300 CATALYZING INQUIRY
9.2 Cellular and Organismal Modeling,
A living cell is a remarkable package of biological molecules engaged in an elaborate and robust
choreography of biological functions. Currently, however, we have very incomplete knowledge about
all of the components that make up cells and how these components interact to perform those functions.
Understanding how cells work is one of biology’s grand challenges. If it were possible to understand
more completely how at least some of the machinery of cells works, it might be possible to anticipate the
onset and effects of disease and create therapies to ameliorate those effects. If it were possible to
influence precisely the metabolic operations of cells, they might be usable as highly controllable facto-
ries for the production of a variety of useful organic compounds.
However, cell biology is awash in data on cellular components and their interactions. Although
such data are necessary starting points for an understanding of cellular behavior that is sufficient for
prediction, control, and redesign, making sense out of the data is difficult. For example, diagrams
tracing all of the interactions, activities, locations, and expression times of the proteins, metabolites, and
nucleic acids involved have become so dense with lines and annotations that reasoning about their
functions has become almost impossible.
Box 9.1
On Challenge ProblemsChallenge problems have a history of stimulating scientific progress. For example:- The U.S. High Performance Computing and Communications Program focused on problems in applied
fluid dynamics, meso- to macroscale environmental modeling, ecosystem simulations, biomedical imaging
and biomechanics, molecular biology, molecular design and process optimization, and cognition.^1 These
problem domains were selected because they drove applications needs for very high-performance computing.
•A second example is the Text REtrieval Conference (TREC), sponsored by the National Institute of Standards
and Technology, in cooperation with the National Security Agency and the Defense Advanced Research Projects
Agency. The purpose of this conference is to “support research within the information retrieval community by
providing the infrastructure necessary for large-scale evaluation of text retrieval methodologies.... The TREC
workshop series has the following goals: to encourage research in information retrieval based on large test
collections; to increase communication among industry, academia, and government by creating an open forum
for the exchange of research ideas; to speed the transfer of technology from research labs into commercial
products by demonstrating substantial improvements in retrieval methodologies on real-world problems; and to
increase the availability of appropriate evaluation techniques for use by industry and academia, including devel-
opment of new evaluation techniques more applicable to current systems.”^2 TREC operates by presenting a
problem in text retrieval clearly and opening it up to all takers. It makes available to the community at large all
basic tools, and its structure and organization have attracted a large number of research sites. - Still another approach to challenge problems is to offer prizes for the accomplishment of certain well-
specified tasks. For example, in aeronautics, the Kremer Prize was established in 1959 for the first human-
powered flight over a specific course; this prize was awarded to Paul MacReady for the flight of the Gossamer
Condor in 1977. The Kremer Prize is widely regarded as having stimulated a good deal of innovative research
in human-powered flight. A similar approach was taken in cryptanalysis, in which nominal prizes were of-
fered for the first parties to successfully decrypt certain coded messages. These prizes served to motivate the
cryptanalytic community by providing considerable notoriety for the winners. On the other hand, pressures to
be the first to achieve a certain result often strongly inhibit cooperation, because sharing one’s own work may
eliminate the competitive advantage that one has over others.
(^1) See http://www.ccic.gov/pubs/blue96/index.html.
(^2) See http://trec.nist.gov/overview.html.
(^2) Section 9.2 is based largely on A.P. Arkin, “Synthetic Cell Biology,” Current Opinion in Biotechnology 12(6):638-644, 2001.