| Programmable 
        DNA debutsBy 
      Kimberly Patch, 
      Technology Research News
 The DNA molecule is the mechanism nature 
        uses to construct every living being. Scientists are beginning to use 
        the same mechanism to compute, but most of the rudimentary DNA computers 
        built so far require researchers to manually trigger each step of a molecular 
        calculation.
 
 Researchers from the Weizmann Institute in Israel have found a way to 
        automatically carry out several computational steps at once in a test 
        tube of short, artificially-constructed DNA molecules. They put the DNA 
        through a series of steps that, once begun, carried through to the end 
        of a computation.
 
 Although it takes minutes for DNA to do a single computation, many molecules 
        can compute at once in a very small amount of space. "We get a trillion 
        computers doing a billion operations per second in [a drop] of solution," 
        said Ehud Shapiro, an associate professor in the departments of computer 
        science and biological chemistry at the Weizmann Institute of Science 
        in Israel.
 
 This computation DNA, like biological DNA, is made up of four types of 
        bases attached to long sugar-phosphate chains. Two of these chains, with 
        bases attached, zip together, pairing up the bases on each chain to form 
        DNA's classic double-helix shape.
 
 Biological DNA uses specific sequences of the bases as blueprints to build 
        the many proteins involved in the chemical reactions of life. The same 
        sequences can represent numbers and be manipulated mathematically to compute.
 
 The computation method uses two types of DNA molecules: software, or computation 
        molecules, which are about 40 base pairs long and contain the instructions 
        for the computation, and input molecules, which contain strings of six 
        bases that represent the problem to be solved. A computation happens when 
        these two types of molecules interact. Each has a sticky end, meaning 
        one strand of the double helix is longer than the other, exposing a sequence 
        of bases that are not paired.
 
 When the sticky end of an input molecule bumps into a software molecule 
        that has a sticky end that fits, the bases of the two sticky ends join 
        together, and an enzyme present in the solution seals them together. The 
        molecule is then cut in a different place by a second enzyme, exposing 
        another sticky end so that a second step can take place. The number of 
        steps depends on the number of computations coded into the software DNA 
        strand.
 
 For example, to answer the question 'does the sequence of letters "bab" 
        contain an even number of b's?' the input DNA molecules would represent 
        each of the three letters using a segment of DNA six bases long. The software 
        molecules would contain a logical series of steps for determining whether 
        the input has an even number of b's.
 
 When the computation ends, the remaining sticky ends connect to one of 
        two marker molecules of different lengths. One of the marker molecules 
        contains a sequence of bases that will stick to the computation molecules' 
        sticky end if the answer turned out to be even, and the other contains 
        the correct sequences if the answer turned out to be odd.
 
 Once the microscopic reshuffling of DNA bases is done, the researchers 
        read the answer using gel electrophoresis, a process that involves putting 
        DNA on a gel, and passing electrical current through electrodes attached 
        to the gel. "[You] place the DNA near the minus electrode. The DNA travel 
        slowly inside the gel towards the plus electrode at a speed that is a 
        function of the molecule size. If you stop the process at the right time, 
        you have a spread of the molecules according to... length," which makes 
        it apparent which marker molecule has connected to the computation molecule, 
        Shapiro said.
 
 The researchers' DNA computer can run 735 sample programs made up of sequences 
        of the eight basic operations that are possible using six-base input strings.
 
 Previous experiments that used DNA to compute had to be designed to solve 
        a single problem, although some could handle varied inputs, said Nadrian 
        Seeman, a chemistry professor at New York University. "Here, several different 
        questions can be asked of the same system," he said. The work could lead 
        to more generally programmable approaches to DNA-based computation, he 
        added.
 
 In the researchers' experiments, the DNA took nearly 17 minutes to carry 
        out each operation; eventually DNA will probably be able to carry out 
        an operation in a few seconds, said Shapiro.
 
 Compared to silicon computer chips, which compute in millionths or billionths 
        of a second, this would still be very slow, but because millions or trillions 
        of DNA molecules could compute in parallel, this type of DNA computer 
        could handle very large problems; more important, it works in a test tube.
 
 The work is "different from most experimental work on DNA computers in 
        that we do not attempt to compete with silicon computers by solving difficult 
        problems faster. The potential is... operation in a biochemical environment," 
        said Shapiro.
 
 The method is "an ingenious construction that provides the capability 
        of a basic sort of computation at the molecular scale," said John Reif, 
        a computer science professor at Duke University. It is not new to use 
        the molecular configuration of DNA to store the result of a computation, 
        but this work provides a very general mechanism for using that result 
        to then compute a further result, he said.
 
 This type of work could eventually lead to molecular computers that could 
        be used to control molecular processes like complex assemblies and molecular 
        robotic devices, Reif said.
 
 The method could be used to screen libraries of DNA in five to ten years, 
        and could eventually be used to carry out more complicated tasks like 
        detecting DNA anomalies and synthesizing drugs to fix them, Shapiro said, 
        adding that this use is decades away.
 
 Shapiro's research colleagues were Yaakov Benenson, Tamar Paz-Elizur, 
        Rivka Adar and Zvi Livneh from the Weizmann Institute, and Ehud Keinan 
        from the Weizmann Institute and the Scripps Research Institute. They published 
        the research in the November 22, 2001 issue of Nature. The research was 
        funded by the Weizmann Institute.
 
 Timeline:   5-10 years, several decades
 Funding:   University
 TRN Categories:  Biological, Chemical, DNA and Molecular 
        Computing
 Story Type:   News
 Related Elements:  Technical paper, "Programmable and Autonomous 
        Computing Machine Made of Biomolecules," Nature, November 22, 2001.
 
 
 
 
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 | November 
      28, 2001
 
 Page 
      One
 
 Programmable DNA debuts
 
 Device would boost 
      quantum messages
 
 Virtual computers 
      reconfigure on the fly
 
 Software sorts video 
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      won't hit quantum barrier
 
 
 
   
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