Jim Burns’ Ph.D Thesis

Originally Posted on March 27, 2012 by hsauro

Why on earth should anyone want to download a Ph.D thesis that is now almost 40 years old and presumably way out of date and completely irrelevant in today’s terabyte data world? Well for one, Jim’s thesis is an important historical document relating to the origin of Metabolic Control Theory (MCT).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. In a sense, it continues where enzyme kinetics becomes unmanageable though it uses a completely different approach. 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 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 reasons but also as a source of inspiration for future work.

Here is the thesis

I am grateful to Jim Burns for allowing me to upload the text of his thesis. Also thanks to Jannie Hofmeyr who assisted in the conversion process.

Favorite Quotes

Original posting date: Posted on March 11, 2012 by hsauro

I was reminded again the other day of one of my favorite quotes which relates directly to one of the potential pitfalls of mathematical modeling. I thought I would repeat the quote here but also give another quote that rings true for today’s metabolic engineers from Monod, 1949.

Suárez Miranda, Viajes de varones prudentes, Libro IV, Cap. XLV, Lérida, 1658

Borges, J. L. 1998. On exactitude in science. P. 325, In, Jorge Luis Borges, Collected Fictions (Trans. Hurley, H.) Penguin Books.

“On Exactitude in Science….

… In that Empire, the Art of Cartography attained such Perfection that the map of a single Province occupied the entirety of a City, and the map of the Empire, the entirety of a Province. In time, those Unconscionable Maps no longer satisfied, and the Cartographers Guilds struck a Map of the Empire whose size was that of the Empire, and which coincided point for point with it. The following Generations, who were not so fond of the Study of Cartography as their Forebears had been, saw that that vast Map was Useless, and not without some Pitilessness was it, that they delivered it up to the Inclemencies of Sun and Winters. In the Deserts of the West, still today, there are Tattered Ruins of that Map, inhabited by Animals and Beggars; in all the Land there is no other Relic of the Disciplines of Geography.”

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From THE GROWTH OF BACTERIAL CULTURES BY JACQUES MONOD Annu. Rev. Microbiol. 1949.3:371-394.

“It has often been assumed that the overall rate of a system of linked reactions may be governed by the slowest, or master, reaction. That this conception should be used, if at all, with extreme caution, has also been emphasized (17, 18). On theoretical grounds, it can be shown that the overall rate of a system of several consecutive reversible enzymatic reactions depends on the rate and equilibrium constant of each. The reasons for this are obvious, and we need not go into the mathematics of the problem. A master reaction could take control only if its rate were very much slower than that of all the other reactions. Where hundreds, perhaps thousands, of reactions linked in a network rather than as a chain are concerned, as in the growth of bacterial cells, such a situation is very improbable and, in general, the maximum growth rate should be expected to be controlled by a large number of different rate-determining steps.”

Favorite Quotes

March 11, 2012 6:32 pm

I was reminded again the other day of one of my favorite quotes which relates directly to one of the potential pitfalls of mathematical modeling. I thought I would repeat the quote here but also give another quote that rings true for today's metabolic engineers from Monod, 1949.

Suárez Miranda, Viajes de varones prudentes, Libro IV, Cap. XLV, Lérida, 1658

Borges, J. L. 1998. On exactitude in science. P. 325, In, Jorge Luis Borges, Collected Fictions (Trans. Hurley, H.) Penguin Books.

“On Exactitude in Science....

… In that Empire, the Art of Cartography attained such Perfection that the map of a single Province occupied the entirety of a City, and the map of the Empire, the entirety of a Province. In time, those Unconscionable Maps no longer satisfied, and the Cartographers Guilds struck a Map of the Empire whose size was that of the Empire, and which coincided point for point with it. The following Generations, who were not so fond of the Study of Cartography as their Forebears had been, saw that that vast Map was Useless, and not without some Pitilessness was it, that they delivered it up to the Inclemencies of Sun and Winters. In the Deserts of the West, still today, there are Tattered Ruins of that Map, inhabited by Animals and Beggars; in all the Land there is no other Relic of the Disciplines of Geography.”

---

From THE GROWTH OF BACTERIAL CULTURES BY JACQUES MONOD Annu. Rev. Microbiol. 1949.3:371-394.

“It has often been assumed that the over-all rate of a system of linked reactions may be governed by the slowest, or master, reaction. That this conception should be used, if at all, with extreme caution, has also been emphasized (17, 18). On theoretical grounds, it can be shown that the over-all rate of a system of several consecutive reversible enzymatic reactions depends on the rate and equilibrium constant of each. The reasons for this are obvious, and we need not go into the mathematics of the problem. A master reaction could take control only if its rate were very much slower than that of all the other reactions. Where hundreds, perhaps thousands, of reactions linked in a network rather than as a chain are concerned, as in the growth of bacterial cells, such a situation is very improbable and, in general, the maximum growth rate should be expected to be controlled by a large number of different rate-determining steps.”