> In the most recent issue of Proc. Natl. Acad. Sci. USA that I have seen
> (vol. 94, pp. 13388-13389 (1997)), Roy Pollock and Michael Gilman deliver
> themselves of the following opinion: ...
This opinion is so preposterous that it almost deserves no notice except that
it is so pervasive among biologists that it must be fought and ultimately (one
hopes) extirpated. If limited information is adequate for treatment of disease,
why has it been so difficult to treat AIDS? We know the genetic sequence of the
virus and the proteins encoded. We understand the proteolytic processing of the
genetic transcript. We know the identity of the target cells and the receptors
required for viral entry. And yet nothing we try is any more than a temporary
palliative.
Biochemical pathways are not "linear pathways of protein-protein interactions."
They are full of feedback loops caused by shared cofactors and activation or
inhibition by metabolic intermediates produced remote in the pathway from their
sites of action. Many enzymes exhibit highly nonlinear kinetics or cooperative
effects of ligands, leading to responses of the entire pathway that are not
proportionsal to a given perturbation. How then can "[i]ntervention at a single
known point in the pathway often [be] sufficient to capture that pathway in
its entirety"? SHOW ME THE EVIDENCE. This kind of hand-waving is the antithesis
of science.
"The only way to understand systems is to study systems." Engrave it on the
lintels of your doorways.
--
Michael C. Kohn
Laboratory of Computational Biology and Risk Analysis
National Institute of Environmental Health Sciences
P.O. Box 12233, Mail Drop A3-06
Research Triangle Park, NC 27709-2233
Telephone:
919-541-4929 (voice)
919-541-1479 (fax)
e-mail:
kohn at valiant.niehs.nih.gov
WWW home page:
http://valiant.niehs.nih.gov
