The project is a scientific melting pot requiring the participation of experts in such far-flung disciplines as molecular genetics, computational biology, nanotechnology and electrophysics. The scale is certainly smaller, but the sweep of research now underway or in the offing could be compared to a mini-Manhattan project – aimed at developing not a weapon but a fuel cell.

Delighted pretty much sums up how Nealson feels to be working on a set of problems he loves in a setting – USC – where the sophisticated team needed to solve them is already in place.

“Almost anywhere else,” he says, “I would have to go thousands of miles to find all the different kinds of expertise we need for this. Here, it’s all within 200 meters.”

Nealson’s career path was set early, in a way that’s not uncommon for young scientists – a charismatic mentor pointed out an unexplored path of promise. For Nealson it happened at the Scripps Institution of Oceanography, where he had landed after getting his PhD in biochemistry at the University of Chicago and completing a three-year post-doc at Harvard.

As a junior scientist at Scripps, he was studying spectacular glow-in-the-dark “bioluminescent” bacteria when he came to the attention of senior chemist Edward Goldberg.

The glow-bugs were “neat stuff,” Goldberg had acknowledged, but Nealson remembers the distinguished older scientist asking: “Why don’t you do something important? Something like understanding the relationship between microbes and metals?”

Nealson took Goldberg’s words to heart. It was very apparent, even back then, that many aspects of marine metal distribution and activity could not be explained by chemistry alone. The quantities were wrong, the rates of reaction far too rapid.

The young biochemist turned his attention to geobiology – the study of how microbes interact with the geosphere, how they alter the Earth through their extensive repertoire of microbial tricks. But could a bacterium’s insatiable appetite for energy actually speed up geochemical reactions? In their presence, could processes that normally take years occur in days, hours or even minutes?

Receiving a Guggenheim fellowship, Nealson spent a sabbatical year studying marine chemistry at the University of Washington. He embarked on a voyage that has led him to far-flung bodies of water: from Lake Baikal in Siberia to the depths of the Pacific. It has even led to investigations off the planet.

Most notably, in 1987, it led Nealson to Lake Oneida in upstate New York, where he hit the mother lode. Previously published rates of metal (manganese and iron) release from the lake’s sediments were the highest in the world there, and far too rapid to be explained by chemistry alone. Testing of these sediments indicated that something in the lake had a ravenous appetite for metal. That something turned out to be a bacterium capable of using solid manganese and iron oxides (rust) as an oxygen substitute for respiration – something long suspected but previously unknown to the scientific world. The genus of this organism, Shewanella, was familiar, but its ability to “breathe rocks,” as Nealson puts it, was totally new. The creature was named oneidensis after the lake, and MR-1, denoting its status as the first metal-reducing microbe to be identified.

Working with his discovery, Nealson soon solved a theoretical riddle dogging his research. Conventional wisdom held that no bacterium could possibly cause the geological changes he was chasing. This misperception, however, reflected a major bias in the field, attributable to the fact that the great majority of bacterial research, up to that point, had been limited to germs associated with human disease.

For years, bacteriologists had believed it impossible for microbes to interact with solid rock or metal surfaces because their metabolic machinery is sealed inside a semipermeable membrane. Unless a micro-particle of metal somehow found its way inside the membrane, experts believed, no reaction could result. A macro-sized chunk of metal or rock would be completely inaccessible to microbe metabolism.

But in the laboratory, S. oneidensis yielded its simple, amazing secret: it’s inside out. Unlike all previously studied organisms, MR-1 packs the business-end of much of its metabolic machinery outside the plasma membrane. The powerful enzymes that catalyze its metal-devouring reaction are arranged on the outer surface of the organism. “It was a new paradigm,” Nealson notes. “Bacteria doing something they aren’t supposed to be doing.”

With this insight, the hunt was on. His group has isolated and cultured many strains of metal-reducing Shewanellae. More than 100 strains have now been identified around the world. The entire genome of S. oneidensis was sequenced in 2004, and now Nealson and other colleagues have sequenced the genomes of 15 MR-1 strains with more in progress.

“When we began isolating S. oneidensis MR-1, I proclaimed to the lab that this one organism might keep us busy for the next 15 years,” he recalls. “And in fact, it has now been 17 years and we’re still learning.”

Florian Mansfeld is one of those learners. The USC Viterbi School of Engineering materials scientist has been working with bacteria for years, helping to pioneer a turnabout in his field. For decades, engineers knew that bacteria could and would attack metals, causing corrosion, tarnishing or rusting – three names for the same process occurring in different substances. The reaction even has a name: microbiologically-influenced corrosion (MIC).

Mansfeld and colleague Joseph Devinny, also at the USC Viterbi School, worked on an egregious example of the phenomenon a decade ago, unraveling how concrete sewers were systematically devoured by bacteria. Paradoxically, the cleaner the water passing through the sewer, the faster the germs consumed the concrete.

