Scott O'Neill wants to rid the world of dengue fever by infecting mosquitoes with bacteria so they can't carry the virus that causes the disease.
A Scientist's 20-Year Quest To Defeat Dengue Fever
This summer, my big idea is to explore the big ideas of science. Instead of just reporting science as results — the stuff that's published in scientific journals and covered as news — I want to take you inside the world of science. I hope I'll make it easier to understand how science works, and just how cool the process of discovery and innovation really is.
A lot of science involves failure, but there are also the brilliant successes, successes that can lead to new inventions, new tools, new drugs — things that can change the world
That got me thinking that I wanted to dive deeper into the story of an Australian scientist named Scott O'Neill. Scott had come up a clever new way for combating dengue fever.
Dengue is a terrible disease. It sickens tens of millions and kills tens of thousands. There's no cure, no vaccine and pretty much no way to prevent it. It's one of those diseases transmitted by a mosquito, like malaria.
"Success for me is having a significant impact on dengue disease in communities," says Scott O'Neill, holding a container of mosquitoes.
About 20 years ago, a lot of scientists got excited about the idea of genetically modifying mosquitoes so they couldn't transmit these diseases. People are still pursuing this approach. But I thought genetically modifying mosquitoes would be really hard to do. Even if you were able to make these disease-blocking mosquitoes in the lab, I didn't see how you would ever get them to survive in the wild, and displace the disease-transmitting mosquitoes that were already there. There was also a societal problem with the scheme. Most people probably wouldn't be thrilled about having swarms of genetically modified mosquitoes released in their backyards.
But last summer, when I read about O'Neill's work, it really knocked me out. His big idea was to infect mosquitoes with a naturally occurring bacteria called Wolbachia. Turns out that by some unknown quirk of biology, Wolbachia-infected mosquitoes can't carry the dengue virus.
Let me repeat that, because this is a key point: A mosquito infected with the bacteria called Wolbachia can't transmit the virus that causes dengue. One microbe defeats the other.
When I interviewed O'Neill by phone last year, he told me the idea seemed to be working. He had released his Wolbachia-infected mosquitoes into two small communities in northeastern Australia.
"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," O'Neill told me.
That was enough success for me to do a short news story about O'Neill's work. But I knew there was more. I convinced my editor to let me go to Australia to learn more about O'Neill and his big idea.
'Incredibly Frustrating Work'
One of the first things I learned when I got to his lab at Monash University in Melbourne was a surprise: It had taken O'Neill 20 years to get his big idea to work.
"You know, I was incredibly persistent in not wanting to give this idea up," O'Neill said. "I thought the idea was a good idea, and I don't think you get too many ideas in your life, actually. At least I don't. I'm not smart enough. So I thought this idea was a really good idea."
The problem was that O'Neill couldn't figure out how to infect mosquitoes with Wolbachia. Remember, a Wolbachia infected mosquito can't transmit dengue.
You can't just spread Wolbachia bacteria around and hope the mosquitoes catch it. Instead, 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.
"It's incredibly frustrating work," O'Neill says.
His colleague Tom Walker spends hour after hour, day after day, trying to inject the embryos. Even though he's become an expert at this, Walker can do no more than 500 a day.
Then the scientists have to wait a week until the adult mosquitoes emerge to see if any are infected with Wolbachia. Walker says in this latest round of work he's injected 18,000 eggs — with nothing to show for it. "The success rate is very low," says Walker, in something of an understatement.
"We don't have any windows that can open in this building, so people like Tom can't jump out of them," O'Neill adds with a laugh. He sounds like he's only half kidding.
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. 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. Pretty soon, everybody who's anybody in that mosquito community is infected.
Success: 'A Significant Impact On Dengue Disease In Communities'
Now as I said, O'Neill has been pushing this idea of using Wolbachia to control dengue for decades, for a most of that time without any success. I asked him what it takes to stick with something for that long.
