Jim Burns' Ph.D Thesis
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Studies on Complex Enzyme Systems by J. A. Burns
I (HMS) should say a few words as to why on earth anyone would
want to download a Ph.D thesis that is now almost 40 years old and
presumably way out of date and completely irrelevant in today's
terabyte genome sequences? Well for one, Jim's thesis is an important
historical document relating to the origin of Metabolic Control
Theory (MCT). For those who don't know, MCT (or BST as developed
by M. Savageau) is the first, clear, practical and theoretically
useful treatment of complex cellular enzyme networks yet devised.
In a sense it carries on where enzyme kinetics becomes unmanageable
though it uses a completely different approach. At the moment MCT
is the only approach that is useful to understanding complex biochemical
networks, and I mean understand, not just simulating* or just blind
cataloging as so much of modern biology is. There could and most
likely will be other approaches but none has yet emerged to better
MCT. One of the nice aspects of MCT is that it is actually quite
simple and is amenable to anyone with a basic understanding of differential
calculus. Anyone who calls themselves a scientist with have this
knowledge, those who don't can't. Those who dismiss MCT or pass
over it without much thought have pretty much missed the point.
What is the point? Well.....
- It's a formal language to describe complex cellular networks.
- To those who are willing to spend time studying MCT, it forces
clarity of thought.
- It connects genome and environment with phenotype.
- It helps to uncover the cause and effects in a complex system;
who does what, how and why.
- It helps to give direction in the search for novel drug targets
and the rational manipulation of metabolism.
What I find most remarkable about Jim's text is it's modern feel
which suggests to me that the content was decades ahead of his time.
One finds in the thesis work that was anticipated by later workers,
even results which were later presented, unknowingly of course,
as novel by subsequent researchers. So I hope the thesis will be
of interest, not only for historical reason but also as a source
of inspiration for future work.
I am grateful to Jim Burns for allowing me to upload the text of
his thesis. Also thanks to Jannie Hofmeyr who waved the magic wand
which converted the TeX document into pdf!
* Simulation is of course an essential tool to help in our understanding
metabolism and is a perfect partner for MCA.
As you can see, I've not uploaded many chapters yet........no promises
as to when the rest will appear but I shall investigate an OCR
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