On the surface, genetic and electrical engineering appear to have little in common. One field revolves around carbon and the other is built upon silicon; one makes RNA from DNA and the other converts AC to DC.

Some biologists have begun to apply the concepts of electrical engineering to living cells, literally programming them for data storage and computation. Image courtesy of Timothy Lu and Yan Liang.

But some creative biologists have begun to apply the concepts of electrical engineering to living cells. “We view ourselves as biological programmers,” says Timothy Lu, a member of the Synthetic Biology Group at the Massachusetts Institute of Technology (MIT). Lu and others are engineering circuits into bacterial cells, literally programming them for functions, such as data storage and computation. DNA’s straightforward, self-replicating helices are easy to amplify, modify, and are generally quite stable, says Lu. And since each position of DNA can encode four different pieces of information—A, T, G, or C—instead of just two, as with classic binary silicon systems, DNA could someday, in principle, store more data in less space. “The same properties that make DNA a great genetic code for living organisms also makes it an interesting substrate to engineer,” says Lu.

The quest to engineer DNA began with chemist Marvin Caruthers, who first strung together short sequences of DNA back in the early 1980s. Each new strand—six to eight sets of 20 nucleotides each—took him one to two days to build. Today, biomedical researchers and others can synthesize one of Caruthers’ strands in seconds.

In 2000, researchers at Boston University and Princeton University took these biological engineering feats in a new direction. They built the first synthetic biological circuits within Escherichia coli—namely a ring oscillator and a toggle switch (1, 2)—demonstrating that it was possible to control genes through artificial biological circuitry.

Back then, Lu, the son of an electrical engineer, was an MIT undergraduate studying electronic circuit design. But a project to build a cochlear implant sparked Lu’s interest in the interface of electronics and health, and he went on to complete a joint doctorate and medical degree in medical engineering from MIT and Harvard.

Lu’s first foray in synthetic biology didn’t entail DNA data storage. He engineered bacteriophage—viruses that infect bacteria—to more effectively target and kill bacteria to break apart biofilms (3), and later started a laboratory focused on designing microbes for human health applications.

But the 34-year-old researcher never really abandoned his roots in electrical engineering and has become one of a handful of researchers attempting to use DNA for computation. Over the course of five years, Lu has developed tools and techniques to program bacterial cells to perform binary (4) and analog computation (5). Using enzymes called recombinases, which recognize specific sequences of DNA, Lu programmed cells to remove a piece of DNA and flip it or cut it out in response to some stimuli, creating a “bit” of data, like a 1 or 0, the basis of binary computation. For analog computation, which processes continuous, varying measurements rather than the discrete 1s and 0s of binary, Lu combined the actions of three transcription factors to construct two cellular circuits that together detect and compute various amounts of compounds outside a cell.

“While our level of engineered [biological] systems are nowhere near where they [are] in other systems, like electrical or mechanical, we’re eager to learn and keep developing these platforms,” says Boston University biomedical engineer Ahmad “Mo” Khalil, who worked alongside Lu as a postdoctorate. “Engineering biological systems is a new way of studying biology and programming useful applications.”

Last year, Lu and graduate student Fahim Farzadfard devised a way to write memory, continuously and over time, into the DNA of a population of bacteria (6). The two identified and adapted an E. coli system, described 30 years ago in the literature, capable of expressing single-stranded DNA. The researchers engineered cells to express such DNA in response to a chemical or light stimulus. The DNA, targeted to a specific location on the genome, totes along an enzyme to modify the genome when it gets there, like recording information onto a tape recorder. In this way, an external stimulus can be recorded permanently into the genome and “read” back later.

Such bacteria could be programmed as environmental sensors, for example, to record levels of toxins in landfills or waterways, and later be collected and analyzed by researchers at their convenience. The same could be done in the mammalian gut, where the microbes could detect and record instances of infection, for example, or bleeding, then be collected and processed after passing through the system. With that goal in mind, Lu’s laboratory has already tested engineered bacteria in mice (7). The bacteria successfully sensed and recorded differences in gut composition based on food supplements fed to the rodents.

Other advances in the field include E. coli genetic toggle switches to detect and report “The same properties that make DNA a great genetic code for living organisms also makes it an interesting substrate to engineer.” —Timothy Lu on cellular DNA damage or antibiotic activity (8, 9), a multicellular system that forms a visible pattern in the presence of a chemical (10), and synthetic gene networks that count (4).

Lu, meanwhile, keeps eyeing innovations. At his bustling, 30-person MIT laboratory, in among the students, postdoctorates, and crowded benchtops, there are sheets of cells lined with gold nanowires that can be remodeled into various patterns over time (11). The sheets are constructed by programming E. coli to produce fibers that grab onto gold nanoparticles in the presence of certain chemicals and arrange those particles into nanowires, creating a living material that conducts electricity.

If DNA synthesis costs continue to drop, Lu imagines a world in which DNA could even replace silicon hard drives for long-term storage. “You might encode the entire Library of Congress on DNA, or archive Hollywood movies,” says Lu. “We’ve built a bunch of circuits, and it’s just the first wave of applications.”