290 CATALYZING INQUIRY
Cellular circuits capable of logic operations have been demonstrated. For example, Elowitz and
Leibler designed and implemented a three-gene network that produced oscillations in protein concen-
tration.^124 The implemented network worked in only a fraction of the cells but did, in fact, oscillate.
Gardner et al. built a genetic latch that acted as a toggle between two different stable states of gene
expression.^125 They demonstrated that different implementations of the general designs yielded more
or less stable switches with differing variances of concentration in the stable states. While both of these
applications demonstrate the ability to design a simple behavior into a cell, they also demonstrate the
difficulty in implementing these circuits experimentally and meeting design specifications.
In a step toward clinical application of this type of work,^126 Benenson et al. developed a molecular
computer that could sense its immediate environment for the presence of several mRNA species of
disease-related genes associated with models of lung and prostate cancer and, upon detecting all of
these mRNA species, release a short DNA molecule modeled on an anticancer drug.^127 Benenson et al.
suggest that this approach might be applied in vivo to biochemical sensing, genetic engineering, and
medical diagnosis and treatment.
8.4.2.3 Broader Views of Synthetic Biology
While cellular logic emphasizes the biological network as a substrate for digital computing, syn-
thetic biology can also use analog computing. To support analog computing, the biomolecular networks
involved would be sensitive to small changes in concentrations of substances of interest. For example, a
microbe altered by synthetic biology research might fluoresce with an intensity proportional to the
concentration of a pollutant. Such analog computing is in one sense closer to the actual functionality of
existing biomolecular networks (although of course there are many digital elements in such networks as
well), but is more alien to the existing engineering approaches borrowed from electronic systems.
For purposes of understanding existing biology, one approach inspired by synthetic biology is to
strip down and clean up genomes for maximal clarity and comprehensibility. For example, Drew
Endy’s group at MIT is cleaning the genome of the T7 bacteriophage, removing all unnecessary se-
quences, editing it so that genes are contiguous, and so on.^128 Such an organism would be easier to
understand than the wild genotype, although such editing would obscure the evolutionary history of
the genome.
While synthetic biology stresses the power of hand-designing biological functions, evolution and
selection may have their place. Ron Weiss’s group at Princeton University has experimented with using
artificial selection as a way to achieve desired behavior.^129 This approach can be combined with engi-
neering approaches, using evolution as a final stage to eliminate unstable or faulty designs.
The most extreme goal of synthetic biology is to generate entirely synthetic living cells. In principle,
these cells need have no chemical or structural similarity to natural cells. Indeed, achieving an under-
standing of the range of potential structures that can be considered living cells will represent a profound
step forward in biology. This goal is discussed further in Section 9.3.
(^124) M.B. Elowitz and S. Leibler, “A Synthetic Oscillatory Network of Transcriptional Regulators,” Nature 403(6767):335-338,
2000.
(^125) T.S. Gardner, C.R. Cantor, and J.J. Collins, “Construction of a Genetic Toggle Switch in Escherichia coli,” Nature 403(6767):339-
342, 2000.
(^126) Y. Benenson, B. Gil, U. Ben-Dor, R. Adar, and E. Shapiro, “An Autonomous Molecular Computer for Logical Control of
Gene Expression,” Nature 429(6990):423-429, 2004.
(^127) In fact, the molecular computer—analogous to a process control computer—is designed to release a suppressor molecule
that inhibits action of the drug-like molecule.
(^128) W.W. Gibbs, “Synthetic Life,” Scientific American 290(5):74-81, 2004.
(^129) Y. Yokobayashi, C.H. Collins, J.R. Leadbetter, R. Weiss, and F.H. Arnold, “Evolutionary Design of Genetic Circuits and Cell-
Cell Communications,” Advances in Complex Systems, World Scientific, 2003.