"I think being obsessive," he replied. "Being maybe a little ill in that regard. And it's just that I seem to have focused my obsession onto Wolbachia instead of on to postage stamps or model trains."
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. "Success for me is having a significant impact on dengue disease in communities," he says.
To do that, he'll have to release his mosquitoes in a place where there's a lot of dengue, and then see if that brings down the number of cases of the disease in humans. Those studies are being planned now.
The stakes are high. By some estimates, more than a billion people around the world are at risk for getting dengue. Even if it doesn't kill you, I'm told a case of dengue can make you feel so bad, you wish you were dead.
"[It's] pretty much the worst disease I've ever had. It was not fun," says Steven Williams, a tropical disease researcher at Smith College in Northampton, Mass. Williams was bitten by a dengue mosquito while on a trip to French Polynesia. He says for 10 days he had a high fever, horrible headache and terrible pain in his muscles and joints.
One other delightful thing about dengue: There are no specific drugs to treat it. "You basically just have to ride it out," says Williams.
Moments Of Triumph, With Trepidation
With no cure and no vaccine, O'Neill's Wolbachia-infected mosquitoes could make a huge difference. Although proving that is still years 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. He told me looking back on it, it was. But at the time it didn't seem that way.
Releasing Mosquitoes To The Wild
"Because you're so used to failure that you don't believe anything when you see it," he says. "And so you can think back to when there was a Eureka moment, but at the time, you're probably, 'This looks good but I've been burnt thousands of times before. Let's go and do it again, and the do it another time, and check and check and make sure it's actually real.' "
O'Neill says the day his team really enjoyed was last year when they tested to see if their mosquitoes would take over from the other mosquitoes in the wild.
O'Neill's colleague Scott Ritchie recorded the event for posterity on his cellphone.
That got me interested in O'Neill's work last summer. He and his colleagues have now completed a second release, and the results are looking promising. But O'Neill says it's not yet time to celebrate.
"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 at any day," he says.
'Eliminate Dengue' Team Has A Deep (Lab) Bench
Every profession has its symbols of success. For opera singers, it's performing at La Scala or the Met. For mountain climbers it's making it to the top of Everest. For scientists, if you get two papers published in the same issue of a prestigious journal like Nature, you're hot.
So when an Australian named Scott O'Neill had two papers published in Nature last year describing his big idea for combating a disease called dengue, the world took notice. O'Neill is a medical entomologist and dean of the faculty of science at Monash University in Melbourne.
"We were getting bombarded by people around the world, from different governments, wanting us to come work in their countries because people are so desperate for something to try and stop dengue," says O'Neill.
Dengue is nasty. It's transmitted by a mosquito and can be a deadly disease. But even if it doesn't kill you, it knocks you out with a week or more of high fever and a pounding headache. Billions of people around the world are at risk for getting dengue if they get bitten by a mosquito carrying the dengue virus.
O'Neill's big idea for stopping dengue didn't involve a vaccine or a medicine. Instead, it involved attacking the mosquito that transmits the disease.
There are two parts to the idea. First, find a way to treat mosquitoes in the lab so they could no longer transmit dengue. That took him more than a decade to figure out. And five years ago, O'Neill finally managed to do it.
Next, release those dengue-proof mosquitoes and show that they will not only survive outside the lab but actually drive out the native population of mosquitoes that can transmit dengue. That's what O'Neill showed in those two Nature papers last year.
Now, I say O'Neill has done this, but that's misleading, because science is now a team sport. "We don't work in isolation in any projects in science these days," he says. "The days of having someone beavering away by themselves in the backroom have long gone, I think. So we're working in large teams always."
O'Neill's team is also spread around the world — he has collaborators in the United States, Brazil, Vietnam and Thailand, and in the tiny town of Babinda in northeastern Australia, where I went to visit.
