Molecular Computers May Let Patients Diagnose and Treat Themselves

A microscopic computer constructed from a portion of a DNA molecule has been successfully tested in vitro, suggesting that such a device might someday be able to detect the presence of a disease in an individual and then produce a drug molecule to combat it.

Investigators at the Weizmann Institute of Science (Rehovot, Israel; www.weizmann.ac.il) developed the molecular computing device, which is so small that nearly a trillion of them can be contained in 1 ml of liquid. The molecular computing device belongs to the class of finite computers, which is a simplified version of the Turing machine, a mathematical model of computation developed by the British mathematician Alan Turing in the 1930s. As such, the molecular computer has three components: an input molecule, which stores the data to be processed as well as the fuel needed for the computation; software molecules, which encode program rules; and a hardware molecule that performs the computation, as directed by the software and the input. The molecules are suspended in a saline solution needed for the operation of the hardware molecule.

Details of the molecular computer were published April 28, 2004, in the online edition of Nature. They revealed that the input molecule is a double-stranded DNA molecule with a "sticky-end” single-stranded protrusion obtained by having one strand longer than the other. The software DNA molecules also have "sticky-ends,” each matching a different input combination. Through spontaneous DNA hybridization the input molecule and a matching software molecule temporarily bind to each other.

The hardware is an enzyme called FokI that attaches to DNA in a specifically coded location and cuts both strands at a fixed distance from that location, creating a sticky end. By employing additional chemical and mathematical tricks, the software molecules can be designed so that the hardware enzyme attaches to them and, once a software molecule hybridizes with an input molecule, the hardware enzyme cuts the input molecule in a programmed location, exposing a new sticky end that encodes the next state to be processed. The final sticky end, obtained at the end of the computation, encodes the computation result.

A unique property of the design of the molecular computer is that the DNA input molecule is also the source of the power that runs the computer. The energy is inherent to the chemical structure of DNA and is independent of the actual data it encodes, but is dependent on the length of the molecule.

Each molecular computer is rather slow. On average, it performs one operation per 20 seconds. On the other hand a 5 ml spoonful of these computers would be able to perform nearly 330 trillion operations per second, which is more than 100,000 times faster than the fastest personal computer, with an energy efficiency more than a million times that of a personal computer.

To demonstrate that the device actually works, the investigators successfully programmed the computer to identify and analyze mRNA of disease-related genes associated with models of small-cell lung cancer and prostate cancer, and to produce a single-stranded DNA molecule modeled after an anticancer drug.

Senior author Dr. Ehud Shapiro, a professor in the departments of computer sciences and applied mathematics at the Weizmann Institute said, "It is clear that the road to realizing our vision is a long one; it may take decades before such a system operating inside the human body becomes reality. Nevertheless, only two years ago we predicted that it would take another 10 years to reach the point we have reached today.”




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Weizmann Institute of Science