Densmore says the three parts necessary for any engineering project, be it computer chips or living cells, are clear: Figure out what you’re trying to build; the specific parts you need to build it; and your constraints. Once you’ve broken down a system like that, “you can actually look at each of those pieces in a very systematic way,” says Christopher Voigt, an associate professor of biological engineering at MIT.
In synthetic biology, those standardized pieces come in the form of DNA snippets, coded in strings of letters, each one representing a nucleotide in the alphabet of the molecule itself. Engineers’ design challenge is to build genomes from scratch by combining these small but specific pieces of genetic material. For each snippet, scientists have to figure out how it functions on its own and how that function changes when combined with other pieces.
When Voigt started engineering biology a decade ago, he was literally cutting and pasting strings of letters in Microsoft Word. He memorized the functions for each particular sequence of DNA and tried to assemble them into working genomes. This method was time-consuming, and the outcomes were riddled with error.
Today, scientists are starting to piece together possible genomes using complex computer algorithms that do the sequence- and rule-memorizing for them. In many ways, writing DNA code is becoming like writing computer code, but instead of ones and zeros, it’s written in As, Cs, Ts and Gs — abbreviations for the four interconnecting nucleotides that form DNA’s ladderlike structure. This four-letter language of life allows scientists to see inside biological systems and attempt to reprogram them.
Programming is what drew Densmore into the field of synthetic biology in the first place. A few years ago, Densmore was doing postdoctoral research at Berkeley when Voigt commissioned him to make a prototype computer system that streamlined biological engineering’s testing process to avoid redundancy. “Right now, we have the DNA, we build things, we learn, we feed that back into the algorithms, and we keep doing that loop,” Densmore says. Ever the analogist, he compares it to building cars. We don’t have to crash-test every single car to know how it will hold up. We test a few to determine what does and doesn’t work and then input those findings into a growing database to inform future designs.
The ultimate goal, of course, is to build designs with predictable outcomes. Want to make a plant that glows green when it’s lacking nitrogen? Densmore envisions a day when you can type such an outcome into a computer, whose algorithms will sift through the databases of known functions and find the specific DNA sequence necessary to achieve such a goal.
From Lab to Living Room
At this point, synthetic biology takes place mainly at lab benches, but this technology is aimed at mainstream uses and is becoming more accessible to mainstream users. (See “Biological Engineering in the Basement,” page 3). The applications for biological engineering, then, are limited only by our collective imagination.
“Because you’re treating it like engineering, the kinds of things you can do are much more substantial,” Keasling says. “You can do synthetic biology to produce a product, and they tend to be products either that evolution would not have selected for — like a fuel, for instance — or that evolution would not select to produce enough of — engineering microbes to produce artemisinin.”
Twelve years ago in his Berkeley lab, Keasling figured out how to program baker’s yeast to produce a chemical precursor to artemisinin, the world’s most potent anti-malarial drug. “We took the genes out of the [wormwood] plant and put them into a yeast,” Keasling explains. The yeast eats sugar and, using the genetic code from the wormwood as a blueprint, spits out artemisinic acid, a precursor to the drug. “It’s a process that’s just like brewing beer,” Keasling says.
A quick chemical conversion turns the acid into a semi-synthetic version of the drug that hit the market in April. The pharmaceutical company that has licensed the technology plans to produce 100 million malaria treatments a year, covering between 25 and 33 percent of the global need. (See “Brewing Better Malaria Drugs,” page 3).
Giving Fossil Fuels the Boot
Keasling also sees these microbial factories as a solution to the energy crisis. “In fact, artemisinin is not too far off of a good diesel fuel,” he says. Gasoline, diesel and jet fuel are extracted and refined from crude oil. What was once organic material has been subjected to millions of years of pressure, which yields energy-rich organic molecules called hydrocarbons. But Keasling and his colleagues at the U.S. Department of Energy’s Joint BioEnergy Institute think there is a better (not to mention faster) way to turn the energy in organic materials into hydrocarbons.
Keasling’s method feeds agricultural waste such as cornstalks and wheat straw to E. coli bacteria engineered to break down the sugars and produce biologically synthesized hydrocarbons that burn and function just like those in fossil fuels. In addition to improved efficiency, these fuels can work within our existing transportation infrastructure, so there’s no need to engineer new cars or gas stations.
“We have a billion tons of biomass that go unutilized in the U.S. on an annual basis, and if we could turn that into fuel, we could roughly produce a third of the need in the U.S.,” Keasling says. Since the fuels wouldn’t rely on burning petroleum products, it would also decrease the U.S. carbon footprint by roughly 80 percent.
The importance of petroleum isn’t limited to the stuff we pump into our gas tanks, either. It also comprises much of the manufactured world around us. Keasling uses the chair he’s sitting in as an example. The seat is upholstered in a petroleum-based fabric and stuffed with petroleum-based filler. The wooden frame is coated in a petroleum-based varnish. The linoleum floor? Petroleum as well. And that polyester shirt, too.
Keasling says the ubiquity of petroleum and the chemical products derived from it mask the fact that they are not the best materials for their respective jobs. For example, why is carpet made of nylon? “It’s not because that’s the best molecule for a fiber,” Keasling says. “It’s what you can get from petroleum.” Since we extract and refine copious amounts of crude oil these days for fossil fuels, it makes sense to use the nonfuel portions as well.
If scientists can replace petroleum-based fuels with ones derived from sugars, Keasling posits, then we ought to be able to use the same fermentation process to derive petroleum’s other chemicals from sugars as well. Keasling thinks it is only a matter of time before manufacturers phase out petroleum products in favor of more profitable and sustainable biosynthetic versions. A key component in Keasling’s work, be it anti-malarial drugs or biofuels, is the fact that the methods are open source and the technology can be produced on a large scale.