In article <32F9FD35.1488 at ibsm.cnrs-mrs.fr>, Athel <athel at IR2CBM.CNRS-
MRS.FR> writes
>Paul Schlosser wrote:
>>But one can go further, and I think this is also implicit in Henrik's
>earlier papers. Starting around 1965, and continuing over a quarter of a
>century, David Garfinkel and his group did a great deal of work
>modelling all sorts of things in great detail, but I have the impression
>that very little of lasting value has survived: why not? Fashion? or
>because it is very difficult to see the wood for the trees (i.e. to
>understand what's going on) in a highly detailed model that lacks any
>kind of simplifying assumption?
Funnily enough, one of the most significant events in my life was the
day I came across one of Garfinkel's papers in JBC, I still have the
memory in my mind as I turned the page. It was such an exciting
discover. I thought all I needed to do in order to understand metabolism
was collect all the enzyme data I could lay my hands on, shove it into
our local ICL 2900 and I'd be able to underatand all about it. As the
months went by I became more and more disappointed with the results.
Maybe it was just me but I couldn't understand what all those graphs and
tables of figures that the computer produced were telling me. The answer
was there somewhere but it was too hard to find. I went back to the
literature and I discoverd instead BST and MCA, and it made such a
difference. Here were tools that made you think about what was going on
in the pathway, and bit by bit I began to understand how pathways
worked. The lesson I learned was if you want a computer to pretend to be
a cell, then simulate, if you want to understand the cell, then do
theory (or to put it another way: deductive reasoning on the basic
knowledge biochemists have collected over the years).
However, simulation and theory often go hand in hand, the reason why
SCAMP was developed was not so that I could produce realistic models but
so that I had an in numero laboratory to be used in conjunction with
theoretical analysis.
Interestingly, both Henirk and Jim Burns did quite a bit of simulation
early on in the development of MCA and in fact the summation theorem was
'discovered' through a computer simulation. They reasoned that if there
was one relationship there might be more, and with more searching they
came across the connectivity theorem. At first they thought that these
theorems might have been specific to the model they were running, so
they tried, and successfully showed that both the summation and
connectivity theorems were completely general.
>>Athel
>>Herbert
--
Herbert M Sauro
email: HSauro at fssc.demon.co.uk
Telephone: 01974 282428
-----------------------------------------------------------------------
"He who cannot draw on 3000 years is living from hand to mouth" Goethe
"Ah, but a man's reach should exceed his grasp, or what's a heaven for?"
R Browning.
