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GHARIB: I think one can claim the Caltech version has converged with something that we think will address very certain principles of bioengineering, biosynthesis and biomimetics, and learn from nature's design, to come up with physics, analysis, and better devices. But you know, we can't just jump into it. You cannot just mimic nature. You have to first understand it. You have to mimic both function and, for example, geometry, in terms of reality. So, that's why we put together this program. It's not 100% complete, but there are different aspects that require a strong synergy between biology, engineering, chemistry, chemical engineering, and physics. Paul and Steve can add to this from their perspectives...

STERNBERG: As an experimental biologist, I'm trying to reverse engineer nature, to look at these organisms, to figure out how they do the wonderful things they do. And at some point, you say, we think we understand how it works. But, the proof of that understanding is turning it into engineering. And really, that's part of the excitement here—to demonstrate that for certain systems, whether they be molecular systems or gadgets, we can make something that's new.

QUAKE: Bioengineering at Caltech is M.S.G.: molecules, systems, and gadgets. Those are the three broad categories that capture what the central people in our Option are doing. In the area of molecules, we have some really clever and sharp faculty who are interested in this problem of molecular design, particularly for biological molecules. So Nature, the tinkerer and the designer, she's handed us 200,000 proteins to play with, but people at Caltech aren't satisfied with that. They're trying to come up with very clever ways to make new molecules. We have a very strong group in this respect. It's cool because they have a nice interplay between biology and engineering. For example, one of the ways Frances Arnold [Dickinson Professor of Chemical Engineering and Biochemistry] tries to design is to design by using evolution, which is not something that's in a normal engineering tool kit. But she's taking the principles of biological evolution and applying them to protein design.

Guys like Steve Mayo [Associate Professor of Biology and Chemistry; Associate Investigator, Howard Hughes Medical Institute] are trying to use very sophisticated computational methods to do evolutionary design. Systems engineers are good at making systems and have worked out a number of principles for doing that. Nature has done it, too, but historically biologists just haven't really appreciated that part of nature's designs. This has become a very interesting area to look at: to try to understand how biological systems function as a whole. Many people think that maybe nature uses similar design principles that engineers have worked out and they're trying to push that analogy and see how far it will take them.

GHARIB: These collaborations between biologists and engineers are not new. They work together on devices and approaches to systems. All the devices that helped the genomic revolution were designed by engineers and biologists working together. But, now that we have sequenced DNA, we ask ourselves how to put it back together in order to reconstruct big molecules, and eventually organs and systems.

Medical robot prototype. The goal of this device is to access, in a minimally invasive fashion the portions of the small intestine that cannot be accessed by conventional endoscopes.

QUAKE: The third area is gadgets. That's what engineers do--they make gadgets. And again we have a very strong group at Caltech. Guys like Mory are trying to take lessons from nature and look at the fundamental physics of how nature makes devices. How a growing heart develops, and how a heart pumps.

GHARIB: How does nature pump in general?

QUAKE: So he's trying to look at nature, understand what nature does and then try to engineer man-made gadgets that use those principles. Because in many cases, they're actually quite transposable and useful.

ENGENIOUS: So it's a very different viewpoint from a strict engineering perspective.

GHARIB: That's right. And also different from other bioengineering or biomedical programs because most of them try to build the pump that works inside someone's body. They build micro-fluidic devices without looking at the concept in nature. They have good solutions, but that's different from what we're trying to do.

ENGENIOUS: Look at nature and work backwards? So you're taking a much more biologically focused approach?

STERNBERG: Philosophically biological in approach, yes, but the outcomes might be different. You don't actually have to make it look like something in nature. You could use the principle, a design principle, and then come up with something new.

QUAKE: There's a very famous example of that which was done here at Caltech in the '80s. Done by the CNS group [Computation & Neural Systems], right? The general idea was trying to understand how the brain computes. The mathematical, physical models—neural networks—were sort of discovered and explored, and the pioneers were here. At the end of the day, I think they weren't that useful for understanding biology, but the principles that came out of them have found a number of applications in the engineering world. And so you'll find neural nets all over the place now as a computational tool. It's something that was inspired by biology, but it's got applications in engineering.

STERNBERG: But again, the interface is pretty interesting. Here's a little historical project that led to gadgets: Shuki Bruck [Gordon and Betty Moore Professor of Computation and Neural Systems and Electrical Engineering], some students, and I were trying to model certain aspects of development and function of a worm we were working on. We realized immediately that we were not collecting data fast enough. To get a good model you need a great deal of data. And the biologists, you know, are used to painstakingly doing it by themselves without any gadgets.

So we started to design something that could look at the worm to see how it wiggles, and where it moves in a sine-like wave. We developed a system that's proven to be very useful to quantitatively obtain information about what the worm looks like as a function of time. We could see how it wiggles and you can basically use that information to do the genetics of a sine-like wave, and try to model it.

QUAKE: Science always advances on gadgets. There's a long history of this. You can look in physics how it's happened. Physics in the 20th century has been driven by essentially two big projects from World War II. One is the radar lab at MIT. The development of microwave radar led to the development of the maser, development of the laser, atomic clocks, the precision frequency standards, high precision tests of QED [quantum electro-dynamics]. You can trace it all very clearly back to the development of laser technology. And likewise Los Alamos had a huge influence on the development of particle physics.

GHARIB: Every time you have a new device, it leads to new understanding and, boom, new information comes.

STERNBERG: Much of this is on the analytical side and that's very useful. And then as you start to build things, you can say, all right, we have this device which has part of a living organism. Now we can start engineering. We can use things that we know that we've done in the laboratory to make this organism do something to our specifications. It's a very different kind of approach and there are some simple things you may find out that you never even asked about before—low hanging fruit. >>Next Page

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