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Leonard Adleman sends his regrets. In an e-mail FAQ he uses to fend off journalists seeking interviews, the University of Southern California computer scientist and world-famous cryptographer who invented the field of DNA computing confesses that “DNA computers are unlikely to become stand-alone competitors for electronic computers.” He continues, somewhat apologetically: “We simply cannot, at this time, control molecules with the deftness that electrical engineers and physicists control electrons.”

It was in 1994 that Adleman first used DNA, the molecule that our genes are made of, to solve a simple version of the “traveling salesman” problem. In this classic conundrum, the task is to find the most efficient path through several cities-given enough cities, the problem can challenge even a supercomputer. Adleman demonstrated that the billions of molecules in a drop of DNA contained raw computational power that might-just might-overwhelm silicon. But since then, scientists have run into tough practical and theoretical barriers. As Adleman and others in the field have come to realize, there may never be a computer made from DNA that directly rivals today’s silicon-based microelectronics.

But that doesn’t mean they’ve given up. Far from it. Although computer scientists haven’t found a clear path from the test tube to the desktop, what they have found amazes and inspires them. Digital memory in the form of DNA and proteins. Exquisitely efficient editing machines that navigate through the cell, cutting and pasting molecular data into the stuff of life. What’s more, nature packs all this molecular hi-fi equipment into a bacterium not much bigger than a single transistor. Viewed through the eyes of computer scientists, evolution has produced the smallest, most efficient computers in the world-and the beige-box set is hooked.

As Adleman now sees it, DNA computing is a field that’s less about beating silicon than about surprising new combinations of biology and computer science that are pushing the limits in both fields-sometimes in unexpected directions. Scientists are still working hard on ways to tap the awesome number-crunching abilities of DNA for specialized types of applications, such as code breaking. But beyond that, the innate intelligence built into DNA molecules could help fabricate tiny, complex structures-in essence using computer logic not to crunch numbers but to build things.

Among the most promising of these new approaches are smart “DNA tiles” invented by Erik Winfree, a 30-year-old computer scientist at California Institute of Technology (see “100 Young Innovators,” TR November/December 1999). Winfree’s brainstorm is to create nanoscopic building blocks out of DNA that not only can store data but are designed-Winfree likes to say “programmed”-to carry out mathematical operations by fitting together in specific ways. Normally, DNA exists as two intertwined strands of the chemical letters A, G, C and T-the familiar double helix. But Winfree’s DNA tiles are made by knotting together three or more of these strands, forming “tiles” about 15 nanometers (billionths of a meter) on their longest side. Taking advantage of DNA’s ability to selectively recognize other strands of DNA, Winfree has “coded” the edges of these tiles so that they come together in just the right way to form tiny built-to-order structures.

In fact, programming DNA in this way could give chemists the kind of deft control “that may allow them to build more complex structures than any considered so far,” says Paul Rothemund, a doctoral student in Adleman’s USC lab.

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