The Cell Hijackers

Back in the 1940s, John Von Neumann-a giant in the development of modern computers-investigated the theoretical possibilities of self-reproduction. He essentially asserted that a self-reproducible machine would require a “tape” or other description of itself. During reproduction, this tape would serve as the set of instructions for building a copy of the machine and would itself be copied to create the seed necessary for the next generation.

DNA, of course, turned out to have precisely these properties. What a beautiful story! One of the very first computer scientists, a mathematician and engineer, made a prediction of the fundamental mechanism of life that biologists subsequently discovered. The truth, of course, turns out to be a little more complicated. But in a forthcoming denouement, engineering is poised for a triumphant comeback in molecular biology.

The last fifty years of molecular biology have largely been devoted to understanding the incredibly complex mechanisms that govern life. Scientists have developed wonderful analytic tools to study what goes on in cells. Now, we are on the brink of an engineering revolution that will transform our ability to manipulate the biological world. The results could be everything from cell-based computers to custom-made microbes that neutralize toxic waste or manufacture chemicals. It’s a leap as large as that from ancient alchemy to today’s materials science.

This engineering revolution is coming to be known as synthetic biology, and what follows are two examples of some early progress in the field.

The first: a bacterium that computes. At MIT, Tom Knight, Drew Endy, and their students have been modifying protein production processes to turn E. coli cells into primitive digital computers. The researchers used one protein to turn on and off a gene that codes for another protein. The resulting high or low concentration of the second protein corresponded to a 1 or 0. Of course, from this fundamental “not” gate, as computer scientists call it, all digital logic follows. Knight and Endy’s goal isn’t to use cells to build future PCs. Rather, it is to gain digital control over the production of certain proteins and thus to hijack the cells for their own purposes. The cells they use provide a self-sustaining, living chassis that can readily make copies of itself and the altered DNA. The researchers have initiated a multiuniversity project to produce a catalogue of parts that will enable engineers to rapidly produce new circuits and perform computations in cells.

Progress continues: last year, teams of MIT students attempted to create oscillators that turned a jellyfish gene for fluorescence on and off so that E. coli cells containing the gene visibly blinked under a microscope. And this year a different group of MIT students attempted to genetically program a sheet of identical cells to recognize their relative spatial arrangement so that groups of them could fluoresce, making patterns on the sheet.

Obviously, these and similar feats at other universities are mere lab demonstrations of this promising technology. But the next few years may see applications that include the creation of cells that are genetically altered to deliver drugs within a person’s body: one still theoretical idea is to program a cell to sense blood sugar levels and produce just the right levels of insulin in response. Another application could be in chemical manufacturing-biologically based factories in which worker cells follow molecular messages detailing which chemicals to produce.

The second example of synthetic biology is a rather different engineering project at the Institute for Genomic Research in Rockville, MD, founded by Craig Venter (yes, the same Craig Venter who sequenced the human genome). Venter and colleagues are working with a very simple bacterium, Mycoplasma genitalium, which has only 517 genes. They knocked out genes from the bacterium in an effort to construct a laboratory organism that has the minimal number of genes needed to sustain life and thereby identify a set of functional requirements for a living system. Their goal is to mix and match genes with those functions from different organisms to create a unique living system. Now that’s engineering!

If they succeed, the benefits will be myriad. Right now, Knight, Endy, Venter, and others are limited to experimenting with existing cell lines. This is similar to saying every wheeled vehicle has to use a chassis from some finite set of automobiles, like Detroit’s offerings from 1970. But when it becomes possible to engineer whole new cells from basic components, future engineers will be able to create custom organisms, their own DeLoreans, to perform specific biochemical tasks, such as producing hydrogen.

Where does this lead? Whereas now we grow a tree, cut it down, and build a table, in fifty years we might simply grow a table. As more engineers work on biological systems, our industrial infrastructure will be transformed. Fifty years ago it was based on coal and steel. Now it is based on silicon and information. Fifty years from now it will be based on living systems. Sort of like a new agricultural age, only of a radically different kind.