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Pomona College Magazine is published three times a year by Pomona College
550 N. College Ave, Claremont, CA 91711
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The Taste Maker
As chief scientific officer at the biotech
firm, Senomyx, Mark Zoller '75 is looking for a few good molecules.
By Adam Rogers '92
Mark Zoller ’75 is hell-bound for sushi.
He’s a tall guy, and he’s taking long strides over the landscaping around a San Diego strip mall. The parking lot was full, but this
restaurant is supposed to be pretty good. So he parked on the street, and he’s cruising toward raw fish, full speed ahead, explaining how the sense of taste works as he goes.
“Taste is in the mouth,” Zoller says. “Smell is in your nose. Flavor is the combination.” You smell food. You taste it. And then you smell it again—food chemicals get vaporized by the heat of the mouth and reach the olfactory receptors via the back of the mouth. It’s called retronasal olfaction. And the four tastes? Everyone knows sweet, bitter, salty and sour. Most researchers who work on this stuff accept the fifth one, umami—the savory taste of the amino acid glutamate.
 “Then there’s capsaicin,” Zoller says, talking about the chemical that makes chili peppers spicy. “That’s hot. And menthol is cold. And there’s fat. It could be mouthfeel, but that’s mediating something, right?” And what about the metallic flavor of a zinc throat lozenge? Or astringent?
He reaches the sushi joint, pulls in behind a party of two but ahead of a party of four. It’s time to eat.
Zoller’s interest in taste isn’t academic. He’s the chief scientific officer at Senomyx, a biotechnology company nestled amid hundreds of others in the pine tree-lined hills around UC San Diego. But instead of trying to come up with medicines that kill tumors or stave off aging, Zoller’s company is working on making food taste better. The researchers there are, quite literally, tastemakers.
The industrial-scale version of that work is decades old— everyone’s familiar with the “artificial flavors” listed on a can of soda pop. Zoller’s team is working on a more subtle approach. They’re using the still-young science of taste genetics to find chemicals that trick the human tongue into believing that processed food tastes good, and it’s healthy, too.
Taste and smell—gustation and olfaction—are what scientists call the chemical senses. And until the late 1990s, they were research backwaters.
About taste, researchers knew only the basics. Spread around the tongue are circular folds called circumvallate papilla. Down inside them are onion-shaped taste buds, collections of 50 to 100 cells connected to neurons that lead to the brain. In those cells, the chemicals in food, called tastants, get translated into the sensations at the root of flavor.
Figuring out how a person tastes things, though, proved tougher. “The physical senses, like sight and hearing, are so much more readily subjected to experimental manipulation,” says Charles Zuker, a biologist at UC San Diego. “The input-output relationship and causality can be exquisitely controlled. The chemical senses are far more challenging.”
Fortunately, genetics offered a new approach. On the outsides of those cells in the taste buds are receptors, proteins that run through the cellular membrane and send back information about the outside world. In 1998, researchers at the University of Miami found a protein that rats use to sense glutamate. They hypothesized that it was the receptor for umami. The field cracked open. In 2000, Zuker’s group helped find the genes that code for the bitter receptor, and the sweet receptors soon after that. Zuker’s team published their explanation of how the tongue senses sour flavors in the summer of 2006. Once you’ve identified the receptors, you can start finding chemicals that set the receptors off. In one of his most famous experiments, Zuker created genetically engineered mice that think bitter things are sweet—they can’t get enough bitter water. The question was, could you use that knowledge?
When Zoller was a kid, he didn’t know he was going to be a scientist. At Pomona, he aimed first at politics. A course on modeling the future flipped him over to chemistry. As a graduate student at UCSD, he wasn’t particularly interested in the senses, except in the ways they came into play when drinking wine.
His roommate, Gary Chikami ’75—who’d also been his senior year roommate at Pomona—had a buddy with a vineyard in Temecula. Together, they headed out there to pick 1,000 pounds of grapes and bottle their own booze. Zoller even used lab gear from school for a step called malolactic fermentation, converting malic acid into lactic acid for a softer flavor.
After graduation, he worked for the pioneering genetics company Genentech, and wrote a textbook with John Watson, one of the co-discoverers of the structure of DNA. And he got interested in signal transduction—the way cells use receptors, basically. He built the genomics group at the Boston biotech company Ariad, and when the transnational pharmaceutical company Aventis bought his division out, he went looking for a new gig.
