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Welcome to one of the world’s most prestigious microbiology labs. It’s one part theater, one part brilliance — all overseen by an aerobics-teaching diva who loves bacteria.
BY TRACY STATON. PHOTOGRAPHS BY SEAN McCORMICK. PHOTO ILLUSTRATION BY ANN E. CUTTING.
BONNIE BASSLER CARRIES A FLASK INTO A SMALL, WINDOWLESS ROOM AND CLOSES THE DOOR BEHIND HER. SHE TURNS OFF THE LIGHT. A FLUORESCENT BLUE-GREEN GLOW EMANATES FROM THE FLASK, HIGHLIGHTING HER HANDS, TINGING HER SKIN. INDUSTRIAL CHEMICAL? RADIOACTIVE ISOTOPE? THE WARM, MUSTY ODOR IN THE ROOM SAYS NO — ONLY SOMETHING LIVING COULD SMELL LIKE DECOMPOSING GUPPY FOOD. AND IN A WAY, THAT’S WHAT THIS IS: IT’S AN OCEANGOING BACTERIA CALLED VIBRIO HARVEYI, WHICH LIGHTS UP WHEN IT’S PRESENT IN NUMBERS.
V. harveyi is the bacterium that launched Bassler into a field of microbiology known as quorum sensing — named for bacteria’s ability to alert one another when a critical mass of their brethren is nearby — with her own eponymous lab at Princeton University. It’s the bacterium that ushered her into the select group of MacArthur Fellows and into the National Academy of Sciences. It’s the bacterium that taught Bassler its language.
You could say that Bassler loves V. harveyi. She even loves its funky scent, which works its way into the throat and sinuses, where it lingers. Standing in the dark lab, holding up the luminescent flask, her face lit by her glowing offspring, she might be a parody of a Fra Angelico Madonna and Child.
“Ahhh,” she says, inhaling deeply. “Smells like fish poop.”
THE BASSLER LAB started out translating V. harveyi’s communications, but now it’s teasing apart the language spoken by the entire bacterial family tree. Several years ago, Bassler and her lab associates discovered that one of the chemicals V. harveyi uses to communicate is also used by hundreds of other species — in fact, by most species they’ve tested.
The chemical is known as auto-inducer 2 (AI-2), a rather bland, pedestrian name for a substance that could eventually cure cholera, strep, staph — any bacterial disease, anywhere in the world.
The potential that’s there is why Bassler and the 18 students and employees who work in her lab spend hundreds of hours a week digging into the minute workings of AI-2 (and its cousins auto-inducers 1 and 3). And it’s also why she’s a scientific celebrity, the sort of scientist who, when appearing at conferences, inspires a chorus of whispers. Like V. harveyi when it’s about to glow, people signal to each other, pointing and saying, “There she is: Bonnie Bassler. Should we talk to her? Let’s talk to her.”
A bit ironically — but only a bit — Bassler drinks from a coffee mug inscribed “Diva.” She doesn’t consider the label insulting; she embraces it. Diva behavior gets results. She’s officially a genius now, thanks to the “genius grant” bestowed on her by the John D. and Catherine T. MacArthur Foundation, so why not put the diva personality trait to work?
It’s useful for dealing with the National Institutes of Health, for instance. Since she started the lab, Bassler has applied for an NIH grant many times. For the first several years, she could guess why she was turned down: The idea of quorum sensing had not really caught on. Bacteria communicate? Oh, yes, that’s interesting, but it’s hardly a cure for cholera. Application rejected.
But when the NIH turned her down again in 2002 — after the MacArthur came through — Bassler decided to pick up the phone. “I explained the situation,” she says politely. “And my qualifications.” Whatever she said, it worked. She got funding from the NIH a few months later.
Now, grabbing the telephone in her office and speaking into the receiver, she jokes, “They think I’m a genius! So what’s your problem?”
 GETTING FUNDING MAY be routine now, but for years, Bassler ran this lab on tiny grants collected a few at a time, like coins in a cookie jar.
Bassler flew to Princeton 13 years ago with all her belongings. Her sole companion was a cat. She was fresh off a postdoctoral fellowship at the Agouron Institute in La Jolla, California, where she studied with the godfather of quorum sensing, Mike Silverman. When she moved, she had nothing but empty rooms in the Lewis Thomas Laboratory building on the Princeton campus and a budget for filling them.
