166 CATALYZING INQUIRY
(^94) A.D. McCulloch and G. Huber, “Integrative Biological Modelling in Silico,” pp. 4-25 in ‘In Silico’ Simulation of Biological
Processes No. 247, Novartis Foundation Symposium, G. Bock and J.A. Goode, eds., John Wiley & Sons Ltd., Chichester, UK, 2002.
equally good guesses of the upcoming epidemic strain and equally appropriate for manufacture) should
be resolved in favor of the strain that is most different from the one used in the previous year, because
this choice would reduce the effects of negative interference and thus potentially increase vaccine
efficacy in recipients of repeat vaccines.
5.4.4.4 The Heart
The heart is an organ of primary importance in vertebrates, and heart disease is one of the primary
causes of death in the Western world. At the same time, the heart is an organ of high complexity.
Although it is in essence an impulsive pump, it is a pump that must operate continuously and repair
itself if necessary while in operation. Its output must be regulated according to various physiological
conditions in the body, and its performance is affected by the characteristics of the arterial and vein
networks to which it is connected.
The heart brings together many subsystems that interact mutually through fundamental physi-
ological processes. As a general rule, physiological processes have both functional and structural di-
mensions. For example, cells are functionally specialized—blood cells and myocytes (heart cells) do
different things. Furthermore, blood cells and heart cells are themselves part of a collective of other
blood cells and heart cells; thus, the structure within which an individual cell is embedded is relevant.
An integrated computational model of the heart would bring together all of the relevant physiologi-
cal processes (Box 5.14).^94 Were such a model available, it would be possible to investigate common
FIGURE 5.11 Microarray expression groupings indicating known clinically important subgroups of childhood
acute lymphoblastic leukemia (ALL). Note in particular the second column from the right, labeled “novel.” In this
instance, the hierarchical clustering of gene expression reveals a novel subtype of childhood ALL. SOURCE:
Courtesy of L. Wong, Institute for Infocomm Research, Singapore, 2003.