Caltech Researchers Scale up DNA Computing

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Researchers from the California Institute of Technology have built what they claim is the world's largest computational circuit based on DNA (deoxyribonucleic acid), using a technology that they said could easily scale to even greater complexity.

The development of the new approach, funded by the U.S. National Science Foundation, is a significant step in the march toward controlling biological systems with standard information-processing techniques. One day, DNA computing could execute logical functions much like regular silicon-based computers do today. But DNA computers would be much smaller and more easily integrated into biological systems, such as the human body. For example, biological circuits could be directly embedded in cells or tissues to detect and treat diseases.

Caltech researchers Erik Winfree and Lulu Qian published an account of their work in the June 3 issue of Science. "This is basically a technology foundations paper," Winfree wrote in an e-mail.

While simple DNA computational systems have been built before, this demonstration system is larger than other prototypes to date.

"The approach adopted by Qian and Winfree marks an important advance in DNA-based computations," wrote John Reif, a professor of computer science at Duke University, in a commentary that accompanied the work.

The researchers formed 130 different synthetic DNA strands that can be used to compose logic circuits. From this source material, they created one 74-molecule, four-bit circuit that can compute the square root of any number up to 15 and round down the resulting answer to the nearest integer.

In their setup, the multi-layered strands of DNA are fashioned into biochemical logic gates that can perform the basic Boolean AND, OR and NOR operations executed by today's transistor-based computer processors. Like the silicon-based integrated circuits, these molecular logic gates produce binary, or on-or-off, output signals, using binary signals as inputs.

Computational operations are conducted by DNA sequence binding and replication. The pre-engineered DNA molecules are immersed in a solution in a test tube. When they bump into one another, they can bind and produce offspring molecules that, in turn, can connect to other strands of DNA, producing a logic chain.

The researchers have also developed a compiler, which maps user-manipulated logic operations to the DNA circuits.

The work is a follow-up from earlier tests, carried out in 2006, which used a total of 12 DNA molecules. Since then, the researchers concentrated on making the process simpler and more reliable, which could lead to larger DNA-based systems.

The researchers' particular approach has a number of advantages, explained Reif, who was not involved in the research. One is simplicity. The biochemical reactions needed to encode the DNA are well-established. The process is also inherently scalable, meaning it could be used as a basis for much larger systems.

Reif also pointed out a few downsides. One is the speed of calculation. The execution of a single gate can take anywhere from 30 to 60 minutes. Executing a four-bit square root could take up to 10 hours.

However, the researchers believe this slowness can be overcome. "Improving the molecular components to reduce crosstalk and leak could allow us to use higher concentrations, which could speed things up 10 to 100 times, if it works," Winfree wrote. "Or, as we propose at the end of the paper, localizing the molecular components on a surface should provide a wide range of advantages, including higher speeds for large circuits."


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