The Last Word On Nothing

The first time I heard about bacterial photography, I thought, “Wow, that’s so rad! I’m not sure what they’re gonna use it for, but anyway, it sure is cool!”

The bacterial photography project involved transplanting a light sensor into an Escherichia coli bacterium so that it could take “pictures” in Petri dishes. It sprang from a field called synthetic biology, in which scientists engineer biology to perform new functions.

Here is a sampling of some of the other things that synthetic biologists have done since the bacterial photography project: they’ve made cheese from the bacteria that grow on human skin. They’ve engineered yeast to make lysergic acid, the precursor of the psychedelic drug LSD. They’ve made plants whose leaves change color when they detect explosive chemicals, and bacteria that digest the pesticide Atrazine.

These are not necessarily the accomplishments that synthetic biologists point to when extolling the enormous potential of their work. Synthetic biologists mine biological pathways for useful components, then wire these components together to make new biological circuits. “The hallmark of synthetic biology,” said one of the field’s leaders, Chris Voigt, at the fifth synthetic biology meeting last week, is a “lack of respect for species barriers.”

So far, the field’s poster child is a biotechnology company called Amyris, in Emeryvile, Calif., that engineered yeast to make the antimalarial drug artemisinin, which is currently derived from the wormwood plant. In 2008, Amryis signed a partnership with the drug giant Sanofi, which is racing to scale up synthetic production of synthetic artemisinin and bring it to market by the end of this year to remedy a worldwide shortage of this lifesaving drug. Amyris’s next project is production of the cosmetic ingredient squalane, currently harvested from endangered deep-sea sharks.

Amyris’s artemisinin is the example that proves the promise of synthetic biology: that by applying engineering approaches to biology, scientists will be able to make better, cheaper drugs, biofuels, materials and other goods. But the artemisinin example is starting to feel a bit worn, because the field has not accomplished anything as remotely useful as making synthetic artemisinin for half a decade. Last week, at the synthetic biology meeting, which ran from 15 to 17 June at Stanford University in Palo Alto, Calif., Emory University’s Justin Gallivan, creator of the atrazine-eating bacteria, told his colleagues that this is becoming a problem. “We need to move beyond parlor tricks. We need to understand how to make these systems more robust,” Gallivan said.

Everyone in the field realizes this, and would love to devise the next synbio “killer app.” But there’s a yawning gap between what synthetic biologists dream and what they can do. One of the founders of the field, Stanford’s Drew Endy, laid this on the table at the opening of the meeting last week. Referencing the seven-word description coined by Eric Lander to describe the culmination of the human genome project in 2003 (“Genome: Bought the book. Hard to read”), Endy offered his own seven-word description of the state of the synthetic biology field today: “Synthesis: can write DNA. Little to say.”

Synthetic biology now has more tools at its disposal than ever before, and it is clearly making progress: everyone at the meeting last week was impressed by how much higher the “data to hype” ratio was compared to the last synbio meeting, which took place in Hong Kong in 2008. But it’s still difficult to use different tools together to assemble life on an industrial scale,  and this must happen if synthetic biology is to live up to its billing. The question is whether this will ever happen if scientists continue working as they are, each working on their own projects in small-scale academic labs, or whether this will only happen if companies come along to industrialize the field.

The argument in favor of industrialization is obvious: it’s the most efficient way to develop efficient manufacturing systems from disparate parts. The argument against it is, oddly enough, bacterial photography.

One of the students who worked on the photographic E. coli project, Jeff Tabor, is now an assistant professor at Rice University in Houston, Texas. In 2009, Tabor and other colleagues led by Andy Ellington of the University of Texas, Austin, refined the bacterial photographic film they had made so that it could detect the edges between light and dark. It turns out that edges are crucial in biology: organisms organize their bodies by creating gradients of chemicals that set the pattern for their physical development. Tabor was just awarded a multimillion dollar grant from the National Science Foundation to use his edge-detecting technology to study how organisms develop.

“Science is not a linear process,” Theresa Good of the U.S. National Science Foundation reminded the synbio meeting last week. A certain finding that seems off the wall might actually turn out to help us understand something new about biology, and that would likely be lost in the guts of some industrial-scale SynBio, Inc. In time, of course, the field must move beyond gee-whiz one-off projects. But it’s tricky to predict whether any one feat is a parlor trick – or a proof of concept.

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Image: bacterial “coliroid” image made using light-sensitized E. coli bacteria. Ellington/UT/UCSF