Mansfeld was among the first to show that the opposite could also be true: that bacteria could protect materials. That particular example didn’t involve concrete, but metals. “At the time nobody ever thought bacteria inhibited corrosion: it was just the opposite.” Mansfeld gave the phenomenon its name: “microbiologically-influenced corrosion inhibition,” or MICI.

S. oneidensis proved to be a MICI star. When specimens of MR-1 were evaluated in his laboratory, Mansfeld and doctoral student Esra Kus MS ’04 discovered its astonishing potency. Kus incubated copper, aluminum, steel and brass in a liquid containing nutrients, but not MR-1 bacteria. The metals did what metals often do in liquid: rusted, tarnished, pitted and corroded. But not when MR-1 was present.

Scientists measure a metal’s corrosion susceptibility by determining its so-called polarization resistance in the presence of corrosive substances, like water: low resistance correlates with high levels of corrosion. With MR-1, the polarization resistance shot up the moment the bacteria were introduced. The longer the bacteria incubated, the higher the resistance went. Copper protected by MR-1 registered resistance values similar to copper coated by paint.

Protecting metals from corrosion using paints, other coatings and corrosion inhibitors is a multibillion-dollar industry, making this a find of potentially great importance.

In another study, Mansfeld’s team built a simple, conventional battery – two kinds of metal in a medium, electrons flowing “downhill” to a metal with a large appetite for them, away from a metal that binds them only loosely. Without MR-1, the battery exhibits the behavior found in any elementary physics demonstration: it runs for a few days, then runs down. With MR-1 in the liquid, however, the power steadily increases over the 90-day experiment.

The research continues. Mansfeld is now trying to determine exactly what is happening on a chemical level in the biofilm – a pinkish, translucent layer on the metal surface that is actually a complex, highly organized and interactive bacterial community.

Years ago he pioneered a laboratory method called “electrochemical impedance spectroscopy,” which measures much more precisely the polarization resistance changes associated with corrosion and electrical effects. Using EIS, his team is now racing to see how much can be learned, and how quickly, about all aspects of MR-1.

Assisting Mansfeld in his work with the microbial fuel cell is doctoral student Orianna Bretschger. The physics-trained engineer/materials scientist has become a Shewanella oneidensis expert, interfacing with Nealson, Mansfeld and their collaborators across the disciplinary board. She looks right at home at her bench in a bacteria-filled lab. On a recent day, she was running an experiment comparing the power output produced by one MR-1 strain with a set of genetically altered Shewanella mutants whose electron transfer capabilities had been knocked out. “It’s been a lot of fun. I’ve learned a ton about how to work with these guys,” Bretschger says, referring to the bacteria, not the biologists around her.

Promising as it is in the abstract, bacterial energy production carries a heavy chemical burden when it comes to practical applications. Conventional fuels like gasoline are highly concentrated, packing vast quantities of energy in a small volume. By contrast bacterial output is meager, at least initially.

The challenge is to apply a whole set of fixes on at least three levels (molecular, biological and mechanical) to kick up power output. “For the applications we’re talking about, such as a bacteria-powered car, we need to increase energy output many thousand-fold from where we started,” Nealson says.

Enter USC Viterbi researcher and NASA backup astronaut Paul Ronney. One of the world’s leading experts on combustion, he has spent much of his career learning to understand flames – technically defined as flows of fuel and energy that, if conditions are right, continually build on themselves in a feedback loop. More heat creates faster reactions, creating more heat, creating faster reactions, up to the limits of available fuel and oxygen.

Knowing Nealson by reputation, the USC aerospace engineer sought out the USC geobiologist. Ronney threw himself into the proposal-writing process that would net USC a $5 million DoD Multidisciplinary University Research Initiative grant to develop a bacterial fuel cell – or a “bactery.”

But what does flame have to do with harnessing germ-based energy? The MR-1 reaction is not hot, but the way the microbe multiplies resembles a combustion feedback loop, with more bacterial food meaning more bacteria, which consume more food creating more bacteria.

Ronney is applying the techniques developed in his previous work to model a cold bacterial MR-1 flame. Working with fellow mechanical engineers Hai Wang and Andreas Lüttge (of Rice University, the only non-USC team member), Ronney is analyzing the MR-1 reaction with the classic and proven tools used in the study of conventional combustion. Here’s the drill:

1. Possible factors influencing the reaction are varied, factor by factor, in the lab.

2. Results are studied and incorporated into a mathematical model, which is tested and re-tested for its accuracy in predicting experimental results over the whole range of varying factors.

3. Scientists use the model to design the best possible system.

The process is classic and well tried. What’s new is that mechanical engineers are applying it not to car engines but to the life-cycle of a bacterium.