Babinda's main claim to fame is winning the Golden Gumboot. A gumboot is the Australian term for a waterproof boot, what the Brits call a Wellington. The Golden Gumboot is a tongue-in-cheek award given each year to the Australian town that gets the most rain.
O'Neill's team here drives through the community in a minivan, releasing lab-reared mosquitoes. Martin Durkan is on the mosquito release team. When his day starts, there are dozens of small plastic containers in the back of the van, each with about two dozen of O'Neill's mosquitoes. I watch as he drives up to a house, jumps out, walks over to the front yard, and pries the lid off the container. "And away they go," he says. "The little angels are flying."
The Challenge Of Managing Science
These little angels are the key to combating dengue. The mosquitoes native to Babinda can transmit dengue. Scott's little angels can't. If the angels can take over from the natives, then in theory there will be no more dengue in Babinda. Not that there was ever a lot of dengue here, but you've got to start somewhere.
So how do you know if the angels are winning? Well, you could ask, but sometimes it's hard to tell what mosquitoes are saying. So a better way is to collect mosquito eggs. By analyzing the eggs, you can tell whether they came from O'Neill's angels, or the local riffraff.
The analysis is done in O'Neill's's lab at Monash University, where the mosquito eggs are ground up and put into a machine that will show whether the eggs are from those nasty wild mosquitoes or whether they are descendants of O'Neill's's angels.
So far this year, it looks like the angels are taking over from the natives. But it just as easily could have gone the other way.
O'Neill couldn't have found that out without relying on his team. He told me he's seen a lot of science projects fall over because teams couldn't hang together. "Finding a way to manage a group of people who are all quite individualistic and having them work together towards this common goal is critical," he says. "So I think there's a big management component to science that's not fully appreciated."
By all accounts O'Neill is a pretty good manager. But that means at times telling people things they don't want to hear. Michael Turelli, who works at the University of California, Davis, and is a devoted member of O'Neill's team, says O'Neill is a great team leader, "but that means that if part of the team isn't working, that part of the team is cut off without ceremony. I've seen him do that. And he does it in a way that people aren't offended. They realize, 'Yes, you can't give me another million dollars, because I haven't produced anything.' So that's that."
O'Neill is moving into a critical stage of his project — he's got his special mosquitoes, he's shown they can take over in the wild, but he still has to show they can stop dengue. That's going to mean taking on a bigger challenge: releasing them in countries like Vietnam and Thailand, where dengue is a huge problem.
The Balance Between 'Self-Promotion' And 'Cautious Conservatism'
O'Neill's colleague Scott Ritchie old me about another challenge O'Neill faces that has nothing to do with management. It's about how you portray your work. He says take the name they have given their project: Eliminate Dengue.
Scott O'Neill is leading a global effort to rid the world of dengue fever. "Finding a way to manage a group of people who are all quite individualistic and having them work together towards this common goal is critical," he says.
"That's really putting yourself up there," says Ritchie, "to say that we're going to eliminate dengue. And I think a lot of scientists are saying, 'Yeah, you bet. I'll bet you haven't thought of this, you haven't thought of that, you're making big promises before you've got the evidence to say that you're going to do it.' On the other hand, a name like that draws attention. It's certainly generated a lot of attention in the media. I mean, you're here, Joe. So I think you need to find this balance between self-promotion, but also a bit of cautious conservatism."
It's the entrepreneur in O'Neill that made him choose a bold name like Eliminate Dengue. He knows there are risks.
"We need the exposure; we need people to know about what we're doing. We want to have communities supporting what we're doing. But at the same time we need to be careful," says O'Neill. "This has the potential be difficult for the team, if it comes across that this is all Scott's idea and it's all because of Scott."
O'Neill and his colleagues have learned a lot in the past 20 years. And a goal as big as this, to change an entire species of mosquitoes in the world, could take another 20 years.
"Success for me is having an impact on dengue disease in communities. That's what we're really looking for," says O'Neill.NPR