For several years, she filled her budgetary cookie jar grant by grant. She cobbled together enough money to operate the lab and to fund her students’ work, and slowly her team grew: She added a lab assistant, a PhD student, another PhD student, a postdoc, and then another postdoc. By the time they discovered the gene for AI-2 in 1999, seven people worked at the Bassler Lab, and no one outside microbiology had ever heard of them.
The lab team kept toiling away. Bassler got married in 2002. Students graduated; more came to take their places.
Then, in September 2002, the MacArthur Foundation called, and she got the genius label. “It was totally over the top,” Bassler says, “such a validation that somewhere out there, scientists think we’re doing great stuff.” Bouquets of flowers arrived. The phone started ringing.
“You’re in a lab with no exposure to the popular press, and suddenly, people want to interview you,” says Mike Federle, a postdoc who arrived just before the world discovered that Bassler is a genius. “You pick up the phone in the lab, and it’s some reporter, and they start asking questions.”
Now, the lab’s cookie jar overflows. The lab is packed with equipment, including a petri-picking robot and an afluorescence cell sorter, each worth around a half-million dollars and courtesy of the Howard Hughes Medical Institute. Eighteen people work there now, growing bacteria, creating mutants, testing hypotheses, writing papers, and smelling fish poop.
 ONE OF THE THINGS the Bassler Lab is working on is finding a way to moderate a bacterium’s virulence. Here’s a for instance that uses E. coli O157:H7, a germ that’s caused a handful of fierce outbreaks in recent years: When E. coli finds its way into a human body, it doesn’t start attacking immediately. It waits until it has a quorum, and then, pow! Virulence factors turn on, and the human gets really sick. In the case of E. coli, the bacteria start to produce a toxin that wreaks havoc. The idea is to trick the E. coli into thinking that only a few other E. coli are around. Then no virulence factors turn on, so there’s no toxin, no grave illness.
The concept is simple enough, but the process isn’t. Postdoc Chris Waters has been studying how the auto-inducers work in Vibrio cholerae, a V. harveyi relative and, yes, a human pathogen. The funny thing about V. cholerae is that its signals behave almost exactly opposite to those in most bacteria. This bacterium doesn’t wait until it’s swimming in a critical mass of fellow bacteria to turn on virulence. It’s virulent from the get-go; it attacks immediately. What Waters would really like to do is trace the early-stage signals V. cholerae uses and figure out a way to interfere with them. If he could do that, the strategy could then be used on a lot of different pathogens. “It could be something simple like an amino acid or a sugar,” Waters says. “You might not need a complex drug to treat illness.”
That V. cholerae is a germ that gets humans sick is one reason Waters is working with it and not with V. harveyi. Another reason is Bassler. She wants her students to have their own research they can take with them when they leave so that they can compete with her for grant money — and win. If their research is too much like hers, she’ll beat them every time.
Take Federle, the postdoc whose bacterium of choice is strep, the familiar pathogen that causes strep throat and scarlet fever. He’s working on mucking up strep’s ability to make AI-2 so the germ can’t get the message that it’s time to go virulent. “If we come up with inhibitors, we could alter their ability to cause disease,” Federle says. “That’s the ultimate promise of quorum sensing. We identify how they talk, and then, if we mess with their communication, we change their behavior.”
Strep, then, is Federle’s territory, the platform he’ll use to fund the rest of his career. Just as Bassler did when she started out, he’ll find a research institution to fund a lab just for his work, and he’ll write for grants to pay for ongoing operations. “Bonnie doesn’t want anything to do with it,” he says. “It’s wise to find your own niche. I can’t compete with Bonnie; she’s a superstar.”
Besides, making her students hack their own trails through the bacterial world encourages independent thinking, radical ideas — just what Bassler likes. She gives her researchers time and space to work out their own strategies and do their own experiments. The long leash isn’t unheard of in science, but it isn’t universal. “I came from a lab where I had to meet with someone every day, and it was easy to get lost in the details,” Federle says. “I was really taking orders.”
Twice a week, the lab’s researchers take turns presenting their work to the group for critique and direction. In between, they go to Bassler for help when they’re stuck, when they need ideas.
“She likes to think big ideas,” Waters says. “Ideas that will change the way people think about bacteria. A lot of people in science get so focused on their little pieces — this little gene and this little protein. The real leaders change paradigms and set new ones. She’s one of those people.”
