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Winter 2008
With the friendly help of guide dog Vance, Tim Cordes has navigated UW - Madison's labs and labyrinths with aplomb.

A single piano key sounds into the darkened lab, mostly empty on this late autumn evening. Tim Cordes adjusts the volume on his laptop computer and types a short command. Another note, softer and higher.

“That’s a carbon atom,” he says. “A little bit away from us.”

A few more keystrokes, and a different tone sounds, this time an organ, high and strong. “Oxygen,” he notes. “You can tell it’s higher in the structure from the pitch.”

With each click, Cordes is burrowing deeper inside the molecular structure of a protein, one of the hundreds of thousands of proteins that carry out the work of living cells. Like snowflakes, no two of these remarkable molecules are quite alike. They’re formed by unique combinations of 20 different amino acids, which fold up on top of each other like a wad of tangled spaghetti, and it’s these distinctive shapes that interest researchers such as Cordes.

A 31-year-old medical resident, who last fall completed a Ph.D. in biomolecular chemistry to go along with an M.D. he earned in 2004, he has been studying proteins for eight years, probing their atomic makeup for information that might help researchers design new drugs or combat genetic diseases. Any one of the thousands of atoms inside that tight bundle might be a clue about how the protein works—or, in the case of proteins that cause infections and diseases, how to stop them from working.

Unable to see the intricate contours of protein molecules, Cordes wrote a program to translate their structures (shown on screen) into sound.

But proteins are tiny and complex, too intricate to study with microscopes, and so science has had to invent tools to analyze them. Most protein researchers rely on computer graphics programs, which take data on the positions of thousands of individual atoms inside a protein and create a brightly colored, three-dimensional ball that scientists can rotate and probe for interesting features. These programs typically give scientists the power to see the invisible, seeking out places where drugs might bind or proteins might interact. But the models don’t do much good for Tim Cordes, for whom all of life is invisible. That’s because he is blind.

Early on in his research, Cordes tried using the graphics packages, attempting to memorize coordinates and get a picture of certain regions of a protein in his head. Two years ago, he had a better idea. A dabbling musician who’s recently been teaching himself accordion, he began experimenting with turning structure into sound, using audio tones to represent the physical arrangement of atoms along a protein’s backbone.

Now, like a biochemical Bach, he conducts a symphony in which proteins play their shapes to him, an alternative world where oxygen sounds like an organ and carbon plays the piano.

“It’s pretty intuitive,” he says, demonstrating the software. “Every visualization of a protein is just a mental abstraction anyway, so I figured, why not use sound?”

It seems likely that Tim Cordes would have stood out at UW – Madison if he had 20/20 vision. Even among graduate students, no collection of alsorans, his resume was uncommonly stoked with accomplishments. As an undergraduate at the University of Notre Dame, he logged two years at a lab bench studying antibiotics and ticked off a 3.99 grade point average while majoring in biochemistry. (His only blemish: an A-minus in Spanish.) He wrote computer programs, won awards as a wrestler and even earned a black belt in jujitsu.

That he did it all blind sometimes struck people as the least interesting of his qualities. “If I had to describe Tim, the fact that he’s blind would probably be about the 10th or 12th thing I would list,” says Adam Hofer, who assisted Cordes with his laboratory research while earning his degree in microbiology. “He has so many other distinguishing characteristics and achievements.”

In a world that often treats people with disabilities as heroes or victims, Cordes has spent much of his life trying to avoid being either. Diagnosed with Leber’s disease, a rare degenerative condition of the retina, when he was just five months old, he gradually lost his sight as a boy. By 16, his world was darkness. Yet he embraced his passions with little regard for the presumed boundaries of ability. Although he could not drive, he read Road & Track in Braille and learned the mechanics of combustion engines.He water-skied and went hiking in the wilderness. As a teenager, when he was asked on a survey to evaluate the effect of blindness on his life, he answered “minor inconvenience.”

“I just tried to do the things that I wanted to do,” he says. “Everybody has circumstances in their lives, and I think you just go forward and deal with what you’re dealt.”

