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RENEE MONTAGNE, HOST:

It's MORNING EDITION, from NPR News. Good morning. I'm Renee Montagne.

DAVID GREENE, HOST:

And I'm David Greene. This week, we're starting a new project taking us behind the scenes in science; looking at how scientists and inventors create new things, and answer big questions about our world. This idea on how innovation happens, came from NPR science correspondent Joe Palca. So we've come up with what we think is an appropriate name for the project. We're calling it "Joe's Big Idea."

JOE PALCA, BYLINE: Great name; wish I'd thought of it. The plan, really, is to talk about scientists' big ideas. So today, I'm going to talk to you about an Australian scientist who has a big idea about how to put a dent in a devastating global disease.

But before I tell you about the idea, I've got to tell you about the disease. It's called dengue fever. Even if you've heard of it, you might not know how bad it is. In fact, I wasn't entirely clear myself, so I called someone who knew firsthand.

STEVEN WILLIAMS: Pretty much the worst disease I've ever had. It was not fun.

PALCA: That's Steven Williams. He's a college professor in Massachusetts. He's a friend of a high school buddy of mine. Dengue is transmitted by a mosquito. Williams was bitten while on a trip to French Polynesia.

WILLIAMS: High fever - my fever spiked to about 105; horrible headache...

PALCA: Williams also had terrible pain in his muscles and joints. Dengue is sometimes called break-bone fever.

WILLIAMS: But I'd say the worst thing, for me, was the headache. The head pain was pretty awful.

PALCA: Oh, and one other delightful thing about dengue: There are no specific drugs to treat it.

WILLIAMS: You basically just have to ride it out.

PALCA: Ten miserable days, and then a few weeks of feeling like a wrung-out dishrag. That's if you're lucky. Tens of thousands of people die each year from a severe form of the disease known as dengue hemorrhagic fever.

Dengue isn't a big problem in the United States. But with climate change, it could become one. There are scientists working on all sorts of ways to combat dengue, but I'm going to tell you about what Scott O'Neill is working on. His idea is to focus on the mosquito that transmits the disease. He's found a way to infect mosquitoes with a bacteria called Wolbachia. It's a naturally occurring bacteria that's harmless to humans.

Why does he do this? Well, it turns out that Wolbachia-infected mosquitoes can't carry the dengue virus. Let me repeat that - Scott O'Neill infects mosquitoes with the bacteria called Wolbachia because a Wolbachia-infected mosquito can't carry the dengue virus. No one knows exactly why. But it seems that somehow, one microbe defeats the other. Last year, he released his Wolbachia mosquitoes into two small communities in northeastern Australia.

SCOTT O'NEILL: Over a very short period of time, the Wolbachia was able to invade the wild mosquito population until close to 100 percent of all mosquitoes had the Wolbachia infection and so, we presume, greatly reduced ability to transmit dengue between people.

PALCA: That's from a phone interview I did with O'Neill last summer. I thought O'Neill was really on to something, so I did a radio story about his work. Normally, that would've been the end of it. But with this new beat, I have a chance to tell you more of the story, more about O'Neill and how he got his big idea to work. So I told my editor, I needed to go visit O'Neill in Australia.

ANNE GUDENKAUF: What?

PALCA: It took a little convincing, but I can be persuasive. And after all, there's nothing like Australia.

(SOUNDBITE OF TOURISM JINGLE, "THERE'S NOTHING LIKE AUSTRALIA")

UNIDENTIFIED SINGERS: There's nothing like Australia. There's nothing like...

PALCA: You probably know this already, but Australia is a long ways off.

(SOUNDBITE OF AIRPLANE ENGINES)

O'NEILL: You ready?

(SOUNDBITE OF DOOR OPENING)

PALCA: When I finally got to O'Neill's lab in Melbourne, I learned something surprising. It took O'Neill 20 years to get his big idea to work.

O'NEILL: You know, I was incredibly persistent about not wanting to give this idea - I thought the idea was a good idea and, you know - and I don't think you get too many good ideas in your life, actually. At least, I don't. I'm not smart enough. But - so I thought this idea was a really good idea.

PALCA: There was just one problem with this good idea. It didn't work - at least, not at first. The problem was, he couldn't get the Wolbachia bacteria to infect mosquitoes. It's really hard to do that in a laboratory. You have to puncture a mosquito egg - or embryo - about the size of a poppy seed, with a hair-thin needle containing the bacteria; peering through a microscope the entire time, so you can see what you're doing.