BASSLER’S ALARM rings at 5:42 every weekday morning. Bleary-eyed and grumbling, she makes her way to the YMCA to teach aerobics. She’s been teaching aerobics for 23 years, and every day, she tells herself it’s the last.
If she weren’t teaching, though, she wouldn’t show up at all. So teaching is her version of willpower.
This morning is the first day back at class after a school holiday. She’s shouting as loudly as she did at the NIH, and the intent is similar. She’s shouting, trying to goose some slow people into movement. “Don’t stop now!” she hollers. She kicks, crouches, and lunges, calling people by name. “You’re late! Are you taking another break? Come on! Do it!”
After class, the sweaty students rush up to a visitor to offer their assessments of Bassler, scientist extraordinaire. They know the drill — PBS came a few weeks ago to film an episode of Nova. Unique individual. Caring. Compassionate. Kind and giving. Great communicator. Down to earth. Not at all pretentious. Don’t know how she does everything.
Her students and postdoc fellows say the same sort of things about her at the lab. Generous. Inspiring. Brilliant. Sympathetic. Supportive. High energy. True to herself.
They also say she’s neurotic. She says so herself. “I’m a really insecure person,” she says. “Every time I write a paper, I think I’ll have no more ideas.”
Bassler says, “My whole life is about guilt. A monologue is always going on in my head: Could I have been better, stronger, faster?”
The other consensus is that she’s an actress, a performer — that she loves the spotlight. She must, to be willing to take her message about bacterial communication on the road the way she has. Of course, she presents the lab’s research at big conferences where scientists from all over the world gather, but she also lectures for conclave after conclave of students and faculty, each group made up of a handful of researchers of one single, solitary biology department.
Does she shout for them too? Does she cross her eyes for emphasis like she does at home? Whatever she does, she’s never subdued. She may have multiple personalities, but shrinking violet isn’t one of them.
“People think I’m histrionic,” she says. “Imagine that.”
THE BASSLER LAB is abuzz with the news: Danielle Swem is pregnant with twins. The lab assistant (who’s the wife of one of the postdocs) told a few people about a half hour ago, and now, to make sure that no one’s left out, Bonnie walks into the room where Swem is setting up test tubes and shouts, “Hello! Attention! Danielle and Lee are having twins! Twins!”
Swem accepts the attention calmly; she’s probably accustomed to Bassler’s turning the spotlight on her. Not much big personal news stays secret in this lab. Everyone knows Mike Federle is interviewing for jobs at Stanford and the University of Chicago, and that Chris Waters’s third child will be born in a few days. In fact, pictures of Bassler with the newborn wrapped in his hospital blanket, with the hospital bracelet still on his tiny wrist, surface on the lab’s website soon after the birth.
In those photos, Bassler looks as proud as the baby’s parents. She may have multiple personalities, but one of them dominates: She’s a matriarch. Her students and fellows become her offspring, their families her extended family. She even adopts the reporters who drop in, picking them up at the train station, taking them to her house for dinner, inviting them to play board games. “I’ve had thirteen babies in my lab,” she says proudly.
Bassler runs the lab more as a parent than as a boss. She’s nurturing her students’ careers, not ordering people around. Her goal is to guide them toward fruitful work, to help them work through any snarls along the way. “They’re suffering when they work on these experiments, because they’re working in the dark,” she says. “Mostly what I can do is recognize the difference between something that’s total crap and something that’s creative and off the beaten path.”
Her pride in her students’ work is much more than professional — it’s personal, maternal. Even when she grouses, she’s proud. Chris Waters is going to put me out of business. Sine may be the smartest grad student I’ve ever had.
Ideally, when they leave here, they’ll be able to run their own labs, fund their own work. But when they’re stuck, Federle says, “We’ll call Bonnie.”
When Bassler’s students talk about their work, a moment comes when they confess how much they rely on her emotionally. I never leave her office feeling like our idea isn’t going to work. She doesn’t take us for granted. I’m not afraid to go in there crying.
Like their biological mothers do, though, she sometimes annoys them. She walks in with big news about Internet culture, and they laugh. My mother sent me that weeks ago, they think. Sometimes she gives them unwelcome advice, insistently. And when they don’t listen, she worries.
“It’s totally like motherhood,” she says. “And my fantasy is to populate the field with all my offspring.”
TRACY STATON is an American Way contributing editor.
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