In graduate school, however, Cordes sought out a path where blindness seemed anything but a minor inconvenience. He applied to the UW School of Medicine and Public Health’s medical scientist training program, a brutally demanding odyssey that involves completing both medical school and Ph.D.-level academic research at the same time. As a medical student, Cordes faced anatomy labs that required him to identify internal organs and blood vessels—he did it by feel—and patient consultations on everything from heart murmurs to skin rashes. He found a specialty in psychiatry and is now a resident in the psychiatric unit of the William S. Middleton Memorial Veterans Hospital in Madison.

For his Ph.D. research, Cordes wound up doing something no less visual in nature: creating and analyzing molecular models of proteins. Inspired by his experience studying antibiotics at Notre Dame, he wanted to explore the biology of disease-causing microbes, which he thought might connect well with his clinical training and open the door to a career in medical research. That led him to Katrina Forest, a CALS professor of bacteriology who studies pathogenic bacteria by isolating the proteins they use to interact with host cells. Using a technique known as X-ray crystallography, Forest’s graduate students grow large crystals of proteins and then bombard them with X-rays to figure out their molecular structure, a first step in designing new antibiotics or devising strategies for treating infectious diseases.

When Forest met Cordes in 1998, she was new to the faculty and had hardly worked with graduate students, much less a blind one. But she saw no reason Cordes could not contribute to her team. For one thing, he was a computer whiz who had written code since he was 10. Forest initially figured he would dive into the mountain of data created by crystallography trials and help resolve the structures of the bacterial proteins her lab was studying. But when that task was completed, “Tim’s project evolved in a different way,” says Forest. “He ended up doing a lot of lab work, which I wouldn’t have expected to be right up his alley.”

Mostly, it was. Cordes put Braille labels on bottles of reagents and installed voice software on lab equipment, allowing him to grow and purify proteins and test their functions. For times when seeing was absolutely necessary— if needed to see whether protein crystals were forming correctly, for example—the lab employed an undergraduate assistant to act as his eyes. Adam Hofer did that job for a semester, making precision measurements and occasionally describing how a reaction was progressing. But Hofer says he was the one who benefited most.

“I learned a ton by working with Tim,” Hofer says. “Sometimes I felt like he was giving me responsibilities just so I had something to do.He could pour volume, and he knew where all the reagents were.Honestly, if you walked into the lab and didn’t see Vance (his guide dog) sitting under his desk, you’d have no idea he was blind.”

But Cordes’ blindness is impossible to ignore because that fact alone makes him extraordinary in the sphere of laboratory science. In the United States, only 139 blind or visually impaired people earned doctorates in science and engineering fields from 2001 to 2005—around one-tenth of 1 percent of the total number of doctorates in those fields, according to data from the National Science Foundation. At UW – Madison, Cordes became the first blind student to earn a medical degree, and one of only two blind or visually impaired students to receive a doctorate of any kind since 2001.

This bucks a more-promising trend in access to higher education generally. The percentage of students with disabilities enrolled in U.S. universities has more than tripled in the past 30 years, from less than 3 percent in 1978 to more than 11 percent in 2004. While spurred by federal legislation requiring that disabled students’ needs be accommodated, the rise is also closely connected to a boom in technology, which is making it far easier to open doors for students with sensory or physical disabilities.

Cordes manipulates a model of a protein he studied in his doctoral research. Created by a printer that builds three-dimensional objects layer by layer, these models can help blind students create a mental picture of complex structures.

“Technology is changing everything,” says Cathy Trueba, director of UW – Madison’s McBurney Disability Resource Center, which works with faculty to accommodate students with disabilities in classes. She cites advances such as e-mail, voice-recognition software and automated document readers, all of which have made it far simpler for professors to provide learning materials in accessible formats. UW-Madison also now owns a rapid prototyping printer, a device that builds three-dimensional models of objects such as atoms, proteins or even bones, which can help visually impaired students learn spatial relationships in a more meaningful way. UW’s Nanoscale Science and Engineering Center recently used the printer to make models of nano-sized objects to interest blind students in the field.