Another source for improvement in the microbial fuel cell’s efficiency comes from the work of USC chemist G.K. Surya Prakash, holder of the Olah Nobel Laureate Chair in Hydrocarbon Chemistry and co-investigator on the MURI project. The co-inventor of a liquid-methanol fuel cell that has found its way into laptop computers and portable power generators, Prakash brings crucial expertise to the task of improving the heart of the fuel cell: the membrane that allows hydrogen – and only hydrogen – to pass one way.

Without membranes, a fuel cell is nothing more than a battery. In the latter, only negatively charged electrons move. In the former, positively charged protons move from one side of a permeable barrier – the membrane – to the other. While batteries provide a lot of power for a limited time, fuel cells provide less power, but (theoretically, at least) can work for years.

The original prototype of Nealson’s microbial fuel cell had been a commercially made membrane, with mediocre results. The membrane was leaky, letting wood alcohol and excessive water move across the barrier, degrading the fuel cell’s overall performance. Prakash supplied a much more efficient model, one inspired by membranes used to filter alcohol out of non-alcoholic beer; it was patented by USC in 2002. He also has given the team a better design for the electrodes used in the fuel cell.

“We’re experimenting with a number of newer designs for the microbial fuel cells too, which we expect will increase the efficiency even more,” Prakash says.

But problem-solving on the physical and engineering side represents only half the effort to boost the MR-1 fuel cell’s power output. On the life-sciences side, microbiologist Steven Finkel of USC College has teamed with Nealson in the hope of breeding a better bug.

Fluent in the language of genetics, Finkel wants to increase the survival time and growth for Shewanella living in the fuel cell, and to make each cell crank out more electrons – ergo, more juice. He is going about it in new ways.

“We think we know some of the genes involved in the process of electron transport,” Finkel says. “Through genetic engineering, we could turn them ‘on’ or ‘off.’” But a better, faster approach, he thinks, is to deploy the power of directed-evolution. The technique involves intentionally triggering mutations by putting bacterial cells under stress.

“That way, we’re not limited by what we know, or don’t know, in coming up with a solution,” he explains. “We are just selecting for those cells that have the qualities we want – they may grow more robustly, survive better, or produce more electricity.”

A member of the USC Center for Excellence in Genomic Science, Finkel has long studied the molecular mechanisms underlying genetic mutation and evolution in E. coli. He has focused particularly on how E. coli, under certain conditions, spontaneously can change its own DNA.

In bacteria, he explains, one cell with an advantageous mutation can quickly repopulate an entire culture, enabling whole populations to survive under harsh conditions – for example, where nutrients are scarce.

Imagine a bacteria fuel cell that’s biochemically engineered to do more with less when it starts to run down.

One promising direction, says Finkel, involves growing Shewanella on a souped-up, proton-rich carbon source. This high-energy, super-rich diet would increase the cell’s electric output. But excess protons mean, inevitably, higher acidity. “So we need to find the MR-1 that can tolerate high acid levels,” he says. By growing the bacteria in an acidic environment, Finkel can select for the Shewanella that – through randomly generated genetic mutations – have “adapted” to out- compete ordinary cells. “In a fraction of an ounce, you can have bacteria with every possible mutation represented in the population – including cells with advantageous mutations,” he notes.

And because bacteria reproduce so rapidly, Finkel can monitor genetic changes over many generations in a single day.

Choose the right criteria, he says, and “you can get solutions you’d never find any other way. We need to listen to the bugs.”

Finkel isn’t only listening to MR-1. He plans to add other bacteria to the mix to see if any can enhance fuel-cell performance – by breaking down waste, using materials MR-1 can’t use, changing acidity and who knows what other parameters.

“Then once we have an optimal cell,” he says, “the engineers will start looking at how to make this a thousand times bigger or a thousand times smaller.”

The efforts of the USC team may turn out to have implications far beyond a better fuel cell. It has become clear to Nealson that the Earth itself is affected, for better and worse, by organisms we are still only vaguely aware of. A study published in the July 31 issue of Science found that seawater contains a dumbfounding roster of different forms of bacteria – at least 10 times more than expected.

The Science study coincided with “Altered Oceans,” a five-part series in the Los Angeles Times. Alarmingly, this exposé concluded certain microorganisms whose very existence is barely known to scientists have – because of man-made changes in the biosphere – suddenly emerged as nuisances or even threats. The process, according to the Times series, is accelerating.

As it does, geobiology may prove not only a path to building a more fuel-efficient machine. It may also offer insights into preserving and protecting the planet we share with MR-1 and its silent but influential kindred. In the meantime, Nealson’s bactery-powered vehicle promises to be a remarkable machine.

Eva Emerson, a senior editor with the USC College of Letters, Arts and Sciences, contributed to this story. To ask a question or make a comment on this article, please send email to <magazines@usc.edu>.