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A Biologist's Listening Guide to Bacteria
Richard Harris, NPR
Bonnie Bassler is a member of the august National Academy of Sciences, a MacArthur genius award recipient, and runs a well-funded lab at Princeton University. Bassler admits she's incredibly driven, but also says what keeps a scientist sharp is self-doubt.
All Things Considered, September 12, 2006 · Every young scientist dreams of doing an experiment that changes the world. A remarkable biologist at Princeton University has done just that. Bonnie Bassler's discovery about how bacteria talk to one another has led to a whole new field of research -- and maybe someday drugs that would be effective against all bacteria.
But forget for a moment that Bassler won a MacArthur genius award a few years ago. Forget that she's just been elected to the august National Academy of Sciences, or that the Howard Hughes Medical Institute has lavished more than $1 million on her lab this past year.
Bassler is remarkable for other reasons as well. The same drive that made her a noted professor at Princeton University also drags her out of bed at 5:42 every morning to teach an aerobics class at the YMCA.
For an hour and a quarter, under a mop of dark curls, Bassler, 44, puts a doting class through its paces. She has been doing this for half her life.
"Bonnie's a lot of fun and she makes the time go very quickly, though we're huffing and puffing and getting a good workout," says Kathie Wilcox, who has been coming to Bassler's class for the past five years.
Bassler not only huffs and puffs and works out, she talks through it all. "Is that fair or what, on top of everything else?" says Wilcox.
The Hidden Talents of Bacteria
People in the world of science have also been dazzled and left gasping for breath in Bassler's presence.
But her story is not simply one of super achiever, as she explains while walking between the buildings on the Princeton campus. She's amazed that she landed here.
"It's the only job interview I had," she says with a laugh. "I was looking for a job and sent out all these applications. And Princeton bit. It's really neat the way it worked out for me because I've been incredibly happy here."
We head upstairs in the Lewis Thomas biology building, toward a large suite of labs that Bassler now runs. It's on the lower life-forms floor.
In her lab, 14 young scientists, an even mix of men and women, are buzzing about, determined to unlock the secrets of how bacteria talk to one another.
"What's great about bacteria is you have a surprise every day waiting for you because they're so fast, they grow overnight," she says. "So you run in here and you open that incubator and you take out those plates every morning and there are colonies when there shouldn't be or there aren't colonies when they should be, or they're glowing when they shouldn't be. And the first word out of your mouth is a cuss word.
"And you think, 'I hate this, this is awful. How could this not work?' And the next thing you say is, 'Well, maybe I could try this, maybe I could try that.' We must be stupid! We just come in day after day for this torture. But when you get the good days, where you really figure something out like the structure of a molecule or the gene you've been looking for, those days last a long time."
Bassler has had more than her share of those blissful days. In fact, this whole field basically didn't even exist before she came along. Now more than 100 labs around the world are working on it. She simply stumbled into it herself.
Decoding Bacteria Speak
One day, back when she was getting her Ph.D., she came across a reclusive scientist named Mike Silverman.
"I happened to hear one of the only talks he gave in like 10 years because he never traveled much," Bassler says. "He was sort of a gentleman scientist." She says she barely understood the talk, since Silverman was a geneticist and she was a chemist.
But this much she got. Silverman said one species of glow-in-the-dark bacteria appeared to be talking to one another.
"I remember sitting there thinking, 'Get outta here! They're bacteria. They can't do that, '" she recalls. "Which, of course, is what we all thought. Then I remember thinking, 'He thinks about them as these little personalities and he's found this amazing thing. I just have to work on that!'"
She rushed up to the podium right after his talk and begged for a job in his tiny institute. He said yes. So she spent the next four years there. And she figured out how these bacteria talk to one another. They use not just one but two chemical signals.
We head into a pitch-black room with a rack of Petri dishes, so she can demonstrate this bacteria's hidden talent. She shakes the dishes and they emit a blue glow.
"This is how this whole field started," she says. "You're looking at this bacterium, which is a marine bacterium."
