Klim Verba
PhD student
University of California, San Francisco

Jay, Great Britain

How far off are scientists from making a synthetic cell?

Klim Verba
HHMI lab associate,
PhD student,
Macromolecular Structure Group,
University of California, San Francisco
It depends on how one defines "synthetic cell". For example, Craig Venter and colleagues in their 2010 Science article (“Creation of a bacterial cell controlled by a chemically synthesized genome”) claimed that they created a synthetic cell. However, I think some scientists would disagree with that assessment. The authors basically took the genetic code of one organism and synthesized the exact same DNA chemically in the laboratory. They then injected the synthesized DNA into a bacterial cell; the cell thus became controlled by the DNA synthesized by the scientists. So, the physical DNA bases were synthetic, but the coding sequence, the actual meaning of the DNA, was still derived from nature. If one imagines a cell being like a computer, and DNA being a program, in this example, scientists took a natural program, reprinted it, and loaded it into a cell for it to run. If "synthetic cell" is defined as a cell in which humans devise the logic of its program, that is, pick and arrange the genes, then such a cell has not yet been created. However, the field of synthetic biology is working toward this goal.

So far in synthetic biology, manipulations have been limited to designing different genetic circuits by reshuffling some of the natural genes to perform a particular task and moving metabolic pathways from one organism into another. For example, the Keasling group engineered a metabolic pathway in Escherichia coli that produces precursors to the antimalaria drug artemisinin. Currently, the drug is harvested from the Artemisia annua plant, but it is very expensive to produce. However, these researchers also reproduced this plant metabolic pathway in yeast, allowing for an inexpensive way to produce the drug. Furthermore, the Voigt group engineered E. coli to produce spider silk, one of the strongest fibers known. Another area where there is progress in synthetic biology is designing almost digital-like circuits by perturbing gene control at different levels (transcriptional, translational, posttranslational). For example, scientists can currently design circuits that perform Boolean logic (i.e., involving AND, OR, and NOT operations). In this way, biological organisms can act as sensors, for example, producing an output only when they sense "A" AND they sense "B." In an effort to push the field further, several organizations are trying to make parts of genetic circuits more modular, so that one could just pick the desired parts and combine them like interlocking bricks to have a desired logic/output performed (e.g., see http://biobricks.org/).

However, many challenges still exist. Compared to electronics, biological systems have a lot of noise; rather than predictably producing an exact output, they generate drastically variable results. A lot of “bricks” are not well-defined; therefore, they work either only in a particular organism or only under particular conditions. The circuits are not as predictable as one would think, because of unknown interactions with the host organism machinery. Finally, way too much is still not known about natural biological processes and circuits, leading to more of a “black box testing” scenario, rather than purposeful design. However, because the price of DNA synthesis and sequencing has dropped over the past few years, allowing more and more scientists to tinker with genetic circuits, it is only a matter of time before a very simple synthetic cell is designed.

10/04/12 16:26