Biology Reference
In-Depth Information
how can we distinguish those assertions about higher order functions that can
be explained in molecular terms from those that cannot?
The answer is near at hand if we examine what biological scientists actually
do. We are, in fact, quite opportunistic using whatever starting points or methods
available. We adopt neither a top-down approach starting from a fixed view of
the properties of biological system, nor a bottom-up view in which molecular
features would be studied regardless of their possible relevance to function.
Robert Brandon (Brandon, 1996) analyzed scientific methodology by rejecting
both holism in which the higher order function is clear and distinct, as well
as the reductionist assumption that enough knowledge about biomolecules will
somehow explain the function. Brandon claimed that biology follows neither
approach. Nor, he argues, should it. Instead, he says, biologists are indifferent to
this distinction and move freely in both directions. Their goal is to find a causal
mechanism, and such an understanding can only be achieved, he suggests, by
considering parts and whole together. The piston can only be understood as part
of an automobile engine. The engine and the car itself must be regarded in these
explanations as physical entities. Many disciplines have developed functions for
the automobile - for the psychologists it may represent power and freedom, for
the oil industry it is the customer with wants and needs, for the sociologist and
the economist it plays important roles in technical societies - and although these
concepts have great insights in their particular fields they would not help the
automotive engineer to design or repair an automobile. We seek to explain the
function of living systems in terms of its constituent molecules and their behavior
as described in physical and chemical laws. This is possible provided that the
function itself can be described in molecular terms. To define the function in
nonphysical terms, for example as correlates for psychological or evolutionary
concepts is not wrong, but it does beg the question and leave for future study the
more difficult problem of molecular mechanism that connects the neural correlate
with a psychological concept or the genetic correlate with an inheritable trait.
The methodology which forms my approach to these problems builds upon
the experimental program my laboratory has been following for the past three
decades (for a review see Shulman & Rothman, 2001 and 2005). I propose
to build upon this methodology and, with relevant results achieved by others,
to offer a philosophy that can satisfy the multilevel explanations demanded
by systems biology. Systems biology, as defined in the introductory chapter
of this topic, is based on recent research directions. Its first requirement was
for novel 'quantitative experimentation under physiological conditions'. The
new methodology that I propose can support a practical philosophy of systems
biology is an NMR method for following the concentrations and reaction rates of
metabolites noninvasively,
in vivo
. This method has been applied to the study of
metabolism in humans, animal models, and microorganisms. It is called magnetic
resonance spectroscopy (MRS). It resolves and measures NMR spectroscopic
