The most recent E. coli epidemic in the U.S. struck late last year, when 33 people in Arizona, California and Nevada suffered from abdominal cramps, nausea and diarrhea after eating grab-and-go chicken salads. For two patients, the infection produced toxic substances that killed their red blood cells, which then clogged and damaged the tiny blood vessels in their kidneys, crucial for filtering out waste products and regulating blood pressure. Since treatments like dialysis often lead to a full recovery, no one died; but the condition can lead to potentially fatal kidney failure, or long-term kidney damage that may require medication or dietary changes to keep blood pressure low.
Foodborne illnesses affect 48 million - or 1 in 6 - Americans, and kill 3,000 each year, according to CDC estimates. Usually a quick sniff test or glance at the expiration date can reveal whether or not a food item is past its prime. But it’s tricky with E. coli contamination, which is impossible to detect by smell, taste or appearance alone.
But what if an alarm system could alert us to contamination? It’s a possibility, thanks to research led by Manuel Porcar, a synthetic biology researcher at the University of Valencia in Spain. His group engineered harmless strains of E. coli bacteria to emit different colors of light depending on the surrounding heat, acidity and oxygen levels. The next step is to use a microprocessor to convert those light waves into speech. That means we could add these engineered bacteria to food packaging, and if they detect environmental conditions that indicate contamination, they can tell us - literally - to avoid eating the package’s contents.
“It seems like science fiction,” Porcar says. “But it’s a simple idea, and it worked well.”
And food safety is just one application. For example, pharmacists can place a sample of a drug containing the engineered bacteria in a special machine outfitted with a microprocessor, so the bacteria can let them know whether they made the drug correctly by producing proteins that emit different colors of fluorescent light depending on the amount of a certain ingredient. Distillers can use the engineered bacteria in a similar way to determine whether their alcohol is ready to bottle.
The project, published online in Letters in Applied Microbiology, was Porcar and his students’ entry to the 2012 International Genetically Engineered Machine (iGEM) competition, in which undergraduate student teams build biological systems from a library of DNA sequences that encode specific biological parts.
One of Porcar’s students asked a simple yet tantalizing question: Can we talk to bacteria through light pulses?
To find out, the team engineered four strains of E. coli to produce proteins that emit different colors and amounts of fluorescent light depending on environmental factors considered crucial for survival. They designed one strain to glow cyan under low glucose conditions, another to glow red with increasing temperature, and a third to glow green with decreasing oxygen levels. Finally, they designed a fourth strain to fluoresce yellow under low-nitrogen conditions.
Sure enough, when the researchers tweaked the environment in which the E. coli bacteria were growing, the amount of light they emitted went up or down depending on their comfort level. For example, exposing the heat-sensitive strain to pulses of increasing temperatures caused it to glow red more brightly each time.
The next step is to use a microprocessor to convert vocal questions into light pulses that stimulate the engineered E. coli to produce fluorescent light-emitting proteins. Then the microprocessor would convert that light into vocal responses, depending on its wavelength. So if the microprocessor detects wavelengths that result in bright red light, “the machine would say, ‘I’m very warm. Please refresh me,’” Porcar explained.
So far, the researchers have designed a microprocessor that can convert speech into light pulses, and vice-versa, but they haven’t integrated it into a complete system. Porcar has no plans to continue the project and, as far he knows, no one else has taken up the charge. But Victor de Lorenzo, a microbiologist at the Spanish National Center for Biotechnology, is engineering cells to command each other to perform sophisticated computations. These cells can then serve as building blocks for circuits to perform even more complex tasks, such as cleaning up toxic metals.
Nonetheless, Porcar’s study - the first-ever attempt to communicate with bacteria - highlights the importance of regular “check-ins” with bacteria to optimize their performance. “On one hand, the domesticated biological object must follow predictably the orders of the master,” de Lorenzo says. “But we have thus far not cared about the other direction - how bacteria feel while responding to our orders. Are they happy, are they stressed, will they refuse to obey?”
Today, Porcar is continuing to investigate bacteria’s potential. His group has developed a device that converts the heat that bacteria emit - for example, when they digest sugar during alcohol production - into electricity to power small electronics.
But Porcar’s work also raises the controversial question of whether engineering principles can be applied to living systems - a central tenet of synthetic biology often trumpeted by the popular media. “The main reason is that, in my opinion, cells are not machines because they’re not designed,” he says. “They arise from natural selection and evolution.”
If living systems really were machines, then each part should behave independently of each other. But Porcar thinks the opposite is true. A major limitation of the “talking bacteria” project was that growing different strains together failed to provide readouts of multiple environmental conditions; for example, the strain designed to sense oxygen could no longer do so.
Porcar is testing his hypothesis for this year’s iGEM entry. The results might vastly change the way scientists approach synthetic biology. “We might be unable to make bacteria behave exactly as we want by rational design,” he says. Porcar thinks “rational design plus some room for fine-tuning with natural selection” might be more effective.
Typically, scientists insert one specific DNA sequence - encoding an anti-malarial protein, for example - into bacteria, allowing them to replicate, forming clones. Procar instead suggests allowing bacteria to naturally accumulate mutations in their DNA over the course of a few weeks, perhaps with the help of UV radiation, generating different variants of the protein and growing them with the malaria-causing parasite to select which one works best.
Porcar is challenging and stretching the way we think of bacteria. More than just cogs in a machine, they’re living systems themselves, meaning that our best chance of benefiting from them may be working with them - and even asking them how they’re doing.