Catalyzing Inquiry at the Interface of Computing and Biology

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ILLUSTRATIVE PROBLEM DOMAINS AT THE INTERFACE OF COMPUTING AND BIOLOGY 303

[B]iological systems exhibit the characteristics of reactive systems remarkably, and on many levels; from
the molecular, via the cellular, and all the way up to organs, full organisms, and even entire populations.
It doesn’t take much to observe within such systems the heavy concurrency, the event-driven discrete
nature of the behavior, the chain-reactions and cause-effect phenomena, the time-dependent patterns, etc.

Harel concludes that biological systems can be modeled as reactive systems, using languages and
tools developed by computer science for the construction of man-made reactive systems (briefly dis-
cussed in Section 5.3.4 and at greater length in the reference in footnote 4 of this chapter).
If the Harel effort is successful, a model of C. elegans would result that is fully executable, flexible,
interactive, comprehensive, and comprehensible. By realistically simulating the worm’s development
and behavior, it would help researchers to uncover gaps, correct errors, suggest new experiments,
predict unobserved phenomena, and answer questions that cannot be addressed by standard laboratory
techniques alone. In addition, it would enable users to switch rapidly between levels of detail (from the
entire macroscopic behavior of the worm to the cellular and perhaps molecular levels). Most impor-
tantly, the model would be extensible, allowing biologists to enter new data themselves as they are
discovered and to test various hypotheses about aspects of behavior that are not yet known.


9.3 A Synthetic Cell with Physical Form,


The most ambitious goal of synthetic biology (Section 8.4.2) is the biochemical instantiation of a
real—if synthetic—cell with the capability to grow and reproduce. Such an achievement would
necessarily be accompanied by new insights into the molecular dynamics of cells, the origins of life
on Earth, and the limits of biological life. In practical terms, such cells could be engineered to
perform specific functions, and thus could serve as a platform for innovative industrial and bio-
medical applications.
Cellular modification has a long history ranging from the development of plasmids carrying bio-
synthetic genes, or serving as “engineering blanks” for production of new materials, to the creation of
small genetic circuits for the control of gene expression. However, the synthetic cells being imagined
today would differ from the original cell much more substantially than those that have resulted from
modifications to date. In principle, these cells need have no chemical or structural similarity to natural
cells. Since they will be designed, not evolved, they may contain functions or structures unachievable
through natural selection.
Synthetic cells are a potentially powerful therapeutic tool that may be able to deliver drugs to
damaged tissue to seek and destroy foreign cells (in infections), destroy malignant cells (in cancer),
remove obstructions (in cardiovascular disease), rebuild or correct defects (e.g., reattach severed nerves),
or replace parts of tissue that was injured—and doing so without affecting nonproblematic tissues,
while reducing the side effects of current conventional treatments.
The applications of synthetic cells undertaking cell-level process control computing are not limited
to those of medicine and chemical sensing. There are also potential applications to the nanofabrication
of new and useful materials and structures. Indeed, natural biology exhibits propulsive rotors and
limbs at the microscale, and synthetic cells may be an enabling technology for nanofabrication—the
building of structures at the microscopic level. There may be other techniques to accomplish this, but
synthetic cells offer a promise of high efficiency through massively parallel reproduction. The gene
regulatory networks incorporated into synthetic cells allow for the simultaneous creation of multiple
oligonucleotide sequences in a programmable fashion. Conversely, self-assembled DNA nanostructures
can potentially be used as control structures that interact with intracellular components and molecules.
Such control could enable the engineering construction of complex extracellular structures and precise
control of fabrication at the subnanometer level, which might in turn lead to the construction of complex
molecular-scale electronic structures (Section 8.4.3.2) and the creation of new biological materials, much
as natural biological materials result from natural biological processes.

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