title: Emergence of the silicon human and network targeting drugs.
abstract: The development of disease may be characterized as a pathological shift of homeostasis; the main goal of contemporary drug treatment is, therefore, to return the pathological homeostasis back to the normal physiological range. From the view point of systems biology, homeostasis emerges from the interactions within the network of biomolecules (e.g. DNA, mRNA, proteins), and, hence, understanding how drugs impact upon the entire network should improve their efficacy at returning the network (body) to physiological homeostasis. Large, mechanism-based computer models, such as the anticipated human whole body models (silicon or virtual human), may help in the development of such network-targeting drugs. Using the philosophical concept of weak and strong emergence, we shall here take a more general look at the paradigm of network-targeting drugs, and propose our approaches to scale the strength of strong emergence. We apply these approaches to several biological examples and demonstrate their utility to reveal principles of bio-modeling. We discuss this in the perspective of building the silicon human.
authors.affiliation: Molecular Cell Physiology, VU University Amsterdam, de Boelelaan 1085, NL-1081 HV Amsterdam, The Netherlands.
authors.forename: Alexey
authors.initials: A
authors.lastname: Kolodkin
authors.forename: Fred C
authors.initials: FC
authors.lastname: Boogerd
authors.forename: Nick
authors.initials: N
authors.lastname: Plant
authors.forename: Frank J
authors.initials: FJ
authors.lastname: Bruggeman
authors.forename: Valeri
authors.initials: V
authors.lastname: Goncharuk
authors.forename: Jeantine
authors.initials: J
authors.lastname: Lunshof
authors.forename: Rafael
authors.initials: R
authors.lastname: Moreno-Sanchez
authors.forename: Nilgun
authors.initials: N
authors.lastname: Yilmaz
authors.forename: Barbara M
authors.initials: BM
authors.lastname: Bakker
authors.forename: Jacky L
authors.initials: JL
authors.lastname: Snoep
authors.forename: Rudi
authors.initials: R
authors.lastname: Balling
authors.forename: Hans V
authors.initials: HV
authors.lastname: Westerhoff
mesh_terms: D003198:Computer Simulation; D015195:Drug Design; D005786:Gene Expression Regulation / Q000187:drug effects; D006706:Homeostasis; D006801:Humans; D008954:Models, Biological; D058990:Molecular Targeted Therapy; D015398:Signal Transduction / Q000187:drug effects*; D049490:Systems Biology; D018511:Systems Integration; D014584:User-Computer Interface