Steven Chu Interview: Conversations with History; Institute of International Studies, UC Berkeley
|Photo by Jane Scherr|
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Bring us now to where you're moving, because you are going into biology; you already touched on that earlier. You are bringing physics to the table of biology, so to speak. Tell us a little about what you're seeing. You quoted Yogi Berra yesterday about that; that it's amazing what you can see when you look ...
Well, Yogi is one of my heroes. He's the great American philosopher of the twentieth century. One of the things he said is, "You can see a lot by watching." He said other wonderful things like, "If you come to a fork in the road, take it." Or, "We may be lost, but we're making great time." And many, many other things.
But, anyway, my entrée into biology was exactly what I was telling you about. I was working on atoms -- cooling atoms, holding onto atoms with light. I said, "Well, the same technology can be tweaked a little bit, and we can maybe hold onto individual molecules with light if you play some tricks. What could you do with these individual molecules?" Naturally, I thought about biology: "Let's first try to hold onto a piece of DNA." It's strictly a technological thing, and that worked. Then I had some ideas of looking at enzymes, proteins walking up and down the DNA and seeing what you could do in biology. But first we glued little plastic spheres to the end of this big DNA molecule -- so big that it's length was something like 15, 20 microns, which could easily be seen in an optical microscope. Now, you can't really see a piece of DNA, because sideways it's only 20 angstroms, and it's not resolved by an optical microscope. But you do a trick, you put little dye molecules, florescent molecules; think of it as a string of Christmas tree lights. You can't really see the string; it's too thin. But you see the light coming from that. It shines very nicely in an optical microscope, and you can move it around. So the first thing we did was, "Okay, let's stretch it out. Wow, it's stretched out. Well, let's see if we can break it." So we stretched and stretched it harder and harder, and we couldn't break it. It's very strong along that dimension, which is good because it holds your family jewels. You don't really want to break it that way.
In the end what happened, it pulled out the optical tweezers, which were these plastic handles we'd glued onto the ends of the DNA. And it sprang back like a rubber band. It just went "boink" and crumpled back up. I said, "Holy smokes! It looks like a rubber band. Why does it look like a rubber band?" And the reason it looks like a rubber band is because when a molecule is straight, it's in a very unlikely state. If it were up to its own devices, it's being battered around by water molecules, it wants to do some random coil geometry. That's a much more likely state. So the reason it springs back has nothing to do with chemical bonds and forces pulling it back; it has to do with whether it's more likely to be found in some random coil or straight. It's the same reason if you push all the molecules of the air into a corner of the room and let go of them. They don't even have to bounce on each other. They would say, "Where would I likely be?" Well, equally likely anywhere in this room. And so the pressure evens out very quickly. That's why it would spring back like a rubber band.
I said, "Well now, I can do this on a single molecule." What things could you do there? Well, you can understand polymers. Polymers are long, skinny molecules. You can look at it one at a time. So it was a back-door entrée into polymer physics, and we did that for a half-dozen years. Finally I started getting back into biology because of the things we were finding out in polymers, I said, "Well, this is unexpected. They all are behaving differently, even though they're put in identical situations. They should do the identical thing, but they don't. Well, maybe biology is not as simple as we thought." So I said, "Okay, let's go back and look in biology." But it's the same thing, with a little technical trick or two. Usually when you're doing a technical trick or two, in the past, you say, "Well, I don't really know biology. There's a lot of fancy names, and it's a different culture, so I'll develop the technique and hand it over to the biologists." But this time I wanted none of that. You know, why should they have all the fun?
You're seeing even in these early stages of your work -- what did you call that? -- "molecular individuation," as opposed to looking at these things and reaching a conclusion on averages.
Right, right. While doing polymer experiments we found that molecules act as individuals. In fact, they act as individuals with moods. Meaning, you think you start with a molecule. It is precisely the same situation. You ask it to stretch. It would stretch in one way with a particular geometry. You put the same molecule back, same conditions, ask it to stretch to again, and it would do something differently. And we realized finally, from doing computer simulations, that the reason it was doing that is because it wasn't exactly the same, because it's bouncing around, it's in water, Brownian motion. When you ask it to do something, it's trapped in its particular state. If you asked it to do something fairly rapidly, it doesn't have time to look around and find the best path. It just does what it has to do.
Imagine you're in the New York or Japanese subway. It's very crowded. There are two subway trains; one's the right way; one's the wrong way. All you know is the doors are going to close very quickly. There's this mob pushing you from behind. You're not going to make the right decision. You're going to go with the flow. If the fork in the road comes, you're going to take it, and depending on whether you're a little to the left, a little to right of this, you're going to be pushed forward into one of the cars. The same thing was happening to the molecules: depending on the initial starting conditions, it's going to take a certain path that gets magnified. If you start with a slightly different random starting condition, you're going to take another path.
The profound thing that was affecting me is not that. That, once you think about it, is trivial. But this is an out-of-equilibrium process, and many things in biology at the molecule level might be out of equilibrium also. The way to look at it is to look with these methods, and then to think of the non-equilibrium parts. We were trained to think in equilibrium, because equilibrium things are things we could measure easily with the techniques that we had before; but now, you can follow a single molecule and say, "Okay, non-equilibrium is a major part of this. Now we get to look at it." We can look at how molecules change their shape in real time. Again, it's going back to what I learned here at Berkeley: use the new technology and have a first peek.
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