At about the same time, Zuker and a colleague were working on a method for discovering new drugs called high-throughput screening. The idea is to figure out what a molecule with potential medical usefulness might look like, and then test millions of compounds to see if any of them turn out to be that molecule. They realized they could do the same thing for taste compounds, and they went looking for someone to run the screening program. They found Zoller.
At Senomyx on a typically sunny winter’s day in San Diego, Zoller walks into a closet-sized room with a couple of lab benches against the walls. On one is an industrial-strength microscope with a tube leading from its tray to six fat syringes on a stand, all manifolded. Company researchers make frog eggs with specific taste receptors, like those for sweet. And then a lab worker drips compounds onto the cells, one at a time, looking for a response.
“What the traditional flavor discovery company would do is just taste everything,” Zoller says. “What we do is use the receptor as a filter. They can look at 1,000 things per year, but with the high-throughput technology we borrowed from the pharmaceutical industry, we can screen, I think, 1.5 million compounds per year.”
 Compounds that light up the frog eggs—or, for a different kind of receptor, mammalian cells used in roughly the same way—get passed on to the high-throughput screening machines in a bigger lab down the hall. They look like refrigerators attached to conveyor belts, with robot arms that squirt hundreds of different kinds of molecules into hundreds of tiny vials. Given the right library of molecules to test, the process is fast and totally automated.
“When we put sweet receptors in that assay it perfectly recognizes every sweetener known to man,” Zoller says. “We can actually find things that you couldn’t find with your sense of taste.”
The proof, though, is ultimately in the pudding. Upstairs, Zoller walks into the kitchen. It’s a weird combination of lab equipment—beakers and flasks, microscopes, desiccator cabinets— and the kind of gear you’d find in any well-equipped kitchen. A Mixmaster sits next to an ice cream maker on a counter, amid plastic bags of arcanely-labeled white powders. A young woman is stirring white, bubbly stuff in a saucepan on a hotplate. “Don’t say anything about what you’re doing,” Zoller says as he walks by. Senomyx works with a lot of major food companies, and most of the research is secret.
He heads for a clear, plastic cabinet about the size of a box of printer paper. From a shelf he removes a small, white canister labeled “Savory Flavor S336.” “One of our partners, we can’t say which one, is going into commercialization with this next year.” It looks like confectioners’ sugar, but it’s actually a flavor enhancer 1,000 times more potent than monosodium glutamate. MSG’s effective amount is about 2,000 parts per million; S336 makes things taste savory at 1 ppm, so little that it doesn’t have to be named on a package’s list of ingredients. Senomyx has similar projects going with salt and with artificial sweeteners, too.
Zoller’s office is decorated with samples from the companies Senomyx works with. He has a few bottles of Coke Blak, a coffee-flavored version of Coca-Cola. Next to it on the shelf sit a few different iterations of Campbell’s chicken noodle soup and a box of Kraft Easy Mac. To be honest, they’re all foods that could stand to taste better, or be healthier, or both.
“Just as the world is getting into personalized medicine, we’re also getting into personalized nutrition,” Zoller says. “The statistic about salt is that 70 to 80 percent of the salt you eat is in processed food. Why is it in there? For the most part, because it makes things taste better. But 20 percent of the population would be improved by a low-sodium diet.”
Good intentions aside, it’s hard to get past that pills-for-food, Soylent Green vibe. There’s a big difference between making something taste sweet and making something taste like Mom used to make. “Just assuming for the moment that Senomyx could come up with a virtual apple, even if it tasted identical to one from an orchard in Sebastopol, they’d have very different histories,” says Harold McGee, author of the nerd chef’s bible On Food and Cooking and a member of Senomyx’s scientific advisory board. “Part of the experience of eating is everything you know about where that food came from and what it is.”
Knowing how your tongue is translating chemicals into flavor can change that eating experience, too. “I think I’ve become more sensitive,” Zoller says. He’s still a wine enthusiast—and not the kind who puts bottles up to age. “I pretty much drink what I buy,” he says. “If I go to a restaurant, I’m thinking, what are the flavors?” Recently, one of Senomyx’s bankers took him to Masa, a $500-a-person Japanese restaurant in Manhattan. “It was incredible. Every course had a different taste, and there were something like 30 courses.”
Even professional tastemakers can be surprised now and then. |
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