In 1991 he published a 64-page review article on neutron scattering in biology. The last sentence referred to plans, then on the drawing board at Oak Ridge National Laboratory, for a new reactor-based neutron source called the Advanced Neutron Source, concluding: "We await their fruition with some excitement."
Ultimately, plans for the ANS were dropped and subsequently replaced by the accelerator-based Spallation Neutron Source, whose first neutrons flew last spring. Meanwhile, Smith was developing his résumé as an internationally renowned molecular biophysicist with a penchant for combining neutron scattering with high-performance computer simulation to understand the physics of biological molecules. Smith built two successful interdisciplinary groups, first at the French national laboratory at Saclay, near Paris, and then at the University of Heidelberg. Having turned down offers of professorships in six countries, last fall Smith became the first University of Tennessee-Oak Ridge National Laboratory Governor's Chair and Director of the ORNL Center for Molecular Biophysics.
Smith says he was attracted to Oak Ridge both by the SNS and by the establishment of the Laboratory's Leadership Computing Facility, which will this year become home to one of the fastest open-science supercomputers in the world.
Q. Briefly describe your research background.
I decided to leave Britain at the age of 22. The choice was then either to go to graduate school at Yale or to work in the south of France, at the Institut Laue-Langevin in Grenoble, which at the time had the world's best neutron source. The Ph.D. work in France was quicker, the pay better, and I also liked the idea of learning a foreign language and how to ski. And I was really keen on French women! so Grenoble is where I started research into probing motions in proteins with neutrons, and I have been involved in this field for the last 25 years. The results of the neutron experiments in Grenoble needed interpreting, which I learned to do with computer simulation. We initiated a research field that combines these two techniques and is now clipping along nicely. I subsequently spent four wonderful years learning computational chemistry at Harvard and then tried to reproduce the creative atmosphere there in my own two research groups, in Saclay and Heidelberg.
Q. What are some specific ways you'll be able to apply the Spallation Neutron Source and Leadership Computing Facility to your research?
With a neutron source, like the SNS, which instruments you build determines what kind of science you can actually do. SNS has decided to build instruments that will aid in the study of materials. That is perfect for biology, because biology is, in a way, just the study of particularly beautiful and complex materials. So many of the planned instruments will be useful to us. To interpret the experiments we will need to do large-scale simulations using the Laboratory's supercomputers, from which we will calculate the neutron scattering spectra and understand them. High-performance computing will also be useful for understanding a range of other problems not directly accessible with neutrons.
Q. How will your research aid in bioenergy production?
I'm involved in research related to hydrogen production and bioethanol. We hope to understand how hydrogenase enzymes work. These are very clever enzymes that enable bacteria to evolve hydrogen and use it as a metabolic agent. You just take one mole of this enzyme and in only two hours you can produce enough molecular hydrogen to fill the main liquid hydrogen tank of the space shuttle. We need to understand how hydrogenases work and then build robust synthetic nanoscale mimics. For bioethanol production, if one can chew up plant cell-wall cellulose into sugars then one can make ethanol out of the sugars pretty easily. The problem is plant cell walls are recalcitrant to being chewed up. So we would like to understand what about cell walls makes them recalcitrant, by combining computer simulation and neutrons again. Now microbes produce special molecular machines that do overcome cell-wall recalcitrance and we want to find out how they work, too. Once you've understood these processes, you can think about doing them yourself.
Q. What other areas of research are you involved in?
We've been involved in designing an instrument based on single-molecule spectroscopy that detects many cancers very early and works very well. We are also involved in AIDS research, designing vaccines using computer simulation. Another longstanding interest of ours is another field of research that the Department of Energy is potentially interested in, the atomic-detail physics of photosynthesis—biological light-driven energy transformation. For example, one particularly interesting purple protein absorbs light and then uses the energy to pump protons across a membrane. We are very interested in finding out how that works, and the principles we learn could also be useful in fuel cell design. More generally we want to understand enzyme reactions and how enzymes use chemical energy to make molecular machines work, such as the proteins in muscle contraction, vision or cancer-cell growth. We are also trying to find out why cholesterol was chosen by nature to be incorporated into biological membranes, rather than some other similar molecules that are easier to make.
Q. Will you teach classes at the University of Tennessee?
Yes, certainly. Molecular biophysics sits exactly at the junction of biology, physics, chemistry and computer science, and so here at ORNL I find myself positioned among four directorates—those of biological and environmental sciences, computational sciences, physical sciences and neutron sciences. And I have much in common with all of them. Likewise, for teaching we require students with strong interests in physics and chemistry, who are also okay with math and computers, but are driven by a desire to understand biological systems. What I'd like to do is set up an international, elite UT-ORNL graduate program in molecular biophysics that I would teach with the ORNL research staff and UT junior faculty who will be associated with my Governor's chair. I am sure we could attract top students from various backgrounds who have the mental agility for strongly interdisciplinary study. I think an important part of my work will be to help stimulate interaction between UT and ORNL. Both have a lot to win from forging stronger links. Oak Ridge needs more hyperactive, caffeine-drinking, midnight-oil-burning graduate students to get the research done, and UT needs to make optimal use of the facilities here in order to elbow up in the university research rankings. Both badly need this synergy.
Q. You are an avid soccer fan and a skilled player. What is your take on American football?
I'll tell you one thing: no european has any idea what college football is about. I'll lay a quid that if you went to any Frenchman in a Grenoble brasserie and asked, "What if I were to float the idea to you of 104,000 people crowding into a stadium in east Tennessee seven times a year, all wearing strident orange and fervently identifying with a bunch of inexperienced college students running around wearing motorcycle helmets?" he would retort, "Are you kidding me? No way!"
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