But in scientific fields, especially, technology advances run up against long-held misconceptions about what disabled students can and can’t do—and how that may affect their careers as scientists. “I think there’s a presumption that science is not easily adaptable (to students with disabilities), but really, in most cases, it’s very adaptable,” says Andrew Hasley, a first-year student in the CALS genetics program who is legally blind. “And even when it isn’t … a blind person might not be able to see through a microscope, but he is probably smart enough to tell someone else what to look for.”

Jo Handelsman, chair of the bacteriology department, says changing these beliefs is part of the greater process of science recognizing the value of diversity. “We still have a somewhat rigid view of what a scientific community looks like and how it functions,” she says. “We need to get to the point where accommodation is not a favor, but something we do from entirely selfish perspectives, because science will be richer and more dynamic by bringing in people with different ideas.”

To Handelsman, that’s what makes Cordes’ work so striking. “There’s something about the intrinsic inconsistency of it,” she says. “It’s not like he did theoretical physics. He did visualization of structure. It’s such an aggressive challenge to the assumptions about who can do what in science.”

But Cordes isn’t so sure. Asked about the visual nature of his science, he considers the question for a moment, and then replies: “It is, and it isn’t. When you compare it to something like microscopy, where it’s all images, crystallography is far less dependent on sight. It’s essentially coordinates of numbers, and you can access those numbers by different means.

“That’s true for a lot of science,” he adds. “It’s perceived as a visual discipline in many ways, with graphs and figures and protein structures. But the data that underpin it all aren’t necessarily visual.”

Therein lies the genius of Cordes’ protein visualization software, which he calls TimMol. (The abbreviation stands for Tonal Interface to MacroMolecules, which he says only coincidentally spells its author’s name.) Since no one can see proteins anyway, why should a blind student be at a disadvantage studying them? At the protein level, we’re all blind.

Cordes’ invention, like so many, was birthed from necessity. The standard programs for studying protein structures “are sort of like playing video games,” says Katrina Forest. “You get this graphical model on the screen that you can spin around, and that helps you see it in three dimensions.” But to make any sense of the interface, Cordes had to copy data into a separate file and then try to extrapolate how atoms related to each other in his head. “I couldn’t do a whole protein,” he says, “but maybe I could think about one active site.”

TimMol’s alternative concept is quite simple. It replaces the three spatial dimensions with three different kinds of audio cues, so that atoms inside a protein become like speakers in a surround-sound system. From a given point inside a protein, a user can hear what other atoms are nearby, placing them by the pitch and orientation of the sounds they make. A higher or lower pitch indicates that the atom is above or below the user’s position. Louder means closer, while softer means farther away. Atoms to the left play in the left ear of the user’s headphones, and those to the right play in the right. To help distinguish different kinds of atoms, Cordes assigned each a a musical instrument—piano for carbon, organ for oxygen. “I picked kind of a cool, jazzy vibraphone for nitrogen,” he says, “because nitrogen is usually shown in blue in models.”

Partly for amusement, Cordes included a function that plays an entire protein by tracing its backbone of amino acids, creating a meandering trail of rising and falling notes. It sounds like some kind of minimalist sonata, but the tune is deep with significance. “Usually, when I come to a new protein, one of the first things I do is to play it atom by atom,” Cordes says. “It helps you get an overall sense of what you’re looking at, and you can get a feel for its shape and structure.”

Although he began building the model primarily to help him complete his doctoral thesis—its invention is the topic of one chapter—Cordes is enthusiastic about making it publicly available. A beta version is already on the web, and he is waiting to hear from a top educational journal about publishing his work.

“I think this can help shift that balance in science, where everything is so visually loaded, so that more people who are not visually inclined can get access to this kind of information,” he says.

But if he wanted an example of how visually loaded science can be, he need only consider his own thesis experience. Late last year, when he went before his committee to defend his work and polish off his doctorate, the committee had a few final requests. One struck him as profoundly ironic. While the reviewers widely praised Cordes’ scholarship and methodology, they said his presentation needed brushing up. The group suggested more graphics.

“That didn’t surprise me,” says Cordes. “It doesn’t help me any, making these representations. But at the same time, it is the language of science right now, and I have to speak that language, too.” In the end, it was only a minor inconvenience.

 

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