Bionic cells can do basic arithmetic

FORGET smartphones, how about a smart arm? Human cells capable of performing simple arithmetic could one day be implanted in your body as a biological computer to diagnose disease, administer drugs or interface with electronic devices.

Martin Fussenegger and colleagues at the Swiss Federal Institute of Technology in Zurich created biological versions of two key digital circuits inside two sets of embryonic kidney cells: a half adder and half subtractor. As the names suggest, they add or subtract two binary numbers. These are the most complex biological circuits ever created, and could form the building blocks of more advanced computational circuits.

Biological circuits capable of simpler computations have been developed before, but most are made of DNA molecules or bacteria, which would be difficult to implant in humans. "In order to be of any therapeutic relevance in the future, you need to establish these things in mammalian cells," says Fussenegger.

Ordinary computers use the presence or absence of electrons to represent 1s and 0s to encode information. Fussenegger's cells use two naturally occurring molecules: erythromycin, an antibiotic, and phloretin, a substance found in apple trees. These act as inputs, switching a reaction within the two types of cell on or off. The reaction leads to the production of a red or green fluorescent protein that signals the result of the calculation (Nature, DOI: 10.1038/nature11149). For example, in the half adder cell, the presence of both molecules makes it glow red (see diagram).

These reactions take place without interfering with the cells' ordinary functions, allowing them to speak the binary language of computers while continuing to work as normal cells.

The cell computers are more flexible than their electronic counterparts, because both the input molecules and the output proteins can be replaced with other biological signals, while traditional computers are limited to just one signal, the electron. That means a computer could be designed to take a signal from an infection as its input, for instance, and the output would be to deliver an appropriate treatment.

Visual signals like the red and green fluorescent proteins used in Fussenegger's proof of principle experiment could also be used, causing a skin patch to glow red in the presence of an infectious agent, say. Implanted, cell computers could even communicate directly with electronic computers. "Now we have the same logic, we hope that machines can talk better to cells," says Fussenegger.

"The team have taken this to the next level by showing how one can encode decision-making logic into cells rather than just producing a response," says Martyn Amos at Manchester Metropolitan University, UK.

It remains to be seen how well their approach scales to larger computational circuits, as the output from one cell cannot yet be used as the input to another. "The next challenge is to engineer these devices so that they can communicate," says Amos.

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