The Big Science Challenge With Biofuel: A Chat with ISB’s Nitin Baliga

Talk to any biofuels entrepreneur, and you are likely to hear a passionate riff on why their technology trumps all the up-and-comers.

Some, like San Diego-based Sapphire Energy, say you’ve got to harness free sunlight and the magic of photosynthesis, to grow oil-rich algae in open ponds at the scale of modern agriculture.


Others, like South San Francisco-based Solazyme, say that will never work at commercial scale, and you need the controlled environment of industrial fermenters to keep out all kinds of curveballs Mother Nature might throw in the mix. The critics shoot back that the bioreactors will be too expensive to really scale up to meet energy needs for a world with a voracious appetite for energy, in a $7 trillion annual marketplace.

 These are what you’d call engineering risks. But what about the basic science risks? Scientists have been working for a long time on various alternatives to fossil fuels as the fundamental unit of energy, without much success. No one person or institute has all the answers here, but Nitin Baliga, a professor at the Institute for Systems Biology in Seattle, runs a lab that works on a wide variety of relevant research projects with implications for human health, environmental cleanup, and biofuels.

The scientific challenge with biofuels has definitely been top of mind for me the past few weeks, as I get ready to moderate our next event, “Separating Hype from Reality in Alternative Fuels” at the ISB’s new headquarters in Seattle on May 19. Thinking through the challenges the past couple years has been sobering, Baliga says.

“I’ve become smarter about knowing what the challenges are,” Baliga says. “I’m not a pessimist yet, but my optimism is more guarded (than a couple years ago). I know now where it is more likely to work, and less likely to work. I do think there’s enormous potential that’s still really untapped, because we don’t understand how the systems work.”

When Baliga and his colleagues talk about systems, they are talking about not just studying one gene, one protein, or one organism in isolation. He’s talking about how whole networks of genes, or whole ecosystems in some cases, adjust and adapt in response to some new stimuli. One of his big discoveries from a couple years ago was about how a microbial cell will respond to a variety of environmental assaults, such as radiation and certain metals. Lately, he’s expanded on that idea to become interested in how whole communities of microbes adapt to change in the environment. For example, can you figure out how communities of microbes collaborate, compete, or even re-calibrate their genomes, when, say, the ocean becomes more acidic?

Nitin Baliga

The U.S. Department of Energy and the National Science Foundation are interested in some of these fundamental questions, which might help us better predict what might happen, if say, engineered microbes were dumped into the Gulf of Mexico to clean up an oil spill. Oil companies have a different interest—like how efficient a microbe might be at converting sugars or sunlight into oil.

Baliga sees plenty of tricky scientific questions that need to be asked in all of those scenarios.

“Whichever organism you want to use for oil, whether it’s algae, cyanobacteria or something else, preferably you’d capture free solar energy, but then you run up against the efficiency of how much light energy gets sequestered, and how you harvest it. The first challenge in an open pond is that it’s hard to maintain monocultures.” That means you create a thriving pool for other species to hop in and do other things to compete for survival, doing things other than creating the desired stream of oil. “They take over,” Baliga says.

While a controlled bioreactor might keep the opportunistic species out of the pond, and create the desired stream of oils, they are expensive, and require energy to run themselves.

In the near term, Baliga says he sees promise in bioreactor-based approaches in which yeast or bacteria like E.coli get modified to produce specialty chemicals. Quite a few biofuel companies, Solazyme among them, have sought to diversify their offerings by starting with low-volume, high-value commodity chemicals that go into products like food additives or skin creams.

“If you have good understanding of the systems biology, you can optimize the pathway so you can get not just one product, but several,” Baliga says.

Sapphire, for one, has done some interesting work in scaling up its process, and putting a lot of thought into water chemistry in open ponds, and how the algae react to the wind, and temperature variations, Baliga says.

The number of variables in the natural environment sounded almost impossible to calculate to me, and so I wondered if Baliga thinks it’s more challenging to study how microbes react in the ocean or open ponds than they do, in, say, the human body. Not so, he says—the systems of the the human body are still even more complicated.

“If you think of the number of kinds of cells, and the molecular mechanisms at play, you have 100 trillion cells in the body, and on top of that, you have 100 times as many microbial cells in the body,” Baliga says. “We need to think about these things in an abstract sense. If you think in detail, you’ll get lost and overwhelmed easily. You have to ask questions that can be addressed.”

In the environmental health work, you can sequence various microbial organisms, count various kinds of microbes in the environment, and build “reasonably good models of who lives there, and what their genomes look like, and how they work with each other,” Baliga says.

I’m not sure if that means we’ll see progress with biofuels before we see the systems approach pay off with personalized medicine that ISB president Lee Hood often talks about. And Baliga was careful not to overpromise about the payoff from all this systems biology understanding. He’s not going so far as to say biofuels will ever truly dominate energy production like fossil fuels do today. The smart grid, solar power, wind, and biofuels all need to play a role, he says. “These are complex problems, and you need a cocktail of solutions,” Baliga says.

Luke Timmerman is the National Biotech Editor of Xconomy, and the Editor of Xconomy Seattle. You can e-mail him at, or follow him at