DNA is assumed to rescue us from a computing rut. With advances using silicon petering out, DNA-based computers hold the promise of massive parallel computing architectures that are now impossible
But there's a problem: The molecular circuits built so far have no flexibility at all. Today, using DNA to compute is "like having to build a new computer out of new hardware just to run a new piece of software," says computer scientist David Doty. So Dot, and professor at UC Davis, and his colleagues set out to see what it would take to implement a DNA computer that was in fact reprogrammable
, Doty and his colleagues from Caltech and Maynooth University have demonstrated just that. They showed that it is possible to use a simple trigger to coalesce the same basic set of DNA molecules into implementing many different algorithms. Although this research is still exploratory, reprogrammable molecular algorithms could be used in the future to program DNA robots that have already successfully delivered drugs to cancerous cells
"This is one of the landmark papers in the field," says Thorsten- Lars Schmidt, an assistant professor of experimental biophysics at Kent State University who was not involved in the research. "There was an algorithmic self-assembly before, but not to this degree of complexity."
In electronic computers like the one you are using to read this article, bits are the binary units of information that tell a computer what to do . They represent the discrete physical state of the underlying hardware, usually the presence or absence of an electrical current. These bits, or rather the electrical signals they implement, are passed through circuits made of logic gates, which perform an operation on one or more input bits and produce one bit as an output.
By combining these simple building blocks over and over, computers are able to run remarkably sophisticated programs. The idea behind DNA computing is to substitute chemical bonds for electrical signals and nucleic acids for silicon to create biomolecular software. According to Erik Winfree, a computer scientist at Caltech and a co-author of the paper, molecular algorithms leverage the natural information processing capacity baked into DNA, but rather letting nature take the reins, he says, "computation controls the growth process. "
Over the past 20 years, several experiments have used molecular algorithms to do things like playing tic-tac-toe or assemble various shapes. In each of these cases the DNA sequences had to be painstakingly designed to produce one specific algorithm that would generate the DNA structure. What is different in this case is that the researchers designed a system where the same basic pieces of DNA can be ordered to arrange for totally different algorithms ̵
The process begins with DNA origami, and technique for folding a long piece of DNA into a desired shape. This folded piece of DNA serves as the "seed" that kicks the algorithmic assembly line, similar to how a string dipped in sugar water acts as a seed when growing rock candy. The seed remains largely the same, regardless of the algorithm, with changes made to only a few small sequences within it for each new experiment.
Once the seed has been created, it is added to a solution of about 100 other DNA strands, known as DNA tiles. These tiles, each of which consists of a unique arrangement of 42 nucleobases, are taken from a larger collection of 355 DNA tiles created by the researchers. To create a different algorithm, the researchers would choose a different set of starting tiles. So a molecular algorithm that implements a random walk requires a different group of DNA tiles than an algorithm used for counting. As these DNA tiles link up during the assembly process, they form a circuit that implements the selected molecular algorithm on the input bits provided by the seed.
Using this system, the researchers created 21 different algorithms that could perform tasks like recognizing multiples of three, electing a leader, generating patterns, and counting to 63. All of these algorithms were implemented using different combinations of the same 355 DNA tiles
Writing code by dumping DNA tiles in a test tube is worlds away from ease of typing on a keyboard, of course, but it represents a model for future iterations of flexible DNA computers. Indeed, if Doty, Winfree, and Woods have their way, the molecular programmers of tomorrow will not even have to think about the underlying biomechanics of their programs, just as computer programmers today do not need to understand the physics of transistors to write good software
This experiment was a basic science at its purest, a proof of concept that generated beautiful, though useless, results. But according to Petr Sulc, an assistant professor at the Arizona State University's Biodesign Institute, who was not involved in the research, the development of reprogrammable molecular algorithms for nanoscale assembly opens the door for a wide range of potential applications. Sulc suggested that this technique may be useful for the creation of nanoscale plants that assemble molecules or molecular robots for drug delivery. He said it could also contribute to the development of nanophotonic materials that could pave the way for computers based on light, rather than electrons
"With these types of molecular algorithms, one day we might be able to assemble any complex object on and nanoscale level using a generic programmable tile set, just as living cells can assemble into a bone cell or a neuron cell just by selecting which proteins are expressed, "says Sulc
The potential use of this nanoscale assembly technique boggle the mind , but these predictions are also based on our relatively limited understanding of the latent potential in the nanoscale world. After all, Alan Turing and the other progenitors of computer science could hardly have predicted the Internet, so perhaps some equally unfathomable applications for molecular computer science
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