Sat, May 22, 2010 page9

• New research aims to build a ‘bacterial brain’

  • By Louise Tickle / THE GUARDIAN
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  “When I started thinking about how to do this project, I got colleagues from six universities in Europe to meet up in Manchester and said, ‘I want to build a bacterial brain in a dish.’ Everyone went very quiet, thinking, ‘We’ve come all the way to Manchester and now it turns out this guy’s insane,’” Martyn Amos said.

  Amos, senior lecturer in computing and mathematics at Manchester Metropolitan University, sounds entirely unrepentant, possibly even gleeful.

  His brain in a dish idea, he says, was intended to be provocative, but in essence, that’s what he and academics from universities in France, Spain, Belgium and Germany are now hoping to create. Their three-year “synthetic biology” project has 2 million euros (US$2.5 million) of EU funding, and involves engineering living cells in the hope of persuading them to do certain human-defined tasks.

  The more colloquial name for synthetic biology is “bacterial computing.” It sounds a bit messy, and, according to Amos, it is.

  “It currently works rather like a scrapheap challenge, where scientists add genetic parts to a basic bacterial ‘chassis,’ then bash the whole thing with a chemical ‘hammer’ to make it work,” he explains.

  However, this approach is rather time-consuming and very hit-and-miss, so Amos and his team have decided to try a different tack. What the team will be doing over the next three years is harnessing evolutionary processes to get bacteria to perform jobs to which traditional silicon-based computers are poorly suited. Environmental clean-up is just one example of how bacterial computing could help in the future.

  “In places such as Bangladesh, drinking water is often contaminated with arsenic and villagers have little choice but to use it,” Amos says. “Arsenic poisoning causes terrible damage to people, and detecting it is fraught with practical problems such as how to get rid of waste products safely. A brilliant team of undergraduates at Edinburgh have developed a prototype arsenic detector, based on engineered bacteria that recognize the contaminant and flag up its presence. In principle, it’s cheap and easy to use and its waste products are harmless.”

  The key difference with his research, says Amos, is that bacterial cells will not only be tasked with a job and given the genes that allow them to do it: Where it gets clever is that Amos’s team will harness cells’ inherent evolutionary qualities so that each subsequent generation gets better and better at doing that job.

  How will this “selection” happen then, in the not-very-­natural environment of a petri dish?

  Well, says Amos, let’s start by imagining that the job is to get a population of bacterial cells to fluoresce in response to a pulse of light.

  “On-off, on-off, like Christmas tree lights but made of bacteria?” I ask.

  “That kind of principle,” he says, kindly.

  “To help them do the job, we might throw into a dish of E. coli the genes for detecting light, the genes for emitting a response and the genes that would allow the cell to connect those two things,” he says. “We then let the cells suck them up, and see what happens.”

  Because of a special “comparator” component his team is working on, which also goes into the mix, each cell will then be able to tell whether it has done the job well or badly.

  “Most of the results will be rubbish. A cell might suck in a lot of light-detecting components but no responder ones and no connectors. But another cell might take a detector and a responder and manage to form some sort of connection, and will therefore give a feeble response to a pulse of light,” he says.

  “Going with Richard Dawkins’s observation on how evolution works, ie, that even a very poor eye is better than no eye at all, we’ll have created an internal system in our petri dish that says, ‘Right, you, not-very-well-functioning fluorescing cell, you’ve done better than the others, so you get to survive to the next generation,’” he says.

  Those successful cells, he says, will replicate lots of copies of their “good-at-the-job” DNA, which will then be taken up by other cells and used to piece together slightly better solutions next time round.

  “What we hope to see is the fitness of the population improving as the cells get better at solving the problem of how to do the job,” he says.

  Apart from bio-remediation of drinking water, what could these clever bacteria be used for?

  “This is really speculative,” says Amos, reluctantly, aware of the dangers of promising too much, “but there’s the possibility, way in the future, of taking cells from a patient and re-engineering the cell so it can detect a problem and construct its own chemical response. Once reinserted, that means that the cell — which wouldn’t be rejected, as it’s the patient’s own — could act at the site of the problem. You wouldn’t need to blast someone with antibiotics, for instance — it’s a much more exquisite solution.”

  What does he anticipate the scientists on his project will struggle with?

  “The main risk is that the comparator doesn’t work,” he says. “That would mean the cells can’t tell how well they’re doing at the task, so the ones that perform well couldn’t be ‘rewarded.’ And then we’re stuffed.”

  And what would success look like — on a trivial note, might we see fluorescing bacterial Christmas tree lights?

  “Well, actually, bacterial Christmas tree lights have already been done,” he says with a laugh. “But they were made by researchers manually engineering cells to do the job. Success for us would be to get our cells ‘learning’ how to be Christmas tree lights all by themselves.”
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