158 CATALYZING INQUIRY
ing decision logic, and executes stored programs [in the DNA] that guide cellular differentiation ex-
tending over many cell generations.”^82 Table 5.2 describes some of the similarities.
Of course, taking an engineering view of biological circuits does not make understanding them
trivial. For example, consider that cellular regulatory circuits implement a complex adaptive control
system. Understanding this system is greatly complicated by the fact that at the biochemical implemen-
tation level, the distinction between the controlling mechanisms and the controlled processes is not as
clear as it is when such control is engineered into a human-designed artifact. In a biochemical environ-
ment, control reactions and controlled functions are composed of intermingled molecules interacting in
ways that make identification of roles much more complex.
Nor does the analogy to electrical circuits always carry over perfectly. Because critical molecules are
often present in the cell in extremely small quantities, to take the most notable example, certain critical
reactions are subject to large statistical fluctuations, meaning that they proceed in fits and starts, much
more erratically than their electrical counterparts.
5.4.3.4 Combinatorial Synthesis of Genetic Networks,
Guet et al. have demonstrated the feasibility of creating synthetic networks, composed of well-
characterized genetic elements, that provide a framework for understanding how diverse phenotypi-
TABLE 5.2 Points of Similarity Between Genetic Logic and Electronic Digital Logic in Computer
Chips
Characteristic Electronic Logic Genetic Logic
Signals Electron concentrations Protein concentrations
distribution Point-to-point (by wires Distributed volumetrically by
or by electrically encoded diffusion or compartment-to-
addresses) compartment by active
transport mechanisms
Organization Hierarchical Hierarchical
logic type Digital, clocked, sequential Analog, unclocked (can
logic approximate asynchronous
sequential logic; dependent on
relative timing of signals)
Noise Inherent noise due to discrete Inherent noise due to discrete
electron events and chemical events and
environmental effects environmental effects
Signal-to-noise ratio Signal-to-noise ratio high in Signal-to-noise ratio low in
most circuits most circuits
Switching speed Fast (>10–9 s–1) Slow (<10–2 s–1)
SOURCE: Excerpted with permission from H. McAdams and A. Arkin, “Simulation of Prokaryotic Genetic Circuits,” Annual
Review of Biophysics and Biomolecular Structure 27:199-224, 1998, available at http://caulo.stanford.edu/usr/hm/pdf/
1998_McAdams_simulation_genetic_circuits.pdf. Originally published by Annual Review of Biophysics and Biomolecular Structure.
(^82) H.H. McAdams and A. Arkin, “Simulation of Prokaryotic Genetic Circuits,” Annual Reviews of Biophysical and Biomolecular
Structure 27:199-224, 1998.
(^83) Section 5.4.3.4 is based on C.C. Guet, M.B. Elowitz, W. Hsing, and S. Leibler, “Combinatorial Synthesis of Genetic Net-
works,” Science 296(5572):1466-1470, 2002.