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Credit: Mark Ostow

David Berry, 29

Renewable petroleum from microbes

Flagship Ventures

David Berry is sitting in a midtown Manhattan coffee shop, taking a break from a carbon-trading conference across the street, when a news report on the wall-mounted television catches his eye. The CNN dispatch describes how scientists have shown, in animal experiments, that Viagra might be used to alleviate symptoms of jet lag.


"It's interesting," Berry says, chuckling, as his eyes wander back to the screen. "We were talking about a year ago of using Viagra to treat jet lag." One side effect of Viagra widely reported in the medical literature has been the perception of blue light, he continues, and blue light has also been shown to reset circadian clocks in humans. "I like when I see these things actually come true," he says.


It's one thought that never went beyond a blue-sky conversation among his venture capital colleagues. But it reflects how easily ideas come to Berry, a Harvard-trained MD who earned his PhD through the Biological Engineering Division at MIT and for the past two years has been a principal in the venture capital firm Flagship Ventures in Cambridge, MA.


Since receiving his bachelor's degree from MIT in 2000, Berry has helped develop a way to treat stroke, thought up a new approach to cancer therapy, and, most recently, created a system to genetically engineer microbes to produce biofuels. He has 21 patent applications pending, and his intellectual curiosity touches on therapeutic medicine, diagnostic devices, and now, most notably, alternative energy technologies. His innovations in energy form the conceptual basis of LS9, a California-based renewable-petroleum company that has received $5 million in venture funding from Flagship and Khosla Ventures in California (see "Better Biofuels," July/August 2007).


Berry points out that a number of the pioneering biotech companies were thinking about energy and biofuels, specifically ethanol, in the 1970s. "What's interesting," he says, "is that, as a field, we're making a full circle and going back to the things biotechs thought about way back then. But now we're bringing new technological tools to make the same problems more tractable."


On the first working day of each week, Flagship Ventures holds a group meeting to review investments and discuss new ideas. One day this May, David Berry was the youngest, and probably the most earnest, of about a dozen VCs gathered in Flagship's seventh-floor conference room, with its grand view of sailboats plying the Charles River. The meeting ran a little long, and Berry apologized when he finally emerged. "We were talking about a potential new idea in drug delivery," he explained. Although the details of that technology remained discreetly fuzzy, it was very clear that these are heady, palpably exciting conversations for him. "You're discussing some of the hottest, most compelling new technologies around," he says. "I'm having a blast."


Berry took a seat at that conference table with no formal training in finance but a track record in technology. In gradu­ate school, he began tinkering with a molecule that could pass through the blood-brain barrier and showed promise as a stroke treatment. The protein, an engineered version of fibroblast growth factor 2, produced functional improvement in a test animal modeling symptoms of stroke, and it brought out in Berry another quality conducive to innovation: restlessness. Berry realized that studying the protein could lead to a PhD far more quickly than most projects, and he seized the occasion. He got his PhD in 2005 (finishing his MD a year later), and the biotech company ViaCell briefly attempted to develop the molecule as a drug.


Berry also experimented with ways to reversibly attach polymers to sugar molecules and came up with a way to kill cancer cells by binding polymers to heparin, the well-known blood thinner. Berry's polymer packaging makes cancer cells absorb heparin more quickly; once inside the cells, the heparin disrupts biochemical pathways, ultimately leading to cell death. The technology garnered the attention of Momenta Pharmaceuticals, a biotech company in Cambridge, MA; Berry garnered another publication, and another patent application.


"What makes David unusual is that there's nothing that's going to stop him," says Robert Langer, a chemical engineer at MIT in whose lab Berry studied. "He has no fear. He's willing to tackle any idea, and he has lots of ideas. The breadth of his scientific curiosity and his belief in himself are pretty remarkable for somebody his age."


