Tuesday, July 29, 2008

The youngest DNA author?

Earlier this year an interesting opportunity presented itself at the DNA foundry where I am employed. For an internal project we needed to design 4 stuffers. Stuffers are the stuff of creative opportunity!

A stuffer is a segment of DNA whose only purpose is to take up space. Most commonly, some sort of vector is to be prepared by digesting with two restriction enzymes and the correct piece then purified by gel electrophoretic separation and then manual cutting from the gel. If you really need a double digestion then the stuffer is important so that single digestion products are resolvable from the desired product; the size of the stuffer causes single digests to run at a discernibly different position.

Now, we could have made all 4 stuffers nearly the same, but there wasn't any significant cost advantage and where's the fun in that? We did need to make sure this particular stuffer contained stop codons guarding its frontiers (to prevent any expression of or through the stuffer), that it possess the key restriction sites and that it lack a host of other sites possibly used in manipulating the vector. It also needed to be easily synthesizable and verified by Sanger sequencing -- no runs of 100 As for example. But beyond that, it really didn't matter what went in.

So I whipped together some code to translate short messages written in the amino acid code (obeying the restriction site constraints) and wrap that message into the scaffold framework. And I started cooking up messages or words to embed. One stuffer contains a fragment of my post last year which obeyed the amino acid code (the first blog-in-DNA?); another celebrates the "Dark Lady of DNA". Yet another has the beginning of the Gettysburg Address, with 'illegal' letters just dropped. Some other candidates were considered and parked for future use: The opening phrase to a great work of literature ("That Sam I am, That Sam I am" -- the title also work!), a paen to my wagging companion,.

But the real excitement came when I realized I could subcontract the work out. My code did all the hard work, and another layer of code by someone else would apply another round of checks. The stuffer would never leave the lab, so there was no real safety concern. So I offered the challenge to The Next Generation and he accepted.

He quickly adapted to the 'drop illegal letters' strategy and wrote his own short ode to his favorite cartoon character, a certain glum tentacled cashier. I would have let him do more, but creative writing's not really his preferred activity & the novelty wore off. But, his one design was captured and was soon spun into oligonucleotides, which were in turn woven into the final construct.

So, at the tender age of 8 and a few months the fruit of my chromosomes has inscribed a message in nucleotides. For a moment, I will claim he is the youngest to do so. Of course, making such a claim publicly is the sure recipe to destroying it, as either someone will come forward with a tale of their toddler flipping the valves on their DNA synthesizer or will just be inspired to have their offspring design a genome (we didn't have the budget!).

And yes, at some future date we'll sit down and discuss the ethics of the whole affair. How his father made sure that his DNA would be inert (my son, the pseudogene engineer!) and what would need to be considered if this DNA were to be contemplated for environmental release. We might even get into even stickier topics, such as the propriety of wheedling your child to provide free consulting work!


Ryan said...

Grat work on getting your son involved!

Randy said...

I'm really enjoying your blog. Your posts are informative, and you always manage to inject a little thought provoking fun into the mix. It's neat that you let your son have some fun on this project as well. Thanks, Randy