Tuesday, May 29, 2007

Wimpy Synthetic Organisms?

Synthetic biology is on the cutting edge of molecular genetic technology. The idea that a library of interchangeable biological parts - coded in DNA - can be used to create all kinds of different living machines. As a 2005 Wired article poinsts out, this is more engineering than biology.
If the notion of hacking DNA sounds like genetic engineering, think again. Genetic engineering generally involves moving a preexisting gene from one organism to another, an activity Endy calls DNA bashing. For all its impressive and profitable results, DNA bashing is hardly creative. Proper engineering, by contrast, means designing what you want to make, analyzing the design to be sure it will work, and then building it from the ground up. And that's what synthetic biology is about: specifying every bit of DNA that goes into an organism to determine its form and function in a controlled, predictable way, like etching a microprocessor or building a bridge. The goal, as Endy puts it, is nothing less than to "reimplement life in a manner of our choosing."
For an overview, check out the comic "Adventures in Synthetic Biology" and Discover's December interview with chemical engineer and synthetic biologist Jay Keasling.

When bioengineered microorganisms show up in science fiction, they often threaten to slip from our control and run amok - think of the noocytes in Greg Bear's Blood Music or the polluting bacteria in Neal Stephenson's Zodiac (among many examples). Computer science professor and science fiction writer Rudy Rucker doesn't think we should worry so much. in his essay in this week's issue of Newsweek, he argues that any organisms we build will have a hard time competing out in the wild.
One big worry is what nanotechnologists call the “gray-goo problem.” What’s to stop a particularly virulent SynBio organism from eating everything on earth? My guess is that this could never happen. Every existing plant, animal, fungus and protozoan already aspires to world domination. There’s nothing more ruthless than viruses and bacteria—and they’ve been practicing for a very long time.

The fact that the SynBio organisms are likely to have simplified Tinkertoy DNA doesn’t necessarily mean they’re going to be faster and better. It’s more likely that they’ll be dumber and less adaptable. I have a mental image of germ-size MIT nerds putting on gangsta clothes and venturing into alleys to try some rough stuff. And then they meet up with the homies who’ve been keeping it real for a billion years or so.

Rucker may be right that synthetic organisms would lose a fight with critters that evolved naturally, but they won't have any natural predators either. The fact that antibiotics are used fairy indiscriminately all over the world just might open up niches in which the simpler synthetics can thrive. To my mind it only makes sense to take precautions, in case our creations turn out to be tougher than expected.

Read Rucker's whole essay for more about the cool stuff synthetic biology could be used for.

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6 comments:

Ford said...

I agree that any organisms we design from scratch (assuming this becomes possible over the next few decades) are unlikely to take over. But as long as we're designing them from scratch anyway, why not use a different genetic code, so they can't exchange genes with natural species. This would also let us design viruses that would kill them (if necessary) without infecting any natural organism, just like a Designer could have made us completely immune to animal viruses (smallpox, AIDS, flu) by giving us a different genetic code, so their viruses couldn't replicate in our cells. Of course, doing so would also have made it really obvious that we were created independently of other life, which would probably have made us all worship the Designer, who probably has better things to do than to listen to adoring groupies. Ever read Microcosmic God?

Peggy said...

Making life based on a different chemistry than our own might prevent some of the potential problems, especially if we could design predators (viruses) that would specifically kill them. However, I think it would be extremely difficult to make organisms that use a completely different code. It's not just creating a code that works as effectively as the one we already have - it's redesigning the cellular machinery that "decodes" the DNA, including the enzymes that replicate the DNA, the enzymes that transcribe the DNA into RNA, the ribosomes that translate the RNA into protein, etc. And it's not just proteins. The nucleic acids involved in this process, such as ribosomal RNA and the amino-acid carrying transfer RNA would have to be rebuilt too.

Synthetic biologists are still just learning how to use the system that's already in place to create the gears and knobs (and enzymes) they design, so I'd say creating a whole new system from scratch is not going to happen anytime soon.

Peggy said...

Also, just to add: back in mid-1970s, when genetic engineering was in its infancy, a group of scientists and interested officials met at the Asilomar Conference Center in California. The outcome of the Asilomar conference was a set of strict guidelines for the use of recombinant DNA technology. One of guidelines was that only bacteria that are "unable to survive in natural environments" should be used. That's why the common lab strains of E. coli are so wimpy compared to the bugs in the wild. A similar kind of restriction should probably be made on synthetic organisms - with built in nutritional or growth rate limitations they would be less likely to thrive outside the lab.

Ford said...

You seem to be thinking of something more complex than what I had in mind. I'm not suggesting using new amino acids or even changing the entire code. Just enough of it to prevent compatibility with existing life. Two step process:
1) since you're synthesizing the whole genome, you can choose to use only one of the 4 codons for glycine (say GGG)
2) then you only need to engineer the one tRNA that normally recognizes GGA to attach to tyrosine instead of glycine. Because GGA is never used, that has no effect in the designed organism, but only viruses designed using the same code could replicate in it.

Each designer could use a different variant of the above, so we could target a virus against one lab's creations without killing them all. And we'd know who to blame if something ran amok.

This sort of thing should be possible:
Anderson JC, Wu N, Santoro SW, Lakshman V, King DS, et al. (2004) An expanded genetic code with a functional quadruplet codon. Proc Nat Acad Sci 101: 7566-7571.

Peggy said...

That's an interesting article about expanding the genetic code. I'm still puzzling a bit over how you would use that to replace the entire genetic code (as opposed to supplementing the genetic code). It's not that it couldn't be done, but that it would require massive reengineering. Maybe that's the point, right?

John said...

This sort of amino acid swapping is entirely doable and is in fact being actively pursued by the Church lab. It is a purely technical problem of being able to resynthesize the E. coli genome. If you resynthesize with a codon removed--say replace all instances of AGA/AGG with CGN codons, you could then delete the argU/argW tRNA genes. You then add back, say, a seryl tRNA with an AGG anticodon, and resynthesize the genome again replace various seryl codons with AGG.