Research marks a leap forward for DNA-based computers

Caltech researchers have produced the most sophisticated DNA-based computer yet, a wet chemistry system that can calculate the square roots of numbers as high as 15.

The system is composed of 74 strands of DNA that make up 12 logic gates comparable to those in a silicon-based computer, the researchers reported Thursday in the journal Science. But the system operates a little more slowly than a conventional computer: It takes as much as 10 hours to obtain each result.

The new findings mark a major change in the direction of DNA-based computing, which researchers have been working on for two decades. “We are no longer trying to compete with silicon computers,” said Caltech bioengineer Erik Winfree, senior author of the study. Instead, they are trying to develop computers that can interact directly with components within living cells.

Scientists envision injecting more advanced versions of such systems into cells to monitor levels of key chemicals within them and perhaps even to cure diseases, computer scientist John H. Reif of Duke University in Durham, N.C., wrote in an editorial accompanying the report.


Winfree’s work “is crossing the gulf between chemistry in the laboratory and chemistry in the cell,” said USC computer scientist Leonard M. Adleman, who was the first to program a mathematical equation into DNA in the early 1990s. “The goal is no longer to be massively fast, or to do a lot of operations. The goal is to be able to carry out computations and algorithms in a wet molecular environment.”

The system developed by Winfree and postdoctoral fellow Lulu Qian relies on the modern ability to construct segments of DNA with specific sequences rapidly and reliably, along with the ability of single DNA strands to bind to other strands if they have DNA sequences that chemically match one another.

Winfree, who received a MacArthur “genius” grant in 2000, developed a clever family of DNA strands that allowed the researchers to produce logic gates with “and,” “or” and “not” functions similar to those in silicon-based computers. Certain DNA strands are used to input the starting values in digital format and others are used as reporter molecules that change colors to signify the answer.

The individual strands are essentially plug-and-play components that can be easily reconfigured to rewire the circuit, Winfree noted.

The Caltech pair combined these elements to provide a test-tube system that can calculate the square roots (rounded up to integers) of numbers from 1 to 15 or, in digital form, 0000 to 1111. Four colored reporter molecules reveal the two-digit answer: 00, 01, 10 or 11.

“The chief significance of the system is its complexity,” said chemist Andrew Ellington of the University of Texas at Austin. “It’s a tour de force.”

Although calculating a simple square root may not seem to be an especially advanced achievement, Ellington noted that the first electronic calculator was also very simple. “This sets the stage for much bigger things,” he said.

One of the key points about the system is that it can be scaled up to perform more complex calculations.


Indeed, Winfree said that his original calculations indicate that it should be possible to make the system 20 times larger. Of course, it would then be 20 times slower, he added. To overcome the speed problem, he envisions attaching the individual DNA strands to some type of fixed substrate to hold them in close proximity so that individual molecules would not have to slowly diffuse to the next step in the reaction.

“We hope that, by having localized reactions, even with a very large circuit we wouldn’t introduce delays,” he said.

A further complication for ultimate use of such computers is that cells are filled with enzymes that chew up DNA, Reif said. To get around this problem, it may be necessary to design systems that use unusual chemical building blocks that are resistant to attack to produce the DNA.