is necessarily contingent, and then to
seek connections with the ultimate molecular properties of a gene or a particular
protein, while it might succeed in the rare case, does not offer the general
approach to systemic function that systems biology considers its goal.
No one would deny the value of great revolutionary scientific hypotheses that
might relate a specific molecule or section of DNA to a systemic function, but
while waiting I suggest it is more profitable to continue employing MCA and in
vivo MRS to study systemic questions by normal science. These methods reflect
a reductionist philosophy in which physical understanding is the least contingent
goal and where other fascinating but contingent insights about the world are
only valued insofar as they usefully lead to physical understanding.
4. CONCLUSION
I have proposed a methodology built upon experimental in vivo MRS experiments
whose results are analyzed by MCA. To fulfill the goals of systems biology, i.e.,
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