In 2004, Berry had no greater ambition than to run an academic lab, develop new technologies, and hustle them out into the commercial world. But then, in 2005, Flagship Ventures sought his input on a life science company it was starting. By the end of the year, that consulting job had evolved into an invitation to join the firm as a principal. In Flagship's emphasis on developing the core concepts for new companies in-house, Berry saw an irresistible opportunity to jump-start innovation by funding it at its earliest stages. Although Flagship's previous startups tended to focus on traditional life sciences like genomics, the company was increasingly interested in taking biology in a new direction: energy. "Back in 2005," Berry recalls, "we were saying, 'What would be interesting in the fuel space?'" The project ended up in Berry's hands.


Berry's goal was nothing less than "to develop a novel and far-reaching solution to the energy problem." In col­laboration with genomics researcher George Church of Harvard Medi­cal School and plant biologist Chris Somerville of Stanford University, Berry and his Flagship colleagues set out to do something that had never been attempted commercially: using the tools of synthetic biology to make microörganisms that produce something like petroleum. Berry assumed responsibility for proving that the infant company, dubbed LS9, could produce a biofuel that was renewable, better than corn-derived ethanol, and cost-­competitive with ­fossil-based fuels.


Ethanol is the most common biofuel, but many observers, including Berry, have reservations about corn-based ethanol as a long-term solution to the fuel crisis. Ethanol has only about two-thirds as much intrinsic energy as petroleum, and producing it requires considerable agricultural resources.


Berry took the lead in designing a system that allowed LS9 researchers to alter the metabolic machinery of ­micro­örganisms, turning them into living hydrocarbon refineries. He began with biochemical pathways that microbes use to convert ­glucose into energy-storing molecules called fatty acids. Working with LS9 scientists, he then plucked genes from various other organisms to create a system of metabolic modules that can be inserted into microbes; in different combinations, these modules induce the microbes to produce what are, for all practical purposes, the equivalents of crude oil, diesel, gasoline, or hydrocarbon-based in­dustrial chemicals.


Along the way, Berry and his colleagues had to soup up the activity of certain genes to increase the output of specific intermediate molecules. They also had to determine how to selectively block other metabolic pathways so that their microbes would stay focused on producing hydro­carbons. And they figured out how to make the microörganisms secrete the final product in such a way that it could easily be collected.


"David is responsible in large part for LS9's intellectual-property real estate," says Noubar Afeyan, Flagship's CEO. "If you strip away his contributions, there's no company."


Since the technology is proprietary and still in the early stages of development, Berry won't identify the types of organisms and the specific cellular processes involved. LS9 has been optimizing its system and trying to increase the yields of its designer biofuels at its California facility. Current yields in the lab are an order of magnitude lower than those for ethanol produced from cellulose, Afeyan says, but the company hopes to reach a comparable yield within a year.


Nonetheless, LS9 has no products so far and many ­hurdles to surmount. Berry's system, for example, is designed to exploit glucose-based feedstocks such as cellulose. Berry says he is "agnostic" about what source of cellulose might drive the LS9 system on an industrial scale; he lists switchgrass, wood chips, poplar trees, and Miscanthus, a tall grass similar to sugarcane, as potential sources of biomass. But a cost-­effective and efficient source of cellulose is one of the more significant bottlenecks in the production of any biofuel.


Despite these uncertainties, Berry's method offers many of the advantages of biofuels in general. The raw feedstock would be agricultural and homegrown; it would be renewable; and it would, in principle, provide a more environmentally friendly source of energy than traditional crude oil (which requires smoke-belching refineries). With microbes doing all the work, fuels could be produced in large fermentation tanks of the sort used by biotech companies.


The biological synthesis of hydrocarbons is "a tech­nology with really game-changing potential," Berry says. "It has security benefits. It has sustainability benefits. And the value of that, on top of a cost benefit, makes it a very compelling technology." And one of the most compelling parts of the story behind that technology is that it was developed by a doctor in his 20s.



Credit: LS9

David Berry used biochemical pathways from a number of organisms to design synthetic bacteria (left) that can produce and secrete renewable petroleum fuels. The bacteria are grown in fermentors (right); because the petroleum products are organic, they separate from the aqueous nutrient mixture that allows the bacteria to grow without the use of complex cultivation techniques.

--Stephen S. Hall

2007 TR35 Winners

David Berry

Renewable petroleum from microbes

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Rachel Segalman

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