Moreover, recent studies have shown that the phar- macologic blockade of noradrenergic receptors pre- vents the exacerbation of cancer that is otherwise observed following immobilization stress in mice, an indication that -adrenergic signaling is critical in mediating the effects of stress on tumor growth in this model.45 Some comparable data in humans are begin- ning to emerge. For example, it has been demonstrated that norepinephrine upregulates vascular endothelial growth factor, which, in turn, stimulates angiogenesis in two human ovarian cancer cell lines.46 This catechol- amine also increases human colon cancer–cell migra- tion, and both epinephrine and norepinephrine pro- mote the invasion of ovarian cancer cells in vitro. Taken together, data such as these indicate that a complex matrix of psychological, social, and biological factors in cancer, ranging from social isolation to viral infection, affects known physiological processes that influence cancer progression. Continued research in this area may yield targeted interventions to influence behavior, biology, or both to reduce the burden of cancer.
Programmatic Direction #3. Systems Science and Health
orientation that defines a systems approach can be summarized as follows:
a paradigm or perspective that considers connec- tions among different components, plans for the implications of their interaction, and requires transdisciplinary thinking as well as active engage- ment of those who have a stake in the outcome to govern the course of change.25
Systems science is not a single discipline; rather, it is a linkage of disciplines to bring about problem under- standing and solving under the paradigm described above.
Systems science does not refer to a single methodol- ogy; rather, it encompasses a wide range of methods and tools (e.g., system dynamics simulation, agent- based modeling, network analysis, Markov modeling, soft-systems analysis, discrete-event modeling). While technology is used to maximize the effectiveness of systems approaches, systems science is not a technology. For an in-depth introduction to this topic, readers are encouraged to view webcasts of the 2007 Symposia Series on Systems Science and Health. 47
The term systems science is used here to refer to bringing to problem solving a perspective in which the problem space is conceptualized as a system of interrelated component parts (i.e., the “big picture”). This term was chosen in lieu of several others that may be synony- mous, such as systems thinking or complexity, because some terms are associated with a particular “brand” of thought, and the authors feel that systems science is neutral while also inclusive. The system is viewed as a coherent whole, while the relationships among the components are also recognized and seen as critical to the system, for they give rise to the emergent properties of the system. Emergent properties are those properties that can only be seen at the system level and are not attributes of the individual components themselves (e.g., a flock emerges when a group of birds flies together; it is a property of the system, not of any individual bird). Systems science offers insights into the nature of the whole system that often cannot be gained by studying the component parts in isolation. More- over, in a systems approach, there is recognition that embedded in the system are feedback loops, stocks and flows, that change over time (i.e., dynamic, nonlinear, complexity of the system).
The advantages of utilizing systems science as a complementary method for addressing complex prob- lems include the fact that nonlinear relationships, the unintended effects of intervening in the system, and time-delayed effects are often missed with traditional reductionist approaches, whereas systems approaches excel at detecting these. The common conceptual
By embracing systems science, the research community will be better equipped to handle the policy-resistant problems that abound in public health. Policy resistance refers to the “tendency for interventions to be defeated by the system’s response to the intervention itself.” 21 In the last decades of the 20th Century, almost in parallel to the developments that spawned systems biology, the social– ecologic model emerged as a dominant world view in searching for explanations of the broader population- level causes of the very same common, chronic diseases that are the focus of biomedicine today. 48 –51
Other troubling causes of poor health and shortened life expectancy, such as access to care and disparities and inequality in healthcare delivery, have also been studied. The population, behavioral, and social sci- ences advanced beyond single discipline and simple causal views toward another valid systems view of un- derstanding health and disease. In this world view, human behavior can be broadly defined as hierarchi- cally organized along levels of complexity, from indi- vidual behavior to collective behavioral patterns within groups to higher levels of the clustering of patterns of behavior that are embodied in neighborhoods, work- sites, schools, communities, cultural, ethnic, or reli- gious affiliations, to even broader patterns determined by societal norms, financial incentives, and policies. These higher-order levels of factors interact in com- plex, dynamic, and multifactorial ways to produce the so-called “causes of the causes” of the complex com- mon, chronic diseases.2 In this ecologic perspective, the view of the ultimate “causes of the causes” lies as much in the behavioral–social–ecologic environment as it
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