TED 2008: Craig Venter’s Modest Hope

Craig Venter has been responsible for some of the most amazing revolutions in genetics. His talk this morning has the basic theme: “You ain’t seen nothing yet.” His work, he tells us, has been about taking the mystery of life and paring it down to its basics. These basic can be digitized. His question now – “Can we generate new life from this digitized information?”

Venter shows us a map of the chromosome of a very small organism, one with 500 genes. He believes we can knock out about 100 of these genes, but simplifying it any further would kill it. Is it possible to create a chromosome, synthetically, for this organism and bring it to life, allowing it to reproduce.

His work in this field started with a long bioethical review, and has recently focused on the mechanics of synthesizing DNA. This is difficult – we’ve got tools that make small strings, but the longer they get, the more errors you get. Most methods focus on making small sequences, connecting them together and error correcting. An early success involved building a 5000 letter sequence and putting it into a bacterium. The sequence coded for a virus. As the bacteria grew, they produced a virus… which killed the bacteria. “The software can build its own hardware in a bacterial system.” He told this to friends in the oil industry that this was, at root their model… and got a better laugh from them than he did from the TED audience.

Once you can write in genetic code, you can produce words, letters and thoughts – “at the moment, we’re just signing our names.” New systems are putting together much larger pieces of DNA. To get pieces larger than 72,000 base pairs, Venter and others have been studying homologous recombination, which is what nature uses to put DNA together. He points to an organism called D. Radiodurans – this organism can have its chromosomes “blown apart by radiation” and it’s able to put its genetic material back together.

The most recent success was the complete chemical synthesis of a chromosome, with 582,970 base pairs. The challenges, now, are making the complete transplant of a chromosome from one species, introduced and activated in another. In the lab, Venter has created a new, tagged chromosome, and introduced it into a new cell. There are situations in nature where new chromosomes simply coexist with existing genetic material – Venter is looking for solutions where these chromosomes can knock out existing material and essentially recreate the genetic material of the cell, to “knock out the existing traits and introduce completely new traits.” There are early successes in work in this field.

Why tinker with creating synthetic life? Because we need to. He refers to the expanding human population, our amazing oil and coal usage and the concomitant rise in global CO2 levels. “We’ve got 20 million genes discovered to date. I consider these to be design components for the future. Think of what electrical engineers have been able to do with just a few electrical components.” He points out that this field, combinatorial genomics, has gotten much more efficient, with robots that can make 1 million chromosomes a day.

His current target is “fourth generation fuels”. Second and third generation biofuels attempt to go from sugars to butanol or octane more efficiently than current biofuel strategies. In the fourth generation, he’s working with CO2 as feedstock and trying to turn it into methane. “I have the modest goals of replacing the whole petrochemical industry,” which might help lower our gobal CO2 in the process. He closes with an even less modest hope – the possibility of synthetic branches to the evolutionary tree. “I hope we survive long enough to have it happen.”

The first audience question accuses Venter of being the most dangerous human in the world, and wonders what he does for security. He points out that there are freezers of terrible toxins around the world – synthesizing new bioweapons from scratch seems like a lot of work. He points out that the E.Coli used in many experiments has a “suicide gene”, a killswitch built into the organism by early scientists so they can prevent the organism from growing indefinitely.

Venter takes questions about carbon sequestration from Larry Page – he explains that he’s less interested in burying CO2 than finding ways to turn it back into fuel. Venter explains that he’s frustrated by the modest ambitions of most industrialists – they seem to have bought into the idea of not escaing our existing carbon cycle.

Chris Anderson says, “When we spoke before, I accused you of playing God. You said, ‘We’re not playing.'” Venter agrees – he’s not playing, and this is the direction he plans to continue working in.

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