Professor Pamela Silver of Harvard Medical School (HMS) believes in biology’s potential to change the world.

For example: scientists routinely wield microbes against disease, using computers to turn bacteria into microscopic drug factories rapidly assembled from off-the-shelf biological parts; crops ease world hunger and convert sunlight into biomass; and the cells of astronauts remember if they’ve been damaged by gamma rays, alerting doctors before cancer starts to grow.

Silver, a leader in the relatively new field of synthetic biology, is working toward that future, running multiple projects in two labs that employ nearly two dozen fellows, graduate students, undergraduates, and staff.

“I’ve always thought that biology is quite modular,” Silver said. “Biological parts … have defined properties such that you can put them together and build logical circuits inside cells to get cells to do useful things.”

Researchers are taking at least three major approaches to achieve that predictability, Silver said:

• Understand the properties of biological units so well that they can be plugged into a computer, allowing scientists to use computer-aided design (CAD) to create and optimize biological systems that do specific tasks, such as producing a vaccine for a new disease.
• Use high-throughput screening to quickly examine many different options — microbes carrying particular genes or entire synthetic chromosomes, for example — to find the one best suited to a particular task.
• Let evolution contribute to the work. In Silver’s lab, for example, researchers try to engineer bacteria to use carbon dioxide to create organic compounds. This process, called carbon fixation, is normally only performed by photosynthetic organisms. Silver’s engineered E. coli do the trick, but they aren’t very good at it, so researchers grow the bacteria in conditions that favor those that fixed carbon and let evolution do the rest.

Key to the rise of synthetic biology has been the rapid advance in DNA sequencing and synthesis in recent years, which are fostered in synthetic biology labs.

“The beauty of cheap sequencing is it’s going to change how we do genetics,” Silver said. “We can evolve a system to make it better and then … see what mutations made it better. If you can march through and find those sequences faster, you can use synthetic biology to get your organism to do what you want. That’s the vision.”

If the field lives up to its promise, Silver said, cheap, fast genetic sequencing will allow scientists to isolate important functional genes, put them in bacteria engineered to produce and excrete drugs, and then collect the desired product, all for a fraction of the cost of an analogous process today.

She used the example of the recent development of a known drug for malaria from the wormwood plant, financed by a starter grant of $40 million and then augmented with additional funding. The result was a drug produced by microbes genetically engineered with key genes and regulatory circuits. Though effective, the effort consumed a lot of time and resources, a problem that synthetic biology could ease.

“You don’t want every project to cost over $100 million. You want every project to cost less than $5,000. You want your students to say, ‘I feel like making this,’ and you want it to be so cheap that they can do it without even asking [permission],” Silver said.

Synthetic biology projects

Silver’s lab is engaged in a variety of projects: working with E. coli bacteria, photosynthetic cyanobacteria, plants, and even the immune system; bacterial batteries; microbes that make biofuels, and a photosynthetic fish. She receives funding from the Defense Department’s DARPA program and the Energy Department’s ARPA-E program.

Though synthetic biology works on a variety of scales, much attention is focused on microbes, which can be manipulated genetically and grown by the millions in the lab.

Cyanobacteria, powered through photosynthesis, hold extra attraction because they’re solar-powered. Danny Ducat, a postdoctoral fellow with an interest in the environment, has transformed these bacteria into microscopic sugar factories and is now exploring how to foster symbiosis with alcohol-producing yeast cells. If he can get the two organisms to thrive together, he will have created a mini biofuels factory, with the cyanobacteria producing sugar that the yeast then use to create ethanol, which can be used as a fuel.

Cyanobacteria are naturally photosynthetic, but normally hold onto the sugars they create. The first step was to add the genes that produced cellular transporter molecules that would shepherd the sugar across the cell membrane, releasing it outside the bacteria. Ducat developed a strain that secretes 80 percent of the sugar it produces — sugar from the sun, in essence — and is now working to pair it with yeast that grows in the same conditions as the cyanobacteria.

Microbial biofuel factories

The creation of microbial biofuel factories could answer some of the problems facing biofuels today. Biofuel production, which uses corn and sugar cane as feedstock, diverts potential food crops and causes food prices to fluctuate. Some question not just biofuels’ economic impact, but also the morality of using food to make fuel in a world where there are people who go to bed hungry every night.

A microbial biofuels factory, however, could be built on marginal land, leaving arable land free to grow food, Ducat said. But that factory is still a long way off. Even if researchers succeed in getting the yeast and cyanobacteria to work together, the system would still have to be scaled up to industrial size.

“The scale-up is really the big bottleneck in a lot of these projects,” Ducat said. “It’s not a trivial engineering issue.”

Genetic engineers have long faced criticism that they’re tampering with nature. Silver counters that even some of our most entrenched public health strategies, like taking vaccines to fight disease, are at heart “messing with nature.” Still, a focus of Silver’s lab is creating genetic self-destruct traits, termed “auto-delete,” as a way to ensure that genetically modified organisms don’t escape into the environment.

“There’s a certain amount of nervousness about playing around with nature, but we’ve been playing around with nature for a long time,” Silver said.

The field is on the verge of an explosion in both what scientists can do and in what the public — including governments and business — understands is possible, she said.