It turns out that when one of these bacteria is all alone, it doesn't glow. After all, that would be a waste of effort because nothing could ever see such a tiny amount of light. But it does send out chemical signals that say, hey I'm here ... and it listens back for other bacteria sending the same signal.
When enough bacteria are doing this, they know they have a quorum. All of a sudden, they light up and do all sorts of other things to act in concert, like a super-organism.
"So they turn on and off 100 different genes, to let them turn off behaviors that are good when you're alone and turn on genes that are good when you are a community. And for reasons we don't understand, the gene that lets them make this beautiful blue light is one of the genes they turn on," Bassler says.
At first, the scientific reaction that these luminescent bacteria use these chemicals to talk to each other was, big whoop. But the molecular biology department at Princeton was willing to bet that there was more to the story. Tom Silhavy was head of the search committee at Princeton that hired Bonnie Bassler 12 years ago. He said he just had a feeling.
"It's hard to know how a newly hired faculty member is going to do in their first independent position, so you have to trust your instincts," Silhavy says. "She's now more famous than all the rest of us combined, actually."
Bassler surprised even herself.
"The goal of scientists is you hope that the thing you're working on is bigger than the thing you're pipetting into that tube at that moment," Bassler says. "We always knew we were working on something bigger than bioluminescence, but we didn't think it would be what it turned out to be. It's just been so much better."
That's because once Bassler got to Princeton, she started asking whether this chemical communication was just the trick of this one species, Vibrio harveyi. It turned out that communication is universal among all bacteria, including the nasty ones.
"Melissa Miller, a graduate student in the lab, went on to show that cholera has a circuit like Vibrio harveyi's and what it does, it doesn't make light, it makes toxins, and so that's what it does as a group," Bassler explains. "So they can't make you sick as one, but if they wait and they launch their attack together, it's fantastic."
Collectives All Around
And what's more, Bassler came to realize that bacteria don't just talk to others of their same kind. One chemical she discovered serves as a universal language that all species of bacteria can understand. So all bacteria can talk to all other bacteria. She also realized that because bacteria evolved first, they must have invented chemical communication, which is now used to organize all giant collections of cells into organisms.
"This is what happens in your body," she says. "It's all this chemical communication. We call them hormones, and your kidney cells don't get mixed up with your heart cells because there are these different languages. And that's exactly what this bacterium is doing."
In an odd way, her life is also based on this strategy. She's an individual, but also part of a larger collective; think of her aerobics class.
"As you saw, we're practically the Rockettes," she says with a twinkle.
OK, that's not a great example. But in her lab, Bassler really is not just a lone operator, but part of what you can think of as an intellectual super-organism.
Bassler constantly wanders through her labs, touching base with her young and energetic crew.
"Everybody's lab takes on the personality of the adviser. So the people who come to me are these fun-loving, excited, honest and really hard-working people who are totally neurotic," she says. "Everybody, as soon as they do a good experiment, their first thought in this lab is, 'That can't be right. I must have screwed it up. What did I do wrong?'
"And that's the best kind of scientist because they're filled with this self-doubt. And if I'm going to be honest, that's who I am. And it's what drives me. It's a terrible part of my personality. Nothing's ever good enough, I'm not smart enough. This is part of my mantra. I need to work harder, and if I were only smarter, I could help them with their struggle better."
Sure, she won the MacArthur award, the Eli Lilly Prize, she's a Howard Hughes scholar and even a member of the National Academy of Sciences. But she says that doesn't really count.
Bassler says, sometimes it's hard to see which ideas are really hers. She grudgingly will admit she is a good scientist. And she is setting the course for her group's future. They're trying to find some way to interfere with the universal language of bacteria, to prevent them from ganging up against us. It would be a super antibiotic.
"But it would be fantastic if out of this crazy glow-in-the-dark bacterium that came out of the ocean, something really really good, like a new antibiotic, came out of this guy," she says.
And, she hastens to add, it would be a collective victory, not simply her own.
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