Open Source Synthetic Biology

Today I watched this video at Edge from last year, and read the unabridged transcript that follows. It's a one-sided interview with Drew Endy, a passionate assistant professor of Bioengineering at Stanford. It's a light, easy interview to digest; he mostly stays focused on long-term goals rather than the details of their current research.

But the talk encompasses most of the range of feelings that I have about genetic and biological engineering, and added some new hopes and fears. I'll cover a few excerpts from the video, hopefully briefly, that I think will illuminate my bioengineering angst. If you want a summary, skip to the bottom.

The big question, to come back to it, is, how do we make biology easy to engineer, and then the parallel question that comes along with that is, what are the consequences of success?

Let's not talk about it, let's actually go do it, and then let's deal with the consequences in terms of how this is going to change ourselves ...

There's nothing specifically wrong with "shoot first, ask questions later", but it doesn't exactly make me comfortable, you know?

... That's an example of what an engineer would call reliable physical composition. Take two objects and put them together. The other thing that happens is when you have the nut and the bolt together as a composite object, when you pull on the nut, it stays put. It doesn't come flying off. The composite object has the expected behavior, it doesn't have some emergent property. That's reliable functional composition. The function of the two things when you put them together is what you expect. [...] Engineers hate complexity. I hate emergent properties. I like simplicity. I don't want the plane I take tomorrow to have some emergent property while it's flying.

He doesn't explicitly say it here, but one of the big question marks of modern genetic engineering is emergence. If you add a gene to a corn plant to make it more resistant to a particular pesticide, how can you tell what the side effects of that gene might be? Well, you have no idea. It'll probably do nothing. It might interfere with the expression of another gene, or have effects that only emerge on a large scale. As he says later, "I would want one behavior, and when I went to make the change, exactly the opposite would happen."

Perhaps the reactions being stimulated today around this technology are a direct result of the fact that the people who are promoting the technology in this way tend to favor exclusive ownership, limited access, and present themselves as God-like creators; as opposed to, we're constructing things, we could use your help, anything we do today is going to pale in comparison to what's coming, so let's figure out how to work together on this.

People conversant with the software patent debate might find this familiar.

The Open Source world is one thing; if you're trying to invent a language for programming DNA, having a proprietary language seems stupid. If Oxford University had supported privatization of the English language hundreds of years ago, the dictionary they made wouldn't have been so useful. And so to a first approximation, there's going to be a core collection of standardized genetic objects that can define families of languages people can use to program DNA. And those have to be made a public resource.

Well, I think it sounds practical. I linked to them above, but what he's talking about here is collecting BioBricks (pre-assembled cellular parts with well-understood behavior) and organizing them into an open-source Registry of Standard Biological Parts which anyone can use to make whatever they want. They've got about 2000 parts so far.

I'd estimate the cost of synthesizing the DNA of every human being on the planet that'll be born in the next year at $10 trillion dollars. That's 20 percent of the world's economy. That number is dropping by about a factor of two every 12 to 18 months.

Gattaca is possible in less than 20 years, is basically what he's saying.

Tom had self started in biology five years earlier and is now, in addition to being one of the best engineers I've ever met, one of the best microbiologists I've ever met. Tom was interested in it from his own perspective, having mostly to do with building computers . We need to use biology not to be a computer, but rather to build our computers, because we're going to need to put atoms exactly where we want ...

He goes into a little more detail, but this brings up the idea of using bioengineered microbes as easily programmable nanomachines.

In summary: traditional genetic engineering, where you modify the DNA of existing organisms, is messy and somewhat unpredictable. Endy and others are promoting synthetic biology, in which you build totally new organisms from the ground up. They're putting together a collection of open-source biological Legos that make it easier to create your own organisms to do specific things.

Some of the possible uses of this incredibly versatile approach are mentioned above: synthesizing human DNA to select desirable traits, using viruses as nanomachines to construct computers (or anything) on an atomic level.

Another thing they've started doing is rewriting or refactoring the genetic code of existing organisms (in this case they ended up replacing 30% of the virus' genome) to make it neat, organized, and efficient, instead of the jumbled spaghetti it is now.

Finally, they have an international undergraduate competition called iGEM; this year they expect over 1200 participants. As Endy says near the end of his talk,

It is interesting for me to learn how difficult it is for folks to appreciate what an exponential technology really implies. The fact that sequencing goes from approximately zero to human genomes in ten years. [...] it's doubling every year. How do you actually live in a world where you're surfing that exponential in a way that's constructive and responsible? Very few people get that.