Think of a biological cell as a tiny programmable device that happens to be alive, and you have the basic idea behind an emerging field called synthetic biology. Instead of trying to unravel the complexities of natural biological systems, “synthetic biologists” ultimately want to build highly predictable, simple living cells from scratch, using off-the-shelf parts. No one has done that just yet, but a growing number of scientists and engineers are now taking the first steps toward manufacturing life-forms to order.
Figuring out how to program an artificial cell is high on the list of priorities. The functions of a natural cell are controlled by complex networks, or circuits, of interacting genes. Much the way that engineers can assemble toggle switches and oscillators in an electronic circuit, the new breed of biologists hopes to build modular “plug and play” genetic circuitry.
One such module was described by James J. Collins and his colleagues at Boston University in the June 1, 2004, issue of the Proceedings of the National Academy of Sciences USA. Collins's team designed genetic toggles—on/off switches—that could control natural networks, such as those that direct the production of proteins, inside a bacterial cell. The work not only demonstrates that cells can be programmed using modular-design strategies, it also serves as a model for a new class of therapeutics that could regulate the networks. Collins is now busy attempting to reverse-engineer some genetic networks—a technique that may someday help scientists determine the molecular targets of new drugs.
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Collins's genetic modules were constructed using standard cloning techniques, basically by cutting and pasting natural DNA into place. Late last year another group of scientists, led by George M. Church of Harvard Medical School, described a new method of making synthetic DNA. Assembling DNA, life's programming code, has existed as a laboratory technique for many years. Church and his colleagues used the new method, however, to manufacture all 21 genes needed to make a subunit of a ribosome, the cellular machine that assembles proteins. The ability to construct long sequences of synthetic DNA gives scientists the power to create genes that never existed before.
More recently, Church announced a new DNA-sequencing technology that promises to be faster and about one ninth the cost of conventional methods. It is a crucial step toward developing affordable genome maps that could become part of everyone's medical record.
As scientists begin to manufacture genetic circuits and artificial molecules in greater numbers, they will undoubtedly wish to package them inside a membrane of their own design—in due course producing a truly artificial cell. Last December, Albert Libchaber of the Rockefeller University described the creation of a cell-like assembly, which he called a “vesicle bioreactor.” The vesicle consists of a fluid extracted from Escherichia coli bacteria that is encircled by a laboratory-made lipid bilayer—much like the membrane of a real cell. The vesicles did not have their own DNA, but they were able to metabolize nutrients acquired from the surrounding medium through special proteins in the membrane. Libchaber thinks of the vesicles as enclosed laboratories that not only may have practical applications in chemistry and medicine but also might help us understand how the first natural cells evolved.