O'NEILL: Oh, it's incredibly frustrating work.

PALCA: O'Neill's colleague Tom Walker is the microinjection expert in O'Neill's lab. He says Tom spends hours a day at it.

O'NEILL: He can maybe do 500 in a day.

PALCA: Then you have to wait a week until the eggs become larvae and then pupae and then adult mosquitoes, to see if any are infected with Wolbachia. Tom says in this latest round of work, he's injected 18,000 eggs - with nothing to show for it.

TOM WALKER: The success rate's very low - very low.

O'NEILL: And we don't have any windows that can open in this building, so that the people like Tom can't jump out of them.

(LAUGHTER)

WALKER: Exactly.

PALCA: O'Neill was only partly kidding about that, I can tell you. Anyway, the good news is that if you can manage to get the bacteria into even one mosquito, nature will take care of spreading it for you because any mommy mosquito that's infected, will also infect all her darling offspring - all 100 or more of them. And when those baby mosquitoes become mature in about 10 days, the new mommies among them will pass Wolbachia to their babies. Turns out, uninfected females don't breed very effectively when Wolbachia is around. So pretty soon, everybody who's anybody in that mosquito community is infected with Wolbachia.

Now as I said, Scott's been pushing this idea of using Wolbachia to control dengue for decades - for most of the time, without any success. I asked him what it takes to stick with something for that long.

O'NEILL: Well, I think being obsessive; being a little - maybe ill, in that regard. And it's just that I seem to have focused my obsession onto Wolbachia, rather than onto postage stamps or model trains.

PALCA: And even though his obsession has brought him to the point where he's shown he can get his Wolbachia-infected mosquitoes to spread in the wild, that's not the success he's ultimately after.

O'NEILL: Success, for me, is having a significant impact on dengue disease in communities.

PALCA: Although that ultimate goal is still years - if not decades - off, there have been moments of triumph in the 20-year slog that's brought him this far. Take the day in 2006, when one of O'Neill's graduate students told him he thought he'd finally succeeded in infecting a dengue mosquito with Wolbachia. I figured this must have been a red-letter day for O'Neill, a day of sheer elation. O'Neill told me, looking back on it, it was. But at the time, it was hard to tell success from failure.

O'NEILL: Because, you know, you're so used to failure, and you don't believe anything when you see it. And so you can think back to when there was a eureka moment but at the time, it's probably - you're like, oh, this looks pretty good but, you know, I've been burnt thousands of times before. Let's go and do it again, and let's do it another time; and check and check and check, and make sure it's actually real.

PALCA: That's science, in a nutshell. You want to be really sure about your result before you believe it yourself - let alone, tell the world about it.

There was one day that O'Neill and his team were able to enjoy in real-time. It was the day last year when they tested to see if their mosquitoes would take over from the other mosquitoes in the wild. A small crowd had gathered to watch.

SCOTT RITCHIE: The inaugural release of the Wolbachia mosquitoes.

PALCA: O'Neill's colleague Scott Ritchie recorded the event for posterity, on his cellphone. It doesn't look like a big deal. In the shaky video, you can see Scott O'Neill wearing jeans and a khaki shirt, walking past a red picket fence and up the driveway of a modest, suburban house in a community in northeast Australia. He's carrying a small, plastic container - like the ones you get potato salad in.

RITCHIE: One, two, three...

PALCA: He pries off the lid, and gives the container a shake.

RITCHIE: There they go. Smile for the camera, Scott.

PALCA: That was in 2011. A year later, O'Neill says all the mosquitoes in the two communities where they released their mosquitoes, are now infected with Wolbachia. He and his colleagues have now released their mosquitoes in two more communities, and the results are looking promising. But O'Neill says it's not time to celebrate.

O'NEILL: We've got some good preliminary data, and we're on the path. And it's looking good. But, you know, I am a realist. It could fall over on any day.

PALCA: Somehow, even if that happens, I don't think O'Neill's going to give up. Tomorrow, I'll tell you more about the challenges a scientist faces when his work starts to be successful.

Joe Palca, NPR News.

(SOUNDBITE OF MUSIC)

GREENE: And you can see video of that first release of mosquitoes that Joe mentioned, and also read more about Scott O'Neill's big ideas, at our website, NPR.org.

(SOUNDBITE OF MUSIC)

GREENE: You're listening to MORNING EDITION, from NPR News.

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