Agent-based modeling: a systematic assessment of use cases and requirements for enhancing pharmaceutical research and development productivity.

A crisis continues to brew within the pharmaceutical research and development (R&D) enterprise: productivity continues declining as costs rise, despite ongoing, often dramatic scientific and technical advances. To reverse this trend, we offer various suggestions for both the expansion and broader adoption of modeling and simulation (M&S) methods. We suggest strategies and scenarios intended to enable new M&S use cases that directly engage R&D knowledge generation and build actionable mechanistic insight, thereby opening the door to enhanced productivity. What M&S requirements must be satisfied to access and open the door, and begin reversing the productivity decline? Can current methods and tools fulfill the requirements, or are new methods necessary? We draw on the relevant, recent literature to provide and explore answers. In so doing, we identify essential, key roles for agent-based and other methods. We assemble a list of requirements necessary for M&S to meet the diverse needs distilled from a collection of research, review, and opinion articles. We argue that to realize its full potential, M&S should be actualized within a larger information technology framework--a dynamic knowledge repository--wherein models of various types execute, evolve, and increase in accuracy over time. We offer some details of the issues that must be addressed for such a repository to accrue the capabilities needed to reverse the productivity decline

Tracing the Biological Roots of Knowledge

The essay is a critical review of three possible approaches in the theory of knowledge while tracing the biological roots of knowledge: empiricist, rationalist and developmentalist approaches. Piaget's genetic epistemology, a developmentalist approach, is one of the first comprehensive treatments on the question of tracing biological roots of knowledge. This developmental approach is currently opposed, without questioning the biological roots of knowledge, by the more popular rationalist approach, championed by Chomsky. Developmental approaches are generally coherent with cybernetic models, of which the theory of autopoiesis proposed by Maturana and Varela made a significant theoretical move in proposing an intimate connection between metabolism and knowledge. Modular architecture is currently considered more or less an undisputable model for both biology as well as cognitive science. By suggesting that modulation of modules is possible by motor coordination, a proposal is made to account for higher forms of conscious cognition within the four distinguishable layers of the human mind. Towards the end, the problem of life and cognition is discussed in the context of the evolution of complex cognitive systems, suggesting the unique access of phylogeny during the ontogeny of human beings as a very special case, and how the problem cannot be dealt with independent of the evolution of coding systems in nature

Theories about architecture and performance of multi-agent systems

Multi-agent systems are promising as models of organization because they are based on the idea that most work in human organizations is done based on intelligence, communication, cooperation, and massive parallel processing. They offer an alternative for system theories of organization, which are rather abstract of nature and do not pay attention to the agent level. In contrast, classical organization theories offer a rather rich source of inspiration for developing multi-agent models because of their focus on the agent level. This paper studies the plausibility of theoretical choices in the construction of multi-agent systems. Multi-agent systems have to be plausible from a philosophical, psychological, and organizational point of view. For each of these points of view, alternative theories exist. Philosophically, the organization can be seen from the viewpoints of realism and constructivism. Psychologically, several agent types can be distinguished. A main problem in the construction of psychologically plausible computer agents is the integration of response function systems with representational systems. Organizationally, we study aspects of the architecture of multi-agent systems, namely topology, system function decomposition, coordination and synchronization of agent processes, and distribution of knowledge and language characteristics among agents. For each of these aspects, several theoretical perspectives exist.

Engineering simulations for cancer systems biology

Computer simulation can be used to inform in vivo and in vitro experimentation, enabling rapid, low-cost hypothesis generation and directing experimental design in order to test those hypotheses. In this way, in silico models become a scientific instrument for investigation, and so should be developed to high standards, be carefully calibrated and their findings presented in such that they may be reproduced. Here, we outline a framework that supports developing simulations as scientific instruments, and we select cancer systems biology as an exemplar domain, with a particular focus on cellular signalling models. We consider the challenges of lack of data, incomplete knowledge and modelling in the context of a rapidly changing knowledge base. Our framework comprises a process to clearly separate scientific and engineering concerns in model and simulation development, and an argumentation approach to documenting models for rigorous way of recording assumptions and knowledge gaps. We propose interactive, dynamic visualisation tools to enable the biological community to interact with cellular signalling models directly for experimental design. There is a mismatch in scale between these cellular models and tissue structures that are affected by tumours, and bridging this gap requires substantial computational resource. We present concurrent programming as a technology to link scales without losing important details through model simplification. We discuss the value of combining this technology, interactive visualisation, argumentation and model separation to support development of multi-scale models that represent biologically plausible cells arranged in biologically plausible structures that model cell behaviour, interactions and response to therapeutic interventions