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Paul Rothemund Casts a Spell with DNA March 1, 2007

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Paul Rothemund shows how he makes DNA origami by making patterns out of protein folding in DNA.


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There's an ancient and universal concept that words have power, that spells exist, and if we could only pronounce the right words, then, whooosh! You know, an avalanche would come and wipe out the hobbits, right? So this is a very attractive idea because we're very lazy, like the sorcerer's apprentice, or the world's greatest computer programmer. And so, this idea has a lot of traction with us. We love the idea that words, when pronounced - they're just little more than pure information, but they evoke some physical action in the real world that helps us do work. And so, of course, with lots of programmable computers and robots around, this is an easy thing to picture. So how many of you know what I'm talking about? Raise your right hand. OK. How many of you don't know what I'm talking about? Raise your left hand. OK. All right. So that's great. So that was too easy. You guys have very insecure computers, OK?

So now, the thing is that this is a different kind of spell. This is a computer program made of zeros and ones. It can be "pronounced" on a computer. It does something like this. The important thing is we can write it in a high-level language. A computer magician can write this thing. It can be compiled into this - into zeros and ones - and "pronounced" by a computer. And that's what makes computers powerful: these high-level languages that can be compiled.

And so, I'm here to tell you, you don't need a computer to actually have a spell. In fact, what you can do at the molecular level is that if you encode information - you encode a spell or program as molecules - then physics can actually directly interpret that information and run a program. That's what happens in proteins. When this amino acid sequence gets "pronounced" as atoms, these little letters are sticky for each other. It collapses into a three-dimensional shape that turns it into a nanomachine that actually cuts DNA. And the interesting thing is that if you change the sequence, you change the three-dimensional folding. You get now a DNA stapler instead. These are the kind of molecular programs that we want to be able to write, but the problem is, we don't know the machine language of proteins; we don't have a compiler for proteins. So I've joined a growing band of people that try to make molecular spells using DNA.

We use DNA because it's cheaper. It's easier to handle. It's something that we understand really well. We understand it so well, in fact, that we think we can actually write programming languages for DNA and have molecular compilers. So then, we think we can do that. And my first question doing this - or one of my questions doing this - was: How can you make an arbitrary shape or pattern out of DNA? And I decided to use a type of DNA origami, where you take a long strand of DNA and fold it into whatever shape or pattern you might want.

So here's a shape. I actually spent about a year in my home, in my underwear, coding, like Linus [Torvalds], in that picture before. And this program takes a shape, spits out 250 DNA sequences. These short DNA sequences are what are going to fold the long strand into this shape that we want to make. So you send an e-mail with these sequences in it to a company, and what it does - the company pronounces them on a DNA synthesizer. It's a machine about the size of a photocopier. And what happens is, they take your e-mail and every letter in your e-mail, they replace with 30-atom cluster, one for each letter, A, T, C, and G in DNA. They string them up in the right sequence, and then they send them back to you via FedEx. So you get 250 of these in the mail in little tubes. I mix them together, add a little bit of salt water, and then add this long strand I was telling you about, that I've stolen from a virus. And then what happens is, you heat this whole thing up to about boiling. You cool it down to room temperature, and as you do, what happens is those short strands, they do the following thing: each one of them binds that long strand in one place, and then has a second half that binds that long strand in a distant place, and brings those two parts of the long strand close together, so that they stick together.

And so the net effect of all 250 of these strands is to fold the long strand into the shape that you're looking for; it'll approximate that shape. We do this for real in the test tube. In each little drop of water you get 50 billion of these guys. You can look with a microscope and see them on a surface. And the neat thing is that if you change the sequence and change the spell, you just change the sequence of the staples. You can make a molecule that looks like this, and, you know, he likes to hang out with his buddies, right. And a lot of them are actually pretty good. If you change the spell again, you change the sequence again. You get really nice 130 nanometer triangles. If you do it again, you can get arbitrary patterns. So on a rectangle you can paint patterns of North and South America, or the words "DNA."

So that's DNA origami. That's one way. There are many ways of casting molecular spells using DNA. What we really want to do in the end is learn how to program self-assembly so that we can build anything, right? We want to be able to build technological artifacts that are maybe good for the world. We want to learn how to build biological artifacts, like people and whales and trees. And if it's the case that we can reach that level of complexity, if our ability to program molecules gets to be that good, then that will truly be magic. Thank you very much. (Applause)

Courtesy of TED

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Source: TED

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