In 1977, a small group of researchers in California changed the world when they wrangled a common gut bacterium into producing a human protein. Using every technique in the book—and inventing some of their own—they scavenged, snipped, and glued together genetic components to synthesize a tiny filament of DNA. They then inserted the new segment into some Escherichia coli cells, tricking them into making the human hormone somatostatin.
A year later, these scientists had an E. coli strain that produced insulin, an invaluable drug in the treatment of diabetes. With that, the era of biotechnology was born. A plethora of novel—or at least cheaper—drugs seemed to loom on the horizon.
Thirty-odd years on, molecular biologists have delivered on many parts of that early promise, engineering microbes to produce a wide range of pharmaceuticals, including experimental antimalarial medicines and antibiotics. A quick glance in the pantry or storage closet is likely to reveal other products of genetic engineering, too, including foods, food additives and colorings, and even laundry detergent. The list goes on and on.
The economic impact of all this has been enormous. Genetic engineering and other forms of biotechnology account for some 40 percent of the recent growth in the U.S. gross domestic product, for example. The biotech sectors in other countries have also made sizable contributions to their economies. And you can expect that trend to continue as genetically engineered organisms tackle even more diverse challenges, such as producing renewable fuels and cleaning up toxic waste.
Genetic engineers have indeed accomplished a great deal, but they’ve also run up against many obstacles in transforming microbial cells into factories that churn out useful substances. In a real-world factory, you need all your production machinery and employees operating in sync to run an efficient business. A cell also has components that act like machines, producing complex biological molecules, and other parts that act like messengers, ferrying around information in the form of chemical signals. Bioengineers have to do quite a bit of tricky fine-tuning to their cellular factories, manipulating the operation of many subcellular components so the cells don’t die as they crank out the desired product in copious amounts.
For the bioengineers who do that tuning, a more apt analogy than the factory is that of an electronic circuit. We essentially want to make a cell programmable. We’d like to give it a command and have it perform a new function, just as if it were a tiny computer. To gain this power, we first need to amass a collection of well-characterized biological circuit elements that we can arrange however we like. This is one core focus of a subset of bioengineers, known as synthetic biologists, who are trying to revamp how genetic engineering is done.
Synthetic biologists take their circuit analogy quite seriously, despite the fact that a cell is a whole lot squishier than a silicon wafer or circuit board. A cell is basically a little bag full of biomolecular signals that cause cellular machinery to read chunks of DNA and with that information produce other useful biomolecules, typically proteins. Millions of different kinds of proteins are found in nature, and they participate in countless cellular processes, including the very ones that govern their production.
In a cell, certain proteins can influence pieces of DNA that code for something else. Those gene products can in turn affect other stretches of DNA and so on, forming complex webs of biochemical interaction. Think of these as the genetic circuits making up the cell’s CPU. If you want to program a cell to do something specific, you need a way to build—or at least control—these genetic circuits.
Developing the requisite cellular control mechanisms is one of this century’s great technical challenges. The two of us belong to two of the largest academic groups pursuing this goal: the Synthetic Biology Engineering Research Center, based at the University of California, Berkeley, and the BIOFAB: International Open Facility Advancing Biotechnology, which has its headquarters in nearby Emeryville, Calif. The goal of both projects is to help genetic engineers configure organisms the same way electrical engineers configure complex circuits. You could say we’re trying to put some honest-to-goodness engineering into the 30-year-old discipline of genetic engineering.