There are many computers in California, but only one of them is running inside a living yeast cell.

Future models of the living computer, made from the DNA-like molecule RNA, could be used to run calculations in vivo – that is, inside human cells – to release drugs or prime the immune system at the first hint of illness.

DNA shares its essential features with computers – it stores, processes and communicates information. And in the late 1990s, researchers successfully created a set of DNA molecules – a DNA computer – able to solve simple mathematical problems.

DNA computers since have since proved unbeatable at tic-tac-toe (noughts and crosses), but they are not really suited to high-speed number crunching like a conventional computer.

The real strength of these molecular devices is in working and computing inside biological systems, where DNA has evolved to be at home.

Glowing results
Now the California Institute of Technology (Caltech) has developed RNA computers that are the most advanced realisation of that concept yet. Maung Nyan Win and Christina Smolke have created an RNA device that acts as a logic gate, the basis of electronic computing.

The Caltech device processes input signals in the form of natural cell proteins and produces an output in the form of green fluorescent protein (GFP) (see a slideshow of images of GFP in use).

At the computers heart is a ribozyme – a short RNA molecule able to catalyse changes to other molecules. That is attached to an RNA sequence that the cell can translate into GFP, and a third RNA molecule that acts like a trigger for the ribozyme.

That trigger can be designed to bind to specific molecules inside the cell like proteins or antibiotics. When it does, the catalytic ribozyme destroys the GFP sequence and prevents the cell from making any more glowing protein.

The whole assemblage is a NOT logic gate: when an input protein is present production of GFP stops. Using two trigger sections produces a NAND gate, the output of which depends on the presence or absence of two input proteins.

Multiple NAND gates can be used to write any other logical operation, making them "the most celebrated example of a device enabling universal computation," says Smolke.

DNA doctor
The Caltech team think it should be simple to transfer their gate into mammalian or bacterial cells in future, and to chain logic gates together to perform more complex operations. That offers the potential of a revolutionary approach to studying and healing biological systems.

Test-tube experiments in 2004 demonstrated how such a DNA computer doctor might work. Ehud Shapiro at the Weizmann Institute of Science created a system that could detect a marker molecule associated with prostate cancer and release an anti-cancer drug.

Using strings of logic gates, a similar system could combine signals from several different biomarkers to produce more complex responses, for example, cocktails of drugs or hormones.

"This is an important step forward in the field of synthetic biology and in vivo computing," says Kobi Benenson at Harvard University.

In 2007, Benenson's team was the first to put a computing device inside a cell (Nature Biotechnology, DOI: 10.1038/nbt1307). That system needed artificial DNA strands as its input signals, while the Caltech computer can use natural cell molecules.

...journal reference: http://technology.newscientist.com/article/dn14965-molecular-computer-runs-calculations-inside-living-cell.html