Both systems get by on nothing more than the zipping and unzipping of complementary DNA sequences. In the case of the new circuits, these Velcro-like maneuvers carry out logical operations such as "if A and C, then D" (called an A AND C gate), which lie at the core of electronic computing. But instead of having voltages in a solid-state circuit represent A, C and D, in this case high concentrations of different DNA sequences do the job.
A group of so-called logic gates performs each operation. In the A AND C operation, for example, one gate would consist of strand B intertwined with strand A', which prefers strand A to strand B. When researchers introduce A into a test tube containing this gate, A' exchanges B for A, leaving B floating free.
To yield D as an output, researchers would add strand C to the test tube along with a second logic gate that contains strand D intertwined with two other sequences. One of these sequence latches onto B, the other to C, and D then floats free, as intended.
The new system can perform relatively complex sequences of operations because it allows the output strand of one operation, such as D, to serve as the input for another logical operation, says synthetic biologist Erik Winfree of the California Institute of Technology, whose group designed the technique. The researchers successfully combined up to 12 different gates in five cascading levels, although the process takes hours, they report in the December 8 Science. In an accompanying editorial, systems biologist Walter Fontana of Harvard University calls the demonstration "dazzling."
"The ability to do sophisticated computations relies on the ability to build [these] networks," Winfree says. "We've opened the door to being able to build quite large and complex systems." Other approaches to DNA computing, such as a system that plays tic-tac-toe, rely on gates made from DNA- or RNA-based enzymes, which have not yet proven as capable of turning their own outputs into inputs.
A crucial part of combining so many gates is purifying noisy input signals, Winfree says. In electronic circuits a whole range of voltages, say 0 to 0.5 volt, would all represent a single input. To accomplish the same effect his group designed gates that act as thresholds, soaking up stray strands until they reach a preset concentration. Other gates amplified correct but weak signals by producing more of a given strand.
Winfree says such a system might aid in controlling hypothetical DNA-based schemes for manufacturing nanoscale objects. The precursor to one such scheme may lie in the simple DNA robot reported in the same issue of Science. The device consists of a gridlike array of DNA pieces that contains gaps at regular intervals.
Nadrian Seeman and Baoquan Ding of New York University inserted into these gaps specially designed DNA cassettes, each of which contains a flipper that swivels from a fixed point on the cassette. Each flipper can project from the array's surface in one of two different directions, depending on input strands of DNA that are added to the cassettes.
For now the flippers, about 100 total per array, all swivel identically in unison like windshield wipers, but in principle they could be oriented in other ways and controlled individually by specific input strands, Seeman says.