Flexible DNA computer finds square roots

DNA, the molecule of life, turns mathlete.

Using the natural zipping and unzipping behavior of DNA strands, researchers at Caltech have developed a new and adaptable method for turning the molecules into calculators. The design opens up a range of possible circuits built entirely from DNA, capable of crunching basic math problems, the team reports in the June 3 Science.

“This is way beyond cool,” says Andrew Ellington, a biotechnologist at the University of Texas at Austin. “This is complex and sophisticated.”

The Caltech team’s initial design, a circuit made from 130 unique DNA strands, calculates the square root of numbers up to 15. In this number cruncher, different types of DNA strands represent 1s and 0s, the binary numbers used in standard digital circuits.

Scientists have been substituting DNA for binary numbers since 1994, when mathematician Leonard Adleman laid out the concept of DNA computation in Science. But the Caltech group’s design, like a model railroad set, contains basic parts that can be mixed and matched, which the team hopes will enable the widest range of computations yet. “This is not a toy,” Ellington says.

Study coauthors Lulu Qian and Erik Winfree took advantage of DNA’s natural ability to zip, in which two single strands of DNA bind together at complementary sites, and unzip. The basic design incorporates two types of synthetic DNA in a test tube: single-stranded DNA molecules that float free like lone wolves and double-stranded ones that carry a small notch of open DNA called a “toehold.” The single-stranded DNA cruises solo until bumping into an entwined pair of DNA strands with a matching toehold. The lone wolves anchor onto that toehold by zipping, eventually booting off one of the original two strands. After the zipping and unzipping is done, a new double-stranded molecule and single-stranded lone wolf float around the test tube.

By precisely designing these DNA cascades, the team could squirt molecules representing 1001 in binary notation, or 9, into the mix and isolate a binary answer once the resulting reactions finished. In this case, that answer was a square root: binary 11, or 3. But the cascades, like the model trains, are customizable, and the team could have easily designed a circuit to do addition or subtraction instead. “It’s the simplicity that enables the complexity,” says Winfree, a bioengineer. Unlike a whip-quick calculator, however, this test tube abacus takes close to 10 hours to suss out a square root, he adds.

Limitations aside, circuits that use this design could diagnose medical illnesses by the presence of certain molecules in the blood, Ellington says.

Surprisingly, the Caltech team’s design is “very reminiscent of what the cell does in organizing and computing its future,” says Adleman, of the University of Southern California in Los Angeles. Like an organic supercomputer, the cell itself churns out circuit-like computations on a daily basis — and fast. The biggest applications of such experiments may lie in exploring how biology turns DNA bits into a dynamic organism.