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Buckyballs and Screaming Cells

The amazing miniature world of UCLA chemist Jim Gimzewski

Finally, they play me a recording of a yeast cell that has been doused in isopropyl (rubbing) alcohol, and the sound it makes is distinctly higher in pitch than the previous samples, the clicking more sharply pronounced. "They're screaming!" Gimzewski declares. The pair want to record cells in a wide variety of conditions, including under the influence of various chemical substances. In particular they are interested in the effects of compounds that interfere with the underlying cytoskeletal structure of the cell, which Gimzewski theorizes may be causing these cellular vibrations.

I suggest that once sound artists get wind of these recordings, Gimzewski will be inundated with requests for tapes. Turns out there's already been one snooping around — perhaps this could be the basis of a new genre of noise music. "I'll play the drums," Gimzewski enthuses, riffing on a set of air bongos.

The process of recording cells is cumbersome at the moment — every time Pelling wants to alter a cell sample, he has to take it out of the AFM enclosure. So while he can record the sound of a living cell, or one that's been killed, he cannot listen to the sound of cells dying. "That's my goal. It's a bit morbid, but that's what I'm hoping to achieve." Up till now, all the cells he has listened to have been at roughly the same stage in their life cycle. The long-term goal, however, is to record yeast cells at every stage of their growth cycle and to create a sonic map of a cell's life.

Gimzewski has coined a name for this fledging science, "sonocytology" — cytology being the branch of biology that deals with cells. He is hoping this technique will develop into a new form of diagnostic tool that will enable doctors to determine by listening to cells if they are healthy or sick, young or old, or potentially even cancerous. To that end Gimzewski is teaming up with Mike Teitell, head of UCLA's Department of Pediatrics and Developmental Pathology. Teitell's lab specializes in cancers of the lymphocytes, which include lymphomas and leukemias, and he is planning a series of experiments with Gimzewski that would begin to explore the potential of this technique with mammalian cells, including cancers. Teitell admits that they don't yet know if mammalian cells will exhibit a definite sonic signature, but there is every reason to be hopeful. For one thing, mammalian cells have much thinner walls than the thick-skinned yeasts; if something as gross as yeast has a distinct signal, the chances are that a mammalian signal would be even stronger.

"You never know how anything will pan out," Teitell says. "That's the nature of experimental science." But he is preparing to "ramp up" this research ASAP and is currently trying to recruit a new postdoctoral student for that task. There is what Teitell calls "the dream scenario" where "in your wildest dreams every cancer turns out to have a unique and clear signal." Then there is "the nightmare scenario" where the signal is just a jumbled mess. And then, of course, there's the "in-between scenario" (which is probably the most likely), where you see a signal but it takes time and practice to figure out what it means. Teitell compares this new field to the early days of PET scans, a technology that is now one of our primary diagnostic tools. Whether sonocytology turns out to be the next PET or MRI, only time will tell, but when I ask Teitell when he expects to begin the mammalian work, his answer sums up the palpable excitement surrounding this research: "We want to do this yesterday."

Gimzewski is now setting his sights on even greater medical challenges. One of his research groups is currently working on a hybrid STM/AFM, which he hopes will open up further directions for cellular diagnostics. He speculates that with such a machine we might be able to watch as the pores in a cell wall open and close, and then monitor the flow of ions through the channel. Being able to observe such intricate cellular processes in situ would give doctors an enormously powerful analytical tool.

How far down might these machines take us? Until recently, most physicists believed single atoms were the smallest things we could see microscopically — any smaller and you'd have to resort to a particle accelerator. There is, however, tantalizing evidence that STMs may be able to take us inside the atom to see the orbits of individual electrons. According to quantum theory, electron orbits come in a wide variety of shapes, from the common spherical orbit to exotic dumbbell and doughnut shapes. Just as STMs have given us tangible images of atoms (objects long theorized but hitherto unseen), so these magical devices may finally help us to see figures of the subatomic realm.

It's exactly 20 years since Gimzewski began imaging atoms and molecules and, he says, we've come a long way. "But there is so much further we can go." As he speaks, I find myself thinking of Sergeant MacCruiskeen in Flann O'Brien's comic masterpiece about atomic science, The Third Policeman. MacCruiskeen has devoted himself to constructing a series of ever smaller boxes, each minuscule marvel nested inside the previous ones like a set of Russian Matryoshka dolls. After 29 boxes, MacCruiskeen is hovering at the very edge of perception, and the reader is no longer sure if he has crossed over into make-believe. The smallest of his caskets is so tiny, it is "half a size smaller than ordinary invisibility." How far can you go? O'Brien asks. Will there always be a smaller possible box? Or is there a limit to the littleness man can perceive? I put the question to Gimzewski, and his answer is worthy of MacCruiskeen himself: "When we're at the level of needing a microscope to see the microscope, then we'll know we are there."

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